Incidence and risk factors of chronic kidney disease (CKD) in lymphoma survivors

Abstract Background:Recent advances in the treatment of non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL) have significantly improved long-term survival. Assessing for and managing the late effects of lymphoma has become an important aspect of survivorship care. Complications of lymphoma such as hyperuricemia, exposure to intravenous contrast, and the use of nephrotoxic therapies are known to transiently impair kidney function. Limited evidence exists on whether repeated exposure to these nephrotoxic elements leads to chronic kidney disease (CKD). In a single center retrospective study of 397 lymphoma survivors, the incidence of CKD was 31% at 10 years (Desai, 2020). This study however lacked a direct comparison of CKD incidence to a population without lymphoma and lacked the power to conduct complex modelling of risk factors for CKD development due to a small sample size. Here, we evaluated the cumulative incidence of CKD during the first 10 years of survivorship in a large cohort of lymphoma survivors diagnosed and treated at the University of Minnesota. Methods:Data was collected by retrospective review of electronic health records. We aimed to detect incidence of clinically significant CKD in lymphoma survivors. CKD was defined as a glomerular filtration rate (GFR) of less than 60 mL/min/1.73 m² for 3 months or more. ICD10 codes wereused to extract consecutive adults with biopsy proven lymphoma who were diagnosed between 2010 - 2024. From this cohort, patients who had survived for a minimum of one year after lymphoma diagnosis were included. Patients who had CKD diagnosed prior to or concurrently with lymphoma diagnosis were excluded. GFR was recorded at diagnosis and 1, 2, 5 and 10 years after diagnosis from electronic medical records using the CKD-EPI equation. Lymphoma grade and stage, age, and gender were recorded. Study objectives included CKD-free survival, estimated using the Kaplan-Meier method, and the 10-year cumulative incidence of CKD, estimated using the cumulative incidence function with non-CKD mortality defined as a competing risk. Results:Between January 1st, 2010, and May 24th, 2024, 1192 patients were diagnosed with lymphoma, of whom 244 patients did not meet criteria and were excluded. Time-to-event analyses included 948 patients who were CKD-free and alive at 1 year. The median age at diagnosis was 59.1 (17.4 - 95.7) and 539 patients (57%) were male. Out of 948 patients, 476 (50%) had indolent B cell lymphomas, 436 (46%) had aggressive B-cell lymphomas, and 36 (4%) had T-cell lymphomas. Specifically, 244 (26%) had diffuse large B-cell lymphoma, 187 (20%) had follicular lymphoma, 156 (16%) had chronic lymphocytic leukemia, 115 (12%) had classical HL, and 246 (26%) had other subtypes. Also 488 (51%) patients had advanced-stage (51%) at diagnosis, while 368 (38%) had early-stage. Over a median follow-up of 8.5 years (1 - 15), 189 patients developed CKD. The 10 year cumulative incidence of CKD was 23% (CI95 20 - 27), and 19% (CI95 16 - 22) died without CKD. CKD developed early in survivorship, with a cumulative incidence of 6% at 2 years, increasing to 23% at 10 years. The 10-year CKD-free survival was 57% (CI95 54 - 61). Older age (65 years) at diagnosis was associated with a higher risk of CKD development (p 0.01; 10-year cumulative incidence of 34% vs. 18% for age 65). Smaller differences were observed for other risk factors with female sex, indolent lymphomas, and late-stage disease having a slightly higher incidence of CKD (p = 0.05). Conclusion: In a preliminary analysis, we observed a 23% cumulative incidence of CKD at 10 years. This was higher than the risk of death and appears to be higher than the cumulative incidence of CKD of 14% in the general population as reported by the National Institute of Diabetes and Digestive and Kidney Diseases. We found a higher incidence of CKD in adults older than 65 years, females, and survivors of indolent lymphoma. Preliminary results of this study validate the findings of prior, smaller studies in a large and independent cohort. CKD is a significant potential comorbidity to which lymphoma survivors are susceptible and for which they require careful monitoring. Further analyses including a rigorous comparison of CKD incidence in lymphoma survivors with age- and sex-matched controls, and analyses of factors (i.e., comorbidities, stem cell transplant, chemotherapy) associated with CKD development will be presented at the conference.