Faculty Bibliography

OBJECTIVE:To investigate changes in pediatric kidney transplant outcomes over time and potential variations in these changes between the early and late posttransplant periods and across subgroups based on recipient, donor, and transplant characteristics. METHODS:Using multiple logistic regression and multivariable Cox models, graft and patient outcomes were analyzed in 17,446 pediatric kidney-only transplants performed in the United States between 1987 and 2012. RESULTS:Ten-year patient and graft survival rates were 90.5% and 60.2%, respectively, after transplantation in 2001, compared with 77.6% and 46.8% after transplantation in 1987. Primary nonfunction and delayed graft function occurred in 3.3% and 5.3%, respectively, of transplants performed in 2011, compared with 15.4% and 19.7% of those performed in 1987. Adjusted for recipient, donor, and transplant characteristics, these improvements corresponded to a 5% decreased hazard of graft loss, 5% decreased hazard of death, 10% decreased odds of primary nonfunction, and 5% decreased odds of delayed graft function with each more recent year of transplantation. Graft survival improvements were lower in adolescent and female recipients, those receiving pretransplant dialysis, and those with focal segmental glomerulosclerosis. Patient survival improvements were higher in those with elevated peak panel reactive antibody. Both patient and graft survival improvements were most pronounced in the first posttransplant year. CONCLUSIONS:Outcomes after pediatric kidney transplantation have improved dramatically over time for all recipient subgroups, especially for highly sensitized recipients. Most improvement in graft and patient survival has come in the first year after transplantation, highlighting the need for continued progress in long-term outcomes.

BACKGROUND: The correlation between histopathologic phenotypes and allograft outcomes among patients desensitized for donor-specific antibody (HLA-incompatible) is unknown. METHODS: We analyzed 1-year biopsies from desensitized recipients transplanted between 1999 and 2010 and estimated graft survival for each histologic phenotype identified. Median time posttransplant for the 1-year biopsy was 367 days (interquartile range 357-388 days) and median follow-up of all patients post-1-year biopsy was 42 months (interquartile range 19.5-65 months). RESULTS: Transplant glomerulopathy was present in 25.0% of biopsies and resulted in worse graft survival (66.7% vs. 96.7%, P<0.001). C4d positivity and transplant glomerulopathy together portended exceptionally poor graft survival (33.3% vs. 97.2%, P<0.001). Microcirculation inflammation was prevalent, with glomerulitis and peritubular capillaritis found in 60.0% and 47.6% of 1-year biopsies, respectively. Glomerulitis was associated with worse graft survival (82.1% vs. 98.1%, P=0.004), whereas capillaritis was not (88.1% vs. 97.7% respectively, P=0.091). Among C4d-negative HLA-incompatible recipients (82.6% of biopsies), no difference in graft survival was observed between patients with or without microcirculation inflammation in contrast to previous reports by other investigators. Patients who had no C4d deposition, transplant glomerulopathy, or microcirculation inflammation had a 100.0% graft survival. On Cox regression analysis, no independent histopathological parameter was associated with graft survival. CONCLUSIONS: We have identified several histopathologic phenotypes in HLA-incompatible kidney recipients that correlate with allograft outcomes. Characterization of these phenotypes is the first step towards better understanding the pathophysiologic basis of chronic antibody-mediated allograft injury and individualizing therapeutic intervention.

Current studies of complications following donor hepatectomy may not be generalizable to all hospitals performing this procedure. To address this, live liver donors were identified in the Nationwide Inpatient Sample (2000-2008). Complications after donor hepatectomy were categorized using International Classification of Diseases, Ninth Revision codes and risk factors for complications were tested using logistic regression. Negative binomial regression models were used to estimate the increase in length of stay and hospital charge associated with complications. Among 555 donors (representing 2783 donors nationwide), 23% had 1 or more complications and 5% had a major complication. The most common complications were ileus (27%) and atelectasis (26%). No patient or hospital factors were associated with complications. Having any complication was associated with increased length of stay (incidence rate ratio, 1.36; 95% CI, 1.16-1.58; P < .001) and hospital charge (incidence rate ratio, 1.25; 95% CI, 1.09-1.44; P = .002). Approximately 25% of liver donors have complications immediately postoperatively but most are minor, lending support to current practices in live liver donation and donor selection.

BACKGROUND: Kidney transplantation (KT) is the treatment for end-stage renal disease in appropriate HIV-positive individuals. However, acute rejection (AR) rates are over twice those of HIV-negative recipients. METHODS: To better understand optimal immunosuppression for HIV-positive KT recipients, we studied associations between immunosuppression regimen, AR at 1 year, and survival in 516 HIV-positive and 93,027 HIV-negative adult kidney-only recipients using Scientific Registry of Transplant Recipients data from 2003 to 2011. RESULTS: Consistent with previous reports, HIV-positive patients had twofold higher risk of AR (adjusted relative risk [aRR], 1.77; 95% confidence interval [CI], 1.45-2.2; P<0.001) than their HIV-negative counterparts as well as a higher risk of graft loss (adjusted hazard ratio, 1.51; 95% CI, 1.18-1.94; P=0.001), but these differences were not seen among patients receiving antithymocyte globulin (ATG) induction (aRR for AR, 1.16; 95% CI, 0.41-3.35, P=0.77; adjusted hazard ratio for graft loss, 1.54; 95% CI, 0.73-3.25; P=0.26). Furthermore, HIV-positive patients receiving ATG induction had a 2.6-fold lower risk of AR (aRR, 0.39; 95% CI, 0.18-0.87; P=0.02) than those receiving no antibody induction. Conversely, HIV-positive patients receiving sirolimus-based therapy had a 2.2-fold higher risk of AR (aRR, 2.15; 95% CI, 1.20-3.86; P=0.01) than those receiving calcineurin inhibitor-based regimens. CONCLUSION: These findings support a role for ATG induction, and caution against the use of sirolimus-based maintenance therapy, in HIV-positive individuals undergoing KT.

BACKGROUND:Racial disparities in health outcomes after living donation have been reported, but generalizability is not known. METHODS:We linked Organ Procurement and Transplantation Network (OPTN) registry data for 4,007 living kidney donors in 1987 to 2008 with Medicare billing claims (2000-2008). Cox regression with left and right censoring was used to estimate the frequencies and relative risks of postdonation medical diagnoses according to race. Patterns were compared with findings from a previous linkage of OPTN donor records and private insurance claims. RESULTS:Among the Medicare-insured donors, 8% were African American and 5.7% were Hispanic. Diagnosis frequencies at 5 years after donation in the Medicare- versus privately insured donors included the following: malignant hypertension, 5.0% versus 0.9%; diabetes, 18.5% versus 4.1%; and chronic kidney disease, 21.8% versus 4.9%. After age and sex adjustment in the Medicare sample, African Americans, as compared with white donors, experienced higher risks of any hypertension diagnosis, including 2.4 times the likelihood of malignant hypertension (adjusted hazard ratio [aHR], 2.35; 95% confidence interval [CI], 1.40-3.93), and more common diabetes (aHR, 1.50; 95% CI, 1.12-2.04), chronic kidney disease (aHR, 1.84; 95% CI, 1.37-2.47), and proteinuria (aHR, 2.44; 95% CI, 1.45-4.11) diagnoses. Relative patterns for privately insured African American versus white donors were similar, including approximately three times the risk of malignant hypertension (aHR, 3.27; 95% CI, 1.82-5.88) and twice the relative risks of chronic kidney disease and proteinuria. CONCLUSIONS:Consistent demonstration of racial variation in postdonation medical conditions regardless of sample/payer source supports the need for continued study of mediators and consequences of outcomes in non-white donors.

IMPORTANCE: Risk of end-stage renal disease (ESRD) in kidney donors has been compared with risk faced by the general population, but the general population represents an unscreened, high-risk comparator. A comparison to similarly screened healthy nondonors would more properly estimate the sequelae of kidney donation. OBJECTIVES: To compare the risk of ESRD in kidney donors with that of a healthy cohort of nondonors who are at equally low risk of renal disease and free of contraindications to live donation and to stratify these comparisons by patient demographics. DESIGN, SETTINGS, AND PARTICIPANTS: A cohort of 96,217 kidney donors in the United States between April 1994 and November 2011 and a cohort of 20,024 participants of the Third National Health and Nutrition Examination Survey (NHANES III) were linked to Centers for Medicare & Medicaid Services data to ascertain development of ESRD, which was defined as the initiation of maintenance dialysis, placement on the waiting list, or receipt of a living or deceased donor kidney transplant, whichever was identified first. Maximum follow-up was 15.0 years; median follow-up was 7.6 years (interquartile range [IQR], 3.9-11.5 years) for kidney donors and 15.0 years (IQR, 13.7-15.0 years) for matched healthy nondonors. MAIN OUTCOMES AND MEASURES: Cumulative incidence and lifetime risk of ESRD. RESULTS: Among live donors, with median follow-up of 7.6 years (maximum, 15.0), ESRD developed in 99 individuals in a mean (SD) of 8.6 (3.6) years after donation. Among matched healthy nondonors, with median follow-up of 15.0 years (maximum, 15.0), ESRD developed in 36 nondonors in 10.7 (3.2) years, drawn from 17 ESRD events in the unmatched healthy nondonor pool of 9364. Estimated risk of ESRD at 15 years after donation was 30.8 per 10,000 (95% CI, 24.3-38.5) in kidney donors and 3.9 per 10,000 (95% CI, 0.8-8.9) in their matched healthy nondonor counterparts (P < .001). This difference was observed in both black and white individuals, with an estimated risk of 74.7 per 10,000 black donors (95% CI, 47.8-105.8) vs 23.9 per 10,000 black nondonors (95% CI, 1.6-62.4; P < .001) and an estimated risk of 22.7 per 10,000 white donors (95% CI, 15.6-30.1) vs 0.0 white nondonors (P < .001). Estimated lifetime risk of ESRD was 90 per 10,000 donors, 326 per 10,000 unscreened nondonors (general population), and 14 per 10,000 healthy nondonors. CONCLUSIONS AND RELEVANCE: Compared with matched healthy nondonors, kidney donors had an increased risk of ESRD over a median of 7.6 years; however, the magnitude of the absolute risk increase was small. These findings may help inform discussions with persons considering live kidney donation.

BACKGROUND:Use of antihypertensive medications (AHM) after living kidney donation is not well described. METHODS:We examined a database wherein national transplant registry data for 4,650 living kidney donors in 1987-2007 were linked to pharmacy claims from a US private health insurer (2000-2007 claims) to identify post-donation AHM fills. Cox regression with left- and right-censoring was used to estimate the frequencies and relative likelihood (adjusted hazards ratios, aHR) of post-donation AHM fills according to donor demographic traits. Medication possession ratio (MPRs), defined as (days of AHM dispensed)/(days observed), were also compared among donors and non-donor general beneficiaries. RESULTS:Overall, 17.8% of the sample filled at least one AHM by 5 years post-donation. As compared with White living donors, African-Americans had 37% higher relative likelihood of any AHM use after donation (aHR 1.37, p < 0.0007), including significantly higher likelihoods of filling diuretics (aHR 2.25, p < 0.0001), ACEi/ARBs (aHR 1.46, p < 0.01), calcium channel blockers (aHR 1.56, p = 0.03), and vasodilators/other agents (aHR 2.17, p = 0.03). MPRs for any AHM and subcategories were lower among donors compared with age- and sex-matched non-donors. However, AHM MPRs rose in donors with multiple hypertension diagnoses, and prescription fill exposure for all AHM classes except diuretics was similar among donors and general non-donors with ≥ 3 hypertension diagnoses. CONCLUSIONS:While AHM requirements are lower after kidney donation than among unscreened general persons, racial variation in AHM use occurs in privately insured donors. Demonstration of pharmaceutical care needs of insured donors supports the need for long-term follow-up and healthcare access for all donors.