Revised renal stratification and progression models for predicting long-term renal outcomes in immunoglobulin light chain amyloidosis

Abstract

Renal prognosis in light-chain amyloidosis (AL) is determined by categorizing patients into three renal stages at diagnosis and assessing Renal Response or Renal Progression following chemotherapy after 6 months. We evaluated, in a test (N=1935) cohort of patients with renal AL amyloidosis who were followed for a median of 95 months, a modified 4-stage model where Renal Stage 2 was sub-categorized according to preserved (2A) or reduced (2B) estimated Glomerular Filtration Rate (eGFR). A hybrid model for evaluation of Renal Progression was also introduced, using an eGFR cut-off of 30ml/min/1.73 m2. These models were compared with existing models; namely those of Palladini and Kastritis, and results were validated in a multicenter cohort (N=438).

The risk of progression to renal replacement therapy (RRT) increased progressively across all Renal Stages of the revised staging model (Hazard ratio [HR]: 3.25, 5.13, 10.66 for Stages 2A, 2B and 3 respectively vs Stage 1, each p<0.001). Our revised criteria for Renal Response (HR 0.26 [95% CI: 0.18-0.38] at 60 months) and Renal Progression (HR 8.15 [95% CI: 6.1-10.9]) were independently predictive of RRT and outperfomed existing criteria at all follow up timepoints. Renal Progression was independently associated with mortality (HR 1.5, 95% CI: 1.26-1.86, p<0.001). The enhanced performance of these refined renal staging and response models enables timely and appropriate chemotherapy adjustment in patients with renal AL amyloidosis.