Rates Of End-stage Kidney Disease Research Articles

Sex differences in risk factors for end-stage kidney disease and death in type 2 diabetes: A retrospective cohort study.

This study investigated the sex differences in the risk of end-stage kidney disease (ESKD) and mortality, as well as the effect modification of sex on associated factors in patients with type 2 diabetes. This multicenter observational cohort study included 4328 patients with type 2 diabetes. Hazard ratios (HRs) with 95% confidence intervals (CIs) of sex for ESKD and death were estimated using Cox proportional regression with adjustment for baseline covariates. For assessing risk modification, HRs and incidence rates for ESKD and death were compared between sexes across patient characteristics using Cox proportional and Poisson regression models. During a median follow-up of 7 years, 276 patients (70% men) developed ESKD, and 241 patients (68% men) died. Men had higher risks of ESKD (HR 1.34; 95% CI 1.02-1.75; p=.034) and death (HR 1.64; 95% CI 1.24-2.16; p=.001) versus women after adjusting for multiple covariates. Among patients with microalbuminuria, men had a substantially higher risk of ESKD versus women, compared to those with normo- and macroalbuminuria (p for interaction .04). Incidence rates were also increased in men versus women with albuminuria of around 300 mg/g. No differences were detected in the association of sex and death across baseline patient subgroups. In type 2 diabetes, men had an increased risk of ESKD and death versus women. Moderately increased albuminuria was strongly associated with sex difference in developing ESKD.

Incident heart failure and the subsequent risk for progression to end stage kidney disease in South East Asian people with type 2 diabetes

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Singapore National Medical Research Council grants: CSA-INV/0020/2017 and CS-IRG (MOH-000066) Background Heart failure (HF) is a common but often unrecognized complication of type 2 diabetes (T2D). Both low eGFR and high albuminuria are strong risk factors for development of HF in diabetic population. However, data on the role of HF in long-term kidney disease outcome are sparse. Aim We sought to study the risk for progression to end stage kidney disease (ESKD) after incident HF in multi-ethnic South East Asian people with type 2 diabetes. Participants and Methods A total of 1,756 individuals with type 2 diabetes recruited from a regional hospital were followed for a median of 7.3 (interquartile range 6.8-7.8) years. Incident HF was identified according to European Society of Cardiology 2016 criteria. HF was subtyped into preserved ejection fraction (HFpEF) and reduced ejection fraction (HFrEF) with ventricular ejection fraction (LVEF) cut-off at ≥50% and <50% respectively. Progression to ESKD was defined as patients with sustained eGFR <15ml/min per 1.73m2 with confirmation measurement 3 months apart, or on sustained dialysis for at least 3 months or death attributable to renal cause, whichever occurred first. The risk of progression to ESKD after HF was assessed using Cox proportional hazard models. Results Average age of participants was 57±11 years with diabetes duration of 11 (IQR 4-15) years. There were 52% Chinese, 22% Malay and 26% Asian Indian in the study participants. We identified 113 incident HF events (65 HFpEF and 48 HFrEF) during 11,869 patient-years (crude incidence rate 9.5 per 1000 patient-years). Individuals with HF occurrence were older, had a longer diabetes duration, higher body mass index, HbA1c and systolic blood pressure, and prevalent diabetic kidney disease (DKD). We identified 75 ESKD events in the follow-up (incidence rate 6.0 per 1000 patient-years) and 22 occurred after incident HF. Cox regression model showed that incident HF was associated with 7.4-fold (95% CI 4.5-12.2) unadjusted risk for progression to ESKD. The association of HF with subsequent risk for ESKD remained statistically significant (adjusted hazard ratio, HR 2.3, 95% CI 1.3-4.2) after adjustment for multiple clinical risk factors including baseline eGFR and albuminuria. Similar outcome was obtained when death attributable to non-renal cause was taken as a competing risk for ESKD. In a fully adjusted model, both HFpEF and HFrEF patients had a higher risk for progression to ESKD (adjusted HR 2.8, 95%CI 1.4-5.9, and 2.2, 95%CI 1.0-4.7, respectively), as compared to those with no HF events. The incidence rate of ESKD in patients with incident HF was 5.6 per 100 patient-years whilst in propensity score-matched patients without HF event, the rate was 2.1 per 100 patient-years. Conclusion Incident HF is a strong independent risk factor for progression to ESKD in individuals with T2D. Our data highlight the importance for prevention, early diagnosis and treatment of HF to improve the renal outcomes in individuals with type 2 diabetes.

Age-Dependent Effects of Acute Kidney Injury on End-Stage Kidney Disease and Mortality in Patients with Moderate to Severe Chronic Kidney Disease

Introduction: Old age has been considered as a positive modifier of chronic kidney disease (CKD), but the progression of CKD is often accelerated by acute kidney injury (AKI) in older adults. This study aimed to investigate this paradoxical interplay and identify age-specific predictors of end-stage kidney disease (ESKD). Methods: This retrospective cohort included 6,101 patients with CKD stage 3B-5 followed at a single center during 2005–2018. Participants were stratified into four age groups to explore age-dependent influences on the risk of ESKD and all-cause mortality. Multivariate Cox proportional hazard regression model with competing risk analysis was used to identify predictors of outcomes. Results: During a median follow-up of 2.68 years, 1,650 (27.0%) patients developed ESKD and 541 (8.9%) patients died. The rate of ESKD decreased with advancing age, being lowest in the very old-aged (>75 years) group who displayed the slowest rate of estimated glomerular filtration rate (eGFR) decline. Multivariate Cox proportional hazard regression adjusted for competing death showed that younger ages, compared with patients aged >75 years, together with AKI episodes and several traditional risk factors were identified as predictors for ESKD. The impact of AKI episodes on ESKD development was most prominent in patients aged >75 years. These results were confirmed with subgroup analyses in patients with outcomes of different ages. Conclusion: Older adults with CKD exhibited a slower decline rate of eGFR, yet they were more likely to develop ESKD following AKI episodes. These results suggest tackling AKI is needed to prevent accelerated initiation of renal replacement therapy in elderly patients with pre-existing CKD.

A low rate of end-stage kidney disease in membranous nephropathy: A single centre study over 2 decades.

Membranous nephropathy is the commonest cause of nephrotic syndrome in non-diabetic Caucasian adults over the age of 40 years. Primary membranous nephropathy is limited to the kidneys. Clinical management aims to induce remission, either spontaneously with supportive care, or with immunosuppression. Here, we describe the natural history of this condition in a large tertiary centre in the UK. 178 patients with primary membranous nephropathy were identified over 2 decades. We collected data on demographics, baseline laboratory values, treatment received and outcomes including progression to renal replacement therapy and death. Analysis was performed on the whole cohort and specific subgroups. Univariate and multivariate Cox regression was also performed. Median age was 58.3 years with 63.5% male. Median baseline creatinine was 90μmol/L and urine protein-creatinine ratio 664g/mol. Remission (partial or complete) was achieved in 134 (75.3%), either spontaneous in 60 (33.7%) or after treatment with immunosuppression in 74 (41.6%), and of these 57 (42.5%) relapsed. Progression to renal replacement therapy was seen in 10.1% (much lower than classically reported) with mortality in 29.8%. Amongst the whole cohort, those who went into remission had improved outcomes compared to those who did not go into remission (less progression to renal replacement therapy [4.5% vs 28%] and death [20.1% vs 67%]. Those classified as high-risk (based on parameters including eGFR, proteinuria, serum albumin, PLA2R antibody level, rate of renal function decline) also had worse outcomes than those at low-risk (mortality seen in 52.6% vs 10.8%, p<0.001). The median follow-up period was 59.5 months. We provide a comprehensive epidemiologic analysis of primary membranous nephropathy at a large tertiary UK centre. Only 10.1% progressed to renal replacement therapy. For novelty, the KDIGO risk classification was linked to outcomes, highlighting the utility of this classification system for identifying patients most likely to progress.

Attenuated Risk Association of End-Stage Kidney Disease with Metformin in Type 2 Diabetes with eGFR Categories 1-4.

Type 2 diabetes (T2D)-associated end-stage kidney disease (ESKD) is a global burden, while the renoprotective effects of metformin remain controversial. In a population-based cohort (2002–2018) including 96,643 patients with T2D observed for 0.7 million person-years, we estimated the risk association of metformin and its dose-relationship with ESKD in a propensity-score overlap-weighting (PS-OW) cohort by eGFR categories. Amongst 96,643, 83,881 (86.8%) had eGFR-G1/G2 (≥60 mL/min/1.73 m2), 8762 (9.1%) had eGFR-G3a (≥45–60 mL/min/1.73 m2), 3051 (3.2%) had eGFR-G3b (≥30–45 mL/min/1.73 m2), and 949 (1.0%) had eGFR-G4 (≥15–30 mL/min/1.73 m2). The respective proportions of metformin users in these eGFR categories were 95.1%, 81.9%, 53.8%, and 20.8%. In the PS-OW cohort with 88,771 new-metformin and 7872 other oral glucose-lowering-drugs (OGLDs) users, the respective incidence rates of ESKD were 2.8 versus 22.4/1000 person-years. Metformin use associated with reduced risk of ESKD (hazard ratio (HR) = 0.43 [95% CI: 0.35–0.52] in eGFR-G1/G2, 0.64 [0.52–0.79] in eGFR-G3a, 0.67 [0.56–0.80] in eGFR-G3b, and 0.63 [0.48–0.83] in eGFR-G4). Metformin use was associated with reduced or neutral risk of major adverse cardiovascular events (MACE) (7.2 versus 16.0/1000 person-years) and all-cause mortality (14.6 versus 65.1/1000 person-years). Time-weighted mean daily metformin dose was 1000 mg in eGFR-G1/G2, 850 mg in eGFR-G3a, 650 mg in eGFR-G3b, and 500 mg in eGFR-G4. In a subcohort of 14,766 patients observed for 0.1 million person-years, the respective incidence rates of lactic acidosis and HR in metformin users and non-users were 42.5 versus 226.4 events/100,000 person-years (p = 0.03) for eGFR-G1/G2 (HR = 0.57, 0.25–1.30) and 54.5 versus 300.6 events/100,000 person-years (p = 0.01) for eGFR-G3/G4 (HR = 0.49, 0.19–1.30). These real-world data underscore the major benefits and low risk of lactic acidosis with metformin use down to an eGFR of 30 mL/min/1.73 m2 and possibly even 15 mL/min/1.73 m2, while reinforcing the importance of dose adjustment and frequent monitoring of eGFR.

Long-term prognosis of primary focal segmental glomerulosclerosis in children

Objective: To investigate risk factors for the long-term prognosis of primary focal segmental glomerulosclerosis (FSGS) and associated with renal prognosis in children. Methods: A retrospective study was conducted by collecting clinical data including general information, clinical features and renal pathological findings of 124 children with primary FSGS in Department of Pediatrics of Jinling Hospital from January 2003 to December 2019. The cumulative renal survival rate was calculated by Kaplan-Meier survival analysis. The risk factors related to renal prognosis were identified by Cox regression risk model analysis and receiver operating characteristic (ROC) curve. Results: Among 124 children, 94 were males (75.8%) and 30 were females (24.2%). The children were 16 (14, 17) years of age at the time of kidney biopsies. There were 102 cases (82.3%) aged from 13 to 18 years. The period of follow-up was 64.8 (32.1, 86.0) months. There were 49 cases (39.5%) with nonspecific variant, 33 cases (26.6%) with tip variant, 22 cases (17.7%) with collapsing variant, 14 cases (11.3%) with cellular variant and 6 cases (4.8%) with periportal variant. The data of Kaplan-Meier survival analysis showed that cumulative renal survival rates of end-stage kidney disease (ESKD) or ≥50% decline in estimated glomerular filtration rate (eGFR) from baseline at the year of 5, 10 and 15 after renal biopsies were 66.9%, 51.4% and 21.0% respectively. Multivariate Cox regression analysis showed that hypertension, glomerular segmental sclerosis ratio, moderate to severe chronic tubulointerstitial lesions were independent risk factors for progressing to ESKD or ≥50% reduction in eGFR from baseline in pediatric FSGS (HR=5.28, 1.03, 7.81, 95%CI 2.77-10.05, 1.01-1.04, 4.08-14.98, all P<0.01). ROC curve analysis showed glomerular segmental sclerosis ratio (AUC=0.734, P<0.05, optimal cut-off value=25.4%, sensitivity=50.0%, specificity=88.6%), moderate and severe chronic renal tubulointerstitial lesions (AUC=0.724, P<0.05, sensitivity=46.3%, specificity=98.6%) had good efficacy in evaluating renal outcomes of FSGS. Conclusions: The long-term prognosis of FSGS in children is poor. The risk factors of poor prognosis in children with FSGS are hypertension, moderate to severe chronic renal tubulointerstitial lesions and glomerular segmental sclerosis (≥25.4%).

Associations between frailty trajectories and cardiovascular, renal, and mortality outcomes in chronic kidney disease.

BackgroundFrailty is characterized by the loss of biological reserves and vulnerability to adverse outcomes. In individuals with chronic kidney disease (CKD), numerous pathophysiological factors may be responsible for frailty development including inflammation, physical inactivity, reduced energy intake, and metabolic acidosis. Given that both CKD and frailty incur a significant healthcare burden, it is important to understand the relationship of CKD and frailty in real‐world routine clinical practice, and how simple frailty assessment methods (e.g. frailty indexes) may be useful. We investigated the risk of frailty development in CKD and the impact of frailty status on mortality and end‐stage kidney disease (ESKD).MethodsA retrospective cohort study using primary care records from the Clinical Practice Research Datalink linked to Hospital Episode Statistics and the UK Office for National Statistics was undertaken in 819 893 participants aged ≥40 years, of which 140 674 had CKD. Frailty was defined using an electronic frailty index, generated electronically from primary care records. Cox proportional hazard and flexible parametric survival models were used to investigate the risk of developing frailty and the effect of frailty on risk of all‐cause and cardiovascular mortality, and ESKD.ResultsThe mean age of those with CKD was 77.5 (SD 9.7) years [61.0 (SD 12.1) years in no‐CKD group]; 62.0% of the CKD group were female (compared with 53.3% in no‐CKD group). The mean estimated glomerular filtration rate of those with CKD was 46.1 (SD 9.9) mL/min/1.73 m2. The majority of those with CKD (75.3%) were frail [vs. 45.4% in those without CKD (no‐CKD)]. Over 3 years (median), 69.5% of those with CKD developed frailty. Compared with no‐CKD, those with CKD had increased rates of developing mild (hazard ratio: 1.02; 95% confidence interval: 1.01–1.04), moderate (1.30; 1.26–1.34), and severe (1.50; 1.37–1.65) frailty. Mild (1.22; 1.19–1.24), moderate (1.60; 1.56–1.63), and severe (2.16; 2.11–2.22) frailty was associated with increased rates of all‐cause and cardiovascular‐related mortality (mild 1.35; 1.31–1.39; moderate 1.96; 1.90–2.02; and severe 2.91; 2.81–3.02). All stages of frailty significantly increased ESKD rates.ConclusionsFrailty is highly prevalent and associated with adverse outcomes in people with CKD, including mortality and risk of ESKD. Preventative interventions should be initiated to mitigate the development of frailty. The use of a simple frailty index, generated electronically from health records, can predict outcomes and may aid prioritization for management of people with frailty.

Challenges and opportunities in real-world evidence on the renal effects of sodium-glucose cotransporter-2 inhibitors.

With increasing population aging and prevalence of type 2 diabetes (T2D) worldwide, prevention of diabetic complications remains a major unmet need. While cardiovascular outcomes of diabetes are improving over time, diabetic kidney disease (DKD) still leads to an exceedingly high rate of end‐stage kidney disease (ESKD). A game‐changing opportunity is offered by treatment with sodium‐glucose cotransporter‐2 (SGLT2) inhibitors. Randomized controlled trials (RCTs) have indisputably shown that SGLT2 inhibitors reduce the rate of DKD progression, the decline in estimated glomerular filtration rate (eGFR), and the development of ESKD. In parallel, SGLT2 inhibitors improve cardiovascular outcomes, especially the risk of hospitalization for heart failure. Real‐world studies (RWSs) have largely confirmed the findings of RCTs in broader populations of subjects with T2D followed under routine care. In the present paper, we review RWSs exploring the renal effects of SGLT2 inhibitors and highlight the most critical challenges that can be encountered in designing and conducting such studies. Channelling bias (confounding by indication), time‐lag bias, conditioning on the future, database heterogeneity, linearity of eGFR change over time, and duration of observation are critical issues that may undermine the robustness of RWS findings. We then elaborate on the new opportunities to overcome such limitations by describing the design and objectives of the DARWIN (DApagliflozin Real‐World evIdeNce)‐Renal study, a new RWS promoted by the Italian Diabetes Society. Fine‐tuning of methods for comparative observational research will improve evidence derived from RWSs on the renal effects of SGLT2 inhibitors, aiding the evolving discussion regarding the place of SGLT2 inhibitors in T2D treatment algorithms in different stages of DKD.

Two-year longitudinal trajectory patterns of albuminuria and subsequent rates of end-stage kidney disease and all-cause death: a nationwide cohort study of biopsy-proven diabetic kidney disease

IntroductionData on the association between longitudinal trajectory patterns of albuminuria and subsequent end-stage kidney disease (ESKD) and all-cause mortality in diabetic kidney disease (DKD) are sparse.Research design and methodsDrawing on...

End-stage kidney disease in patients with clinically manifest vascular disease; incidence and risk factors: results from the UCC-SMART cohort study

BackgroundPatients with cardiovascular disease (CVD) are at increased risk of end-stage kidney disease (ESKD). Insights into the incidence and role of modifiable risk factors for end-stage kidney disease may provide means for prevention in patients with cardiovascular disease.MethodsWe included 8402 patients with stable cardiovascular disease. Incidence rates (IRs) for end-stage kidney disease were determined stratified according to vascular disease location. Cox proportional hazard models were used to assess the risk of end-stage kidney disease for the different determinants.ResultsSixty-five events were observed with a median follow-up of 8.6 years. The overall incidence rate of end-stage kidney disease was 0.9/1000 person-years. Patients with polyvascular disease had the highest incidence rate (1.8/1000 person-years). Smoking (Hazard ratio (HR) 1.87; 95% CI 1.10–3.19), type 2 diabetes (HR 1.81; 95% CI 1.05–3.14), higher systolic blood pressure (HR 1.37; 95% CI 1.24–1.52/10 mmHg), lower estimated glomerular filtration rate (eGFR) (HR 2.86; 95% CI 2.44–3.23/10 mL/min/1.73 m2) and higher urine albumin/creatinine ratio (uACR) (HR 1.19; 95% CI 1.15–1.23/10 mg/mmol) were independently associated with elevated risk of end-stage kidney disease. Body mass index (BMI), waist circumference, non-HDL-cholesterol and exercise were not independently associated with risk of end-stage kidney disease.ConclusionsIncidence of end-stage kidney disease in patients with cardiovascular disease varies according to vascular disease location. Several modifiable risk factors for end-stage kidney disease were identified in patients with cardiovascular disease. These findings highlight the potential of risk factor management in patients with manifest cardiovascular disease.Graphic abstract

Advances in Membranous Nephropathy.

Membranous nephropathy (MN) is a rare auto-immune disease where the glomerulus is targeted by circulating auto-antibodies mostly against podocyte antigens, which results in the formation of electron-dense immune complexes, activation of complement and massive proteinuria. MN is the most common cause of nephrotic syndrome in adults leading to severe thrombotic complications and kidney failure. This review is focused on the recent therapeutic and pathophysiological advances that occurred in the last two years. For a long time, we were lacking a head-to-head comparison between cyclophosphamide considered as the gold standard therapy and other medications, notably rituximab. Substantial progress has been achieved owing to three randomized controlled trials. MENTOR (Membranous Nephropathy Trial of Rituximab) and STARMEN (Sequential Therapy with Tacrolimus and Rituximab in Primary Membranous Nephropathy) conclusively established that calcineurin inhibitor-based regimens are slower to result in an immunologic response than rituximab or cyclophosphamide, achieve fewer complete clinical remissions, and are less likely to maintainremission. Rituximab Versus Steroids and Cyclophosphamide in the Treatment of Idiopathic Membranous Nephropathy (RI-CYCLO) suggested that competition between cyclophosphamide and rituximab remains open. Given the technological leap combining laser microdissection of glomeruli and mass spectrometry of solubilized digested proteins, four “new antigens” were discovered including NELL-1 and Semaphorin 3B in so-called primary MN, and exostosins 1 and 2 and NCAM 1 in lupus MN. NELL-1 is associated with about 8% of primary MN and is characterized by segmental immune deposits and frequent association with cancer (30%). Semaphorin 3B-associated MN usually occurs in children, often below the age of two years, where it is the main antigen, representing about 16% of non-lupus MN in childhood. Exostosins 1/2 and NCAM 1 are associated with 30% and 6% of lupus MN, respectively. Exostosins 1/2 (EXT1/2) staining is associated with a low rate of end-stage kidney disease (ESKD) even in mixed classes III/IV+V. These findings already lead to revisiting the diagnostic and therapeutic algorithms toward more personalized medicine.

Trends in the Incidence, Prevalence, and Mortality of End-Stage Kidney Disease in South Korea.

Knowledge of the epidemiologic characteristics of end-stage kidney disease (ESKD) patients is essential. The trends in the prevalence, incidence, and mortality rates of ESKD were analyzed retrospectively using the Korean National Health Insurance Service-National Sample Cohort database between 2006 and 2015. From 2006 to 2015, the incidence of ESKD decreased from 28.6 to 24.0 per 100,000 people and showed a decreasing pattern with or without diabetes mellitus. However, the incidence of those aged ≥75 years increased, as did the mean age at the onset of ESKD. From 2007 to 2015, the prevalence of ESKD increased in all age groups, but particularly in those aged ≥75 years. The prevalence of ESKD differed by sex and diabetes mellitus status and this gap widened over time. Mortality rates in ESKD patients remained relatively constant throughout the study period. However, mortality rates in ESKD without diabetes decreased over the same period.

Long-term outcomes following vehicle trauma related acute kidney injury requiring renal replacement therapy: a nationwide population study

Acute kidney injury (AKI) is a frequent complication of traumatic injury; however, long-term outcomes such as mortality and end-stage kidney disease (ESKD) have been rarely reported in this important patient population. We compared the long-term outcome of vehicle-traumatic and non-traumatic AKI requiring renal replacement therapy (AKI-RRT). This nationwide cohort study used data from the Taiwan National Health Insurance Research Database. Vehicle-trauma patients who were suffered from vehicle accidents developing AKI-RRT during hospitalization were identified, and matching non-traumatic AKI-RRT patients were identified between 2000 and 2010. The incidences of ESKD, 30-day, and long-term mortality were evaluated, and clinical and demographic associations with these outcomes were identified using Cox proportional hazards regression models. 546 vehicle-traumatic AKI-RRT patients, median age 47.6 years (interquartile range: 29.0–64.3) and 76.4% male, were identified. Compared to non-traumatic AKI-RRT, vehicle-traumatic AKI-RRT patients had longer length of stay in hospital [median (IQR):15 (5–34) days vs. 6 (3–11) days; p < 0.001). After propensity matching with non-traumatic AKI-RRT cases with similar demographic and clinical characteristics. Vehicle-traumatic AKI-RRT patients had lower rates of long-term mortality (adjusted hazard ratio (HR), 0.473; 95% CI, 0.392–0.571; p < 0.001), but similar rates of ESKD (HR, 1.166; 95% CI, 0.829–1.638; p = 0.377) and short-term risk of death (HR, 1.134; 95% CI, 0.894–1.438; p = 0.301) as non-traumatic AKI-RRT patients. In competing risk models that focused on ESKD, vehicle-traumatic AKI-RRT patients were associated with lower ESKD rates (HR, 0.552; 95% CI, 0.325–0.937; p = 0.028) than non-traumatic AKI-RRT patients. Despite severe injuries, vehicle-traumatic AKI-RRT patients had better long-term survival than non-traumatic AKI-RRT patients, but a similar risk of ESKD. Our results provide a better understanding of long-term outcomes after vehicle-traumatic AKI-RRT.

Circulating B Cells, Plasma Cells, and Treg Associate with ANCA Levels in ANCA-associated Vasculitis

Circulating B Cells, Plasma Cells, and Treg Associate with ANCA Levels in ANCA-associated Vasculitis

A National Registry Study of Patient and Renal Survival in Adult Nephrotic Syndrome

IntroductionWe aimed to determine the mortality rate, cause of death, and rate of end-stage kidney disease (ESKD) in adults with nephrotic syndrome (NS).MethodsWe conducted a national registry–based study, including all 522 adults who had a kidney biopsy for NS in Scotland in 2014–2017. We linked the Scottish Renal Registry to death certificate data. We performed survival and Cox proportional hazards analyses, accounting for competing risks of death and ESKD. We compared mortality rates with those in the age- and sex-matched general population.ResultsA total of 372 patients had primary NS; 150 had secondary NS. Over a median follow-up of 866 days, 110 patients (21%) died. In patients with primary NS, observed versus population 3-year mortality was 2.1% (95% CI 0.0%–4.6%) versus 0.9% (0.8%–1.0%) in patients aged <60 years and 24.9% (18.4%–30.8%) versus 9.4% (8.3%–10.5%) in those aged ≥60 years. In secondary NS, this discrepancy was 17.1% (5.6%–27.2%) versus 1.1% (0.9%–1.2%) in <60-year-olds and 49.4% (36.6%–59.7%) versus 8.1% (6.6%–9.6%) in ≥60-year-olds. In primary NS, cardiovascular causes accounted for 28% of deaths, compared with 18% in the general population. Eighty patients (15%) progressed to ESKD. Incidence of ESKD by 3 years was 8.4% (95% CI 4.9%–11.7%) in primary and 35.1% (24.3%–44.5%) in secondary NS. Early remission of proteinuria and the absence of early acute kidney injury (AKI) were associated with lower rates of death and ESKD.ConclusionsAdults with NS have high rates of death and ESKD. Cardiovascular causes account for excess mortality in primary NS.

Incidence and risk factors for end-stage kidney disease in patients with clinically manifest vascular disease; results from the UCC-SMART cohort study

Abstract Background Patients with cardiovascular disease are at increased risk of developing chronic kidney disease, potentially leading to end-stage kidney disease (ESKD). On the other hand, kidney disease is associated with an increased risk of adverse cardiovascular outcomes and mortality. Previous studies have identified several risk factors for ESKD in the general population. However, little is known about the impact of these risk factors for ESKD in patients with clinically manifest cardiovascular disease. Purpose The aim of this study was to determine the incidence rates of ESKD in patients with clinically manifest cardiovascular disease and to assess the relation between risk of ESKD and risk factors, including systolic blood pressure (SBP), type 2 diabetes mellitus, estimated glomerular filtration rate (eGFR) and albuminuria (urinary albumin/creatinine ratio (uACR)), body mass index (BMI), dyslipidemia (non-HDL cholesterol), smoking, kidney length and exercise, in this high-risk population. Methods Patients (n=8402) from the ongoing UCC-SMART cohort (1996–2018) with clinically manifest cardiovascular disease were included. Occurrence of ESKD during follow up was defined as kidney transplantation, chronic dialysis or chronic kidney disease stage 5 (persistent eGFR &amp;lt;15 mL/min/1.73m2). Incidence rates for ESKD were determined and stratified according to vascular disease location. Cox proportional hazard models were used to assess the risk of ESKD for every determinant adjusted for potential confounders. Results A total of 65 events of ESKD were observed in 75,282 person-years (median follow-up time 8.6 years, IQR 4.7–12.8 years). The overall incidence rate for ESKD was 0.9 per 1000 person-years and was lower in patients with only cerebrovascular (0.6 per 1000 person-years) or cardiovascular disease (0.6 per 1000 person-years). A higher incidence rate was observed in patients with polyvascular disease (1.8 per 1000 person-years) (Figure 1A). Presence of type 2 diabetes (HR 1.83; 95% CI 1.06–3.16) and higher SBP (HR 1.37; 95% CI 1.24–1.52 per 10 mmHg) were associated with an elevated risk of ESKD. Lower eGFR and higher uACR were associated with a higher risk of ESKD (Figure 1B). Kidney length was inversely associated with risk of ESKD. Smoking, physical exercise, BMI and non-HDL cholesterol were not related to ESKD. Conclusions The incidence of ESKD is higher in patients with polyvascular disease compared to patients with cerebrovascular or cardiovascular disease. Type 2 diabetes, SBP, eGFR, uACR and kidney length are associated with a higher risk of ESKD. In patients with symptomatic vascular disease, secondary cardiovascular prevention focused at these risk factors may also reduce the risk of ESKD. Figure 1 Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): University Medical Center Utrecht

Association of Infection With Human Papillomavirus and Development of End-Stage Kidney Disease in Taiwan

The association between human papillomavirus (HPV) infection status and the natural process of kidney diseases has been neglected as an area of research. Further studies are needed to clarify factors that may alter the progression of end-stage kidney disease (ESKD). To describe the rates of ESKD among patients with and without HPV infection. In this nationwide, population-based retrospective cohort study, data were collected from the National Health Insurance Research Database of Taiwan. A total of 76 088 individuals with HPV infection were enrolled from January 1, 2000, to December 31, 2012, and compared with a control group of 76 088 individuals who had never been diagnosed with HPV infection (at a 1:1 ratio propensity-score matched by age, sex, index year, and comorbidities) in the context of the risk of developing ESKD. Statistical analysis was performed between November 2019 and July 2020. HPV infection was defined according to the International Classification of Diseases, Ninth Revision, Clinical Modification codes. The main outcome was ESKD, as recorded in the Catastrophic Illness Patients database. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% CIs, with the control group as a reference. Of 152 176 individuals (79 652 [52.3%] women; mean [SD] age, 34.4 [19.1] years), 76 088 individuals (50.0%) had HPV and 463 individuals (0.3%) developed ESKD. Incidence of ESKD was lower in individuals with HPV history than in those without HPV history (3.64 per 10 000 person-years vs 4.80 per 10 000 person-years). In the fully adjusted multivariate Cox proportional hazards regression model, individuals with a history of HPV infection had a significant decrease in risk of ESKD (adjusted HR, 0.72; 95% CI, 0.60-0.87) after adjusting for demographic characteristics, comorbidities, and comedications. In the subgroup analysis, individuals ages 50 to 64 years with HPV infection had a statistically significantly lower risk of ESKD compared with individuals ages 50 to 64 years with no HPV infection (adjusted HR, 0.48; 95% CI, 0.34-0.68; P < .001), while there was no significant reduction in risk for the other age groups (ie, 0-19, 20-49, and 65-100 years). In this study, a history of HPV infection was associated with a lower risk of subsequent ESKD. The mechanism behind this protective association remains uncertain. Future studies are required to clarify the possible biological mechanisms.

Long-term renal survival and related risk factors for primary membranous nephropathy in Chinese children: a retrospective analysis of 217 cases.

Primary membranous nephropathy (PMN) is a rare pathological finding in paediatric patients. Data on PMN in children have been restricted to studies with small samples and fairly short follow-up periods. Therefore, we conducted this single-centre study to evaluate the long-term renal survival and related risk factors for PMN in children, and the clinical and histological characteristics were also described. Two hundred and seventeen children with PMN were enrolled from July 2008 to September 2017. Patients with follow-up durations < 12months were excluded, except for patients who progressed to end-stage kidney disease (ESKD) or experienced a related death within 12months. Long-term renal survival and related risk factors were analysed. The sex ratio was 1.33:1 (male vs female), and the median age was 15.0 (14.0-17.0) years old. The most prominent clinical manifestation was nephrotic syndrome (130 59.9%), which was accompanied by various degrees of oedema (142 65.4%), hyperlipidaemia (151 69.6%), hypoalbuminemia (130 59.9%), and nephrotic proteinuria (135 62.2%). Hypertension occurred in 36.4% of children with PMN. After a median follow-up of 45.0 (23.5-74.0) months, 11 patients (5.1%) developed ESKD, and the cumulative kidney survival rates of ESKD at 5 and 10years after renal biopsy were 95.3% and 67.8%, respectively. The cumulative kidney survival rates of the combined event of ESKD and/or 30% decline in estimated glomerular filtration rate (eGFR) at 5 and 10years after renal biopsy were 92.6% and 59.5%, respectively. Cox multivariate regression and Kaplan-Meier analysis demonstrated that hypertension and proteinuria ≥50mg/kg/day were associated with renal outcome. In this study, the 5-year and 10-year cumulative renal survival rates of ESKD in children with PMN were reported for the first time as 95.3% and 67.8%, respectively. In addition, this is the first report to find that hypertension and proteinuria ≥50mg/kg/day are associated with renal outcome in children with PMN.

Detection of Mesangial hypercellularity of MEST-C score in immunoglobulin A-nephropathy using deep convolutional neural network

Immunoglobulin A (IgA)-nephropathy (IgAN) is one of the major reasons for renal failure. It provides vital clues to estimate the stage and the proliferation rate of end-stage kidney disease. IgA stage can be estimated with the help of MEST-C score. The manual estimation of MEST-C score from whole slide kidney images is a very tedious and difficult task. This study uses some Convolutional neural networks (CNNs) related models to detect mesangial hypercellularity (M score) in MEST-C. CNN learns the features directly from image data without the requirement of analytical data. CNN is trained efficiently when image data size is large enough for a particular class. In the case of smaller data size, transfer learning can be used efficiently in which CNN is pre-trained on some general images and then on subject images. Since the data set size is small, time spent in collecting large data set is saved. The training time of transfer learning is also reduced because the model is already pre-trained. This research work aims at the detection of mesangial hypercellularity from biopsy images with small data size by utilizing the transfer learning. The dataset used in this research work consists of 138 individual glomerulus (× 20 magnification digital biopsy) images of IgA patients received from All India Institute of Medical Science, Delhi. Here, machine learning (k-nearest neighbour (KNN) and support vector machine (SVM)) classifiers are compared to transfer learning CNN methods. The deep extracted image features are used by machine learning classifiers. The different evaluation parameters have been used for comparing the predictions of basic classifiers to the deep learning model. The research work concludes that the transfer learning deep CNN method can improve the detection of mesangial hypercellularity as compare to KNN, SVM methods when using the small data set. This model could help the pathologists to understand the stages of kidney failure.

An opt-out model for kidney transplant referral: The time has come.

Disparities that affect equity in access to kidney transplantation for patients with kidney failure have been well described. Many robust clinical trials have tested the effectiveness of interventions to reduce disparities and equilibrate access to kidney transplantation. Moreover, policy changes have been enacted to achieve the same aims. Despite these efforts, rates of kidney transplant waitlisting within the first year of end-stage kidney disease have remained unchanged over the past 2 decades, while incident rates of end-stage kidney disease have climbed. Because prior interventions have not durably increased transplant access, disruptive change is clearly needed. The Advancing American Kidney Health Executive Order sets bold goals to transform kidney care for patients and caregivers. In this spirit, we discuss an Opt-Out for Transplant Referral Model as a compelling solution to improve equity in access to kidney transplantation.