Caren Rose

Sirolimus Is Associated with New-Onset Diabetes in Kidney Transplant Recipients

New-onset diabetes (NOD) is associated with transplant failure. A few single-center studies have suggested that sirolimus is associated with NOD, but this is not well established. With the use of data from the United States Renal Data System, this study evaluated the association between sirolimus use at the time of transplantation and NOD among 20,124 adult recipients of a first kidney transplant without diabetes. Compared with patients treated with cyclosporine and either mycophenolate mofetil orazathioprine, sirolimus-treated patients were at increased risk for NOD, whether it was used in combination with cyclosporine (adjusted hazard ratio [HR] 1.61; 95% confidence interval [CI] 1.36 to 1.90),tacrolimus (adjusted HR 1.66; 95% CI 1.42 to 1.93), or an antimetabolite (mycophenolate mofetil orazathioprine; adjusted HR 1.36; 95% CI 1.09 to 1.69). Similar results were obtained in a subgroup analysis that included the 16,861 patients who did not have their immunosuppressive regimen changed throughout the first posttransplantation year. In conclusion, sirolimus is independently associated with NOD. Given the negative impact of NOD on posttransplantation outcomes, these findings should be confirmed in prospective studies or in meta-analyses of existing trials that involved sirolimus.

Impact of Acute Rejection and New-Onset Diabetes on Long-Term Transplant Graft and Patient Survival

BACKGROUND AND OBJECTIVES Development of new therapeutic strategies to improve long-term transplant outcomes requires improved understanding of the mechanisms by which these complications limit long-term transplant survival. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS The association of acute rejection and new-onset diabetes was determined in the first posttransplantation year with the outcomes of transplant failure from any cause, death-censored graft loss, and death with a functioning graft in 27,707 adult recipients of first kidney-only transplants, with graft survival of at least 1 yr, performed between 1995 and 2002 in the United States. RESULTS In multivariate analyses, patients who developed acute rejection or new-onset diabetes had a similar risk for transplant failure from any cause, but the mechanisms of transplant failure were different: Acute rejection was associated with death-censored graft loss but only weakly associated with death with a functioning graft. In contrast new-onset diabetes was not associated with death-censored graft loss but was associated with an increased risk for death with a functioning graft. CONCLUSIONS Acute rejection and new-onset diabetes have a similar impact on long-term transplant survival but lead to transplant failure through different mechanisms. The mechanisms by which new-onset diabetes leads to transplant failure should be prospectively studied. Targeted therapeutic strategies to minimize the impact of various early posttransplantation complications may lead to improved long-term outcomes.

Survival among nocturnal home haemodialysis patients compared to kidney transplant recipients

BACKGROUND Kidney transplantation is the gold standard renal replacement therapy. Nocturnal haemodialysis (NHD) is an intensive dialysis modality (6-8 h/session, 3-7 sessions/week) associated with a significant improvement of clinical and biochemical parameters compared to conventional dialysis. To date, no studies have compared survival in patients treated with NHD and kidney transplantation. METHODS Using data from two regional NHD programmes and the USRDS from 1994 to 2006, we performed a matched cohort study comparing survival between NHD and deceased and living donor kidney transplantation (DTX and LTX) by randomly matching NHD patients to transplant recipients in a 1:3:3 ratio. The independent association of treatment modality with survival was determined using Cox multivariate regression. RESULTS The total study population consisted of 177 NHD patients matched to 1062 DTX and LTX recipients (total 1239 patients) followed for a maximum of 12.4 years. During the follow-up period, the proportion of deaths among NHD, DTX and LTX patients was 14.7%, 14.3% and 8.5%, respectively (P = 0.006). We found no difference in the adjusted survival between NHD and DTX (HR 0.87, 95% CI 0.50-1.51; NHD reference group), while LTX survival was better (HR 0.51, 95% CI 0.28-0.91). CONCLUSIONS These results indicate that NHD and DTX survival is comparable, and suggest that this intensive dialysis modality may be a bridge to transplantation or even a suitable alternative in the absence of LTX in the current era of growing transplant waiting lists and organ shortage.

Nephrectomy After Transplant Failure: Current Practice and Outcomes

The role of transplant nephrectomy after transplant failure is uncertain. We report the use and consequences of transplant nephrectomy among 19 107 transplant failure patients between 1995 and 2003 in the United States. Among 3707 patients with early transplant failure (graft survival <12 m), nephrectomy was performed in 56%, and was associated with an increased risk of death (HR 1.13, 95% CI 1.01–1.26). In contrast, among 15 400 patients with late transplant failure (graft survival ≥12 m), nephrectomy was performed in 27%, and was associated with a decreased risk of death (HR 0.89, 95% CI 0.83–0.95). In early transplant failure patients, nephrectomy was associated with a lower risk of repeat transplant failure (HR 0.72, 95% CI 0.56–0.94), while among late transplant failure patients; nephrectomy was associated with a higher risk of repeat transplant failure (HR 1.20, 95% CI 1.02–1.41). Definitive conclusions are not possible from this observational study. The role of nephrectomy in the management of dialysis treated transplant failure patients, and the implications of nephrectomy for repeat transplantation should be further studied in prospective studies.

Cancer Mortality in Kidney Transplantation

Immunosuppression is associated with an increased risk of cancer in kidney transplant recipients compared to the general population. It is less clear whether standardized cancer mortality ratios (SMRs) are also increased. This studys hypothesis is that SMRs are not increased because of competing risks of death. During the median follow‐up of 5.05 years (Q1–Q3: 2.36–8.62), there were 1937 cancer deaths and 36 619 noncancer deaths among 164 078 first kidney‐only transplant recipients captured in the United States Renal Data System between January 1990 and December 2004. The observed cancer death rate was 206 per 100 000 patient‐years compared to an expected rate of 215 per 100 000 patient‐years in the general population. The overall age‐ and sex‐adjusted SMR was only 0.96 (95% CI 0.92–1.00). However, patients <50 years had SMRs significantly greater than unity while patients >60 had SMRs lower than unity. Up to 25% of cancer‐related deaths occurred after allograft failure. These findings challenge the notion that cancer is a major cause of premature death in all kidney transplant recipients and has implications for design of cancer prevention strategies in kidney transplant recipients.

The Pregnancy Rate and Live Birth Rate in Kidney Transplant Recipients

Fertility is one of the potential benefits for women undergoing kidney transplantation; however, population‐based information about the likelihood of pregnancy and successful fetal outcome is not available. In this observational study of 16 195 female kidney transplant recipients aged 15–45 years in the United States between 1990 and 2003, we determined the pregnancy rate and live birth rate using Medicare claims data from the first three posttransplant years. The pregnancy rate was 33 per thousand female transplant recipients between 1990 and 2003 and progressively declined from 59 in 1990 to 20 in 2000. The live birth rate between 1990 and 2003 was 19 per thousand female transplant recipients and declined in parallel with the pregnancy rate. Despite a decrease in therapeutic abortions over time, the proportion of pregnancies resulting in fetal loss (45.6%) remained constant during the study due to an increase in spontaneous abortions and other causes of fetal loss. The pregnancy rate in kidney transplant recipients was markedly lower and declined more rapidly than reported in the general American population during the same period. The live birth rate was substantially lower than reported in voluntary registries of transplant recipients, and the proportion of pregnancies resulting in unexpected fetal loss increased over time.

A Systematic Review of Patient Inflammatory Bowel Disease Information Resources on the World Wide Web

BACKGROUND AND AIMS:The Internet is a widely used information resource for patients with inflammatory bowel disease, but there is variation in the quality of Web sites that have patient information regarding Crohns disease and ulcerative colitis. The purpose of the current study is to systematically evaluate the quality of these Web sites.METHODS: The top 50 Web sites appearing in Google™ using the terms “Crohns disease” or “ulcerative colitis” were included in the study. Web sites were evaluated using a (a) Quality Evaluation Instrument (QEI) that awarded Web sites points (0–107) for specific information on various aspects of inflammatory bowel disease, (b) a five-point Global Quality Score (GQS), (c) two reading grade level scores, and (d) a six-point integrity score.RESULTS: Thirty-four Web sites met the inclusion criteria, 16 Web sites were excluded because they were portals or non-IBD oriented. The median QEI score was 57 with five Web sites scoring higher than 75 points. The median Global Quality Score was 2.0 with five Web sites achieving scores of 4 or 5. The average reading grade level score was 11.2. The median integrity score was 3.0.CONCLUSIONS: There is marked variation in the quality of the Web sites containing information on Crohns disease and ulcerative colitis. Many Web sites suffered from poor quality but there were five high-scoring Web sites.

The survival benefit of kidney transplantation in obese patients.

Obese patients have a decreased risk of death on dialysis but an increased risk of death after transplantation, and may derive a lower survival benefit from transplantation. Using data from the United States between 1995 and 2007 and multivariate non‐proportional hazards analyses we determined the relative risk of death in transplant recipients grouped by body mass index (BMI) compared to wait‐listed candidates with the same BMI (n = 208 498). One year after transplantation the survival benefit of transplantation varied by BMI: Standard criteria donor transplantation was associated with a 48% reduction in the risk of death in patients with BMI ≥ 40 kg/m2 but a ≥66% reduction in patients with BMI < 40 kg/m2. Living donor transplantation was associated with ≥66% reduction in the risk of death in all BMI groups. In sub‐group analyses, transplantation from any donor source was associated with a survival benefit in obese patients ≥50 years, and diabetic patients, but a survival benefit was not demonstrated in Black patients with BMI ≥ 40 kg/m2. Although most obese patients selected for transplantation derive a survival benefit, the benefit is lower when BMI is ≥40 kg/m2, and uncertain in Black patients with BMI ≥ 40 kg/m2.

Access to kidney transplantation among remote- and rural-dwelling patients with kidney failure in the United States.

CONTEXT US residents with end-stage renal disease (ESRD) may live far away from the closest transplant center, which could compromise their access to kidney transplantation. OBJECTIVE To assess access to kidney transplantation as a function of distance from the closest transplant center or as a function of rural rather than urban residence. DESIGN, SETTING, AND PARTICIPANTS Observational study of 699,751 adult patients with kidney failure who had initiated renal replacement in the United States between 1995 and 2007 and were thus placed on a prospective mandatory registry list. MAIN OUTCOME MEASURES Time to placement on the kidney transplant waiting list and time to kidney transplantation, both measured at the start of renal replacement. RESULTS During a median follow-up of 2.0 years (range, 0.0-12.5 years), 122,785 (17.5%) patients received a kidney transplant. Median distance to the closest transplant center was 15 miles. Participants were classified into distance categories by miles from a transplant center with 0 to 15 miles serving as the referent category. Compared with the referent category, the adjusted hazard ratios of deceased or living donor transplantation within each category follows: 16 to 50 miles, 1.03 (95% CI, 1.02-1.05); 51 to 100 miles, 1.11 (95% CI, 1.09-1.12); 101 to 136 miles, 1.14 (95% CI, 1.11-1.17); 137 to 231 miles, 1.16 (95% CI, 1.13-1.20); 232 to 310 miles, 1.20 (95% CI, 1.12-1.28); and more than 310 miles, 1.16 (95% CI, 1.09-1.23). When residence location was classified using rural-urban commuter areas, 79.6% of patients lived in urban; 10.3%, micropolitan; and 10.0%, rural areas. Compared with those living in metropolitan areas, the adjusted hazard ratios of deceased or living donor transplantation among patients residing in micropolitan communities was 1.13 (95% CI, 1.11-1.15) and 1.15 (95% CI, 1.13-1.18) for rural areas. Results were similar for both deceased donor and living donor transplantation and were consistent in multiple sensitivity analyses. CONCLUSION Remote or rural residence was not associated with increased time to kidney transplantation among people treated for ESRD in the United States.

Living Donor Age and Kidney Allograft Half-Life: Implications for Living Donor Paired Exchange Programs

BACKGROUND AND OBJECTIVES Living donor paired exchange programs assume that kidneys from living donors are of comparable quality and anticipated longevity. This study determined actual allograft t(1/2) within different recipient age groups (10-year increments) as a function of donor age (5-year increments), and juxtaposed these results against the probabilities of deceased donor transplantation, and exclusion from transplantation (death or removal from the wait-list). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Data from the US Renal Data System (transplant dates 1988-2003 with follow-up through September 2007) were used to determine allograft t(1/2), whereas data from patients on the United Network for Organ Sharing waiting list between 2003 and 2005 (with follow-up through February 2010) were used to determine wait-list outcomes. RESULTS With the exception of recipients aged 18-39 years, who had the best outcomes with donors aged 18-39 years, living donor age between 18 and 64 years had minimal effect on allograft t(1/2) (difference of 1-2 years with no graded association). The probability of deceased donor transplantation after 3 years of wait-listing ranged from 21% to 66% by blood type and level of sensitization, whereas the probability of being excluded from transplantation ranged from 6% to 27% by age, race, and primary renal disease. CONCLUSIONS With the exception of recipients aged 18-39 years, living donor age between 18 and 64 years has minimal effect on allograft survival.