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.
require lower-extremity amputation. LDL-apheresis has been initiated as a supportive treatment for patients with chronic limb-threatening ischemia (CLTI), especially in cases where revascularization by endovascular therapy (EVT) is not sufficiently effective. In 2021, a new adsorption-type blood purification device, Rheocana, that can selectively remove LDL-C and fibrinogen, was developed. In a clinical trial, 45.9% of the ulcers were healed using Rheocana. Since then, it has been widely used for dialysis patients with CLTI in Japan; however, hypotension during LDLapheresis is still a major adverse event.Design and Methods: Case report.Results: An 83-year-old Japanese man presented with a right leg ulcer. He had started undergoing hemodialysis 3 years prior because of diabetic kidney disease. CLTI was recognized 6 months prior, and repeated EVT was ineffective and failed to improve the ulcer. His blood pressure was 129/71 mmHg and antihypertensive agents were not used. LDL-apheresis with Rheocana was initiated; however, his systolic blood pressure decreased to 60 mmHg, and LDL-apheresis was stopped immediately. After discontinuing LDL-apheresis, the his blood pressure recovered. Anticoagulants were changed from heparin to nafamostat mesylate, and LDL-apheresis was restarted. His blood pressure did not decrease after anticoagulation therapy, and his leg ulcer was successfully healed.
Keywords: thrombotic thrombocytopenic purpura, plasma exchange, ADAMTS13, PLASMIC score 〈Abstract〉 Thrombotic thrombocytopenic purpura (TTP) is a highly lethal disease requiring urgent intervention. The diagnostic criteria for TTP include a reduction in ADAMTS13 activity to below 10%. However, because it takes time to obtain data regarding ADAMTS13 activity, in some cases treatment should be started before such test results are available. Herein, we report a fulminant case of acquired TTP, which rapidly deteriorated, resulting in death, even though plasma exchange was performed immediately. The patient was a 46 year old male. Approximately one week after the onset of flu like symptoms, he showed an acute deterioration of his renal function (a serum creatinine level of 3.37 mg/dL), together with thrombocytopenia and the appearance of schistocytes in his peripheral blood, which made a diagnosis of TTP highly likely. On day 2, plasma exchange therapy was initiated, but the patient responded poorly to this treatment. He then developed a disturbance of consciousness, which
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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