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Abstract: PO2191

Double Trouble with Pembrolizumab: Immune Checkpoint Inhibitor-Induced Type 1 Renal Tubular Acidosis and Secondary Adrenal Insufficiency

Session Information

  • Onco-Nephrology - 2
    October 22, 2020 | Location: On-Demand
    Abstract Time: 10:00 AM - 12:00 PM

Category: Trainee Case Report

  • 1500 Onco-Nephrology


  • Adoor, Dayyan M., University Hospitals, Cleveland, Ohio, United States
  • Tariq, Hafsa, University Hospitals, Cleveland, Ohio, United States
  • Rashidi, Arash, University Hospitals, Cleveland, Ohio, United States

Pembrolizumab is a novel immune checkpoint inhibitor (ICI) that targets programmed cell death protein (PD-1) signaling. Checkpoint inhibitor associated nephrotoxicity is an immune-mediated process that can manifest with a variety of clinical presentations. Here, we report a unique case of Pembrolizumab induced distal renal tubular acidosis (RTA) and secondary adrenal insufficiency (AI) which was successfully treated with steroids.

Case Description

A 72-year-old male with a history of stage IIIC malignant melanoma, who had recently completed 3 cycles of therapy with Pembrolizumab was admitted with generalized fatigue, weakness, and anorexia.

Initial work up was notable for severe hyponatremia, and a non-anion gap metabolic acidosis (NAGMA); (Na: 120 mmol/L, Cl: 89 mmol/L, K: 3.8 mmol/L , HCO3: 20 mmol/L and creatinine 0.67mg/dL). Urine anion gap was positive at 8meq/L, urine osmolar gap was low at 57 mosm/kg and urine pH was 6.0. Subsequent laboratory work up was notable for AM cortisol of 1.0 ug/dL, serum ACTH 1.4 pg/mL and DHEA 12 ng/dl. Other pituitary hormones including LH, TSH and FSH were normal. An MRI of the sella was negative for hypophysitis. CT scan of the abdomen showed no adrenal hemorrhage or necrosis. Extensive serologic work-up including serum ANA, ANCA, anti-SSA/SSB, Hepatitis B, Hepatitis C, C3 and C4 levels were all unrevealing.

A presumptive diagnosis of immune mediated central AI and distal RTA was made. A positive urine anion gap and low positive osmolar gap (<150mosm/kg) in the setting of NAGMA was highly suggestive of a distal RTA. Although this condition is associated with hypokalemia, simultaneous AI could have offset this finding. He was started on hydrocortisone 40 mg daily. This was accompanied by improvement in serum sodium and bicarbonate levels. Two days later, the patient's hyponatremia and metabolic acidosis had resolved. He was eventually discharged on a tapering dose of steroids.


Recent studies have shown that acute interstitial nephritis is the most common type of Pembrolizumab associated nephrotoxicity. We report a novel case of Pembrolizumab toxicity, where distal RTA concurrently manifests with secondary AI. Rapid resolution of both these conditions upon initiation of steroids suggests that they are both immune mediated adverse effects associated with Pembrolizumab.