In sub-Saharan Africa, the prevalence of hypertension has assumed epidemic levels and currently accounts for numerous complications such as stroke, heart failure, and kidney damage. Management of hypertension involves both drug and nonpharmacological approaches. Self-monitoring of blood pressure is an important nonpharmacological approach that facilitates early detection of deteriorating blood pressures and complications.  We determined the practice and sociodemographic factors influencing self-monitoring of blood pressure among Ghanaians with hypertension. t-test analysis were done to determine the relationship between the practice of self-monitioring and other sociodemographic variables. Data analayses were conducted at a significant level  and power of 95% confidence. Thus, p < 0.05 was considered statistically significant.  In a cross-sectional design, we recruited four hundred and forty-seven (447) Ghanaians with hypertension receiving care at the hypertensive Outpatient Department (OPD) Clinics of the Medical Department at the Korle-Bu Teaching Hospital (KBTH). The respondents were sampled using a simple random sampling technique of balloting without replacement. A structured questionnaire was used to gather data on the practice of self-monitoring of blood pressure and sociodemographic factors influencing self-monitoring in the respondents. We also measured some anthropometric and haemodynamic indices of the respondents. The data was entered in Microsoft Excel 2010 and exported into SPSS 21.0 to aid with the data analysis. A chi-square test and Student's  The practice of self-monitoring of blood pressure was 25.3% with more female respondents claiming to practice self-monitoring as compared to their male counterparts (28.6% vs. 20.7%). Awareness of self-monitoring of blood pressure was associated with increased practice of self-monitoring of blood pressure. Health workers (46.8%), colleague patients (39.8%), relatives/spouses (6.7%), and the media (6.7%) were identified as the sources of information about self-monitoring of blood pressure. Awareness of self-monitoring, level of education, valid health insurance, occupation, income levels, and marital status had a significant relationship with self-monitoring of blood pressure among the respondents. Thus, respondents with higher education, awareness of self-monitoring, valid health insurance, formal employment, and higher income were likely to monitor their blood pressure.  Several sociodemographic factors influence the practice of self-monitoring of blood pressure in Ghanaians with hypertension. Thus, targeted hypertension education and social-cognitive interventions should focus on these sociodemographic factors so as to improve self-monitoring of blood pressure in order to reduce the complications of hypertension. Hypertension, also known as high blood pressure (BP), is now a global public health problem associated with serious health complications . HyperteThe current management of hypertension involves pharmacological and nonpharmacological strategies , 5. The Proper management of hypertension requires adherence to management by patients as well as self-monitoring of blood pressure . Self-moWe determined the practice and sociodemographic factors influencing self-monitoring of blood pressure among Ghanaians with hypertension. In Ghana, complications and mortalities associated with hypertension are still high despite the marked improvement in care . Self-moIn this study, we employed a descriptive cross-sectional design. Ghanaians with hypertension receiving care at the Hypertensive Clinic of the Outpatient Department (OPD) of the Medical Department of the Korle-Bu Teaching Hospital (KBTH) were sampled. The philosophical underpinning of the study was the positivist strategy. In adopting the positivist approach to research, which is quantitative, the researcher embarks on the study of the reality by maintaining a distance between him/her and the researcher . ContrarThe study was conducted at the Korle-Bu Teaching Hospital (KBTH), a resource-constrained health facility in Ghana where there is consistent shortage of staff coupled with increasing patient numbers . Thus, eThe sample size for the study was determined using the Cochran formula for determining the sample size . Thus, tWe included male and female hypertensive patients visiting the Hypertensive OPD Clinics of the Medical Department at the KBTH for review post discharge. The inclusion criteria for the selection of the study respondents included Ghanaian hypertensive patients between the ages of 35-65 years, a history of previous admission with hypertension, and being well oriented to time and place with no signs of mental illness.A simple random sampling technique of balloting without replacement was done using the patients' folders at the Hypertensive OPD Clinics of the Medical Department usually in the morning during waiting time. The patients' folders were numbered, and the corresponding numbers were written on small pieces of paper. The small pieces of paper with the numbers were then placed in a covered container and shaken thoroughly after which thirty (30) papers with corresponding numbers representing patients' folders were selected without replacement. The consent of those selected was obtained, and if they refused to consent, they were replaced by picking other small pieces of paper with the numbers corresponding to specific folders of patients until a total of thirty respondents were selected. The data collection was done on Fridays during a period of fifteen weeks  excluding public holidays.A pretested questionnaire was used as the data collection tool. Prior to the data collection, the questionnaire was pretested among hypertensive patients at the Polyclinic of the KBTH. The questionnaire contained sections which asked about the sociodemographic characteristics such as age of respondents, sex of respondents, highest educational level, marital status, occupation, income level, having a valid health insurance, awareness of normal blood pressure, and self-monitoring, as well as the practice of self-monitoring of blood pressure. The data was entered into Microsoft Excel 2010. The data was then exported into the Statistical Package for Social Sciences (SPSS) version 21.0 to aid with the analysis.χ2 test particularly for the dichotomous variables while using Student's t-test for a continuous variable (age). In determining the association between self-reported practice of self-monitoring of blood pressure and the sociodemographic variables, we used Pearson's χ2. In this study, p < 0.05 was considered statistically significant.We analyzed the data using the Statistical Package for Social Sciences (SPSS) version 21.0. During the analysis, we did a gender comparison of sociodemographic variables using Pearson's The study data was part of data collected on a protocol titled: Adherence to Management and Quality of Life of Ghanaian Hypertensive on a Structured Health Education Programme (SHEP) approved by the Scientific and Technical Committee and the Institutional Review Board of the Korle-Bu Teaching Hospital (protocol identification number KBTH-IRB/0004/2018). We obtained permission from the Deputy Director of Nursing Service of the Central Outpatient Department prior to data collection. Also, we explained the purpose of the study to each respondent before obtaining written informed consent for the study. Further, we ensured confidentiality of the data collected by assigning unique codes to each response. We also maintained privacy and ensured anonymity throughout the data collection and analysis of the data.A total of four hundred and forty-seven (447) respondents took part in the study. As depicted in The majority (59.3%) of the respondents said they were aware of their normal blood pressure even though most of them could not state the said normal blood pressure. Only, 194 (43.4%) of the respondents said they were aware of self-monitoring of blood pressure with majority claiming not to be aware of self-monitoring. On the sources of information about self-monitoring of blood pressure, 90 (46.4%) claimed health workers, 76 (39.2%) cited colleague patients with only 10 (5.7%), and 18 (9.3%) cited spouses and media houses as sources of self-monitoring information .The practice of self-monitoring of blood pressure in the respondents was 25.3%. Awareness of self-monitoring of blood pressure was associated with the practice of self-motoring. The study revealed that higher educational qualification was associated with practice of self-monitoring of blood pressure. Respondents with formal employment were likely to self-monitor their blood pressure as compared to their counterparts. Also, having a valid health insurance was associated with the practice of self-monitoring. Further, a high income level was associated with self-monitoring of blood pressure. The results revealed that respondents who were single did more self-monitoring of their blood pressure as compared to married, widowed, and divorced counterparts .The results as shown above indicate that the majority of hypertensive patients who seek care at the KBTH were females. Most of the respondents had low or no formal education with the majority under the low income brackets. The results indicate that the awareness of self-monitoring as well as the practice of self-monitoring of blood pressure was low even though awareness of normal blood pressure was reportedly high. The practice of self-monitoring of blood pressure was low and was associated with awareness of self-monitoring, educational level, valid health insurance, income level, and marital status.A total of 447 respondents were involved in the study, and the majority of the respondents were females indicating that more females sought health care rather than males. This finding is in line with the study done by , 15 who On the source of information about self-monitoring, health workers served as the main source of information. The media and relatives/spouses as a medium for information on self-monitoring were minimal. This result is in line with the study conducted by , 17. AlsAlso, the critical potential of family/spousal support in self-monitoring was found to be low as few of the respondents claimed their family members/spouses helped them with self-monitoring of their blood pressure or even made them aware of it. This finding is in contrast to the findings of –21 who oIn our study, we found that the educational level of the respondents was found to be a significant determinant of practice of self-monitoring of blood pressure. The practice of self-monitoring increased marginally with the rising level of education among the respondents. Similar findings have been reported in other studies , 20 wherThe study found that the practice of self-monitoring of blood pressure increased with increasing self-reported income levels of respondents. Just as found in this study, other studies –18 reporThe study further found that those who had valid health insurance cards practiced self-monitoring of blood pressure as compared to their counterparts without valid health insurance. It is possible that those with valid health insurance were more likely to be regular in their clinic visitation; hence, they became aware of self-monitoring because it was taught at the OPD by nurses and doctors as compared to their counterparts without valid health insurance. Also, having valid health insurance could reduce the cost of the patient procuring their medications and hence providing alternative income to buy blood pressure devices for self-monitoring. According to , 17, resThe study used a cross-sectional design making it difficult to infer causation. Also, since the study depended on a pretested questionnaire which largely depended on the respondents' responses and recall, there is high possibility of recall bias. Further, income levels are usually associated with some social status in society; hence, some of the respondents could claim to be in the high social brackets when actually they are not and vice versa.


Our aim was to investigate factors predicting blood pressure (BP) variability during diagnostic cerebral angiography and associations between BP variability and clinical outcomes in patients with acute and subacute ischemic stroke and intracranial artery stenosis. 114 patients with ischemic stroke and intracranial artery stenosis (stenosis rate >50%) were recruited. Patients who underwent cerebral angiography within 3 days and 3–14 days of disease onset are referred to be Group A and Group S, respectively. BP variability in Group A was defined as the coefficient of variance (CV) of BP. Univariate and multivariate regression analyses were used to identify predictors of CV of BP and associations between CV of BP and clinical outcomes at discharge. In Group A patients, advanced age was associated with increased CV of SBP and diastolic blood pressure (DBP), and antihypertensive use was associated with lower CV of SBP. Male was associated with lower CV of DBP. In Group S, higher CV of SBP was associated with hypertension and antihypertensive use. Males had lower CV of SBP than females. The calcium channel blocker was associated with lower CV of DBP. Higher scores of the Stroke Scale at admission were significantly associated with poor clinical outcomes for both groups, while BP variability was not. Factors associated with BP variability are significantly different between stroke patients undergoing angiography within 3 days vs. 3–14 days after disease onset. BP variability is not significantly associated with clinical outcomes at discharge. Blood pressure (BP) variability and instability, including visit-to-visit BP variability, night-time BP variability, nocturnal hypertension, and stress-related hypertension (white-coat hypertension), are reported to be associated with adverse cardiovascular events and poor clinical outcomes –6. BP vaDiagnosis and treatment of patients with acute stroke have become increasingly reliant on interventional procedures. The standard of care for acute ischemic stroke includes intravenous thrombolysis and endovascular thrombectomy, both of which have resulted in good outcomes when treatment was initiated in a timely manner . We haveIn a cohort of acute ischemic stroke, patients with ipsilateral internal carotid artery (ICA) occlusion BP variability, assessed in the acute phase, were associated with poor clinical outcome. These preliminary exploratory findings are worthy of further study to be conducted to confirm or confute the role of BP variability in predicting stroke outcome. In order to obtain more comprehensive information, it would also be appropriate to consider the possibility of acquiring data related to the pathophysiology of stroke and to cerebral hemodynamic changes . TherefoThis prospective observational study recruited a total of 114 patients with acute and subacute ischemic stroke and intracranial artery stenosis (stenosis rate >50%) who received catheter cerebral angiography within two weeks of onset between March 2012 and November 2015. Patients were divided into two groups on the basis of the timing of cerebral angiography in relation to disease onset, as follows: patients who underwent cerebral angiography within 3 days of disease onset (Group A) and patients who underwent cerebral angiography 3–14 days after disease onset (Group S). Indications for angiogram included acute thrombectomy, further confirming diagnosis of intracranial artery stenosis. Cerebral angiography was performed under local anesthesia and with electrocardiographic monitoring. Patients who received general anesthesia during the procedure were excluded.∗ 100%.BP was recorded (1) upon admission, (2) immediately after entering the room in which the procedure would be performed (angio-room), (3) immediately before the procedure, and (4) every 15 min after the start of the procedure, using an upper arm cuff sphygmomanometer. Variability  of BP during the procedure was calculated using the formula: variability of BP during procedure = (standard deviation/average) Patients were placed in a supine position and received focal anesthesia (1% lidocaine) in the groin. The right femoral artery was punctured . Whole cerebral angiography was performed with the 5F catheter using an isotonic nonionic iodine contrast agent. The contrast was diluted with normal saline at a ratio of 2 : 1 in order to reduce the stimulation to the blood vessel and the nervous system. During the procedure, heparin  was infused via a Y valve through the catheter. After angiography, an endovascular suture device  was used for femoral artery wound closure. The wound was then compressed with an elastic bandage for further hemostasis.p < 0.05 in the univariable model were then used to perform multivariable model analysis. For clinical outcome at discharge, results were represented as odds ratio (OR) with corresponding 95% confidence intervals (95% CI) for logistic regression analysis; for CV of preoperative SBP and DBP, results were represented as β (regression coefficient) with corresponding 95% CI for linear model analysis. When only one factor with p < 0.05 was found for an outcome in univariate analysis, multivariable analysis was not performed. All statistical assessments were two-tailed, and p values <0.05 were considered statistically significant. Statistical analyses were performed using SAS® 9.4 .Demographics and clinical characteristics are presented as mean ± standard deviation (SD) or median  for numerical variables and frequency (%) for categorical variables. Simple linear regression analysis was performed to identify the effectors  of coefficient of variation (CV) of preoperative SBP and diastolic blood pressure (DBP). Variables with significance level of The present study recruited a total of 114 patients, including 33 patients in Group A who underwent cerebral angiography within 3 days of disease onset and 81 patients in Group S who underwent cerebral angiography between 3 and 14 days after disease onset. Patient demographic and clinical characteristics at admission, medical history, medication history, and preoperative characteristics are summarized in Results for effectors of CV in SBP and DBP during the angiography procedure are shown in Tables β = 0.02, 95% CI = [−0.01 to 0.05]) and DBP  in Group A patients. The use of CCBs was associated with lower CV of SBP  in this group, and anterior circulation of intracranial artery stenosis was associated with CV of DBP   at the time of discharge are shown in This prospective study investigated the effectors of BP variability during cerebral angiography and explored associations between BP variability and clinical outcomes in patients with ischemic stroke based on whether they underwent cerebral angiography within 3 days (acute) of disease onset or 3–14 days (subacute) after disease onset. In patients with intracranial artery stenosis, BP variability could be the cause of cerebral hemodynamic abnormality which potentially leads to the ischemic stroke , 15. In Significant differences were shown between the two groups in initial characteristics at admission, BP variability, factors affecting BP and BP variability, and factors that affected patients' outcomes. However, BP variability did not affect patients' clinical outcomes at discharge, regardless of how soon after disease onset they underwent cerebral angiography.p < 0.05, multivariate adjusted model). The use of CCBs was associated with lower CV of SBP in group A. Intracranial artery stenosis within anterior circulation was shown to be associated with CV of DBP. It is indicated that arterial stenosis is related to the CV of DBP and is an independent factor.Results of the present study also showed that male gender was associated with a lower CV of DBP compared with females among Group A patients and was associated with a lower CV of SBP among Group S patients. Advanced age also was associated with increased CV of SBP and DBP. These findings agree with those of previous studies showing that sociodemographic factors such as older age and male gender were associated with higher variability in SBP , 17. In A previous systematic review of 22 studies suggested that blood pressure variability was affected by hypertension and the use of antihypertensive medications . In the Visit-to-visit SBP variability has been shown to be a predictor of long-term all-cause and cardiovascular mortality after lacunar infarct, independent of conventional risk factors, including average BP . PatientBP variability after intravenous thrombolysis in acute stroke was also reported to predict poor outcomes, although it did not increase risk for intracerebral hemorrhage . MoreoveNIHSS is extensively applied in assessing clinical outcomes in stroke patients. It has also been widely used to evaluate the measurement property and accuracy of NIHSS in predicting clinical outcomes; however, it is critiqued due to its complexity and variability. Higher NIHSS scores at the time of admission were significantly associated with poor clinical outcomes for patients in both groups, regardless of how soon after disease onset cerebral angiography was performed. These data are consistent with previous findings showing that NIHSS at admission is an independent predictor of in-hospital mortality .This study has a few limitations, including that this was a single-center study with a limited number of participants of the same ethnic origins. While observing the effects of factors predicting BP variability during diagnostic cerebral angiography, we did not explore effects or cerebral dynamics associated with the particular antihypertensive drug regimens on BP variability except to note whether they occurred or not in each study group. We also did not determine the possible impact of stroke severity on BP variability and how that may also affect functional outcomes.Factors associated with BP variability are significantly different between stroke patients undergoing cerebral angiography within 3 days vs. 3–14 days after disease onset. BP variability is not significantly associated with clinical outcomes at discharge. Having higher NIHSS scores at admission is associated with poor clinical outcomes regardless of the time of undergoing cerebral angiography after disease onset. Results of the present study may be useful in the clinical management of patients with acute ischemic stroke. Further studies are needed to determine the impact of BP variations on health outcomes and which factors may be more influential.


Objective: There is paucity of studies on the association between pulse pressure and the development of dementia, although this association has already been established. This study aimed at investigating the association between pulse pressure and the onset of dementia. Methods: We used the South Korean National Health Insurance Service claims cohort data to select 149,663 patients without dementia aged ≥60 years. We calculated adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for dementia using Cox proportional hazard models according to a pulse pressure classification . Results: Compared to women with pulse pressure <50, those with pulse pressures of 50–59, 60–69, and 90+ had higher HRs for dementia . These associations were particularly strong in those on Medicaid insurance and from rural regions. However, there were no statistically significant results among men. Conclusions: A higher pulse pressure was associated with an elevated risk of dementia in women aged >60 years, particularly those on Medicaid and from rural regions, possibly due to their inability to access hypertension and other medical treatment. The establishment of dementia indicators will help to guide future health policies for the prevention of dementia. Dementia is a major neuropsychiatric disorder, and is the fifth most common cause of death worldwide. Its prevalence has increased rapidly, leading to a high economic burden as a result of the growing social burden and costs related to the treatment to patients and their families . TherefoBlood pressure is known to be an important indicator for predicting cardiovascular disease . HoweverPrevious studies on hypertension have mainly focused on diastolic blood pressure in cognitive function and dementia and in the investigation of the relationship between a high blood pressure and the onset of dementia ,11,12. TWhile systolic and diastolic blood pressure have been reported as indicators of the onset of dementia in some studies, there are no consistent results regarding the relationship between pulse pressure and dementia ,16,17,18This study used data from the South Korean National Health Insurance Service-Health Screening Cohort (NHIS-HEALS) database. This dataset included information gathered on approximately 515,000 patients between 2002 and 2013 and represents a random sample of 10% of the patient cohort stratified according to age, sex, health insurance type, income level, individual total medical costs, and clinical test results. The data also included a list of diagnoses according to the International Classification of Diseases version 10 (ICD-10), medical costs claimed, prescribed drugs, and medical history .We conducted a cohort study using a random sample of national health insurance service claims data. We excluded patients diagnosed with dementia between 2002 and 2003. We also excluded patients with missing values for the covariates. From the 2004 to 2010 claims data, we selected patients without preonset of dementia who were aged ≥60. This resulted in a cohort of 149,663 patients. The onset of dementia was defined by the ICD-10 codes G30, G31.1, G31.9, G31.8, F00, F03, and F05.1. Blood pressure was measured using an automated sphygmomanometer during routine health screenings conducted every two years as part of a national health screening program. Pulse pressure was defined as follows: systolic blood pressure–diastolic blood pressure. This information was obtained from the NHIS-HEALS database. Pulse pressures were classified into six groups, namely, ≤50, 50–59, 60–69, 70–79, 80–89, and ≥90. Demographics and socioeconomic factors such as age, household income, and type of insurance were obtained from the NHIS-HEALS database. Patients were stratified into three groups based on their age as 60–69, 70–79, and ≥80 years. Patients were further stratified into quintiles based on their household income. In Korea, health care contributions are calculated according to household income. Patients who paid 0% of health insurance premiums were classified as Medicaid, those who paid up to 20% were classified as low income, those who paid 21–80% were classified as middle income, and those who paid over 80% of the premium were classified as high income. We used the Charlson comorbidity index (CCI) to measure comorbid conditions. The CCI assesses 19 diseases: myocardial infarction, congestive heart failure, peripheral vascular disease, cerebrovascular disease, dementia, chronic pulmonary disease, rheumatic disease, peptic ulcer disease, mild liver disease, diabetes without chronic complication, diabetes with chronic complication, hemiplegia or paraplegia, renal disease, any malignancy , moderate or severe liver disease, metastatic solid tumor, and AIDS/HIV. The CCI was calculated 1 year before patients were enrolled in the study . The durhttps://www.R-project.org/). Statistical significance was set at p < 0.05.We used descriptive statistics for the baseline characteristics of the study population. Differences between groups were determined using a chi-square test, t-test, and analysis of variance. Cumulative rates and incidence curves were constructed and compared using the Gray’s test for equality of cumulative incidence functions. Thereafter, we estimated the adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for dementia by applying a Cox proportional hazard regression analysis according to sex. In this model, we adjusted for systolic and diastolic blood pressure; age; region; household income; type of insurance body mass index (BMI); disability status; charlson comorbidity index (CCI); duration of treatment for hypertension, diabetes mellitus, dyslipidemia, and hyperglycemia; hospital classification; and year. Lastly, we conducted a subgroup analysis according to the type of insurance and region. All statistical analyses were conducted with SAS version 9.4  and R version 3.6 with package “cmprsk” (R Core Team (2018). R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. URL: n = 51,303), 27.7% , and 2.6% (n = 1918) in men, 67.3% , 29.8% , 2.9% (n = 2178) in women respectively.p = 0.01) and women (p < 0.0001).This study examined the association between pulse pressure and the onset of dementia among men and women. After controlling for several covariates, elderly women with a high pulse pressure were shown to have a significantly higher rate of onset of dementia than those with a low pulse pressure. Moreover, these associations were strong among women in the Medicaid group who lived in rural areas. The results from this study showed that high pulse pressure levels were associated with the risk of developing dementia. These results are similar to those from previous studies that reported the association between an elevated pulse pressure and decreased cognitive function in community members aged 55–64 years using data from the Framingham Offspring Cohort Study conducted to identify risk factors for cardiovascular disease during the 1998–2009 period . In addiAnother possibility is that pulse pressure has a high positive correlation with plasma B-type natriuretic peptide (BNP), and high BNP levels have a high correlation with microvascular damage. Therefore, damage and disease in the microvessels of the cerebrum cause the denaturation of blood vessels. These negative changes in the blood vessels destroy the function of the blood–brain barrier, thereby increasing the accumulation of β-amyloid due to increased permeability and protein runoff in the cerebral cortex ,31,32,33In contrast, atherosclerosis, a vascular disease, of the blood vessels leads to a rise in the blood pressure. Vascular rigidity and atherosclerosis increase the risk of dementia, indicating that vascular diseases impose a similar risk as cardiovascular disease ,35,36. IIn this study, the association between a high pulse pressure and the high risk of developing dementia was evident only in women. This observation was similar to that of previous studies conducted in elderly ,45. One Our study had several limitations. First, because the follow-up period from the medical examination to the onset of dementia took place over a 10-year-period, it is possible that we under- or over- estimated the link between the measurement of blood pressure and fasting blood glucose depending on the time of the examination or the current health condition of the patient. In addition, we could not include patients who did not undergo blood pressure testing or a health check-up every 2 years. However, blood pressure was measured at a clinical laboratory; therefore, the measurements were reliable. Second, although we used the ICD-10 codes for the diagnosis of dementia, this might have been overestimated due to up-coding errors or misclassification biases associated with the claims data. Therefore, the results should be interpreted with caution. Finally, there is an added potential for the overestimation or undervaluation of statistical results due to unadjusted confounding factors.Although our findings need further confirmation, we believe that there is an association between pulse pressure and the incidence of dementia. A higher pulse blood pressure is associated with an elevated risk of dementia in individuals aged >60 years, but only in women. Furthermore, the results from the subgroup analysis revealed that elderly women with Medicaid living in rural areas should be targeted so that interventions aimed at preventing dementia can be implemented among this population.


To investigate the predictive factors associated with rapid progressive chronic kidney disease (CKD) in patients with primary glomerular disease (PGD).  Baseline data, clinical biochemistry, laboratory data, and imaging data were collected from 112 PGD patients in CKD stages 3 and 4 who were hospitalized at the Third Xiangya Hospital. Patients were divided into rapid progression group (Group R) and no rapid progression group (NR) according to the definition of rapid progression of CKD. β2-microglobulin (sβ2-MG), urinary α1-microglobulin (uα1-MG), and cardiothoracic ratio (CTR) of the R group were significantly higher than the NR group. However, the size of the kidney, high-dense lipoprotein (HDL), hemoglobin (Hb), and hematocrit of the R group were significantly lower than the NR group (P < 0.05). Binary logistic regression analysis showed that baseline CTR, SBP, size of the kidney, and HDL were independent risk factors for rapid progression of PGD. At the end of follow-up, CTR and SBP of group R were higher than the NR group, and the size of the kidney and HDL of group R were lower than the NR group.  The age, systolic blood pressure (SBP), serum  Increased baseline CTR and SBP and decreased baseline HDL and renal volume could be the predictors of rapid progression in patients of PGD at the CKD stages 3 and 4. A meta-analysis of 100 articles indicated that the average global prevalence rate of chronic kidney disease (CKD) is about 13.4%, among which the prevalence rate of CKD stages 1-5 is 3.5%, 3.9%,7.6%, 3.5%, and 0.1%, respectively , 3. HighTherefore, this study is aimed at identifying risk factors and predictors of rapid progression of CKD caused by PGD. Our results help establish a diagnostic standard of rapid progression of PGD with high sensitivity and specificity.n = 11); (2) patients suffering severe infection, cardiovascular, cerebrovascular disease, liver failure, and respiratory failure (n = 63); (3) patients using hormones or immunosuppressants (n = 15); (4) patients who did not participate regularly follow-up examination for 2 years (n = 61); (5) Patients with missing data > 20% (n = 44). Finally, 112 eligible patients were included in this study.This study was approved by the Ethics Committee of Third Xiangya Hospital, and no informed consent was required because this is a retrospective study. A total of 306 PGD patients were screened who were hospitalized at the nephrology department in the Third Xiangya Hospital from January 2014 to September 2016 and initially diagnosed as chronic CKD stages 3-4 caused by PGD. Patients were excluded if they met the exclusion criteria: (1) patients who have been treated with renal replacement therapy (The standard diagnosis of PGD conformed to the definition of 2012 KDIGO guidelines for glomerulonephritis. The standard diagnosis of hypertension: SBP ≥ 130 mmHg and (or) diastolic blood pressure (DBP) ≥ 80 mmHg according to America College of Cardiology/American Heart Association in 2017. The standard diagnosis of diabetes: the history of diabetes, fast plasma glucose (FPG) ≥ 7.0 mmol/L, or 2 hours postprandial blood glucose (PBG) ≥ 11.1 mmol/L, or random blood glucose (RBG) ≥ 11.1 mmol/L. The standard diagnosis of rapid progressive primary glomerular disease (PGD): reduction in eGFR of at least 30% from baseline within 2 years and/or commencement of dialysis.β2-MG, and uRBP. The eGFR was calculated with the formula modified for Chinese: GFR = 169 × (Cr/88.4)−0.608 × CysC−0.63 × Age−0.157 [The baseline data were collected from the patients, including age, sex, body mass index (BMI), basal metabolic rate (BMR), mean arterial pressure (MAP), size and lesion of parenchyma of kidney testing by ultrasound, cardiothoracic ratio (CTR) obtained by chest X-ray and serum indicators such as hemoglobin (Hb), creatinine (Cr), blood urea nitrogen (BUN), potassium (K), chlorine (Cl), albumin (Alb), total cholesterol (TC), cystatin C (CysC), factor B, homocysteine (Hcy), ceruloplasmin (CP), and urinary indicators such as uACR, ut-test. Data not in normal distribution were expressed as median (25th to 75th percentiles) and compared by nonparametric test (Wilcoxon rank-sum test). Qualitative variables were expressed as percentages and compared by the Chi-square test. Logistic regression analysis was used to identify risk factors and predictors. P < 0.05 indicated statistical significance.Data in normal distribution were expressed as mean ± SD and compared by ANOVA and A total of 112 patients  with CKD caused by PGD participated in the study, including 60 males and 52 females. According to the stage of CKD, there were 52 patients in stage 3 and 60 patients in stage 4. After the 2-year follow-up, there were 18 patients in stages 1-2, 21 patients in stage 3, 35 patients in stage 4, and 38 patients in stage 5, which indicated that most patients have entered into end-stage within 2 years.β2-MG, uα2-MG, and CTR were significantly higher in the R group than in the NR group, while the kidney size, HDL, Hb, and Hct were significantly lower in the R group than in the NR group (P < 0.05). Other factors showed no significant differences between the two groups such as diabetes history, CRP, LDL-C, TC, TG, ESR, CP, prealbumin (PA), Alb, ferritin, transferrin, α1-MG, RBP, serum β-d-glucosaminidase (sNAG), and urinary β-d-glucosaminidase (uNAG) . To test the predictive performance of the regression formula, we constructed a receiver operating characteristic (ROC) curve  curve . The areP < 0.05). However, such changes were not observed in the NR group. At the end of the follow-up, CTR and SBP were significantly higher, and HDL was significantly lower in the R group than in the NR group , HDL significantly decreased compared with the baseline, and the baseline and renal volume of follow-up cases did not show significant differences. In patients with CKD stage 4, the follow-up endpoints CTR and SBP increased significantly, and the renal volume and HDL decreased significantly compared to the baseline value (P < 0.05).In different CKD stages, the change of corresponding indicators was observed . In the At the baseline, BP reaching threshold (BP < 130/80 mmHg) was about 34%. At the endpoint, BP reaching threshold was 25.3%. The qualified rate of BP control in the R group dropped from 20% to 13%.It is generally acknowledged that CTR directly reflects cardiac size, relating to cardiac failure , 8. ThisSome studies suggested that hypertension with renal failure is more difficult to control, and the risk of cardiovascular disease significantly increases , 12. IndCurrent evidence indicates that dyslipidemia is closely related to the occurrence and progress of CKD. The mechanism of abnormal blood lipids affecting kidney diseases is manifold and is related to oxidative stress, proteinuria, and lipoprotein transport disorders . In kidnRenal function may decline rapidly with parenchymal lesions and nephrons loss. In addition, the kidney size is proportional to the number of nephron and is significantly associated with renal function . TherefoIn addition, there were 18 patients in stages 1 and 2 after the 2-year follow-up. This is a remarkable finding. There is a possibility of renal function recovery in the early stages of disease, or there are some factors that affect the SCr and eGFR when they are tested, such as diet, exercise, and medicine. Our study has some limitations. While we showed that 4 parameters  could be the predictors of rapid progression of PGD, it remains to decide whether the presence of a single parameter is important or complete the set of 4 parameters is indispensable for the prediction.In conclusion, increased baseline CTR and SBP and decreased baseline HDL and renal volume could be the predictors of rapid progression of PGD in patients of PGD at the CKD stages 3 and 4.


Although protective mechanical ventilation (MV) has been used in a variety of applications, lung injury may occur in both patients with and without acute respiratory distress syndrome (ARDS). The purpose of this study is to use machine learning to identify clinical phenotypes for critically ill patients with MV in intensive care units (ICUs).A retrospective cohort study was conducted with 5013 patients who had undergone MV and treatment in the Department of Critical Care Medicine, Peking Union Medical College Hospital. Statistical and machine learning methods were used. All the data used in this study, including demographics, vital signs, circulation parameters and mechanical ventilator parameters, etc., were automatically extracted from the electronic health record (EHR) system. An external database, Medical Information Mart for Intensive Care III (MIMIC III), was used for validation.Phenotypes were derived from a total of 4009 patients who underwent MV using a latent profile analysis of 22 variables. The associations between the phenotypes and disease severity and clinical outcomes were assessed. Another 1004 patients in the database were enrolled for validation. Of the five derived phenotypes, phenotype I was the most common subgroup  and was mostly composed of the postoperative population. Phenotype II  led to the most severe conditions. Phenotype III  was associated with high positive end-expiratory pressure (PEEP) and low mean airway pressure. Phenotype IV  was associated with high driving pressure, and younger patients comprised a large proportion of the phenotype V group . In addition, we found that the mortality rate of Phenotype IV was significantly higher than that of the other phenotypes. In this subgroup, the number of patients in the sequential organ failure assessment (SOFA) score segment  and 87 of 480 (18.1%) unique patients, respectively, was significantly higher than those of the other phenotypes. There were consistent phenotype distributions and differences in biomarker patterns by phenotype in the validation cohort, and external verification with MIMIC III further generated supportive results.Five clinical phenotypes were correlated with different disease severities and clinical outcomes, which suggested that these phenotypes may help in understanding heterogeneity in MV treatment effects. Ventilator-associated lung injury (VALI) commonly occurs in patients hospitalized in the intensive care units (ICUs). A growing body of studies have shown that VALI is not limited to patients with acute respiratory distress syndrome (ARDS) but might occur in patients undergoing mechanical ventilation (MV) without lung injury; improper placement of the ventilator can also cause VALI , 2. The Previous clinical studies of MV in critically ill patients have analyzed MV as a homogeneous disease or only discussed how to perform pulmonary protective ventilation in patients with ARDS –7. In adUsing the administrative database of Peking Union Medical College Hospital and the data from our previously published study in Critical Care Medicine, we conducted a retrospective study of patients undergoing MV . From MaLung-protective strategies for MV were performed on all of the patients who were admitted to the ICU. When the patients were under adequate sedation and analgesia but without spontaneous breathing, volume-controlled or pressure-controlled ventilation was used. Once the patient had spontaneous breathing, controlled ventilation was immediately converted to pressure support ventilation.2), pulse oxygen saturation (SpO2%), mean airway pressure (Pmean), peak airway pressure (Ppeak), positive end-expiratory pressure (PEEP), tidal volume (VT), partial pressure of oxygen (pO2) and partial pressure of carbon dioxide (pCO2)), circulatory and perfusion variables (heart rate (HR), mean arterial pressure (MAP), central venous pressure (CVP), static arterial carbon dioxide partial pressure (Pv-aCO2), lactate, P(v-a)CO2/C(a-v)O2 ratio, perfusion index (PI) and hemoglobin (Hb)) and a persistence variable . For each variable, we computed the mean value during the first 24 h of hospital presentation. To derive the phenotypes of MV, we first evaluate the distribution, missingness, and correlation of the above candidate variables. Due to the scarcity of the data samples, the missing variables were not simply eliminated. Instead, multiple imputation with chained equations was used to account for missing data. We also excluded highly correlated variables using rank-order statistics in the sensitivity analysis with threshold value of 0.75. Because the data type of the candidate variables was numerical, we used latent profile analysis (Gaussian mixture model) to recover hidden groups based on the means of the continuous variables observed. It always involved multiple constraint conditions: “model_1” involved equal variance and zero covariance, and “model_2” involved varying variance and zero covariance. An algorithm, the “expectation maximization” (EM) algorithm, was used to find the means and standard deviations of these distributions through two steps. First, we started with some initial starting guesses of the means and standard deviations. Based on these guesses, we assigned a posterior probability of being in a certain group to each patient. Second, these posterior probabilities were then used to update our guesses of the within-class parameters, which, in turn, were used to update the posterior probability, and so on until nothing seemed to change much anymore. Then, “model_1” was adopted in this manuscript. In the latent class analysis, the optimal phenotype number was confirmed using a combination of Bayesian information criteria, adequate size, high median probabilities of group membership with each phenotype, maximum entropy, and clinical features of hidden groups.We selected 22 candidate variables based on their relevance to MV. These mainly included demographic characteristics (age and temperature (T)), scores  II scores and sequential organ failure assessment (SOFA) scores), respiratory variables (respiratory rate (RR), oxygen concentration in the inhalation gas  ranked plots of the variables by the mean and standardized difference among the phenotypes, (2) t-distributed stochastic neighbor embedding (t-SNE) plots , and (3) alluvial plots .Since the SOFA score is used to track a person's disease severity during their stay in the ICU and determine the extent of his or her organ function or rate of failure, we also performed an analysis to determine the relationship between the new phenotypic classification and the SOFA score, which included determining (1) whether the traditional SOFA score reflects the severity of the disease; (2) whether the phenotypes overlap with the SOFA score area on the chord graph; and (3) the deaths associated with each phenotype and the corresponding quartile of the SOFA score . The mortality rate of different phenotypes was significantly different across regions, which was evaluated a posteriori by a clustering phenotypic method.To further verify the phenotyping results yielded from Peking Union Medical College Hospital cohort, we then used another open database for external verification. The selected database is Medical Information Mart for Intensive Care III (MIMIC-III) database, which is a large, freely available database comprising deidentified health-related data associated with over 40,000 patients who stayed in critical care units of the Beth Israel Deaconess Medical Center between 2001 and 2012. According to the same inclusion criteria, data from 9457 patients were enrolled in our external verification study.Summary information on our patient population is shown in Table entclass1pt{minimai categorized as the nth phenotype wasConsequently, the probability of an observation xi of  in the variable space as an example, we can calculate the five-class probabilities  with Eqs. (2) and (3). Taking the phenotype of the maximum probability implied that observation xi was categorized as phenotype V.With an observation xP < 0.05. Several analyses were conducted to ensure that the phenotypes were not simply recapitulations of more traditional clinical groups. To that end, we first assessed the associations between the score variables and measures of illness severity, such as the APACHE II and SOFA scores. The mean APACHE II/SOFA scores for phenotypes II and IV were 23.40/11.45 and 21.31/9.79, respectively, which were significantly higher than those for phenotypes I, III and V . For RR, FiO2, Pmean and Ppeak in terms of respiration, the means for phenotype IV were approximately 97.8, 48.9, 11.8, and 218, respectively; these values exceeded those of the other for phenotypes by 498%, 23%, 30.9% and 19%, respectively. Furthermore, for the HR in terms of circulation and perfusion, the differences across phenotypes IV and I, II, III, and V were also large. The mean for phenotype IV was 18.9, which was only 23.3%, 18.9%, 21.3% and 19.2% of that of the other four profiles. Phenotype III had a mean PEEP of 17.42, while the PEEP of phenotypes I, II, IV and IV was 5.74, 8.14, 10.21, and 5.9, respectively; the value for phenotype III exceeded those of the other phenotypes by 203%, 114%, 70.6%, and 195%, respectively. Phenotype V corresponded to an average age of 40.17 years, which was much lower than that of the other four phenotypes, which were 66.58, 58.54, 59.37 and 55.2 years.As shown in Fig. 1, x2, probability} was thus formed. Therefore, as shown in Fig. The means and standard deviations of the five phenotypes are shown in Table 2, Pmean, and Ppeak) and circulatory characteristics (HR) of phenotype IV were significantly different from those of the other four phenotypes, we used the SOFA score as an example by dividing it into four score intervals: , , 23 (20.2%), 6 (3.85%), 25 (28.4%) and 3 (1.46%). Then, we calculated the PSI for the phenotype populations and mortality across the two datasets. The final values were 0.0045 and 0.007, which indicated an insignificant difference in both the population size and mortality rate between the validation cohort and study cohort.2%, RR, pO2 and PEEP), circulation and perfusion features  and residual features .We used MIMIC III cohort for further verification. To minimize the impact of database differences, we finally chose 15 variables and divided them into four groups: demographics (age and temperature (T)) and scoring features (SOFA score and SAPSII score), respiratory features  within 24 h of the day. For these five types of respiratory phenotypes, we used a chord diagram to suggest that the interaction among the SOFA score, profile, and death toll showed that Profiles IV and II had the highest mortality. Survival curve analysis revealed that the 28-day survival rate of Profile IV and Profile II was significantly lower than the those of the other three profiles. We constructed five ventilator-related phenotypes with mathematical expressions using a potential profile approach and used validation data sets to predict and validate the existence of the five phenotypes. Additionally, the experiments on the MIMIC III cohort confirmed these phenotypes. The implementation of this study facilitates the identification and treatment of these mechanically ventilated patients in clinical practice, improving patient survival and improving prognosis.2O) at a PEEP lower than the required level. Therefore, we urgently need to use new methods to examine traditional clinical problems.Inappropriate ventilation strategies during MV result in lung injury, and the mechanisms include high airway pressures or tidal volumes resulting in lung pressure/volume injury. Excessively low expiratory lung volumes or atelectasis lead to repeated opening and collapsing of the terminal lung unit. In addition, in patients undergoing MV, even without anatomical changes in the lung tissue, the effects of various forces can induce the release of pro-inflammatory cytokines and the recruitment of white blood cells, and the initiation of local inflammatory processes is called biological injury . The fir2O significantly affects the prognosis of patients [Through analysis, we found that MV patients could be divided into five subtypes. For example, in MV patients of Peking Union Medical College Hospital, Profile IV showed a high mean airway pressure, a high peak airway pressure, a fast respiratory rate and a slow heart rate. Profile III showed a high pure PEEP. Based on the survival analysis, we can clearly see that the mortality rate was the highest for Profile IV compared with the other profiles. Namely, the prognosis of patients who show improved oxygenation by increasing the airway pressure is worse than that of patients who show improved oxygenation by increasing the PEEP without increasing the airway pressure. The occurrence of VILI depends on the interaction of the ventilator and the lungs, i.e., the pressure, volume, flow rate and frequency of the ventilator applied to the lungs and the reactivity of the lung parenchyma. The pressure generated in the lung tissue when MV is used to expand the lung is called stress, which is reflected as transpulmonary pressure. The driving pressure may better reflect the actual ventilation state in terms of the MV phenotype. Namely, with the same tidal volume, the larger the amount of functional residual gas there is, the smaller the strain generated, the smaller the probability of the occurrence of VILI, and the better the prognosis of the patient. In 2015, Amato et al. proposed that for patients with ARDS undergoing MV, the VT, PEEP, and driving pressure (DP) are independent factors . Among tpatients .Our studpatients , 15.Phenotype V represents a younger but higher-scoring patient, and this phenotype may become an independent phenotype, probably due to lung compliance. The parameters of MV did not appear to have an effect on these aspects of the patients, and the prognosis of the patients were good. Phenotype II is different from phenotype III, as the patients classified as phenotype II have higher scores, but they are not considerably different in terms of age. These patients had poor organ function which may not be only reflected from the lung-related variables, so these patients may form an independent group as phenotype II. The last group is phenotype I, which represents the majority of clinical patients and the most homogeneous group. We further analyzed the departments in which the patients were admitted and found that phenotypes I, III, and V were from surgery, and phenotypes II and IV were from internal medicine.This study also has some limitations. First, although it was a big data study, there was a training set combined with a verification set to validate five phenotypes. We used the data from the MIMIC III cohort to demonstrate our findings. However, this model still needs to be clinically verified by a prospective study. Second, the study included general information, ventilator parameters and circulation and perfusion indicators, as well as the balance of input and output  within 24 h of the day, which take into account some of the indicators commonly considered in clinical use of MV. It is not known whether it is necessary to include all the indicators that can be obtained and recorded in the clinic or to combine some indicators. Third, many of the parameters included in this study are related to clinical decision making. For example, PEEP, VT and other parameters are more decisions of the clinician than the patient's own respiratory mechanics. Therefore, phenotypic analysis in different institutions may conclude different results. The current conclusion of this study requires further multicenter validation if possible.In this retrospective analysis, respiratory and circulatory data were obtained from patients undergoing MV from two databases. Five ventilator-related phenotypes were obtained, and from these five phenotypes, Profiles II and IV were both related to mortality, and Profile IV was more significant in higher mortality caused by mechanical ventilation parameters. These five new identified phenotypes of critically ill patients undergoing MV may be helpful in the future identification and interpretation of clinically high-risk patients.


In a subgroup analysis, the risk of pyuria for ESRD was modified by CKD stages. We investigated the effects of UTI (urinary symptoms and treated by antibiotics) and pyuria without UTI (urine WBC < 50 to ≥ 10/hpf without any episodes of ≥ 50 WBC/hpf or UTI), while both groups were associated with clinical outcomes. In conclusion, CKD stage 3–5 patients with frequent pyuria or UTI episodes have increased risks of renal outcomes.Pyuria is common in chronic kidney disease (CKD), which could be due to either urinary tract infection (UTI) or renal parenchymal inflammation. Only little is known regarding the association of pyuria or UTI with renal outcomes. We investigated 3226 patients with stage 3–5 CKD. Pyuria was defined as ≥ 50 WBC per high-power field (hpf) and was correlated to old age, female, diabetes, hypoalbuminemia, lower eGFR, and higher inflammation status. In Cox regression, patients with more than one episode of pyuria in the first year (11.8%) had increased risks for end-stage renal disease (ESRD) [hazard ratio (95% CI): 1.90 (1.58–2.28);  To the best of our knowledge, pyuria is highly prevalent in CKD, which does not always indicate the presence of urinary tract infection (UTI)3. While pyuria is broadly defined as the appearance of leukocytes in the urine, various possible causes, including acute febrile illness, structural abnormalities of the genitourinary tract, or interstitial nephritis can also lead to sterile pyuria4. Previous data from a small CKD patient sample by Kwon et al. showed that the degree of pyuria was associated with UTI in patients with CKD, with the majority of their urinary WBCs being neutrophils3. Moreover, Hwang et al. reported that recurrent and persistent pyuria may contribute to the decline of kidney function in patients with autosomal dominant polycystic kidney disease (ADPKD)5.Chronic kidney disease (CKD) is a global health problem due to its increasing incidence and prevalence worldwide6, comorbidities especially diabetes, advanced age, and urinary tract obstruction are common risks for UTI and CKD progression accordingly7. A short-term study of single episode UTIs8 and a long-term study of asymptomatic bacteriuria in diabetes revealed that there was no faster decline of renal function9. In fact, on the contrary,in patients with polycystic kidney disease10 and who had post-kidney transplantation11, UTI could be associated with renal function progression. Several factors have been proposed, particularly virulence factors such as P fimbriae on uropathogenic E. coli, to induce chronic inflammation13. More importantly, uremic condition in CKD alters both cellular and humoral immunity, which increases the susceptibility to a broad range of infections. However, whether pyuria or UTI has a negative impact on end-stage renal stage (ESRD) in CKD patients has never been investigated; we test this hypothesis in different definitions from an observational cohort.CKD could be a risk factor for UTI, which may be present with asymptomatic bacteriuria or symptomatic UTIs requiring treatment. In addition to reduced host immunityOut of the total of 3226 patients with stage 3–5 CKD who were not on dialysis, 1366 (42.3%) of them were female and 1448 (44.9%) had type 2 diabetes  of 1125 (411–2553) mg/g  for pyuria (Group 1 and Group 2) Table . In contP < 0.001) when compared with Group 0 , 79 (39.7%), and 163 (44.5%) of the patients developed end-stage renal disease (ESRD) in Groups 0, 1, and 2, respectively  for 699 (26.5%), 55 (27.6%), and 146 (40.0%) of the patients, respectively. In a fully adjusted multivariate logistic regression, Group 2 was significantly associated with an increased risk for rapid eGFR decline with an odds ratio of 1.49 , whereas Group 1 was not associated with an increased risk (Table P < 0.001) when compared with Group 0 (Table The median eGFR slope was –2.2 mL/min/1.73 mP < 0.001) (Table ≥ 50/hpf) and then divided them by episodes of pyuria (urine WBC < 50 to ≥ 10/hpf). > 2 episodes of pyuria without UTI (Group 2) were associated with an increased risk of ESRD with a HR of 3.53   was associated with an increased risk of ESRD with a HR of 1.90 .Pyuria defined as urine WBC ≥ 10/hpf within first year after enrollment was present in 18.1% of males and 29.4% of females, and it was also present in 27.1% non-diabetic patients and 43.9% diabetic patients (Supplement Table  ≥ 50/hpf) and ESRD was modified by CKD stages (P for interaction < 0.05). > 1 episode of pyuria was associated with a higher risk for ESRD with a HR of 2.310  in CKD stage 4 and HR of 2.228  in CKD stage 5  or frequent UTI episodes, defined as > 1 episode in the first year, were associated with a higher risk for multiple relevant outcomes, including ESRD, rapid renal function progression, and all-cause mortality. However, frequent sterile pyuria (urine WBC < 50 to ≥ 10/hpf) without UTI (high probability of sterile pyuria) was significantly associated with renal outcomes. In addition, we also found that pyuria was correlated with old age, being female, diabetes, hypoalbuminemia, a lower eGFR, and a higher inflammation status in CKD patients.3. A further analysis of 86 participants with pyuria reported that predisposing factors of UTI include the degree of pyuria, percentage of neutrophils, and presence of urinary nitrites3. Our study expanded the evidence to a greater CKD population, and around 17.5% of patients with stage 3–5 CKD had pyuria. Old age, being female, the presence of diabetes, hypoalbuminemia, a lower eGFR, and a higher inflammation status were related to pyuria.Pyuria, defined as the presence of leukocytes in the urine, is present in almost every patient with symptomatic UTI and bacteriuria. The presence of pyuria could differentiate between true infection or transient colonization under the condition of asymptomatic bacteriuria. A recent study found that asymptomatic pyuria was more common in patients with CKD than in the non-CKD population and even increased with the CKD stages 2. Since the prevalence of pyuria increased in the CKD population, it has been assumed that sterile pyuria in CKD may be due to chronic renal parenchymal inflammation. Regardless of the underlying etiology, CKD is present in a final common pathway of fibrosis as the initial insults, including nonimmune-mediated  and immune-mediated (such as glomerulonephritis) kidney conditions, followed by inflammatory processes15. Under the activation of both innate and adaptive immunity, renal inflammation is characterized by inflammatory cells infiltrating in the glomeruli and tubulointerstitium, including neutrophils, macrophages, and lymphocytes16. Even in CKD patients with sterile pyuria, the predominant urinary WBCs were neutrophils but with a lower percentage compared with the UTI group3. Our study demonstrated that pyuria was associated with tubulointerstitial nephropathy but not with glomerulonephropathy. It could be supposed that tubulointerstitial injury possibly results in leakage of inflammatory cells and sterile pyuria. However, the precise correlation between the degree of cellular infiltrates and pyuria has not been elucidated. In addition, Hwang et al. found that the patients with ADPKD who had experienced recurrent and persistent pyuria in the first year had higher incidences of eGFR decline and ESRD than those without pyuria or transient pyuria5. The overt UTI group exhibited an even greater eGFR decline than the pyuria groups5. Our study showed the similar results that pyuria without UTI was associated with poor outcomes. We supposed that pyuria, especially frequent episodes, may be an indicator of chronic parenchymal inflammation, leading to poor clinical outcomes.Pyuria may persist in the absence of infection because of underlying inflammatory changes in the kidney, such as urinary tract stones, polycystic kidney disease, interstitial nephritis, interstitial cystitis, or systemic lupus erythematosus17. CKD could be a risk factor for UTI in addition to the elderly, female and diabetes which are common risk factors in the general population18. Because CKD is a chronic inflammatory state which increases susceptibility to a broad range of infections, and the comorbidities accompanied with CKD also contribute to UTI including diabetes and incomplete emptying of the urinary bladder8. However, there are few data available that survey for the prevalence of UTI in CKD population. In addition to virulence factors of the microorganism, an accumulation of uremic toxins impairs both cellular and humoral immunity, including the activity of phagocytosis, T lymphocytes and antigen presenting cells20. Oxidative stress and inflammatory cytokine generation in CKD also disrupt immunity22. Moreover, urinary uromodulin  which decreases in CKD23, has been shown to protect against UTI by binding a type I-fimbriated bacteria24. These conditions may promote UTI development and determine the severity of the infection in CKD.As for the UTIs, the clinical spectrum ranges from asymptomatic bacteriuria, to symptomatic UTIs, or to sepsis requiring hospitalization25. Furthermore, an acute infection of the urinary tract may lead to AKI, which is an independent risk factor for CKD development and progression26. Factors contributing to renal injury include direct infection of the renal parenchyma, sepsis, obstruction, vesicoureteral reflux, renal papillary necrosis, and urinary calculi29. Thakar et al. suggested that multiple episodes of AKI occur in one third of patients with AKI who survive after an initial hospitalization, and each subsequent episode doubled the risk of reaching stage 4 CKD in patients with DM30. As for the renal outcome of an urinary tract infection in CKD patients, the only evidence from our previous short-term study found that a single episode of UTI in a diabetic with advanced CKD possessed AKI risks and the eGFR eventually recovered8. This study is the first large cohort to demonstrate that multiple UTI episodes in patients with CKD resulted in renal function deterioration and increased risk of mortality. This result may imply that the severity of structural damage in the kidney accelerates the course of renal function progression when a UTI is present.Although a lower amount of UTI do not promote a decline in renal function, recurrent episodes of UTI may influence the course of a pre-existing renal disease and result in kidney function deterioration. Salo et al. demonstrated recurrent childhood UTIs as a main cause of CKD as observed in patients with structural kidney abnormalities3. We chose urine WBC ≥ 50/hpf to study the effect of nonsterile pyuria and WBC < 50 to ≥ 10/hpf without UTI to study the effect of sterile pyuria. Second, the differentiation between pyuria with UTI and pyuria without UTI in patients with CKD is challenging. We did not perform urine culture to confirm bacteriuria in most episodes of pyuria. Asymptomatic bacteriuria could also be present in pyuria without UTI. Third, the frequency of pyuria and UTI was arbitrarily defined as the total episodes within the first year. The total measurements among patients could be different, and the frequency could be underestimated in patients reaching endpoints of less than one year. Fourth, the frequency of UTI could be underestimated due to the incomplete record from local clinics. Patients classified as pyuria without UTI might also have UTI episodes. Fifth, the causes of CKD were diagnosed clinically, not by renal biopsy.There are several limitations to our findings. First, the definition of clinically significant pyuria is unknown. A previous study had shown that nonsterile pyuria is correlated with the number of urine WBCsIn conclusion, we found that the frequency of pyuria and UTI episodes determined the clinical outcomes in CKD stage 3–5 patients. With different definitions of pyuria, patients with more frequent episodes were at greater risk of renal outcomes independent of other major risk factors of progression. In addition, similar associations existed in patients with frequent UTI episodes. Further studies are needed to explore the effects of frequent pyuria without UTI on renal outcomes.This was a prospective observational study, the Integrated CKD Care Program Kaohsiung for Delaying Dialysis, involving two affiliated hospitals of Kaohsiung Medical University in Southern Taiwan. The study was conducted from November 11, 2002 to May 31, 2009 with follow-up until May 31, 2010. We included patients who were not on renal replacement therapy and excluded patients with AKI, which we defined as more than a 50% decrease in eGFR within 3 months. Among the 3749 patients that were eligible for the study, we excluded 356 patients with stage 1–2 CKD and 77 patients with a urinary tract obstruction. After the exclusions, 3226 patients were recruited for this study. The study protocol was approved by the institutional review board of the Kaohsiung Medical University Hospital, and informed consent was obtained from all of the patients in this study. The study was carried out in accordance with relevant guidelines and regulations.31. Hypertension was defined as having a systolic blood pressure (SBP) ≥ 140 mmHg, a diastolic blood pressure (DBP) ≥ 90 mmHg, or the use of antihypertensive medication. CV diseases were defined as having a clinical diagnosis of heart failure, acute or chronic ischemic heart disease, or cerebrovascular disease. Causes of CKD were classified as glomerulonephropathy, tubulointerstitial nephropathy, diabetes, hypertension and others. Glycated hemoglobin (HbA1c) was measured using an automated cation-exchange high-performance liquid chromatography. Biochemical data  were obtained after midnight fasting.The baseline comorbidities, clinical conditions, and biochemical parameters of the patients were collected. The demographic features were recorded at the first visit, and the medical history was recorded using a chart review. DM was defined according to the World Health Organization or by the use of medicationWe performed urinalysis on patients at least every 3 months after their enrollment. Midstream urine was obtained and processed within one hour of voiding. After centrifugation, a microscopic examination was performed to determine the presence of pyuria. Urinary WBCs were counted as 0–2, 3–5, 6–10, 11–25, 26–50, 51–99, and ≥ 100 per hpf. UTI was defined as pyuria with urinary symptoms and was treated by antibiotics. We chose urine WBC ≥ 50/hpf in Tables 2 = 186 × serum creatinine−1.154 × age−0.203 × 0.742  × 1.212 (if the patient was black). The annual eGFR decline (ml/min per 1.73 m2/y) for each patient was calculated by simple linear regression with varying intercept and without covariates. A rapid eGFR decline was defined as an annual eGFR decline more than − 5 ml/min/1.73 m2/year. The survival status and cause of death were determined on the basis of death certificates, patients’ charts, and the National Death Index. The details of the CKD Care Program were described elsewhere33.ESRD was defined as the initiation of hemodialysis, peritoneal dialysis, or renal transplantation. The initiation of renal replacement therapy was determined by reviewing the charts and the catastrophic illness cards. Kidney function was examined using the simplified modification of diet in the renal disease study equation: eGFR mL/min/1.73 m33. The model was adjusted for age, sex, eGFR, log-transformed UPCR, hypertension, cardiovascular disease, diabetes, current smoker, mean blood pressure, ACE inhibitor/ARB, HbA1c, hemoglobin, albumin, BMI, log-transformed cholesterol, log-transformed CRP, and phosphorus. A P value of < 0.05 was considered statistically significant. Statistical analysis was performed using the R 2.15.2 software  and Statistical Package for Social Sciences Version 19.0 for Windows .The summarized statistical results of the baseline characteristics of patients were expressed as counts and percentages for the categorical data, means with standard deviation, and medians with interquartile ranges (IQR) determined for continuous variables with approximately normal distributions. A Cox proportional hazard model with a competing risk analysis was used for assessing the relationship between pyuria and renal outcomes. A multivariate logistic regression analysis was used to evaluate the relationship between pyuria and rapid renal function progression. Covariates were selected and modified from our previous studies, and continuous variables with skewed distributions were log transformed to obtain normal distributionsSupplementary information


However, summary effects of more than one of these five variables were statistically significant associated with greater than 50% failure rate of SIAI (p < 0.05). When employing the five-variable model, validation cohort subjects displayed dehydration, obesity, vein invisibility, vein impalpability and hyperactive status had a 67.5% likelihood of failed first attempt on SIAI . For the first time, we developed the difficult model for SIAI. We found that dehydration, obesity, vein invisibility, vein impalpability and hyperactive status of the infant patients are the independent and significant predictors associated with SIAI failure. Our predicted model indicates that infant patients with combination of more than one of the five variables contribute to greater than 50% failure rate of indwelling needle in SIAI.Infant intravenous access poses a significant challenge to the operator. Scalp vein is the ideal location for emergency medical staff to perform intravenous access for administration of fluids or medications. To tackle this challenge, we developed a clinical rule for the difficulty prediction on scalp intravenous access in infants (SIAI) conducting a prospective cohort study in a pediatric emergency room. A total of 658 infant patients who underwent SVI from January 2017 to September 2018 were recruited in this study. The failure rate of SIAI on the first attempt was 20.2%. Five variables, including dehydration condition, obesity, vein invisibility, vein impalpability and hyperactive status of infant, were independently and statistically associated with failure rate of SIAI. Furthermore, we indicated that any one alone of the above five variables did not significantly lead to greater than 50% failure rate of indwelling needle SIAI ( However, infant intravenous access poses a significant challenge to the operators, such as nurses and doctors. Failure of intravenous access not only aggravates pain and dissatisfaction of patients, but also enlarges the burden of the operators. Thus, it is a great benefit for emergency medical staff to reduce the failure rate of infant venous puncture.Intravenous access for sampling of blood or administration of medications is widely used in pediatric emergency departmentet al. previously developed a difficult peripheral intravenous access score3. Furthermore, they found that it is more difficult to perform peripheral intravenous access on infants, compared with children older than 1 year3. Similarly, Riker et al. observed that there existed high failure rate for operator to establish intravenous access in infants4. However, both of these two studies did not specify the locations of peripheral venous access, such as veins of upper limb, lower limb, external jugular or scalp. Therefore, the difficulty model of intravenous access on a specific location of infants remains to be developed.In order to predict the difficulty of peripheral intravenous access in children, Yen 1. On the other hand, most operators prefer to choose the superficial veins of upper limb or lower limb as the first attempt in clinical practice. Locations of peripheral intravenous placement mainly include superficial veins of upper limb (e.g. hand back vein and antebrachium vein), lower limb , external jugular and scalp. Nevertheless, it is very common that peripheral veins of upper limb and lower limb in infant patients are not completely developed, which increases the difficulty of peripheral intravenous access on both upper limb and lower limb in infants, owing to small and deeply-located veins5. As the neck of infant patients is relatively flexible and difficult to stable, the external jugular vein is not a reliable site for infant intravenous access6. However, the appearances of vein visibility and vein palpability are relative clear in scalp venous of infants. Therefore, it is an optimal location for emergency medical staff to choose scalp vein for venous access in infants.Most of the infant inpatients have weak constitution and are prone to serious complications, leading to adverse events. Therefore, it is significant that the emergency medical staffs to determine an ideal venous access to perform the treatment administration to the infant patients in the shortest possible time frame. Overall, locations of intravenous placement include peripheral venous access and central venous access. However, central venous access is not the first option and rarely used in pediatric emergency department, as the complications caused by central venous access can place massive physical burden on children patientsWith the goal of tackling the challenge of scalp intravenous access in infants (SIAI), we tried to develop a clinically predictive rule for SIAI. Preliminarily, we performed a prospective feasibility study to explore the candidate variables for the failure rate of scalp venous indwelling needle insertion in infants. We further sought to determine the potential independent variables for failed venous insertion on the first attempt. Ultimately, we aimed to develop a SIAI difficult degree model that is simple to apply and useful for the perdition of the failure rate of indwelling needle intravenous access in infants.A total of 658 infants were enrolled. The male-female ratio was 1:1.1. The age range was 0 to 12 months. Of the subjects, 11.1% were younger than 4 weeks (neonate), 42.9% were aged from 4 weeks to 6 months, and 46.0% were aged from 6 months to 1 year. Representative image of scalp indwelling needle intravenous access in infants was presented in Fig. p < 0.05).Initially, in order to reveal the candidate variables associated with failure rate in SIAI placement, we included candidate variables of both patient and operator. As shown in Table p < 0.05; Table To determine the independent and significant predictor variables, we further performed a multivariate logistic regression analysis to evaluate the statistically significant factors in univariate analysis. All the ten significant variables were appraised by a multivariate logistic regression model in a backward stepwise regression screening. In all significant predictor variables, we found that the following five variables, including body mass, location of intravenous access, prematurity history, reason for intravenous attempt and nursing prediction of difficulty level, were weakly predictive. Finally, the other five strongly predictive variables were retained in the predicted model: dehydration condition, obesity, vein visibility, vein palpability, and calm status of infant (p > 0.05). On the contrary, all results of the two-variable model, three-variable model, four-variable model and five-variable model indicated that their summary effects are statistically significant related to more than 50% SIAI failure rate (p < 0.05).To validate the difficulty of SIAI, we performed the multiple-variable model to test their summary effects of ROC curve and the AUC Table . In regap < 0.001). So, validation cohort subjects with dehydration, obesity, vein invisibility, vein impalpability and hyperactive status of infant patients had a 67.5% of failed first attempt on SIAI  or lower limb  for intravenous access if the above attempts of SIAI are failed. It is also recommended that the attempts of venous access into superficial veins of limbs should be limited to 3. Peripherally inserted central catheters (PICC) maybe the other choice of venous access, if the peripheral venous access was not succeeded9. Besides, VeinViewer and ultrasound-assisted approaches should be used for delineating the running course of subcutaneous veins, rather than blind approach in a complicate situation10. In addition, peripherally inserted central venous catheters are potential options for intravenous access in infant patients11.Since the success rate of SIAI on the first attempt in infants was 79.8%, we believed that scalp intravenous access is the optimal option for operator to perform venous access. In clinical practice, an experienced operator is needed if SIAI needs to be performed on an infant displayed more than one of five variables . Moreover, it is advised that SIAI attempts should be limited to 3. The emergency medical staff could choose superficial veins of upper limb  requiring venous insertion were eligible for inclusion in this study. Skin shade of all involving participants was yellow. We excluded subjects who required immediate emergency care, puncture point with apparent arteriopalmus or had skin disease on scalp. Both doctors and nurses who had been working for emergency service more than five years were eligible to participate in this study. Before the placement attempt was performed, demographic data of the study were recorded. Candidate predictor variables included the following twenty-two items: age, sex, mass, height, dehydration condition, obesity, interval time of last intravenous access, sterilization method, parent inside therapy room, local anesthesia, location of intravenous attempt, vein visibility, vein palpability, drawing marker before intravenous access, calm status of the infant, prematurity history, reason for intravenous attempt, parental prediction of cooperativeness, parental prediction of difficulty, nursing prediction of difficulty, nursing prediction of cooperativeness and self-confidence of nursing.2) index more than 18 was considered as obesity12. Vein visibility referred to the nurse’s ability to see the vein before SIAI. Vein palpability was labeled as the nurse’s ability to feel the vein before SIAI. Patients born at less than 38 week-gestation were considered as a positive history of prematurity13. In addition, the primary endpoint was defined as failed SIAI on first attempt. Conversely, a successful venous insertion referred to a saline flush could be injected without compromising the vein and ready for use.Such special outcome measures were described as following. Infant with Kaup . Statistical significance of the remaining candidate variable was assessed using hazard ratio (HR) with 95% confidence interval (CI). Later, the decision rules were based on the ROC curve and the AUC as its summary index. The concordance (C) statistic was performed to measures discrimination of ROC and AUC (range from 0.5 to 1.0)16.All data were computed using the Statistical Software Package for the social Sciences . Preliminarily, the association between predictor variables and the failure of first intravenous attempt was calculated using Pearson chi square for trends or Fisher’s exact test, depending on the condition of data. A two-tailed


In addition to the well-known risk factors of cold ischemic time and acute rejection episodes, the number of antihypertensive drugs after one year, which reflects the severity of hypertension, is a strong predictor of unfavorable allograft survival.Arterial hypertension affects the survival of the kidney graft and the cardiovascular morbidity and mortality of the recipient after kidney transplantation (KTx). Thus, antihypertensive treatment is necessary for a vast majority of these patients. Long-term data on antihypertensive drugs and their effects on allograft function after KTx is still limited, and further investigation is required. We retrospectively analyzed a cohort of 854 recipients who received a kidney transplant at our transplant center between 2007 and 2015 with regard to antihypertensive treatment and its influence on graft function and survival. 1-y after KTx, 95.3% patients were treated with antihypertensive therapy. Of these, 38.6% received mono- or dual-drug therapy, 38.0% received three to four drugs and 8.1% were on a regimen of ≥5 drugs. Beta-blockers were the most frequently used antihypertensive agents (68.1%). Neither the use of angiotensin-converting enzyme inhibitor/angiotensin receptor blockers (51.9%) and calcium channel blockers (51.5%), nor the use the use of loop diuretics (38.7%) affected allograft survival. Arterial hypertension and the number of antihypertensive agents were associated with unfavorable allograft outcomes (each  Cardiovascular disease (CVD) is the leading cause of mortality and morbidity in kidney transplant (KTx) recipients . Thus, aMost kidney transplant recipients have a long-term history of chronic kidney disease (CKD) associated with vascular pathologies leading to elevated systolic blood pressure (SBP) and increased pule pressure . After KIn KTx recipients, donor factors such as the donor’s pre-existing AHT, higher donor age, poor allograft quality and genetic donor factors can also influence the recipient’s blood pressures .To date, there have not been randomized controlled trials on optimal blood pressure limits or favorable treatment strategies in patients after KTx . TherefoNevertheless, there are substantive differences in the treatment of non-transplant patients, as, for example, some of the factors mentioned above that contribute to AHT in KTx recipients are transplant-specific.A recent cross-sectional study from Poland showed that beta-blockers were the most commonly used antihypertensive agents, followed by Calcium channel blockers (CCB), angiotensin-converting enzyme inhibitors (ACE-I)/Angiotensin-II-receptor-blockers (ARB), and diuretics . The remIn CKD patients, the blockage of RAAS has been proved to slow down the progression of diabetic and non-diabetic (protein-rich) kidney disease ,15. SeveTo date, however, there is no data demonstrating an association between the use of beta-blockers or diuretics and the long-term outcome of kidney allografts and KTx recipients although both drug classes are widely used. The frequent co-incidence of different therapeutic indications especially for beta-blockers and/or diuretics in addition to the treatment of AHT in the KTx setting, e.g., treatment of congestive heart failure or atrial fibrillation, is a problematic pitfall in this matter ,19. EspeThe present study was conducted in order to shed some light on the relationship between antihypertensive drugs and long-term outcomes for KTx recipients in the present era, taking into account that former studies are predominantly ten to twenty years old and KTx recipient outcome has changed rapidly within the last years . Our anaWe analyzed the data of 850 adult patients  who were transplanted at our center between 1 January 2007 and 31 December 2015. The demographics and clinical characteristics of the patients were recorded at the time of KTx, and written informed consent was obtained from all patients to record their data. The data was taken from the patients’ files, and the personal information was made anonymous prior to the analysis. This study was performed in accordance with the Declaration of Helsinki and the International Conference on Harmonization of Good Clinical Practice guidelines and approved by the local ethics committee . Induction therapy was chosen based on the immunological risks of the patients. The triple immunosuppressive standard regimen consisted of tacrolimus (6–10 ng/mL), mycophenolate mofetil and steroids . EstimatBlood pressure was measured manually during the outpatient one-year routine follow-up according to the 2013 European Society of Hypertension (ESH)/European Society of Cardiology (ESC) Guidelines for the management of AHT  and the We categorized antihypertensive medication into ACE-I/ARB, CCB and diuretics, subclassified into loop diuretics, thiazids and aldosterone-antagonists, beta-receptor-blockers, alpha1-receptor-antagonists, anti-sympathotonics and vasodilators.p-value below 0.05 was considered statistically noticeable.The data was analyzed with IBM SPSS Statistics 26 . The results are expressed as a mean with standard deviation, median with interquartile range (IQR) or number/percent. The categorical parameters were analyzed by Fisher’s exact test and the chi-square test and continuous parameters were analyzed by Mann–Whitney U-test and Kruskal–Wallis test, respectively. A Linear regression analysis was performed to test association between two continuous variables. The cumulative probability of developing allograft failure in the kidney transplant cohort was calculated by Kaplan–Meier analysis , and theThe baseline characteristics of the study population are presented in Of the initial 850 patients, 765 patients could be evaluated for antihypertensive medication after 1-y; 21 patients died with functioning allograft (2.5%), 37 patients (4.3%) developed terminal allograft failure and 27 patients (3.2%) were lost to follow-up during the first year.In our patient cohort, beta-blockers were the most frequently used antihypertensive drug group one year after KTx, prescribed to 582 patients (68.1%). ACE-Is/ARBs were prescribed to 443 (51.9%), while 440 patients (51.5%) were treated with CCRBs and 375 (43.9%) with diuretics. Among them, loop diuretics were by far the most frequently prescribed , while 29 patients (3.4%) received a thiazide diuretic and 23 (2.7%) received an aldosterone antagonist. In 94 (11%) patients, anti-sympathotonic drugs were administered, together with at least three other antihypertensive drugs. The same applies to alpha1-receptor blockers and vasodilators, which were prescribed to 30 (3.5%) and 20 (2.3%) patients, respectively.p < 0.001). Moreover, patients with a maximum of two antihypertensives were significantly younger (p < 0.001). Due to the higher percentage of living donations in younger patients, the cold ischemia time was significantly shorter (p < 0.001) in this group than in the group of older patients receiving three or more antihypertensives after one year.Clinical outcome parameters are presented in p < 0.001). In contrast, the mean diastolic blood pressure did not differ between the groups (p = 0.374). Clearly, the mean systolic blood pressure after one year was associated with impaired allograft function in terms of lower eGFR one , two  and five years after KTx . There was no association of diastolic blood pressure with eGFR after one , two  and five years .Despite intensified antihypertensive medication, the systolic blood pressure was higher one year after KTx in patients with a higher number of prescribed antihypertensive agents . After one year, patients without antihypertensives had a mean UPCR of 160 ± 181 mg/g creatinine, while those with six antihypertensives had a noticeably higher mean UPCR of 443 ± 696 mg/g creatinine . Mean allograft survival for patients without antihypertensives was 10.0 years (CI 9.1–10.9), for patients with one or two antihypertensives 10.6 years (CI 10.4–10.8) and for patients with three or four antihypertensives 9.9 years (CI 9.6–10.3), .Recipients treated with beta-blockers had an inferior allograft survival compared to those who were not ,  and the occurrence of at least one acute rejection episode (any type of rejection) , Cox regression analysis confirmed the number of antihypertensive agents one year after transplantation as independently associated with death-censored allograft failure . Neither the use of beta-blockers  nor the use of loop diuretics  was independently associated with allograft failure.A multivariable Cox regression analysis was performed to assess whether the number of antihypertensive drugs or medication with loop diuretics or beta-blockers was associated with inferior allograft survival independent from other known risk factors. The analysis included several known risk factors for reduced allograft survival and the number of antihypertensives at 1-y after KTx, as loop diuretics were usually used as 3rd or 4th line therapy . In addip = 0.023) and 3–4 (p = 0.015) were significant.To further clarify whether antihypertensive drugs themselves may be harmful for allograft function, we studied the relation between the number of antihypertensive drugs after one year and the eGFR-change from year one to two and from year one to five. Overall, eGFR improved slightly during both periods. From year one to two, there were no significant differences between the groups . From yeAHT is one of the main risk factors for cardiovascular events after KTx . Since pIn the present study, we analyzed data from our transplant center and divided patients into four groups based on the number of different antihypertensive drugs. The distribution of main antihypertensives used in our cohort was comparable to that of other transplant studies . Our datAs expected, KTx recipients with severe hypertension were older, received less frequently living donations, and had a longer cold ischemic time associated with a higher rate of delayed graft function (DGF). In accordance with the literature, these factors can be regarded as confounders for inferior allograft outcome and have an impact on the development of AHT ,6.p = 0.025), whereas the number of antihypertensives usually reflects the severity of AHT. Interestingly, our data show that a higher number of antihypertensive drugs administered to patients (three or more) compared to patients treated with two or less antihypertensives is not associated with a higher eGFR-loss over time (Cox regression analysis confirmed that the number of antihypertensive agents prescribed to a patient after one year is independently related to death-censored allograft failure (ver time . AlthougIn terms of renal function, KTx recipients who received loop diuretics, usually administered as third- or fourth line medication , showed In CKD patients, Ishikawa et al. observed that the intake of loop diuretics was associated with sarcopenia . NeverthThe use of beta-blockers was also associated with inferior allograft survival in the Kaplan–Meier analysis. However, multivariable Cox regression could not confirm beta-blockers as a risk factor for reduced death-censored allograft survival. Although they are the most frequently used antihypertensive agents after KTx in our cohort as well as in others ,33, dataWith regard to the results of a former study from our transplant center , we coulOne explanation for these results could be that patients treated with ACEI/ARB and/or CCB for AHT—a proven risk factor for poor allograft survival—are compared to patients without hypertension. Therefore, comparable allograft survival in these AHT patients may potentially be interpreted as a beneficial effect of these drugs.Our study has several limitations. Since it is a retrospective analysis, it possesses only a hypothesis-generating character. In addition, the study design does not allow the distinguishing of direct effects of antihypertensive drugs on allograft function from specific factors that may be indicative, such as fluid overload due to reduced diuresis or congestive heart failure, which in turn is associated with poor graft function .In summary, this study provides a current overview of the association between antihypertensive therapy and allograft outcome after KTx. Arterial hypertension, the severity of which reflects the number of antihypertensive drugs prescribed to a patient, remains one of the major factors in allograft failure. As our analyses suggest, allograft and/or recipient specific factors that cause AHT, rather than antihypertensive treatment itself, determine the increased risk for allograft failure in patients with advanced antihypertensive medication. Since AHT manifests in a vast majority of KTx patients prospective controlled trials are necessary the further investigate these findings. We must raise the awareness of transplant physicians with regard to monitoring and pharmacological treatment of AHT as it is an important risk factor for chronic dysfunction and failure of allografts, which can be—at least partially—influenced. One should keep in mind that KTx recipients receiving ≥3 different antihypertensive drugs are patients at risk who deserve special attention.