Long-Term Outcomes in Nephrotic Syndrome by Kidney Biopsy Diagnosis and Proteinuria

Background: The UK Registry of Rare Kidney Diseases (RaDaR) Idiopathic Nephrotic Syndrome cohort includes adults and children with genetic nephrotic syndrome, Focal Segmental Glomerulosclerosis (FSGS) and minimal change disease. This study examines long-term patient outcomes as a function of kidney biopsy diagnosis and proteinuria control. Methods: 2467 adults and 1599 children were followed to establish outcomes including eGFR slope and kidney survival by diagnosis, analysed as a function of proteinuria from disease onset for FSGS and minimal change disease. Enrollment began in 2010, with follow-up to September 2023. Index date for the survival analyses was date of disease onset. Results: The cohort had median [IQR] follow up of 8.2 [4.3-13.1] years; 30% of patients reached kidney failure or died. 1303 patients had FSGS, 1153 minimal change disease, 105 monogenic nephrotic syndrome. Children showed relatively preserved mean kidney function at disease onset (eGFR>100 ml/min/1.73m 2 ), compared to adults (FSGS 61ml/min/1.73m 2 ; minimal change disease 76ml/min/1.73m 2 ). Kidney survival probability (95% CI) at 10 years varied with diagnosis: Genetic 29% (20-38), FSGS 58% (55-61), minimal change disease 87% (85-89) with mean (SD) rates of eGFR loss -26.5 (34.7), -6.2 (14.3), and -1.9 (10.2) ml/min/1.73m 2 per year respectively. FSGS 10-year kidney survival (95% CI) for 6-12 months lowest proteinuria value in complete remission (<0.3g/g), partial remission (0.3-3.5g/g) and no remission (>3.5g/g) was 88% (70-96). 65% (50-76) and 37% (26-48), respectively. Time-averaged proteinuria of <1.5g/g over 6-24 months from disease onset was associated with 90% 10-year kidney survival. For minimal change disease, patients’ 10-year kidney survival (95% CI) stratified by 6-12 months lowest proteinuria value was: complete remission 89% (79-94), partial remission 75% (51-89), and no remission 64% (41-81). In FSGS and minimal change disease 10-year eGFR slope was strongly correlated with absolute levels of proteinuria. Conclusions: Kidney outcomes were poor in genetic nephrotic syndrome; in FSGS outcomes were strongly associated with proteinuria level. Minimal change disease patients had better proteinuria control than FSGS and had better outcomes at each proteinuria level.