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A Multicenter Study of the Predictive Value of Crescents in IgA Nephropathy
Mark Haas1, Jacobien C Verhave2, Zhi-Hong Liu3
1Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, California; mark.haas@cshs.org.
Insights
Glomerular crescents in IgA nephropathy predict worse kidney outcomes, especially in patients not on immunosuppression. The study proposes new crescent scores (C1, C2) to enhance the Oxford Classification for better risk stratification.
Area of Science:
- Nephrology
- Pathology
- Renal Medicine
Background:
- The Oxford Classification for IgA nephropathy (IgAN) is crucial for prognostication but omits glomerular crescents.
- Previous studies on crescents' predictive value were limited by excluding patients with severe renal insufficiency.
Purpose of the Study:
- To evaluate crescents as a predictor of renal outcomes in a large IgAN cohort.
- To determine if the proportion of crescent-containing glomeruli impacts survival from a composite endpoint of ≥50% eGFR decline or End-Stage Renal Disease (ESRD).
Main Methods:
- A pooled analysis of 3096 patients from four retrospective IgAN studies.
- Statistical analysis adjusted for covariates from the original Oxford classification.
- Assessment of crescents' association with a combined renal event (≥50% eGFR decline or ESRD).
Main Results:
- Overall, crescents predicted a higher risk of the combined renal event, particularly in patients not receiving immunosuppression.
- Having crescents in ≥1/4 of glomeruli was associated with a significantly increased hazard ratio for the combined event (HR 2.29; 95% CI 1.35-3.91).
- This association remained significant independently in both immunosuppression and non-immunosuppression groups.
Conclusions:
- Glomerular crescents are significant independent predictors of poor renal outcomes in IgAN.
- Proposed crescent scores (C0, C1, C2) can refine the Oxford Classification for improved risk stratification.
- These scores can identify patients at high risk, guiding treatment decisions, even with immunosuppression.
Abstract:
The Oxford Classification of IgA nephropathy does not account for glomerular crescents. However, studies that reported no independent predictive role of crescents on renal outcomes excluded individuals with severe renal insufficiency. In a large IgA nephropathy cohort pooled from four retrospective studies, we addressed crescents as a predictor of renal outcomes and determined whether the fraction of crescent-containing glomeruli associates with survival from either a ≥50% decline in eGFR or ESRD (combined event) adjusting for covariates used in the original Oxford study. The 3096 subjects studied had an initial mean±SD eGFR of 78±29 ml/min per 1.73 m2 and median (interquartile range) proteinuria of 1.2 (0.7-2.3) g/d, and 36% of subjects had cellular or fibrocellular crescents. Overall, crescents predicted a higher risk of a combined event, although this remained significant only in patients not receiving immunosuppression. Having crescents in at least one sixth or one fourth of glomeruli associated with a hazard ratio (95% confidence interval) for a combined event of 1.63 (1.10 to 2.43) or 2.29 (1.35 to 3.91), respectively, in all individuals. Furthermore, having crescents in at least one fourth of glomeruli independently associated with a combined event in patients receiving and not receiving immunosuppression. We propose adding the following crescent scores to the Oxford Classification: C0 (no crescents); C1 (crescents in less than one fourth of glomeruli), identifying patients at increased risk of poor outcome without immunosuppression; and C2 (crescents in one fourth or more of glomeruli), identifying patients at even greater risk of progression, even with immunosuppression.
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