Investigation of Proteinuria in a Simultaneous Heart-Kidney Transplant Recipient with AL Amyloidosis

Introduction: Although they are two of the most affected organs by AL amyloidosis, simultaneous heart and kidney transplants (SHK) are rarely performed regardless of the underlying disease process. Diagnostic work up for proteinuria requires a comprehensive work up and multidisciplinary shared decision making with management. Case Description: A 57-year old male presents with worsening proteinuria. Notable history includes SHK 4 years prior for severe cardiac AL amyloidosis with chronic kidney disease stage 4. Initially he suffered delayed graft function requiring dialysis for 3 weeks post-transplant. Surveillance biopsy after 3 months showed cortical necrosis and renal MAG3 scan showed about 23% of the split differential function. Bortezomib and daratumumab were discontinued for recurrent CMV viremia. He was switched to sirolimus for tacrolimus toxicity sparing. Creatinine (Cr) improved to baseline of 1.8-2 mg/dL with urine protein-creatinine ratio (UPCR) average of 0.2 mg/mg. Relevant labs on presentation included Cr of 2 mg/dL, UPCR 2.98 mg/mg, HbA1c of 9.2%, and normal kappa/lambda free light chain ratio albeit elevation of the lambda light chain to 32.5. A repeat MAG3 scan showed 82% of native kidney function and 17% allograft kidney function. With these findings, he had biopsies of both native and transplant kidneys. The former revealed AL amyloidosis and the latter revealed subclinical Banff 2A acute cellular rejection in allograft without amyloid deposition. Sirolimus was switched to tacrolimus, and he was treated with pulse steroids for subclinical rejection. Kidney function remains at baseline and UPCR has improved to 1mg/mg at most recent follow up. Discussion: The patient’s progressive proteinuria presented a diagnostic dilemma. The repeat MAG3 scan findings guided the decision to biopsy both native and allograft kidneys. Presumably native kidney amyloidosis was present pre-transplant, and this was less likely the culprit in the absence of allograft deposition or serologic evidence of recurrence. However, subclinical rejection in the allograft was notable and treated in addition to switching sirolimus to tacrolimus causing reduced proteinuria. The value of MAG3 studies and kidney biopsies in this case remain evident and may guide future diagnostic decisions.