The global burden of chronic kidney disease is rising. The etiologies, heterogeneous, and arterial hypertension, are key factors contributing to the development and progression of chronic kidney disease. Arterial hypertension is induced and maintained by a complex network of systemic signaling pathways, such as the hormonal axis of the renin-angiotensin-aldosterone system, hemodynamic alterations affecting blood flow, oxygen supply, and the immune system. This review summarizes the clinical and histopathological features of hypertensive kidney injury and focusses on the interplay of distinct systemic signaling pathways, which drive hypertensive kidney injury in distinct cell types of the kidney. There are several parallels between hypertension-induced molecular signaling cascades in the renal epithelial, endothelial, interstitial, and immune cells. Angiotensin II signaling via the AT1R, hypoxia induced HIFα activation and mechanotransduction are closely interacting and further triggering the adaptions of metabolism, cytoskeletal rearrangement, and profibrotic TGF signaling. The interplay of these, and other cellular pathways, is crucial to balancing the injury and repair of the kidneys and determines the progression of hypertensive kidney disease. Arterial hypertension has a large prevalence in the general population and is associated with a wide range of cardiovascular complications and chronic damage to the heart, brain, vasculature, eyes, kidney, and other organs. Hypertensive nephropathy is regarded as the second leading cause of end-stage renal disease (ESRD), outnumbered only by diabetic nephropathy. However, in many cases, it is hard to determine the primary underlying cause of chronic kidney disease (CKD). Arterial hypertension is a typical complication of CKD, irrespective of its etiology, and it is often difficult to differentiate whether increased blood pressure is the cause and/or consequence of impaired kidney function. In any case, coexisting arterial hypertension accelerates the progression of CKD and increases the cardiovascular risk in CKD patients . The cliArterial hypertension is caused and sustained by a complex network of systemic signaling pathways. The renin-angiotensin-aldosterone-system (RAAS) is one important hormonal axis in hypertension. In addition, several other hormones, such as corticosteroids, catecholamines, thyroid hormones, sex hormones, and others contribute to the regulation of blood pressure. Furthermore, it has been shown that the immune system plays an important role in the development and maintenance of hypertension. For example, the balance between IL17 producing T lymphocytes (Th17) and regulatory T cells (Treg) is dysequilibrated in hypertensive patients, favoring Th17 cells. Other conditions favoring Th17 cells can drive hypertension. In this review we aim to provide a brief overview of clinical and histopathological characteristics of kidney injury in hypertensive kidney disease, and of the systemic signaling pathways and important aspects of the immune system, in arterial hypertension. Moreover, we will describe molecular mechanisms in hypertensive kidney injury and repair, including angiotensin II (Ang II) signaling in different cell types, hypoxia signaling, distinct pro-inflammatory pathways, and TGF-associated profibrotic signaling.“Hypertensive nephropathy”, also known as “hypertensive nephrosclerosis”, is traditionally characterized by a combination of pathological changes of the pre- and intra-glomerular microvasculature and the tubulointerstitium. The histopathology can hardly distinguish whether arterial hypertension is the primary cause of kidney dysfunction or whether increased blood pressure occurs as a comorbidity, which drives CKD progression. Thus, the term hypertensive nephropathy summarizes both conditions. The severity of blood pressure elevation often correlates with the degree of renal damage. In many cases, hypertensive nephrosclerosis shows a slow progression, which is historically classified as “benign nephrosclerosis”. In contrast, accelerated nephrosclerosis, histopathologically characterized by fibrinoid necrosis and/or myointimal cell proliferation, is classified as “malignant nephrosclerosis” and frequently leads to ESRD . HyperteAnother hallmark of hypertensive kidney injury is tubular atrophy, accompanied by interstitial fibrosis. Following a loss of functional nephrons, the surviving nephrons initially maintain total kidney function, but the concomitant hemodynamic adaptations results in an oxygen supply-demand mismatch and ultimately tubulointerstitial hypoxia . TubuloiFor decades, the pathophysiology of arterial hypertension has primarily been attributed to vasoconstriction hormones, including RAAS , prostagET1 expression may be regulated by inflammatory mediators, shear stress, and glucose. ET1 has an ambiguous role on the vascular tone. Binding of ET1 to the ET1 receptor A (ETA) of vascular smooth muscle cells causes vasoconstriction, while binding to the ET1 receptor B (ETB) has an indirect vasodilating effect via increased release of nitric oxide (NO). ETA antagonists are clinically used in pulmonary arterial hypertension. Further, ETA antagonists may slow the progression of diabetic nephropathy, but until recently, ET1 antagonists are not licensed in arterial hypertension. Sympathetic activity may be induced by central nervous regulation associated with stress, pain, or cold, It is affected by the RAAS and modifies peripheral resistance. In the last years, several non-pharmacological approaches addressing the autonomic nervous system in arterial hypertension have been developed. Renal sympathetic denervation, carotid baroreflex activation therapy, central iliac arteriovenous anastomosis, carotid body ablation, median nerve stimulation, vagal nerve stimulation, and deep brain stimulation continue to be evaluated with respect to their capacity to lower blood pressure and blood pressure associated target organ damage .Carotid baroreflex activation therapy resulted in a sustained reduction of arterial blood pressure in patients with resistant hypertension in the Rheos Pivotal Trial . Since r+ lymphocytes are key cell types involved in the balance between Treg and Th17 cells, which originate from naive CD4+ cells under specific skewing conditions. Several drivers of hypertension, including Ang II-induced signaling, dietary NaCl, the gut microbiome, at least partly exert their effect via immune mechanisms, and in particular, the regulation of the Treg/Th17 balance , such as the AT1R, ETA, ETA and b-adrenergic receptors. Current pharmacological approaches mainly target these GPCRs. The sensitivity of hormone-induced GPCR activation is modified by G-protein coupled receptor kinases (GRKs), and the regulator of G-Protein Signaling proteins . It has Another important mechanism, contributing to hypertensive nephrosclerosis, is hypoxia . ChronicBesides the development of hypoxia, the hemodynamic changes associated with a defective renal autoregulation of blood pressure, during hypertensive nephropathy, and other types of chronic kidney disease, are associated with flow- and shear-stress dependent signaling in endothelial cells . In respFurther, infiltration of IL17 secreting T lymphocytes may lead to vascular dysfunction. IL17 acts on vascular smooth muscle cells and perivascular fibroblasts, in order to increase reactive oxygen species (ROS) production, collagen synthesis, and chemokine production. In parallel, IL 17 reduces the bioavailability of NO and, vasodilatation, enhances vascular stiffness and the recruitment of immune cells .Despite recent advances in the understanding of molecular mechanisms, contributing to hypertensive nephropathy, the interplay between the different signaling networks in each cell type and—even more complex—between distinct cell types, is still incompletely deciphered. However, “omics” approaches such as single-cell proteomics and metabolomics, in conjunction with advanced imaging techniques, comprise excellent opportunities to gain further insight into this complex signaling network. So far, clinical management of hypertensive CKD focusses on the deceleration of CKD progression. A major aim is to stop all comorbidities, which are known to drive the progression of hypertensive CKD: Blood pressure should ideally be normalized, blood glucose control should be excellent, dietary salt may be restricted, and nephrotoxic medications are to be avoided. Further, pharmacological Ang II blockade has beneficial effects on the progression of hypertensive end-organ damage. Therapeutic approaches to other signaling pathways, such as HIF stabilization, ET1 blockade, anti-inflammatory therapy or immunosuppression, have so far either not been tested or not proven safe and efficient. In pre-clinical research, stem cell based approaches are evaluated to improve kidney regeneration in CKD. However, in nephrology in general, and especially with regard to hypertensive nephropathy, regenerative medicine techniques are still in their children’s shoes. Studies are carried out with embryonic stem cells, mesenchymal stem cells, adipose stem cells, amniotic fluid stem cells, and renal progenitors, but also pluripotent cells. So far, the results from these studies are conflicting. However, even if stem cells and multipotent cells might not directly differentiate and replace damaged cells, they might produce protective and regenerative factors, and thereby enable functional improvement ,61. The bench-to-bedside transition of insight into the molecular mechanisms of CKD in hypertensive patients, and also a profound understanding of the molecular pathogenesis of CKD with other/mixed etiology, may lead to the development novel treatment approaches. Classifying CKD, based on the individual predominant molecular pathology, rather than traditional clinical etiologies would be an important step in developing focused molecular treatments. There is still a long way ahead, but once achieved, personalized medicine holds promise in CKD.


To evaluate the hemolysis biomarkers of packed red blood cells transfused bytwo different linear peristaltic infusion pumps at two infusion rates. An experimental and randomized study was designed simulating the clinicalpractice of transfusion. Two linear peristaltic infusion pumps fromdifferent manufactures were studied in triplicate at 100 mL/h and 300mL/hinfusion rates. The chosen hemolysis biomarkers were total hemoglobin, freehemoglobin, hematocrit, potassium and degree of hemolysis. They wereanalyzed before and after each infusion. Potassium showed statistically significant variations in all scenarios of theexperiment (P<0.010). In a separated analysis, potassium increased mainlyat 300mL/h rate (P=0.021) and free hemoglobin had significant variation whencomparing infusion pumps from different manufacturers (P=0.026). Althoughhematocrit, total hemoglobin and degree of hemolysis had increased afterinfusion, no statistically significance variations were identified. Hemolysis risk induced by a linear peristaltic infusion pump was identifiedby an increase in free hemoglobin and potassium markers. As the potassiumbiomarker is often increased in aged packed red blood cells, we do notrecommend using them in this scenario. Additional studies should beperformed about other markers and using larger samples in order to reinforcethe transfusion practice in nursing. Several models of IPs are available in the market with differentpropulsion mechanisms, such as peristaltic, shuttle, piston cassette, syringe anddiaphragm-,-Electronic infusion devices have brought innovation to the intravenous therapythrough rigorous fluid controlling, security in pressure and air alarms; however,the concern with the safety of this equipment in blood transfusions remainsThe existing evidence does not precisely define the result of the mechanical actionsof infusion devices over the red blood cells. Also, there are few and conflictingstudies about the impact of using IPs on the integrity of RBCs--Peristaltic mechanisms were evaluated in some studies and the results revealed majorrisk of hemolysis-Infusion rate is also a variable mentioned in different studies, and it may haveeffect on the integrity of RBCs. Researchers have observed higher degree ofhemolysis when there are higher RBC infusion rates in peristaltic IPsVolumetric linear IPs have been widely used in health services in Brazil and areprovided by many manufacturers. Decision-making in the nursing area supporting theuse of IPs in RBC transfusion is based on the information provided by themanufactures, but such facts are not consistently evidence-based and are rarelypresented on the device manuals.The aim of the current study was to evaluate the hemolysis biomarkers of packed RBCstransfused by two different linear peristaltic infusion pumps at two infusionrates.This experimental study was performed at the Nursing Experiments Laboratory (LEEnf)after approval from the Research Ethics Committee of the Federal University of SãoPaulo (no. 56518/12).The hemolysis risk was prospectively evaluated in three moments: control samples 1(C1), taken from the blood bags before the experiment had started; control samples 2(C2), collected after the infusion lines were filled; and the last phase, with theinfusion velocity (V), collected after infusion on IPs in the selected rate. Forpost-infusion analyses, the blood volume within the infusion lines was discarded sothat there was no interference in the free flow filling on post-infusion samples.The chosen biomarkers for hemolysis outcome were hematocrit (%), total hemoglobin(g/dL), free hemoglobin (g/dL), degree of hemolysis (%) and potassium (mmol/L).Four packed RBCs units were necessary for the experiment. The amount of packed RBCswas calculated based on the number of analyses to assess the five markers during thestudy phases, resulting in 180 analyses.The included devices were from two different manufacturers, namely infusion pump A(IPA), with horizontal peristaltic system, and B (IPB), with vertical peristalticsystem. Each IP manufacturer was analyzed in triplicate, with a total of six devicesevaluated, and the IPs were randomized according to the rate. The chosen ratessimulated transfusions in adults within 4 hours and rapid transfusion, as inemergency situations, that is, 100mL/h and 300mL/h, respectively. Infusionaccessories, such as blood-filtering kits and infusion extenders, were suitable forthe equipment, as indicated by the manufacturers of the IPs.In experiments with IPA, blood-filtering kits were suitable to the IP, with a totallength of 230 centimeters (cm), and 16mL was the volume needed to fill thelumen.For the IPB, there were no corresponding blood-filtering kits supplied bymanufacturer. Therefore, the manufacturer recommended the use of extension tubesfrom other manufacturers, which were connected to the device for blood components.The total length of the infusion lines, including the extender and the indicateddevice, totaled 270cm, being 26mL the volume needed to fill the lumen.The devices were randomized at each infusion rate and each packed RBC was directed tothree IPs.The four packed RBC were A+ type and were preserved within citrate, phosphate,dextrose and adenine (CPDA-1) anticoagulant solution. The storage time varied from19 to 30 days. Regarding the exposition time of the RBC to the environment in theexperimental phase, the higher amount was 176 minutes, found at 100 mL/h flow inIPB.Before the experiments, the packed RBCs were stored at 2º C to 6º C and during theexperiments it varied from 21.1ºC to 25.3 ºC in the experiments with IPA, and from19.3º C to 24.1º C in those with IPB, monitored through infrared thermometer.In vitro measurements were analyzed according to the suitablebiomarker evaluation technique. Hematocrit assessment was conducted throughcentrifugation and, subsequently, the percentage result was set and double-checkedthrough reading in a specific ruler. The spectrophotometry and the colorimetryassessment techniques were applied to the markers total hemoglobin, free hemoglobin,degree of hemolysis and potassium using the SP-22 Digital Spectrophotometer,Bioespectro® brand, in a range of 325 nanometers (nm) to 1000 nm.Other variables related to blood components and environmental conditions in thelaboratory were measured and controlled, such as the storage time, temperature andexposure time to environment, laboratory temperature and air humidity. Statistical analyses were performed using the Statistical Package for the SocialSciences (SPSS) software, version 20.0. Variables were pre-tested for equal standarddeviations and were estimated to follow a Gaussian distribution according to theKolmogorov-Smirnov test. The distribution of these outcomes was examined usinghistograms. Normally distributed data were presented as mean ± standard deviation(SD), whereas non-normally distributed data were presented as medians andinterquartile range (IQR).P value less than 0.05 (P<0.05) was considered statistically significant.Hemolysis markers were assessed by repeated measures analysis of variance test(ANOVA) and the Bonferroni post hoc test to discover which specific means differedone from another. A This study covered the assessment of five markers in the different phases of theexperiment conducted in each device (IPA and IPB); and in the rates of 100 mL/h and300 mL/h selected in each IP.The outcome variables are regarded in Free hemoglobin presented values from 0.046g/dL to 0.651g/dL in the IPA, and from0.047g/dL to 0.694g/dL in the IPB, thus reaching higher levels in the rate of300ml/h, both in the IPA and IPB. The minimum degree of hemolysis found in the experiment phases with IPA was 0.06%, atinfusion rate of 100mL/h; the maximum degree of hemolysis was 0.81%, found atinfusion rate of 300mL/h. The degree of hemolysis in the IPB have varied from 0.06%,in the experiment phases at infusion rate of 100 mL/h, and 0.83%, at infusion rateof 300mL/h, which corresponded to the moment C1 at the data collection time.Potassium presented minimum value of 39.1mmol/L and maximum value of 43.7mmol/L inthe IPA; and minimum of 37.4mmol/L and maximum of 44.5mmol/L in the IPB..The hematocrit percentage showed non-parametric distribution behavior in thedistribution normality analysis of the variables according to Kolmogorov-SmirnovtestThe effect of infusion system (C2) and infusion pump (V) on the RBC (C1), regardlessof the flow and IP, are summarized in P=0.064). Potassiumconcentration increased during the experiment from 39.5±2.0 mmol/L in C1; 40.1±3.03mmol/L, in C2; 40.9±2.5mmol/L, in V (P < 0.01). The percentage of hematocrit, the total hemoglobin concentration, the free hemoglobinand the degree of hemolysis did not present significant variation in the threemoments of the experiment, regardless of IP and infusion rate. Despite of thestatistical significance, free hemoglobin increased from 0.298±0.20g/dL in C1,0.312±0.21g/dL in C2, and 0.31±0.20g/dL in V . These results, shown inThese multiple comparisons applied to potassium concentration showed statisticallysignificant increase between the control samples of the packed RBC and post-infusionsamples in all infusion rates (The level of hemolysis markers of RBC was assessed according to the IPs (IPA and IPB)and infusion rates (100 and 300 mL/h), as shown in P=0.021).The other markers did not present statistically significant variation regardless ofthe infusion rate.Potassium concentration increased regardless on the programed infusion rate, but witha significant increase on experiments at rate of 300mL/h  and potassium(P=0.022) concentration presented significant increase when the RBCwere submitted to IPA and IPB, respectively.Regarding the additional variables, thelaboratory temperature ranged from 21.2ºC to 26.9ºC and the relative air humidityremained in the mean of 56.7 ± 2.9% during the experiments. The temperature of theblood components varied from 19.3ºC to 25.3ºC during the phases.There was no statistically significant difference in hematocrit, total hemoglobinconcentration and degree of hemolysis, regardless of the IP used in the experiment.The free hemoglobin  , in order to preserve the original features of the blood component andto avoid the damaging effects caused by its storage <0.010) in the p <0.010)  due to t <0.010) , potassi--The analyses of the markers according to the infusion pump  presente-The other markers, such as hematocrit, increased in all the phases of the conductedexperiments, but such increase was not statistically significant. Hematocrit hasbeen associated with the viscosity of the blood components in some publications;thus, the higher the hematocrit value is, the more viscous the blood productComparisons between the studied linear peristaltic IPs were not designed and this isa limitation of the current study. This option was made because of the small sample.There is, though, the need of extending the experiments in further studies toextrapolate the results. Additionally, other device-related variables are essentialfor the definition of the mechanism of action of devices on the RBCs, such asinfusion and occlusion pressure; delimitation of the scenario applied to the devicein order to assess the possible differences between manufacturers; andconsiderations about the environmental variables and blood components.The variables related to the environment and to blood components are extremelyimportant to the global assessment of markers in different moments of the experimentsince they are possible confounding variables. They need to be analyzed in details.Thus, further studies about the theme must be conducted.The development of further research is essential to substantiate the bloodtransfusion clinical practice and the nursing clinical practice of blood componentsadministration. Detailed analyses of the variables related to IP, RBC and additionalbiomarkers, such as the lactate dehydrogenase, haptoglobin, among other injurymarkers, must be carried out.There is, though, the need of extending the experiments in further studies toextrapolate the results. Additionally, the analysis of device-related variables areessential for the definition of the action of IPs over the RBC, such as infusion andocclusion pressures; delimitation of the scenario in order to assess the possibledifferences between manufacturers; besides considerations about the environmentaland the blood components variables.Hemolysis risk induced by a linear peristaltic infusion pumps was identified in thisstudy by an increase in free hemoglobin and potassium markers.Potassium appeared to be an important parameter to assess the fragility of theplasmatic membrane of erythrocytes. There was also a significant increase inevolution of the experiments when it was assessed in all scenarios, as well asgreater increase predisposition at flow of 300mL/h. As the potassium biomarker isoften increased in aged packed red blood cells, we do not recommend using them inthis scenario. Additional studies must be conducted on this theme.


Long waiting time for deceased donor kidney transplant is inevitable due to the scarcity of donor, resulting in highlighting the importance of waiting time care. We analyzed the Korean Network for Organ Sharing (KONOS) database to assess the impact of waiting time on post-transplant survival outcomes and investigate risk factors for mortality by waiting time based on a complete enumeration survey in Korea.We analyzed all persons aged over 18 years in deceased donor kidney transplant cases enrolled in the Korean Network for Organ Sharing (KONOS) database from January 2000 to January 2015. The primary end point was all-cause mortality after enrollment.Of the 24,296 wait-listed subjects on dialysis, 5,255 patients received kidney transplants from deceased donors, with a median waiting time of 4.5 years. Longer waiting times had distinct deleterious effects on overall survival after transplantation. While waiting for a transplant, patients with diabetes were more likely to die before transplantation . Age was another significant risk factor for mortality. Only 56% of people aged 65 years survived after 10 years of waiting, whereas 86% of people aged 35 years survived after 10 years. Moreover, women on the waiting list were more likely to live longer than men on the list.More attention should be focused on patients with a higher risk of mortality while waiting for a deceased donor kidney transplant, such as patients with diabetes, those of advanced age, and those who are male. The number of patients with end-stage renal disease (ESRD) is increasing rapidly at a rate of 5–7% per year . In Sout2 or serum creatinine level ≥ 3.0 mg/dL, hypotensive episode ≥ 3, proteinuria (++) ≥ 2, and non-heart beating donor [In South Korea, if a patient with ESRD who should undergo renal replacement therapy prefers to undergo deceased donor kidney transplantation, each authorized clinic center evaluates the patient for recent malignancy, mental illness, drug addiction, severe liver disease, severe lung disease, active and untreated current opportunistic infection, or active ischemic heart disease . If therng donor . The waiLonger waiting times on dialysis can negatively affect overall mortality and graft outcomes , 11. AccPatients who are on the waiting list for deceased donor kidney transplantation are generally younger and healthier than patients who are not on the list , 15. TheThe KONOS is a government-affiliated organization under the Centers for Disease Control (CDC) that manages deceased donor organ transplantation exclusively in South Korea. The study sample consisted of patients with ESRD who were enrolled on waiting lists for deceased or living donor kidney transplantation in 27 medical centers around the country since January 2000. Among these incident cohort patients, we included adult patients older than 18 years of age who were active on the waiting list or had already undergone deceased donor kidney transplantation. All patients were monitored from the time of registration until death or until the study end date of January 2015. Patients who became medically unsuitable for transplantation or refused a transplant remained on the waiting list until death. Patient demise was obtained from national statistics collected from information recorded at death registration.At the time of registration, demographic and clinical data were entered into the KONOS database, including age, gender, height, body weight, start date of dialysis, cause of ESRD, ABO and Rh blood type, human leukocyte antigen (HLA) type , panel reactive antibody (PRA) positivity, and any prior kidney transplant experience.The original data files from KONOS database are not available for public use because of the personally identifiable information. Concerning privacy risks, the data is managed only by authorized executive supervisor. The authors could perform this study after research agreement from KONOS. The raw data was provided after de-identification so that informed consent from each patients were not required. All analysis performance has never included any identifying process of patients’ personal information.Normally distributed continuous variables were expressed as the mean ± standard deviation (SD) and were compared using Student’s t-test. For non-normally distributed continuous variables, the median and inter-quartile range were used to express the center of the distribution, and Mann-Whitney tests were applied to compare two groups. Chi-square tests were performed to compare percentages.For risk analysis during the waiting time, the primary outcome of our study was patient death. Comparisons between the survival curves of wait-listed patients and transplant recipients were performed using the log rank test. Moreover, we adopted time-dependent Cox regression analysis to eliminate a time-to-treatment bias when analyzing the overall mortality risk of deceased donor kidney transplant recipients according to waiting time. No patients were lost to follow-up for the primary outcome of the study, resulting in no censored cases. To analyze the risk factors during the waiting time for kidney transplant, a multivariate Cox proportional hazards model was used. The Cox proportional hazard models were adjusted for age, gender, blood type, causes of ESRD, and previous kidney transplant experience.The probability of kidney transplantation among wait-listed patients was also analyzed. Multivariate Cox regression was adopted to examine the effects of various clinical factors on transplant probability. The primary outcome was the transplant rate, and time was censored at the transplantation date.The statistical analysis was performed using STATA version 11.0  and SPSS 18 , and statistical significance was defined as a p value less than 0.05.Of the 24,296 wait-listed dialysis subjects, 5,255 patients underwent deceased donor kidney transplantation, and 19,041 patients remained on dialysis. st quartile (35.2 ± 5.7 years) 75.2%, 2nd quartile (47.2 ± 2.6 years) 56.1%, 3rd quartile (54.9 ± 2.0 years) 43.9%, and 4th quartile (64.6 ± 4.8 years) 30.9%. On the other hand, the gender ratio did not show a significant difference between the groups.Regarding patient demographics, kidney transplant recipients were younger than the patients who remained on dialysis . The probability of undergoing deceased donor kidney transplantation after a 10-year wait differed according to age quartile: 1The causes of ESRD in the two groups were as follows: chronic glomerulonephritis (GN) (18.7%), diabetes (15.2%), and hypertension (14.9%) for the transplant recipients, and diabetes (21.4%), chronic GN (18.7%), and hypertension (10.1%) for the remaining patients.The proportions of ABO blood types in the two groups were also different: type A (35.1%), type B (27.7%), type O (22.5%), and type AB (14.6%) in the transplant recipients, and type A (32.8%), type O (29.8%), type B (27.2%), and type AB (10.1%) in the remaining patients. Although 28% of the patients on the overall waiting list had blood type O, these patients accounted only for 22.5% of the deceased donor kidney recipients. Compared with patients with blood type O, the probability of undergoing deceased donor kidney transplantation was 1.49-times higher for patients with blood type A, 1.41-times higher for patients with blood type B, and 2.08-times higher for patients with blood type AB. In other words, patients with blood type O must wait much longer to receive deceased donor kidney transplantation compared to patients with other blood types.PRA positivity and body mass index (BMI) were available only in kidney transplant recipients. Only approximately a quarter (25.3%) of the recipients had information for PRA positivity.th quartile of waiting time (8.13 ± 1.53 years) presented a hazard ratio (HR) of 2.934 with a 95% confidence interval (CI) ranging from 1.808 to 4.763, with a p value lower than 0.001 in a comparison to subjects in the 1st quartile (1.22 ± 0.71 years)  . When we1 years) .After adjusting for recipient age, gender, waiting time, blood type, prior kidney transplant status, and cause of ESRD, we determined that older age and longer waiting time adversely influenced mortality outcomes.th quartile group of a mean age of 64.5 years had a 3.5-times higher mortality ratio than that of the 1st quartile group of age 35.2 years; in other words, aging was another significant risk factor for mortality during waiting time. Female gender groups were less likely to die during waiting time than male groups. ABO Blood type and prior kidney transplant experience did not have a significant impact on overall mortality during waiting time.During waiting time, various demographic and clinical factors were associated with increased mortality. We performed multivariate regression analysis on the success rate of receiving a kidney transplant according to various demographic variables to analyze which patients received deceased donor kidney allografts earlier . Our anaIn the present study, we performed risk factor analysis based on waiting time for 24,296 individuals with ESRD on the waiting list for renal transplantation. Longer waiting periods had an obvious negative effect on overall mortality after transplantation. During that time, patients who were male, of advanced age, or had diabetes were vulnerable to death. We also found that patients who were of advanced age, had diabetes, had blood type O, or had prior kidney transplant experience received donor kidneys later than others on the list.Younger and healthier patients tend to receive kidney transplantation earlier, and longer waiting times should therefore be associated with higher mortality rates. However, in our analysis, we adjusted for demographic and clinical factors, such as age and the cause of ESRD. As a result, longer waiting time was identified as an independent risk factor for post-transplant mortality, which has also been shown in previous studies , 11.This study mainly showed which risk factors may affect mortality or kidney transplantation rates during waiting times. The prevalence of mortality is known to increase significantly with age or diabetes in patients with ESRD –19. AlthIn general, women have a survival advantage over men in the general population. Even in patients with chronic kidney disease, women tend to progress to ESRD at a slower rate than men do, regardless of disease etiology . HoweverIn our study, we determined that patients with blood type O or prior kidney transplant experience were disadvantaged in terms of receiving a deceased donor kidney in a timely manner. Patients with advanced age or diabetes may acquire more comorbidities as waiting time progresses, so a reduced probability of undergoing transplantation over time is expected. However, patients with blood type O suffer from a disadvantage in the prioritization of receiving deceased donor kidney allografts due to biological differences. ABO-compatible kidney transplantation rules allocate blood type O kidneys to non-blood type O recipients; consequently, patients with blood type O on dialysis who can only receive kidneys from the same blood type have a lesser likelihood of receiving these organs. According to the annual statistical report by the KONOS, 4~7% of deceased donor kidney transplantations were performed on non-identical–but ABO-compatible–blood types in the last 5 years . As a reIn addition, not only patients with blood type O or history of kidney transplantation were less likely to undergo deceased donor kidney transplant in a timely manner but also those with causes of ESRD other than DM tended to undergo deceased kidney at a later time. In our study, the analysis was limited in at least three respects. First, missing or unknown data represented 36% of the data on ESRD causes. Another limitation was knowledge regarding the origin of kidney disease in all patients with ESRD because kidney biopsy was not performed in all patients to determine the cause of ESRD. Nevertheless, the fact that more than one-third of the data were unknown or missing causes an interpretation bias. Second, socioeconomic status was not provided for the wait-listed candidates. In Korea, at least 10 thousand dollars per patient is required for kidney transplantation surgery, even if these patients benefit from national health services . TherefoIn conclusion, this study indicated the risk factors of mortality during waiting time for deceased donor kidney transplantation and the characteristics of patients who received deceased donor kidney transplantation after longer waiting times. Considering the deleterious effect of longer waiting time on mortality, identifying vulnerable patients during the waiting time and providing more intensive care for these patients are important.S1 File(ZIP)Click here for additional data file.S1 Table(DOCX)Click here for additional data file.S2 Table(DOCX)Click here for additional data file.


To determine the effect of different hypertension management guidelines and of basing diagnosis on a single reading of blood pressure on the hypertension prevalence in the Indian population.Fourth national family health survey, 2015 to 2016, over all districts in India. We calculated the proportion of the population within three different age groups  with raised blood pressure according to six different guidelines, and how prevalence changed if diagnoses were based on a single blood pressure measurement.We performed a secondary analysis of data acquired as part of the We observed that the Government of India and the American College of Cardiology/American Heart Association guidelines consistently yielded the lowest and highest prevalence of raised blood pressure; in the combined age group, we calculated the proportion of the population categorized as having raised blood pressure as 7.5% : 7.4 to 7.7) and 40.1% (95% CI: 39.7 to 40.7), respectively. When basing diagnosis on a single reading of blood pressure only, a total of 56 million individuals would be erroneously categorized as hypertensive following the Government of India guidelines. We also showed that prevalence of hypertension in India varies with guidelines adhered to; in the combined age group, the national hypertension prevalence was three times higher when following the American College of Cardiology/American Heart Association compared with the Government of India guidelines.To optimize current clinical practice, health-care providers need to follow universally agreed, evidence-based methods of diagnosing hypertension. Although clinical care guidelines are only recommendations, the decision to follow a specific set of guidelines by a health-care provider should be based on the local context of need, availability and affordability, especially in low- and middle-income countries.,,–Blood pressure measurement is one of the most common non-invasive clinical practice tools used to assess the cardiovascular status of an individual and predict the likelihood of future cardiovascular events. An individual’s blood pressure can change quickly and regularly, and is influenced by respiration, temperature, bladder distension, pain levels, emotion, diet, time since last exercise and whether alcohol has recently been consumed.,––Over the past 25 years, the availability of health-care services have increased in India, and the country has adopted a universal health coverage programme.Here we have analysed the impact of inconsistent practices on the calculated prevalence of hypertension. We have focused on the particular blood pressure measurements at which hypertension is diagnosed and whether a single reading or the recommended number of readings was taken, for six different hypertension guidelines.We used data from the most recent large-scale health survey, the Fourth National Family Health Survey,The six different guidelines that we used in this study for the calculation of hypertension prevalence are published by the European Society of Cardiology,The number of readings taken, the number of visits required by the patient and the blood pressure at which hypertension is diagnosed  for each of these six guidelines are listed in From the sample, we excluded participants having at least one missing blood pressure measurement or having unfeasible (i.e. systolic blood pressure < 30 mm Hg or < diastolic blood pressure) readings. We calculated the proportion of individuals within various blood pressure categories for age groups 18 to 34, 35 to 49 and 18 to 49 years of age for all six guidelines. We applied sampling weights and adjusted confidence intervals (CIs) at the primary sampling unit level to obtain nationally representative estimates with precise CIs. To calculate prevalence, we defined participants having hypertension if they had stage I/grade I or higher blood pressure, taking prescribed medicine to control blood pressure or being informed at least twice by the health professional that they had raised blood pressure or hypertension. We estimated the total population within each age group from Census of India 2011 age distribution data,We calculated the number of individuals across India within each category for each guideline by multiplying the proportion within each blood pressure category according to the Fourth National Family Health Survey by the calculated population within each age group. To confirm that the exclusion of participants did not cause significant difference in terms of age, sex and place of residence in the final data set, we performed a sensitivity analysis by comparing prevalence estimates from the clean data set with those from the full data set. We performed all analyses using Stata software, version 15.0 .The Fourth National Family Health Survey obtained ethical clearance from the Ethics Committee of the International Institute for Population Sciences.We obtained data on 797 161 individuals from the survey. We excluded 45 691 patients with missing data and 1594 participants with unusual blood pressure measurements.We observe that the Government of India and the American College of Cardiology/American Heart Association guidelines consistently yield the lowest and highest prevalence of measured raised blood pressure, respectively . For theWe also observe an increase in the weighted proportion of the population classified as having raised blood pressure when only a single blood pressure reading (i.e. the first reading taken) is considered, compared with measuring blood pressure from several readings as recommended by the guidelines . If the By neglecting to follow any guidelines precisely and by basing diagnosis on a single reading of blood pressure only, a total of 56 million would be erroneously categorized as hypertensive instead of normotensive following the American College of Cardiology/American Heart Association guidelines . The lar,,This study compares the difference in hypertension prevalence when using six hypertension management guidelines in India. Our findings, that prevalence of hypertension varies according to guidelines followed and according to the number of blood pressure readings taken, are in concordance with other studies.Another recent studyOur study had several limitations. We may have overestimated hypertension prevalence by our definition of hypertension being based on blood pressure measurements taken during one occasion; a clinical diagnosis of hypertension requires raised blood pressure on at least two different occasions.,Our results show that the current use of several different guidelines in India results in inconsistent prevalence data, which could result in poor health outcomes. We therefore urge global bodies to discuss and propose a universal guideline, similar to the cut-off for body mass index, malnutrition and anaemia. In our opinion, the European Society of Hypertension guidelines are most suited for India; these guidelines have the same definitions of blood pressure categories as the Government of India guidelines, but diagnosis is made from the last two readings (out of three) instead of the lowest reading (out of two or three). This recommendation is supported by two different studies.To optimize current clinical practice in India, health-care providers need to follow universally agreed, evidence-based methods of diagnosing hypertension. The importance of multiple measurements and its impact on health management must be emphasized to health-care professionals. Once such guidelines have been agreed upon, their display at prominent locations within hospitals could help to improve the health literacy of the general population.


Gout is a common inflammatory arthritis associated with adverse clinical outcomes. Under treatment is common in the general population. The aim of this study was to determine the prevalence of gout and its treatment among patients with chronic kidney disease (CKD).We conducted a multi-centre cross sectional study of patients (n = 522) who attended specialist nephrology clinics in Ireland. Standardized data collection tool recorded clinical characteristics and medication use at clinic visits and kidney function was assessed with standardised creatinine measurements and Estimated Glomerular Filtration Rate (eGFR). The prevalence of gout and the corresponding use of urate lowering therapies (ULT) were determined. Multivariate logistic regression explored correlates of gout expressed as Odds Ratios (OR) and 95% Confidence Intervals (CI) adjusting for demographic and clinical characteristics.P< 0.005. Prevalence increased with age (P < 0.005) and was higher in men than women (19.1% versus 10.3% P< 0.005). Overall, 67.9% of gout patients with CKD were treated with ULT, and the percentage increased with advancing stage of CKD from 55.6% in Stage 1–2 to 77.4% in Stage 4–5, P<0.005. Multivariable modelling identified men (vs women), OR, 1.95 (0.95–4.03), serum albumin, OR 1.09 (1.02–1.16) per 1 g/L lower, poorer kidney function, OR 1.11 (1.01–1.22) per 5 ml/min/1.73m2 lower, and rising parathyroid hormone levels, OR 1.38 (1.08–1.77) per 50 pg/ml higher as disease correlates.Overall prevalence of gout was 16.6% and increased significantly from 7.5% in Stage 1–2 CKD to 22.8% in stage 4–5 CKD, Gout is common in CKD and increases with worsening kidney function in the Irish health system. Over two thirds of patients with gout were receiving ULT, increasing to 77% of patients with advanced CKD. Greater awareness of gout in CKD, its treatment and the effectiveness of treatment strategies should be vigorously monitored to improve patient outcomes. Gout is a common inflammatory arthropathy caused by the deposition of monosodium urate crystals in joints and soft tissues. In the general population, the prevalence of gout varies worldwide from 0.1% to approximately 10% and incidence rates vary from 0.3 to 6 cases per 1,000 person-years –4. Gout 2. Adjusting for confounding, individuals with severe renal impairment had a 6-fold higher prevalence of gout compared to those with normal kidney function . The study was approved by the Ethics Committee of University Hospital Limerick.2 (Stages 1–2), 30–59 (Stage 3) and <30 (Stages 4–5).Gout was defined as the presence of a documented clinical diagnosis of gout on medical case records and/or physician clinic letters or if the patient was receiving ULT. The Estimated Glomerular Filtration Rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation  and CKD Descriptive statistics were calculated for continuous variables  and categorical variables (reported as numbers and percentages). Comparisons across groups were made using Fisher’s exact tests for categorical variables and Kruskal-Wallis test for continuous variables. Multivariable logistic regression models were fitted to explore the associations of demographic and clinical factors with prevalent gout. Sequential age, and age and sex adjusted models were developed to examine relationships. The explanatory variables included age modelled as 5-year intervals, sex, comorbid medical conditions, laboratory values recorded prior to clinic visit, and prescribed medications. A final multivariate model was constructed to identify the relative contributions of demographic, clinical and treatment factors with the presence of gout. Model performance was assessed using the c-statistic and the adequacy of the logistic models was tested using the Hosmer and Lemeshow goodness-of-fit test. Associations were expressed as odds ratios (ORs) and 95% confidence intervals (CIs) and all analyses were performed using R statistical software .2. The principal causes of CKD were hypertension (26.8%), glomerulonephritis (18.1%) and diabetes (12%), although for a large proportion the primary cause was classified as unknown in 13.6%.2 (p < 0.005) and significantly greater proteinuria . Gout patients also experienced significantly lower serum albumin concentrations and significantly higher parathyroid hormone concentrations than those without gout, all p<0.001.The overall prevalence of gout in the entire cohort was 16.6% and increased significantly from 7.5% in CKD stages 1–2 to 22.8% in CKD stages 4–5, p < 0.005 . When goOverall, 67.9% of patients with gout were receiving ULT as shown in 2 decrease in eGFR]. Similarly, higher levels of proteinuria quantified by protein/creatinine ratio estimation were correlated with greater likelihood of gout [log2 PCR 1.45 (1.09–1.93), p<0.05). Lower serum albumin levels and worsening secondary hyperparathyroidism were also associated with greater likelihood of gout [OR 1.09 (1.03–1.14) per 1 g/dL decrease in albumin, and OR 1.33 (1.14–1.56) per 50 pg/mL increase in PTH, all p <0.005. Use of diuretics and beta-blockers also correlated with gout [OR 2.72 (1.61–4.60) and OR 1.81 (1.08–3.02) respectively.The relationship of demographic and clinical factors with gout is illustrated in In the fully adjusted model, lower eGFR and worsening serum albumin remained significant correlates of gout as illustrated in 2). Gout was more common in men than in women and rates increased with advancing age. Adjusting for differences in age and sex, we found that patients with lower kidney function, lower serum albumin, and worsening secondary hyperparathyroidism were more likely to have gout. Overall, almost 68% of gout patients with CKD were receiving ULT agents, with allopurinol being the most commonly prescribed ULT. Importantly and encouragingly, we observed a significant trend of increasing ULT use from 55.6% in Stage 1–2 to 77.4% in Stage 4–5, evidence that supports better recognition and treatment of gout in this high-risk population.In this large multi-centre study, we found a substantial burden of gout among Irish patients with CKD (16.6%) that increased significantly from 7.5% in patients with mild CKD to 22.8% among patients with moderate to severe CKD . However, unlike Germany, the principal ULT in Ireland were uricostatic , as no patient was recorded as receiving uricosuric therapy. Encouragingly, we reveal that rates of ULT use have increased from 55.6% among patients in CKD stage 1–2 to 77.4% for patients with more advanced CKD 4–5 suggesting a propensity to greater ULT prescribing. This trend in prescribing patterns may reflect the increasing recognition by kidney specialists in Ireland that gout is eminently treatable or that gout and/or hyperuricaemia are emerging risk factors for CKD progression %. Howeve. It is eDespite the moderately high proportion of CKD patients with gout receiving ULT therapy in this study, a substantial proportion of patients (~32%) nevertheless were untreated. Studies have consistently shown that the treatment of gout is suboptimal in the general population . PrescriPrior studies have identified strong relationships between hyperuricaemia, the precursor to gout, and several metabolic markers . In the We also uncovered a very strong independent association between elevated PTH and the occurrence of gout. This is an intriguing finding, which suggests that progressive secondary hyperparathyroidism serves to increase the likelihood of gout in the setting of CKD. Previous studies have suggested a strong biological influence of PTH on serum uric acid levels possibly mediated by reduced renal excretion of uric acid –35. HoweFirst, the design of the study was cross-sectional in nature with reliance on medical records for data extraction. Therefore, we cannot infer causality between explanatory covariates and gout. Second, although joint aspiration for monosodium urate crystals remains the gold standard for diagnosis in clinical practice, our study relied on a clinical diagnosis from medical records based on physician-diagnosis and/or use of ULT. Inclusion of ULT medications ensured greater capture of clinical gout that may not have been recorded on the patient’s medical record. Third, we lacked data on serum uric acid concentrations, and thus were unable to correlate gout or ULT use with target thresholds. Notwithstanding these limitations, the study was multicentre, with participation from a diverse range of nephrology clinics across Ireland, thus strengthening the generalisability. Although a probability sampling strategy would have been preferred, we argue that the application of consecutive sampling to a homogenous population, attending renal clinics across multiple sites reduces bias in relation to the representativeness of the study population. The large sample included a detailed description of patient characteristics including comorbid conditions, measures of kidney function including proteinuria. Finally, our analysis included a detailed description of current prescribed ULT medications as well as medications for acute flares and flare prophylaxis.Our study is not with limitations. In conclusion, our findings demonstrate a substantial burden of gout among patients with CKD in the Irish health system that increases with advancing CKD. Male gender, worsening kidney function, malnutrition and secondary hyperparathyroidism were identified as independent correlates. Almost 68% of patients with CKD were receiving ULT that increased to 77% among patients with Stage 4–5 CKD. Patients with both gout and CKD represent a high-risk group for considerable morbidity and mortality, compounded by the individual contribution of each to adverse clinical outcomes. Given the substantial burden of gout in CKD patients, greater awareness, screening and treatment of gout are key to improving patient outcomes in this population. Future studies should examine dosing of ULT among CKD patients and the extent to which treatment targets are achieved in order to prevent the complications of gout and potentially slow the progression of CKD.S1 Appendix(DOC)Click here for additional data file.


The incidence of intra-abdominal hypertension (IAH) is high and still underappreciated by critical care physicians throughout the world. One in four to one in three patients will have IAH on admission, while one out of two will develop IAH within the first week of Intensive Care Unit stay. IAH is associated with high morbidity and mortality. Although considerable progress has been made over the past decades, some important questions remain regarding the optimal ventilation management in patients with IAH. An important first step is to measure intra-abdominal pressure (IAP). If IAH (IAP > 12 mmHg) is present, medical therapies should be initiated to reduce IAP as small reductions in intra-abdominal volume can significantly reduce IAP and airway pressures. Protective lung ventilation with low tidal volumes in patients with respiratory failure and IAH is important. Abdominal-thoracic pressure transmission is around 50%. In patients with IAH, higher positive end-expiratory pressure (PEEP) levels are often required to avoid alveolar collapse but the optimal PEEP in these patients is still unknown. During recruitment manoeuvres, higher opening pressures may be required while closely monitoring oxygenation and the haemodynamic response. During lung-protective ventilation, whilst keeping driving pressures within safe limits, higher plateau pressures than normally considered might be acceptable. Monitoring of the respiratory function and adapting the ventilatory settings during anaesthesia and critical care are of great importance. This review will focus on how to deal with the respiratory derangements in critically ill patients with IAH. Intra-abdominal hypertension (IAH) is defined as a sustained increase in intra-abdominal pressure (IAP) equal to or above 12 mmHg .IAH is associated with increased morbidity and mortality , 4 and iIAH directly impacts on organ function of the abdominal organs such as kidney and liver. Furthermore, IAH can affect the function of organs outside the abdominal cavity including the brain, the cardiovascular system and the lungs . Figure IAH affects mainly respiratory mechanics and only in part oxygenation. IAH causes a cephalad shift of the diaphragm thereby increasing intra-thoracic pressures and reducing chest wall compliance and lung volumes . Table 1The aim of this review is to discuss the effects of IAH on respiratory function and the ventilatory management of patients with IAH, needless to state that the ventilatory management of patients with IAH has to take into account not only the respiratory effects of IAH but also the consequences of any underlying chronic lung disease or a newly acquired lung injury.Around one in four to one in three patients present with IAH on admission to intensive care unit (ICU) while around one in two will develop IAH within the first week of ICU stay , 9. More2/FiO2 ratio < 300 mmHg, or receiving positive end-expiratory pressure (PEEP) > 10 cmH2O or having a peak airway pressure > 28 cmH2O are more likely to have IAH /2 or simplified: plateau pressure target − 7 + 0.7 * IAP in mmHg.It follows that in the presence of IAH airway pressures could be corrected by using ATT. In critically ill subjects IAP is on average 10 mmHg = 13.6 cmH2O , 9, 82 a2O and an IAP of 20 mmHg the corrected target plateau pressure would be: 30 − 7 + 0.7 * 20 * = 37 cmH2O. In the absence of IAH, plateau pressures target would not require any correction. For example, for target plateau pressure of 30 and IAP 10 mmHg the corrected plateau pressure target would be 23 + 10 * 0.7 = 30 cmH2O.For example, for a target plateau pressure of 30 cmHIn summary, although higher airway pressures might be acceptable in ARDS patients with IAH we are lacking any supporting clinical data to make any recommendations.In more recent years, driving pressure (pressure difference between plateau airway pressure and PEEP) as a measure of protective lung ventilation has gained more attention.2O is associated with improved hospital survival in patients with ARDS [2O in patients with IAH.Driving pressure appears to be helpful to optimize tidal volume and to avoid excessive dynamic strain. Using data from nine randomized trials and a total of 3562 patients with ARDS, it has been demonstrated that the driving pressure has a greater influence on mortality than plateau airway pressure, tidal volume or PEEP . A largeith ARDS . In obesith ARDS . No studDriving pressure may also be useful in titrating PEEP and has been tested with promising physiological results in obese patients undergoing general anaesthesia , 87 and To date, the best PEEP to be used in the setting of IAH remains unknown . As stat2O) were unmatched to the level of IAP [2O, while PEEP was only set up to a maximum of 15 cmH2O. In a second study, conducted in 9 pigs with healthy lungs, IAH was again created with an inflatable balloon, the PEEP levels were now matched for IAP [2 insufflation up to 20 mmHg, the PEEP levels (27 cmH2O) were matched for IAP [Different animal studies have examined different levels of PEEP in the setting of IAH. A first study was conducted in 13 pigs with healthy lungs and IAH was created with an inflatable balloon, the PEEP levels  in patients with ARDS. The patients with extrapulmonary ARDS had IAH (IAP of 16 mmHg) and PEEP improved CRS due to a reduction in CCW. In contrast, the patients with pulmonary ARDS had normal IAP (4 mmHg) and PEEP worsened CRS due to an increase in CL.Gattinoni et al.  applied Talmor et al. , 96 founIn a pilot study of 15 patients with IAH (IAP of 17 mmHg), different levels of PEEP were applied that were matched to the level of IAP . In cont2O) to be set to the level of IAP (mmHg).It is difficult to draw any conclusions from these experimental and clinical studies. In principle, it makes sense to apply higher PEEP levels in the context of IAH. Furthermore, it is appealing to apply an easy to use bedside formula for setting the PEEP level in patients with IAH, e.g. PEEP (cmH2O and average IAP increase of 1 mmHg) [2O in 30 patients with ARDS and found that IAP increased predominantly in patients with IAH (i.e. IAP increased from 15 to 20 cmH2O).There is a concern that increasing PEEP can increase IAP. Many published studies found PEEP to have only minimal influence on IAP (increasing PEEP from as low as 0 to as high as 15 cmH 1 mmHg) . In cont 1 mmHg)  examinedIn summary, while PEEP can counteract the negative effects of IAH on lung volume and chest wall compliance, there is no evidence that a certain PEEP level improves outcome in patients with IAH. In the absence of any evidence we recommend to set the PEEP according to the best respiratory system compliance .Assisted breathing is the most common type of ventilation in critically ill patients  and evenLittle is known about the optimal ventilation mode to be applied in patients with IAH but some experimental data exist. Several experimental evidences of ARDS without IAH showed reduced lung injury during assisted ventilation –104. RecIn conclusion, we suggest a cautious use of assisted ventilation in patients, especially if in the presence of severe IAH.Prone position improves respiratory mechanics, oxygenation and reduces over-distension . Prone v2 and decreases in ventilation perfusion heterogeneity. The observed decrease in IAP (estimated via gastric pressure), resulting in a concomitant decrease in pleural pressure in the prone position may be a possible explanation for these observations, hence facilitating regional ventilation in the dependent lung zones near the diaphragm.In the setting of IAH, there seems to be some merit by suspending and offloading the abdomen during prone ventilation. Mure et al.  demonstr2O) and supine (11.0 ± 4.2 cmH2O) positions when targeting lung compliance.In a recent experimental study in 12 pigs that underwent pulmonary saline lavage and injurious ventilation to simulate ARDS, the authors showed that prone position and PEEP independently improved lung compliance without interaction . As expeDe Jong et al.  successfPlacing patients with ARDS in the prone position either does not change or only has mild influence on IAP levels with more pronounced effects in patients with IAH , 112. FoCCW, while the suspension at the level of the symphysis pubis will ensure a free suspended abdomen and thereby limiting transmission of IAP towards the dorsobasal lung regions and diaphragm. This decreases IAP and improves abdominal compliance and reduces atelectasis via dorsobasal recruitment. The theoretical benefits of proning a patient with IAH need to be outweighed against the practical risks (e.g. patients with an open abdomen).The use of chest and pelvic suspension has a large influence on IAP pressures . The preCCW and improving abdominal compliance  over IAP gradient .In the absence of IAH (RAP > IAP), increasing IAP levels can increase venous return and improve cardiac output by redistribution of blood from the abdominal to the thoracic compartment. In the presence of IAH however (RAP < IAP), venous return and cardiac output are reduced. It is possible that increasing PEEP in the presence of IAH might favourably change the RAP over IAP gradient (RAP > IAP) and thereby improving both venous return and cardiac output.There are only a few animal and human studies examining combined haemodynamic effect of IAH and PEEP. In animal studies PEEP (ranged of 4–22 mmHg) had a stronger negative impact on cardiac output than IAP (range of up to 26 mmHg) , 19, 55.2O) in 20 patients with ARDS but did not find any cardiovascular differences between the patients with and without IAH.Krebs et al.  applied In a pilot study of 15 patients with IAH but healthy lungs, different PEEP levels were applied and no difference in blood pressure or heart rate was found probably due to small sample size .2O was applied and echocardiography was performed [In 8 volunteers with inflated medical anti-shock trousers (IAP not measured), additional PEEP of 10 cmHerformed . It was In summary, limited experimental and clinical data suggest that the negative haemodynamic effect of PEEP is to some degree counteracted in patients with IAH. However, it is difficult to draw any conclusions from above studies and the clinician should be cautious when applying higher PEEP levels in patients with IAH as cardiovascular response to higher PEEP levels is difficult to predict.Medical management strategies for raised IAP may be divided into five categories according to their proposed mechanism of action. First, improvement of abdominal wall compliance ; second, evacuation of intra-luminal contents ; third, drainage of intra-abdominal fluid collections (paracentesis or percutaneous catheter drainage); fourth, avoidance of excessive fluid resuscitation and correction of a positive patient fluid balance ; and fifth, organ support (respiratory and cardiovascular monitoring as outlined above) , 122. ItMonitoring extravascular lung water and pulmonary vascular permeability  can provide useful additional information. Deep sedation with a short course of neuromuscular blocking agents may be useful in selected patients or as a bridge towards decompressive laparotomy.Although considerable progress has been made over the past decades, some important questions remain relating to the optimal ventilation management in patients with IAH. When looking after patients with IAH and ARDS requiring mechanical ventilation, an important first step is to measure IAP and aim to reduce IAP in order to reduce airway pressures keeping in mind that small reductions in intra-abdominal volume can significantly reduce IAP and airway pressures .Although challenging, the measurement of oesophageal pressure as surrogate for intra-thoracic pressure can provide trans-pulmonary pressures that can help guide ventilation . It is o2O. Higher than recommended plateau pressures of 30 cmH2O might be required in the setting of IAH. Taking normal IAP of 10 mmHg and ATT of around 50% into account, 23 cmH2O + 0.7 * IAP in mmHg might be an appropriate upper limit of plateau pressure.During lung-protective ventilation, we recommend the application of protective lung ventilation with low tidal volumes of 6–8 mL/kg and maximum driving pressure of 15 cmH2O) equal to 50% of IAP in cmH2O. In the absence of any evidence, we recommend to set the PEEP according to the best CRS.In addition, in patients with IAH, higher PEEP levels might be required to prevent end-expiratory lung collapse. However, the best PEEP in the setting of IAH is still unknown. Pressure-volume loops or the use of oesophageal pressure might be useful to determine the best PEEP in patients with IAH. Knowing that the ATT is around 50%, it may be appropriate to set PEEP  interventions aimed at reducing IAP and improving abdominal compliance will ultimately improve outcomes in patients with IAH and abdominal compartment syndrome.


To study blood pressure alterations after microvascular decompression (MVD) surgery in patients with hemifacial spasm (HFS).A retrospective study was performed to review HFS patients who received MVD surgery between January 2014 and December 2016. Vessels that were considered to be responsible for HFS were determined by reviewing the brain magnetic resonance imaging, magnetic resonance angiography, and surgical video. Blood pressure measurements were performed 1 day before (preoperative) and 7 days after (postoperative) the MVD surgery. Pre‐ and postoperative blood pressure measurements were compared.p = .01) or without  hypertension. Diastolic blood pressure only had statistically significant decrease in patients with hypertension . Analyses in all the study patients and in the subgroup of patients with hypertension showed that more statistically significant blood pressure reductions were observed when left‐side vessel or vertebrobasilar artery was involved.A total of 374 patients were included in the study, with 118 (31.6%) male patients, age 53.8 ± 9.9 years old, and 141 (37.7%) patients with hypertension. Systolic blood pressure had statistically significant decrease in patients with  surgery in patients with hemifacial spasm (HFS). We found that in patients with HFS, MVD not only decreased blood pressure in patients with hypertension but also affected blood pressure in patients without hypertension. Blood pressure reductions were more prominent when left‐side vessel or vertebrobasilar artery was involved. Patients were placed in the lateral decubitus position, and the infratentorial–retrosigmoid approach was used. A 4‐centimeter skin incision was made at the affected occipital area. The scalp, muscle, and periosteum were open, and a 2 × 2 cm bone window was created by a driller and rongeur at the squamous part of occipital bone. The outer edge of the bone window was the sigmoid sinus, and the lower edge was close to the skull base. The dura mater was cut open in a "⊥" shape and suspended. Under the microscopic examination, the cerebellum was exposed and loosened in order to fully expose the facial nerve REZ area. After confirming the responsible vessel for HFS, a polyester cotton pad was used to separate the vessel and nerve at a single or multiple compression points. A biological glue was used to stick the thick vertebral artery to the petrous bone if necessary in order to ensure the complete pressure relief for the cranial nerve. The dura mater and skull were closed after complete hemostasis was achieved.2.3Blood pressure was measured 1 day before the surgery (preoperative measurement) and 7 days after the surgery (postoperative measurement). On the day of the measurement, blood pressure was checked manually three times at 6:00 a.m., 2:00 p.m., and 6:00 p.m. The mean number from these three blood pressure measurements was recorded as the blood pressure value for that day. Systolic and diastolic pressures were documented separately.2.4SD, and categorical data were presented as percentages. Pre‐ and postoperative blood pressure measurements in the same patients were compared by the paired t test. Comparisons between different groups were performed by t test or chi‐square analysis when appropriate. A p < .05 was considered statistically significant. All the statistical analyses were performed with SPSS .Numerical data were presented as mean ± 33.1Altogether, 389 patients received the MVD surgery during the study period and 374 patients were identified, with 118 (31.6%) male patients and age 53.8 ± 9.9 years old  and in patients with VA involvement. But we have not found the other BP value alternation in the other features of HFS, as gender and the disease duration of HFS. These were found in all the study patients and in the subgroup of patients with a previous diagnosis of hypertension. The higher incidence of HFS and blood pressure alteration in patients with left‐side vascular compression might be due to the more profuse vagus nerve and C1 adrenergic nerve distribution on the left side of medulla oblongata, which could affect the afferent and efferent nerves to the left ventricles (Boogaarts et al., In addition to affecting the cardiovascular function, brainstem medulla and pons have important structures to regulate vital physiological activities, including respiration, consciousness, swallowing, bladder control, and sleep cycle. There were previous reports that MVD surgery could treat hemiplegia, type II diabetes, apnea, dysphagia, and intractable hiccups (Hoffman & Stiller, It was suspected that symptomatic treatment, such as botulinum toxin injections, could decrease blood pressure. As a retrospective study, we did not study botulinum toxin injection in this study. We also did not have accurate records on botulinum toxin injection on every patient. We will consider to address this question in future investigations.Limitations in the current study included single‐center study, retrospective biases, a small number of patients in the subgroup analysis, and short follow‐up time period. In addition, various factors might influence the accuracy of blood pressure measurements during the preoperative period in this retrospective study. Future prospective studies with a large sample size and long observation time are required to confirm our findings.5In patients with HFS, MVD surgery could not only decrease the blood pressure in patients with hypertension but also affect systolic blood pressure in patients without hypertension. This blood pressure‐lowering effect was more prominent when the responsible vessel was on the left side and when VA was involved.None declared.Hongtao Sun designed the study, Xuegang Niu and Fei Yuan prepared the manuscript, Zhengjun Wei and Xuyi Chen collected the data, Hang Wang and Jibin Ren searched the references and made data analysis, and Jian Zhang and Weixin Li polished and revised the manuscript. All the authors approved the final version of this manuscript.


Hypertension is the single greatest contributor to human disease and mortality affecting over 75 million people in the United States alone. Hypertension is defined according to the American College of Cardiology as systolic blood pressure (SBP) greater than 120 mm Hg and diastolic blood pressure (DBP) above 80 mm Hg measured on two separate occasions. While there are multiple medication classes available for blood pressure control, fewer than 50% of hypertensive patients maintain appropriate control. In fact, 0.5% of patients are refractory to medical treatment which is defined as uncontrolled blood pressure despite treatment with five classes of antihypertensive agents. With new guidelines to define hypertension that will increase the incidence of hypertension world-wide, the prevalence of refractory hypertension is expected to increase. Thus, investigation into alternative methods of blood pressure control will be crucial to reduce comorbidities such as higher risk of myocardial infarction, cardiovascular accident, aneurysm formation, heart failure, coronary artery disease, end stage renal disease, arrhythmia, left ventricular hypertrophy, intracerebral hemorrhage, hypertensive enchaphelopathy, hypertensive retinopathy, glomerulosclerosis, limb loss due to arterial occlusion, and sudden death. Recently, studies demonstrated efficacious treatment of neurological diseases with deep brain stimulation (DBS) for Tourette’s, depression, intermittent explosive disorder, epilepsy, chronic pain, and headache as these diseases have defined neurophysiology with anatomical targets. Currently, clinical applications of DBS is limited to neurological conditions as such conditions have well-defined neurophysiology and anatomy. However, rapidly expanding knowledge about neuroanatomical controls of systemic conditions such as hypertension are expanding the possibilities for DBS neuromodulation. Within the central autonomic network (CAN), multiple regions play a role in homeostasis and blood pressure control that could be DBS targets. While the best defined autonomic target is the ventrolateral periaqueductal gray matter, other targets including the subcallosal neocortex, subthalamic nucleus (STN), posterior hypothalamus, rostrocaudal cingulate gyrus, orbitofrontal gyrus, and insular cortex are being further characterized as potential targets. This review aims to summarize the current knowledge regarding neurologic contribution to the pathophysiology of hypertension, delineate the complex interactions between neuroanatomic structures involved in blood pressure homeostasis, and then discuss the potential for using DBS as a treatment for refractory hypertension. Hypertension affects 32.6% of the US adult population and is one of the greatest risk factors for cardiovascular disease . The 201Despite multiple treatment options, fewer than 50% of hypertensive patients achieve appropriate blood pressure control with medication and up to 0.5% of patients are refractory to medical treatment . RefractPatients with resistant hypertension have a higher risk of myocardial infarction, cardiovascular accident, aneurysm formation, heart failure, coronary artery disease, end stage renal disease, arrhythmia, left ventricular hypertrophy, intracerebral hemorrhage, hypertensive enchaphelopathy, hypertensive retinopathy, glomerulosclerosis, limb loss due to arterial occlusion, and sudden death . AdditioRecent clinical applications of deep brain stimulation (DBS) are mainly in neurological diseases including Tourette’s , depressThe regulation of blood pressure is a complex process that involves the interplay of a many organ systems, with contributions from the central nervous system (CNS), autonomic nervous system, kidneys, heart, and vasculature . A simplThe central autonomic network (CAN) is the CNS integration circuit of autonomic information from the periphery and functions to effect an appropriate autonomic response to the environment . Input tThe CAN also contains higher structures that have the capability to alter autonomic activity without input from the periphery, such as in instances where an increase in activity is solely imagined . The corThe hypothalamus plays an important role in the pathogenesis of hypertension . AntidiuSalt-sensitive changes in sympathetic outflow are mediated by the paraventricular nucleus of the hypothalamus acutely, and by the forebrain hypothalamus chronically . HyperteThe exact mechanism of salt sensitivity is largely unknown. Genetic studies reveal that sodium-bicarbonate cotransporters, SLC4A4, and SLC4A5, as well as striatin mediate salt sensitivity . Recent The arcuate nucleus of the hypothalamus plays a significant role in the regulation of sympathetic outflow . The arcInflammation, from circulation or prostaglandin E2 made locally by perivascular macrophages, can activate the periventricular nucleus of the hypothalamus, and cause an increase in sympathetic outflow and ACTH release . FurtherLeptin levels are increased in obese patients and have been correlated with increased BP . Leptin Electrical stimulation of a variety of targets has caused changes in blood pressure in both human and animal models. In 1894, it was reported that changes in autonomic output, such as an elevation in blood pressure, were observed when the orbital surface of the frontal lobe was stimulated in animals . In the Within the PAG, there are four functional columns . StimulaLasting changes in blood pressure have been reported with PAG D/BS  , althouFurther evidence for DBS of the ventral PAG in treating hypertension was described in 2017 by The rostral suballosal neocortex has reciprocal connections with the ventral PAG/PVG and the lateral hypothalamic nuclei as well as many lower centers, including the rostral ventrolateral medulla that is speculated to be the effector location at which sympathetic outflow was decreased in the efferent component of the baroreceptor reflex . InterruPatients with Parkinson’s Disease who underwent stimulation of the STN with a frequency of over 100 Hz were reported to have a modest increase in heart rate and blood pressure  . The STNFound in the diencephalic area of the brain and responsible for homeostatic and vegetative functions, the posterior hypothalamus regulates neurotransmitter release connecting the amygdala, hippocampus, and retina . StimulaSystolic and diastolic arterial pressure rose in 8 of 12 patients who received bilateral stimulation of the rostrocaudal cingulate gyrus (in 1949), and one patient had a reduction in these pressure . This grIn 1949, 6 of 9 patients had an increase in blood pressure when the orbital surface of the frontal lobes was electrically stimulated . RecentlThe insular cortex has been found to have varied effects when stimulated in human subjects. The homeostatic mechanisms that function to maintain blood pressure are complex and intimately related to the CNS. Because the brain is involved in control of these processes, neuromodulation of structures offer promise in the treatment of hypertension. The most thoroughly studied target is the periaqueductal gray, although other areas such as the rostral subcallosal neocortex and insular cortex have also been described. If chronic modulation of these structures is able to produce sustained normalization of blood pressure, DBS might become a treatment modality for patients who do not otherwise respond to antihypertensive therapy.JM designed and directed the project. JM and TO provided the technical expertise. RE and AG underwent literature review and wrote the paper with input from all authors.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Background: We aimed to evaluate the relationship between biopsy-proven kidney lesions, subclinical markers of atherosclerosis and intrarenal resistive index (RRI) in chronic kidney disease (CKD) patients.Methods: This cross-sectional, single-center study prospectively enrolled 44 consecutive CKD patients  years, median eGFR 28.1 (15.0–47.7) mL/min) diagnosed by renal biopsy during 6 months in our clinic. RRI, carotid intima-media thickness (IMT), Kauppila score for abdominal aortic calcification (AACs) were assessed. Traditional and nontraditional atheroscleosis risk factors were also evaluated.Results: Most of the patients had a diagnosis of glomerular nephropathy, with IgA nephropathy and diabetic nephropathy being the most frequent. RRI increased proportionally with CKD stages. Patients with RRI >0.7 (39%) were older, had diabetic and vascular nephropathies more frequently, higher mean arterial blood pressure, increased systemic atherosclerosis burden (IMT and AACs), higher percentage of global glomerulosclerois, GBM thickness, arteriolosclerosis and interstitial fibrosis/tubular atrophy. RRI directly correlated with age  and with all the studied atherosclerosis markers . Also, global glomerulosclerosis  and interstitial fibrosis/tubular atrophy  were directly correlated with RRI. In multivariable adjusted binomial logistic regression models, only arteriolosclerosis was retained as independent predictor of RRI >0.7.Conclusion: The analysis of RRI may be useful in the evaluation of the general vascular condition of the patient with CKD, supplying information about both microvascular and macrovascular impairment. Moreover, RRI correlates well with renal histopathologic characteristics, particularly with arteriolosclerosis. The renal resistive index (RRI) measured by Doppler sonography in intrarenal arteries, describes the percentage reduction of end diastolic blood flow in renal vessels in relation to the maximal systolic blood flow. Data suggest that the RRI reflects the intrinsic state of vascular and parenchymal renal abnormalities. However, the resistive index also depends on central hemodynamic factors like the aortic pulse pressure and aortic stiffness . The relTherefore, we performed a prospective study to evaluate in detail the relationship between biopsy-proven kidney lesions, subclinical markers of atherosclerosis and intrarenal resistive index in chronic kidney disease (CKD) patients.This prospective, cross-sectional study enrolled 44 consecutive patients referred to ‘‘Dr. Carol Davila’’ Teaching Hospital of Nephrology, Bucharest, Romania in a 6-month period, who underwent a diagnosis kidney biopsy.Inclusion criteria were a biopsy-proven chronic kidney disease with a light microscopic specimen that included more than 5 glomeruli, age older than 18 years, and sufficient clinical data. Exclusion criteria were acute kidney injury, hepatic disease, valvular heart disease, renal artery stenosis, and urinary tract obstruction and refusal to give an informed consent.The following data at kidney biopsy were available: age, mean arterial pressure (MAP defined as diastolic blood pressure plus 1/3 of pulse pressure), presence of hypertension (defined as a blood pressure >140/90 mmHg or the use of antihypertensive agents), inflammatory status , lipid profile (serum cholesterol and triglycerides), serum albumin, eGFR (four variable CKD-EPI formula), proteinuria (24-h urine protein-to-creatinine ratio - UPCR) and hematuria (red blood cells per milliliter).In order to evaluate the atherosclerotic burden, we used a semiquantitative score based on the clinical involvement of cerebral, carotid, coronary and peripheral vascular territories. Each affected territory was scored with one point; the maximum score was four. Patients were considered to suffer from coronary artery disease after coronary artery bypass surgery or in the presence of at least one diameter stenosis in coronary angiography; cerebrovascular disease if they had a previous ischemic stroke or a transient ischemic attack; carotid artery disease if they had previously undergone carotid surgery or if a significant stenosis could be detected by duplex sonography; peripheral artery disease was diagnosed after a previous peripheral revascularisation or if an ankle-brachial index of less than 0.9 could be detected in at least one pedal artery.Abdominal aortic calcifications (AAC) were evaluated on a lateral lumbar X-ray (with the patient in standing position), as described by Kauppila .For intima media thickness (IMT) determination B-mode ultrasonography imaging of the carotid artery was performed with a transducer frequency of 7 MHz . Up to 4 cm of the common carotid artery, the carotid bifurcation and the internal carotid 2 cm distally from bifurcation were scanned bilaterally using longitudinal and transverse sections. IMT was defined as the distance between the leading edge of the first echogenic line (lumen-intima interface) and the second echogenic line (media-adventitia interface) in plaque-free arterial segments . All meap < 0.001). The use of antihypertensive medication was not suspended before RRI measurement. Ultrasonographic examination that included RRI assessment was performed the day before the renal biopsy. In order to avoid inter-observer variability, all Doppler examinations were performed by the same examiner who was unaware of the study or the clinical details of the patients.For Doppler ultrasonography examination a real-time ultrasound device with color Doppler capacity (Samsung HM70A) and a 3.5 MHz convex-type transducer (CA1-7AD) were used. The examination was performed early in the morning, after 8-h overnight fast, with the patient in supine position and after at least 15 min rest. The signals were obtained from interlobar and arcuate arteries in the upper, middle, and lower parts of the kidney. The RRI was calculated as [(peak- systolic velocity – end-diastolic velocity)/peak systolic velocity]. The RRI value for each kidney was the mean of all 6 measurements. A mean RRI value was obtained for each patient by averaging the two kidneys’ mean RRIs . All subjects signed an informed consent prior to any study procedure.For each biopsy specimen, light microscopy, immunofluorescence and electron microscopy were routinely performed. One pathologist and one nephrologist reviewed independently the slides without knowledge of the original biopsy diagnosis, typically several months after the original pathology report.The histological analysis included an in-depth review of the glomerular, tubulointerstitial and vascular compartments. Definitions of histologic variables used in our study were derived from the Mayo Clinic/Renal Pathology Society Consensus  and are Continuous variables are presented as mean or median and 95% confidence interval, according to their distribution, and categorical variables as percentages.2 test, and Mann–Whitney U test, as appropriate. The Pearson and Spearman test were used to assess correlations according to distribution.Patients were categorized into two groups based on the commonly used cutoff value of RRI of 0.7 . Group cThe associations between RRI  and IMT, AAC score, global glomerulosclerosis, interstitial fibrosis/tubular atrophy and arteriolosclerosis as covariates, adjusted for the traditional cardiovascular risk factors were investigated by multivariable adjusted binomial logistic regression.p < 0.05 was considered statistically significant.A Analyze-it  and SPSS  software were used to analyze the data.The mean age of the whole cohort was 54 years old, 57% were men. The median eGFR was 28 mL/min, and median proteinuria was 3.3 g/g creatinine. Approximately three quarters of the patients were treated for arterial hypertension and one quarter had diabetes mellitus .Most of the patients had a diagnosis of glomerular nephropathy, with IgA nephropathy and diabetic nephropathy being the most frequent .Intrarenal resistive index proportionally increased with CKD stages . PatientPatients with global and segmental glomerulosclerosis, arteriolosclerosis, severe arteriosclerosis and endothelial swelling had higher RRI .Intrarenal resistivity index was directly correlated with age and with all the studied atherosclerosis markers, atherosclerosis score, AAC score and IMT. Regarding the histopathologic parameters, global glomerulosclerosis and interstitial fibrosis/tubular atrophy were directly correlated with RRI. .The association between RRI and atherosclerotic markers and categories of histopathologic lesions was tested separately in five distinct multivariable adjusted binomial logistic regression models, the remaining covariates - age, diabetes mellitus, arterial hypertension, eGFR, UACR - being the same. Only arteriolosclerosis was retained as independent predictor and made statistically significant contribution to the model .We evaluated the relative contributions of renal lesions histopathologically assessed and subclinical atherosclerosis markers to the intrarenal resistivity index. To our knowledge this is the first report to address the full spectrum of intrarenal lesions. We found that RRI was associated with the atherosclerotic burden, global glomerulosclerosis, interstitial fibrosis/tubular atrophy and arteriolosclerosis. However, after adjustment for traditional cardiovascular risk factors only arteriolosclerosis was independently associated with RRI.The studies on the relationship between histopathological findings and RRI in renal disease had conflicting results. Most of the studies did not include an evaluation of all renal compartments, i.e., glomeruli, tubulo-interstitium, and vascular. Moreover, histopathologic assessment was performed based only on a dichotomous scale or used vague criteria. In order to overcome these limitations, we studied all these components concurrently as damages are closely related to each other and their influence on RRI could be cumulative.et al, only arteriolosclerosis out of all histologically studied parameters independently correlated with RRI in CKD [et al found a significant relationship of RRI with glomerulosclerosis, arteriolosclerosis, and tubulo-interstitial damage [According to Ikee I in CKD . AnotherI in CKD . Moreovel damage .Remarkably, arteriolosclerosis seems to be the only kidney biopsy finding that, in most of the studies, was independently correlated with the increase in RRI. Our results are in line with these observations: we found that only arteriolosclerosis was retained as an independent determinant of RRI after adjustment for traditional cardiovascular risk factors.Hyaline arteriolosclerosis is a common vascular lesion, found in many different situations, including aging, arterial hypertension, diabetes mellitus, focal and segmental glomerulosclerosis. It is generated by the accumulation of serum proteins in the subendothelial space, often extending into the media . ArterioIn accord with other reports, we found that high RRI values are related to more severe tubulo-interstitial damage score, probably due to the increased stiffness of renal vessels due to interstitial fibrosis. Tubular atrophy and interstitial fibrosis correlate closely with renal function and long term prognosis, which may underlie the utility of RRI as an independent marker of renal and clinical outcome in CKD . MoreoveIn earlier reports, glomerulosclerosis association with increased RRI was not constant. Only one of the former studies reported a significant direct association of RRI with glomerulosclerosis. However, RRI was significantly lower when the glomerular involvement was isolated, i.e., not associated with any vascular and/or tubulo-interstitial damage ,15,19,20As previously reported ,19,21–23In chronic kidney disease patients, many authors found a RRI of 0.70 or higher to be an independent risk factor for CKD progression regardless of the baseline eGFR, proteinuria, or arterial hypertension ,30. ThesSome limitations of this study should be acknowledged. First, the data resulted from a cross-sectional design with a small sample size from a single center, which can limit the statistical power. Second, the selection criteria for kidney biopsy influenced the composition of the cohort, i.e., we included mostly patients with glomerular nephropathies and only a few had vascular and tubulo-interstitial diseases. However, the final cohort reasonably describes the patients seen in daily practice. Finally, Doppler ultrasonography is an operator dependent method; nevertheless, the risk of inter-observer variability was reduced in our study because only one experienced examiner performed all ultrasound assessments.In conclusion, the analysis of intrarenal resistivity index may be useful in the evaluation of the general vascular condition of the patient with CKD, supplying information about both microvascular and macrovascular impairment. Moreover, RRI correlates well with renal histopathologic characteristics, particularly with arteriolosclerosis.All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee at which the studies were conducted and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.Informed consent was obtained from all individual participants included in the study.