Seven hundred and twenty-seven renal transplant patients are reviewed with respect to the occurrence of urinary tract infection (UTI) after renal transplantation. UTI was defined as the detection of both bacteriuria (10(5) CFU/ml) and pyuria (10 leukocytes/hpf). UTI developed in 11 of the inpatients (20.8%) and in 30 (4.2%) of the outpatients during a one-year period. Among outpatients, 12 had symptomatic infections, comprising seven with acute pyelonephritis and five with acute cystitis. Asymptomatic UTI was detected in 18 patients. In addition, asymptomatic bacteriuria without pyuria was observed in ten (1.4%) patients. UTI was more common in patients with diabetes, and underlying urinary tract complications were present in some patients. Administration of trimethoprim-sulfamethoxazole for about 4 months is suggested to reduce the frequency of UTI in the early period after renal transplantation.

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Antibody mediated rejection (ABMR) is a major barrier to long-term kidney graft survival. Dysregulated donorspecific antibody (DSA) responses are induced in CCR5deficient mice transplanted with complete major histocompatibility complex (MHC)-mismatched kidney allografts, and natural killer (NK) cells play a critical role in graft injury and rejection. We investigated the consequence of high DSA titers on kidney graft outcomes in the presence or absence of NK cell activation within the graft. Equivalent serum DSA titers were induced in CCR5-deficient B6 recipients of complete MHC mismatched A/J allografts and semi-allogeneic (A/J x B6) F1 kidney grafts, peaking by day 14 posttransplant. A/J allografts were rejected between days 16-28, whereas B6 isografts and semi-allogeneic grafts survived past day 65. On day 7 post-transplant, NK cell infiltration into A/J allografts was composed of distinct populations expressing high and low levels of the surface antigen NK1.1, with NK1.1 low cells reflecting the highest level of activation. These NK cell populations increased with time post-transplant. In contrast, NK cell infiltration into semi-allogeneic grafts on day 7 was composed entirely of NK1.1 high cells that decreased thereafter. On day 65 post-transplant the semi-allogeneic grafts had severe interstitial fibrosis, glomerulopathy, and arteriopathy, accompanied by expression of profibrogenic genes. These results suggest that NK cells synergize with DSA to cause acute kidney allograft rejection, whereas high DSA titers in the absence of NK cell activation cannot provoke acute ABMR but instead induce the indolent development of interstitial fibrosis and glomerular injury that leads to late graft failure.

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The impact of hepatitis B virus (HBV) infection on the outcome of renal transplantation (Tx) has been controversial. To determine the indication of renal Tx in patients infected by HBV, we investigated the long-term outcome of renal transplant patients with hepatitis B surface antigen (HBsAg). We analyzed 980 patients, including 18 HBsAg carriers, who underwent renal Tx and were immunosuppressed with cyclosporin in our institute. Fourteen out of 18 patients (77.8%) showed hepatic dysfunction after an average period of 17.8 months (range 1-65) after Tx. Four out of 14 patients (28.5%) with hepatic dysfunction died of liver failure due to fulminant hepatitis with functioning grafts between 15 and 71 months after Tx. The remaining 10 patients with hepatic dysfunction are alive up to the time of last follow-up; however, 5 of them lost their grafts because of rejection between 44 and 92 months after Tx. Their liver function improved after withdrawal of cyclosporin. Only 4 patients did not develop chronic liver disease and have had functioning grafts for between 44 and 147 months. One patient died of subarachnoid hemorrhage 22 months after Tx. HBe antigen, antibody and HCV antibody status were not related to the occurrence of liver dysfunction after Tx. Four HB V-DNA-positive patients showed deteriorated liver function. Three patients with chronic active hepatitis confirmed by the biopsy were treated with interferon. Interferon improved liver function in 2 patients, however, 1 patient died of liver failure despite interferon therapy. Our data suggested that the presence of HBsAg is often associated with chronic liver disease leading to liver failure regardless of HBe and HCV status after Tx. The indication of renal Tx in patients with HBsAg should be determined carefully giving consideration to these results.

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ABSTRACT:Aim: Calcineurin inhibitors reduce the acute rejection rate and greatly improve renal allograft survival. However, they are associated with some adverse events, including nephrotoxicity, a risk factor for allograft failure. Chronic calcineurin inhibitor-induced nephrotoxicity causes irreversible damage to renal components, such as arteriolar hyaline thickening. The aim of this study is to investigate the risk factors for tacrolimus-induced chronic nephrotoxicity using zero-time biopsy specimens.Methods: Between January 2001 and December 2010, 483 patients who underwent living-related kidney transplantation and had also been placed on a tacrolimus-based regimen were enrolled in this study. There were 1859 specimens evaluated comprising 483 zero-time biopsy specimens and 1376 protocol and for-cause biopsy specimens. De novo arteriolar hyaline thickening due to tacrolimus-induced chronic nephrotoxicity was scored according to the Banff classification aah score. In this study, tacrolimus-induced nephrotoxicity was defined as a positive aah score. Results:Of the 483 patients, 108 patients (22.4%) had biopsy-proven tacrolimus-induced chronic nephrotoxicity. Multivariate analysis showed that interlobular arteriosclerosis proven by zero-time biopsy (OR: 2.23, 95%CI: 1.38-3.58, P < 0.01) and acute rejection episodes (OR: 1.58, 95%CI: 1.00-2.47, P = 0.04) were independent risk factors for tacrolimus-induced chronic nephrotoxicity. However, tacrolimus-induced chronic nephrotoxicity did not affect long-term graft survival.Conclusion: This is the first report showing that arteriosclerosis in zero-time biopsy specimens is a risk factor for histological tacrolimus-induced chronic nephrotoxicity.There is no doubt that calcineurin inhibitor (CNI) reduce the acute rejection rate and greatly improve short and long-term renal allograft survival. While CNI contributed to an improved clinical course after kidney transplantation, they carry the risk of adverse events including nephrotoxicity, neurotoxicity, glucose intolerance, liver dysfunction, hypertension, neoplasm, and infectious complications. Among them, CNI-induced chronic nephrotoxicity has been considered a significant risk factor for allograft survival and function. Arteriolar hyaline thickening is a typical histological feature of CNI long-term toxicity. [1][2][3][4][5][6] Previous studies have established that chronic CNI nephrotoxicity is a cause of allograft failure. 7 Even with appropriate trough level control, nephrotoxicity is inevitable as long as the patient is exposed to CNIs. However, the risk factors for CNI nephrotoxicity are not yet fully established. At our institution, zero-time renal allograft biopsy has been routinely performed in all cases. We have previously reported that zero-time biopsy data have a strong clinical impact on various aspects of kidney transplantation. 8 In this study, we seek to establish risk factors for CNI toxicity by analyzing our pre-transplant patient characteristics, including zero-time biopsy. METHODSThis retrospective s...