Long-Term Outcomes in IgA Nephropathy

BACKGROUND: IgA nephropathy can progress to kidney failure, and risk assessment soon after diagnosis has advantages both for clinical management and the development of new therapeutics. We present relationships among proteinuria, eGFR slope and lifetime risks for kidney failure. METHODS: The IgA nephropathy cohort (2,299 adults, 140 children) of the UK National Registry of Rare Kidney Diseases (RaDaR) was analyzed. Patients enrolled had a biopsy-proven diagnosis of IgA nephropathy, plus proteinuria >0.5 g/day or eGFR <60 mL/min/1.73m 2 . Incident and prevalent populations were studied as well as a population representative of a typical phase 3 clinical trial cohort. Analyses of kidney survival were conducted using Kaplan-Meier and Cox regression. eGFR slope was estimated using linear mixed models with random intercept and slope. RESULTS: Median (Q1, Q3) follow-up was 5.9 (3.0, 10.5) years; 50% of patients reached kidney failure or died in the study period. Median (95% CI) kidney survival was 11.4 (10.5, 12.5) years; mean age at kidney failure/death was 48 years, and most patients progressed to kidney failure within 10-15 years. Based on eGFR and age at diagnosis, almost all patients are at risk of progression to kidney failure within their expected lifetime unless a rate of eGFR loss ≤1 ml/min/1.73m 2 /year can be maintained. Time-averaged proteinuria was significantly associated with worse kidney survival and more rapid eGFR loss in incident, prevalent, and "clinical trial" populations. 30% of patients with time-averaged proteinuria of 0.44 to <0.88 g/g and approximately 20% of patients with time-averaged proteinuria <0.44 g/g developed kidney failure within 10 years. In the "clinical trial" population each 10% decrease in time-averaged proteinuria from baseline was associated with a hazard ratio (95% CI) for kidney failure/death of 0.89 (0.87-0.92). CONCLUSIONS: Outcomes in this large IgA nephropathy cohort are generally poor with few patients expected to avoid kidney failure in their lifetime. Significantly, patients traditionally regarded as being "low-risk", with proteinuria <0.88 g/g (<100 mg/mmol), have high rates of kidney failure within 10 years

Effects of rare kidney diseases on kidney failure: a longitudinal analysis of the UK National Registry of Rare Kidney Diseases (RaDaR) cohort

Individuals with rare kidney diseases account for 5-10% of people with chronic kidney disease, but constitute more than 25% of patients receiving kidney replacement therapy. The National Registry of Rare Kidney Diseases (RaDaR) gathers longitudinal data from patients with these conditions, which we used to study disease progression and outcomes of death and kidney failure.People aged 0-96 years living with 28 types of rare kidney diseases were recruited from 108 UK renal care facilities. The primary outcomes were cumulative incidence of mortality and kidney failure in individuals with rare kidney diseases, which were calculated and compared with that of unselected patients with chronic kidney disease. Cumulative incidence and Kaplan-Meier survival estimates were calculated for the following outcomes: median age at kidney failure; median age at death; time from start of dialysis to death; and time from diagnosis to estimated glomerular filtration rate (eGFR) thresholds, allowing calculation of time from last eGFR of 75 mL/min per 1·73 m2 or more to first eGFR of less than 30 mL/min per 1·73 m2 (the therapeutic trial window).Between Jan 18, 2010, and July 25, 2022, 27 285 participants were recruited to RaDaR. Median follow-up time from diagnosis was 9·6 years (IQR 5·9-16·7). RaDaR participants had significantly higher 5-year cumulative incidence of kidney failure than 2·81 million UK patients with all-cause chronic kidney disease (28% vs 1%; p Background Methods Findings Interpretation Funding</p