Background: Pembrolizumab, a highly selective humanized monoclonal IgG4κ isotype antibody against PD-1, is one of the immune checkpoint inhibitors approved for treatment of various cancers. The most frequent immunerelated adverse events include skin, gastrointestinal, and endocrine abnormalities. In rare cases, however, adverse events on the kidney do occur. Case presentation: We here report a case of acute kidney injury presenting thrombocytopenia and hemolytic anemia with the presence of schistocytes, which developed in a 68-year-old man with urothelial cancer, 7 months after initiation of pembrolizumab treatment (10 cycles) and 3 weeks after treatment cessation. The patient had previously undergone unilateral nephrectomy and prior treatment with combined gemcitabine and carboplatin regimen. Although corticosteroid, hemodialysis, and plasma exchange were initiated, the patient died within a few days of respiratory failure. Pathological examination at autopsy revealed multiple carcinomas including the lung, liver, and spine, together with the diagnosis of thrombotic microangiopathy by electron microscopy findings of the renal tissue. To our knowledge, this is the first report describing severe thrombotic microangiopathy in a patient possibly associated with pembrolizumab, leading to death. Conclusion: Physicians should be aware of this potential side effect in patients presenting acute kidney injury and thrombocytopenia.
Alport syndrome (AS) is a rare hereditary disease that presents with chronic kidney disease and sensorineural hearing loss, and is diagnosed by its clinical features, pathological features on renal tissue, and mode of inheritance. We report a woman in her 20 s who exhibited persistent haematuria with normal renal function and sensorineural hearing loss. Her family members exhibited the same clinical findings among three generations and were suspected of having autosomal dominant AS (ADAS). Renal biopsy showed minor glomerular abnormalities on light microscopy and extensive thinning of the glomerular basement membrane on electron microscopy. Whole-exome analysis revealed a known COL4A4 (type IV collagen α4) mutation (c. 2510 G > C: p. Gly837Ala). Two pedigrees with the same variant have been reported previously, one as ADAS and the other as autosomal recessive AS. However, these two cases exhibited no sensorineural hearing loss. The analysis in the present case revealed another missense variant in ESPN (Espin), an actin-bundling protein, which is a causative gene for sensorineural hearing loss. Although the pathophysiological significance of this novel missense variant needs to be clarified, computational analysis predicted that the variant creates a new phosphorylation site for protein kinase C. Our case suggests a possible association of hereditary sensorineural hearing loss with ADAS. Whole-exome analysis should be considered to diagnose hereditary and multiple-organ disorders.
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