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Abstract: SA-PO492

A Novel Form of Renal Tubular Acidosis (RTA) Associated With Immune Checkpoint Inhibitors: A Case Report and Literature Review

Session Information

Category: Fluid‚ Electrolyte‚ and Acid-Base Disorders

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


  • Weiner, I. David, Gainesville VAMC, Gainesville, Florida, United States
  • Lee, Hyun-Wook, University of Florida College of Medicine, Gainesville, Florida, United States
  • Clapp, William L., University of Florida College of Medicine, Gainesville, Florida, United States
  • Shah, Chintan Vimalkumar, University of Florida College of Medicine, Gainesville, Florida, United States

Immune checkpoint inhibitors (ICI) are increasingly being used as anti-neoplastic therapy. This report describes a case linking ICI therapy to a novel form of RTA, which we term Type V RTA.

Case Description

A 46 yo female with metastatic cancer was treated with Carboplatin-Paclitaxel-Pembrolizumab followed by maintenance pembrolizumab. Three months after starting maintenance pembrolizumab, she developed hypokalemic (K, 3.2 mM) normal-gap metabolic acidosis (tCO2, 15 mM). Renal function was preserved (creatinine, 0.6 mg/dl), and the urine pH was 6.0. Urinary ammonia, estimated using urine anion gap (+27 mM) and urine osmole gap (83 mOsmol/kg H2O), was not elevated. Urinary citrate in a 24-hour collection was undetectable. A diagnosis of ICI-associated RTA was made, and pembrolizumab was held. A kidney biopsy showed proximal tubule vacuolization but no tubulitis, tubular necrosis, or interstitial nephritis. K-citrate treatment normalized the acidosis and hypokalemia; urine pH remained 6.0 during therapy. The RTA spontaneously resolved over four months.

Immunohistochemistry of the biopsy specimen for key acid-base transporters, NBCe1, H-ATPase, and Rhesus C Glycoprotein, showed normal expression and localization compared to control tissue. Ultrastructural analysis showed proximal tubule apical and basolateral vacuolization. A review of medical literature identified 7 previous cases of RTA associated with PD-1 therapy. Urine pH was 6.0 in 3, 6.3 in one, 6.5 in two, and 6.7 in one case.


This case represents a novel form of RTA, which we term Type V RTA. Type II (proximal) RTA is excluded given the persistent urine acidification during alkali therapy and undetectable urinary citrate. Intact urine acidification excludes Type I (distal) RTA. The absence of hyperkalemia excludes Type IV (hyperkalemic) RTA. Instead, we postulate that this case represents a novel form of RTA, Type V RTA, which is characterized by normal gap metabolic acidosis, impaired ammonia excretion despite intact urine acidification, the absence of hyperkalemia, and intact ability to decrease urinary citrate. A case review identifies several similar cases, all associated with anti-PD1 therapy. We suggest the etiology is impaired proximal tubule ammonia generation, which may be related to the proximal tubule vacuolization observed.