Urothelial Carcinoma in Kidney Transplant Recipients: Conversion From Calcineurin Inhibitor to Proliferation Signal Inhibitor?

Abstract

We read with interest the elegant report by Lemy et al,1Lemy A. Wissing K.M. Rorive S. et al.Late onset of bladder urothelial carcinoma after kidney transplantation for end-stage aristolochic acid nephropathy: A case series with 15-year follow-up.Am J Kidney Dis. 2008; 51: 471-477Abstract Full Text Full Text PDF PubMed Scopus (95) Google Scholar who addressed the importance of prophylactic bilateral native nephroureterectomy (BNU) and the high incidence of upper urinary tract and bladder urothelial carcinoma (UC) occurrence after exposure to aristolochic acid with a long follow-up. We totally agree with the recommendation of long-term regular cystoscopic surveillance and prophylactic BNU in patients with herbal supplement nephropathy who had undergone renal transplantation. As mentioned in our previous report, we performed BNU for renal transplant recipients who had gross or microscopic hematuria, visible tumors in the upper urinary tract by means of ureterorenoscopic examination, or filling defect by means of retrograde pyelography or magnetic resonance urography. However, the exact timing of prophylative BNU (ie, how long before or after kidney transplantation) was not specified in the cohort of Lemy et al.1Lemy A. Wissing K.M. Rorive S. et al.Late onset of bladder urothelial carcinoma after kidney transplantation for end-stage aristolochic acid nephropathy: A case series with 15-year follow-up.Am J Kidney Dis. 2008; 51: 471-477Abstract Full Text Full Text PDF PubMed Scopus (95) Google Scholar In our series, bladder recurrence after upper-tract UC was initially 42.8% in renal transplant recipients followed up for a mean of 28 months.2Liao C.H. Chueh S.C. Lai M.K. Chen J. Transitional cell carcinoma in renal transplant recipients.Transplant Proc. 2004; 36: 2152-2153Abstract Full Text Full Text PDF PubMed Scopus (39) Google Scholar Conversely, the bladder recurrence rate was greater at 70.5% (12 of 17 patients with upper-tract UC) in the longer follow-up described in the study by Lemy et al.1Lemy A. Wissing K.M. Rorive S. et al.Late onset of bladder urothelial carcinoma after kidney transplantation for end-stage aristolochic acid nephropathy: A case series with 15-year follow-up.Am J Kidney Dis. 2008; 51: 471-477Abstract Full Text Full Text PDF PubMed Scopus (95) Google Scholar Concerning the greater incidence of malignancy in transplant recipients, some articles have suggested that immunosuppression with such proliferation signal inhibitors (PSIs) as sirolimus was associated with a decreased incidence of cancer, particularly in patients converted from a regimen including a calcineurin inhibitor, such as cyclosporin.3Campistol J.M. Eris J. Oberbauer R. et al.Sirolimus therapy after early cyclosporine withdrawal reduces the risk for cancer in adult renal transplantation.J Am Soc Nephrol. 2006; 17: 581-589Crossref PubMed Scopus (436) Google Scholar Luan et al4Luan F.L. Hojo M. Maluccio M. Yamaji K. Suthanthiran M. Rapamycin blocks tumor progression: Unlinking immunosuppression from antitumor efficacy.Transplantation. 2002; 73: 1565-1572Crossref PubMed Scopus (222) Google Scholar found that sirolimus treatment prolonged the survival of mice inoculated with T24 human bladder cancer cells. Although there is no study to investigate the anticancer properties of PSI-based regimens in patients with posttransplantation UC, preclinical and clinical studies provide reasonable evidence for the conversion from calcineurin inhibitor to PSI in the management of patients with UC after renal transplantation. We have performed such immunosuppressant manipulation in our renal transplant recipients with evidence of UC in their native urinary tracts. However, the results were not completely satisfactory. Four of 6 patients still experienced UC recurrence in their bladder despite BNU and conversion to a sirolimus-based regimen. Support: None. Financial Disclosure: None. Late Onset of Bladder Urothelial Carcinoma After Kidney Transplantation for End-Stage Aristolochic Acid Nephropathy: A Case Series With 15-Year Follow-upAmerican Journal of Kidney DiseasesVol. 51Issue 3PreviewAristolochic acids are nephrotoxins and predispose to upper-tract urothelial carcinoma. The risk of bladder urothelial carcinoma after kidney transplantation and its relationship to upper-tract urothelial carcinoma is not well defined. Full-Text PDF In ReplyAmerican Journal of Kidney DiseasesVol. 52Issue 3PreviewWe agree with Chung et al1 that the timing of the prophylactic bilateral native nephroureterectomy (BNU) in our study2 was not calculated by taking into account the date of kidney transplantation. We preferred to quantify the period between the interruption of aristolochic acid intake and the detection of neoplastic lesions in BNU material. However, this parameter is easy to evaluate. Considering the relative variability in reaching end-stage aristolochic acid nephropathy (AAN) and in receiving a kidney transplant, BNU was performed in patients who were still undergoing dialysis (namely, a few months after their admission into the dialysis unit) or patients who had already received a kidney transplant (ie, several months or years after renal transplantation). Full-Text PDF