Kidney Biopsy Proven Thrombotic Microangiopathy in a Heart Transplant Recipient

ABSTRACT

Introduction: Thrombotic Microangiopathy (TMA) after non renal solid organ transplantation is very rare. While few cases of TMA following liver and lung transplants have been published, it has been very rarely reported following orthotopic heart transplant (OHT). We report the first case of kidney biopsy proven De Novo TMA after OHT. Case Description 58-year-old male with non ischemic cardiomyopathy undergoes OHT in Jan 2021. He had normal renal function pre transplantation. Post-operatively he had pericardial effusion and in that setting developed oliguric AKI from ATN requiring dialysis. His renal function recovered and was discharged without dialysis. He was on tacrolimus, MMF and steroid regimen. Frequent heart biopsies were negative for rejection. In March 2021 the patient was admitted for GI bleed and again noted to have AKI. However, during this episode he developed proteinuria of over 2gm, new compared to previous urine studies. He was discharged with a serum creatinine of 2.6mg/dL. By July 2021 renal function worsened and he underwent a renal biopsy on 7/30/21 which showed acute and chronic TMA, related to calcineurin inhibitor use. Viral causes and other medications were ruled out (CMV, BK, adenovirus, SARs-COV2). Tacrolimus was held and he was initiated on Everolimus. Genetic and complement testing revealed normal complement levels, an elevated SC5b-9 complex, heterozygous for the APOL1 gene mutation (c.[1024A>G;1152T>G] p.[Ser342Gly;Ile384Met] (G1 allele)), and heterozygous for the CFHR5 gene mutation, suggestive for complement mediated TMA. He was initiated on Eculizumab. After two doses of Eculizumab he was again admitted with acute respiratory failure requiring intubation secondary to mTOR induced pneumonitis. His renal function worsened and he was reinitiated on dialysis. After a multidisciplinary discussion, he was transitioned to cyclosporine for immunosuppression. He continues to be on dialysis and cyclosporine with eculizumab without other non-renal findings of TMA. He is currently being evaluated for kidney transplantation. He has no signs of OHT rejection on heart biopsies. Discussion(s) The early identification and treatment of TMA in OHT is important in preventing further complications associated with it. Although rare as compared to other solid organ transplants, it is essential to maintain TMA as a differential diagnosis for AKI following OHT.