A DOUBLE WHAMMY – A CHALLENGING CASE OF POST-RENAL TRANSPLANT THROMBOTIC MICRO-ANGIOPATHY AND A RARE SUBCUTANEOUS FUNGAL INFECTION

Introduction:

Renal transplant is currently the best treatment for end stage renal failure. Renal transplant recepient maintenance treatment is mostly based on a triple therapy containing calcineurin inhibitors, corticosteroids and antiproliferative agents. In addition to the desired effect, the use of immunosuppressive drugs carries risk of certain adverse effects. Among the less common but potentially severe complications is thrombotic microangiopathy linked to tacrolimus usage thus highlighting intricate relationship between tacrolimus and thrombotic microangiopathy beyond immunosuppression. Other major risk in solid organ transplant recipients are opportunistic fungal infections. Medicposis species are rare fungal pathogens that are difficult to identify morphologically, can occur even after remote exposure and typically present with soft tissue infection without dissemination.Here we present a case of kidney transplant recepient who developed tacrolimus induced thrombotic microangiopathy and an unusual subcutaneous fungal infection by organism Medicopsis romeroi which belongs to group Phaeohypomycosis Only 12 cases are reported till date worldwide of fungal mycetoma caused by this organism. Both these adverse events occurred 8 months post-transplant during similar time frame causing a double whammy. 

Methods:

A 50 year old gentleman, known hypertensive presented with features of uremia and volume overload. With UPCR of 10.5, underwent a renal biopsy and was diagnosed with PLA2R + membranous glomerulonephritis with fibro cellular crescents and severe IFTA. He received 5 sessions of hemodialysis and was treated with pulse methyl prednisolone and rituximab and was on maintenance steroids for next 2.5 years. In July 2023 he was initiated on hemodialysis in view of severe renal dysfunction and was worked up for renal transplant. Underwent swap renal transplant after 4 months with 125mg Anti-Thymocyte Globulin and 1 gm methylprednisolone as induction agent. Patient achieved nadir creatinine of 1mg/dl and was discharged on triple immunosuppression consisting of tacrolimus, mycophenolate mofetil and wysolone. In April – May 2024 – Presented with severe acute gastroenteritis that turned out to be cholera infection and was treated with doxycycline. This episode was associated with leucopenia, thrombocytopenia and acute allograft dysfunction with peak creatinine of 2.3mg/dl. Tacrolimus levels at this point were 8.9g/dl on 5mg BD dose at 6 months post-transplant hence dosage of tacrolimus was reduced. In view of recurrent gastrointestinal disturbances mycophenolate mofetil was changed to azathioprine. However, he persisted to have renal dysfunction with worsening of thrombocytopenia requiring platelet transfusions and new onset hemolytic anemia (LDH – 1600). He underwent allograft biopsy suggestive of glomerular thrombotic microangiopathy. Workup done for etiology of thrombotic microangiopathy was negative and hence tacrolimus was stopped and switched to cyclosporine and he underwent 3 sessions of plasmapheresis for treatment of TMA. In May 2024 he developed swelling over the right lower limb, gradually progressive, painful, associated with blackish discoloration of the overlying skin. He underwent incision and drainage of the abscess and cultures were sent. Cultures grew organisms belonging to the group called Phaeohypomycosis. DNA sequencing showed that this organism was Medicopsis romeroi. This infection was treated with surgical excision of wound and voriconazole. The patient is on triple immunosuppression with cyclosporine, azathioprine and wysolone. Anemia and thrombocytopenia have resolved and creatinine has settled to 1.7mg/dl. 

Results:

Conclusions:

This case highlights intricate relationship of striking balance bteween achieving adequate immunosuppression and prevent severe adverse effects of toxicity. High level of suspicion should be kept to diagnose Thrombotic microangiopathy in post-transplant patients even with normal tacrolimus levels. Rare fungal infections can occur in post-transplant patients which maybe difficult to treat since no published guidelines for treatment are available. 

I have no potential conflict of interest to disclose.

I did not use generative AI and AI-assisted technologies in the writing process.