Risk Factor For Kidney Failure Research Articles

Etiology, clinical profile, and outcomes of crescentic glomerulonephritis in children: a systematic review.

Crescentic glomerulonephritis, if not managed promptly, is associated with unsatisfactory outcomes. There are limited studies reporting the outcomes of crescentic glomerulonephritis in children. This systematic review is aimed at synthesizing the data on etiology, clinical profile, and outcomes of crescentic glomerulonephritis in children. We performed a literature search using PubMed, Embase, and Web of Science from inception to January 2024 without language or geographic restrictions. Cohort and cross-sectional studies with at least 10 participants reporting etiology, clinical features, and outcomes on crescentic glomerulonephritis in children were considered eligible. Children aged less than 18years with crescentic glomerulonephritis. We used a tool by Hoy et al. for assessing the quality of studies. We calculated pooled estimates using random effect meta-analyses. Primary outcome was the pooled proportion of patients progressing to kidney failure. From 1706 records, we included 36 studies (1548 participants) from 16 countries. Etiology was immune-complex glomerulonephritis in 76% (95% CI 67 to 85), pauci-immune in 19% (13 to 25), and anti-GBM disease in 5% (3 to 7) of patients. Gross hematuria, oliguria, edema, and hypertension were observed in 63% (41 to 82), 57% (34 to 79), 79% (65 to 90), and 64% (49 to 77), respectively. In-hospital mortality, reported in 11 studies, was 7% (4 to 11). Progression to kidney failure and chronic kidney disease was reported in 27% (21 to 33) and 50% (29 to 71) ofpatients, respectively. Risk factors for kidney failure included oliguria, dialysis requirement at onset, estimated GFR, proportion of fibrous crescents, and pauci-immune glomerulonephritis as the underlying etiology. High heterogeneity in pooled estimates of the outcomes. Immune-complex glomerulonephritis is the most common etiology in children, with edema, hypertension, gross hematuria, and oliguria being the chief presenting manifestations. Almost one in every four patients with crescentic glomerulonephritis progressed to kidney failure. PROSPERO registration number CRD42024500515.

Characteristics of Complement Protein Deposition in Proliferative Glomerulonephritis with Monoclonal Immunoglobulin Deposition.

Hypocomplementemia and complement co-deposition with monoclonal immunoglobulins in glomeruli are not rare in proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID). Deposition of monoclonal immunoglobulins in glomeruli has been suggested to activate complement and cause kidney injury. However, the profiles of complement activation in PGNMID and their clinical and pathologic significance need to be clarified. Forty-six patients with PGNMID were enrolled. Proteomic analysis of glomeruli using laser microdissection and mass spectrometry was performed for ten patients with PGNMID to determine the composition of glomerular deposits. Kidney deposition of complement components was detected by immunohistochemistry and immunofluorescence. Urinary and plasma levels of complement components were measured by an enzyme-linked immunosorbent assay. Group differences were assessed using t tests or Mann-Whitney U tests depending on the distribution. Correlation analysis was performed using Spearman rank correlation or Pearson correlation. Laser microdissection and mass spectrometry-based proteomic analysis showed that complement components were the most enriched proteins deposited in the glomeruli of patients with PGNMID. Glomerular deposition of C3c, C4d, and C5b-9 was detected in most patients. Levels of urinary and plasma C3a, C5a, soluble C5b-9, C4d, Bb, and C1q as well as urinary mannose-binding lectin were significantly higher in patients with PGNMID compared with healthy controls. The intensity of C3c and C4d deposition in glomeruli correlated with serum creatinine and the percentage of crescents, respectively. Furthermore, levels of urinary complement components correlated positively with serum creatinine, urinary protein excretion, percentage of crescents, and global glomerulosclerosis in kidney biopsies, whereas plasma levels of most complement components did not show a significant correlation with clinicopathologic parameters. In multivariable analysis, a higher level of urinary C4d was identified as an independent risk factor of kidney failure. The complement system was found to be overactivated in PGNMID, and levels of urinary complements correlated with disease severity. A higher level of urinary C4d was identified as an independent risk factor of kidney failure.

#5476 SEX DIFFERENCES IN INCIDENT KIDNEY FAILURE AND THE IMPACT OF RISK FACTORS IN A POPULATION STUDY

Abstract Background and Aims Chronic kidney disease (CKD) has different effects on women and men. Women are more likely to have CKD, but men are more likely to develop kidney failure requiring treatment (KFRT: dialysis or transplantation). Recent studies have highlighted sex differences in CKD progression and there is a need to determine if this relates to differential effects of risk factors. Method We used primary care data stored within the electronic health records repository Secure Anonymised Information Linkage Databank (SAIL) for adults with CKD stages G3/4 (estimated glomerular filtration rate (eGFR) 15-59 mL/min/1.73 m2) living in Wales, UK. We studied the relationship between sex and the development of kidney failure (KFRT or incident eGFR<15 mL/min/1.73 m2 for ≥3 months). Sex-specific rates of kidney failure were compared using an event plot with patients censored on the date of death. Cox proportional hazards models tested associations between sex and kidney failure, before and after adjustment for other known risk factors (age, baseline eGFR, smoking, social deprivation, diabetes mellitus and hypertension). Interactions between sex and risk factors were sought and interaction terms were retained if these were statistically significant (p-value<0.05). Models were then stratified by sex to compare the impact of risk factors in men and women. Results 135,635 patients (median age 78 years, 57% female, median baseline eGFR 50 mL/min/1.73 m2) were followed up for a median of 6.8 years, representing a total of 782,237 patient years. 1.1% of women and 2.3% of men developed kidney failure. An unadjusted Cox model including both sexes showed a hazard ratio of 2.06 (95% confidence interval 1.89-2.24) for men. After adjustment for all risk factors and inclusion of interaction terms (between sex and baseline eGFR and sex and age), men were not more likely to develop kidney failure (aHR 0.91, 0.60-1.38) (Figure 1A). In sex-stratified models, kidney failure was most likely to develop in those with low baseline eGFR, younger age, current and ex-smokers, patients with diabetes mellitus and patients with hypertension (Figure 1B). Diabetes was a more important risk factor for kidney failure in women (aHR in women 1.73 (1.51-1.98) compared with men (aHR 1.56, 1.39-1.74). Hazard ratios for other risk factors were similar in men and women. Conclusion We found that sex differences in rates of kidney failure are related to a differential impact of risk factors – in particular diabetes – on CKD progression. These results warrant further investigation with a need to determine whether risk reduction strategies should be different in men and women with CKD, or whether current diagnosis, monitoring and treatment strategies are either applied differentially or have different benefit and harms by sex.

Genetic spectrum of CAKUT and risk factors for kidney failure: a pediatric multicenter cohort study.

Congenital anomalies of the kidney and urinary tracts (CAKUT) are the leading cause of kidney failure in children with phenotypic and genotypic heterogeneity. Our objective was to describe the genetic spectrum and identify the risk factors for kidney failure in children with CAKUT. Clinical and genetic data were derived from a multicenter network (Chinese Children Genetic Kidney Disease Database, CCGKDD) and the Chigene database. A total of 925 children with CAKUT who underwent genetic testing from 2014 to 2020 across China were studied. Data for a total of 584 children wereobtained from the CCGKDD, including longitudinal data regarding kidney function. The risk factors for kidney failure were determined by the Kaplan-Meier method and Cox proportional hazards models. A genetic diagnosis was established in 96 out of 925 (10.3%) children, including 72 (8%) with monogenic variants, 20 (2%) with copy number variants (CNVs), and 4 (0.4%)with major chromosomal anomalies. Patients with skeletal abnormalities were more likely to have large CNVs or abnormal karyotypes than monogenic variants. Eighty-two patients from the CCGKDD progressed to kidney failure at a median age of 13.0 (95% confidence interval, 12.4-13.6) years, and twenty-four were genetically diagnosed with variants of PAX2, TNXB, EYA1, HNF1B and GATA3 or the 48, XXYY karyotype. The multivariate analysis indicated that solitary kidney, posterior urethral valves, bilateral hypodysplasia, the presence of certain variants and premature birth were independent prognostic factors. The genetic spectrum of CAKUT varies among different subphenotypes. The identified factors indicate areas that require special attention.

Clinical characteristics and risk factors for kidney failure in patients with autosomal dominant polycystic kidney disease: A retrospective study.

Autosomal dominant polycystic kidney disease (ADPKD) is a hereditary and progressive renal disease. By the age of 65 years, 45% to 70% of patients with ADPKD reach end-stage renal disease (ESRD). Although there are various treatments for this condition, no standard therapy exists to delay the progression of ADPKD. Hence, understanding the factors that affect disease progression may be helpful for the treatment of ADPKD. The medical records of 288 patients with ADPKD at Keimyung University Dongsan Medical Center between January 1989 and August 2018 were analyzed retrospectively. Furthermore, we inspected the risk factors involved in the progression of ADPKD and the kidney survival rates of patients using the Cox proportional hazards model and Kaplan-Meier survival analysis. The mean age at the time of diagnosis was 43.1 ± 14.1 years, and there were 146 males (50.7%). In total, 197 patients (68.4%) had hypertension and 11 patients (3.8%) had cerebral aneurysm. Stroke occurred in 35 patients (12.1%), including 11 cases of cerebral hemorrhage and 24 cases of cerebral infarction. Twenty-eight patients (9.7%) died during the follow-up period (117.1 ± 102.1 months). Infection (42.9%) was the most common cause of mortality, followed by sudden cardiac death (25.0%). Overall, 132 patients (45.8%) progressed to ESRD and 104 patients (36.1%) required renal replacement therapy (RRT). The mean duration from diagnosis to RRT was 110.8 ± 93.9 months. Age at diagnosis after 30 years (odd's ratio [OR], 2.737; 95% confidence interval [CI], 1.320-5.675; P = .007), baseline serum creatinine levels (OR, 1.326; 95% CI, 1.259-1.396; P < .001), and cyst infection (OR, 2.065; 95% CI, 1.242-3.433; P = .005) were the independent risk factors for kidney failure in multivariable analysis. To delay the advance of ADPKD to ESRD, early diagnosis and close observation for the onset of cyst infection are crucial.

Particulate matter of air pollution may increase risk of kidney failure in IgA nephropathy

IgA nephropathy (IgAN) is characterized by deposition of galactose-deficient IgA1 (Gd-IgA1) in glomerular mesangium associated with mucosal immune disorders. Since environmental pollution has been associated with the progression of chronic kidney disease in the general population, we specifically investigated the influence of exposure to fine particulate matter less than 2.5 μm in diameter (PM2.5) on IgAN progression. Patients with biopsy-proven primary IgAN were recruited from seven Chinese kidney centers. PM2.5 exposure from 1998 to 2016 was derived from satellite aerosol optical depth data and a total of 1,979 patients with IgAN, including 994 males were enrolled. The PM2.5 exposure levels for patients from different provinces varied but, in general, the PM2.5 exposure levels among patients from the north were higher than those among patients from the south. The severity of PM2.5 exposure in different regions was correlated with regional kidney failure burden. In addition, each 10 μg/m3 increase in annual average concentration of PM2.5 exposure before study entry (Hazard Ratio, 1.14; 95% confidence interval, 1.06-1.22) or time-varying PM2.5 exposure after study entry (1.10; 1.01-1.18) were associated with increased kidney failure risk after adjustment for age, gender, estimated glomerular filtration rate, urine protein, uric acid, hemoglobin, mean arterial pressure, Oxford classification, glucocorticoid and renin-angiotensin system blocker therapy. The associations were robust when the time period, risk factors of cardiovascular diseases or city size were further adjusted on the basis of the above model. Thus, our results suggest that PM2.5 is an independent risk factor for kidney failure in patients with IgAN, but these findings will require validation in more diverse populations and other geographic regions.

Genotype-Phenotype Correlations for Pathogenic COL4A3-COL4A5 Variants in X-Linked, Autosomal Recessive, and Autosomal Dominant Alport Syndrome.

Alport syndrome is inherited as an X-linked (XL), autosomal recessive (AR), or autosomal dominant (AD) disease, where pathogenic COL4A3 – COL4A5 variants affect the basement membrane collagen IV α3α4α5 network. About 50% of pathogenic variants in each gene (major rearrangements and large deletions in 15%, truncating variants in 20%, splicing changes in 15%) are associated with “severe” disease with earlier onset kidney failure, and hearing loss and ocular abnormalities in males with XL inheritance and in males and females with AR disease. Severe variants are also associated with early proteinuria which is itself a risk factor for kidney failure. The other half of pathogenic variants are missense changes which are mainly Gly substitutions. These are generally associated with later onset kidney failure, hearing loss, and less often with major ocular abnormalities. Further determinants of severity for missense variants for XL disease in males, and in AD disease, include Gly versus non-Gly substitutions; increased distance from a non-collagenous interruption or terminus; and Gly substitutions with a more (Arg, Glu, Asp, Val, and Trp) or less disruptive (Ala, Ser, and Cys) residue. Understanding genotype-phenotype correlations in Alport syndrome is important because they help predict the likely age at kidney failure, and the need for early and aggressive management with renin-angiotensin system blockade and other therapies. Genotype-phenotype correlations also help standardize patients with Alport syndrome undergoing trials of clinical treatment. It is unclear whether severe variants predispose more often to kidney cysts or coincidental IgA glomerulonephritis which are recognized increasingly in COL4A3-, COL4A4 - and COL4A5-associated disease.

Activation of complement C1q and C3 in glomeruli might accelerate the progression of diabetic nephropathy: Evidence from transcriptomic data and renal histopathology.

ABSTRACTAims/IntroductionIt is not unclear whether the complement system is involved in the pathogenesis of diabetic nephropathy (DN). We explored the role of the complement system in glomeruli from patients with DN using integrated transcriptomic bioinformatics analysis and renal histopathology.Materials and MethodsFour datasets (GSE30528, GSE104948, GSE96804 and GSE99339) from the Gene Expression Omnibus database were integrated. We used a protein–protein interaction network and the Molecular Complex Detection App to obtain hub genes. Gene ontology and the Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were carried out to identify significant pathways. We also investigated the associations of C1q and C3 deposition on renal histopathology with clinical data, pathological parameters and renal survival in DN patients.ResultsWe identified 47 up‐ and 48 downregulated genes associated with DN. C3, C1QB and C1QA were found to be complement‐related hub genes. The gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses identified complement activation and humoral immune response as the significant oncology terms, with C1QB and C3 positioned at the center of the pathway. Regarding renal histopathology, patients with both C1q and C3 deposition had more severe glomerular classes. Multivariate Cox proportional hazards regression showed that the deposition of glomerular C1q and C3 was an independent risk factor for kidney failure. Patients with high C1q, C3 or C4d expression in glomeruli were more likely to progress to kidney failure, whereas glomerular mannose‐binding lectin was rare.ConclusionsComplement activation is involved in the development of DN, and activation of the classical complement pathway in glomeruli might accelerate disease progression.

Fasting Glucose Variability as a Risk Indicator for End-Stage Kidney Disease in Patients with Diabetes: A Nationwide Population-Based Study.

Given the fact that diabetes remains a leading cause of end-stage kidney disease (ESKD), multi-aspect approaches anticipating the risk for ESKD and timely correction are crucial. We investigated whether fasting glucose variability (FGV) could anticipate the development of ESKD and identify the population prone to the harmful effects of GV. We included 777,192 Koreans with diabetes who had undergone health examinations more than three times in 2005–2010. We evaluated the risk of the first diagnosis of ESKD until 2017, according to the quartile of variability independent of the mean (VIM) of FG using multivariate-adjusted Cox proportional hazards analyses. During the 8-year follow-up, a total of 7290 incidents of ESKD were found. Subjects in the FG VIM quartile 4 had a 27% higher risk for ESKD compared to quartile 1, with adjustment for cardiovascular risk factors and the characteristics of diabetes. This effect was more distinct in patients aged < 65 years; those with a long duration of diabetes; the presence of hypertension or dyslipidemia; and prescribed angiotensin-converting enzyme inhibitors, metformin, sulfonylurea, α-glucosidase inhibitors, and insulin. In contrast, the relationship between baseline FG status and ESKD risk showed a U-shaped association. FGV is an independent risk factor for kidney failure regardless of FG.

C3 Glomerulopathy and Related Disorders in Children: Etiology-Phenotype Correlation and Outcomes.

Membranoproliferative GN and C3 glomerulopathy are rare and overlapping disorders associated with dysregulation of the alternative complement pathway. Specific etiologic data for pediatric membranoproliferative GN/C3 glomerulopathy are lacking, and outcome data are based on retrospective studies without etiologic data. A total of 80 prevalent pediatric patients with membranoproliferative GN/C3 glomerulopathy underwent detailed phenotyping and long-term follow-up within the National Registry of Rare Kidney Diseases (RaDaR). Risk factors for kidney survival were determined using a Cox proportional hazards model. Kidney and transplant graft survival was determined using the Kaplan-Meier method. Central histology review determined 39 patients with C3 glomerulopathy, 31 with immune-complex membranoproliferative GN, and ten with immune-complex GN. Patients were aged 2-15 (median, 9; interquartile range, 7-11) years. Median complement C3 and C4 levels were 0.31 g/L and 0.14 g/L, respectively; acquired (anticomplement autoantibodies) or genetic alternative pathway abnormalities were detected in 46% and 9% of patients, respectively, across all groups, including those with immune-complex GN. Median follow-up was 5.18 (interquartile range, 2.13-8.08) years. Eleven patients (14%) progressed to kidney failure, with nine transplants performed in eight patients, two of which failed due to recurrent disease. Presence of >50% crescents on the initial biopsy specimen was the sole variable associated with kidney failure in multivariable analysis (hazard ratio, 6.2; 95% confidence interval, 1.05 to 36.6; P<0.05). Three distinct C3 glomerulopathy prognostic groups were identified according to presenting eGFR and >50% crescents on the initial biopsy specimen. Crescentic disease was a key risk factor associated with kidney failure in a national cohort of pediatric patients with membranoproliferative GN/C3 glomerulopathy and immune-complex GN. Presenting eGFR and crescentic disease help define prognostic groups in pediatric C3 glomerulopathy. Acquired abnormalities of the alternative pathway were commonly identified but not a risk factor for kidney failure.

COVID-19 and acute kidney injury in the intensive care unit

Die akute Nierenschädigung („acute kidney injury“, AKI) ist eine häufige und schwere Komplikation bei COVID-19(„coronavirus disease 2019“)-Patient*innen auf der Intensivstation. Dabei zeigt sich eine enge Assoziation zwischen der Schwere des Krankheitsverlaufs von COVID-19 und dem Auftreten von Nierenversagen. Den Hauptrisikofaktor für ein nierenersatztherapiepflichtiges Nierenversagen stellt die Notwendigkeit einer invasiven Beatmung dar, wobei der Beginn des Nierenversagens häufig eng mit dem Intubationszeitpunkt assoziiert ist. Zusätzlich stellen Risikofaktoren für schwere COVID-19-Verläufe gleichzeitig Risikofaktoren für ein schweres Nierenversagen dar. AKI bei COVID-19 weist eine hohe Mortalität auf und führt bei einem Teil der Patient*innen zu anhaltender Niereninsuffizienz. Allerdings kommt es bei einem recht großen Teil der dialysepflichtigen Überlebenden zu einer Erholung der Nierenfunktion. Im Hinblick auf Vermeidung und Therapie des COVID-19-assoziierten Nierenversagens gelten bislang dieselben Empfehlungen wie für AKI anderer Ursachen (Kidney Disease: Improving Global Outcomes, KDIGO-Bundles). Bei hohem Patient*innenaufkommen und entsprechend ausgelasteten Ressourcen kann die Durchführung von extrakorporalen Nierenersatzverfahren im Kontext einer krankheitsassoziierten Hyperkoagulabilität kritisch werden. Zur Vermeidung von Triage-Situationen wurde in einzelnen Zentren die akute Peritonealdialyse als Alternative zu den extrakorporalen Verfahren eingesetzt.

Renal disease associated with myeloproliferative neoplasms and myelodysplastic syndrome/myeloproliferative neoplasms.

Renal changes in patients with myeloproliferative neoplasms (MPNs) or myelodysplastic syndrome (MDS)/MPNs have been addressed by few, respectively no, reports. The aim of this study was to focus on a systematic evaluation of renal biopsies in patients with MPNs or MDS/MPNs. The cohort comprised 29 patients (23 men) aged 67±11years (mean±standard deviation), diagnosed with chronic myeloid leukaemia (n=5), polycythaemia vera (n=9), primary myelofibrosis (n=5), essential thrombocythaemia (n=2), or chronic myelomonocytic leukaemia (n=4), as well as MPNs or MDS/MPNs not otherwise specified (n=4). Patients manifested with proteinuria (93%), partially in the nephrotic range (46%), haematuria (72%), and impaired kidney function (93%). The most prominent histological findings included double-contoured glomerular basement membranes (71%), acute endothelial damage (68%), intracapillary platelet aggregation (62%), mesangiolysis (21%), thrombotic microangiopathy (24%), segmental glomerulosclerosis (66%), mesangial hypercellularity and sclerosis, extramedullary haematopoiesis (17%), and also IgA nephropathy (21%) and glomerulonephritis (GN) with features of infection-related GN (21%). MPN and MDS/MPN patients showed significantly more chronic changes than age-matched and sex-matched controls, including global and segmental glomerulosclerosis, mesangial sclerosis, and hypercellularity, whereas the extent of arteriosclerosis was comparable. MPN and MDS/MPN patients show glomerular scarring that exceeds age-related phenomena. Ongoing endothelial damage, growth factors released by platelets and deposition of immune complexes are probably the causative mechanisms. Early recognition of renal failure heralded by proteinuria and haematuria, and consequent control of risk factors for kidney failure, should be recommended for MPN and MDS/MPN patients.

Risk Factors of Kidney Failure Patients in Sardjito Hospital Yogyakarta

The purpose of this study is to identify patients at high risk of kidney failure in order to plan treatment. Cross-sectional research method, carried out at the CAPD Outpatient Installation of Dr. Sardjito General Hospital, from October 2018 to November 2018. The results showed three major risk factors for kidney failure, namely hypertension (49.1%), diabetes (17.5%) %) and nephrotoxic (15.8%). The conclusion from the study is hypertension is the highest risk factor for kidney failure.

Melatonin Suppresses Renal Cortical Fibrosis by Inhibiting Cytoskeleton Reorganization and Mitochondrial Dysfunction through Regulation of miR-4516.

Renal fibrosis, a major risk factor for kidney failure, can lead to chronic kidney disease (CKD) and is caused by cytoskeleton reorganization and mitochondrial dysfunction. In this study, we investigated the potential of melatonin treatment to reduce renal fibrosis by recovering the cytoskeleton reorganization and mitochondrial dysfunction. We found that miR-4516 expression was downregulated in the renal cortex of CKD mice and P-cresol-treated TH1 cells. Decreased miR-4516 expression stimulated cytoskeleton reorganization and mitochondrial dysfunction, and induced renal fibrosis. Melatonin treatment suppressed fibrosis by inhibiting cytoskeleton reorganization and restoring mitochondrial function via increased miR-4516 expression. More specifically, melatonin treatment increased miR-4516 expression while decreasing ITGA9 expression, thereby inhibiting cytoskeleton reorganization. In addition, increased expression of miR-4516 by melatonin treatment reduced ROS formation and restored mitochondrial function. These findings suggest that melatonin may be a promising treatment for patients with CKD having renal fibrosis. Moreover, regulation of miR-4516 expression may be a novel strategy for the treatment of renal fibrosis.

P0820EMERGENCY DEPARTMENT UTILIZATION BY PATIENTS WITH ADVANCED CHRONIC KIDNEY DISEASE AND DIALYSIS: A POPULATION BASED STUDY

Abstract Background and Aims Chronic Kidney Disease (CKD) is a potent risk factor for kidney failure, cardiovascular events and all cause hospitalizations. In addition to higher outpatient resource use, patients with CKD may present more frequently to the emergency department (ED) and may be more likely to be admitted for hospitalization. In Manitoba, we previously demonstrated an 8-fold increase in the frequency of ED presentations by patients on dialysis as compared to a non-dialysis population. Comparable data on ED visits remain sparse for patients with CKD G3-G5, not on dialysis. Here, we aim to describe the frequency of ED visits and highlight differences in reasons for visit in patients with CKD stages G3-G5 and Those on dialysis when compared to a non-renal population. Method We performed a retrospective cohort study using administrative health data from the Winnipeg Regional Health Authority, Canada. We included all adults (≥ 18 years) with CKD stages G3-G5 and patients undergoing dialysis between January 1st, 2010 and December 31, 2014. Secular trends in the in the rates of ED visits were calculated for those with CKD, those on dialysis and in the non-renal population. Results Over the study period, patients undergoing dialysis had the highest incidence of ED visits, followed by patients with CKD and those with normal kidney function (150 vs 106 vs 34 per 100 persons per year respectively). These rates were stable over the period studied. Among the non-renal population, the most common reasons for an ED visit were musculoskeletal complaints (25.6%), followed by gastrointestinal (11.04%) and cardiovascular complaints (10.26%). In the CKD and dialysis cohort, ED visits were more commonly secondary to cardiovascular complaints (21.54% and 18.99% respectively), followed by respiratory and gastrointestinal complaints. Admission to hospital was higher in CKD and dialysis populations than in the non-renal population (29.56%, 26.07% vs 10.61%, respectively). Conclusion Patients with CKD present frequently to the ED, and are often admitted after presentation. Cardiovascular and respiratory complaints are more common in the CKD population.

P123: Emergency department utilization by patients with advanced chronic kidney disease and dialysis: A population based study

Introduction: Chronic Kidney Disease (CKD) is a potent risk factor for kidney failure, cardiovascular events and all cause hospitalizations. In addition to higher outpatient resource use, patients with CKD may present more frequently to the emergency department (ED) and may be more likely to be admitted for hospitalization. In Manitoba, we previously demonstrated an 8-fold increase in the frequency of ED presentations by patients on dialysis as compared to a non-dialysis population. Comparable data on ED visits remain sparse for patients with CKD G3-G5, not on dialysis. Here, we aim to describe the frequency of ED visits and highlight differences in reasons for visit in patients with CKD stages G3-G5 and those on dialysis when compared to a non-CKD population. Methods: We performed a retrospective cohort study using administrative health data from the Winnipeg Regional Health Authority, Canada. We included all adults (≥ 18 years) with CKD stages G3-G5 and patients undergoing dialysis between January 1st, 2010 and December 31, 2014. Secular trends in the in the rates of ED visits were calculated for those with CKD, those on dialysis and in the non-CKD population. Results: Over the study period, patients undergoing dialysis had the highest incidence of ED visits, followed by patients with CKD and those with normal kidney function (150 vs 106 vs 34 per 100 persons per year respectively). These rates were stable over the period studied. Among the non-CKD population, the most common reasons for an ED visit were musculoskeletal complaints (25.6%), followed by gastrointestinal (11.04%) and cardiovascular complaints (10.26%). In the CKD and dialysis cohort, ED visits were more commonly secondary to cardiovascular complaints (21.54% and 18.99% respectively), followed by respiratory and gastrointestinal complaints. . Admission to hospital was higher in CKD and dialysis populations than in the non-CKD population (29.56%, 26.07% vs 10.61%, respectively). Conclusion: Patients with CKD present frequently to the ED, and are often admitted after presentation. Cardiovascular and respiratory complaints are more common in the CKD population when compared to the general population.

Donor-Recipient Relationship and Risk of ESKD in Live Kidney Donors of Varied Racial Groups

Risk factors for kidney failure are the basis of live kidney donor candidate evaluation. We quantified risk for end-stage kidney disease (ESKD) by the biological relationship of the donor to the recipient, a risk factor that is not addressed by current clinical practice guidelines. Retrospective cohort study. A cohort of 143,750 US kidney donors between 1987 and2017. Biological relationship of donor and recipient. ESKD. Donors' records were linked to national dialysis and transplantation registries to ascertain development of the outcome. Donors were observed over a median of 12 (interquartile range, 6-18; maximum, 30) years. Survival analysis methods that account for the competing risk for death were used. Risk for ESKD varied by orders of magnitude across donor-recipient relationship categories. For Asian donors, risks compared with unrelated donors were 259.4-fold greater for identical twins (95% CI, 19.5-3445.6), 4.7-fold greater for full siblings (95% CI, 0.5-41.0), 3.5-fold greater for offspring (95% CI, 0.6-39.5), 1.0 for parents, and 1.0 for half-sibling or other biological relatives. For black donors, risks were 22.5-fold greater for identical twin donors (95% CI, 4.7-107.0), 4.1-fold for full siblings (95% CI, 2.1-7.8), 2.7-fold for offspring (95% CI, 1.4-5.4), 3.1-fold for parents (95% CI, 1.4-6.8), and 1.3-fold for half-sibling or other biological relatives (95% CI, 0.5-3.3). For white donors, risks were 3.5-fold greater for identical twin donors (95% CI, 0.5-25.3), 2.0-fold for full siblings (95% CI, 1.4-2.8), 1.4-fold for offspring (95% CI, 0.9-2.3), 2.9-fold for parents (95% CI, 2.0-4.1), and 0.8-fold for half-sibling or other biological relatives (95% CI, 0.3-1.6). Insufficient sample size in some race and relationship groups. Absence of data for family history of kidney disease for donors biologically unrelated to their recipients. Marked differences in risk for ESKD across types of donor-recipient relationship were observed for Asian, black, and white donors. These findings warrant further validation with more robust data to better inform clinical practice guidelines.

Quantitative Intraoperative Measurement of Tissue Perfusion of Transplanted Kidneys by Indocyanine Green Angiography

Postoperative delayed graft function (DGF) after kidney transplantation is a risk factor for kidney failure and reduced kidney allograft survival after transplantation. The aim of this study was to measure the quantitative perfusion of kidney transplants during kidney transplantation and to investigate whether differences in perfusion predict the development of DGF. Over a period of one year, intraoperative quantitative ICG perfusion measurements were performed with the IC-View camera (Pulsion®) in 36 patients for whom informed consent for ICG perfusion measurement had been obtained. The groups were divided into donation after brain death and living donors and into the occurrence or absence of a DGF. An area with sufficient and low ICG perfusion was determined intraoperatively. The maximum perfusion was significantly decreased in the DGF group compared to living donors in areas with sufficient ICG perfusion and the slope of perfusion in these areas was documented. In addition, the maximum perfusion ratio was investigated. Evaluation was carried out by IC-Calc software (Pulsion). A total of 36 patients were included in this study. DGF occurred in 10 of the patients. No DGF was found in the group of living donors. The maximum perfusion and the slope of perfusion in the defined areas were fewer, but not significant in the group with BDB donor. The less perfused areas showed significant differences between DGF and living donors in maximum perfusion, absolute slope of perfusion and ratio to the standard area. A difference between BDB donor without DGF and the DGF group could not be predicted. This study shows that quantitative perfusion of kidney transplants can be evaluated safely during kidney transplantation. DGF being defined as one or more dialyses after kidney transplantation can only be detected postoperatively, however, it may be predicted intraoperatively.

Microangiopathic Lesions in IgA Nephropathy: A Cohort Study

Renal arteriolar microangiopathic lesions may occur in immunoglobulin A nephropathy (IgAN), but their role in disease progression remains unclear. We sought to understand the prevalence and character of microangiopathic lesions in IgAN and their role in disease progression. A retrospective cohort study. In this study, we enrolled a Chinese cohort with 944 adult patients with IgAN who had been followed up for at least 1 year. Renal arteriolar microangiopathic lesions. Composite kidney end point event defined as a>50% reduction in estimated glomerular filtration rate, end-stage kidney disease, or death. All kidney biopsies were independently reviewed by 2 investigators. Renal arteriolar microangiopathic lesions were detected using light microscopy. Multivariable Cox regression analysis was used to test the association between microangiopathic lesions and the outcomes. Overall, 194 (20.6%) patients had renal arteriolar microangiopathic lesions. Patients with microangiopathic lesions presented with higher blood pressures, more severe proteinuria, and lower estimated glomerular filtration rates (allP<0.001) than patients without microangiopathic lesions. After a median follow-up of4.2 years, 75 (38.7%) patients with microangiopathic lesions and 83 (11.1%) patients without these lesions reached the composite kidney end point (P<0.001). In a multivariable Cox regression model adjusting for clinical and pathologic variables available at thetime of biopsy, the presence of microangiopathic lesions was an independent risk factor for kidney failure (HR, 1.95; 95% CI, 1.34-2.83; P<0.001). Renal vascular sclerosis (arterial intimal fibrosis or arteriolar hyalinosis) was not a risk factor for kidney disease progression (P= 0.5). A single Chinese center's experience, retrospective study, most patients were not tested for hemolytic markers (for example, haptoglobin level, lactate dehydrogenase level, and schistocytes). Renal arteriolar microangiopathic lesions are frequent in IgAN and their presence is independently associated with progression to kidney failure. If confirmed in other patient cohorts, such lesions could be considered for inclusion in formal classification schemes of IgAN.

Podocyte GSK3 is an evolutionarily conserved critical regulator of kidney function

Albuminuria affects millions of people, and is an independent risk factor for kidney failure, cardiovascular morbidity and death. The key cell that prevents albuminuria is the terminally differentiated glomerular podocyte. Here we report the evolutionary importance of the enzyme Glycogen Synthase Kinase 3 (GSK3) for maintaining podocyte function in mice and the equivalent nephrocyte cell in Drosophila. Developmental deletion of both GSK3 isoforms (α and β) in murine podocytes causes late neonatal death associated with massive albuminuria and renal failure. Similarly, silencing GSK3 in nephrocytes is developmentally lethal for this cell. Mature genetic or pharmacological podocyte/nephrocyte GSK3 inhibition is also detrimental; producing albuminuric kidney disease in mice and nephrocyte depletion in Drosophila. Mechanistically, GSK3 loss causes differentiated podocytes to re-enter the cell cycle and undergo mitotic catastrophe, modulated via the Hippo pathway but independent of Wnt-β-catenin. This work clearly identifies GSK3 as a critical regulator of podocyte and hence kidney function.