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Proteinuria remission and long-term kidney outcome in children with IgA nephropathy
Rosanna Coppo1, Giuseppe Lucisano2, Licia Peruzzi3
1Fondazione Ricerca Molinette, Regina Margherita Hospital, Turin, Italy.
Insights
Achieving complete and sustained proteinuria remission (CSR) in children with Immunoglobulin A nephropathy (IgAN) is linked to better long-term kidney function. This study highlights factors associated with CSR and its protective effect on estimated glomerular filtration rate (eGFR) decline.
Area of Science:
- Pediatric Nephrology
- Glomerular Diseases
- Immunoglobulin A Nephropathy
Background:
- Current guidelines recommend proteinuria <0.2 g/day/1.73m² for pediatric IgAN, but long-term outcomes of this target are unclear.
- Previous studies on proteinuria remission in IgAN were limited to small, monoethnic groups.
Purpose of the Study:
- To investigate clinical and histological factors associated with complete and sustained proteinuria remission (CSR) in a multiethnic cohort of children with IgAN.
- To evaluate the impact of CSR on long-term estimated glomerular filtration rate (eGFR) decline.
Main Methods:
- Analysis of a multiethnic cohort of 709 children with IgAN and proteinuria ≥0.2 g/day/1.73m² at biopsy.
- Assessment of complete and sustained proteinuria remission (CSR) lasting >90 days.
- Evaluation of clinical (age, eGFR) and histological (MEST-C score) factors, and treatment (RASB, IS) associated with CSR and eGFR decline.
Main Results:
- CSR occurred in 55.7% of children and was maintained in 47.3% throughout follow-up.
- Children achieving CSR showed significant protection from eGFR decline at 4 and 5 years.
- Factors associated with CSR included younger age, higher eGFR, absence of segmental sclerosis, and treatment with RASB and IS. Japanese and Chinese ethnicities showed a strong effect.
Conclusions:
- Achievement of CSR in pediatric IgAN is associated with improved long-term eGFR outcomes.
- Identifying factors associated with CSR can help optimize treatment strategies for children with IgAN.
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.
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