Background: Improved management of lymphoma patients has resulted in increasing numbers of long term survivors suffering from a broad spectrum of late effects of treatment. In particular lymphoma patients are exposed to nephrotoxic insults from therapy and its complications such as sepsis and tumor lysis syndrome, as well as from repeated contrast-enhanced imaging studies. Multiple episodes of acute kidney injury (AKI) can lead to chronic kidney disease (CKD) in survivors. In a recent retrospective cohort study 34% of lymphoma patients were found to have CKD at 3 year follow up (1). Here we describe the progressive development of CKD in a cohort of lymphoma survivors over a 10-year period.
Methods: Three hundred and ninety-seven consecutive adults with biopsy proven lymphoma diagnosed and treated at our center between 2003 and 2017 were included in this study. Baseline characteristics including lymphoma subtype, age, race, gender, lymphoma therapy, number of CT scans and episodes of AKI were recorded. CKD, hypertension, diabetes mellitus (DM), body mass index (BMI), uric acid levels and infection with human immunodeficiency virus or hepatitis were also recoded at baseline. Obesity was defined as BMI ≥ 30. Glomerular filtration rate (GFR) was calculated using the CKD-EPI equation at diagnosis (time 0 or baseline) and after 1, 2, 5 and 10 years to calculate rate of GFR decline over time. CKD was defined as GFR <60 ml/min. Statistical analysis was performed in SAS 9.4. Probability of developing CKD over 10 years was derived from Kaplan-Meier analysis. Multivariate regression analysis was used to identify factors predicting development of CKD.
Results: Of 397 patients studied 174 (44%) had high grade and 159 (40%) low grade non-Hodgkin lymphoma (NHL), 61 (15%) had Hodgkin lymphoma and 3 (1%) grey zone lymphoma. Median age was 55 y (18-88), 54% were male, 60% were African Americans. At presentation 42% had hypertension, 15% had DM, 11% had HIV, 13% had hyperuricemia, 32% were obese and 13% had CKD.A total of 61% received chemoimmunotherapy, 24% received chemotherapy, 9% received immunotherapy and 6% were observed without treatment. GFR declined progressively from 96.5 mL/min per 1.73 m2 at baseline, to 77.4 mL/min per 1.73 m2 at 10 years with a rate of decline of 4.6 mL/min per 1.73 m2 per year. CKD developed in 125 patients (31%) over the study period. In multivariate analysis age (HR:1.07, CI95:1.04-1.08, p<0.001), hypertension (HR 2.01, CI95:1.2-3.4, p<0.001), hyperuricemia (HR 1.2, CI95:1.03-1.3, p<0.001), DM (HR 2.5 CI95:1.2-5.3, p<0.05) were associated with higher likelihood and BMI (HR 0.96, CI95: 0.9-0.99, p<0.001) with lower likelihood of CKD development.
Conclusion: In this study CKD was a significant long-term complication in lymphoma survivors. With a progressive fall in their GFR, increasing numbers of lymphoma survivors developed CKD over the study period reaching 31% at 10 years. Age, hypertension, DM and raised uric acid at diagnosis increased the risk of CKD while obesity appeared protective. Renal injury in lymphoma survivors is probably multi-factorial. Further studies are needed to develop treatment approaches with reduced risk of CKD.
1. Ubukata M, Hara M, Nishizawa Y, Fujii T, Nitta K, Ohta A. Prevalence and mortality of chronic kidney disease in lymphoma patients: A large retrospective cohort study. Medicine. 2018;97(2):e9615.
No relevant conflicts of interest to declare.
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