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As long-term outcome studies of acute renal failure (ARF) are scarce and non-homogeneous, we studied 187 consecutive acute tubular necrosis (ATN) patients without previous nephropathies, discharged alive from our hospital between October 77 and December 92 and followed-up until December 99 (range 7–22 years; median 7.2). Variables were analyzed at the time of the acute episode and during follow-up. In 2000–2001 a clinical evaluation was made in 58 of the 82 patients still alive. Ten patients were lost to follow-up and 95 died. In 59% death was related with the disease present when the ATN developed. Kaplan–Meir survival curve showed 89, 67, 50, and 40% at 1, 5, 10, and 15 years, respectively, after discharge. Survival curves were significantly better (log-rank P<0.001) among the youngest, those surviving a polytrauma, those without comorbidity and surprisingly those treated in intensive care units. The proportional Cox model showed that age (hazard ratio (HR) 1.04 per year of age; P=0.000), presence of comorbid factors (HR 4.29; P=0.006), surgical admission (HR 0.45; P=0.000), and male sex (HR 1.72; P=0.020) were the variables associated with long-term follow-up. In the evaluated patients renal function was normal in 81%. Long-term outcome after ARF depends on absence of co-morbid factors, cause of initial admission and age. Although the late mortality rate is high and related with the original disease, renal function is adequate in most patients.Kidney International (2007) 71, 679–686. doi:10.1038/sj.ki.5002086; published online 31 January 2007 [ABSTRACT FROM AUTHOR]

To investigate mechanisms conferring susceptibility or resistance to renal ischemia, we used two rat strains known to exhibit different responses to ischemia-reperfusion. We exposed proximal tubule cells isolated from Sprague Dawley or Brown Norway rats, to a protocol of hypoxia, followed by reoxygenation in vitro. The cells isolated from both rat strains exhibited comparable responses in the disruption of intercellular adhesions and cytoskeletal damage. In vivo, after 24 h of reperfusion, both strains showed similar degrees of injury. However, after 7 days of reperfusion, renal function and tubular structure almost completely recovered and inflammation resolved, but only in Brown Norway rats. Hypoxia-inducible factor-dependent gene expression, ERK1/2, and Akt activation were different in the two strains. Inflammatory mediators MCP-1, IL-10, INF-gamma, IL-1beta, and TNF-alpha were similarly induced at 24 h in both strains but were downregulated earlier in Brown Norway rats, which correlated with shorter NFkappaB activation in the kidney. Moreover, VLA-4 expression in peripheral blood lymphocytes and VCAM-1 expression in kidney tissues were initially similar at 24 h but reached basal levels earlier in Brown Norway rats. The faster resolution of inflammation in Brown Norway rats suggests that this strain might be a useful experimental model to determine the mechanisms that promote repair of renal ischemia-reperfusion injury. [ABSTRACT FROM AUTHOR]

Employing tacrolimus (Tac) for routine immunosuppression in renal transplantation (RT), produced an incidence of new-onset, insulin-treated, diabetes mellitus (newDM) as high as 20%. More recently, several large multicenter kidney studies using Tac as the primary immunosuppressant have been reported in Europe. Between 1997 and 2001, we performed 155 RTs using Tac (0.2 mg/k/per day, targeting whole blood trough levels <15 ng/mL) with a rapid steroid taper. The acute rejection rate was 13%, and 89% of grafts are still functioning. Only 5 Tac-treated patients not previously requiring insulin needed insulin therapy for ≥30 days (3.2%). Eight separate studies employing Tac in at least one arm (N = 2728) have been reported between 1997 and 2002. Tac was combined with azathioprine or MMF, and/or steroids. The incidence of new DM at study end ranged from 2.3% to 8.3%. The only trial with >6% incidence was the first one, using an initial dose of 0.3 mg/kg per day. The most recent studies utilized an initial dose of 0.2 mg/kg per day, targeting whole blood trough levels of <15 ng/mL and a steroid taper, with newDM at <6%. On the basis of these data, we confirm in that the use of Tac as a first-line immunosuppressant in renal transplant patients affords protection against acute rejection with a low level of newDM. The tendency to employ lower oral doses of Tac, lower blood target levels, and a reduced steroid dose appear to minimize glucose disturbances in RT. [Copyright &y& Elsevier]

We have reviewed our experience in selective cytomegalovirus (CMV) infection prophylaxis and treatment in our renal transplant population. Between 1996 and 2001, 263 cadaveric renal transplant recipients had at least 6 months follow up. Immunosuppression was based on cyclosporine Neoral (n = 108) or tacrolimus (n = 155). CMV infection prophylaxis (oral acyclovir or gancyclovir at half usual doses) was only prescribed in recipients receiving a CMV positive ve kidney and in recipients treated with OKT3. CMV infection was diagnosed by a positive pp65 antigenemia upon appearance of CMV-related symptoms, leading to specific treatment (IV ganciclovir) only if symptoms were intense or there was visceral involvement. Thus, no preemptive treatment or programmed or periodic antigenemia was performed in any case.Nineteen episodes of symptomatic CMV infection were diagnosed (prevalence 7.2%). The frequency was similar for all immunosuppressive regimens. Only 9 of 19 (47%) of patients were given IV ganciclovir; the others were not treated. All patients survived without apparent complications, relapses, or recurrences. No oral gancyclovir was delivered after IV treatment.Our CMV prophylaxis protocol was limited to high-risk patients, using lower gancyclovir dosages than those usually advocated. It does not include programmed or scheduled search for CMV antigenemia in asymptomatic renal transplant patients. Despite these factors, our CMV infection rate and severity were similar to those reported with more aggressive protocols, with extended prophylaxis, preemptive therapy, or intense surveillance. [Copyright &y& Elsevier]