1 Department of Renal Medicine, Lothian University Hospitals NHS Trust and 2 Departments of Pathology and 3 Medical Microbiology, The University of Edinburgh, Edinburgh, UK
Keywords: acute allograft rejection; CMV glomerulopathy; cytomegalovirus infection; renal allograft
A 33-year-old man received his second renal allograft, following loss of the first 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 1/1/0 mismatch; T and B lymphocyte and FACS cross-matches were negative. The donor was anti-cytomegalovirus (CMV) IgG seropositive, while the recipient was CMV seronegative. Initial immunosuppression was with tacrolimus (0.1 mg/kg), 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 confirmed 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 re-presented on day 30 with a sudden increase in creatinine. Allograft needle biopsy revealed a lymphocytic 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 tubulitis. Rejection was treated with three 500-mg doses of methylprednisolone, and institution of mycophenolate mofetil (1 g twice daily). Creatinine decreased to 239 µmol/l.
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Ganciclovir was continued for 1 month, mycophenolate mofetil was discontinued, the dose of prednisolone was reduced, and tacrolimus dose was reduced from 0.1 mg/kg to 0.07 mg/kg. The patient continued to require haemodialysis for 2 months, before becoming independent of renal replacement therapy. The most recent allograft needle biopsy, 5 months after transplant, showed mild chronic allograft nephropathy; glomeruli revealed mild tuft retraction and increased mesangial matrix, without evidence of the acute allograft glomerulopathy. Fifteen months after transplant, plasma creatinine is stable at 270 µmol/l, he has no further symptoms of CMV disease, and his last CMV PCR assay was negative.
This case illustrates the association of a distinctive glomerular lesionacute allograft glomerulopathy with CMV viraemia [1,2]. Cytomegalic cells are not a feature of CMV-induced acute allograft glomerulopathy. CMV has been suggested to trigger this unusual glomerular injury indirectly, through interferon-stimulated upregulation of endothelial class I major histocompatibility complex antigens, which in turn stimulates the alloimmune response [3]. Acute allograft glomerulopathy is envisaged as the product of an altered form of acute rejection, targeting glomerular and arterial endothelium, and precipitated by CMV, among other causes.
Notes
Correspondence and offprint requests to: G. Browne, Department of Renal Medicine, Lothian University Hospitals NHS Trust, Edinburgh, UK.
References