Wcn26-5508 Dual Renal Immune-Related Adverse Events After Pembrolizumab: Acute Interstitial Nephritis and Type 4 Renal Tubular Acidosis—a Case Report

Introduction: Pain and nausea are known causes of the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Pain and nausea are common during treatment for malignancy. This study aimed to investigate associations of analgesics and antiemetics, as surrogates for pain and nausea respectively, with hyponatremia among patients with malignancy. Methods: This is a retrospective cohort study among patients with malignancy at our university hospital from 2018 to 2023. We utilized mixed-effects logistic regression analyses to examine the associations of acetaminophen, non-steroidal anti-inflammatory drugs (NSAIDs), opioids, and antiemetics with hyponatremia (Na #130 mmol/L). To account for the different strengths of analgesics, we created a "Pain score" defined as the sum of the following points: 1 point for acetaminophen, 2 points for NSAIDs, and 3 points for opioids. The association between "Pain score" and hyponatremia was also examined. Results: We enrolled 5506 patients. Median age was 68 (57-75) years, and median eGFR was 70. 2 (57. 5-82. 9) mL/min/1. 73. Of these, 1313 (23. 9%) developed hyponatremia at least once during the study period. Acetaminophen, NSAIDs, and opioids were all significantly associated with hyponatremia Odds Ratio OR 1. 27 95% confidence interval (CI) 1. 16-1. 39, OR 1. 41 95% CI 1. 27-1. 55, and OR 1. 33 95% CI 1. 15-1. 55, respectively. However, antiemetics were not associated with hyponatremia OR 1. 06 (95% CI 0. 89-1. 26). A higher "Pain score" was progressively associated with hyponatremia: 1 point OR 1. 38 (95% CI 1. 21-1. 57), 2 points OR 1. 53 (95% CI 1. 32-1. 77), 3 points OR 1. 75 (95% CI 1. 54-2. 00), 4 points OR 1. 83 (95% CI 1. 45-2. 32), 5 points OR 2. 06 (95% CI 1. 51-2. 80), and 6 points OR 2. 53 (95% CI 2. 06-3. 11) as compared to 0 points (P for trend <0. 01). The associations were stronger among patients with impaired renal function (eGFR <60 mL/ min/1. 73;p for interaction = 0. 03), but not among renin-angiotensin system (RAS) inhibitor users (p for interaction = 0. 37).