#901 Natural history of idiopathic nephrotic syndrome: the UK National RaDaR Idiopathic Nephrotic Syndrome Cohort

Abstract

Abstract Background and Aims Idiopathic nephrotic syndrome (INS) is an important class of proteinuric renal disease leading to kidney failure (KF). Here we describe the natural history of INS and congenital nephrotic syndrome (NS) using the UK National Registry of Rare Kidney Diseases Idiopathic Nephrotic Syndrome (RaDaR-INS) Cohort, including retrospective and prospective data from 4610 patients with NS not attributable to glomerulonephritis or systemic disorders recruited from 107 adult and paediatric kidney units across the UK since 2010. Method Participant eligibility of RaDaR-INS Cohort patients included ≥12 months observation from disease onset and no KF (CKD stage 5 or on renal replacement therapy) at or prior to disease onset. Disease onset date was defined as first database occurrence of kidney biopsy, primary diagnosis or protein-creatinine ratio (PCR) ≥1.5 g/g. Participants were sub-categorized into those with a genetic diagnosis (INS-genetic), biopsy-proven FSGS (FSGS-biopsy), biopsy–proven minimal change disease (MCD-biopsy) and those with no genetic or biopsy-proven diagnosis (INS-no genetic or biopsy diagnosis). Participants with a biopsy-proven MCD diagnosis and a subsequent biopsy proven FSGS diagnosis were included in both MCD-biopsy and FSGS-biopsy categories and formed a category of their own (MCD progressing to FSGS). Longitudinal proteinuria, assessed as time-average protein-to-creatinine ratio (TA-PCR), and eGFR slope were calculated over the full duration of follow-up or until KF. Kidney survival was calculated from disease onset to event (KF or death) and censored at last follow-up. Results Of the 4066 patients meeting eligibility, median age at disease onset was 28 years (IQR 6-51), with children (<18 yrs) representing 39% of the study population. Median proteinuria was 6.4 g/g (IQR 3.1-10.8; n = 923), while mean eGFR was 118 mL/min/1.73 m2 (SD 49; n = 240) and 69 mL/min/1.73 m2 (SD 34; n = 906) for children and adults, respectively. Median follow-up duration was 8.2 yrs (IQR 4.3-13.1) with KF/death events occurring in 30% of patients. Mean TA-PCR was greater in children than adults (5.0 g/g (SD 13.9) vs. 1.9 g/g (SD 2.5), as was annual rate of loss of eGFR (−7.4 mL/min/1.73 m2 (SD 21.8) vs. −3.1 mL/min/1.73 m2 (SD 10.2)). Characteristics at disease onset and clinical outcomes of the INS cohort sub-categories are presented in Fig. 1. Kaplan Meier survival plots of each sub-category, and further divided into children and adults, illustrate the poor survival probability for patients with FSGS, particularly INS-genetic patients who are predominantly diagnosed in childhood (Fig. 2). While INS with no genetic or biopsy diagnosis presenting in childhood exhibits disease course and outcomes similar to MCD-biopsy patients, those diagnosed in adulthood have a more rapid disease course similar to FSGS-biopsy patients. Conclusion The RaDaR-INS cohort represents a large study population with lengthy follow-up data. These analyses illustrate the difference in disease progression and survival rates for INS patients with different causes or histological descriptions, highlighting in particular an unmet need for effective treatments for patients with nephrotic syndrome and FSGS.