Long-Term Outcomes in Nephrotic Syndrome by Kidney Biopsy Diagnosis and Proteinuria
Topics: Nephrology FSGS Non-product RaDaR Observational RWE Publication Summary
Pitcher D, Braddon F, Hendry B et al.
10.1681/ASN.0000000610
Summary
Analysis of the UK National Registry of Rare Kidney Diseases (RaDaR) highlights the significant burden of idiopathic nephrotic syndrome1
Background
Idiopathic nephrotic syndrome encompasses distinct subtypes — monogenic nephrotic syndrome, focal segmental glomerulosclerosis (FSGS), and minimal change disease (MCD) — that disrupt the glomerular filtration barrier.1,2
The impact of proteinuria control on long-term kidney outcomes in idiopathic nephrotic syndrome has not been fully characterized across large, well-defined cohorts, but in some subsets, achieving complete or partial proteinuria remission has been associated with better outcomes.1,3
Aim
The aim of this study was to evaluate long-term kidney survival and estimated glomerular filtration rate (eGFR) decline in patients with idiopathic nephrotic syndrome by histologic/genetic subtype and to quantify the relationship between early proteinuria reduction and the risk of kidney failure or death.1
Approach
This retrospective study used data from the UK National Registry of Rare Kidney Diseases (RaDaR) idiopathic nephrotic syndrome cohort (including adults and children with genetic nephrotic syndrome, biopsy-confirmed primary FSGS, or MCD) to assess long-term outcomes.1
Findings
The study population included subgroups of patients in the idiopathic nephrotic syndrome cohort1
The total cohort included 4,066 patients (2,467 adults; 1,599 children) with biopsy-confirmed FSGS or MCD, or genetically confirmed nephrotic syndrome.1
Kidney survival rates varied across the nephrotic syndrome subgroups1
Kidney survival rate at 10 years1:
- Genetic nephrotic syndrome: 29% (95% confidence interval [CI]: 20-38)
- FSGS: 58% (95% CI: 55-61)
- MCD: 87% (95% CI: 85-89)
Survival from kidney failure correlated with greater proteinuria remission (stratified by lowest proteinuria value 6-12 months after baseline)1
Survival rate in patients with FSGS at 10 years1:
- Complete remission (<0.3 g/g): 88% (95% CI: 70-96)
- Partial remission (0.3-3.5 g/g): 65% (95% CI: 50-76)
- No remission (>3.5 g/g): 37% (95% CI: 26-48)
Survival rate in patients with MCD at 10 years1:
- Complete remission (<0.3 g/g): 89% (95% CI: 79-94)
- Partial remission (0.3-3.5 g/g): 75% (95% CI: 51-89)
- No remission (>3.5 g/g): 64% (95% CI: 41-81)
In both FSGS and MCD subtypes, eGFR slope over 10 years strongly correlated with absolute levels of proteinuria1
Patients with FSGS experience a more rapid decline in kidney function and higher rates of kidney failure despite receiving treatments targeting proteinuria reduction.1 Patients with MCD generally experienced better outcomes than those with FSGS.1
Key takeaway
In idiopathic nephrotic syndrome, long-term kidney survival varies markedly by diagnosis.1 At the same levels of proteinuria, patients with biopsies showing FSGS are at a higher risk for poor outcomes than those with biopsies confirming MCD.1 Achieving early, sustained proteinuria reduction significantly improved outcomes, underscoring proteinuria as a critical prognostic and therapeutic target in clinical care and trial design in nephrotic syndrome.1
Footnotes
This work was supported by Travere Therapeutics, Inc. Please see the publication for the full list of disclosures.
CI, confidence interval; eGFR, estimated glomerular filtration rate; FSGS, focal segmental glomerulosclerosis; MCD, minimal change disease; RaDaR, National Registry of Rare Kidney Diseases.
- Pitcher D et al. J Am Soc Nephrol. 2025;36(7):1398-1413.
- Colby E et al. Clin Kidney J. 2024;17(8):sfae096.
- Troyanov S et al. J Am Soc Nephrol. 2005;16(4):1061-1068.
MA-DS-25-0089 | September 2025