Incidence, predictors and outcomes of transplant renal artery stenosis after kidney transplantation: analysis of USRDS.

OBJECTIVE: We analyzed the United States Renal Data System registry to study the risks, predictors, and outcomes of transplant renal artery stenosis (TRAS) in contemporary practice. METHODS: The study sampled comprised adults with Medicare primary insurance who received kidney transplants in 2000-2005. We examined associations of recipient, donor and transplant factors with time-to-TRAS by the Kaplan-Meier method and multivariate Cox regression. Survival analysis methods were employed to estimate graft survival after TRAS, and to model TRAS as a time-dependent outcome predictor. Kaplan-Meier analysis was used to estimate time to allograft loss in patients who did or did not have an angioplasty procedure for TRAS. RESULTS: There were 823 cases of TRAS among 41,867 transplant patients, with an incidence rate of 8.3 (95% CI 7.8-8.9) cases per 1,000 patient-years. Mean time to diagnosis of TRAS was 0.83 + or - 0.81 years after transplant. Factors associated with TRAS were older recipient and donor age, extended criteria donors, induction immunosuppression, delayed graft function, and ischemic heart disease. There was no association of TRAS with deceased donors, prolonged cold ischemia time, acute rejection or cytomegalovirus status. TRAS was associated with increased risk of graft loss (including death; adjusted hazard ratio 2.84, 95% CI 1.70-4.72). Among the 823 patients with TRAS, 145 (17.6%) underwent angioplasty. Graft survival after TRAS was not significantly different in patients treated with angioplasty compared to those without angioplasty. CONCLUSIONS: TRAS is an important complication that predicts adverse patient and graft outcomes. Treatment strategies for TRAS warrant prospective investigation in clinical trials.

Analysis of USRDS: incidence and risk factors for Pneumocystis jiroveci pneumonia.

BACKGROUND: To investigate the effect of modern immunosuppression on the incidence, risk factors, morbidity, and mortality of Pneumocystis pneumonia (PCP) in recipients of kidney transplants. METHODS: We conducted a retrospective cohort study of 32,757 Medicare primary transplant recipients in the United States Renal Data System from January 1, 2000 through July 31, 2004. PCP infection was defined by Medicare claims using International Classification of Disease, 9th Revision codes. The incidence of PCP infections, graft loss, and death were measured. RESULTS: There were a total of 142 cases (cumulative incidence 0.4%) of PCP after kidney transplantation during the study period. By using multivariate analysis with Cox regression, expanded criteria donor, donation after cardiac death, and earlier year of transplant were associated with development of PCP disease. Induction immunosuppression and acute rejections were not associated with risk for PCP infections. However, based on adjusted hazard ratio (AHR), maintenance immunosuppression regimens containing the combination of tacrolimus and sirolimus (AHR 3.60, confidence interval [CI] 2.03-6.39), Neoral and mycophenolate mofetil (AHR 2.09, CI 1.31-3.31), and sirolimus and mycophenolate mofetil (AHR 2.77, CI 1.40-5.47), were associated with development of PCP. As a time dependent variable, PCP was associated with an increased risk of both graft loss and death. CONCLUSION: PCP infections are rare in the modern era of prophylaxis; however, these infections are a serious risk factor for graft loss and patient death, in particular, in patients who are on sirolimus as part of the immunosuppressive regimen. The median time to development of PCP after transplant was 0.80+/-0.95 years, suggesting a longer period of PCP prophylaxis.

Incidence, predictors, and associated outcomes of prostatism after kidney transplantation.

BACKGROUND AND OBJECTIVES: Renal transplantation is increasingly performed in elderly patients, and the incidence of benign prostatic hyperplasia (BPH) increases with age. Anuric males on dialysis may have occult BPH and not develop obstructive symptoms until urine flow is restored after transplantation. If left untreated, BPH poses a risk for numerous complications, including acute urinary retention (AUR), recurrent urinary tract infections (UTI), and renal failure. The authors hypothesized that incident BPH after renal transplantation would adversely affect allograft survival. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Medicare claims for BPH, AUR, UTI, and prostate resection procedures (transurethral resection of the prostate; TURP) were assessed in a retrospective cohort of 23,622 adult male Medicare primary renal transplant recipients in the United States Renal Data System database who received transplants from 1 January 2000 to 31 July 2005 and followed through 31 December 2005. RESULTS: The 3-yr incidence of BPH post-transplant was 9.7%. The incidences of AUR, UTI, and TURP after BPH diagnosis (up to 3 yr posttransplant) were 10.3%, 6.5%, and 7.3% respectively, and each was significantly associated with BPH. Cox regression analysis showed that recipient age per year, later year of transplant, and dialysis vintage were associated with incident BPH. Using Cox nonproportional hazards regression, BPH was significantly associated with renal allograft loss (including death). CONCLUSIONS: BPH is common in males after renal transplant and is independently associated with AUR, UTI, and graft loss. It is unknown whether treatment of BPH, either medical or surgical, attenuates these risks.

Influence of race on kidney transplantation in the Department of Defense healthcare system.

BACKGROUND: We report the influence of race on transplant outcomes in the Department of Defense (DOD) system. METHODS: Retrospective cohort analysis of all kidney transplants performed at WRAMC from 1996 to 2005. Kaplan-Meier analysis was used to assess for differences in graft survival, and Cox regression was used to calculate adjusted hazard ratios for graft loss. For our analyses, we used the cutoff of 6 years (year 2000) when we introduced thymoglobulin induction; maintenance immunosuppression consisted of mycophenolate mofetil and tacrolimus, and rapid steroid taper (completed withdrawal at 6 weeks) was used for all patients. RESULTS: There were 220 transplants (91 Blacks, 107 Caucasians and 22 Asians). Because the curve for graft survival for Blacks over time violated the proportional hazards assumption (at 6 years post-transplant), analysis was segregated into two segments. Through 6 years of follow-up, graft survival was 77% for Blacks and 81% for non-Blacks (p = 0.74 by log rank). Through 9 potential years of follow-up, graft survival for Blacks was 56% and 78% for Whites (p = 0.005). In Cox regression analysis, Black race, compared with non-Black race, was not significantly associated with graft loss at 6 years, but was significantly associated with graft loss occurring after 6 years. CONCLUSIONS: In the DOD health system, no significant differences were seen in graft survival among recipients of different races at 6 years. Black recipients who received a kidney transplant before the year 2000 showed decreased graft survival compared to non-Blacks. This was consistent with change in immunosuppressive regimen in our institution with the introduction of thymoglobulin induction and maintenance therapy with tacrolimus, mycophenolate mofetil and withdrawal of prednisone at 6 weeks.

Progressive multifocal leukoencephalopathy and use of mycophenolate mofetil after kidney transplantation.

Mycophenolate mofetil (MMF) use may be associated with progressive multifocal leukoencephalopathy (PML). We conducted a retrospective cohort study of 32,757 renal transplant recipients using the United States Renal Data System kidney transplant files for the incidence, prognosis, and clinical features associated with PML occurring after kidney transplant. Subjects were transplanted from January 1, 2000 to July 31, 2004 and followed through December 31, 2004. The incidence density of PML in MMF users was 14.4 cases/100,000 person-years at risk versus 0 for non-MMF users (P=0.11) by log rank test. Factors significantly associated with PML were BK virus infection (22.2% vs. 1.1%), pretransplant transfusion (75% vs. 34%), panel reactive antibody more than 20% (56% vs. 14%), and use of antirejection medications in the first year (33% vs. 9.2%), all P less than 0.05. PML is rare in the renal transplant population. There was no significant association between PML and MMF, but MMF use in this cohort is too high to accurately assess an association.

Parathyroidectomy versus cinacalcet hydrochloride-based medical therapy in the management of hyperparathyroidism in ESRD: a cost utility analysis.

BACKGROUND: Previously, patients with end-stage renal disease (ESRD) with uncontrolled hyperparathyroidism had few options other than parathyroidectomy, which was reserved for patients refractory to medical therapy. Newer calcimimetic agents, such as cinacalcet, may be an alternative, but raise the possibility of indefinite medical treatment that also would increase costs. STUDY DESIGN: Cost utility analysis. SETTING & POPULATION: Base case consisted of prevalent adult US patients with ESRD refractory to management with standard medical therapy. Characteristics were obtained from patients who underwent parathyroidectomy in 2001, and, for purposes of comparison, patients in whom cinacalcet was used were assigned similar characteristics. All data came from preexisting literature and trials or from US Renal Data System analysis files. INTERVENTION: Use of cinacalcet hydrochloride versus parathyroidectomy. PERSPECTIVE & TIME FRAME: Medicare and societal costs and quality-adjusted life-years from the date of parathyroidectomy or use of cinacalcet followed up for 2 years, respectively. MODEL & OUTCOMES: Primary outcomes were cost (measured in US dollars) and cost utility measured using cost per quality-adjusted life-years. RESULTS: At base-case surgical and drug costs, surgical and drug success rates, complication rates/costs, and benefit from correction of hyperparathyroidism, parathyroidectomy was found to be both less expensive and more cost-effective at 7.25 +/- 0.25 months. Parathyroidectomy became more cost-effective at 15.28 to 16.32 months at the upper limit of sensitivity analysis, when drug/surgical costs and success/complication rates/costs were maximally weighted to favor cinacalcet-based medical therapy. LIMITATIONS: We assumed current costs of both cinacalcet and parathyroidectomy and assumed cinacalcet use would be indefinite. CONCLUSIONS: For patients with ESRD with uncontrolled hyperparathyroidism who are good candidates for either drug therapy or surgery, cinacalcet hydrochloride is the most cost-effective modality if the patient is to remain on dialysis therapy for 7.25 +/- 0.25 months. Cinacalcet may be more optimal if used in patients who have high risk of mortality or who would expect to receive a kidney transplant quickly. For other subgroups, parathyroidectomy dominated.