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Abstract: SA-PO491

Immune Checkpoint Inhibitor-Induced "Pantubulopathy"

Session Information

Category: Fluid‚ Electrolyte‚ and Acid-Base Disorders

  • 1002 Fluid‚ Electrolyte‚ and Acid-Base Disorders: Clinical

Authors

  • Schlotman, Kelly Elizabeth, Rush University Medical Center, Chicago, Illinois, United States
  • Shahzad, Muhammad Asim, Rush University Medical Center, Chicago, Illinois, United States
  • Gashti, Casey N., Rush University Medical Center, Chicago, Illinois, United States
  • Rodby, Roger A., Rush University Medical Center, Chicago, Illinois, United States
Introduction

Immune checkpoint inhibitors (CPI’s) are widely used, effective cancer therapy agents that utilize the body’s natural immune system to destroy cancer cells. Unfortunately, the immune-mediated cellular damage is not limited to malignant cells and can also occur in healthy tissues including the kidneys. Tubulointerstitial nephritis (TIN) is the most common pathology seen on kidney biopsy in patients with AKI due to CPI’s. Here we present a case of CPI-induced interstitial nephritis which resulted in functional defects throughout the entire nephron.

Case Description

A 67 yo F w/ PMH of HTN, CKD3b (baseline SCr 1.3-1.6 from previous nephrotoxic exposure to carboplatin and bevacizumab), and metastatic endometrial cancer being treated with pembrolizumab (PD-1 inhibitor), lenvatinib (TK inhibitor), and zoledronic acid presented with a SCr of 3.2 mg/dl, hypokalemia (2.5 mmol/l), hypophosphatemia (1.9 mg/dl), hypomagnesemia (1.3 mg/dl), and a non-anion gap metabolic acidosis with [HCO3] 14 mmol/l and arterial blood pH of 7.18. Her urinalysis had a pH of 6.5, 3+ glucosuria (serum blood glucose of 98 mg/dl), 1+ blood, 1+ protein, and 5 WBC's. Her urine P/C ratio was 3.8 g/g and urine A/C ratio was 530 mg/g. The fractional excretion of potassium (FEK) and phosphorus (FEPhos) were elevated (FEK 77% and FEPhos 52%) consistent with potassium and phosphorus wasting. The urine osmolar gap was low (28) and urine anion gap was positive (+11), both consistent with a distal renal tubular acidosis. Her severe electrolyte disturbances required aggressive supplementation. Renal biopsy showed acute on chronic interstitial nephritis with acute tubular necrosis and 20% IFTA. She received 40 mg prednisone with improvement in electrolyte disturbances and SCr to baseline.

Discussion

CPI’s can cause acute interstitial nephritis leading to AKI and a number of tubular defects. Our case had evidence of 1) proximal tubular defects manifested as Fanconi syndrome with non-albuminuric proteinuria as well as renal K, PO4, and glucose wasting 2) a loop of Henle defect with Mg wasting and 3) a distal tubular defect manifested as a distal RTA. While each of these have been reported with CPI’s, we are unaware of a prior case of “pantubulopathy” in which every segment of the nephron was affected by the CPI-induced AIN. Prompt diagnosis and treatment led to complete resolution of AKI and tubular defects.