#3057 outcomes in srns (fsgs) patients in the uk radar idiopathic nephrotic syndrome registry and their relationship with time-averaged proteinuria

Abstract Background and Aims Idiopathic Steroid Resistant Nephrotic Syndrome, SRNS (incorporating FSGS) is an important cause of proteinuric renal disease leading to kidney failure. Here we describe the outcomes of SRNS using the UK National Registry of Rare Kidney Diseases Idiopathic Nephrotic Syndrome (RaDaR-INS) Cohort, including retrospective and prospective data from 4274 patients with nephrotic syndrome (NS) not attributable to glomerulonephritis or systemic disorders, recruited from 107 adult and paediatric kidney units across the UK since 2010. In patients with FSGS, severity of proteinuria at onset and during follow up is associated with renal failure. In this study, we tested for associations between defined proteinuria endpoints with both eGFR slope and renal survival, in children and adults. Method Participants included those with renal biopsy diagnosis of FSGS or minimal change disease (MCD), or monogenic NS. Patients with no proteinuria measurement ≥1.0 g/g >6 months after disease onset were excluded as likely fully steroid-sensitive. Patients with kidney failure (KF) (CKD stage 5 or on renal replacement therapy) at or prior to first proteinuria measurement after baseline were excluded. Disease onset was defined as time of renal biopsy; primary renal diagnosis (PRD) date if no biopsy date recorded, and first proteinuria ≥1 g/g if neither biopsy/PRD date was available. Baseline was defined as first proteinuria ≥1 g/g >6 months after disease onset. Kaplan-Meier methods were used to analyze renal survival, defined as absence of KF or death with survival time calculated from baseline to last follow up. eGFR slope was measured from 6 months after baseline for the duration of follow up. Results Of 612 MCD and FSGS patients meeting eligibility, median time from disease onset to baseline was 1.2 years (IQR 0.6-4.4). Median baseline age was 38 years (IQR 21–56) with paediatric patients representing 21% of the study population. Median proteinuria at baseline was 3.4 g/g (IQR 1.9-6.2), while mean eGFR was 89 mL/min/1.73 m2 (SD 39). Mean rate of loss of eGFR over follow-up was 4.4mL/min/1.73 m2/year (SD 10.9). Complete proteinuria remission (CR) and FSGS partial remission (FPR) were defined as shown in Table 1 using values of time-averaged proteinuria (TA-PU) over months 6–24 from baseline. For patients achieving CR or FPR, the rate of loss of eGFR was slower (Table 1), with a higher probability of survival from KF/death (Table 1 & Figure 1), than patients failing to achieve CR or FPR. Conclusion This is a study of proteinuria and outcomes in a population of patients with FSGS or steroid-resistant MCD. We regard the latter group as likely also to have FSGS. In this population of patients with overt proteinuria, achieving partial or complete remission of proteinuria is associated with slower disease progression and reduced risk of KF/death.