Objective: Antiangiogenic therapies  are being increasingly used in the treatment of solid tumors; hypertension represents a common side effect of these agents. Several mechanisms are involved in the development of hypertension, including microvascular rarefaction and other microvascular alterations. Therefore, the aim of our study was to evaluate whether TKI and direct anti-VEGF agents may affect the structure of retinal arterioles or capillary density.Design and Methods: We investigated 20 patients with a diagnosis of cancer who underwent a treatment with either a TKI or an anti-VEGF antibody. Patients were submitted to ambulatory monitoring blood pressure for blood pressure evaluation. Basal and total capillary density were assessed by capillaroscopy whereas, retinal arteriole morphology was measured by Adaptive Optics. Patients were evaluated before starting the antiangiogenic therapy (T0) and re-evaluated after 3 (T3) and 6 (T6) months after treatment. Fourteen patients completed the study.Results: Systolic and diastolic blood pressure values were similar in all patients at T3 and T6 compared to T0. However, during the study antihypertensive treatment was optimized (increased dose and/or addition of drugs) in 57% of patients (n = 8). No differences were observed in retinal arteriole structural parameters and in large artery stiffness. Basal capillary density was reduced by antiangiogenic drugs after 3 or 6 months.Conclusions: Our data suggest that an increase of antihypertensive treatment is necessary in patients treated with a TKI or a direct VEGF inhibitor, confirming pro-hypertensive effects of these drugs. However, under adequate blood pressure control, microvascular structure seem to be partially preserved, since a worsening of basal capillary density but no changes in retinal arteriole morphology were observed. Angiogenesis (the formation of new blood vessels from a pre-existing vascular system) represents an essential mechanism for tumor growth and dissemination . AlreadyVascular homeostasis is regulated by various pro-angiogenesis and anti-angiogenesis factors. When the pro-angiogenetic factors pre-dominate angiogenesis begins; and when this occurs in a tumoral context this is called “angiogenic switch” . As mentRamucirumab is another monoclonal antibody which acts at the level of the extracellular portion of the VEGF receptor. Multitarget small molecules tyrosine kinase inhibitors (TKI) may block multiple tyrosine kinases, including VEGFRs 1, 2, and 3; stem cell factor receptor (c-KIT); platelet-derived growth factor receptors (PDGFRs) and other tyrosine kinases .Treatment with these drugs is frequently associated with an increase in blood pressure both in hypertensive patients and in normotensive subjects , 10. HypSeveral evidences suggested that an increase in blood pressure, in patients treated with VEGF inhibitors, could be considered a pharmacodynamic biomarker of oncologic response , 12, altIt is known that essential hypertension is associated with the presence of structural alterations in the microvessels , 15. ResBesides structural alterations of small resistance arteries, in hypertensive patients there are also other microvascular changes, including: endothelial dysfunction, increased oxidative stress, and capillary rarefaction . In the Finally, it was suggested that treatment with VEGF inhibitors may increase large artery stiffness, increasing pulse wave velocity (PWV) , althougTherefore, the aim of our study was to evaluate whether TKI and direct anti-VEGF agents may have an impact on microvascular and macrovascular structure, in particular on retinal arteriolar morphology and on capillary density.Twenty patients, 10 males and 10 females, with diagnosis of cancer were included in the study. Demographic and clinical characteristics were detailed in Patients were enrolled between January 2017 and December 2019 in the Oncology Department of our hospital. All patients were evaluated before starting antitumoral treatment (T0) after 3 months (T3) and after 6 months (T6) of treatment.n = 1 due to change in cancer therapy and n = 4 due to worsening of clinical conditions secondary to neoplastic pathology). Therefore, the data analysis was carried out on the remaining 14 patients.One patient, after an initial evaluation at T0 was then excluded from the study because he was no longer suitable, from an oncological point of view, for the previously proposed therapy. Five patients were lost during the follow-up between T0 and T3  for evaluation of 24-h day-time and night-time average pressure values, according to Italian  and EuroThe device calculates: cSBP and cDBP, estimated as the levels of SBP and DBP at the aorta, based on the aortic pulse wave generated by the generalized transfer; augmentation pressure (AP), estimated as the difference of the pressure at second minus the pressure at first inflection point of the systolic phase of pulse wave; AP, and heart rate-adjusted AP [AP(75)], indicative of the augmentation component of aortic SBP because of the premature arrival of the reflected wave; PWV, estimated from the reconstructed aortic pulse waveform via mathematical models taking into account the characteristic impedance and age and assuming a three-element Windkessel model –27. PrevCapillary density, defined as the number of capillaries for unit of skin area, was evaluated trough a capillaroscopy  before and after venous congestion. The examination was performed under standardized conditions: before the start of the procedure the patient was kept at rest in a sitting position in a quiet room at a controlled temperature (21–22°C). The capillaries of the nailfold were analyzed (first row of nail bed capillaries) and the dorsum of the fourth finger of the non-dominant hand using a fiber optic video microscope, in basal conditions  and after venous congestion  in order to visualize the capillaries functionally excluded. Venous congestion was achieved by inflating a cuff of a pediatric sphygmomanometer at 60 mmHg applied to the base of the fourth finger of the non-dominant hand. In addition, the basal and total capillary density at the level of the distal third of the forearm was also evaluated using a standard sphygmomanometer to obtain venous congestion. Further details are reported in reference .All enrolled patients underwent study of retinal arteries with adaptive optics using the Rtx-1 optical camera  , 30. TheIn all patients an echocardiographic assessment and an ultrasonographic investigation of the carotid arteries was performed at baseline. An echocardiogram was repeated in 10 patients during the follow up period. Left ventricular mass index, systolic and diastolic function, as well as the possible presence of intima/media thickening of the carotid artery were evaluated, according to previously published methods and criteria .To quantify carotid artery wall thickness, the following measures were chosen: mean of the maximum wall thickness of 2 sites  for common carotid; the maximum of 2 sites  for common carotid; mean of the maximum of 4 sites  for common carotid and bifurcation (CB Max); mean of the maximum of all 12 sites (4 sites at each of the three segments), or of at least 4 sites for each side: CA Mean Max); the maximum of all 12 sites (4 sites at each of the three segments), or of at least 4 sites for each side.The protocol of the study was approved by the Ethics committee of our Institution, and informed consent was obtained from each participant. The procedures followed were in accordance with institutional guidelines.t-test comparing T0 with T3 and with T6; a one-way ANOVA analysis of variance (ANOVA) (comparison between three time points) was also performed. Statistical significance between groups was assessed by means of chi-square test for dichotomous variables. A value <0.05 was considered as statistical significant. By a post-hoc analysis, our study had a 75% power to detect a difference of 0.02 in the WLR, while it has a power >98% to detected a difference of at least 0.03 in the WLR, than on the bases of previous data may be considered as clinically relevant . In particular, in the first 3 months from the beginning of the antiangiogenic therapy it was necessary to increase the dosage of the drugs for the control of blood pressure values in four patients, while in three patients an antihypertensive therapy was introduced ex novo and only one patient required a reduction in antihypertensive therapy. Between the third and sixth month, two patients further increased the antihypertensive therapy and in one patient antihypertensive drug treatment was started. The therapeutic changes occurred when an elevation of blood pressure (<140/90 mm Hg) was detected by the general practitioner, regardless of the blood pressure assessments performed during the study. The drugs used were, mainly, dihydropyridine calcium antagonists, and angiotensin converting enzyme (ACE) inhibitors.Results are summarized in Results are summarized in Results are summarized in No significant difference was observed between visits in terms of indices or large artery distensibility. Central blood pressures,  were similar at the different time points .The majority patients (92%) had intima-media thickening of the carotid artery at baseline (intima media thickness > 1mm) . No chande novo treatment, increase in the number or in the dose of previous antihypertensive treatment independently from the study evaluations. In fact, eight patients developed an increase in blood pressure values during the follow up period . Probably such prompt therapeutic adjustment allowed both to effectively control blood pressure, with no significant increases at the two time points and also to prevent the development of microvascular damage in the retinal vessels.Our results showed that, during a 6-month follow-up in neoplastic patients treated with VEGF inhibitor drugs or TKI, no statistically significant alterations were observed for the WLR of retinal arterioles; there was a not statistically significant increase in blood pressure values, evaluated by ABPM as well. However, these results were deeply influenced by changes in antihypertensive treatment  is associated to organ damage  and it iIn our study, no change in mechanical properties of large arteries  was observed during treatment with VEGF inhibitor drugs, similar to what observed by Dalbeni et al. . SimilarOur neoplastic patients were mainly treated with ACE inhibitors and calcium channel blockers, according to indication of European Guidelines . ConsensAs mentioned, a limitation of this study is certainly related to the small number of the patients enrolled, possibly exposing to a type 2 error. They had often advanced neoplastic conditions and therefore not all patients were able to complete even a relatively short 6-month follow-up. Only 9 of the 20 enrolled patients were alive 1 year after T0 (11 patients died for the worsening of the neoplastic disease). In addition, in the study protocol no blood chemistry test was scheduled; therefore the reported values were collected retrospectively: for this reason we were not able to perform a correct stratification of the patients' initial cardiovascular risk, or to accurately assess the trend of biohumoral indices over time.Antiangiogenic drugs are widely used in cancer patients, however to date no predictive parameters of efficacy have been identified. Since the efficacy of these drugs could be linked to the extent of the antiangiogenic effect, the assessment of capillary density could be a non-invasive and easily assessable parameter that could be of help in detecting patients destined to respond to treatments and those who do not. This could be an interesting topic for future research.The prognostic impact of changes in blood pressure and/or in vascular morphology is not known in these patients, also considering that life expectancy is very variable on the bases of baseline prognostic factors. The patients evaluated in our study are representative enough of the usual patients undergoing such treatments. However, at least some of them may survive longer enough, and in these patients the impact of hypertension/vascular alterations may became a clinical issue.In conclusion, our data confirm the importance of paying attention to the cardiovascular risk of the patients in antiangiogenic therapy, in particular by maintaining periodic blood pressure monitoring. The need for increased antihypertensive therapy during treatment with TKI or anti-VEGF is confirmed, confirming the pro-hypertensive effects of these drugs. However, in the presence of adequate blood pressure control, no changes in the retinal microcirculation are observed, thus underlining the importance of controlling cardiovascular risk factors also in these patients both for the prevention of events and to ensure greater compliance to the antineoplastic therapy itself.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by Ethics Committees, Spedali Civili di Brescia. The patients/participants provided their written informed consent to participate in this study.MC: clinical handling of patients, data collection, and graphics. CD: design, data analysis, and graphics. CA-R, VB, CR, GC, PM, FF, APe, SC, CA, MN, and APa: data collection. DC and SG: clinical handling of patients. MM, MS, and AB: design and data analysis. DR: data analysis and writing of the manuscript. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


After 2years. they did not differ in terms of BP (125.3 ± 10.69/74.97 ± 7.67 vs. 124.5 ± 9.95/75.21 ± 7.64 mmHg) and body weight (71.14 ± 14.29 vs. 71.50 ± 11.87 kg). Significant differences were seen for UNaV (97.3 ± 23.01 vs. 152.6 ± 49.96 mEq/24 h) and LVMI (86.38 ± 18.17 vs. 103.1 ± 21.06 g/m2). Multiple regression analysis: UNaV directly and independently predicted LVMI variations, either as absolute values , or changes from baseline to +2years. . Systolic BP was a weaker predictor of LVMI , whereas diastolic BP was not correlated with LVMI. The prevalence of left ventricular hypertrophy decreased (29/76 to 15/76) in the first group while it increased in the less compliant patients . Conclusion: LVM seems linked to sodium consumption in patients already under proper BP control by medications.Objective: To evaluate the left ventricular mass (LVM) reduction induced by dietary sodium restriction. Patients and Methods: A simple sodium-restricted diet was advised in 138 treated hypertensives. They had to avoid common salt loads, such as cheese and salt-preserved meat, and were switched from regular to salt-free bread. Blood pressure (BP), 24-h urinary sodium (UNaV) and LVM were recorded at baseline, after 2 months. and after 2years. Results: In 76 patients UNaV decreased in the recommended range after 2 months and remained low at 2 years. In 62 patients UNaV levels decreased after 2 months and then increased back to baseline at 2 years. Initially the two groups did not differ in terms of BP , body weight (72.64 ± 15.17 vs. 73.79 ± 12.69 kg), UNaV (161.0 ± 42.22 vs. 158.2 ± 48.66 mEq/24 h), and LVM index (LVMI; 97.09 ± 20.42 vs. 97.31 ± 18.91 g/m Hypertension is the primary modifiable cardiovascular risk factor ,2. Left Controversies apart, a restriction of sodium intake , can favorably impact hypertensive patients’ health, reducing blood pressure, cardiovascular risk , total mDietary sodium has been proposed to affect the left ventricular size both in normotensive and hypertensive individuals, and to be the best predictor of LVH in hypertension . A low-sn = 11 did not complete the study).We evaluated 153 hypertensive patients, already involved in a previous research protocol carried out by our group . BrieflyOne hundred and thirty-eight 138) patients  completed the study. In all patients, 24-h UNaV and urinary potassium (UKV) were measured immediately before, or shortly after, the BP measurement. Patients, already trained to collect 24-h urine, received written directions. UNaV and UKV were measured by means of commercial Auto Analyzers . BP was measured as a repeated measure recording 38 patien. With thIn our patients, echocardiographic left ventricular mass data were available at the time of the previous study . The echBody surface area (BSA) was calculated using the old Du Bois formula .(2.7) to attain left ventricular mass index (LVMI), since in our population the prevalence of obesity is low [2 in females and above 115 g/m2 in males [The left ventricular mass was calculated with the Devereux’ formula ,24, and y is low , under 9in males .p < 0.0x, instead of the exact p value—GraphPad Software, San Diego, CA): One-way ANOVA followed by Newman-Keuls  or Kruskal-Wallis post-test, with Dunn’s Multiple comparison (non-parametric data), Wilcoxon and Mann Whitney tests (non-parametric data), Paired Student’s t test , contingency analysis (Chi2—binary variables), and linear regression analysis. Multiple linear regression analysis was performed by use of SPSS software version 20.0 for Windows . Significance level was set at p = 0.05. Values are represented as mean ± SD unless otherwise indicated.Standard statistical methods were performed with commercial software package PRISM  are part of a group of treated hypertensive patients (n = 153 from a cohort of 291 patients), administered with a dietary advice, who showed to comply with sodium reduction in a short-term (2 months) observation [n = 76 out of 138) showed a stable or lower UNaV , while the remaining 45% (n = 62 out of 138) showed an increased UNaV . The first group is classified from now on as Reducer (with apparent long-time compliance), while the second is called Non-Reducer  (p < 0.001) (p < 0.001), and at Time 2 . On the other hand LVMI and SBP , LVMI and DBP , LVMI and DDD , and LVMI and age  were not significantly correlated. The links among LVMI, UNaV, systolic BP (SBP), diastolic BP (DBP), DDD, age and body weight, showed a significant level for the relation between LVMI and UNaV at Time 0   and at T< 0.001) . As expep > 0.05; even the apparently large difference between DDDs at Time 2 did not reach the significance level). They did not differ even in terms of LVMI at baseline (Time 0); Wilcoxon and Mann–Whitney tests: p = 0.567 to p = 0.755. A significant difference was found in terms of UNaV at Time 2, with a Δ rank sum  of −168.4 and p < 0.05 , UKV, age, weight, or DDD from Time 0 to Time 2 , while it increased in Non-Reducers .Incidentally, the LVMI decreased significantly in Reducers  and at the end of the study (Time 2), respectively. Similarly, in Non-Reducers we found r = 0.579; p < 0.001 and r = 0.497; p < 0.001 at the baseline (Time 0) and at the end of the study (Time 2), respectively.LVMI and UNaV showed significant relationships also in the two subgroups, first evaluated by use of simple linear regression. Using UNaV as a predictor of LVMI changes, in Reducers we found r = 0.270; p = 0.474 and p = 0.865, respectively), in Reducers we found significant relationships only at Time 2 (the last observation) and only for SBP , with non-significant values for DBP .LVMI and BP relationships in the two groups are complex: while in Non-Reducers we did not find any significant relationship   . Simply = 0.002)  and drug= 0.002)  remainedMultiple regression analysis (see p < 0.001), independently of BP or DDD. At Time 2, LVMI correlated either with UNaV or SBP , irrespective of DBP or DDD.In the whole group, at Time 0, LVMI correlated with UNaV , independently of BP or DDD. At Time 2 LVMI correlated either with UNaV or SBP , irrespective of DBP or DDD.In Reducers, at Time 0, LVMI correlated with UNaV , independently of BP or DDD. At Time 2 LVMI correlated with UNaV , independently of BP or DDD. What has been shown for absolute values seems strengthened by the analysis of the changes over two years, where UNaV is the single, direct, and significant predictor of LVMI change   .p < 0.001; SBP: β = 0.168, p = 0.027). Furthermore, looking to the correlation between LVMI and patients’ parameters within the Non-Reducer group, both simple and multiple regression analyses point out UNaV as the only significant predictor of LVMI changes, .Finally, the LVMI modifications from baseline to Time 2 were substantially different in Reducers vs. Non-Reducers. While in the former group a decrease has been shown, in the latter we have observed an increase instead. This behavior seems unrelated with the antihypertensive drugs employed , since tp > 0.05.No sex-specific differences were found between the groups by ANOVA, Kruskal-Wallis followed by Dunn’s multiple comparison test: Half of our patients who were supposed to follow a low-sodium diet in the long run had benefits in terms of BP control, drug reduction and, above all, LVM reduction and LVH regression.The effects of possible sodium restriction have been observed in our patients: BP control improved and drug consumption decreased, already in the short term . SurprisThe only significant and substantial differences between the two subgroups are represented by LVM and UNaV. The two variables show a highly significant and strict relationship, both in the whole group and in the subgroups.The LVM has been studied in our patients with the standard 2D-guided M mode. Although other methods are capable of more refined results ,28, the In our patients, there was no association between BP and LVM and this might be due to their chronic drug treatment and the resulting acceptable BP values, already before the present observations. Indeed, it’s worth speculating that the paramount effects of the antihypertensive treatments on LVM had been already occurred before the beginning of the present study.High sodium intake is the top dietary risk factor for cardiovascular disease ; sodium The regression of the left ventricular mass, and the reversal of LVH, in severe hypertension under dietary sodium restriction are historical data. Already in the papers by Walther Kempner, the rice-fruit diet, with its very low-sodium content, could normalize both the BP values and the cardiac mass ,10. MoreIn our patients, the favorable effect of the dietary sodium reduction on LVM seems marginally related to the BP values, owing to the only partial relationships between these variables. This is not surprising in view of the previous literature ,19,44,45Patients observed in the present study seem to show a long-term effect of the dietary approach in terms of BP control and drug consumption, which persists even in those who apparently ceased the diet. This apparently “long-term protective effect” by an earlier (and somehow limited in time) sodium-restricted diet was initially assessed in the Kempner’s cohort , and morOur data detected a strong relationship between the LVM values and UNaV (and so with the most reliable measure of sodium intake), more than with BP values recorded at the same time, while no relationship exists with DDD. It may be argued that in treated hypertensive patients the LVM may be subjected more to the sodium intake than to the BP levels when these latter are sufficiently controlled by the drug treatment. The LVM reduction, achieved in the long run by those patients apparently compliant to sodium restriction, may be in a range similar to that achieved by usual antihypertensive drugs ,8. HowevLimitations of the study: We have limited data regarding the sodium consumption of our patients because we could analyze only three 24-h urine collections, while more would have been required . NeverthStrengths of the study: In hypertensive patients already under proper drug treatment, UNaV is significantly related with the LVM. This relationship seems independent of BP values. Our data support the importance of reducing the dietary sodium in hypertensive patients, even in those under proper BP control.LVM decrease (approximately by 11%) under dietary sodium reduction is comparable to what is attained with drug treatment. In hypertensive patients already under active drug treatment and able to follow a dietary sodium restriction, the prevalence of LVH decreases by about half. Without sodium restriction, LVH prevalence increases by a similar extent. In hypertensive patients under chronic drug treatment, the favorable effect of dietary sodium restriction on LVMI seems independent of BP.


Nearly half of US adults with diagnosed hypertension have uncontrolled blood pressure. Clinical inertia may contribute, including patient-physician uncertainty about how variability in blood pressures impacts overall control. Better information display may support clinician-patient hypertension decision making through reduced cognitive load and improved situational awareness.N = 16) and physicians (N = 24) guided iterative design and confirmation phases. Thematic analysis of qualitative data yielded insights into patient and physician needs for hypertension management.A multidisciplinary team employed iterative user-centered design to create a blood pressure visualization EHR prototype that included patient-generated blood pressure data. An attitude and behavior survey and 10 focus groups with patients . This significant innovation has potential to improve quality of care for hypertension through better patient-physician understanding of control and goals. It also has the potential to enable remote monitoring of patient blood pressure, a newly reimbursed activity, and is a strong addition to telehealth efforts. Hypertension affects 70 million US adults and is a major risk factor for morbidity and mortality, contributing to heart disease, stroke, and chronic kidney disease . Neverth“I decided to check my blood pressure with a home monitor before a coming physical examination. The first night, I was startled to find that my systolic pressure was a scary 137. The next night, it was only 117. The next morning, before I saw my doctor, it was a terrifying 152. At the doctor’s office, it was 150. I measured it again that night, and it had plummeted to 110.”Clinical inertia may account for gaps in care in the treatment of hypertension. Clinical inertia is a lack of treatment initiation or intensification despite objective evidence that disease is not controlled –6. At anBecause blood pressure variability adds to uncertainty for both the patient and physician, data visualization tools that can promote better patient and physician understanding of the data can improve the quality of patient-physician negotiations about control and treatment as part of hypertension management , 11. ForHome blood pressures may contribute to the variable data problem but are nevertheless important. Several large studies reveal that home blood pressure measurements predict cardiovascular outcomes as well or better than clinic blood pressure measurements, even after accounting for clinic blood pressure –18. AlthWell-designed graphs based on principles of human cognition and visual perception can “emphasize relationships, focus interest, save time in analyzing data, help recall, uncover previously hidden facts and break down the language barrier,”  as well To identify and satisfy patient and physician information needs for hypertension management, with special attention to the growing evidence for including home blood pressure data, we employed a user-centered design process to incorporate patient home blood pressure data into the clinical EHR and improve data visualization for the care of hypertension. User-centered design is an iterative process that involves understanding user information needs for their work, designing for those needs using known design principals, analyzing if needs are efficiently met by the design, and iterating design with further understanding of needs –37.To create initial candidate designs, our multidisciplinary team used a deep dive approach, incorporating principles of data visualization, graphic and health literacy, human factors, health psychology, the tenets of the Chronic Care Model, and usability best practices, as well as the views of two important user groups, patients and their primary care physicians –40. Our Informed by known visual display concepts and evidence from our literature review, we first designed several candidate data visualizations that included a data table of BP values, and an aligned medication timeline Fig.  23–37, , 37, 42.We iteratively tested and refined the visualization in a series of 7 formative design focus groups, with 5 iterations to reach the final prototype Fig. . Design Family medicine and general internal medicine physicians and their patients age 18 years and older with a diagnosis of hypertension were recruited from eight community-based practices. Prior to the focus groups, we educated physicians about the evidence for home blood pressure use in clinical care in a voluntary grand rounds-type seminar. Physician participants were emailed with information about the opportunity to participate; we conducted focus groups at times and places convenient for the physicians, such as lunchtime in the practice conference room.Patient participants were patients of these practices age 18 and above with a diagnosis of hypertension. We used the EHR hypertension registry to create lists of patients, asked their physicians to eliminate those with cognitive impairment or serious mental health diagnoses, and mailed recruitment letters to remaining patients asking them to call the coordinator to enroll. The study coordinator confirmed hypertension diagnosis, screened for cognitive impairment, and described the focus group procedure. Eligible patients were invited to the focus group. At the start of the focus group, patients were presented with a waiver of documentation of consent, including both the written waiver and a verbal discussion of the study focus group procedures. Patients were given the opportunity to ask clarifying questions about the study to confirm understanding and withdraw if they preferred. Patients received $30 fair compensation for time and travel. A similar consent process occurred at the beginning of physician focus groups. The University of Missouri Health Sciences Institutional Review Board reviewed and approved this study and its human subjects’ participation and consent process.All physician and patient participants completed a pre-focus group survey to characterize sample demographics and typical data collection, data use, and decision making based on clinic and home blood pressure readings. Beyond characterizing sample demographics, the short attitudes and behaviors survey addressed research questions  design element options and 2) the pattern and trend of blood pressures to represent common blood pressure “stories”, e.g. increasing blood pressure trend, addition of new medication and resulting decrease in blood pressure, or a gap in medication adherence associated with blood pressure rising and then returning to goal. Because we were aiming for an intuitive design, focus group participants were challenged to construct meaning from the data visualizations with little to no orientation from the facilitators and to construct stories about the patient represented in the data visualization. For example, the visualization in Fig. We analyzed patient and physician surveys using descriptive statistics to examine demographics, attitudes and behaviors about blood pressure (self-) management. Analysis of focus group qualitative data took place in three phases: an immediate team debrief, preliminary rapid qualitative analysis immediately following each focus group, and final thematic analysis of compiled data. Rapid qualitative analysis is a process where researchers review transcripts and identify key aspects of the data answering research questions relevant to the iterative design process. We used this method after each focus group to quickly identify participant responses to design features, to confirm our designs or identify a need to iterate design features, and to quickly develop a preliminary understanding of remaining unaddressed patient/physician information needs and preferences –46. Our 88%).Focus group participant demographics are reported in Table Our rapid qualitative analysis method, occurring after each focus group, informed our iterative design process by identifying and clarifying information needs for physicians and patients, stimulated design iterations to satisfy those needs, and allowed us to check if participants indicated that our design iterations satisfied those needs. Identified needs and design elements to satisfy those needs are presented in Table “It [data visualization] would make me feel like if it’s important enough to her to bring it up to me, it ought to be doggone important to me and I should pay close attention to it … I mean, blood pressure is the silent killer...I need to know how I’m doing, where I stand, ‘Girl, you are in trouble, you’re on a collision course. You need to make some changes. Snap out of this, or we’re gonna be increasing meds or adding some.’”— Patient, Design Round 5“I think it’s useful to know the values of home versus office and how we’re making decisions on that … I think it will incentivize the patient to do [home monitoring] because we’re making treatment decisions on that … So I think that’s therapeutic.”— Physician, Design Round 4Patients and physicians advocated for the addition of contextual information to aid in decision-making. Examples of such information include behavioral/lifestyle change, weight, stressors, and significant clinical events. For this reason, we designed also for the ability to annotate the visualization with this contextual information , they’re getting ready to have a serious episode and then when they’re in the ER in the crisis they’ll see all of this and it’s like why didn’t we see a doctor, well, nobody told me.”— Patient, Confirmatory Round“I kind of like the idea of having the flag in terms of the [in-person] discussion … but from a population perspective there needs to be something that triggers somebody looking at the data if it has gotten significantly out of line.”— Physician, Confirmatory RoundPatients and physicians were concerned about workflow, especially collecting and transmitting home blood pressure data from the patient to physician. Use of patient-generated home blood pressure data in the visualization increased the patients’ sense of importance for providing home blood pressures to portray an accurate picture of hypertension control. Physicians anticipated using this data in decision-making at appointments. Both groups suggested that Bluetooth data uploaded from home monitors would ease the patient’s reporting burden.We have gained an understanding of primary care physician and patient information needs about blood pressure data for use in their decision-making work for the management of hypertension. We have paid special attention to their needs for home blood pressure information, how they would like to send and receive this information, and their aspirations for using this data in their shared work. Employing a user-centered design process, we synthesized our multidisciplinary expertise with evidence-based knowledge, including cognitive perceptual experiments, and these discovered information needs to create an intuitive and well-received visualization that combines clinical blood pressure data, home blood pressure data, goal ranges, a smoothing algorithm, and a medication timeline , 42. ThiWhile there is growing evidence for use of home blood pressure data for hypertension decision making –18, it iWhile we were inclusive of both patients and physicians, the primary users of these blood pressure data, we did not include another significant stakeholder group, nurses and other members of the patient’s health care team. In addition, our information needs and design work takes a primary care perspective, and we have not considered the needs of specialty physicians. Our rationale for this sampling framework was that the majority of hypertension management occurs in the primary care setting . We haveAs a result of this work, we collaborated with our EHR vendor to implement this visualization into the clinical EHR, including patient portal functions that improve patient upload of home blood pressure data and allow it to be represented in the clinical EHR. Thus far, we have not been able to incorporate annotations to the visualization. Work remains for us to identify ways to add annotations that fit into physician workflow, creating opportunities for physicians to add meaningful information easily in a way that will add value to their work. Additionally, we need to understand the best way to add patient annotations, whether to create standardized categories of annotations, and how to deal with a high density of patient annotations. We also need to add Bluetooth capability for home blood pressure devices to the patient portal. Our algorithms are equipped to handle large amounts of blood pressure data, but it is inevitable that Bluetooth upload from devices will introduce new challenges.A significant next step is to evaluate the ongoing patient and physician use of these tools, not only how much they use these tools, but also how the tools affect the quality and process of care. We will also evaluate how the visualization that includes home blood pressure affects how patients and physicians work together during the outpatient clinic visit to manage hypertension, examining differences between care with and without the visualization with comparison to paper lists of home blood pressures.Use of these home blood pressure EHR tools will be augmented by two new environmental factors. First, the January 2020 introduction of new Medicare-reimbursed current procedural terminology (CPT) codes for home blood pressure management activities could drive adoption . Second,Our blood pressure data visualization that includes home blood pressure data is a significant innovation that has potential to improve the quality of care for patients with hypertension, both through a better patient-physician understanding of blood pressure data, and in creating new ways for patients and physicians to interact around these data in their decision making process during outpatient visits. The patient’s active participation in generating these data might better engage them in the management process and be more convincing for those who resist blood pressure medication intensification by facilitating the “prepared patient and proactive health care team” that are at the heart of the productive interactions that lead to improved outcomes in the Chronic Care Model , 39.


The evaluation of the functional status of blood vessels, especially the arterial system, plays a very important role in the judgment of the condition of septic shock patients and the guidance of resuscitation programs and the judgment of the therapeutic effect. We aimed to design an observational study protocol to explore the correlation of peripheral arterial pulse/resistance index, organ function and inflammation in patients with septic shock.A total of 60 patients with septic shock in the Affiliated Hospital of Southwest Medical University from June 2020 to September 2020 and 20 healthy volunteers will be enrolled. Total of 60 patients with septic shock will be randomly divided into 20 groups by lot method. Group 1: fluid resuscitation; Group 2: fluid resuscitation + norepinephrine; Group 3: fluid resuscitation + norepinephrine + ulinastatin; Group 4: healthy control group. Fluid resuscitation is an early goal-directed fluid resuscitation in which norepinephrine is adjusted by a senior intensive care unit specialist for clinical presentation and ulinastatin is pumped at 20,000 U/h. Index including vascular ultrasound, inflammatory factors, organ function will be collected and analyzed.Existing studies on septic shock focus on hemodynamics of the heart, brain, and kidney, while the differences in blood flow between peripheral blood vessels and protective renal vessels may be consistent, and imaging analysis is still lacking. This study protocol aims to explore the correlation of peripheral arterial pulsation index/resistance index, organ function, and inflammation in patients with septic shock.Chinese Clinical trial registry: ChiCTR2000031565 As the dose of catechol increases, powerful vasospasm leads to decreased perfusion of vital organs, increasing the incidence of cardiovascular adverse events. During the resuscitation of septic shock, it is necessary to pay attention to the matching of cardiac function, blood volume, ventricular ejection, and vascular tone.Septic shock refers to septic syndrome with shock caused by microorganisms and their toxins. Septic shock usually results to damage of various organs, thus affecting the perfusion, cause tissue ischemia hypoxia, metabolic disorders, dysfunction, and even multiple organ failure. Septic shock is one of the most common causes of death in critically ill patients, with a mortality rate of up to 50%.565 However, the correlation of peripheral arterial PI/RI, organ function and inflammation in patients with septic shock need to be further investigated.The evaluation of the functional status of blood vessels, especially the arterial system, plays a very important role in the judgment of the condition of septic shock patients and the guidance of resuscitation programs and the judgment of the therapeutic effect. Blood vessel pulsation index (PI) and resistance index (RI) are commonly used method for the evaluation of blood vessel function, which reflect vascular bed resistance. RI is the measurement of systolic peak velocity (PSV) and end-diastolic blood velocity (EDV) through the arterial blood flow waveform. Calculation formula: RI = (PSV − EDV)/PSV; PI = (PSV − EDV)/mean blood velocity. These parameters can reflect the compliance and elastic resistance of a section of the artery. At present, researches on vascular PI and RI mainly focus on cerebral arteries, renal arteries, and coronary arteries, which are used to evaluate the effects of various chronic systemic diseases, including trauma, surgical intervention.In this study, patients with septic shock will be selected, and the pulse index and resistance index of femoral artery, brachial artery and internal carotid artery will be analyzed by color vascular ultrasound Doppler technique, and the differences between peripheral artery and heart, brain, and kidney artery, as well as the correlation with the level of blood inflammatory factors will be analyzed. At the same time, different fluid resuscitation and vasoconstrictor drug regimens will be set up to compare the difference and treatment effect of peripheral arterial pulse index and resistance index in patients with different treatment regimens, so as to analyze the guiding significance of peripheral arterial pulse index and resistance index to treatment. Research results will be in the existing condition in patients with septic shock judgment on the basis of the traditional methods, add blood vessel function to judge the important indicator, more systematic comprehensive analysis of the circulation situation, guide the liquid recovery and drug use, is expected to be especially severe medical physicians for clinicians improve new means of increasing the success rate of patients with septic shock.22.1Aim 1: To analyze the changes of peripheral arterial pulse index and resistance index in septic shock patients with color Doppler technique.Aim 2: To explore the relationship between peripheral arterial pulse index and resistance index and inflammatory factor level in septic shock patients.Aim 3: To perform the Correlation analysis of peripheral artery and cardiac, cerebral and renal blood flow and function in patients with septic shock.Aim 4: To analyze the effects of fluid resuscitation and vasoactive drugs on peripheral blood pulse index and resistance index in septic shock patients.2.2http://www.chictr.org.cn/index.aspx) with a unique ID of ChiCTR2000031565 on April 4, 2020.The protocol scheme matches PRISMA's reporting standards. This study protocol has been registered on the Chinese Clinical trial registry (2.3Sixty patients with septic shock (diagnosis according to the 2014 guidelines for septic shock) and 20 adult healthy volunteers will be enrolled in this study.2.3.1(1)Patients have clear symptoms of infection;(2)Patients show systemic inflammatory response;(3)The systolic blood pressure is lower than 90 mm hg, or the original base drops by 40 mm hg, which cannot be recovered after 1 hour after fluid resuscitation or requires vasoactive drugs to maintain;(4)Accompanied by organ tissue hypoperfusion, such as urine volume less than 30 mL/h, or with acute consciousness disorders; Blood cultures may contain disease-causing microorganisms.2.3.2(1)The patient already has severe arrhythmia such as ventricular fibrillation;(2)The patient has been diagnosed as brain dead;(3)The patient has developed severe multiple organ failure;(4)The patient had peripheral arterial lesions such as thromboangiitis obliterans.2.4Sixty patients with septic shock in the intensive care unit of Affiliated Hospital of Southwest Medical University from June 2020 to September 2020 and 20 healthy volunteers will be recruited. Written consent will be obtained from all participates, which confirms the participants’ voluntarism.2.5A total of 60 patients with septic shock will be randomly divided into 20 groups by lot method. Group 1: fluid resuscitation; Group 2: fluid resuscitation + norepinephrine; Group 3: fluid resuscitation + norepinephrine + ulinastatin; Group 4: healthy control group. Fluid resuscitation is an early goal-directed fluid resuscitation in which norepinephrine is adjusted by a senior intensive care unit specialist for clinical presentation and ulinastatin is pumped at 20,000 U/h.2.6Detection time point: before recovery, 6 hours, 24 hours recovery.(1)Vascular ultrasoundGE E9 color Doppler ultrasound diagnostic instrument will be used, and the vascular probe frequency will be 3.5 hz. In accordance with the routine requirements of the ultrasound department, the patient will be positioned to expose bilateral internal carotid artery, brachial artery, and femoral artery in turn. The vessel diameter will be measured by 2-dimensional figure, the blood flow velocity will be measured by color Doppler, and the blood flow waveform, pulse index, and resistance index will be analyzed by spectral Doppler. By the same method, the frequency and speed of the probe will be adjusted to measure the intracranial artery, coronary artery, and renal artery. Cardiac function will be measured routinely with a heart probe.(2)Inflammatory factorsPeripheral venous blood will be extracted and enzyme-linked immunosorbent assay will be used to analyze the levels of peripheral venous blood inflammatory factors, such as interleukin-2, 6, 8, 10, tumor necrosis factor-, cell adhesion molecule ICAM-1, endothelin ET, signal molecule NF- p in patients with septic shock.(3)Organ function: according to clinical routine data collection and test resultsCardiac function: heart rate, blood pressure, peripheral circulation, ultrasound, vasoactive drugs; renal function: urine volume, renal function test; brain function: consciousness, pupil, GCS score; Lung function: blood gas, ventilator use.2.7SPSS 20.0 software will be used for data statistics and analysis by professional statisticians.2.8The study protocol was approved by the Affiliated Hospital of Southwest Medical University. The approved protocol was registered. Written informed consent will be obtained from all patients and volunteers. The privacy of all participants will be protected. The study will be performed in accordance with the standards of the International Committee on Harmonization on Good Clinical Practice and the revised version of the Declaration of Helsinki principles.3,8 Vascular waterfall induced shock and high dynamic state and peripheral vascular paralysis coexist causes serious organ hypoperfusion and hypoxia. Therefore, improving organ perfusion, reverse hypoxia is the key to successful resuscitation.The pathophysiological feature of septic shock is the cascade inflammatory response, which leads to circulatory dysfunction, resulting in the inability of the body's oxygen supply and the deterioration of tissue perfusion, thus in turn aggravating the body's inflammatory response. Due to the endogenous cytokines and inflammatory mediators, microcirculation network abnormal vascular tension forms a unique phenomenon named “vascular waterfall.”Due to the high threshold of ultrasound detection technology for coronary arteries, renal arteries, intracranial arteries, and other vessels, it is not appropriate for general clinicians, especially for critical medical physicians, to quickly evaluate the vascular functional status beside the bed and guide the resuscitation treatment of septic shock. Based on these questions, this study protocol hypothesizes that peripheral arteries such as the femoral artery, brachial artery, and carotid artery, which were more easily detected, will be selected to replace the cardiac, cerebral, and renal vessels to help clinicians determine the functional status of vessels in the case of septic shock. In the case of septic shock, patients will show differences in blood flow distribution. Existing studies on septic shock focus on hemodynamics of the heart, brain, and kidney, while the differences in blood flow between peripheral blood vessels and protective renal vessels may be consistent, and imaging analysis is still lacking. This study protocol aims to explore the correlation of peripheral arterial PI/RI, organ function and inflammation in patients with septic shock.Changxue Wu conceived the idea and provided the fund for this study; Bo Leng provided statistical plan; Lirong Hu drafted the protocol. Yuting Xue reviewed the protocol and provided critical feedback. All authors approved the article to be published in Medicine.


RR was started at 10 breaths/min, and 2 breaths/min were added every 60 min until 16 breaths/min was reached. At every point, central venous and arterial blood gas measurements were obtained simultaneously.2 induced by hyperventilation significantly increased, while the central venous carbon dioxide pressure (PvCO2) and the partial pressure of CO2 (PaCO2) in arteries decreased. The decreasing trend of the PaCO2 was more obvious than that of the PvCO2. HCO3− and ctCO2 were markedly decreased, when the RR was increased (P < 0.05). Central venous oxygen saturation (ScvO2) had a decreasing trend between 14 (77.1 ± 8.3%) and 16 (75.2 ± 8.7%) breaths/min; however, the difference was not significant.In this study, gapCO2. Clinicians should cautiously interpret the gapCO2 in hemodynamically stable ventilated septic shock patients and its relationship with low cardiac output and inadequate perfusion.In septic patients undergoing ventilation, respiratory alkalosis induced by hyperventilation caused an increase in the gapCO However, when clinicians face the uncertainty of a high lactate value, they have to identify whether it indicates persistent hypoperfusion or whether it will eventually normalize. Therefore, normalized ScvO2 values and lactate values do not rule out persistent hypoxia and hypoperfusion during initial resuscitation.The current consensus and guidelines for the hemodynamic management of severe sepsis and septic shock advocate clinicians to regard the use of lactate clearance and central venous oxygen saturation  demonstrated prognostic value in different conditions [2 combined with the ScvO2 and lactate values should be used to rule out patients with persistent global hypoperfusion [2 production and oxygen consumption, the gapCO2 was observed to be increased in parallel with the reduction in cardiac output [2 in arteries (PaCO2) and prevent the CO2 stagnation-induced rise in central venous carbon dioxide pressure (PvCO2). Mallat et al. demonstrated that acute hyperventilation provoked a significant increase in gapCO2 and oxygen consumption (VO2) [2 and respiratory rate (RR) in septic shock patients undergoing volume mechanical ventilation. Therefore, in this study, we investigated the underlying effect of the RR on the gapCO2 in septic shock patients undergoing volume mechanical ventilation.A few authors have reported that the central venous-to-arterial COnditions –8 and haerfusion . Under sc output . Howeveron (VO2) . To dateThis observational and prospective study was performed at a single, mixed medical and surgical adult intensive care unit (ICU) with 14 beds at 105 Hospital of Chinese People’s Liberation Army from October 2015 to October 2016. The study was approved by the ethics committee of the 105 Hospital of Chinese People’s Liberation Army. Informed consent was obtained from each subject.2) no greater than 65%, using an 840 Ventilator System.The study included 17 patients within 24 h of septic shock onset. The diagnosis of septic shock was determined according to the Second International Consensus of Definitions for Sepsis and Septic Shock . As partcvO2) > 65% and lactate level < 4 mmol/L after achieving adequate intravascular volume and adequate mean arterial pressure (MAP) > 65 mmHg, as recommended by the Surviving Sepsis Campaign [Sedation with propofol and analgesia with remifentanil were provided so that patients without spontaneous breathing could be included in the study. The inclusion criteria were oliguria, mottled skin , centralCampaign . The exccvO2 was determined in a sample taken from the central venous catheter with the tip (confirmed by X-ray) in the superior vena cava near or at the right atrium. The gapCO2 was calculated as the difference between the central PvCO2 tension and PaCO2 tension.Demographic data, septic shock etiology, and acute physiology and chronic Health evaluation (APACHE) II  and sequVentilation parameters and vasopressor drugs were kept constant during the 60-min period prior to the measurements being taken. After the baseline measurements were taken, an RR of 10 breaths/min was started, and 2 breaths/min were added every 60 min until 16 breaths/min was attained. For each procedure, all parameters were measured. The study ended when arterial hypotension (MAP < 60 mmHg), tachycardia (heart rate > 150 beats/min), acute atrial fibrillation, or changes in the ST segment of the electrocardiogram occurred.Statistical analysis was performed using SPSS 10.0 software. A p value (2-tailed) of 0.05 or less was considered significant. Continuous variables were presented as mean ± standard deviation (SD) if normally distributed, or as median if otherwise, and compared using Wilcoxon–Mann–Whitney test. Comparisons of hemodynamic indexes and blood gas in accordance with the RR from 10 to 16 breaths/min were performed by the Bonferroni method.2, which was related to the combined trend of decreases in PaCO2 and PvCO2  production also led to pulmonary vasoconstriction [2 partial pressure of venous blood is less marked than that of arterial blood. This has been demonstrated by other scholars as well [2 excretion and should increase the alveolar PaO2 provided other factors stay the same. Increased alveolar ventilation causes respiratory alkalosis with immediate changes in hydrogen ion concentrations and bicarbonate concentrations. There should be transcellular shifts with hydrogen ion coming out cells into the plasma and shifts of potassium from the plasma into cells. Respiratory alkalosis can cause peripheral vasoconstriction and decreased flow through various vascular beds. This is probably not a uniform effect in all vessels and may or may not occur in patients with sepsis. However, if blood flow decreases but metabolism is unchanged, then the CO2 content of venous blood should increase, resulting in a gapCO2. If patients with sepsis have dysfunctional cellular metabolism, then the production CO2 may decrease, which would result in a lower gapCO2. This likely varies in the vascular bed from tissue to tissue. CO2 binding hemoglobin may not have an important effect in these experiments.The combination of oxygen and hemoglobin can promote the release of COe effect . Clearlytriction . Nitric triction . As a co as well . The inc2 partial pressure of the venous blood does not obviously decrease compared with the CO2 partial pressure of the arterial blood. For instance, Khambatta et al. reported that mechanically ventilated dogs undergoing 2 h of hyperventilation had 20% CO2 production and 25% O2 consumption [cvO2 significantly increased with the RR increase from 10 to 14 breaths/min, but there was no significant decreasing trend in ScvO2 between 14 and 16 breaths/min, which was consistent with a previous report [2 depends on measurements from the superior vena cava (SVC) but does not reflect measurements from the inferior vena cava (IVC) and tissues draining into the IVC [When vasoconstriction is caused by hypocapnia, poor oxygen delivery may add tissue oxygen extraction . Hence, s report . Moreove the IVC .2 can cause mitochondrial dysfunction [2 production. In summary, our data suggested that in septic patients with mechanical ventilation, respiratory alkalosis induced by hyperventilation enabled the increase of gapCO2. Clinicians should be cautious when interpreting the gapCO2 as low cardiac output and inadequate perfusion in hemodynamically stable ventilated septic shock patients.Patients with septic shock lack an effective circulating blood volume, which leads to systemic anoxia and metabolic acidosis. Acidosis and excess COfunction , 24. Met2 instead of using a mixed venous sample, despite the latter having a better correlation. We cannot state the relationship between the gapCO2 and cardiac output, as we did not include the indexes of cardiac function in this study. We included fewer patients than other studies, and the included patients suffered from different etiological factors, so the results from this study should be further confirmed in the future.However, there were some limitations in our paper. In this study, we used a central venous sample to measure the gapCO


Elevated levels of thyroid-stimulating-hormone (TSH) are associated with reduced glomerular filtration rate (GFR) and increased risk of developing chronic kidney disease even in euthyroid patients. Thyroid hormone replacement therapy has been shown to delay progression to end-stage renal disease in sub-clinically hypothyroid patients with renal insufficiency. However, such associations after kidney transplantation were never investigated. In this study the association of thyroid hormones and estimated GFR (eGFR) in euthyroid patients after kidney transplantation was analyzed. In total 398 kidney transplant recipients were assessed retrospectively and association between thyroid and kidney function parameters at and between defined time points, 12 and 24 months after transplantation, was studied. A significant inverse association was shown for TSH changes and eGFR over time between months 12 and 24 post transplantation. For each increase of TSH by 1 µIU/mL, eGFR decreased by 1.34 mL/min , corresponding to 2.2% eGFR decline, within 12 months. At selected time points 12 and 24 months post transplantation, however, TSH was not associated with eGFR. In conclusion, an increase in TSH between 12 and 24 months after kidney transplantation leads to a significant decrease in eGFR, which strengthens the concept of a kidney-thyroid-axis. This is supported by a study with children suffering from congenital hypothyroidism and renal anomalies3. Thyroid hormones also alter glomerular filtration rate (GFR) by affecting renal blood flow and vascular resistance in adult kidneys6. Large retrospective analyses have shown associations of estimated kidney function with thyroid function, including an inverse association between estimated GFR (eGFR) and prevalence of hypothyroidism7, as well as the risk of developing subclinical and overt hypothyroidism8. Conversely, hypothyroidism and subclinical hypothyroidism have been found to lead to higher prevalence of chronic kidney disease (CKD) over time9. Furthermore, even in the normal reference range low free triiodothyronine (FT3) and resulting high TSH values have been associated with higher risk for the development of CKD10. Low thyroid hormone values, even within the clinically normal reference range, have been shown to be associated with reduced eGFR11. In addition, TSH quintiles in normal range have been consistently and independently associated with decreased GFR, increased urine albumin/creatinine ratio and CKD12. Consequently, it was hypothesized that correction of subclinical hypothyroidism by thyroid hormone replacement therapy (THRT) would stabilize and increase renal function measured by eGFR over time. In a small study with 37 hypothyroid and 14 hyperthyroid patients, den Hollander et al. investigated plasma creatinine levels and eGFR before THRT and after regaining euthyroidism; in previously hypothyroid patients renal function improved significantly after THRT. Conversely, kidney function was shown to decrease after treatment for hyperthyroidism14. Furthermore, thyroid hormone replacement therapy has been shown to preserve renal function and attenuate the decline of eGFR in patients with CKD and subclinical hypothyroidism16.Interactions between thyroid hormones and kidney function have been suggested in previous studies. Data from animal studies show that thyroid hormones are important players in the development and growth of kidneys17. However, the potential effect of thyroid hormones on GFR or the preservation of renal function in kidney transplanted individuals has not been demonstrated. In this study, we analyzed data from 398 euthyroid CKD patients who received kidney transplants between 2003 and 2016 to investigate the effect of the thyroid function parameters TSH, triiodothyronine (T3), free thyroxine (FT4) and thyroxine (T4) and their dynamics on eGFR course.Patients with renal grafts by definition have a chronic kidney disease independent of their eGFR. Still, they differ in many aspects from non-transplant patients with CKD. Continuous long-term therapy with nephrotoxic immunosuppressants and corticosteroids interacting with many organ systems, including the thyroid gland, is one of the reasons that makes this population unique. Also, many CKD effects on thyroid function  normalize after kidney transplantation (KTx)This retrospective cohort study was designed to investigate the effect of thyroid hormone dynamics on renal function parameters. Datasets from 398 kidney transplant patients who received a kidney transplant at the Medical University of Vienna between 2003 and 2016 and were in continuous care at this site were analyzed. Adult patients over 18 years with euthyroid state (TSH 0.44 to 3.77 µIU/mL) 12 months after transplantation were included. Exclusion criteria were age <18 years, pregnancy, malignancy, high dose glucocorticoid treatment with prednisolone >25 mg daily and therapy with lithium, amiodarone or propranolol.24months − eGFR12months = ∆eGFR). Subsequently, it was investigated whether a change in TSH, T3, FT4 and T4 levels within 12 months (i.e. TSH24months − TSH12months = ∆TSH) is associated with a change in eGFR over time (∆eGFR). We have conducted several regression models on eGFR at different time points and periods to investigate the association between TSH, T3, FT4 and T4 and eGFR under the aforementioned conditions.The association between thyroid function, measured by TSH, T3, FT4 and T4 and kidney function, determined by eGFR, was investigated at different time points and over time. First, the association between TSH, T3, FT4 and T4 and eGFR was tested at 12 and 24 months after renal transplantation. In addition, it was examined whether TSH, T3, FT4 and T4 concentration at 12 months after transplantation affects the course of eGFR within the following 12 months  and accredited (ISO 15189:2008) for quality management. Laboratory testing of TSH, T3, FT4 and T4 was performed by a third generation ultrasensitive electrochemiluminescence immunoassay . Testing of serum creatinine was performed by Jaffe reaction and eGFR was calculated by the chronic kidney disease EPI (CKD-EPI) equationMS Excel  and Stata 14  were used for data management and analyses. Continuous data are presented as mean ± standard deviation; categorized data are presented as absolute count and relative frequencies. Distributional properties of continuous variables were assessed and linear regression models were deployed to estimate the association between thyroid function and renal function parameters. Due to the longitudinal design of the study, we used thyroid function and renal function variables at specific time points or delta values between these points over time to avoid within-individual-correlations.Multivariable linear regression models were used to adjust the main effect estimates for potential confounding factors. First-level interactions were assessed by stratified analyses and by introducing interaction terms as co-variables into the models. We report regression coefficients for change in unit outcome per one unit change in predictor with 95% confidence intervals. We quantified hypertension per number of antihypertensive substance class prescribed to achieve current ESC/ESH blood pressure targets. A two-sided p-value less than 0.05 was considered statistically significant.The study protocol was performed in accordance to the 1964 Helsinki Declaration and its later amendments and was approved by the Ethics Committee of the Medical University of Vienna (EK 2038/2017). All study participants were adults over 18 years and gave written informed consent. All procedures were performed in accordance with ethical standards and the relevant regulations and guidelines and no organs/tissues from prisoners were procured.The demographic and clinical characteristics of the study population are presented in Table One percent of study subjects had a urine protein/creatinine ratio above 3000 mg/g at 12 months post transplantation, which did not change in the course of the study.Kidney and thyroid function parameters at baseline (pre KTx), 12 and 24 months after kidney transplantation are presented in Table In a linear regression analysis there was no association between single TSH levels and eGFR examined 12 and 24 months after transplantation. Also, single TSH levels were not associated with a change in eGFR between month 12 and month 24 after transplantation (∆eGFR). However, a significant association between ∆TSH and ∆eGFR could be shown between month 12 and 24 post KTx. With each increase of the TSH value by one µIU/mL, the eGFR decreased by 1.41 mL/min  corresponding to a 2.2% decline of eGFR within 12 months Table .Table 3ATo adjust for potential confounding factors, a multivariate linear regression model including independent variables TSH, age, gender, body mass index (BMI), THRT, BUN/creatinine ratio >20, urine protein/creatinine ratio >3000 mg/g, Tacrolimus level >12 ng/mL, CRP value >5 mg/dL, arterial hypertension and diabetes mellitus was established. Hereby, a significant association between ∆TSH and ∆eGFR was confirmed. Each unit (µIU/mL) increase in TSH led to a decrease in eGFR by 1.34 mg/mL . No association was found between single TSH values and eGFR at specific time points 12 and 24 months post transplantation and between single TSH values and course of eGFR over 12 months Table .No association was found between the thyroid hormones T3, FT4 and T4 and eGFR, neither at the individual time points 12 and 24 months post KTx nor when their differences between these time points  were analyzed . Thyroid hormone replacement therapy, proteinuria with urine protein/creatinine ratio above 3000 mg/g, tacrolimus levels above 12 ng/mL, CRP values above 5 mg/mL and arterial hypertension as potential factors influencing thyroid hormones and eGFR had no significant effect at any time point and interval  TSH increase per year. However, the result was not significant due to the limited sample size.This study was designed to analyze the association of changes of thyroid hormones and estimated glomerular filtration rate (eGFR) in CKD patients in the first two years after kidney transplantation. A significant association between the changes in TSH and eGFR levels in the course of the second year after transplantation between month 12 and 24 time points could be demonstrated.14. These changes were reversible with treatment: thyroid hormone replacement therapy in hypothyroidism led to improvement of renal function after regaining euthyroidism19. Some cohort studies showed an association of TSH levels, even within the normal range, with excretory kidney function. Higher TSH levels led to lower eGFR or higher prevalence of CKD20. The direct and indirect effects of thyroid hormones on renal function have already been described before. In addition to directly affecting renin-angiotensin system activity and ion channels and transporters of the kidney, which lead to upregulation of Na+-K+-2Cl−cotransporter and sodium uptake, the major impact on eGFR seems to be of rather indirect and functional nature. The effect of thyroid hormones throughout the whole body decreases systemic vascular resistance by enhanced nitric oxide synthase activity, increases cardiac output by enhanced inotropy and chronotropy and increases blood volume and hence, blood pressure. Altogether these effects lead to an increased renal plasma flow, reduced renal vascular resistance and as a result to higher GFR23. Unlike in overt hypothyroidism, treatment of subclinical hypothyroidism remains debatable. It is generally recommended by the European and American Thyroid Associations to start treatment with levothyroxine (T4) at TSH levels above 10 µIU/mL and in patients under 65 years of age at TSH levels between 7 and 10 µIU/mL due to higher cardiovascular mortality26. Hormone replacement below these levels is symptom-dependent and controversial27. Beyond that, there are no statements about treatment of euthyroid patients. Patients with a kidney transplant are considered CKD patients, even if their GFR is within the normal range and recommendations do not distinguish between CKD patients with or without kidney transplantation.Past studies in patients without kidney transplantation have already shown an association of overt and subclinical hypothyroidism (elevated TSH levels) with higher serum creatinine levels and lower eGFR, whereas hyperthyroidism was associated with lower serum creatinine and higher eGFRet al. are of note.With regard to treatment of subclinical hypothyroidism, two studies by Shin 16. Only a few studies investigated the interactions between thyroid hormones and transplanted kidneys. A study by Junik et al. proved that renal transplantation might have an impact on thyroid hormones, especially on T3 concentrations17. And while low T3 might be an independent risk factor for renal graft failure29, T3 treatment did not improve graft survival or function30.One retrospective study with 309 patients showed that thyroid hormone therapy preserved renal function better and was also an independent predictor of renal outcome in patients with CKD. In a subsequent study in 113 CKD patients with subclinical hypothyroidism, the decline of eGFR was attenuated by hormone replacement treatment10, euthyroid patients might benefit from low TSH levels12. Yet, there have been no studies examining the association of TSH levels in euthyroid CKD patients with kidney graft function. In our study, we included 398 euthyroid patients who received a kidney transplant between 2003 and 2016. Our data show that in the second post-transplant year an increase of TSH levels over 12 months (∆TSH) results in an annual decrease of eGFR of 1.34 mL/min per unit (µIU/mL) TSH (∆eGFR). However, mean values of eGFR and TSH do not show any differences at single time points 1 year and 2 years post transplantation. Thus, the individual change of TSH values over time and its effect on eGFR is of particular significance. Our data indicate that even within the euthyroid range, decreasing thyroid function, as indicated by an increase in TSH within the reference range, is associated with decreasing transplant function, independently of age, gender, body mass index and thyroid hormone replacement therapy. We also included proteinuria as well as elevated tacrolimus levels, CRP values, arterial hypertension and diabetes mellitus as factors that may influence thyroid hormones and eGFR in our analysis. Of note, a high BUN/creatinine ratio in serum as sign of hypovolemia was associated with reduction of eGFR, but not with TSH values, which was tested in an interaction analysis. In the present study patients with subclinical or overt hypothyroidism were excluded, but data were not censored for the development of subclinical hypo- or hyperthyroidism within the observation period. In a subanalysis, only 14 subjects developed subclinical hypothyroidism within 12 months. These subjects with particularly high increase in TSH showed a clearly higher decrease in eGFR of 8.7% per unit (µIU/mL) increase of TSH, which supports our main study results, although eGFR decrease in the euthyroid study population was lower. Although this finding is not significant due the limited number of patients affected, it supports our basic hypothesis. Forty-eight subjects who were euthyroid due to THRT were excluded in a subanalysis and statistical results remained virtually unchanged after exclusion of these patients in the multivariate analysis. Our study results showed no association between T3, FT4 and T4 and eGFR, neither at individual time points 12 and 24 months post KTx nor over time.Since TSH levels seem to be associated with eGFR and CKD11. To further verify a causal association between thyroid function parameters and eGFR in kidney transplant CKD patients, prospective randomized placebo-controlled trials are underway to investigate whether thyroid hormone replacement therapy targeting low-normal TSH levels can enhance eGFR.The main limitation of this study is the retrospective design. Furthermore, follow-up was limited to 2 years after transplantation. However, our study was strengthened by a large sample size of 398 subjects and a well-characterized cohort of euthyroid CKD patients in the early post-transplantation phase, which led to clear results: the cross-sectional analysis of individual thyroid and renal function parameters at selected times 12 and 24 months after KTx showed no association. However, the assessment of the changes in TSH and eGFR during the second year after transplantation showed a significant dependence between thyroid and transplanted kidney functions: as TSH levels increase over time, eGFR tends to decrease. These results are consistent with previous data demonstrating a decrease in eGFR by 1.9% for each 1 µIU/mL increase in TSHSupplementary Information.


Background: Non-steroidal anti-inflammatory drugs (NSAIDs)-exacerbated respiratory disease (N-ERD) complicates the clinical course of chronic rhinosinusitis with nasal polyps (CRSwNP) and severe asthma. We aimed to determine the detection rate of NERD in patients with CRSwNP, asthma, and history of NSAID intolerance using nasal challenge with acetylsalicylic acid (ASA) and the relationship between the severities of response to ASA challenges and the grade of N-ERD. Materials and methods: Three groups of patients were included: CRSwNP with asthma and clinical history of analgesics intolerance (CRSwNP-AAI n = 18), CRSwNP with asthma but without a clinical history of analgesics intolerance (CRSwNP-A n = 20), and CRSwNP without asthma or analgesics intolerance (n = 18). All subjects were challenged nasally with 16 mg ASA and monitored with active anterior rhinomanometry. Rhinological , pulmonary , and asthma treatment), and psychometric questionnaire scores were recorded and correlated with rhinomanometric data following nasal challenges (flow depressions and symptom scores). Results: Nasal ASA challenge detected N-ERD in 96.7% of CRSwNP-AAI patients and 45% of CRSwNP-A patients. No N-ERD was seen in the CRSwNP group. The control grade of asthma measured with ACT scores was significantly lower in the groups CRSwNP-AAI (MV 18.22) and CRSwNP-A (MV 19.75) when compared to the CRSwNP group (MV 24.39) (p = 0.000). In the CRSwNP-AAI group, 11 patients had uncontrolled asthma (61%), and in the CRSwNP-A group, 9 patients had uncontrolled asthma (45%). No correlation was found between rhinology and pulmonary parameters, nasal symptoms, and the severity of nasal ASA challenges. Specific reactions were detectable under the therapy of prednisolone and omalizumab. Conclusion: N-ERD might not always be detected by screening a patient’s medical history. Nasal ASA challenges are recommended in patients with CRSwNP and asthma. The nasal challenge with ASA positively confirms the N-ERD diagnosis. Moreover, N-ERD is a differential diagnosis in patients with severe asthma with the need for prednisolone or omalizumab therapy. The severity of the reaction to the ASA challenge in controlled and uncontrolled asthma patients is independent of the grade of N-ERD. Patients with CRSwNP and N-ERD frequently undergo nasal surgeries . FurtherInflammatory endotypes of chronic rhinosinusitis have recently been described by Tomassen et al.  based onFor the clinical assessment of NSAIDs hypersensitivity, challenge with ASA via either oral, nasal, or bronchial routes are used. Recommendations for the oral, nasal, and bronchial ASA challenge procedures have been recently published in the European EAACI/GA2LEN guidelines . The guiTo date, little is known about the association between the grade of N-ERD and the severity of the reaction to nasal ASA challenge (a rhinomanometric measurement of flow depression and symptom scores). If the results of the nasal challenge are negative, then oral tests are recommended. However, due to possible adverse reactions, oral and bronchial ASA challenges require hospital admission, whereas the nasal ASA provocation is relatively safe and can be performed in an outpatient department. The EU guidelines recommend using nasal ASA challenges in patients with severe asthma, but to date, there is a lack of systematic studies regarding this topic , 12. OurThe patients admitted to the ENT department were included in the study between 2014 and 2015 upon signing written consent. This prospective study strictly followed the declaration of Helsinki and obtained the permission of the local Ethics Committee. Patients with CRS and nasal polyps as defined by EPOS criteria   and withFollowing inclusion criteria were appliedCRSwNP-AAI: chronic rhinosinusitis with nasal polyps, asthma, history of analgesics intolerance with respiratory symptoms ;CRSwNP-A: chronic rhinosinusitis with nasal polyps, asthma, no history of analgesics intolerance;CRSwNP: patients with CRSwNP, no asthma, no history of analgesics intolerance.General exclusion criteriaAge under 18 years, acute rhinosinusitis or asthma exacerbation, bilateral CRSwNP with total obstruction of the nose.PatientsCRSwNP-AAI: 18 patients, 6 men, 12 women, age mean value (MV) 46.6 years; standard deviation (SD) 15.0;CRSwNP-A: 20 patients, 9 men, 11 women, age (MV) 50.3 years; SD 11.2;CRSwNP: 18 persons, 13 men, 5 women, age (MV) 42.4 years; SD 14.5;ASA intakeCRSwNP-A: no ASA intake in 11 patients (55%), no intolerance reactions in 9 patients despite ASA intake (45%);CRSwNP: no ASA intake in 10 patients (56%), no intolerance reactions in 8 patients despite ASA intake (44%).Parameters evaluatedRhinological parametersThe number of nasal sinus surgeries was noted as a score. The nasal polyps were evaluated using the Davos endoscopy score , and thePulmonary parametersSpirometry was performed with forced expiratory volume 1 (FEV1). Asthma was assessed using the Asthma Control Test (ACT). A score of 25 – 20 points indicated controlled asthma, whereas a score < 20 indicated uncontrolled asthma. Additionally, the severity of asthma was assessed based on current asthma medication, according to the criteria of the Global Initiative for Asthma (GINA) .Questionnaires of CRS symptoms and general quality of lifeThe severity of CRS symptoms such as nasal obstruction, anterior/posterior rhinorrhea, olfactory impairment, and facial pain were scored using a visual analog scale (VAS) . The genRestriction time of medical drugs before ASA challengeRestriction time for nasal α-adrenergic drugs was 24 hours and for antihistamines 3 days. Before the nasal challenge, montelukast was postponed for at least 1 week, omalizumab for 4 weeks, whereas prednisolone  was left unaltered to maintain asthma control.Nasal challenge3/s) was measured on both sides, and the wider side was used for the challenge.The nasal challenge was performed according to the German guidelines . The nasFirst, 80 µL placebo  was applied to the inferior lateral nasal mucosa of the test side. Next, 80 µL of lysine-aspirin solution  containing 16 mg of ASA was applied to the test side. After the ASA application, flow depressions were examined, and symptoms were measured every 10 minutes for a maximum of 3 hours, or until the response occurred. The symptoms were scored semi-quantitatively in agreement with the German guidelines  [16]. N-StatisticsThe Mann-Whitney U test and the Spearman’s rank correlation (p < 0.05) were used. The significance level was set to p < 0.05.In the CRSwNP-AAI group of patients with a previous clinical history of analgesics intolerance, 17 of 18 patients reacted positively to the nasal ASA challenge (94.4%). In the CRSwNP-A group of patients without a clinical history of analgesics intolerance, 9 (45.0%) patients had a positive reaction. In the CRSwNP group, there were no positive reactions.CRSwNP-AAI patients had significantly greater flow depression (MV –47.6% (–7.9 to –100%))  and the Following the nasal ASA challenge, 4 (22.2%) of the CRSwNP-AAI patients developed mild pulmonary symptoms. Following inhalation with salbutamol, the side effects disappeared rapidly. In addition, 2 of these patients received 250 mg prednisolone intravenously.One patient developed conjunctivitis, and 1 patient erythema on the face, but no treatment was necessary in these cases.The CRSwNP-AAI group had significantly more nasal polyps (MV 1.72) than the CRSwNP group , but there were no significant differences when compared to the number of nasal polyps in the CRSwNP-A group (MV 1.25) . The CRSCRSwNP-AAI patients (MV 70.50) had significantly higher VAS scores indicating the severity of disease as compared to the CRSwNP patients . Furthermore, the CRSwNP-A group had higher VAS scores indicating the severity of disease (MV 70.90) and smell impairment (MV 73.15) than the CRSwNP group , but not the CRSwNP-AAI group. The general quality of life  measured by the SF-36 questionnaire indicated a worse quality of life in the CRSwNP-AAI patients (MV 37.58) as compared to the CRSwNP patients  .To determine the possible correlation between the severity of nasal ASA challenge and the grade of disease, “flow depression” and “symptom scores” of nasal challenges were computed with the following parameters:agenasal polyp score, number of nasal sinus surgeries, olfactory testpulmonary parameters scores obtained from VAS and SF-36.The correlations were performed in two groups. The first group consisted of patients with positive nasal reactions after ASA provocation, and the second group consisted of the patients with adverse nasal responses. The only positive significant correlation was identified between the flow depression and the SF-36 score in patients with positive nasal reactions after ASA challenge.In this study, we determined the detection rate of N-ERD using nasal challenge with ASA in patients with CRSwNP, asthma, and uncertain or certain history of hypersensitive reaction to NSAIDs. In the case of an isolated CRSwNP without asthma, there is no recommendation for ASA provocation.Our important new finding is that the degree of rhinomanometric reactions induced by a nasal ASA challenge does not depend on the severity of the disease. Lastly, we demonstrate that patients with uncontrolled asthma can be nasally challenged with ASA, which agrees with only a few existing studies on that topic , 12.The procedure of nasal provocation test using 16 mg of ASA in the present study confirmed N-ERD diagnosis in 94.4% of patients with CRSwNP, asthma, and suspected ASA hypersensitivity-specific reactions. In contrast, other studies report a sensitivity of 38 – 87% during similar testing , 18. OurSzczeklik et al.  performeMiller et al.  obtainedNizankowsla-Mogilnicka et al.  recommenWe observed mild pulmonary reactions affecting 22.2% of the patients with CRSwNP-AAI . This frequency is similar to that described earlier, ranging between 12.5 and 21% [Nasal ASA challenges were also carried out by other research groups in patients with severe asthma, but there was no systematic investigation of patients with severe asthma , 12. In Similarly, no significant differences in the FEV1 values between 20 ASA-intolerant and 14 ASA-tolerant asthma patients were previously found . This isIn contrast to severe asthma, the nasal polyp score observed in the present study was low, which may be due to the preselection of the patients with frequent pulmonary referrals to the university outpatient department.There were no significant differences regarding nasal symptoms measured by VAS, which is similar to our earlier data . The scoThe results of the present study suggest that the degree of flow depressions and symptom scores of nasal challenges do not depend on the severity of N-ERD in patients with controlled and uncontrolled asthma. Similarly to our findings, Vaidyanathan et al.  indicateNasal ASA provocations are useful in CRSwNP patients with asthma and without previously known analgesics intolerance, since the analgesics intoleranceis often not reported in medical history.Nasal ASA challenges effectively confirm the N-ERD diagnosis. Specific ASA reactions are also detectable under therapy with oral corticosteroids or omalizumab. The outcome of nasal ASA provocations is independent of rhinological, pulmonary parameters, or the severity of subjective patient complaints, which applies to both patients with controlled and uncontrolled asthma.None.UFR, AKT, JK, UL, AJS, and HO declare no conflict of interest.


Chronic kidney disease (CKD) is a global public health concern and diabetes is one of the main risk factors for its occurrence and progression. The aim of this research is to determine the prevalence of chronic kidney disease in a cross-sectional population of patients with type 2 diabetes in primary health centers in North West Bank.Patient data including patient characteristics, creatinine level, blood pressure, HbA1c, and hypertension and period of diabetes were obtained from primary health care centers. The eGFR has been determined using the CKD-EPI equation. CKD was staged according to the 2012 Kidney Disease Improving Global Outcomes Framework (KDIGO) guideline. Both univariable and multivariable statistical analysis was conducted using SPSS.The prevalence of chronic kidney disease among diabetic adults in North West Bank was found to be 23.6% (95% CI: 19.4–28.1%) divided as follows: 19.7% had stage 3 CKD, 2.6% had stage 4 CKD and 1.3% had stage 5 CKD. In multivariable logistic regression, CKD was significantly associated with Age ≥ 60 years , hypertension , and smoking .CKD is very prevalent among diabetic adults in Palestine. Co-morbid hypertension, smoking and older age has been shown to increase the risk of developing CKD. Extensive screening for diabetic patients to diagnose CKD at an early stage and to follow more aggressive treatment methods for diabetes as well as other important risk factors, especially hypertension and smoking, is recommended. Non-communicable diseases (NCDs), such as diabetes and kidney disease, are the leading cause of death and morbidity worldwide . DiabeteChronic DM hyperglycemia is known to be one of the main causes of Chronic Kidney Disease (CKD) in addition to hypertension. It is defined as renal structure or function abnormalities, present for > 3 months, with health implications. CKD is graded on the basis of origin, category GFR and category Albuminuria (CGA) .CKD is a major public health problem, both for its high cost of morbidity and treatment. The effects of CKD include not only progression to renal failure, but also decreased complications of renal function and increased risk of cardiovascular disease and overall mortality from all causes . Global Early diagnosis and proper management prevent or delay many complications of CKD. In addition, early detection of kidney disease can delay or avoid deterioration of kidney function through affordable interventions, some of which are on the WHO’s so-called best-buys list for non-communicable disease management .There is a shortage of data in the Middle East on the prevalence of CKD among diabetic patients. However, the prevalence of CKD among the general population was 6.8% in Jordan, 5.7% in Saudi Arabia  and 14.9Common risk factors, including increased duration of diabetes, hypertension, impaired metabolic control, smoking, obesity and hyperlipidemia, have been suggested to raise the risk of diabetic complications. Low blood pressure (BP) and glycemic control have been shown to cause more kidney damage and reduced renal function. Similarly, certain context variables have been shown to be positively linked to CKD, such as age, smoking, and BMI –15.In 2008, a study of diabetic hypertensive patients in North West Bank reported that 35.5% of patients with DM and HTN had decreased renal function, which is significantly correlated with age, duration of DM and number of chronic diseases .GFR is the best indicator of kidney function, taking into account age, race and sex. The two most popular methods for calculating GFR are currently creatinine clearance and the approximate GFR (eGFR) . FormulaThe identification of risk factors for deterioration of renal function is important for the development of preventive measures for the management of diabetic patients and for the prevention of their complications. The objective of this study is to estimate the prevalence of CKD among Palestinian diabetic patients and to determine the associated risk factors.This is a cross-sectional study of Palestinian diabetic adult patients in the West Bank. In Palestine, all patients diagnosed with DM are referred to the Primary Health Care (PHC) directorates in their cities, where they receive diabetes care, treatment and follow-up on a regular basis. Patients with T2DM and > 18 years of age were included in the study. However, type 1 diabetes mellitus, gestational diabetes mellitus, pregnant women and patients who did not have at least 2 serum creatinine readings of at least 3 months apart were excluded from the study.2 * expected CKD prevalence * / (margin of error)2] [The following sample size formula was used to calculate the sample size [Necessary Sample Size = Zerror)2] . A samplSerial serum creatinine data was obtained and eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration formula based on serum creatinine (CKD-EPICr). CKD was described as having reduced eGFR (< 60 ml / min per 1.73 m2) for 3 months. The CKD stage was specified in accordance with the National Kidney Foundation Guideline , in whicThe prevalence of CKD was determined using the National Kidney Foundation Kidney Disease Outcomes Quality Initiative Classification of CKD based on eGFR alone. Albuminuria indicates stage 1 and stage 2 CKD, however, was absent in most enrolled patients and was therefore not considered to assess the level of CKD.Participants were deemed diabetics if they had already been diagnosed with T2DM or were taking insulin or oral hypoglycemic agents. Patients were described as hypertensive if they were previously diagnosed with hypertension (HTN) or antihypertensive drugs. Obesity has been classified as BMI ≥ 30.Blood pressure readings have been obtained by a qualified nurse using an electronic sphygmomanometer. The height and weight were taken at the time of the interview and used to measure the BMI. Creatinine readings were collected from medical records using at least 2 readings of at least 3 months apart and the CKD-Epi formula was used to measure eGFR. Patients with eGFR < 60 mL/min/1.73 m2 in two consecutive occasions at least 3 months apart were considered to have CKD. The last available of HbA1c reading was used.All subjects involved in the study were invited to participate on a voluntary basis after the research purpose, risk and advantage of participation were clarified. We have maintained the privacy and confidentiality of those who have agreed to participate and have been asked to sign informed consent. The approval of the Al-Najah National University Institutional Review Board (IRB), the Scientific Committee and the Palestinian Ministry of Health was received.p value of < 0.05. Additionally, Multivariable logistic regression was performed to estimate the unique relationship between the included variables and CKD status. Variable included in the model were selected based on prior knowledge of the field [Statistical analysis was performed using version 20 of the SPSS. Categorical data were expressed as number (percentage) and continuous data as means ± standard deviation (SD) or median and range, as applicable. Differences in patient’s characteristics and risk factors for CKD were analyzed using the chi-square test and unpaired student’s t-test (two-tailed), as necessary. Statistical significance is taken at a he field . The linThe study recruited 386 T2DM patients from PHC clinics in North West Bank. Almost half of the participants were male (49.7%) and their average age was 60.6 ± 10.4 years. HTN was reported in 278 (75.3%) participants, with an average period of 6.78 ± 7.7 years. The mean duration of diabetes was 12.4 years (3.9 years to 20.9 years) and the HbA1c level ranged from 6.39 to 10.47% with an average of 8.4% ± 2.0. The majority of participants were obese and 30.4% were smokers. Table Using the CKD-EPI equation, the eGFR mean (±SD) for all participants was 75.3 ± 24. Estimated GFR ≥60 ml/min/1.73 m2 was reported among 295 (76.4%) diabetes patients. CKD Stages 3, 4, and 5 were present in 19.7, 2.6, and 1.3% of the participants, respectively. In total, the prevalence of CKD among T2DM patients was 23.6% (95% CI: 19.4–28.1%)   Table .Table 2Post-hoc analysis was performed to examine differences between classes. The ages were significantly different between stage 1 and stage 2, stage 1 and stage 3, stage 1 and stage 4, and stage 2 and stage 3. For systolic BP, the difference between stage 1 and stage 2 and stage 1 and stage 4 was significant. The duration of hypertension was substantially different between stage 1 and stage 3. The duration of the DM was significantly different between stage 1 and stage 2, stage 1 and stage 3 and stage 1 and stage 2. 5.p < 0.001), smoking (p = 0.022), age (p < 0.001), and length of DM (p < 0.001). On the other hand, there was no significant relationship between HbA1c and BMI and CKD (Table P < 0.001 for both).Unvariable analysis was performed to investigate the factors associated with the development of CKD. The findings showed that CKD is significantly associated with HTN , HTN  and smoking  are found to increase the odds of CKD  of diabetic patients in the North West Bank have CKD. Sweileh et al. reported a prevalence of 35.5% of CKD in Palestine in 2008 . This reResults on the prevalence of CKD among diabetic patients are variable; like Finland (16.2%) , SoutherIn order to improve preventive and control measures, it is important to identify the risk factors associated with CKD, in particular the modifiable factors. The prevalence rate of HTN identified in this study among patients with type 2 diabetes (75%) was high. This is more than recorded in neighboring countries; Jordan (72.4%) , Qatar  between BP and kidney damage, represented by decreased eGFR as systolic BP increases . The correlation between smoking and the occurrence of CKD in diabetic patients is clearer, with most research showing a substantial relationship between these two variables. Recently, two meta-analyses indicated evidence of cigarette smoking as an independent risk factor for CKD [Almost one-third of the patients (30.4%) were smokers; with a higher proportion of them among the CKD group (39.6%). In this study, smoking was correlated with renal function progression  for CKD. The overall high prevalence of CKD among elderly people can be explained by the steady decline in GFR with normal ageing, in addition to the high rate of comorbidities among this population, particularly hypertension and diabetes [Age was found to be a significant risk factor (diabetes . It is a2 (±5.8) without a significant correlation with the renal function . However, obesity is a main contributor to hypertension and diabetes [The average BMI of diabetic patients, in this study, was 32.5 kg/mdiabetes . These tdiabetes –33. On tP value = 0.527). Growing evidence suggests that there is a correlation between the glycemic control status and renal damage. There are contradictory details on this relationship. A research in Spain showed that HbA1c levels were significantly higher among CKD diabetic patients  [HbA1c is a recommended standard of care for the monitoring of diabetes. In this study, the mean HbA1c was 8.31%, but it was not significant to the presence of CKD (< 0.001) . However< 0.001) . This is< 0.001) . Other rP = 0.384). The relationship between gender and CKD among diabetic patients is inconsistent in the literature. Many studies have shown female gender as a risk factor [There was no correlation between gender and CKD in this study  of CKD among diabetic patients in Palestine. The rate is higher among hypertensive patients and increases with age. Intensive screening for diabetic patients is recommended for early detection of CKD and for more aggressive treatment of diabetes, as well as other important risk factors, especially HTN and smoking. We also recommend studying the effect of anti-diabetic and anti-hypertensive medications on the rate of renal function deterioration, as well as evaluating the mortality rate and progression to ESRD and dialysis in each eGFR category.