Fu L. Luan

New-onset diabetes mellitus in kidney transplant recipients discharged on steroid-free immunosuppression.

Background. New-onset diabetes after transplant (NODAT) is a serious complication after kidney transplantation. We studied the relationship between steroid-free maintenance regimens and NODAT in a national cohort of adult kidney transplant patients. Methods. A total of 25,837 previously nondiabetic kidney transplant patients, engrafted between January 1, 2004, and December 31, 2006, were included in the study. Logistic regression analysis was used to compare the risk of developing NODAT within 3 years after transplant for patients discharged with and without steroid-containing maintenance immunosuppression regimens. The effect of transplant program-level practice regarding steroid-free regimens on the risk of NODAT was studied as well. Results. The cumulative incidence of NODAT within 3 years of transplant was 16.2% overall; 17.7% with maintenance steroids and 12.3% without (P<0.001). Patients discharged with steroids had 42% greater odds of developing NODAT compared with those without steroids (adjusted odds ratio [AOR]=1.42, 95% confidence interval [CI]=1.27–1.58, P<0.001). The maintenance regimen of tacrolimus and mycophenolate mofetil or mycophenolate sodium was associated with 25% greater odds of developing NODAT (AOR=1.25, 95% CI=1.08–1.45, P=0.003) than the regimen of cyclosporine and mycophenolate mofetil or mycophenolate sodium. Several induction therapies also were associated with lower odds of NODAT compared with no induction. Patients from programs that used steroid-free regimens for a majority of their patients had reduced odds of NODAT compared with patients from programs discharging almost all of their patients on steroid-containing regimens. Conclusion. The adoption of steroid-free maintenance immunosuppression at discharge from kidney transplantation in selected patients was associated with reduced odds of developing NODAT within 3 years.

Six-Month Prophylaxis Is Cost Effective in Transplant Patients at High Risk for Cytomegalovirus Infection

The risk of late-onset cytomegalovirus (CMV) infection remains a concern in seronegative kidney and/or pancreas transplant recipients of seropositive organs despite the use of antiviral prophylaxis. The optimal duration of prophylaxis is unknown. We studied the cost effectiveness of 6- versus 3-mo prophylaxis with valganciclovir. A total of 222 seronegative recipients of seropositive kidney and/or pancreas transplants received valganciclovir prophylaxis for either 3 or 6 mo during two consecutive time periods. We assessed the incidence of CMV infection and disease 12 mo after completion of prophylaxis and performed cost-effectiveness analyses. The overall incidence of CMV infection and disease was 26.7% and 24.4% in the 3-mo group and 20.9% and 12.1% in the 6-mo group, respectively. Six-month prophylaxis was associated with a statistically significant reduction in risk for CMV disease (HR, 0.35; 95% CI, 0.17 to 0.72), but not infection (HR, 0.65; 95% CI, 0.37 to 1.14). Cost-effectiveness analyses showed that 6-mo prophylaxis combined with a one-time viremia determination at the end of the prophylaxis period incurred an incremental cost of

Graft and Patient Survival in Kidney Transplant Recipients Selected for de novo Steroid-Free Maintenance Immunosuppression

34,362 and

Comparison of the long-term outcomes of kidney transplantation: USA versus Spain

16,215 per case of infection and disease avoided, respectively, and

Comparative Risk of Impaired Glucose Metabolism Associated with Cyclosporine Versus Tacrolimus in the Late Posttransplant Period

8,304 per one quality adjusted life-year gained. Sensitivity analyses supported the cost effectiveness of 6-mo prophylaxis over a wide range of valganciclovir and hospital costs, as well as variation in the incidence of CMV disease. In summary, 6-mo prophylaxis with valganciclovir combined with a one-time determination of viremia is cost effective in reducing CMV infection and disease in seronegative recipients of seropositive kidney and/or pancreas transplants.

Abnormal Glucose Metabolism and Metabolic Syndrome in Non-Diabetic Kidney Transplant Recipients Early After Transplantation

Steroid‐free regimen is increasingly employed in kidney transplant recipients across transplant centers. However, concern remains because of the unknown impact of such an approach on long‐term graft and patient survival. We studied the outcomes of steroid‐free immunosuppression in a population‐based U.S. cohort of kidney transplant recipients. All adult solitary kidney transplant recipients engrafted between January 1, 2000 and December 31, 2006 were stratified according to whether they were selected for a steroid‐free or steroid‐containing regimen at discharge. Multivariate Cox regression models were used to estimate graft and patient survival. The impact of the practice pattern on steroid use at individual transplant centers was analyzed. Among 95 755 kidney transplant recipients, 17.2% were steroid‐free at discharge (n = 16 491). Selection for a steroid‐free regimen was associated with reduced risks for graft failure and death at 1 year (HR 0.78, 95% CI 0.72–0.85, and HR 0.73, 95% CI 0.65–0.82, respectively, p < 0.0001) and 4 years (HR 0.83, 95% CI 0.78–0.87, and HR 0.76, 95% CI 0.71–0.83, respectively, p < 0.0001). This association was mostly observed at individual centers where less than 65% of recipients were discharged on the steroid‐containing regimen. De novo steroid‐free immunosuppression as currently practiced in the United States appears to carry no increased risk of adverse clinical outcomes in the intermediate term.

Steroid-free maintenance immunosuppression in kidney transplantation: is it time to consider it as a standard therapy?

BACKGROUND The long-term outcomes of kidney transplantation are suboptimal because many patients lose their allografts or experience premature death. Cross-country comparisons of long-term outcomes of kidney transplantation may provide insight into factors contributing to premature graft failure and death. We evaluated the rates of late graft failure and death among US and Spanish kidney recipients. METHODS This is a cohort study of US (n = 9609) and Spanish (n = 3808) patients who received a deceased donor kidney transplant in 1990, 1994, 1998 or 2002 and had a functioning allograft 1 year after transplantation with follow-up through September 2006. Ten-year overall and death-censored graft survival and 10-year overall recipient survival and death with graft function (DWGF) were estimated with multivariate Cox models. RESULTS Among recipients alive with graft function 1 year after transplant, the 10-year graft survival was 71.3% for Spanish and 53.4% for US recipients (P < 0.001). The 10-year, death-censored graft survival was 75.6 and 76.0% for Spanish and US recipients, respectively (P = 0.73). The 10-year recipient survival was 86.2% for Spanish and 67.4% for US recipients (P < 0.001). In recipients with diabetes as the cause of ESRD, the adjusted DWGF rates at 10 years were 23.9 and 53.8 per 1000 person-years for Spanish and US recipients, respectively (P < 0.001). Among recipients whose cause of ESRD was not diabetes mellitus, the adjusted 10-year DWGF rates were 11.0 and 25.4 per 1000 person-years for Spanish and US recipients, respectively. CONCLUSIONS US kidney transplant recipients had more than twice the long-term hazard of DWGF compared with Spanish kidney transplant recipients and similar levels of death-censored graft function. Pre-transplant medical care, comorbidities, such as cardiovascular disease, and their management in each countrys health system are possible explanations for the differences between the two countries.

Universal prophylaxis is cost effective in cytomegalovirus serology-positive kidney transplant patients.

New onset diabetes after transplantation (NODAT) and impaired fasting glucose (IFG) are common in kidney transplant recipients (KTRs). Calcinuerin inhibitor (CNI) therapy is a causal risk factor. NODAT is associated with increased mortality and diminished graft survival. We studied the incidence of NODAT and IFG in KTRs before and after a medically indicated switch of CNI therapy from cyclosporine (CsA) to tacrolimus (Tac). The study population consisted of 704 nondiabetic KTRs. Of them, 171 underwent conversion from CsA to Tac (group I) and 533 remained on the CsA since transplantation (Group II). Time‐dependent Cox regression and generalized estimating equations were used to account for sequential CNI exposure. NODAT and IFG occurred in 15.2% and 22.1% of group I subjects and 15.6% and 25.8% of group II subjects, respectively (p = 0.90 for NODAT and p = 0.38 for IFG). Accounting for equal follow‐up time since conversion from CsA to Tac, the adjusted 5‐year NODAT‐free survival was 87.4% and 91.4% in group I and group II, respectively (p = 0.90). In conclusion, conversion to Tac, compared to continuous exposure to CsA, carries quantitatively similar risk of impaired glucose metabolism in KTRs in the late posttransplant period.

Early pancreas graft failure is associated with inferior late clinical outcomes after simultaneous kidney-pancreas transplantation

Background. Abnormal glucose metabolism (AGM) and metabolic syndrome (MS) are individually associated with a poor cardiovascular outcome in kidney transplant recipients. We prospectively studied the relationship between AGM and MS in non-diabetic kidney transplant recipients early after transplantation. Methods. A total of 203 de novo kidney transplant recipients underwent standard 2-hr glucose tolerance test 10 weeks after transplantation. Demographic and clinical characteristics were collected. AGM was defined as impaired fasting glucose, impaired glucose tolerance, and new onset diabetes after transplant according to the WHO criteria, and MS was defined according to the National Cholesterol Education Expert Panel criteria. Results. Overall, 97 patients (47.8%) met the diagnosis of AGM and 98 patients (48.3%) met the criteria of MS. AGM and MS are highly associated (&khgr;2, P<0.001). Fasting plasma glucose levels before the transplant are independent predictors common for AGM and MS. Age predicts AGM with and without MS, whereas body mass index before transplant predicts MS. Patients with impaired glucose tolerance and new-onset diabetes after transplant displayed significant worsening of their fasting plasma glucose levels during the 10-week observational period. MS and the components of MS, but not AGM, were associated with reduced transplant renal function (P=0.002). Conclusion. The early screening of AGM and MS should be emphasized, and the role of early therapeutic interventions aimed at both conditions explored. The long-term follow-up of these patients will yield more insight on the significance of such findings.

Metabolic syndrome and new onset diabetes after transplantation in kidney transplant recipients.

Steroid-free immunosuppression in kidney transplantation has been gaining popularity over the past decade, as documented by a continuous and steady rise in the number of kidney transplant patients discharged on steroid-free regimens. This increased interest in steroid-free immunosuppression is fueled by the recognition that half of transplant loss is related to patient death due to cardiovascular disease and/or infectious complications and that the long-term use of steroids contributes to such elevated cardiovascular morbidity and mortality. The availability of newer and more potent immunosuppressive agents has furthered such interest. Many clinical trials over the past two decades have demonstrated the feasibility of steroid-free regimens, at the expense of a slight increase in the rate of acute rejection, which is an important end point in any clinical trial of relatively short duration. The largest epidemiological study to date has reassured the transplant community that the selective use of steroid-free immunosuppression in kidney transplant patients provides no inferior outcome in patient and graft survival at intermediate term. Steroid-free regimens have the potential to improve cardiovascular risk profile. The challenges that remain are to identify the subset of kidney transplant patients who may not benefit from steroid-free immunosuppression and to demonstrate the survival advantage of steroid-free immunosuppresion in suitable kidney transplant candidates.