Key Points:
In nephrotic syndrome, diagnosis was associated with kidney failure risk: very high in monogenic cases, substantial in FSGS, and less but not zero in minimal change disease.
Early control of proteinuria was associated with lower kidney failure risk, and in FSGS levels <1.5 g/g are associated with good kidney outcomes at 10 years.
Monogenic nephrotic syndrome cases had very high proteinuria and rapid progression to kidney failure with little response to current treatments.
Background: The UK National Registry of Rare Kidney Diseases Idiopathic Nephrotic Syndrome cohort includes adults and children with genetic nephrotic syndrome, FSGS, and minimal change disease. This study examines long-term patient outcomes as a function of kidney biopsy diagnosis and proteinuria control.
Methods: Two thousand four hundred and sixty-seven adults and 1599 children were followed to establish outcomes including eGFR slope and kidney survival by diagnosis, analyzed 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 a median (interquartile range) follow-up of 8.2 (4.3–13.1) years; 30% of patients reached kidney failure or died. In total, 1303 patients had FSGS, 1153 had minimal change disease, and 105 had monogenic nephrotic syndrome. Children showed relatively preserved mean kidney function at disease onset (eGFR >100 ml/min per 1.73 m2), compared with adults (FSGS 61 ml/min per 1.73 m2; minimal change disease 76 ml/min per 1.73 m2). Kidney survival probability (95% confidence interval [CI]) at 10 years varied with diagnosis: genetic 29% (20 to 38), FSGS 58% (55 to 61), minimal change disease 87% (85 to 89) with mean (SD) rates of eGFR loss −26.5 (34.7), −6.2 (14.3), and −1.9 (10.2) ml/min per 1.73 m2 per year, respectively. FSGS 10-year kidney survival (95% CI) for 6–12 months lowest proteinuria value in complete remission (<0.3 g/g), partial remission (0.3–3.5 g/g), and no remission (>3.5 g/g) was 88% (70 to 96), 65% (50 to 76), and 37% (26 to 48), respectively. Time-averaged proteinuria of <1.5 g/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 to 94), partial remission 75% (51 to 89), and no remission 64% (41 to 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 the proteinuria level. Patients with minimal change disease had better proteinuria control than FSGS and had better outcomes at each proteinuria level.
Keywords: chronic GN; glomerular diseases; glomerulosclerosis; idiopathic nephrotic syndrome; nephrotic syndrome; pediatric nephrology; primary GN; proteinuria; renal function decline.