Krista L. Lentine

Incidence and Predictors of Myocardial Infarction after Kidney Transplantation

The risk and predictors of post-kidney transplantation myocardial infarction (PTMI) are not well described. Registry data collected by the United States Renal Data System were used to investigate retrospectively PTMI among adult first renal allograft recipients who received a transplant in 1995 to 2000 and had Medicare as the primary payer. PTMI events were ascertained from billing and death records, and participants were followed for up to 3 yr after transplant or until the end of observation (December 31, 2000). Extended Coxs hazards analysis was used to identify independent clinical correlates of PTMI (hazard ratio [HR]) and to examine PTMI as an outcomes predictor. Among 35,847 eligible participants, the cumulative incidence of PTMI was 4.3% (95% confidence interval [CI], 4.1 to 4.5%), 5.6% (95% CI, 5.3 to 5.8%), and 11.1% (95% CI, 10.7 to 11.5%) at 6, 12, and 36 mo, respectively. Risk factors for PTMI included older recipient age, pretransplantation comorbidities (diabetes, angina, peripheral vascular disease, and MI), transplantation from older donors and deceased donors, and delayed graft function. Women, blacks, Hispanics, and employed recipients experienced reduced risk. The hazard of PTMI rose after a diagnosis of posttransplantation diabetes (HR, 1.60; 95% CI, 1.35 to 1.88) and markedly increased after graft failure (HR, 2.78; 95% CI, 2.41 to 3.19). In separate analyses, PTMI predicted death-censored graft failure (HR, 1.89; 95% CI, 1.63 to 2.20) and strongly predicted death in a manner that declined with time after PTMI. Risk factors for PTMI include potentially modifiable posttransplantation complications. Because PTMI in turn predicts graft failure and death, reducing the risk for PTMI may improve outcomes after kidney transplantation.

Racial Variation in Medical Outcomes among Living Kidney Donors

BACKGROUND Data regarding health outcomes among living kidney donors are lacking, especially among nonwhite persons. METHODS We linked identifiers from the Organ Procurement and Transplantation Network (OPTN) with administrative data of a private U.S. health insurer and performed a retrospective study of 4650 persons who had been living kidney donors from October 1987 through July 2007 and who had post-donation nephrectomy benefits with this insurer at some point from 2000 through 2007. We ascertained post-nephrectomy medical diagnoses and conditions requiring medical treatment from billing claims. Cox regression analyses with left and right censoring to account for observed periods of insurance benefits were used to estimate absolute prevalence and prevalence ratios for diagnoses after nephrectomy. We then compared prevalence patterns with those in the 2005-2006 National Health and Nutrition Examination Survey (NHANES) for the general population. RESULTS Among the donors, 76.3% were white, 13.1% black, 8.2% Hispanic, and 2.4% another race or ethnic group. The median time from donation to the end of insurance benefits was 7.7 years. After kidney donation, black donors, as compared with white donors, had an increased risk of hypertension (adjusted hazard ratio, 1.52; 95% confidence interval [CI], 1.23 to 1.88), diabetes mellitus requiring drug therapy (adjusted hazard ratio, 2.31; 95% CI, 1.33 to 3.98), and chronic kidney disease (adjusted hazard ratio, 2.32; 95% CI, 1.48 to 3.62); findings were similar for Hispanic donors. The absolute prevalence of diabetes among all donors did not exceed that in the general population, but the prevalence of hypertension exceeded NHANES estimates in some subgroups. End-stage renal disease was identified in less than 1% of donors but was more common among black donors than among white donors. CONCLUSIONS As in the general U.S. population, racial disparities in medical conditions occur among living kidney donors. Increased attention to health outcomes among demographically diverse kidney donors is needed. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others.)

Transplant Outcomes and Economic Costs Associated with Patient Noncompliance to Immunosuppression

We describe factors associated with immunosuppression compliance after kidney transplantation and examine relationships between compliance with allograft outcomes and costs. Medicare claims for immunosuppression in 15 525 renal transplant recipients with at least 1 year of graft function were used to calculate compliance as medication possession ratio. Compliance was categorized by quartiles as poor, fair, good and excellent. We modeled adjusted associations of clinical factors with the likelihood of persistent compliance by multiple logistic regressions (aOR), and estimated associations of compliance with subsequent graft and patient survival with Cox proportional hazards (aHR). Adolescent recipients aged 19–24 years were more likely to be persistently noncompliant compared to patients aged 24–44 years (aOR 1.49 [1.06–2.10]). Poor (aHR 1.80 [1.52–2.13]) and fair (aHR 1.63[1.37–1.93]) compliant recipients were associated with increased risks of allograft loss compared to the excellent compliant recipients. Persistent low compliance was associated with a

Cardiac Disease Evaluation and Management Among Kidney and Liver Transplantation Candidates A Scientific Statement From the American Heart Association and the American College of Cardiology Foundation

12 840 increase in individual 3‐year medical costs. Immunosuppression medication possession ratios indicative of less than the highest quartile of compliance predicted increased risk of graft loss and elevated costs. These findings suggest that interventions to improve medication compliance among kidney transplant recipients should emphasize the benefits of maximal compliance, rather than discourage low compliance.

Mycophenolate mofetil dose reductions and discontinuations after gastrointestinal complications are associated with renal transplant graft failure.

Endorsed by the American Society of Transplant Surgeons, American Society of Transplantation, and National Kidney Foundation Krista L. Lentine, MD, MS, Co-Chair; Salvatore P. Costa, MD, Co-Chair; Matthew R. Weir, MD, FAHA; John F. Robb, MD, FAHA; Lee A. Fleisher, MD, FAHA; Bertram L. Kasiske, MD; Robert L. Carithers, MD; Michael Ragosta, MD; Kline Bolton, MD; Andrew D. Auerbach, MD; Kim A. Eagle, MD, FAHA, Chair; on behalf of the American Heart Published by Elsevier Inc. http://dx.doi.org/10.1016/j.jacc.2012.05.008

MELD Exceptions and Rates of Waiting List Outcomes

Background. Mycophenolate mofetil (MMF) use in renal transplantation has steadily increased since 1995 because of its ability to lower the risks of rejection and chronic allograft nephropathy. However, significant gastrointestinal (GI) complications may lead to MMF dose reductions and discontinuations. Little is known of the association between MMF dose reductions and discontinuations following GI complications and graft survival. Methods. Using the United States Renal Data System, we identified 3,675 adult recipients (age ≥18) with a diagnosed GI complication who were prescribed MMF at the time of first GI diagnosis and had Medicare as their primary insurer. MMF doses were ascertained from Medicare payment records. We estimated risk of graft loss associated with MMF dose adjustments after GI diagnosis: dosage unchanged (reference), reduced <50%, reduced ≥50%, and MMF discontinued. Patients were followed until graft loss, death, last recorded immunosuppression prescription, or 3 years posttransplant. Results. Compared to those with no MMF dose reductions or discontinuations, the risk of graft failure increased with MMF doses reduction ≥50% (HR=2.36, 95% CI 1.23–4.54) and those with MMF discontinuation (2.72, CI 1.60–4.64). Conclusion. Renal transplant recipients who underwent MMF dose reduction or withdrawal following GI diagnosis are associated with increased risk of graft failure.

Progressive Multifocal Leukoencephalopathy and Use of Mycophenolate Mofetil After Kidney Transplantation

Model for End‐stage Liver Disease (MELD)‐based allocation of deceased donor livers allows exceptions for patients whose score may not reflect their true mortality risk. We hypothesized that organ procurement organizations (OPOs) may differ in exception practices, use of exceptions may be increasing over time, and exception patients may be advantaged relative to other patients. We analyzed longitudinal MELD score, exception and outcome in 88 981 adult liver candidates as reported to the United Network for Organ Sharing from 2002 to 2010. Proportion of patients receiving an HCC exception was 0–21.4% at the OPO‐level and 11.9–18.8% at the region level; proportion receiving an exception for other conditions was 0.0%–13.1% (OPO‐level) and 3.7–9.5 (region‐level). Hepatocellular carcinoma (HCC) exceptions rose over time (10.5% in 2002 vs. 15.5% in 2008, HR = 1.09 per year, p<0.001) as did other exceptions (7.0% in 2002 vs. 13.5% in 2008, HR = 1.11, p<0.001). In the most recent era of HCC point assignment (since April 2005), both HCC and other exceptions were associated with decreased risk of waitlist mortality compared to nonexception patients with equivalent listing priority (multinomial logistic regression odds ratio [OR] = 0.47 for HCC, OR = 0.43 for other, p<0.001) and increased odds of transplant (OR = 1.65 for HCC, OR = 1.33 for other, p<0.001). Policy advantages patients with MELD exceptions; differing rates of exceptions by OPO may create, or reflect, geographic inequity.

A Retrospective Analysis of Immunosuppression Compliance, Dose Reduction and Discontinuation in Kidney Transplant Recipients

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.

Cardiac Disease Evaluation and Management Among Kidney and Liver Transplantation Candidates

We describe factors associated with poor compliance and dose reductions and examine the relative impact of compliance, dose reduction and discontinuation on graft outcome.

Kidney Failure Risk Projection for the Living Kidney Donor Candidate

The challenges inherent in conducting accurate, clinically effective, and cost-effective cardiac evaluations among transplantation candidates relate to the large size of the target population, the prevalence of disease, the limited number of donated organs, and the often extended waiting periods