Validation of Graded Renal Response Criteria in Light Chain Amyloidosis Using Composite Kidney Outcome

Abstract Introduction: Four-level graded organ response criteria provide a more refined alternative to traditional binary classification in systemic light chain (AL) amyloidosis. However, the prognostic value of graded renal responses for kidney outcomes requires further validation. Methods: We retrospectively analyzed 475 patients with renal AL amyloidosis who achieved at least a hematologic partial response. Renal responses were categorized as renal complete response (RenCR), renal very good partial response (RenVGPR), renal partial response (RenPR), and renal no response (RenNR) based on reductions in 24-hour proteinuria, in the absence of a ≥25% worsening of serum creatinine. The composite kidney outcome served as the primary renal endpoint. Results: Among the 475 enrolled patients, RenCR, RenVGPR, RenPR, and RenNR accounted for 17.7%, 46.1%, 15.1%, and 21.1%, respectively. Deeper renal responses were associated with better overall survival (OS) and a lower risk of the composite kidney outcome. The 5-year OS rates were 98.8% (RenCR), 93.5% (RenVGPR), 68.5% (RenPR), and 46.8% (RenNR) (P < 0.001). The median time to composite kidney outcome was not reached, 158 months, 63 months, and 36 months, respectively (P < 0.001). Landmark analyses, time-varying covariate Cox regression, competing risk regression, and subgroup analyses further supported the independent prognostic value of graded renal responses. Time-dependent receiver operating characteristic (ROC) curve analyses demonstrated that graded renal response criteria performed better than two-level classifications for predicting the composite kidney outcome. Conclusions: Graded renal response criteria provided superior discrimination in predicting the composite kidney outcome, with deeper responses associated with better survival.