Thrombotic microangiopathy caused by oral contraceptives in a kidney transplant recipient

Thrombotic microangiopathy (TMA) is characterised by abnormalities in the walls of arterioles and capillaries, precipitated by hereditary or acquired characteristics, and culminating in microvascular thrombosis because of dysregulated complement activity. A number of drugs can precipitate TMA, including vascular endothelial growth factor (VEGF) inhibitors, because of their effects on endothelial repair. Pazopanib is a VEGF inhibitor used for the treatment of renal cell carcinoma (RCC); it is uncommonly associated with TMA. A 52-year-old male, 5 years post his second kidney transplant secondary to immunoglobulin (Ig) A nephropathy, presented with hypertension, fluid overload, and worsening graft function (peak creatinine 275 µmol/L, baseline 130–160 µmol/L) and nephrotic range proteinuria 2 months after commencing pazopanib for metastatic RCC. His maintenance immunosuppression included ciclosporin, mycophenolate, and prednisolone. Haematological parameters were unremarkable. Allograft biopsy demonstrated glomerular and arteriolar changes consistent with chronic active TMA, with overlying fea-tures of borderline cellular rejection. He was treated with intravenous methylprednisolone 250 mg for 3 days and commenced on irbesartan 75 mg daily. Drug-induced TMA from pazopanib was suspected, particularly given the documented association with other tyrosine kinase inhibitors (TKIs). In consultation with his medical oncologist, pazopanib was ceased, and an alternate TKI cabozantinib was commenced. Serum creatinine remained <200 µmol/L 3 months after admission. This is the first reported biopsy-proven case of TMA attributed to pazopanib in a kidney transplant recipient. With increasing clinical indications for and availability of TKIs, clinicians need to be aware of their association with TMA events in kidney transplant recipients, who are already susceptible to TMA due to abnormal vasculature, infectious triggers, ischaemia-reperfusion injury, and use of calcineurin inhibitor.

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Primary Hyperaldosteronism: A Rare Cause of Malignant Hypertension with Thrombotic Microangiopathy in a Kidney Transplant Recipient

Case Reports in Transplantation ◽

10.1155/2021/9261371 ◽

2021 ◽

Vol 2021 ◽

pp. 1-6

Author(s):

Carolina Ormonde ◽

Sara Querido ◽

Nuno Rombo ◽

Rita Roque ◽

Belarmino Clemente ◽

...

Keyword(s):

Transplant Recipient ◽

Kidney Transplant ◽

Thrombotic Microangiopathy ◽

Viral Infections ◽

Kidney Transplant Recipient ◽

Calcineurin Inhibitors ◽

Organ Damage ◽

Primary Hyperaldosteronism ◽

Malignant Hypertension ◽

Antibody Mediated Rejection

Thrombotic microangiopathy (TMA) is a rare disease that presents with haemolysis and organ damage. The kidney is one of the main affected organs, and TMA is associated with serious complications and increased mortality. In transplanted patients, TMA is even less common and has a variety of possible causes, including thrombotic thrombocytopenic purpura (TTP) and haemolytic-uremic syndrome (HUS), infections, drugs, autoimmune disease, tumours, and malignant hypertension. Transplant-related causes, such as antibody-mediated rejection, calcineurin inhibitors, and viral infections, need to be considered as well. The authors report a rare case of TMA in a kidney transplant recipient, whose investigation revealed malignant hypertension secondary to primary hyperaldosteronism.

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