Fever, Dysuria and Elevated Serum Creatinine in a Kidney Transplant Recipient

Abstract

A 22-year-old man with end-stage kidney disease due to immune complex-mediated glomerulonephritis received a three-antigen mismatched deceased–donor kidney allograft. His maintenance immunosuppression consisted of tacrolimus (5 mg twice a day), mycophenolate mofetil (1 g twice a day) and prednisone (5 mg daily). He had an uneventful posttransplant course with the exception of an episode of borderline T cell-mediated rejection 6 months after transplantation, which was treated with pulse steroids. Immunosuppression maintenance remained unchanged. Three years posttransplantation, the patient presented to an outside hospital with fever, chills, dysuria, abdominal pain and nonbloody diarrhea. Urinalysis revealed white blood cells (10–20/hpf) and bacteria. Ceftriaxone was given and vancomycin PO was empirically started. However, urine, blood and stool cultures were negative. Workup for Lyme disease, Babesia and C. difficile were also negative. After 4 days of persistent high-grade fevers, the patient was transferred to our hospital where his antibiotic coverage was broadened to cefepime and vancomycin IV while his mycophenolate mofetil was reduced to 500 mg twice a day. Urinary symptoms improved but the patient remained febrile. White blood cell count was stable. Serum creatinine was elevated (2.5 mg/dL) from a baseline of 1.5 mg/dL and urinalysis revealed protein (3+), red blood cells (4–10/hpf) and white blood cells (0–4/hpf). A pelvic CT scan showed an enlarged allograft without evidence of hydronephrosis, lymphadenopathy or enteritis. Hepatitis panel, viral nasal swab and serum BK PCR were negative. Laboratory workup for CMV, EBV and Giardia were pending. A kidney biopsy was performed (Figures 1 and 2). C4d staining by immunofluorescence microscopy was negative along the peritubular capillaries.Figure 2View Large Image Figure ViewerDownload Hi-res image Download (PPT) 1Based on light microscopy findings (Figure 1), the predominant pattern of parenchymal injury seen in this biopsy is best described as:aGranulomatous interstitial inflammationbSevere tubulitis with tubular necrosiscInfiltrating lymphoproliferative processdNecrotizing and crescentic glomerulonephritiseMicrocirculation inflammation (peritubular capillaritis and transplant glomerulitis)2Based on this morphologic evaluation, which of the following is the single best choice for additional workup?aImmunoperoxidase staining for CD3, CD20 and in situ hybridization for EBV-encoded small RNA (EBER)bIn situ hybridization for kappa and lambda light chainscImmunoperoxidase staining for viral antigens (polyomavirus, adenovirus, CMV and herpes simplex virus [HSV])dSerologic assessment for the presence of circulating donor-specific antibodies (DSA)eSerologic assessment for antiglomerular basement membrane antibodies (anti-GBM) and antineutrophil cytoplasmic antibodies (ANCA)3The most likely diagnosis in this biopsy is:aPolyomavirus nephritisbSevere T cell-mediated rejection (TCMR)cMicroscopic polyangiitis/Wegener’s granulomatosisdAdenovirus nephritisePosttransplant lymphoproliferative disorder (PTLD)4What is the best treatment?aSteroid bolus and increase the dose of tacrolimusbUse stronger immunosuppressive agent (e.g. thymoglobulin)cSignificant decrease in immunosuppression and use of antiviral therapydPlasmapheresis