Complement-Mediated Atypical HemolyticUremic Syndrome as a Cause of Late KidneyGraft Dysfunction

Abstract

Thrombotic microangiopathy (TMA) is a rare complication of kidney transplantation that is associated with poor patient and graft outcomes. We present a case of a 59-year-old male patient with no other relevant medical history besides ADPKD who underwent preemptive living donor kidney transplantation from his wife in March 2020. Induction therapy was with basiliximab, tacrolimus (TAC), mycophenolate mofetil (MMF) and prednisolone (PDN). The post-transplant period was uneventful and he was discharged with base serum creatinine levels of 1.4mg/dl, which remained stable at 1.3–1.5mg/dl for over 3 years. His maintenance therapy consisted on TAC, MMF and PDN (with MMF being switched to Everolimus on account of CMV infection). Three years after transplantation, the patient presented with an acute case of watery diarrhea, low-grade fever and acute kidney injury. Physical examination was unremarkable aside from dehydration. All microbiology test results were negative. At this time, hemoglobin, platelets and LDH levels were within the normal range, urine output was normal, proteinuria was not present and the urinary sediment analysis was unremarkable. The diarrhea subsided shortly after, but the patient's renal function continued to worsen despite optimized fluid therapy. A computed tomography scan of the abdomen and pelvis ruled out obstructive nephropathy and the patient was admitted for acute renal allograft dysfunction, and a renal allograft biopsy was performed that same day. While waiting for the biopsy results and for suspected acute cellular rejection, the patient was started on methylprednisolone pulses (500mg) for 3 days, followed by PDN (40mg/day). An initial improvement in kidney allograft function was noted. However, just 7 days after, the patient presented with worsening renal function, new-onset thrombocytopenia, hemolytic anemia with schistocytes, a negative Coombs test and allograft biopsy findings which were all consistent with TMA. All major causes of secondary TMA were excluded, ADAMST13 activity levels were of 27% and no ADAMST13 autoantibodies were found. A heterozygous mutation in ADAMST13 (NM_139027.8): c.3280C>T p.(Arg1094Cys) of unknown significance was found, as well as a heterozygous deletion of CFHR3-CFHR1 gene deletion. This last mutation is usually considered to be a benign variation, when co-inherited with another mutation, it can be considered a risk factor for TMA. A diagnosis of atypical hemolytic uremic syndrome (aHUS) was made and the patient was started on plasmapheresis, weekly eculizumab and everolimus was replaced with mycophenolate mofetil. After the second administration of eculizumab, the patient showed continuous and sustained improvement of kidney function (SCr 1.9mg/dl) and normalization of his hemoglobin and platelet levels. The patient was later discharged and kept on bimonthly eculizumab administrations for the first 3 months, after which eculizumab administrations were slowly spaced out until finally stopping after 12 months. At the time of writing, the patient has been off eculizumab completely for 3 months, and has displayed normal complement activity levels for the last 8 months of our eculizumab discontinuation protocol with no signs of relapse. The purpose of this paper was to report a rare case of late-onset post-transplant acute renal allograft dysfunction, such as de novo aHUS.