Acute Kidney Injury after Pembrolizumab-Induced Adrenalitis and Adrenal Insufficiency

Abstract

Pembrolizumab is an immune checkpoint inhibitor that targets the programmed cell death protein 1 (PD-1) antigen and induces an immune response against tumor tissues. It has been successful in inducing remission in patients with severe metastatic disease, often refractory to other chemotherapeutic agents. The risk of injury of other organ systems has been noted with reported cases of glomerular disease and endocrine disease. In addition, hypophysitis as well as dermatological and gastroenterological side effects have been reported. Renal injury with immune checkpoint inhibitors like nivolumab and pembrolizumab is usually mediated via interstitial nephritis, though glomerular disease presentations like anti-neutrophil cytoplasmic antibody-associated vasculitis, immune complex disease, and thrombotic microangiopathy have also been reported. We report a 70-year-old Caucasian male who underwent treatment with pembrolizumab for adenocarcinoma of the lung. He developed acute adrenal insufficiency and concomitant severe hypotension upon presentation. He did not require renal replacement therapy, rather his severe acute kidney injury resolved with hydration, normalization of blood pressures with vasopressors, and treatment with high-dose corticosteroids. His urinary indices (fractional excretion of urea, FEUrea) and clinical course were highly suspicious for acute tubular necrosis that resolved quickly after treating his underlying adrenalitis. The urinary sediment, proteinuria, and clinical course were not typical for the usually expected renal lesion of interstitial nephritis in patients treated with immune checkpoint inhibitors.

A Case of Isolated Adrenocorticotropic Hormone Deficiency Caused by Pembrolizumab

“…One case was breast cancer treated with pembrolizumab as neoadjuvant chemotherapy [19]. The other cases were stage IV lung cancer treated with pembrolizumab as systemic chemotherapy [20,21]. There are no case reports showing isolated adrenocorticotropic hormone deficiency caused by pembrolizumab.…”

Immunotherapy-induced endocrinopathies: assessment, management and monitoring

“…It is, however, extremely important to be aware of its occurrence in view of the potentially catastrophic consequences of an unrecognised adrenal crisis. The cases described in the literature were related to treatment with ipilimumab, 62 nivolumab, 63–65 pembrolizumab 66 and avelumab. 67 On imaging, one patient had adrenalitis with bilateral enlargement of the adrenal glands on a computed tomography (CT) scan, a second case had increased uptake on a positron emission tomography-CT scan, and a third case showed atrophic adrenals on follow-up scan post-diagnosis of adrenal insufficiency with positive CYP21 antibodies.…”

Degree of Glomerulosclerosis in Procurement Kidney Biopsies from Marginal Donor Kidneys and Their Implications in Predicting Graft Outcomes

“…Over 700,000 patients in the United States have ESKD, with the United States having the secondhighest incidence rate of treated ESKD in the world [30]. Despite an improvement in dialysis care over the last 15 years, the overall survival on dialysis remains dismal with 22% at one year, 43% at three years and 58% at five years [31]. The risk of death is reduced by up to 66% with kidney transplantation [31].…”

“…Despite an improvement in dialysis care over the last 15 years, the overall survival on dialysis remains dismal with 22% at one year, 43% at three years and 58% at five years [31]. The risk of death is reduced by up to 66% with kidney transplantation [31]. A major limitation to increasing the number of kidney transplantations is the number of donors.…”