Nephrol Dial Transplant (2000) 15: 2063-2064
© 2000 European Renal Association-European Dialysis and Transplant Association
Letters
Post-renal transplant obstruction caused by cytomegalovirus ureteritis
1 Department of Renal Medicine, 2 Department of Anatomic Pathology, Wellington Hospital, Wellington, New Zealand
Sir,
Cytomegalovirus (CMV) infection is the leading cause of infectious complications following renal transplantation. The risk of developing the disease depends on many factors, most importantly the donor and recipient CMV serology status pre-transplant and the level of immunosuppression [1].
We report an unusual case of CMV tissue-invasive disease found incidentally when investigating a patient with post-transplant renal obstruction.
Case.
A 45-year-old Caucasian man was admitted for his third cadaveric renal transplant. He had end-stage renal failure secondary to reflux nephropathy and began CAPD aged 29. After 7 months he received his first cadaveric transplant. This was removed on day 10 with histology consistent with accelerated acute rejection. A second cadaveric transplant 16 months later, failed after 6 years from biopsy proven chronic rejection. CAPD was recommenced and continued for the next 7 years.
The donor for his third cadaveric transplant was a 50-year-old woman, with only one DR mismatch. The recipient was, however, highly sensitized with 70% panel reactive antibodies (PRA). The donor was CMV IgG seronegative and the recipient seropositive. The transplant ureter was implanted into the bladder and a double-J ureteric stent was inserted. The allograft functioned immediately with serum creatinine falling from 812 µmol/l to 145 µmol/l at the time of discharge on day 17.
He was treated with routine cyclosporin A (Neoral) 225 mg b.d., mycophenolate mofetil 1 g b.d. and prednisone 20 mg o.d. In view of his previous transplantations and a high PRA he was also given induction therapy with basiliximab (Simulect) 20 mg on day 0 and 4.
His initial hospital stay was complicated by a perioperative cerebral infarct resulting in a dense right hemiplegia and aphasia. A CT scan confirmed a left parietal infarct. He rehabilitated well and is now living independently.
Progress was complicated by two episodes of presumptive acute rejection, not biopsy proven, on days 9 and 41 treated with pulsed intravenous (i.v.) methylprednisolone. Serum creatinine returned to baseline levels on both occasions and an ultrasound scan on day 48 was normal.
On day 65 he suffered a third episode of acute renal dysfunction with creatinine rising to 339 µmol/l. An ultrasound revealed moderate hydronephrosis with appropriate positioning of the ureteric stent, but no obvious cause of the hydronephrosis was identified.
A percutaneous nephrostomy tube was placed leading to resolution of the acute renal failure. An antegrade nephrostogram study showed complete obstruction of the proximal ureter. The stent was removed by flexible cystoscopy, which revealed an intact vesico-ureteric anastomosis. A further nephrostogram showed an area of irregularity in the mid-portion of the ureter with a stricture distal to this. There were numerous round filling defects seen proximal to the stricture. A small jet of contrast was seen to enter the bladder.
On day 82 the transplant ureter was resected. The renal pelvis was anastomosed to his native ureter. He recovered well and at discharge serum creatinine was 143 µmol/l. The operative findings were of a well vascularized ureter with extrinsic compression from dense fibro-lymphatic tissue. The filling defects seen on the nephrostogram were blood clots. Histology showed areas of focal denudation of the urothelium, an oedematous corium with a moderately dense infiltrate of lymphocytes and neutrophils, together with scattered large cells that had eosinophilic inclusions. Further examination of the resected ureter detected cytomegalovirus specific DNA by nucleic acid amplification.
Comment.
Ureteric obstruction is a well recognized complication of renal transplantation. The most common causes are ischaemic injury and rejection leading to fibrosis and stricture. The cause in our patient was CMV ureteritis which was only diagnosed after resection of the transplant ureter. He had been systemically well without other features of invasive CMV disease.
Tissue invasive CMV disease is well recognized, but only two previous cases of CMV ureteritis in kidney-pancreas and renal transplant patients have been reported [2,3]. In both cases the donor and recipient were IgG seropositive pre-transplant and presented with ureteric obstruction. As with our patient, in neither case were systemic symptoms a feature, and CMV disease was only diagnosed by histology and in-situ hybridization following resection of the transplant ureters at 5 months. Our patient differed from the previous two case reports by receiving a CMV IgG seronegative kidney.
The risk of developing CMV disease is dependent on the CMV IgG serology status pre-transplant and the subsequent level of immunosuppression [1]. Current immunosuppressive agents contribute both to reactivation and the proliferation of CMV. Prednisone, cyclosporin A and tacrolimus promote the persistence and spread of CMV [1]. Azathioprine is a moderate reactivator of CMV but the antilymphocyte antibodies, antithymocyte antibodies and OKT3 which are used as induction and rescue agents, are potent reactivators of CMV [1]. Mycophenolate mofetil in high dose has been shown to lead to increased rates of CMV tissue invasion compared to azathioprine [4]. By comparison, the newer monoclonal agents such as Simulect (Basiliximab) have shown no increase in the incidence of CMV disease [5].
In the first of the two previously reported cases, the patient received OKT3 induction therapy and three months of prophylactic gancyclovir, acyclovir and CMV hyperimmune globulin [2]. The patient in the second case also received oral acyclovir prophylaxis but no induction antibody therapy [3]. The use of prophylactic antiviral therapy in these two cases may account for the later presentation of tissue invasive disease when compared to our case [6].
We postulate that in this case there was an initial injury to the ureter, possibly due to acute rejection. The local inflammation and immunosuppression predisposed this site to CMV infection leading to oedema formation and extrinsic compression of the ureter. We elected not to treat our patient with gancyclovir, as he was systemically well and the localised disease had been surgically removed.
This case highlights the need to be aware of unusual manifestations of CMV disease, the most common post-transplant infection, even in the absence of systemic symptoms.
References
- Rubin RH. Infectious disease complications of renal transplantation. Kidney Int1993; 44: 221–236[Web of Science][Medline]
- Lowell JA, Stratta RJ, Morton JJ, Kolbeck PC, Taylor RJ. Invasive cytomegalovirus infection in a renal transplant ureter after combined pancreas-kidney transplantation: an unusual cause of renal allograft dysfunction. J Urol1994; 152: 1546–1548[Medline]
- Moudgil A, Germain BM, Nast CC, Toyoda M, Strauss FG, Jordan SC. Ureteritis and cholecystitis: two unusual manifestations of cytomegalovirus disease in renal transplant recipients. Transplantation1997; 64: 1071–1073[Medline]
- The Tricontinental Mycophenolate Mofetil Renal Transplantation Study Group. A blinded, randomized clinical trial of mycophenolate mofetil for the prevention of acute rejection in cadaveric renal transplantation. Transplantation1996; 61: 1029–1037[Web of Science][Medline]
- Kahan BD, Rajagopalan PR, Hall M. Reduction of the occurrence of acute cellular rejection among renal allograft recipients treated with basiliximab, a chimeric anti-interleukin-2-receptor monoclonal antibody. Transplantation1999; 67: 276–284[Web of Science][Medline]
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Hibberd PL, Tolkoff-Rubin NE, Conti D et al. Preemptive ganciclovir therapy to prevent cytomegalovirus disease in cytomegalovirus antibody-positive renal transplant recipients. Ann Intern Med1995; 123: 18–26
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