Edward M. Falta

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.

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 ± 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.

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.

Transplantation of A2 kidneys into B and O recipients leads to reduction in waiting time: USRDS experience.

Introduction. Strategy of transplanting kidneys from A2 donors into patients with blood group B and O recipients has been used to alleviate the long waiting times. Materials and Methods. We used an inception cohort of US Renal Data System data base with patients older than 18 years who underwent renal transplantation between January 1995 and July 2006. The primary outcome variable was allograft loss (including death). Bivariate analysis of factors associated with receiving A2 or A2B kidneys was performed with chi-square testing for categorical variables (Fishers exact test used for violations of Cochrans assumptions) and Students t test for continuous variables (Mann-Whitney U test used for nonnormally distributed variables). Results. There were 150,118 first kidney transplants of whom 113 received kidney transplant from A2 to O, and 125 patients received A2 to B kidney transplant. Compared with other recipients from the same blood group, recipients of A2 kidneys had significantly shorter wait times. O recipients had a median wait time of 1.63 years (range 0.00–17.21 years), whereas O recipients who received A2 kidneys had a median wait time of 0.70 years (range 0.02–1.47 years; P<0.001). B recipients had a median wait time of 1.90 years (range 0.00–17.52 years), whereas B recipients who received A2 kidneys had a median wait time of 0.74 years (range 0.10–5.21 years; P<0.001). There was no significant difference in graft loss or death between A2 to O and B versus all other recipients. Conclusions. The results showed that comparatively few patients received A2 to B or O kidney transplant.

Outcomes in African-Americans vs. Caucasians Using Thymoglobulin or Interleukin-2 Receptor Inhibitor Induction: Analysis of USRDS Database

Aim: We used the USRDS database to test the hypothesis that graft survival was similar using either rabbit antithymocyte globulin (rATG) vs. interleukin-2 receptor inhibitor (IL2i) in the Prograf era. We further explored the variable of race in the two groups of patients. Methods: We conducted a retrospective cohort study of kidney transplant patients in the USRDS from 2000 through 2005 to compare graft survival (including death) using rATG vs. IL2i with particular reference to outcomes between African-Americans vs. Caucasians. Kaplan-Meier analysis was performed to assess patient and graft survival after transplantation, stratified by recipient induction with rATG versus IL2i. Cox regression analysis was performed to assess adjusted survival after transplantation, assessing whether induction rATG (vs. IL2i) was significant as an interaction term (i.e. an effect modifier) with black race for graft survival. Propensity score analysis was used to address potential confounding by indication. Results: In stratified Cox Regression analysis limited to IL2i, black race was significantly associated with graft loss (adjusted hazard ratio (AHR) 1.17, 95% CI, 1.09–1.26). In analysis limited to rATG induction, black race was not significant (AHR 1.00, 95% CI, 0.92–1.10). We detected a significant interaction between rATG and black race (in comparison with non-black race) for the development of graft loss (AHR, 0.86, 95% CI, 0.76–0.97). Analysis limited to black recipients showed that while use of rATG was not significantly different from IL2i (AHR 0.95, 95% CI 0.87–1.04), the direction of this association was in the opposite direction of non-blacks. Conclusions: Patient and graft survival were similar in African-American and Caucasian recipients of kidney transplantation using either rATG or IL2i. Limitations of the study are the retrospective nature of USRDS data, center-bias in using rATG vs. IL2i and lack of data on steroid dosage. Results of the present study call for a critical review of induction practices.

Incidence, predictors, costs, and outcome of renal cell carcinoma after kidney transplantation: USRDS experience.

Introduction. We carried out an analysis of the United States Renal Data System to determine the incidence, risk factors, prognosis, and costs associated with the diagnosis of renal cell carcinoma (RCC) after kidney transplantation. Methods. This is a retrospective cohort of 40,821 Medicare primary renal transplant recipients transplanted from January 1, 2000, to July 1, 2005, and followed up till December 31, 2005, excluding those with prior RCC or nephrectomy. Kaplan-Meier analysis was performed to determine the time of occurrence of RCC, and Cox regression was used to determine factors associated with RCC. Results. Three hundred sixty-eight patients were diagnosed with RCC within 3 years after transplant (incidence of 3.16 per 1000 person years). The 3-year incidence of RCC posttransplant was 9.29 per 1000 person years (2.3%) for those with pretransplant cysts and 3.08 per 1000 person years (0.7%) without pretransplant cysts. RCC was diagnosed disproportionately early posttransplant in patients with cysts. Cysts were independently associated with increased risk of RCC, as was male gender, older recipient, donor age, African American recipient, increased time on dialysis and acute rejection within first year posttransplant. RCC was associated with increased risk of mortality with a higher risk with pretransplant cysts. Patients who developed RCC had higher cumulative median costs (

Ethical dilemmas in patient selection for a new kidney transplant program in Guyana, South America.

55,456 at 2 years) than those who did not develop RCC (

Report of the First Peritoneal Dialysis Program in Guyana, South America

40,369). There was no “clustering” of RCC in individual states or centers more than would be expected by chance. Conclusion. RCC was diagnosed disproportionately early in patients with pretransplant renal cysts and was associated with a worse prognosis and increased costs.

Heavy Proteinuria as a Manifestation of Acute Allograft Rejection Presenting Early after Kidney Transplantation: A Retrospective, Single- Center Case Series

INTRODUCTION We describe ethical/moral issues in patient selection in a new living donor kidney transplant program in Guyana, South America. CASE REPORTS Over 3 years, we screened 450 patients with chronic kidney disease among which 70 were suitable for kidney transplantation. There were five patients whose evaluations raised possible ethical dilemmas: one had nonadherence to dialysis; two of Guyanese origin living abroad wished to have the transplant performed in Guyana; a minor wished to donate to her mother; and another subject was considering commercialization of the transplant process. RESULTS Since inception of the renal replacement program in 2008, we have completed 13 living kidney transplantations, 17 peritoneal dialysis placements, and 20 vascular access procedures. In the five patients wherein faced ethical dilemmas, three were rejected for consideration despite having living donors: one was nonadherent, the second excluded due to an attempt to commercialize the process, and the third, a minor who wished to donate to the mother. The other two patients were considered Guyanese ex-patriots acceptable for the program. DISCUSSION The consequence of kidney failure in Guyana prior to introduction of renal replacement therapy was a virtual death sentence. These cases illustrate ethical dilemmas serving to throw into stark relief the implications of decisions made in a developing country versus those in a developing country.

Current Status of Synthetic and Biological Grafts for Hemodialysis

♦ Introduction: In 2008, we initiated the first Guyanese comprehensive kidney replacement program, comprising hemodialysis (HD), peritoneal dialysis (PD), vascular access procedures, and living-donor kidney transplantation. The government of Guyana, US-based philanthropists, US-based physicians, and Guyanese caregivers teamed up to form a public-private partnership. This pilot program was free of cost to the patients. ♦ Methods: From July 2010 to the time of writing, we placed 17 patients with end-stage kidney disease on PD, which was used as a bridge to living-donor kidney transplantation. During the same period, we placed 12 primary arteriovenous fistulae. ♦ Results: The 17 patients who received a PD catheter had a mean age of 43.6 years and a mean follow-up of 5.3 months. In that group, 2 deaths occurred (from multi-organ failure) within 2 weeks of catheter placement, and 2 patients were switched to HD because of inadequate clearance. Technical issues were noted in 2 patients, and 3 patients developed peritonitis (treated with intravenous antibiotics). An exit-site abscess in 1 patient was drained under local anesthesia. The peritonitis rate was 0.36 episodes per patient-year. Of the 17 patients who received PD, 4 underwent living-donor kidney transplantation. ♦ Conclusions: In Guyana, PD is a safe and cost-effective option; it may be equally suitable for similar developing countries. In Guyana, PD was used as a bridge to living-donor kidney transplantation. We have been able to sustain this program since 2008 by making incremental gains and nurturing the ongoing public-private partnership.