Reuse of a previously transplanted kidney: does success come with a price?
A 42-year-old African American male, whose reported cause of end-stage renal disease (ESRD) was hypertension, received a one-antigen-matched deceased donor kidney transplant in June 2005.\nA 38-year Caucasian female (donor B), who developed ESRD due to type 1 diabetes mellitus, received a living donor kidney transplant in 1997, and a pancreas transplant in 2002. Both organs failed and she subsequently received a simultaneous kidney-pancreas (SPK) transplant in April 2005. She was at intermediate risk for cytomegalovirus (CMV) infection at the time of the SPK transplant (D−/R+) and her maintenance immunosuppression consisted of tacrolimus, mycophenolate mofetil (MMF) and prednisone. Her records indicated that she was treated for CMV infection based on symptomatology (fever and diarrhea) with intravenous ganciclovir about a month after SPK transplant for an undetermined period of time followed by prophylaxis with oral valganciclovir at 450 mg/day. Her cause of death was a spontaneous intracranial bleed, and at the time of recovery of her transplanted kidney, CMV IgM was not detected in serum. A frozen section of donor B's kidney revealed normal renal parenchyma with only one obsolescent glomerulus of 100 in the sample. However, the final interpretation, communicated 2 days after the transplant, revealed focal and segmental glomerulosclerosis (FSGS), with collapsing features, diffuse C4d staining in the peritubular capillaries (D) and acute tubular necrosis suggestive of acute humoral rejection. Electron microscopy (EM) revealed diffuse podocyte foot process effacement.\nThe original donor (donor A) was an 18-year-old African American male who had died due to blunt force trauma to the head causing an intracranial bleed.\nWe proceeded with the transplant based on the frozen section findings, terminal creatinine value (1.2 mg/dL) and the total cold ischemia time (27 h and 22 min). Our patient received induction therapy with anti-rabbit thymocyte globulin (ATG) and methylprednisolone; intravenous ganciclovir was used as prophylaxis against the CMV since he had delayed graft function and was receiving ATG. Since the renal allograft had lesions of FSGS, the urine protein-to-creatinine ratio (U P/Cr) was monitored, and the initial ratio was 2.8. ATG was continued for 2 weeks and ganciclovir for 3 weeks (0.625 mg/kg three times a week for 2 weeks followed by 0.625 mg/kg/day for 1 week) after which he received oral valganciclovir 450 mg/day (adjusted to glomerular filtration rate, GFR). Serum creatinine decreased from 13.9 to 3.5 mg/dL on day 13 post transplant, at which point dialysis treatments were stopped and immunosuppression was maintained with tacrolimus, MMF and prednisone.\nOn day 24 post transplant, his white blood cell count decreased to 2400 cells/mm3, which led to the lowering of the MMF (from 2000 mg to 1000 mg/day). The leukopenia persisted for another week and his blood tested positive for CMV DNA by PCR (307 000 copies/mL) at which point MMF was discontinued and intravenous ganciclovir at 2.5 mg/kg/day was substituted for oral valganciclovir. He then became symptomatic with fever and malaise and the CMV levels in the blood rose to 1 199 000 copies/mL over a 2-week period despite adequate doses of ganciclovir. The possibility of mutant CMV strain resistant to ganciclovir was considered and intravenous foscarnet 3 g every 12 h (50 mg/kg every 12 h for estimated GFR of 58 mL/min) was started. His symptoms improved quickly and as depicted in , CMV decreased dramatically over the next 2 weeks to 3000 copies/mL. A mutation for ganciclovir resistance tested positive at the UL-97 location. On day 75 post transplant, CMV was no longer detectable in his blood. Foscarnet was continued for a total of 3 months, his tacrolimus level during this episode was 5–8 ng/mL and the U P/Cr ranged between 1.25 and 2.5. His maintenance immunosuppression was changed to tacrolimus, leflunomide and prednisone.\nA biopsy performed on day 110 post transplant revealed persistent lesions of FSGS (EM revealed only focal foot process effacement) and diffuse C4d staining in the peritubular capillaries (A and E). Since the donor-specific antibodies (DSA) tested negative, no treatment was initiated. A second allograft biopsy at 5.5 months post transplant still revealed FSGS and only focal C4d staining.\nOver the next year, CMV DNA was monitored monthly and was not detected. Another biopsy performed 13 months post transplant still revealed FSGS lesions (C), but C4d staining was negative. However, tubular atrophy increased to ∼40%. The U P/Cr was 0.6–0.8 and the serum creatinine level was 1.6–2.0 mg/dL. At last follow-up, 5 years after transplant, his serum creatinine level was 2.1 mg/dL, with a U P/Cr (obtained several months earlier) of 0.12. The clinical course of our patient is depicted in .