Serum Free Light Chain Levels and Acute Kidney Injury Outcomes in Patients with Plasma Cell Dyscrasias
Authors: Nasirikhaneghah Erfan , Li Zoe , Chiu Edwin , Macedo Etienne 
Published: December 2024

Background: Plasma cell disorders can cause acute kidney injury (AKI) through multiple mechanisms. Myeloma cast nephropathy (MCN), due to elevated free light chain (FLC), is one of the most severe manifestations of AKI in this setting. Rapid identification and treatment of MCN are paramount, as delays can lead to irreversible injury and chronic kidney disease. This study aimed to determine the association of FLC with renal recovery outcomes following AKI in patients with plasma cell disorders.

Design/Method: In this retrospective study, all patients with plasma cell disorders admitted to UC San Diego Health with the first presentation of AKI from 2010 to 2021 were included. Renal function at diagnosis was determined by serum creatinine (sCr) and estimated glomerular filtration rate (eGFR) obtained on the first day of hospital presentation. Renal recovery was assessed at 3 months and 1 year from the initial AKI diagnosis. Through database review, out of the 1174 patients identified, 423 had baseline renal function and elevated FLC and were included in the analysis. Multivariate analysis of factors associated with improvement or decline in renal function at 3 and 12 months was performed using a logistic regression model, including predictors such as age, sex, FLC, baseline average eGFR, and eGFR at diagnosis.

Result: The severity of the AKI stage was higher with increasing levels of ß2-microglobulin and sCr at diagnosis, as well as lower baseline eGFR (p &lt; 0.05). Serum FLC values had no association with renal recovery outcomes. However, those with FLC greater than 500 mg/dL at presentation, compared to individuals with FLC less than 500 mg/dL, had a significantly higher likelihood of improved renal recovery outcomes (OR= 2.17, p=0.04). Of the patients with FLC greater than 500 mg/dL, 107 out of 123 (87%) had full renal recovery. Although not statistically significant (p=0.07), there were increasing FLC levels with a higher AKI stage at presentation. Patients were more likely to have complete renal recovery at the 3-month follow-up if they had a higher eGFR at the time of diagnosis (OR= 1.02, p=0.007) and a lower baseline eGFR (OR= 0.98, p=0.019). Significant predictors of renal recovery at one-year follow-up included age (OR= 0.97, p=0.03), baseline eGFR (OR= 0.98, p=0.01), and eGFR at diagnosis (OR= 1.02, p=0.049). The one-year overall mortality following the initial AKI presentation in our cohort was 56 (13.2%), with increasing age as a statistically significant predictor of overall mortality even after adjusting for baseline kidney function (p=0.02). FLC level was not a significant predictor of overall mortality risk (p=0.69). In secondary analyses of overall mortality in patients with available ß2-microglobulin at presentation (226 [53%]), ß2-microglobulin was a significant predictor of mortality even after adjusting for eGFR at the time of diagnosis (OR 1.06, p=0.03).

Conclusion: To our knowledge, no study has investigated the impact of an initial presentation of AKI and the contribution of various factors on renal recovery and overall survival in patients with underlying plasma cell disorders over a one-year follow-up. This study highlights that FLC values are one of the insulting processes in AKI development, and their levels are not always correlated with renal outcomes. Rapid identification and treatment of conditions such as myeloma cast nephropathy are critical to prevent irreversible kidney damage and progression to chronic kidney disease. Additionally, baseline renal function and renal function at diagnosis were significant predictors of both short-term and long-term renal recovery. These results emphasize the importance of early intervention and continuous monitoring of renal function in patients with plasma cell disorders to improve their prognosis and overall survival.