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Background: Centers for Disease Control and Prevention guidelines recommend caution in prescribing opioids for chronic pain. The characteristics of opioid prescription (OpRx) among kidney transplant (KTx) recipients have not been described in a national population., Methods: We assessed OpRx prevalence among prevalent KTx recipients, and associated duration (long-term, defined as ≥90 days in a year) and dosing (in morphine milligram equivalents per day of <50, 50-89, and ≥90) with outcomes, death and graft loss, among incident KTx recipients using 2006-2010 US Renal Data System files, including Medicare Part D for medication ascertainment. Cox models controlled for recipient factors., Results: Of 36,486 KTx recipients in the 2010 prevalent cohort, approximately 14.6% had long-term OpRx. The strongest association with long-term OpRx after KTx was long-term OpRx before KTx (64%; adjusted odds ratio, 95% confidence interval, 95.2, 74.2-122.1). Incident KTx recipients with long-term OpRx had increased risk of mortality and graft loss compared with those without OpRx or short-term OpRx after KTx. This risk was highest among recipients with long-term OpRx doses of ≥90 morphine milligram equivalents or higher per day (adjusted hazard ratio, 95% confidence interval, 1.61, 1.24-2.10 for death, and 1.33, 1.05-1.67 for graft loss, respectively)., Conclusions: In contrast to either no or short-term OpRx, long-term, and especially long-term high-dose OpRx, is associated with increased risk of death and graft loss in US KTx recipients. Causal relationships cannot be inferred, and OpRx may be an illness marker. Nevertheless, efforts to treat pain effectively in KTx recipients with less toxic interventions and decrease OpRx deserve consideration.

Background: An analysis of income and racial/ethnic disparities on renal transplant outcomes in recipients with lupus nephritis (LN) has not been reported. We analyzed the United States Renal Data System database to assess the impact of these disparities on graft loss and death in the LN and non-LN cohorts., Methods: We identified 4214 patients with LN as the cause of end-stage renal disease in a retrospective cohort of 150,118 patients first transplanted from January 1, 1995 to July 1, 2006. We merged data on median household income from the United States Census based on the ZIP code., Results: In multivariate Cox regression analyses, African-Americans (AF) recipients with LN (vs. non-AF) had an increased risk of graft loss (adjusted hazard ratio [AHR], 1.39; 95% confidence interval [CI], 1.21-1.60) and death (AHR, 1.33; 95% CI, 1.09-1.63). Furthermore, there were significant associations of lower-income quintiles with higher risk for graft loss and death among AF with LN. In comparison, among non-AF recipients with LN, income levels did not predict risk for transplant outcomes. The racial disparity for both graft loss and death outcomes among AF with LN was greater than among AF without LN (AHR, 1.32; 95% CI, 1.29-1.36 for graft loss and AHR, 1.02; 95% CI, 0.99-1.05 for death)., Conclusions: AF kidney transplant recipients with LN were at increased risk for graft loss and death compared with non-AF. Income levels were associated with the risk of graft loss and death in AF but not in non-AF recipients with LN.

Background: Mortality records identify cancer as the leading cause of death among living kidney donors, but information on the burden of cancer outside death records is limited in this population., Methods: We examined a database wherein U.S. Organ Procurement and Transplantation Network identifiers for 4,650 living kidney donors in 1987 to 2007 were linked to administrative data of a U.S. private health insurer (2000-2007 claims) to identify postdonation cancer diagnoses. Skin cancer and non-skin cancer diagnoses were ascertained from International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes on billing claims. Donors were also matched one-to-one with general insurance beneficiaries by sex and age when benefits began. Diagnosis rates within observation windows were compared as rate ratios., Results: The median time from donation to the end of plan insurance enrollment was 7.7 years, with a median observation period of 2.1 years. Skin cancer rates were similar among prior living donors in the observation period and nondonor controls (rate ratio, 0.91; 95% confidence interval [CI], 0.59-1.40). In contrast, the rate of total non-skin cancers was significantly less common among donors than among controls (rate ratio, 0.74; 95% CI, 0.55-0.99), although reduced relative risk was limited to donors captured earlier in relation to donation. Several cases of cancer diagnosis (uterine, melanoma, "other") were identified within the first year after donation. Prostate cancer diagnosis was significantly more common among living donors compared with controls (rate ratio, 3.80; 95% CI, 1.42-10.2)., Conclusions: Continued study of cancer after kidney donation is warranted to ensure that evaluation, selection, and long-term follow-up support overall good health of the donor.

Introduction: The current pattern of evaluation for living kidney donors was investigated., Methods: We designed a 37-question electronic survey to collect information about living kidney donor evaluation. Of the 181 United Network for Organ Sharing (UNOS)-approved centers, 72 responded. Survey responses were coded and downloaded into SPSS. Data was expressed as means and standard deviations or the percentage of centers with specific responses., Results: 66% of the centers used a cut-off of <80 ml/min for exclusion of living kidney donors. 24-hour urine measuring creatinine clearance (CrCl) was the most common screening method for glomerular filtration rate (GFR) assessment in potential living donors. 56% of the centers excluded donors with blood pressure (BP) >140/90, whereas 22.7 and 7.1% excluded patients with pre-hypertension with a cut-off BP of 130/85 and 120/80, respectively. 66% of the centers used 24-hour urine creatinine to assess for proteinuria. 20% of the centers accepted living kidney donors with microalbuminuria and 84% accepted patients with a history of nephrolithiasis. 24% of the centers reported use of formal cognitive testing of potential living donors., Discussion: There were significant variations in exclusion criteria based on GFR, history of kidney stones, body mass index, BP and donors with urinary abnormalities. The definitions for hematuria and proteinuria were variable. There is a need for uniformity in selection and for a living donor registry. We also recommend raising the cut-off for estimated GFR to 90 ml/min to account for 10-15% overestimation when CrCl is used., (Copyright © 2012 S. Karger AG, Basel.)

Background: We investigated the effect of smoking on postkidney transplant outcomes in the United States Renal Data System., Methods: In a retrospective cohort of 41,705 adult Medicare primary renal transplant recipients in the United States Renal Data System database transplanted from January 1, 2000, to June 30, 2006, and followed through October 31, 2006, we assessed Medicare claims for smoking. The association between renal allograft loss and death and smoking as a time-dependent variable was assessed with Cox nonproportional hazards regression., Results: Of 41,705 Medicare primary adult renal transplant patients, there were 9.9% patients who had evidence of prior smoking and 4.6% patients with new claims for smoking after transplant. Incident smoking (new onset smokers) occurred at a mean of 1.29±0.88 years after transplant. In the adjusted analysis, factors associated with new smoking included male gender, history of drug or alcohol use, history of chronic obstructive pulmonary disease, and later year of transplant. Compared with never smokers, incident smoking after transplant was associated with increased risk of death-censored allograft loss (adjusted hazard ratio [AHR] 1.46 [95% confidence interval {CI}: 1.19-1.79]; P<0.001) and death (AHR 2.32 [95% CI: 1.98-2.72]; P<0.001). In a sensitivity analysis excluding patients with history of chronic obstructive pulmonary disease, similar results were obtained with increased risk of death-censored allograft loss (AHR 1.43 [95% CI: 1.16-1.76]; P=0.001) and death (AHR 2.26 [95% CI: 1.91-2.66]; P<0.001)., Discussion: Incident smoking was detrimental to graft and patient survival. Transplant programs should screen those at risk during transplant follow-up and have smoking cessation programs.

Background: We previously reported that posttransplant lymphoproliferative disorders (PTLD) occurred more frequently in non-African American (AF) kidney transplant recipients. An in-depth analysis of racial differences in the development of PTLD has not been reported., Methods: We assessed Medicare claims for PTLD in a retrospective cohort of 53,719 patients who underwent transplantation from January 2000 to September 2006 and followed up through December 2007., Results: There were 719 (1.3%) patients with claims for PTLD. Non-AF recipient race (including all races analyzed separately, adjusted hazard ratio [AHR] 1.38, 95% confidence interval [CI] 1.13-1.68), recipient Epstein-Barr virus (EBV) immunoglobulin G (IgG) seronegative status (AHR 1.88, 95% CI 1.53-2.34), and de novo sirolimus (AHR 1.22, 95% CI 1.03-1.45) were associated with an increased risk of PTLD. Furthermore, de novo sirolimus showed a significant interaction with EBV IgG; among EBV IgG-negative recipients, sirolimus use was significant (P = 0.003), but among EBV IgG-positive recipients, it was not significant (P = 0.18). EBV IgG-seronegative status was significant in all races except for AFs, and racial differences were a significant effect modifier for EBV IgG status and risk of PTLD. Mortality subsequent to PTLD did not differ by race. CONCLUSIONS.: AF kidney transplant recipients were at lower risk for PTLD, irrespective of the recipient EBV IgG serostatus. On the contrary, recipient EBV IgG-seronegative status was associated with a higher risk of PTLD in the non-AF population. De novo sirolimus therapy was associated with increased risk of PTLD in EBV IgG-negative recipients, regardless of race.

Background: Posttransplant neutropenia (PTN) is relatively common after kidney transplantation, and may result in a reduction of immunosuppression, which may precipitate acute rejection. Granulocyte colony-stimulating factors (GCSF) have been used to treat PTN, although outcomes associated with use of this medication in this population are unknown., Methods: In a retrospective cohort of 41,705 adult Medicare primary patients transplanted from January 2001 to June 2006, we assessed Medicare claims for neutropenia, leukopenia, and GCSF use, respectively. Outcomes included allograft loss and death., Results: There were 6043 (14.5%) patients with claims for PTN. Factors associated with PTN included female gender, Caucasian ethnicity, ischemic heart disease, donor cytomegalovirus positive, deceased donor, expanded donor criteria, delayed graft function, elevated panel reactive antibody, higher human leukocyte antigen mismatch, and later year of transplant. Thymoglobulin induction, tacrolimus, and mycophenolate mofetil were also associated. PTN was less frequent among patients with congestive heart failure, recipient cytomegalovirus positive, and interleukin-2 induction. PTN was associated with increased risk of allograft loss (adjusted hazard ratio, 1.59; 95% confidence interval, 1.43-1.76; P<0.001) and death (adjusted hazard ratio, 1.74; 95% confidence interval, 1.59-1.90; P<0.001). Of the 6043 patients with PTN, 740 (12.2%) received GCSF. Patients who received GCSF had a lower risk of death on unadjusted analysis, but this only trended towards significance after adjustment., Conclusions: Neutropenia after renal transplantation is common and is associated with an increased risk of allograft loss and death. GCSF was used in 12% of cases and did not increase risk of allograft loss. Strategies to avoid PTN and greater use of GCSF may be indicated to prevent graft loss and death.

Background: Little is known about associations of family health history with outcomes after kidney donation., Methods: Using a database wherein Organ Procurement and Transplantation Network identifiers for 4650 living kidney donors in 1987 to 2007 were linked to administrative data of a US private health insurer (2000-2007 claims), we examined associations of recipient illness history as a measure of family history with postdonation diagnoses and drug-treatment for hypertension and diabetes. Cox regression with left and right censoring was applied to estimate associations (adjusted hazards ratios, aHR) of recipient illness history with postnephrectomy donor diagnoses, stratified by donor-recipient relationship., Results: Recipient end-stage renal disease from hypertension, as compared with other recipient end-stage renal disease causes, was associated with modest, significant increases in the age- and gender-adjusted relative risks of hypertension diagnosis (aHR, 1.37%; 95% confidence interval [CI], 1.08-1.74) after donor nephrectomy among related donors. After adjustment for age, gender, and race, recipient type 2 diabetes compared with non-diabetic recipient status was associated with twice the relative risk of postdonation diabetes (aHR, 2.14; 95% CI, 1.28-3.55; P=0.003) among related donors. These patterns were significant among white but not among non-white related donors. Recipient type 1 diabetes was associated with postdonation diabetes only in black related donors (aHR, 3.22; 95% CI, 1.04-9.98; P=0.04). Recipient illness did not correlate significantly with outcomes in unrelated donors., Conclusions: These data support a need for further study of family health history as a potential sociodemographic correlate of donor outcomes, including examination of potential mediating factors and variation in risk discrimination among donors of different racial groups.

Background: Limited data are available on the use of potentially cardioprotective medications among U.S. kidney transplant recipients., Methods: We constructed a database wherein Organ Procurement and Transplant Network identifiers for kidney transplant recipients were linked to billing records of a private health insurer (2003-2006 claims). Transplant recipients and general beneficiaries with acute myocardial infarction (AMI) events were identified by diagnosis codes. The healthcare process measures of interest comprised prescription fills for beta-blockers, antiplatelet drugs, angiotensin-converting enzyme inhibitors/angiotensin-2 receptor blockers, and β-hydroxy-β-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors (statins) within 60 days after AMI. Medication use was compared in transplant and general patients by multivariable regression and by one-to-one matching for demographic and clinical factors including comorbidities and revascularization status., Results: We identified 192 kidney transplant recipients and 52,021 general patients who survived with insurance benefits more than or equal to 60 days after AMI diagnosis. In multiple logistic regression, transplant status was independently associated with increased likelihood of beta-blocker (adjusted odds ratio, 2.50; 95% confidence interval, 1.70-3.68; P<0.0001) and statin (adjusted odds ratio, 1.78; 95% confidence interval, 1.28-2.48; P=0.0006) use after AMI. Similarly kidney transplant recipients with AMI more commonly received beta-blockers (83.0% vs. 65.9%; P=0.0001) and statins (72.0% vs. 62.6%; P=0.04) compared with matched controls. Use of antiplatelet agents and angiotensin-converting enzyme inhibitors/angiotensin-2 receptor blockers did not differ significantly by transplant status., Conclusions: Although kidney transplant status does not seem to be a barrier to medication use after AMI, there may be opportunities for improving cardiovascular risk management in high-risk transplant recipients. Administrative records offer a practical tool for monitoring cardiovascular complications and healthcare delivery not tracked in national registries.

Background and Objectives: Influenza vaccination is recommended in all renal transplant recipients. However, immunosuppression in the early period post-transplant may attenuate the immunologic response to the vaccine. Additionally, it has been theorized that vaccination can induce an immune response that could trigger rejection episodes., Design, Setting, Participants, & Measurements: In a retrospective cohort of 51,730 adult Medicare primary patients who were first transplanted from January 2000 to July 2006 and followed through October 2006, we assessed Medicare claims for influenza vaccination and influenza infections, respectively. Outcomes included allograft loss and death., Results: There were 9678 (18.7%) patients with claims for influenza vaccination in the first year post-transplant. Factors associated with vaccination included older age, diabetes, later year of transplant, and tacrolimus or mycophenolate at discharge. Vaccinations were less frequent among men, African Americans, highly sensitized patients, or those receiving induction immunosuppression or expanded criteria donor kidneys. Vaccination in the first year after transplant was associated with lower risk of subsequent allograft loss and death. Claims for influenza infection were reported in 310 (0.6%) patients and were not significantly associated with graft loss, although there was a trend toward death., Conclusions: In the first year after renal transplantation, influenza vaccination was associated with a lower risk of subsequent allograft loss and death. Although this study cannot comment on formation of protective antibodies after vaccination, these data do not support withholding vaccination on the basis of concerns of adversely affecting allograft function., (Copyright © 2011 by the American Society of Nephrology)

Background: We examined the United States Renal Data System registry to analyze trends in renal transplantation in patients with human immunodeficiency virus (HIV) infection., Methods: A retrospective cohort study was performed using the United States Renal Data System, analyzing patients receiving renal transplants from January 1, 1995, to September 29, 2006. Factors independently associated with transplantation in HIV-infected patients with end-stage renal disease were identified., Results: There was a significant increase in renal transplant recipients who were HIV seropositive who received renal transplants from 2001 to 2006 (n=208, 0.26%) versus 1995 to 2000 era (n=43, 0.06%, P<0.001). Before 2001, only 18 states performed renal transplants in HIV-infected patients, whereas most states transplanted HIV-infected patients in the second era. There were more African American recipients with HIV infection from 2001 to 2006 compared with the earlier cohort (n=118 vs. 8, P<0.001). Patients with HIV infection were more likely to have received induction therapy (n=121 vs. 37, P<0.001) and tacrolimus maintenance suppression (n=105 vs. 13, P<0.001) in the latter era. There were also more deceased donor transplants from 2001 to 2006 (n=143 vs. 25, P<0.001). In logistic regression analysis, when adjusted for multiple factors including recipient and donor age, race, gender, and donor type, patients with HIV infection were more likely to have been transplanted after 2001 (adjusted odds ratio, 2.21; 95% confidence interval=1.49-3.28). In analysis adjusted for multiple factors including hepatitis C virus coinfection, HIV infection was not significantly associated with all-cause graft loss., Conclusions: There has been a dramatic increase in the number of transplants among HIV-infected patients. These findings suggest improved access to transplant wait listing and better management of immunosuppression, especially among African American patients., (© 2011 by Lippincott Williams & Wilkins)

Introduction: Alemtuzumab and rabbit antithymocyte globulin (rATG) are being used with increasing frequency as induction agents in kidney transplantation. Using the US Renal Data Base System, we analyzed the safety profile of these agents in the elderly., Methods: In a cohort of patients transplanted from January 2000 to July 2009 and followed through 2009, we assessed the effect of induction on allograft loss and death among elderly recipients. Recipients were censored at dates of allograft loss, death or the end of study. Independent associations between induction agents and allograft loss or death were examined using multivariate analysis with forward stepwise Cox regression., Results: Among 130,402 patients with first transplants, 14,907 were age 65 years or older. 4,466 (30%), 3,049 (20.5%), 1,501 (10.1%), and 999 (6.7%) were induced with thymoglobulin, basiliximab, daclizumab, and alemtuzumab, respectively. After adjusting for baseline differences, induction with alemtuzumab was associated with an increased risk of graft loss and death, with an adjusted hazard ratio (AHR) of 1.26 (95% CI 1.08-1.48). Risk was also present at other age cutoffs [age >60 (AHR 1.16; 95% CI 1.03-1.31; p = 0.014), age >70 (AHR 1.43; 95% CI 1.13-1.81; p = 0.003) and age >75 (AHR 1.68; 95% CI 1.07-2.63; p = 0.024)]., Conclusions: In the elderly, alemtuzumab is associated with an escalating risk of death and graft loss in recipients of kidney transplantations., (Copyright © 2011 S. Karger AG, Basel.)

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

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.)

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 (Fisher's exact test used for violations of Cochran's assumptions) and Student's 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.

Cardiovascular disease is the most common cause of death after kidney transplantation. However, uncertainties regarding the optimal assessment of cardiovascular risk in potential transplant candidates have produced controversy and inconsistency in pretransplantation cardiac evaluation practices. In this review, we consider the evidence supporting cardiac evaluation in kidney transplant candidates, generally focused on coronary artery disease, according to the World Health Organization principles for screening. The importance of pretransplant cardiac evaluation is supported by the high prevalence of coronary artery disease and the incidence and adverse consequences of acute coronary syndromes in this population. Testing for coronary artery disease may be performed noninvasively by using modalities that include nuclear myocardial perfusion studies and dobutamine stress echocardiography. These tests have prognostic value for mortality, but imperfect sensitivity and specificity for detecting angiographically defined coronary artery disease in patients with end-stage renal disease. Associations of angiographically-defined coronary artery disease with subsequent survival also are inconsistent, likely because plaque instability is more critical for infarction risk than angiographic stenosis. The efficacy and best methods of myocardial revascularization have not been examined in large contemporary clinical trials in patients with end-stage renal disease. Biomarkers, such as cardiac troponin, have prognostic value in end-stage renal disease, but require further study to determine clinical applications in directing more expensive and invasive cardiac evaluation., (Copyright 2009 National Kidney Foundation, Inc. All rights reserved.)

Background: There are several case reports of rhabdomyolysis (RM) in renal transplant recipients, but the actual incidence of this complication is not known. Most of the reported cases have been attributed to drug-drug interactions with calcineurin inhibitors, with the majority of interactions reported between cyclosporine and 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins). Pharmacokinetic studies have demonstrated that cyclosporine increases statin drug levels, presumably via competitive inhibition of cytochrome P450 3A4., Methods: In a retrospective cohort of 20 366 adult Medicare primary renal transplant recipients in the USRDS database transplanted from 1 January 2003 to 31 July 2005 and followed through 31 December 2005, we assessed Medicare claims for RM and dyslipidaemia (HPL), which was used as a surrogate for statin use., Results: The incidence rate of RM post-transplant for the study period was 1.4 (95% CI 1.1-1.8) per 1000 person-years. By Cox regression analysis, cyclosporine (versus tacrolimus) use [AHR 2.36 (95% CI 1.23-4.35); P = 0.006] and black race [AHR 2.33 (95% CI 1.30-4.17); P = 0.005] were associated with RM. By Cox non-proportional hazards regression, RM was associated with graft loss (including death) [AHR 2.84 (95% CI 1.70-4.72); P < 0.001]., Conclusions: RM is a rare complication after renal transplantation and is significantly associated with allograft loss (including death). RM is significantly more likely to occur with cyclosporine (versus tacrolimus)-based immunosuppression and possibly in persons of black race. Increased surveillance for RM is warranted in these at-risk patients.

Background: The relationship of body mass index (BMI) with heart failure (HF) risk before and after kidney transplant is not well described., Methods: We examined United States Renal Data System records for 67,591 kidney transplant candidates (1995-2004) with Medicare insurance and BMI data at listing. Heart failure diagnoses were ascertained from Medicare billing claims. Body mass index was categorized per World Health Organization criteria. We modeled time-dependent associations (adjusted hazard ratio, aHR) of transplant with HF risk after listing compared with waiting in each BMI group by multivariable, stratified Cox regression. The time-dependent exposure variables partitioned relative risk of HF after transplant versus waiting into early (90 days) posttransplant periods., Results: The BMI distribution of listed candidates was as follows: 3.7% under, 40.4% normal, 32.0% over, 16.2% obese, and 7.7% morbidly obese weight. The prevalence of HF among patients awaiting transplant reached 57.4% by 3 years. Deceased-donor transplant was associated with increased early HF risk compared with continued waiting-aHRs ranged from 2.23 for normal-BMI to 2.82 for morbidly obese patients. However, transplant reduced the risk of HF in the late posttransplant period from 54% (aHR 0.46) in normal-BMI to 32% (aHR 0.68) for morbidly obese patients. Relative benefits were largest for normal-weight candidates who received live-donor transplants (aHR 0.31)., Conclusions: Heart failure risk improves in obese patients in the long term after kidney transplant, but not as much as for nonobese patients. There is need for close monitoring and for new strategies to reduce HF risk in obese patients before and after transplant.

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.

Background and Objectives: Billing claims are increasingly examined beyond administrative functions as outcomes measures in observational research. Few studies have described the performance of billing claims as surrogate measures of clinical events among kidney transplant recipients., Design, Setting, Participants, & Measurements: We investigated the sensitivity of Medicare billing claims for clinically verified cardiovascular diagnoses (five categories) and procedures (four categories) in a novel database linking Medicare claims to electronic medical records of one transplant program. Cardiovascular events identified in medical records for 571 Medicare-insured transplant recipients in 1991 through 2002 served as reference measures., Results: Within a claims-ascertainment period spanning +/-30 d of clinically recorded dates, aggregate sensitivity of single claims was higher for case definitions incorporating Medicare Parts A and B for diagnoses and procedures (90.9%) compared with either Part A (82.3%) or Part B (84.6%) alone. Perfect capture of the four procedures was possible within +/-30 d or with short claims window expansion, but sensitivity for the diagnoses trended lower with all study algorithms (91.2% with window up to +/-90 d). Requirement for additional confirmatory diagnosis claims did not appreciably reduce sensitivity. Sensitivity patterns were similar in the early compared with late periods of the study., Conclusions: Combined use of Medicare Parts A and B billing claims composes a sensitive measure of cardiovascular events after kidney transplant. Further research is needed to define algorithms that maximize specificity as well as sensitivity of claims from Medicare and other insurers as research measures in this population.

Background: Retrospective comparison of treatment-related kidney transplant outcomes may be facilitated by multivariable statistical adjustments and case-matching., Methods: We studied Organ Procurement and Transplantation Network registry data for kidney transplants in 2001 to 2005 managed with thymoglobulin, basiliximab, or no antibody induction and discharge maintenance immunosuppression regimens of tacrolimus and mycophenolate mofetil. The primary outcome was the 6 month, Food and Drug Administration-approved composite endpoint of rejection, graft failure, or death. Outcomes according to induction exposure were compared using logistic regression analysis, exposure likelihood matching, and outcome risk score matching., Results: All statistical approaches demonstrated lower rates of the 6-month triple endpoint with thymoglobulin compared with basiliximab when steroids were present, with approximately 22% adjusted, relative reduction by logistic regression analysis and 3% absolute reductions by matching approaches. When steroids were absent, risk reduction among thymoglobulin versus basiliximab-treated patients was of larger magnitude but borderline statistical significance. Triple endpoint incidence was lower with both induction regimens compared with no induction across methods. Estimated sample sizes necessary to detect the observed differences between induction types in the presence of steroids in a prospective trial ranged from 1600 to nearly 7000 patients., Conclusions: Consistency across statistical approaches suggests superiority of thymoglobulin compared with basiliximab or no antibody induction therapy for 6-month kidney transplant outcomes in the modern immunosuppression era. As the sample sizes necessary to power a prospective superiority trial are likely prohibitive, studies such as these provide clinically relevant information that may not be otherwise attainable.

Background: Limited data exist on the safety and efficacy of bariatric surgery (BS) in patients with kidney failure., Methods: We examined Medicare billing claims within USRDS registry data (1991-2004) to identify BS cases among renal allograft candidates and recipients., Results: Of 188 BS cases, 72 were performed pre-listing, 29 on the waitlist, and 87 post-transplant. Roux-en-Y gastric bypass was the most common procedure. Thirty-day mortality after BS performed on the waitlist and post-transplant was 3.5%, and one transplant recipient lost their graft within 30 days after BS. BMI data were available for a subset and suggested median excess body weight loss of 31%-61%. Comparison to published clinical trials of BS in populations without kidney disease indicates comparable weight loss but higher post-BS mortality in the USRDS sample., Conclusions: Given the substantial contributions of obesity to excess morbidity and mortality, BS warrants prospective study as a strategy for improving outcomes before and after kidney transplantation.

Introduction: Published data for BK virus allograft nephropathy, a recently emerged graft-threatening complication of kidney transplantation, are from limited-center series. Since June 30, 2004, the Organ Procurement Transplant Network national registry in the United States started collecting data on treatment of BK virus (TBKV) on the kidney follow-up forms. This study determined the rates of TBKV within 24 months posttransplant time and elucidated the risk factors for TBKV from this multicenter database., Methods: We queried the database for all primary and solitary kidney transplant recipients transplanted between January 1, 2003 and December 31, 2006, followed through July 18, 2008, and who were reported to have TBKV. Cumulative incidence of TBKV over time was estimated using Kaplan-Meier (K-M) method to reduce potential under reporting. A Cox proportional hazards regression model was fitted to determine risk factors for TBKV development, and time dependent Cox model was fitted to determine if TBKV was associated with higher risk of graft loss., Results: We included 48,292 primary and solitary kidney transplants from the US Organ Procurement Transplant Network database. The cumulative K-M incidence of BKVAN kept rising over time (0.70% at 6 months posttransplant to 2.18% at 1 year, 3.45% at 2 years and 6.6% at 5 years). Risk for BKVAN was higher with certain immunosuppressive regimens that included rabbit antithymocyte globulin or tacrolimus/mycophenolate combinations. Higher center volume and living kidney donation exerted a protective effect. Of concern, TBKV rates were significantly higher in more recent transplant years. TBKV report was associated with higher risk of subsequent graft loss (adjusted hazard ratio=1.69, P<0.001).

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.

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.

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., ((c) 2008 S. Karger AG, Basel.)

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., (Copyright 2009 S. Karger AG, Basel.)

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.

Background: BK polyomavirus (BKV) infection has emerged as an important cause of renal allograft loss. There is no proven therapy, and much basic clinical information is still lacking., Methods: We serially enrolled 95 outpatient renal transplant recipients (43% of whom were African American) in a single center cross-sectional screening study to determine the prevalence of BKV infection by whole blood polymerase chain reaction, and the prevalence of decoy cells by urinalysis and cytology. We also investigated the demographic and clinical factors associated with BKV infection, and the performance of urinalysis for decoy cells as a screening test for BKV infection., Results: The point prevalence of active BKV viremia was 7.4%. When subjects without active viremia but with a history of viremia and/or nephropathy were included, the overall prevalence was 15.8%. Urinary decoy cells were common, present in 50% of subjects at study entry. Urinalysis for decoy cells as a screen for BKV viremia had a sensitivity of 86%, specificity of 52%, positive predictive value of 13% and negative predictive value of 98%., Conclusions: Decoy cells on urinalysis were the only factor independently associated with an increased risk of BKV infection on multivariate analysis. Although associated with BKV infection on univariate analysis, thymoglobulin, mycophenolate mofetil, and tacrolimus use were not independently associated with BKV infection on multivariate analysis, neither were history of acute rejection, gender, race, nor cause of end-stage renal disease.

Background: The cardiac implications of obesity in kidney transplant recipients are not well-described., Methods: We examined associations of body mass index (BMI) at transplant with posttransplant cardiac risk among 1102 renal allograft recipients at a single center in 1991 to 2004. Cumulative posttransplant incidences of congestive heart failure (CHF), atrial fibrillation (AF), myocardial infarction, and a composite of these cardiac diagnoses were estimated by the Kaplan-Meier method. Bivariate (hazards ratio) and covariate (adjusted hazards ratio) relationships of BMI increments with cardiac risk were modeled by Cox's regression. We also systematically reviewed the literature on BMI and cardiac events after transplant., Results: In the local data, 5-year cumulative incidence of any cardiac diagnosis rose from 8.67% to 29.35% across the lowest to highest BMI quartiles (P=0.02), driven primarily by increases in CHF and AF. In contrast, the rate of myocardial infarction did not differ by BMI quartile (P=0.56). Each 5 U BMI increase predicted 25% higher risk of the cardiac composite (hazards ratio 1.25, 95% CI 1.07-1.47, P=0.005), a relationship that persisted with significance after covariate adjustment (adjusted hazards ratio 1.19, 95% CI 1.00-1.43, P=0.049). BMI independently predicted cardiac risk in subcohorts with pretransplant heart disease and with nondiabetic renal failure. Data from 26 original articles support BMI as a risk factor for posttransplant CHF and AF, whereas findings for coronary/ischemic outcomes are inconsistent and predominantly negative., Conclusions: High BMI at transplant predicts increased cardiac risk, especially of CHF and AF. Further research should examine whether obesity treatment modifies cardiac risk after kidney transplantation.

Background and Objectives: Evaluation for ischemic heart disease (IHD) is a nonstandardized practice before kidney transplantation. We retrospectively studied pretransplant cardiac evaluation (CE) practices in a national sample of renal allograft recipients., Design, Setting, Participants, & Measurements: The USRDS data for Medicare beneficiaries transplanted in 1991 to 2004 with Part A&B benefits from dialysis initiation through transplantation were examined. Clinical traits defining "high" expected IHD risk were defined as diabetes, prior IHD, or > or = 2 other coronary risk factors. Pretransplant CE were identified by billing claims for noninvasive stress tests and angiography. Patients were quantified with claims for coronary revascularization procedures between CE and transplant. Post-transplant acute myocardial infarction (AMI) events were abstracted from claims and death records., Results: Among 27,786 eligible patients, 46.3% underwent CE before transplantation. Overall, 9.5% who received CE also received pretransplant revascularization, but only 0.3% of lower-risk patients undergoing CE had revascularization. The adjusted odds of transplant without CE increased sharply with younger age and shorter dialysis duration. Increased likelihood of transplant without CE also correlated with black race, female sex, and certain geographic regions. Among patients transplanted without CE, 3-yr incidence of post-transplant AMI was 3% in lower-risk and 10% in high-risk groups, and varied by individual traits within these groups. Among lower-risk patients transplanted without CE, blacks were higher risk for AMI than whites (adjusted hazards ratio 1.47, 95% CI 1.11-1.93)., Conclusions: Observed practices demonstrate infrequent use of pretransplant revascularization after CE but also raise concern for socio-demographic barriers to evaluation access.

Background and Objectives: This study examined the risks, predictors, and mortality implications of cerebrovascular disease events after kidney transplantation in a national cohort., Design, Setting, Participants, & Measurements: This analysis used United States Renal Data System registry data to study retrospectively Medicare-insured kidney transplant candidates (n = 51,504), recipients (n = 29,614), and recipients with allograft failure (n = 2954) in 1995 through 2002. New-onset cerebrovascular disease events including ischemic stroke, hemorrhagic stroke, and transient ischemic attacks were ascertained from billing records, and participants were followed until Medicare-end or December 31, 2002. Multivariable survival analysis was used to compare cerebrovascular disease event incidence and risk profiles among the study samples., Results: The cumulative, 3-yr incidence of de novo cerebrovascular disease events after transplantation was 6.8% and was lower than adjusted 3-yr estimates of 11.8% on the waiting list and 11.2% after graft loss. In time-dependent regression, transplantation predicted a 34% reduction in subsequent, overall cerebrovascular disease events risk compared with remaining on the waiting list, whereas risk for cerebrovascular disease events increased >150% after graft failure. Similar relationships with transplantation and graft loss were observed for each type of cerebrovascular disease event. Smoking was a potentially preventable correlate of posttransplantation cerebrovascular disease events. Women were not protected. All forms of cerebrovascular disease event diagnoses after transplantation predicted increased mortality., Conclusions: Along with known benefits for cardiac complications, transplantation with sustained graft function seems to reduce risk for vascular disease events involving the cerebral circulation.

Background and Objectives: Accurate assessment of the use of immunosuppressive medications is vital for observational analyses that are widely used in transplantation research. This study assessed the accuracy of three potential sources of maintenance immunosuppression data., Design, Setting, Participants, & Measurements: This study investigated the agreement of immunosuppression information in directly linked electronic medical records for Medicare beneficiaries who received a kidney transplant at one center in 1998 through 2001, Organ Procurement and Transplantation Network (OPTN) survey data, and Medicare pharmacy claims. Pair-wise, interdata concordance (kappa) and percentage agreement statistics were used to compare immunosuppression regimens reported at discharge, and at 6 mo and 1 yr after transplantation in each data source., Results: Among 181 eligible participants, agreement between data sources for nonsteroid immunosuppression increased with time after transplantation. By 1-yr, concordance was excellent for calcineurin inhibitors and mycophenolate mofetil (kappa = 0.79 to 1.00), and very good for azathioprine (kappa = 0.73 to 0.85). Similarly, percentage agreement at 1 yr was 94.9 to 100% for calcineurin inhibitors, 91.1 to 95.7% for mycophenolate mofetil, and 87.5 to 92.8% for azathioprine. Widening the comparison time window resolved 33.6% of cases with discordant indications of calcineurin inhibitor and/or antimetabolite use in claims compared with other data sources., Conclusions: This analysis supports the accuracy of the three sources of data for description of nonsteroid immunosuppression after kidney transplantation. Given the current strategic focus on reducing collection of data, use of alternative measures of immunosuppression exposure is appropriate and will assume greater importance.

Urinary tract infection (UTI) is the most common infection after kidney transplantation. A previous analysis showed that late (>6 mo after transplantation) UTI is associated with earlier graft loss in adults. It was hypothesized that children who are younger than 18 yr would be at higher risk to develop UTI and develop graft loss after both early and late UTI. The US Renal Data System database was analyzed from 1996 to 2000 for Medicare claims (composite of inpatient and outpatient) for UTI up to 36 mo after transplantation. SPSS software and Cox regression models were used to determine association of UTI and age after adjustment for covariates. Early UTI was defined as occurring <6 mo after transplantation, and late UTI was defined as occurring > or =6 mo after transplantation. The risk for graft loss after early UTI was elevated in all children (adjusted hazard ratio [AHR] 5.47; 95% confidence interval [CI] 1.93 to 15.4; P < 0.001) but not after late UTI (AHR 2.09; 95% CI 0.56 to 7.80; P = 0.27). Risk for posttransplantation death was not increased significantly after either early UTI (AHR 1.23; 95% CI 0.37 to 4.08) or late UTI (relative risk 2.22; 95% CI 0.90 to 5.44). Boys aged 2 to 5 (versus age 13 to <18 years) were at significantly higher risk for UTI. In girls, only those in the youngest age category (0 to 1) had higher risk for UTI. Children are at greater risk for graft loss after early but not necessarily late UTI. UTI was not an independent predictor of death in this population.

The Organ Procurement and Transplantation Network (OPTN) collects intermittent survey data on immunosuppressive medication use that are studied frequently as research measures. Pharmacy billing claims may provide an accurate measure of immunosuppression use over time. Herein is characterized the agreement of Medicare pharmacy claims for immunosuppressive medications with OPTN reports. Data were drawn from the United States Renal Data System. Participants received a kidney transplant in 2000 to 2001 and had an OPTN record and a Medicare pharmacy claim for an immunosuppressive drug at transplant discharge and 6 mo and 1 yr after transplantation. The concordance (kappa) of the OPTN and claims (+/-30 d of survey) for indicated medication use was compared, and sensitivity, specificity, and predictive values for claims were computed, assuming OPTN as a "gold standard." Clinical trial participation and regimen changes were examined as explanations for discordance. A total of 4357 eligible subjects were identified. Concordance over observation ranged from excellent for calcineurin inhibitors (kappa > 0.86) to generally very good for adjunctive agents (kappa = 0.49 to 0.75) to poor for corticosteroids (kappa <0.15). Claims demonstrated high positive predictive values (> or =97%) but low negative predictive values (< or =13%) for OPTN-reported corticosteroid use. Regimen changes (28 to 75%) but not clinical trial participation (< or =21%) were identified frequently among cases with discordant indications of nonsteroid medication use. Close agreement of Medicare billing claims and the OPTN for indicated use of nonsteroid immunosuppressive medications supports both as useful measures of drug exposure. Low detection rates of OPTN-indicated corticosteroid use within claims require further examination.

Background: Older transplant recipients have been shown to be at greater risk for infectious death than younger adults, but no study to date has looked at relative risk of infection and infection profile differences for children versus adults, which may be very different from one another., Methods: Data from primary Medicare renal transplant recipients between 1991 and 1998 (n=64,751), as reported in the United States Renal Data System (USRDS), were analyzed for Medicare claims (both inpatient and outpatient) for infection and type of infection in the first year posttransplant. Cox regression was used to model adjusted hazard ratios (AHR) for infection., Results: Total infections among renal transplant recipients increased significantly in more recent years. Patients transplanted in or after 1995 had a significantly higher adjusted risk for infection compared to those transplanted earlier (AHR 1.34, 95% CI=1.29-1.39). Older adults > or = 51 years of age had the highest percentage of experiencing infection, as compared to adults between 18-50 years and children < or = 17 years (P<0.001). Children were at highest risk of viral infection prior to 1995 but at lowest risk of viral infection after 1995, whereas elderly adults were at highest risk of bacterial infection throughout the study. Children experienced more claims for viral infections, whereas older transplant recipients experienced more claims for bacterial infections., Conclusions: The two extremes of transplant recipient age display very different risks for infection claim frequency and profile.

Background: Hodgkin disease and myeloma were recently included in the classification of posttransplant lymphoproliferative disorder (PTLD). However, because their incidence is low, not much is known about their particular features., Methods: The incidence, characteristics, risk, and prognostic factors of myeloma, Hodgkin disease, and lymphoid leukemia using the United States Renal Data System from 1991 to 2000 among 66,159 Medicare patients were analyzed., Results: In all, 1,169 recipients developed a lymphoid disease: 823 (1.2%) non-Hodgkin's lymphomas (NHL), 160 (0.24%) myelomas, 60 (0.1%) Hodgkin lymphomas, and 126 (0.2%) lymphoid leukemias. Older age was associated with an increased risk of myeloma and leukemia. The incidence of hepatitis C virus infection was higher in recipients with myeloma (6.9 vs. 3.9%, P=0.05). Induction therapy was associated with a greater risk of myeloma and leukemia, but not Hodgkin disease. Azathioprine was associated with a lower risk of myeloma, and tacrolimus with a lower risk of Hodgkin disease. According to the type of malignancy, ten-year survival rates were significantly different: 42, 26, 55 and 39% respectively for NHL, myeloma, Hodgkin disease, and leukemia., Conclusion: These results support specific features and risk factors related to the occurrence of each type of lymphoid-proliferation and suggest for the first time a possible association between hepatitis C virus and myeloma in kidney transplant recipients.

The risk for and predictors of atrial fibrillation (AF) after kidney transplantation are not well described. Registry data that were collected by the United States Renal Data System were used to investigate retrospectively new-onset AF among adult first renal allograft recipients and transplant candidates who received a transplant or were wait-listed in 1995 to 2001 with Medicare as the primary payer. AF events were ascertained from billing records, and participants were followed until loss of Medicare coverage or December 31, 2001. Cox hazards analysis was used to identify independent correlates of posttransplantation AF (adjusted hazard ratio [AHR]; 95% confidence interval [CI]) and to examine AF as an outcomes predictor. Among 31,136 eligible transplant recipients, the cumulative incidence of new-onset AF was 3.6% (95% CI 3.4 to 3.8%) and 7.3% (95% CI 7.0 to 7.6%) at 12 and 36 mo and declined below the demographics-adjusted cumulative incidence on the waiting list by approximately 17 mo. Risk factors for posttransplantation AF included older recipient age, male gender, white race, renal failure from hypertension, and coronary artery disease. Extended pretransplantation dialysis duration, posttransplantation diabetes, and graft failure were identified as potentially modifiable correlates of AF. In separate analyses, AF independently predicted death (AHR 3.2; 95% CI 2.9 to 3.6) and death-censored graft loss (AHR 1.9; 95% CI 1.6 to 2.3). As the population of renal transplant recipients grows older, the incidence and prevalence of AF among these patients will likely increase. Appropriate risk stratification may identify transplant recipients who are in need of close monitoring for and management of this adverse cardiovascular event.

Background: Although cyclosporine use has been associated with an increased risk of new-onset gout after renal transplantation, the incidence and risk factors for new-onset gout have not been reported in the era of modern immunosuppression., Methods: We conducted a retrospective cohort study of Medicare primary renal transplant patients reported in the United States Renal Data System (USRDS), using Medicare claims data to determine the incidence of new-onset gout. Cox regression analysis was used to calculate adjusted hazard ratios (AHR) for cyclosporine (including separate analysis of Neoral) compared directly with tacrolimus, for the risk of new-onset gout, adjusted for baseline demographic factors and posttransplant renal function., Results: The cumulative incidence of new-onset gout was 7.6% at 3 years posttransplant. The following factors were independently associated with an increased risk of new-onset gout: use of Neoral (vs. tacrolimus, AHR 1.25, 95% CI 1.07-1.47) at discharge, recipient male sex (AHR 1.44, 95% CI 1.25-1.67), older age, higher body mass index, and more recent year of transplant. No other immunosuppressive medications were associated with new-onset gout. Diabetes was associated with a significantly lower risk of new-onset gout. The development of new-onset gout was independently associated with decreased patient survival (AHR 1.26, 95% CI 1.08-1.47) as well as death-censored graft survival., Conclusions: Cyclosporine is an independent risk factor for new-onset gout after transplantation. The incidence of new-onset gout appears to be increasing even while the use of cyclosporine is decreasing, and the development of new-onset gout was an independent predictor for death and graft loss in this population.

Background: Posttransplant lymphoproliferative disorders (PTLD) still represent a major preoccupation after renal transplantation, even in the most recent years., Methods: We analyzed the incidence, risk, and prognostic factors of PTLD in a cohort of kidney recipients using the United States Renal Data System., Results: Among 25,127 Medicare patients transplanted between 1996 and 2000, 344 developed a PTLD defined as a non-Hodgkin lymphoma (1.4%). History of pretransplant malignancy (adjusted hazard ratio [AHR]=3.54, CI 2.31-5.43), younger age (AHR=1.91, CI 1.18-3.1), fewer HLA matches (AHR=1.32, CI 1.1-1.59) and treatment by ATG (AHR=1.55, CI 1.2-1.99) and OKT3 (AHR=1.37, CI 1-1.76), especially if given for rejection therapy were associated with an increased risk of PTLD. Mycophenolate and azathioprine were associated with a lower risk of PTLD (AHR=0.6, CI 0.47-0.78 and AHR=0.66, CI 0.46-0.95, respectively). IL2-receptor inhibitors and sirolimus did not modify the risk of PTLD. Patients without induction therapy treated with tacrolimus were at greater risk of lymphoma than those treated with new formulations of cyclosporine and those treated with antimetabolites (mycophenolate and azathioprine) have a lower risk of PTLD than those without. Patients with PTLD had poor survival (64% vs. 80% at 5 years). Older age, pretransplant malignancy and OKT3 were risk factors for death whereas treatment with mycophenolate was associated with a better survival (AHR=0.49, CI=0.28-0.82)., Conclusions: Our study highlights the contribution of patient history and immunosuppression in the risk of PTLD in the era of modern immunosuppression.

Background: We aim to describe the risk, predictors, and outcomes associated with de novo congestive heart failure (CHF) after kidney transplantation., Methods: We used registry data from the US Renal Data System to retrospectively investigate de novo CHF in adult Medicare-insured transplant recipients and wait-listed candidates in 1995 to 2001. Heart failure was ascertained from inpatient and outpatient billing records, and participants were followed up until loss of Medicare or December 31, 2001. We used extended Cox hazards analysis to identify independent correlates of posttransplantation de novo CHF (adjusted hazard ratio [AHR], 95% confidence interval [CI]) and examine de novo CHF as a predictor of death and graft loss after transplantation., Results: In 27,011 transplant recipients, cumulative incidences of de novo CHF were 10.2% (95% CI, 9.8 to 10.6) and 18.3% (95% CI, 17.8 to 18.9) at 12 and 36 months and decreased to less than the demographic-adjusted incidence on the waiting list beyond the early posttransplantation period. Risk factors for de novo CHF included older recipient age, female sex, unemployed status at transplantation, pretransplantation comorbidities (anemia, diabetes mellitus, myocardial infarction, angina, cardiac arrhythmia, and peripheral vascular disease), transplant from older donors, donor cardiovascular death, and delayed graft function. We identified pretransplantation obesity, smoking, and posttransplantation complications, including hypertension, anemia, new-onset diabetes, myocardial infarction, and graft failure, as potentially modifiable correlates of de novo CHF. In separate analyses, de novo CHF predicted death (AHR, 2.6; 95% CI, 2.4 to 2.9) and death-censored graft failure (AHR, 2.7; 95% CI, 2.4 to 3.0)., Conclusion: Although associations may not reflect causality, identification of potentially mutable de novo CHF risk factors suggests targets for improving outcomes that should be evaluated prospectively.

Purpose: Previous studies suggest the association of recipient hepatitis C seropositivity (HCV+) and use of tacrolimus (TAC) with post-transplant diabetes mellitus (PTDM) may differ by manifestations of type I or type II diabetes, but this has not been assessed in the era of current immunosuppression., Methods: We performed a retrospective cohort study of 10,342 Medicare primary renal transplantation recipients without evidence of diabetes at the time of listing in the United States Renal Data System between January 1, 1998 and July 31, 2000, followed until December 31, 2000. Outcomes were hospitalizations for a primary diagnosis of diabetic ketoacidosis (DKA) or hyperglycemic hyperosmolar syndrome (HHS). Cox regression analysis was used to calculate adjusted hazard ratios (AHR) for time to DKA or HHS, stratified by diabetes status at the time of transplant., Results: In Cox regression analysis, use of TAC at discharge was independently associated with shorter time to DKA (AHR, 1.88; 95% CI, 1.05-3.37, p=0.034) but not HHS. In contrast, recipient HCV+ was independently associated with shorter time to HHS (AHR, 3.90; 1.59-9.60, p=.003), but not DKA. There was no interaction between TAC and HCV+ for either outcome., Conclusion: These results confirm earlier findings that TAC and HCV+ may mediate the risk of PTDM through different mechanisms, even in the modern era.

Background: Avascular necrosis (AVN) after renal transplantation has been largely attributed to the use of corticosteroids. However, other risk factors such as microvascular thrombosis and hyperlipidemia have been well described and may be of increased importance in the era of early steroid cessation and avoidance. We hypothesized that maintenance immunosuppressive medications known to be associated with these risk factors for AVN would also be associated with a higher risk of AVN., Methods: By using the U.S. Renal Data System database, we studied 27,772 primary patients on Medicare who received a solitary kidney transplant between January 1, 1996, and July 31, 2000. Cox proportional hazards regression models were used to calculate adjusted hazard ratios (AHRs) for patient- and transplant-related factors (including allograft rejection) with Medicare claims for AVN. The intensity and duration of corticosteroid use could not be assessed., Results: Among patients who were prescribed sirolimus at discharge, 3.5% of patients who received the combination of sirolimus-cyclosporine A (CsA) demonstrated AVN, compared with 1.4% of patients who received the combination of sirolimus-tacrolimus (P=0.06 by chi). In Cox regression, CsA use (vs. tacrolimus) (AHR 1.36, 95% confidence interval, 1.09-1.71) was independently associated with an increased risk of AVN. Sirolimus use showed a trend toward significance (AHR 1.59, 95% confidence interval, 0.99-2.56), with no significant interaction with CsA., Conclusions: Compared with other maintenance immunosuppression, AVN was significantly more common after use of CsA prescribed at the time of discharge for renal transplantation. Whether this increased risk of AVN was directly attributable to hyperlipidemia, microvascular thrombosis, or differences in corticosteroid dosing could not be determined.