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.

Background Atypical hemolytic uremic syndrome is a rare group of disorders that have in common underlying complement amplifying conditions. These conditions can accelerate complement activation that results in a positive feedback cycle. The known triggers for complement activation can be diverse and include, infection, autoimmune disease, and malignancy. Recent reports suggest that certain autoimmune and rheumatological triggers of complement activation may result in atypical hemolytic uremic syndrome that does not resolve despite treating the underlying disorder. Specifically, patients with systemic lupus erythematosus and microangiopathic hemolysis may not respond to treatment of their underlying rheumatological trigger but responded to complement blockade. Case presentations We report two patients with inflammatory bowel disease complicated by development of atypical hemolytic uremic syndrome. In both cases, patients were on treatment for inflammatory bowel disease, that was not well controlled/flaring at the time. The first patient is a male who developed Crohn’s disease and microangiopathic hemolysis at age 5 and was treated with eculizumab successfully. Discontinuation of the medication led to multiple relapses, and the patient currently is being treated with eculizumab and has normal hematological and stable renal parameters. The second patient is a 49-year-old female with Ulcerative Colitis treated with 6-Mercaptopurine. She developed acute kidney injury and microangiopathic hemolysis. Prompt diagnosis and treatment with eculizumab resulted in the recovery of kidney injury along with a complete hematological response. Conclusions These two cases are the fifth and sixth patients to be published in the literature with atypical hemolytic uremic syndrome and inflammatory bowel disease treated with complement blockade. This confirms that C5 complement blockade is effective in treating complement mediated thrombotic microangiopathy/atypical hemolytic uremic syndrome when it is triggered in patients with inflammatory bowel disease.