Proteinuria remission and long-term kidney outcome in children with IgA nephropathy

Abstract Background KDIGO and IPNA guidelines indicate a target of proteinuria < 0.2 g/day/1.73m2 in children with Immunoglobulin A nephropathy (IgAN). However, the value of proteinuria remission to this threshold was limited to small monoethnic cohorts, with unknown long-term kidney outcomes. Methods In a previously described multiethnic cohort of 1 298 children with IgAN, we selected those with proteinuria at kidney biopsy ≥ 0.2 g/day/1.73m² and analyzed the occurrence of complete and sustained proteinuria remission lasting > 90 days (CSR). Aim of the study was to investigate clinical and histological factors associated with CSR and the value on long-term eGFR decline. Results The study enrolled 709 children with different ethnicities (White, Chinese and Japanese). The median age at biopsy was 12.9 years, eGFR 95.7 ml/min/1.73m2 and proteinuria 1.2 g/day/1.73m2. MEST-C scoring detected M1 in 57% of the cases, E1 in 41.3%, S1 in 53.3%, T1-2 in 13.6% and C1-2 in 46.7%. CSR occurred in 395 children (55.7%) after time-averaged observation of 0.7 years (0.4–1.3 years) and was maintained throughout follow-up in 47.3% of the cases. In a sensitivity analysis, children who achieved CSR had significant protection from eGFR decline at 4 and 5-years (p = 0.026 and p = 0.004 respectively). During follow-up, 74.4% were treated with renin-angiotensin system blockers (RASB) and 67.4% with immunosuppressors (IS). In a Cox proportional multivariate model including time-dependent RASB and IS treatment, a significant association with CSR was detected for younger age (p = 0.009), higher eGFR (p = 0.002), absence of segmental sclerosis (p < 0.001) and RASB treatment (p < 0.001). The model including ethnicity showed a strong effect of Japanese and Chinese ethnicity (both p < 0.001) and a significant association of CSR with age, absence of S1 (p < 0.001) and T1-2 (p = 0.016) and RASB and IS treatment (both p < 0.01). Conclusions The observational study showed that the achievement of CSR in children with IgAN was associated with better eGFR outcome.