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

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=1,935) 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 30 mL/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, HR=5.13, HR=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% confidence interval [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 time points. 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.