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Comparative Analysis of Proteinuria and Longitudinal Outcomes in Immune Complex Membranoproliferative
Fernando Caravaca-Fontán1, Remedios Toledo-Rojas2, Ana Huerta3
1Department of Nephrology, Instituto de Investigación Hospital 12 de Octubre (imas12), Madrid, Spain.
Insights
Reducing proteinuria significantly improves kidney outcomes in C3 glomerulopathy (C3G) and immune complex-mediated glomerulonephritis (IC-MPGN). Achieving a 50% reduction in proteinuria is linked to a lower risk of kidney failure and slower decline in kidney function.
Area of Science:
- Nephrology
- Immunology
- Internal Medicine
Background:
- C3 glomerulopathy (C3G) and primary immune complex-mediated membranoproliferative glomerulonephritis (IC-MPGN) are rare kidney diseases with similar pathogenesis.
- The prognostic value of proteinuria reduction in these conditions is not well understood.
Purpose of the Study:
- To compare outcomes in C3G and IC-MPGN.
- To assess how proteinuria reduction impacts kidney prognosis in these rare diseases.
Main Methods:
- Retrospective, longitudinal, multicenter study of 149 patients with C3G or IC-MPGN.
- Utilized linear mixed-effects models for proteinuria trajectories and Cox regression for kidney failure risk.
- Calculated time-averaged proteinuria (TA-P) to evaluate its prognostic impact.
Main Results:
- A 50% or greater reduction in proteinuria over time was associated with a significantly lower risk of kidney failure (HR: 0.61; 95% CI: 0.46-0.75).
- Proteinuria reduction correlated with slower estimated glomerular filtration rate (eGFR) decline, with specific reductions at 6 and 12 months showing benefit.
- Lower time-averaged proteinuria (< 1 g/d) predicted better kidney outcomes.
Conclusions:
- Proteinuria reduction is a significant positive prognostic factor in both C3G and IC-MPGN.
- Achieving substantial proteinuria reduction is associated with improved kidney survival and slower progression of kidney disease.
Introduction:
C3 glomerulopathy (C3G) and primary immune complex-mediated membranoproliferative glomerulonephritis (IC-MPGN) are rare diseases that share a similar pathogenesis; however, the prognostic significance of proteinuria reduction remains poorly characterized. This study compared the outcomes in C3G and IC-MPGN and assessed the impact of changes in proteinuria on kidney prognosis.
Methods:
This retrospective, longitudinal, multicenter study used joint linear mixed-effects models to assess proteinuria trajectories, and Cox regression to evaluate their association with kidney failure. In addition, time-averaged proteinuria (TA-P) was calculated to determine its impact on kidney prognosis.
Results:
The study included 149 patients: 98 with C3G (66%) and 51 with IC-MPGN (34%) with a median age of 35 (interquartile range [IQR]: 22-53) years. During a median follow-up of 65 (IQR: 32-114) months, 44 patients (30%) progressed to kidney failure without differences across C3G or IC-MPGN. A strong association was observed between longitudinal increase in proteinuria and the risk of kidney failure. In addition, a ≥ 50% proteinuria reduction over time was associated with a lower risk of kidney failure (hazard ratio [HR]: 0.61; 95% confidence interval [CI]: 0.46-0.75, P < 0.001). Results were consistent in both C3G and IC-MPGN, and in those with baseline estimated glomerular filtration rate (eGFR) ≥ 30 ml/min per 1.73 m2 and proteinuria ≥ 1 g/d. A ≥30% proteinuria reduction at 6 months or a ≥50% proteinuria reduction at 12 months were associated with a slower eGFR decline. Patients were categorized into 4 subgroups based on TA-P levels, with TA-P values < 1 g/d indicating better kidney outcomes.
Conclusion:
Proteinuria reduction was associated with improved kidney outcomes and slower eGFR decline in both C3G and IC-MPGN.
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