Acute allograft glomerulopathy associated with CMV viraemia.

A 33-year-old man received his second renal allograft, following loss of the ®rst graft after 10 years to chronic allograft nephropathy. His primary renal disease was obstructive uropathy secondary to posterior urethral valves. The second allograft was a 1u1u0 mismatch; T and B lymphocyte and FACS cross-matches were negative. The donor was anti-cytomegalovirus (CMV) IgG seropositive, while the recipient was CMV sero-negative. Initial immunosuppression was with tacro-limus (0.1 mgukg), azathioprine, and prednisolone. The patient received oral acyclovir 200 mg three times daily as CMV prophylaxis. There was no weekly surveillance for CMV DNA by polymerase chain reaction (PCR), which is now performed routinely. After transplantation allograft function was delayed; an ultrasound scan on day 4 con®rmed satisfactory vascular supply, and allograft needle biopsy showed acute tubular necrosis without evidence of acute rejection. On day 13 creatinine reduced spontaneously and the patient became independent of dialysis. He represented on day 30 with a sudden increase in creatinine. Allograft needle biopsy revealed a lympho-cytic glomerulitis (Figure 1a) with modest numbers of endocapillary mononuclear cells in association with acute cellular rejection, Banff type IIA (intimal arteritis, Figure 1b), and low-grade lymphocytic tubu-litis. Rejection was treated with three 500-mg doses of methylprednisolone, and institution of mycopheno-late mofetil (1 g twice daily). Creatinine decreased to 239 mmolul. On day 44, the patient was re-admitted with right upper quadrant pain, malaise, and further deterioration in renal function (creatinine 349 mmolul). Temperature was not raised; he was leukopenic (total leukocyte count 0.9 3 10 9 ul); his haemoglobin had dropped from 85 gul to 76 gul and platelets fell to 95 from 120 (3 10 9 ul); the blood ®lm showed atypical mono-nuclear cells, giant platelets, and occasional fragments were reported. He had developed abnormal serum liver biochemistry (alanine aminotransferase, 297 Uul; gamma glutamyl transpeptidase, 379 Uul, alkaline phosphatase, 265 Uul). Consequently intravenous ganciclovir therapy was begun empirically for presumed CMV infection. The patient became dialysis-dependent. Allograft needle biopsy was performed, revealing intimal arteritis, but now also an acute allograft glomerulopathy (Figure 1c,d) with severe endothelial injury and PAS-positive transcapillary webs. No cytomegalic cells were identi®ed on biopsy, and immunohistochemistry for CMV early antigens was negative. There were no glomerular red cell fragments or congestion and no arterial intimal oedema or intimal neo®brosis, making thrombotic microangio-pathy unlikely. However, acute primary CMV infection was con®rmed by detection of plasma CMV DNA by PCR, rapid detection of CMV early …