Degree Of Renal Function Impairment Research Articles

Reversed diastolic intrarenal flow in page kidney following renal biopsy.

Page's kidney is a condition that occurs due to external renal compression, usually caused by a subcapsular haematoma, generating a renal compartmental syndrome with parenchymal damage and renal perfusion alteration. Classically associated with renal trauma, Page's kidney can also arise after invasive renal procedures, such as renal biopsies or percutaneous nephrostomies. Clinically, it can trigger hypertension due to activation of the renin-angiotensin system induced by hypoperfusion secondary to renal parenchymal compression and can also present with varying degrees of renal function impairment. Furthermore, severe acute renal failure may be found particularly in patients with solitary kidneys or renal transplants. We present two cases of Page's kidney after renal biopsy and their PoCUS ultrasound findings. We would like to highlight the reversed diastolic flow on Doppler ultrasound in this entity, a pattern we have found in all two cases.

Estimation of differential renal function on routine abdominal imaging employing compressed-sensed contrast-enhanced MR: a feasibility study referenced against dynamic renal scintigraphy in patients with deteriorating renal retention parameters

PurposeTo assess whether high temporal/spatial resolution GRASP MRI acquired during routine clinical imaging can identify several degrees of renal function impairment referenced against renal dynamic scintigraphy.MethodsThis retrospective study consists of method development and method verification parts. During method development, patients subject to renal imaging using gadoterate meglumine and GRASP post-contrast MRI technique (TR/TE 3.3/1.6 ms; FoV320 × 320 mm; FA12°; Voxel1.1 × 1.1x2.5 mm) were matched into four equally-sized renal function groups (no-mild-moderate-severe impairment) according to their laboratory-determined estimated glomerular filtration rates (eGFR); 60|120 patients|kidneys were included. Regions-of-interest (ROIs) were placed on cortices, medullary pyramids and collecting systems of bilateral kidneys. Cortical perfusion, tubular concentration and collecting system excretion were determined as TimeCortex=Pyramid(sec), SlopeTubuli (sec−1), and TimeCollecting System (sec), respectively, and were measured by a combination of extraction of time intensity curves and respective quantitative parameters. For method verification, patients subject to GRASP MRI and renal dynamic scintigraphy (99mTc-MAG3, 100 MBq/patient) were matched into three renal function groups (no-mild/moderate-severe impairment). Split renal function parameters post 1.5–2.5 min as well as MAG3 TER were correlated with time intensity parameters retrieved using GRASP technique; 15|30 patients|kidneys were included.ResultsMethod development showed differing values for TimeCortex=Pyramid(71|75|93|122 s), SlopeTubuli(2.6|2.1|1.3|0.5 s−1) and TimeCollecting System(90|111|129|139 s) for the four renal function groups with partial significant tendencies (several p-values < 0.001). In method verification, 29/30 kidneys (96.7%) were assigned to the correct renal function group.ConclusionHigh temporal and spatial resolution GRASP MR imaging allows to identify several degrees of renal function impairment using routine clinical imaging with a high degree of accuracy.

Clinical Characteristics and Prognosis of Diabetic Foot Ulcers Patients of Different Renal Function Statuses

To explore the clinical characteristics and the prognosis of diabetic foot ulcers (DFU) inpatients of different renal function statuses. A retrospective analysis of 962 inpatients with DFU was conducted. The patients were divided into three groups according to their renal function statuses, and the clinical characteristics of the three groups were compared to identify differences. In addition, the patients were followed up in outpatient clinics or by telephone and their prognostic status and risk factors for death were analyzed. Analysis of the clinical characteristics showed that, compared with diabetic patients with normal renal function or mild renal function impairment, diabetic patients with moderate and severe renal function impairment had a longer course of disease ( P<0.001). Patients with foot ulcers of Wagner grade 4 predominates the moderate and severe renal function impairment groups ( P<0.05). Patients in the moderate and severe renal function impairment groups had a relatively higher proportion of comorbidities, including hypertension, coronary heart disease, and peripheral arterial disease ( P<0.05). These patients had relatively lower levels of glycosylated hemoglobin and hemoglobin (all P<0.05) and relatively higher levels of neutrophil ratio and procalcitonin (all P<0.05). Of the two groups, patients in the moderate renal function impairment group were older ( P<0.001) and had lower ankle-brachial index ( P<0.001). The severe renal function impairment group had a higher proportion of patients with foot ulcers of Wagner grades 3 and 5 (all P<0.05). For the purpose of conducting prognostic analysis, 748 patients were followed up in outpatient clinics or by telephone for a median length of 41 months. Among them, 239 died. The all-cause mortality was 31.9%, and the mortality in the three groups was 25.8%, 46.2% ( P<0.001), and 59.4% ( P<0.001), respectively. The survival rate of patients in the moderate and severe renal function impairment groups was significantly lower than those in the normal renal function and mild renal function impairment groups ( P<0.001). Univariate Cox regression analysis showed that age, concomitant coronary heart disease and peripheral arterial disease, degree of renal function impairment, and foot ulcers of Wagner grade 4 and 5 were associated with all-cause deaths. Furthermore, multivariate Cox regression analysis showed that moderate and severe renal function impairment was an independent risk factor for all-cause deaths in DFU patients ( P<0.001). As renal function impairment worsens, patients with DFU present clinical characteristics of greater complexity, higher risks of cardiovascular events, and higher mortality. It is essential to prevent kidney damage and foot ulcers, to pay attention to the cardiovascular risks of DFU patients with moderate and severe renal function impairment, and to reduce mortality.

Dose-dependent effect of impaired renal function on all-cause mortality in patients following percutaneous coronary intervention.

ObjectiveTo determine the risk prediction of various degrees of impaired renal function on all‐cause mortality in patients following percutaneous coronary intervention (PCI).BackgroundPatients with chronic kidney disease (CKD) are at high risk of all‐cause mortality after PCI. However, there are less data of various degrees of impaired renal function to predict those risks.MethodsThis was a subgroup analysis of nationwide PCI registry of 22 045 patients. Patients were classified into six CKD stages according to preprocedure estimated glomerular filtration rate (eGFR) (ml/min/1.73 m2): I (≥90), II (60−89), III (30−59), IV (15−29), or V (<15) without or with dialysis. Baseline clinical and angiographic characteristics were compared among patients in each stage. One‐year all‐cause mortality was reported with risk prediction based on CKD stages and other risk factors.ResultsPatients with CKD stage I−V without and with on dialysis were found in 26.9%, 40.8%, 23.2%, 3.9%, 1.5%, and 3.7%, respectively. PCI procedural success and complication rates ranged from 94.0% to 96.2% and 2.8% to 6.1%, respectively. One‐year overall survival among CKD stages I−V was 96.3%, 93.1%, 84.4%, 65.2%, 68.0%, and 69.4%, respectively (p < .001 by log‐rank test). After adjusting covariables, the hazard ratios of all‐cause mortality for CKD stages II−V as compared to stage I by multivariate Cox regression analysis were 1.5, 2.6, 5.3, 5.9, and 7.0, respectively, (p < .001).ConclusionAmong patients undergoing PCI, lower preprocedure eGFR is associated in a dose‐dependent effect with decreased 1‐year survival. This finding may be useful for risk classification and to guide decision‐making.

Kidney biopsy chronicity grading in antineutrophil cytoplasmic antibody-associated vasculitis.

BackgroundKidney biopsy is valuable for prognostic assessment of renal outcomes in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) with glomerulonephritis (AAV-GN) but the impact of chronic changes is not determined.MethodsWe conducted a retrospective cohort study of myeloperoxidase (MPO)- or proteinase 3 (PR3)-ANCA-positive patients with AAV and active renal disease. We applied the Mayo Clinic Chronicity Score (MCCS) and validated and evaluated its implications on outcome prediction in AAV-GN.ResultsWe analyzed 329 patients with kidney biopsies available to score. The extent of chronicity was graded by MCCS as minimal [102 (31.0%)], mild [106 (32.2%)], moderate [86 (26.1%)] and severe [35 (10.6%)]. The MCCS grades correlated with the degree of renal function impairment at presentation [mean estimated glomerular filtration rate (eGFR) 48.3 versus 29.2 versus 23.7 versus 18.5 mL/min/1.73 m2, respectively; P < 0.0001]. Higher degrees of the individual components of the MCCS (glomerulosclerosis, interstitial fibrosis, tubular atrophy and arteriosclerosis) were associated with lower median eGFR (P < 0.0001) and decreased event-free [kidney failure (KF) and death] survival (P = 0.002, P < 0.0001, P < 0.0001 and P = 0.017, respectively). Patients with lower MCCS grades recovered renal function more frequently (P < 0.0001). Increasing MCCS grades were associated with decreased renal recovery (P = 0.001), more frequent events and shorter time to KF (P < 0.0001), KF and death (P < 0.0001) and death (P = 0.042), independent of the remission induction treatment used (cyclophosphamide or rituximab). The MCCS stratified renal outcomes for each MCCS grade and can be used in clinical practice as a cutoff for KF prediction (MCCS ≥4).ConclusionsChronic changes on kidney histology independently predict renal function, outcomes and response to treatment in AAV-GN.

Acute kidney injury in patients with pneumonia with A/H1N1 influenza

Background . A critical condition of any genesis may be accompanied by the development of multiple organ failure, one of the manifestations of which is acute renal injury. Often, the process is subclinical in nature and the «classical» approaches to diagnose renal damage by creatinine concentration, urea level and assessment of glomerular filtration rate may not fully reflect the degree of impaired renal function, while acute kidney injury is a well-known predictor of high hospital mortality among critically ill patients. Aims. The purpose of this study was to assess functional state of the kidneys by determining the serum concentration of the markers of kidney injury NGAL and Cystatin C in patients with pneumonia associated with influenza A/H1N1. Materials and methods . 85 patients with pneumonia associated with influenza A/H1N1 were examined, 30 patients with severe pneumonia, 55 with non-severe pneumonia. The control group was formed by 15 healthy donors. The serum concentration of NGAL and Cystatin C molecules was determined by flow cytometry on a Beckman Coulter analyzer (USA), using a Human Immune Checkpoint Panel 1 multiplex assay kit (Biolegend, USA). The glomerular filtration rate was calculated using the CKD-EPI formula. Results . It was found that in patients with severe pneumonia with the influenza A/H1N1, the concentration of NGAL increased 3.8 times compared with the control group, the concentration of Cystatin C increased 1.4 times, the glomerular filtration rate did not change. Conclusion . Timely diagnosis of subclinical kidney injury makes it possible to objectify the severity of the condition, make adjustments to therapy, which can help to an increase in the survival rate of critically ill patients.

MO168MANAGEMENT OF ANTICOAGULANT RELATED NEPHROPATHY: SLOVENIAN CASE SERIES AND REVIEW OF CURRENT KNOWLEDGE

Abstract Background and Aims Anticoagulant-related nephropathy is a recently recognized form of acute kidney injury associated with previously underdiagnosed kidney damage in addition to (usually) excessive anticoagulation. It occurs in patients receiving warfarin as well as those receiving direct oral anticoagulants. Method We collected and analyzed cases of Slovenian patients with pathohistologically documented anticoagulant-related nephropathy associated with all types of anticoagulant treatment from the first case in 2014 to 2020. We also performed an analysis of previously documented cases of anticoagulant-related nephropathy in the global literature (PubMed) in the period from their first mention until recently. Results In Slovenia, 13 patients with anticoagulant-related nephropathy have been histologically verified so far. All patients were diagnosed with concomitant underlying renal disease, and 80% had IgA nephropathy, which was disproportionately mild according to the degree of renal function impairment. After supportive measures and reversal of excessive anticoagulation, 8 of 13 patients were further treated with corticosteroids, resulting in significant improvement in renal function. During the follow-up period, a total of one steroid-treated patient died due to infectious complications and one patient progressed to end-stage renal failure. In the worldwide literature, we found 46 case reports or case series of patients with anticoagulant-related nephropathy. Failure of restitution of renal function with the need for maintenance dialysis was reported much more frequently compared to the results of our cohort (up to 67% vs. 8.3%) Conclusion To our knowledge, the Slovenian cohort of patients with histologically established anticoagulant-related nephropathy is the largest reported series to date that received corticosteroid therapy in addition to conservative measures. Our results indicate that steroids have a beneficial effect, likely exerted via suppression of hemoglobin-associated oxidative stress and inflammation. However, considering the polimorbidity of these patients, the benefit of additional steroid therapy must be weighed against the potential risks of side effects, especially life-threatening infections.

POS-276 TO STUDY EFFICACY AND SAFETY OF ANTIRESORPTIVE THERAPY IN CKD STAGE 3-5D PATIENTS

Bisphosphonate therapy improves BMD and lowers the fracture risk in general population. The large randomized trials excluded patients with known renal dysfunction. Only post hoc studies on the subjects with an estimated eGFR lower than 60 have shown that the fracture reduction was similar to subjects with a normal eGFR. This study was done to evaluate efficacy and safety of bisphosphonates in subjects with various degrees of renal function impairment. Eighty patients of CKD stage 3- 5D with age > 18 yrs with informed consent were randomized to placebo versus 35 mg of alendronate, taken once a week for 12 months. Patients with age <18 or > 70 years, h/o of previous use antiresorbtive therapy or steroids in last 6 months, with PTH < 200 and/or bSAP < 30 and renal transplant recipients were excluded. Primary outcomes of study were assessed with help of DEXA scan for improvement in mean T score, Z score and BMD at level of lumbar spine, femur neck and total hip, done at baseline, at 6 month and 12 month and X rays for evidence of fractures and vascular calcification. Secondary out comes were assessed by looking for any adverse reactions related to treatment during each follow up visit and improvement in biochemical parameters like PTH, calcium, phosphorous and ALP levels. A total of 150 patients of CKD age 3-5D presenting to Nephrology ward, OPD and/or dialysis unit were initially screened for the study. A total of 80 patients with T score < -1SD on DEXA scan, meeting inclusion criteria finally completed the study period duration and were included for final analysis. There was improvement in mean T score, Z score and BMD at level of lumbar spine, femur neck and total hip at 6 and 12 months in patients, who received oral alendronate compared to controls. This change in mean of T score, Z score and BMD was statistically significant between two groups at 6 and 12 month irrespective of CKD stage. There was no difference in overall mean ALP level at baseline, 3, 6 and 12 months between control and case group in CKD 3, 4 and 5. But there was statistically significance difference in mean PTH level between control and cases at 12 month (P=0.047) when analyzed as combined irrespective of CKD stage. But this difference was not seen for individual CKD sub stage. There was no increase in base line proteinuria for various CKD stages between case or control group at the end of the study. 2 patients in control group and one in case group had fracture. There was no significant difference in the incidence of fractures between treatment and control arm. The benefit of the treatment was independent of the degree of renal impairment. Five patients had initially GI intolerance to alendronate, one had osteonecrosis of jaw, one had dermatological reaction to alendronate, but none of them required stoppage of drug due to side effects. Our study demonstrated the efficacy and safety of antiresorptive therapy in patients with CKD stage 3-5D. Low-dose alendronate, administered for longer duration, appears to be well tolerated in CKD 3-5D patients without major adverse effects. The BMD, T-scores and Z score declined in the placebo group over 12 months, while there was improvement in the treatment group, suggesting a bone-preserving effect of alendronate. There were no major adverse effects of therapy except for mild GIT intolerance.

A Comparison of Urine Dilution Ability between Adult Dominant Polycystic Kidney Disease, Other Chronic Kidney Diseases, and Healthy Control Subjects: A Case-Control Study.

The final dilution of urine is regulated via aquaporin-2 water channels in the distal part of the nephron. It is unclear whether urine dilution ability in autosomal dominant polycystic kidney disease patients (ADPKD patients) differs from other patients with similar degree of impaired renal function (non-ADPKD patients). The purpose of this case control study was to measure urine dilution ability in ADPKD patients compared to non-ADPKD patients and healthy controls. Methods. Eighteen ADPKD, 16 non-ADPKD patients (both with chronic kidney disease, stage I-IV), and 18 healthy controls received an oral water load of 20 ml/kg body weight. Urine was collected in 7 consecutive periods. We measured free water clearance (CH2O), urine osmolality, urine output, fractional excretion of sodium, urine aquaporin2 (u-AQP2), and urine epithelial sodium channel (u-ENaC). Blood samples were drawn four times (at baseline, 2 h, 4 h, and 6 hours after the water load) for analyses of plasma osmolality, vasopressin, renin, angiotensin II, and aldosterone. Brachial and central blood pressure was measured regularly during the test. Results. The three groups were age and gender matched, and the patient groups had similar renal function. One hour after water load, the ADPKD patients had an increased CH2O compared to non-ADPKD patients (2.97 ± 2.42 ml/min in ADPKD patients vs. 1.31 ± 1.50 ml/min in non-ADPKD patients, p0.029). The reduction in u-AQP2 and u-ENaC occurred earlier in ADPKD than in non-ADPKD patients. Plasma concentrations of vasopressin, renin, angiotensin II, and aldosterone and blood pressure measurements did not show any differences that could explain the deviation in urine dilution capacity between the patient groups. Conclusions. ADPKD patients had a higher CH2O than non-ADPKD patients after an oral water load, and u-AQP2 and u-ENaC were more rapidly reduced than in non-ADPKD patients. Thus, urine-diluting capacity may be better preserved in ADPKD patients than in non-ADPKD patients.

Urine concentration ability is reduced to the same degree in adult dominant polycystic kidney disease compared with other chronic kidney diseases in the same CKD-stage and lower THAN in healthy control subjects - a CASE control study

BackgroundConcentration of the urine is primarily regulated via vasopressin dependent aquaporin-2 water channels in the apical membrane of kidney principal cells. It is unclear whether urine concentration ability in ADPKD differs from other patients with similar degree of impaired renal function (non-ADPKD patients). The purpose of this case control study was to measure urine concentration ability in ADPKD patients compared to non-ADPKD patients and healthy controls.MethodsA seventeen hour long water deprivation test was carried out in 17 ADPKD patients (CKD I-IV), 16 non-ADPKD patients (CKD I-IV), and 18 healthy controls. Urine was collected in 4 consecutive periods during water deprivation (12 h, 1 h, 2 h and 2 h, respectively) and analyzed for osmolality (u-Osm), output (UO), fractional excretion of sodium (FENa), aquaporin2 (u-AQP2) and ENaC (u-ENaC). Blood samples were drawn trice (after 13-, 15-, and 17 h after water deprivation) for analyses of osmolality (p-Osm), vasopressin (p-AVP), and aldosterone (p-Aldo).ResultsU-Osm was significantly lower and FENa significantly higher in both ADPKD patients and non-ADPKD patients compared to healthy controls during the last three periods of water deprivation. During the same periods, UO was higher and secretion rates of u-AQP2 and u-ENaC were lower and at the same level in the two groups of patients compared to controls. P-AVP and p-Osm did not differ significantly between the three groups. P-Aldo was higher in both groups of patients than in controls.ConclusionsUrine concentration ability was reduced to the same extent in patients with ADPKD and other chronic kidney diseases with the same level of renal function compared to healthy controls. The lower urine excretion of AQP2 and ENaC suggests that the underlying mechanism may be a reduced tubular response to vasopressin and aldosterone.Trial registrationCurrent Controlled Trial NCT04363554, date of registration: 20.08.2017.

Biomarker evidence for distal tubular damage but cortical sparing in hospitalized diabetic patients with acute kidney injury (AKI) while on SGLT2 inhibitors

Background Inhibitors of sodium-glucose co-transporter-2 (SGLT2i) were found to improve renal outcome in diabetic patients in large prospective randomized trials. Yet, SGLT2i may acutely reduce kidney function through volume depletion, altered glomerular hemodynamics or intensified medullary hypoxia leading to acute tubular injury (ATI). The aim or this study was to prospectively assess the pathophysiology of acute kidney injury (AKI) in patients hospitalized while on SGLT2i, differing ATI from pre-renal causes using renal biomarkers. Methods Serum and urine Neutrophil Gelatinase-Associated Lipocalin (NGAL) and Kidney Ischemia Molecule (KIM)-1, markers of distal and proximal tubular injury, respectively, were determined in 46 diabetic patients who were on SGLT2i upon hospitalization with an acute illness. Results Serum and urine NGAL, but not KIM-1, were significantly increased in 21 of the patients who presented with AKI upon admission, as compared with 25 patients that maintained kidney function. Both serum and urinary NGAL correlated with the degree of impaired renal function, which in many cases was likely the result of additional acute renal perturbations, such as sepsis. Conclusions Increased urinary and serum NGAL indicates that ATI, principally affecting distal tubular segments, may develop in some of the patients hospitalized with an acute illness and AKI while on SGLT2i. It is suggested that intensified medullary hypoxia by SGLT2i might be detrimental in this injury. By contrast, concomitantly unaltered KIM-1 might reflect improved cortical oxygenation by SGLT2i, and may explain an overall reduced risk of AKI with SGLT1i in large series. The independent potential of SGLT2i to inflict medullary hypoxic damage should be explored further.

Association of renal cortical echogenicity and renal function in chronic kidney disease - sonographic study

Ultrasonographically measured renal cortical echogenicity (RCE) is known to increase in chronic kidney disease (CKD) and of value in predicting the degree of renal function impairment. Renal function is routinely assessed by serum creatinine levels (Scr) and estimated glomerular filtration rate (eGFR). The aim of the study was to evaluate the association of RCE with Scr and eGFR in CKD subjects.

Correlation between eye and renal complications of diabetes

Introduction. Complications of diabetes can affect almost all tissues and organs, causing high morbidity, disability and mortality. The aim of this study was to examine eye and kidney disorders of patients with patients with diabetes, and assess the correlation between them. Material and Methods. This retrospective study included 45 patients suffering from type 2 diabetes for more than ten years. The patients were divided into three groups of 15 subjects each: patients without diabetic retinopathy, patients with non-proliferative retinopathy, and patients with proliferative diabetic retinopathy. Results. The average levels of fasting blood glucose and glycosylated hemoglobin were highest in patients with proliferative diabetic retinopathy (11.27 mmol/l and 8.48%, respectively). Of 30 patients with diabetic eye diseases, diabetic maculopathy was found in 60% of cases; of those, 20% had non-proliferative retinopathy and 40% had proliferative retinopathy. The mean values of best corrected visual acuity, in both eyes, were 0.45 in patients with proliferative diabetic retinopathy, while mean values of serum urea and creatinine, creatinine clearance, and 24-h albuminuria in this group were 7.37 mmol/l, 106.13 ?mol/l, 72.80 ml/min, and 346.31 mg/24h, respectively. Conclusion. Severe forms of diabetic retinopathy and nephropathy were found in patients with poor metabolic regulation. A correlation between diabetic eye and kidney diseases was established, and the level of visual damage correlated with the degree of renal function impairment.

Population pharmacokinetics of pomalidomide in patients with relapsed or refractory multiple myeloma with various degrees of impaired renal function.

Pomalidomide is an immunomodulatory drug for treatment of relapsed or refractory multiple myeloma (rrMM) in patients who often have comorbid renal conditions. To assess the impact of renal impairment on pomalidomide exposure, a population pharmacokinetics (PPK) model of pomalidomide in rrMM patients with various degrees of impaired renal function was developed. Intensive and sparse pomalidomide concentration data collected from two clinical studies in rrMM patients with normal renal function, moderately impaired renal function, severely impaired renal function not requiring dialysis, and with severely impaired renal function requiring dialysis were pooled over the dose range of 2 to 4 mg, to assess specifically the influence of the impaired renal function as a categorical variable and a continuous variable on pomalidomide clearance and plasma exposure. In addition, pomalidomide concentration data collected on dialysis days from both the withdrawal (arterial) side and from the returning (venous) side of the dialyzer, from rrMM patients with severely impaired renal function requiring dialysis, were used to assess the extent to which dialysis contributes to the removal of pomalidomide from blood circulation. PPK analyses demonstrated that moderate to severe renal impairment not requiring dialysis has no influence on pomalidomide clearance or plasma exposure, as compared to those patients with normal renal function, while pomalidomide exposure increased approximately 35% in patients with severe renal impairment requiring dialysis on nondialysis days. In addition, dialysis increased total body pomalidomide clearance from 5 L/h to 12 L/h, indicating that dialysis will significantly remove pomalidomide from the blood circulation. Thus, pomalidomide should be administered post-dialysis on the days of dialysis.

MP23-01 HUMAN URINE-DERIVED STEM CELLS LESSEN INFLAMMATION AND FIBROSIS WITHIN KIDNEY TISSUE IN A RODENT MODEL OF AGING-RELATED RENAL INSUFFICIENCY

You have accessJournal of UrologyInfections/Inflammation/Cystic Disease of the Genitourinary Tract: Kidney & Bladder II1 Apr 2017MP23-01 HUMAN URINE-DERIVED STEM CELLS LESSEN INFLAMMATION AND FIBROSIS WITHIN KIDNEY TISSUE IN A RODENT MODEL OF AGING-RELATED RENAL INSUFFICIENCY Ting Long, Yaodong Jiang, Hua Shi, Liren Zhong, Deying Zhang, Wei Li, Yong Zhang, Dong Chen, Yan Jiao, Debra Diz, and Yuanyuan Zhang Ting LongTing Long More articles by this author , Yaodong JiangYaodong Jiang More articles by this author , Hua ShiHua Shi More articles by this author , Liren ZhongLiren Zhong More articles by this author , Deying ZhangDeying Zhang More articles by this author , Wei LiWei Li More articles by this author , Yong ZhangYong Zhang More articles by this author , Dong ChenDong Chen More articles by this author , Yan JiaoYan Jiao More articles by this author , Debra DizDebra Diz More articles by this author , and Yuanyuan ZhangYuanyuan Zhang More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.729AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Kidney function declines with age; older adults have renal function only 50-60% that of healthy young people. Most older patients have some degree of impaired renal function after renal surgery. Cell-based therapy is a promising alternative method to restore renal function in the treatment of chronic renal insufficiency. The goal of this study is to determine whether human urine-derived stem cells (USCs) can prompt renal tissue remolding in a rodent model of age-related kidney insufficiency. METHODS Urine samples were obtained from healthy men (n=6, 28-35 years old). USCs were isolated and expanded at passage 5. Eighteen male SD rats (50-62 week old) with renal insufficiency (increased levels of urine protein and serum creatinine) were divided into 3 groups (G). G1, animals received 5 intravenous cell implantations of 2 x106 cells/0.2 ml serum-free medium /rat/time period weekly; G2, as in G1 but intraperitoneally delivered; G3, as in G1 but serum-free medium alone. Healthy male SD rats at the same age were controls. RESULTS Cultured USCs secreted >20 kinds of trophic factors, including high levels of matrix metallopeptidase 9, which is involved in extracellular matrix degradation. Histologic and immunocytochemical staining showed that ED1 (inflammatory marker), alpha-smooth muscle actin (myofibroblast marker), and collagen deposition were significantly less within the medulla or cortex in rats with renal insufficiency vs. controls. G1 and G2 rats showed significantly inhibited inflammation and fibrosis in interstitial tissue, and reduced collagen deposits around renal vessels and the basement membrane of renal tubule and glomerular tissue, compared to G3. CONCLUSIONS Renal fibrosis is potentially reversible and therapeutic use of USCs can reverse specifically targeted decrease of influx of inflammatory macrophages, interstitial fibrosis formation and collagen deposition through their paracrine effects. Implantation of USCs has potential in the prevention and treatment of renal insufficiency. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e293 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Ting Long More articles by this author Yaodong Jiang More articles by this author Hua Shi More articles by this author Liren Zhong More articles by this author Deying Zhang More articles by this author Wei Li More articles by this author Yong Zhang More articles by this author Dong Chen More articles by this author Yan Jiao More articles by this author Debra Diz More articles by this author Yuanyuan Zhang More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

MINIMALLY INVASIVE SURGERY FOR CONGENITAL HYDRONEPHROSIS IN CHILDREN

Introduction. Minimal invasive treatment for congenital hydro nephrosis in children remains a controversial topic, both in defining the necessity and timing of operation using laparoscopic techniques in neonates and infants. Materials and methods. This study aims to analyze criteria used for surgery in a series of patients operated in a laparoscopic manner, for congenital hydro nephrosis, at the Emergency Clinical Hospital for Children “Marie Curie” Bucharest, Department of Pediatric Surgery, between 2007-2015. Results. In our series, the most frequent found criteria for surgery were anterior-posterior diameter over 3 cm, followed by 50% reduced parenchymal thickness, decreased renal function under 40% and finally symptomatic criteria – urinary tract infections and flank colicky pain. Both pelvic dilatation and parenchymal thickness correlates with renal function, though reduced parenchymal thickness has a stronger correlation. Infants under 1 year and under 10 kg represented a significant proportion (17.5% and 22.5% respectively). Conclusions. Young age (under 1 year old) and low-weight (under 10 kilos) in children are not reasons to delay classical or laparoscopic surgical treatment for PUJO (pyelo-ureteric junction obstruction). Pyelectasis is not specific to PUJO. It does not always mean obstruction and does not always show a strong correlation with impaired renal function. Best in establishing therapeutic conduct are the magnitude of renal parenchymal restructuring, the degree of renal function impairment and clinical symptomatology. Laparoscopic treatment is an effective surgical approach, that meets all the major advantages of minimal invasive surgery, applicable to infants and small children, regardless of age and weight.

Levels of serum vaspin and tumor necrosis factor-α in patients with type 2 diabetes mellitus in relation to kidney function and glycemic control

Background Diabetes mellitus type 2 (T2DM) is a metabolic disorder that is characterized by high blood glucose in the context of insulin resistance and relative insulin deficiency. Vaspin (visceral adipose tissue-derived serpin) is a member of the broadly distributed serpin (a protein superfamily of serine protease inhibitors of ∼500 genes) and is identical to serpin A12. The upregulation of vaspin can improve insulin resistance. Thus, identification of the protease inhibited by vaspin may lead to the development of novel strategies in the treatment of diabetes and insulin resistance. In patients with chronic kidney disease, the levels of vaspin appear to increase mostly because of reduced renal metabolism of vaspin. Tumor necrosis factor-α (TNF-α) is a cytokine involved in systemic inflammation. Its increased production has been observed in adipose tissue, and it has been implicated as a causative factor in obesity-associated insulin resistance, the pathogenesis of T2DM, and the development of diabetic nephropathy (DN) through several mechanisms. The association of T2DM patients (with and without impaired renal function) with serum vaspin and TNF-α levels is not clearly understood. This study aimed to evaluate the levels of vaspin and tumor necrosis factor (TNF) in T2DM patients and compare their levels with impairment in renal function in T2DM to determine whether circulating vaspin and TNF could be a biomarker of DN. Patients and methods This case–control observational prospective study was conducted on 73 patients with T2DM classified into two groups; group I included 20 T2DM patients with reduced renal function, and group II included 53 T2DM patients with normal renal function. The studied groups were recruited from the Diabetic Unit Outpatient Clinic, Department of Internal Medicine, Sohag University Hospitals, from December 2014 to December 2015. T2DM was diagnosed according to the American Diabetes Association Criteria. Totally, 12 age and sex matched apparently healthy individuals who served as the control group (group III) were enrolled in the study. The study was approved by the ethical committee of Faculty of Medicine, Sohag University, and written informed consent was obtained from each participant. All participants were subjected to thorough history taking, full clinical examination, and anthropometric measurements, including weight, height, and BMI. In addition, peripheral hemogram, random blood glucose evaluation, HbA1c determination, liver function tests, kidney function tests, lipid profile, and serum vaspin and serum TNF-α evaluation were carried out. Results In essence, significant correlations of vaspin and TNF were found with age of T2DM patients, hypertension, BMI, and lipid profile, but not with HbA1c. Moreover, higher levels of vaspin and TNF-α were significantly correlated with the degree of impaired renal function in T2DM patients. Notably, multivariate linear regression shows that BMI and age are negatively correlated with vaspin but not with TNF-α levels in T2DM patient with more impaired renal function. Conclusion Strict monitoring of T2DM can reduce the morbidity and mortality rate and will also improve the quality of life of diabetic patients. The association of renal insufficiency due to diabetes mellitus with serum vaspin and TNF-α levels is not clearly understood. However, vaspin may be beneficial as a positive biomarker for T2DM patients with impaired renal function and can be considered as a new prognostic marker for DN. Large studies are required to establish vaspin and TNF-α efficacy and safety in T2DM.

Is there any Gender Difference in the Association between Obesity, Chronic Kidney Disease and Anemia

Abstract Introduction. Nowadays, obesity has emerged as one of the most independent risk factors for chronic kidney disease (CKD) in both economically developed and undeveloped countries. The number of patients requiring dialysis as a consequence of obesity-related renal diseases, such as diabetes mellitus and hypertension, is increasing worldwide. Moreover, obesity has been shown to favorize the risk of cardiovascular diseases (CVD) with premature death due to CKD and/or end-stage renal disease (ESRD). The aim of the study was to investigate the association between obesity [e.g. body mass index (BMI)], kidney function [e.g. glomerular filtration rate (GFR)] and renal anemia in CKD patients. Methods. Retrospectively, data from the register of 315 pre-dialysis patients with different stages of CKD not on erythropoiesis stimulation agents (ESAs) during the period between 1 Jan 2013-30 June 2013 were used to assess the association between the degree of CKD impairment with the degree of obesity and anemia. The stage and/or progression of CKD was calculated by GFR, while the degree of obesity by the body mass index (BMI). CKD was defined as a glomerular filtration rate (GFR) &lt;60 mL/min per 1.73 m2. Data analysis was performed by means of the simple Microsoft excel program. Results. Within the study population of 315 CKD patients, 123 were males with mean age of 63.4±1.33 years and 192 females of 57.3±1.2 years. The GFR reduced with the increased BMI in both genders, and majority of patients (n=243) were in CKD stage 3, with a mean GFR of 44.5 ml/min/1.73 m2. The BMI values in female patients with first and second degree of obesity negatively correlated with GFR (r=−0.46, p&lt;0.05). Only female patients with second degree of obesity (BMI of 35-39.9 kg/m2) had a positive correlation between the decreased renal function and reduced Hb levels. Conclusions. Our study provided an unconditional evidence not only for the presence of an association between the degree of obesity (BMI) and the degree of renal function impairment (GFR), but also an association between the higher BMI and the higher degree of kidney anemia seen in women with second degree of obesity. Further larger scale trials and interventional studies are required to see the effect of body weight reduction on renal function and especially anemia.

Surgical treatment reduces blood pressure in children with unilateral congenital hydronephrosis

Renal disorders can cause hypertension, but less is known about the influence of hydronephrosis on blood pressure. Hydronephrosis due to pelvo-ureteric junction obstruction (PUJO) is a fairly common condition (incidence in newborns of 0.5-1%). Although hypertensive effects of hydronephrosis have been suggested, this has not been substantiated by prospective studies in humans [1-3]. Experimental studies with PUJO have shown that animals with induced hydronephrosis develop salt-sensitive hypertension, which strongly correlate to the degree of obstruction [4-7]. Moreover, relief of the obstruction normalized blood pressure [8]. In this first prospective study our aim was to study the blood pressure pattern in pediatric patients with hydronephrosis before and after surgical correction of the ureteral obstruction. Specifically, we investigated if preoperative blood pressure is reduced after surgery and if split renal function and renographic excretion curves provide any prognostic information. Twelve patients with unilateral congenital hydronephrosis were included in this prospective study. Ambulatory blood pressure (24 h) was measured preoperatively and six months after surgery. Preoperative evaluations of bilateral renal function by Tc99m-MAG3 scintigraphy, and renography curves, classified according to O'Reilly, were also performed. As shown in the summary figure, postoperative systolic (103 ± 2 mmHg) and diastolic (62 ± 2 mmHg) blood pressure were significantly lower than those obtained preoperatively (110 ± 4 and 69 ± 2 mmHg, respectively), whereas no changes in circadian variation or pulse pressure were observed. Renal functional share of the hydronephrotic kidney ranged from 11 to 55%. There was no correlation between the degree of renal function impairment and the preoperative excretory pattern, or between the preoperative excretory pattern and the blood pressure reduction postoperatively. However, preoperative MAG3 function of the affected kidney correlated with the magnitude of blood pressure change after surgery. Correction of the obstruction lowered blood pressure, and the reduction in blood pressure appeared to correlate with the degree of renal functional impairment, but not with the excretory pattern. Thus, in the setting of hypertension, it appears that the functional share of the hydronephrotic kidney should be considered an indicator of the need for surgery, whereas the renography curve is less reliable. The strength of the present study is the prospective nature and that ambulatory blood pressure monitoring was used. Future longitudinal prolonged follow-up studies are warranted to confirm the present findings, and to understand if a real nephrogenic hypertension with potential necessity of treatment will develop. This novel prospective study in patients with congenital hydronephrosis demonstrates a reduction in blood pressure following relief of the obstruction. Based on the present results, we propose that the blood pressure level should also be taken into account when deciding whether to correct hydronephrosis surgically or not.

Inhibition of Thrombin-Activated Fibrinolysis Inhibitor Increases Survival in Experimental Kidney Fibrosis.

Uncontrolled diabetes, inflammation, and hypertension are key contributors to progressive renal fibrosis and subsequent loss of renal function. Reduced fibrinolysis appears to be a feature of ESRD, but its contribution to the fibrotic program has not been extensively studied. Here, we show that in patients with CKD, the activity levels of serum thrombin-activated fibrinolysis inhibitor and plasmin strongly correlated with the degree of renal function impairment. We made similar observations in rats after subtotal nephrectomy and tested whether pharmacologic inhibition of thrombin-activated fibrinolysis inhibitor with UK-396082 could reduce renal fibrosis and improve renal function. Compared with untreated animals, UK-396082-treated animals had reduced glomerular and tubulointerstitial fibrosis after subtotal nephrectomy. Renal function, as measured by an increase in creatinine clearance, was maintained and the rate of increase in proteinuria was reduced in UK-396082-treated animals. Furthermore, cumulative survival improved from 16% to 80% with inhibition of thrombin-activated fibrinolysis inhibitor. Taken together, these data support the importance of the fibrinolytic axis in regulating renal fibrosis and point to a potentially important therapeutic role for suppression of thrombin-activated fibrinolysis inhibitor activity.