Social Determinants of Health and Race Disparities in Kidney Transplant

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Recipient Criteria Predictive of Graft Failure in Kidney Transplantation

Several classifications systems have been developed to predict outcomes of kidney transplantation based on donor variables.This study aims to identify kidney transplant recipient variables that would predict graft outcome irrespective of donor characteristics.All U.S. kidney transplant recipients between October 25,1999 and January 1, 2007 were reviewed. Cox proportional hazards regression was used to model time until graft failure. Death-censored and nondeath-censored graft survival models were generated for recipients of live and deceased donor organs. Recipient age, gender, body mass index (BMI), presence of cardiac risk factors, peripheral vascular disease, pulmonary disease, diabetes, cerebrovascular disease, history of malignancy, hepatitis B core antibody, hepatitis C infection, dialysis status, panel-reactive antibodies (PRA), geographic region, educational level, and prior kidney transplant were evaluated in all kidney transplant recipients.Among the 88,284 adult transplant recipients the following groups had increased risk of graft failure: younger and older recipients, increasing PRA (hazard ratio [HR],1.03–1.06], increasing BMI (HR, 1.04–1.62), previous kidney transplant (HR, 1.17–1.26), dialysis at the time of transplantation (HR, 1.39–1.51), hepatitis C infection (HR, 1.41–1.63), and educational level (HR, 1.05–1.42).Predictive criteria based on recipient characteristics could guide organ allocation, risk stratification, and patient expectations in planning kidney transplantation.     

Racial and Ethnic Disparities in the VA Health Care System: A Systematic Review

Objectives To better understand the causes of racial disparities in health care, we reviewed and synthesized existing evidence related to disparities in the “equal access” Veterans Affairs (VA) health care system. Methods We systematically reviewed and synthesized evidence from studies comparing health care utilization and quality by race within the VA. Results Racial disparities in the VA exist across a wide range of clinical areas and service types. Disparities appear most prevalent for medication adherence and surgery and other invasive procedures, processes that are likely to be affected by the quantity and quality of patient–provider communication, shared decision making, and patient participation. Studies indicate a variety of likely root causes of disparities including: racial differences in patients’ medical knowledge and information sources, trust and skepticism, levels of participation in health care interactions and decisions, and social support and resources; clinician judgment/bias; the racial/cultural milieu of health care settings; and differences in the quality of care at facilities attended by different racial groups. Conclusions Existing evidence from the VA indicates several promising targets for interventions to reduce racial disparities in the quality of health care.     

Source of Post-Transplant Care and Mortality among Kidney Transplant Recipients Dually Enrolled in VA and Medicare

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Acute Kidney Injury,Microvascular Rarefaction,and Estimated Glomerular Filtration Rate in Kidney Transplant Recipients

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Outcomes Associated with Steroid Avoidance and Alemtuzumab among Kidney Transplant Recipients

Background and objectives

Alemtuzumab is a humanized anti-CD52 monoclonal antibody used as induction in kidney transplantation (KTX) since 2003. Few studies have evaluated long-term outcomes of this agent or changes in outcomes over time.

Design, setting, participants, & measurements

A retrospective cohort study was performed examining United States registry data from 2003 to 2014 of primary KTX recipients receiving induction with alemtuzumab (AZ; n=5521) or antithymocyte globulin (ATG; n=8504) and maintenance immunosuppression with tacrolimus and mycophenolate mofetil and early withdrawal of steroids. The primary outcome was overall death-censored graft survival (DCGS), and secondary outcomes were overall patient survival and 1-year acute rejection. Multivariate models were fit with donor, recipient, and transplant covariates. Because poorer outcomes with AZ may occur from a learning curve impact with the use of a new medication, transplant year was categorized into three time periods to evaluate outcomes over time (2003–2005, 2006–2008, ≥2009), and an interaction term of induction type with transplant year category was included in all models to test for era impacts.

Results

On multivariate analysis of DCGS there was a significant interaction between AZ and era (P<0.001). AZ was significantly associated with inferior DCGS in the earliest 2003–2005 era (adjusted hazard ratio [aHR], 2.21; 95% confidence interval [95% CI], 1.72 to 2.84) but not in the middle 2006–2008 era (aHR, 1.14; 95% CI, 0.96 to 1.36) or the most recent 2009–2014 era (aHR, 1.08; 95% CI, 0.90 to 1.29) compared with ATG. Risk-adjusted patient survival (aHR, 1.32; 95% CI, 1.08 to 1.61; aHR, 1.26; 95% CI, 1.09 to 1.46; and aHR, 1.10; 95% CI, 0.93 to 1.29 by era, respectively) and acute rejection (adjusted odds ratio [aOR], 1.17; 95% CI, 0.96 to 1.42; aOR, 0.94; 95% CI, 0.82 to 1.07; aOR, 0.89; 95% CI, 0.81 to 0.98 by era, respectively) with AZ was comparable with ATG in the most recent era; however, there was no significant interaction with time (P=0.13 and P=0.06, respectively).

Conclusions

Current alemtuzumab utilization is associated with comparable graft and patient survival and acute rejection compared with ATG. Graft survival with alemtuzumab has improved over time.     

Recurrence of 2,8-dihydroxyadenine Crystalline Nephropathy in a Kidney Transplant Recipient: A Case Report and Literature Review

We herein report the case of a kidney transplant patient with recurrence of obstructive nephropathy that was not diagnosed as adenine phosphoribosyltransferase (APRT) deficiency until gene testing identified a pathogenic homozygous variant three years after renal transplantation. Subsequently, the patient was treated with allopurinol, and the allograft function increased progressively to normal. In addition, 20 cases of APRT deficiency in renal transplant recipients were also reviewed. We hope this case increases awareness of APRT deficiency in repeated obstructive nephropathy post-transplantation, which is a treatable disease for which the misdiagnosis or delayed diagnosis should be avoided.     

BK Polyomavirus Micro-RNAs: Time Course and Clinical Relevance in Kidney Transplant Recipients

Background: Kidney transplant recipients (KTRs) are exposed to a high risk of BK polyomavirus (BKPyV) replication, which in turn may lead to graft loss. Although the microRNAs (miRNAs) bkv-miR-B1-3p and bkv-miR-B1-5p are produced during the viral cycle, their putative value as markers of viral replication has yet to be established. In KTRs, the clinical relevance of the changes over time in BKPyV miRNA levels has not been determined. Methods: In a retrospective study, we analyzed 186 urine samples and 120 plasma samples collected from 67 KTRs during the first year post-transplantation. Using a reproducible, standardized, quantitative RT-PCR assay, we measured the levels of bkv-miR-B1-3p and bkv-miR-B1-5p (relative to the BKPyV DNA load). Results: Detection of the two miRNAs had low diagnostic value for identifying patients with DNAemia or for predicting DNAuria during follow-up. Seven of the 14 KTRs with a sustained BKPyV infection within the first year post-transplantation showed a progressive reduction in the DNA load and then a rapid disappearance of the miRNAs. DNA and miRNA loads were stable in the other seven KTRs. Conclusions: After the DNA-based diagnosis of BKPyV infection in KTRs, bkv-miR-B1-3p and bkv-miR-B1-5p levels in the urine might be valuable markers for viral replication monitoring and thus might help physicians to avoid an excessive reduction in the immunosuppressive regimen.     

Primary-care Clinician Perceptions of Racial Disparities in Diabetes Care

Summary Background Primary-care clinicians can play an important role in reducing racial disparities in diabetes care. Objective The objective of the study is to determine the views of primary-care clinicians regarding racial disparities in diabetes care. Design The design of the study is through a survey of primary-care clinicians (response rate = 86%). Participants The participants of the study were 115 physicians and 54 nurse practitioners and physician assistants within a multisite group practice in 2007. Measurements and Main Results We identified sociodemographic characteristics of each clinician’s diabetic patient panel. We fit multivariable logistic regression models to identify predictors of supporting the collection of data on patients’ race and acknowledging the existence of racial disparities among patients personally treated. Among respondents, 79% supported the collection of data on patients’ race. Whereas 88% acknowledged the existence of racial disparities in diabetes care within the U.S. health system, only 40% reported their presence among patients personally treated. Clinicians caring for greater than or equal to 50% minority patients were more likely to support collection of patient race data (adjusted odds ratio [OR] 9.0; 95% confidence interval [CI] 1.2–65.0) and report the presence of racial disparities within their patient panel (adjusted OR 12.0; 95% CI 2.5–57.7). Clinicians were more likely to perceive patient factors than physician or health system factors as mediators of racial disparities; however, most supported interventions such as increasing clinician awareness (84%) and cultural competency training (88%). Conclusions Most primary-care clinicians support the collection of data on patients’ race, but increased awareness about racial disparities at the local level is needed as part of a targeted effort to improve health care for minority patients.     

Association between Kidney Transplant Center Performance and the Survival Benefit of Transplantation Versus Dialysis

Background and objectives

Despite the benefits of kidney transplantation, the total number of transplants performed in the United States has stagnated since 2006. Transplant center quality metrics have been associated with a decline in transplant volume among low-performing centers. There are concerns that regulatory oversight may lead to risk aversion and lack of transplantation growth.

Design, setting, participants, & measurements

A retrospective cohort study of adults (age≥18 years) wait-listed for kidney transplantation in the United States from 2003 to 2010 using the Scientific Registry of Transplant Recipients was conducted. The primary aim was to investigate whether measured center performance modifies the survival benefit of transplantation versus dialysis. Center performance was on the basis of the most recent Scientific Registry of Transplant Recipients evaluation at the time that patients were placed on the waiting list. The primary outcome was the time-dependent adjusted hazard ratio of death compared with remaining on the transplant waiting list.

Results

Among 223,808 waitlisted patients, 59,199 and 32,764 patients received a deceased or living donor transplant, respectively. Median follow-up from listing was 43 months (25th percentile=25 months, 75th percentile=67 months), and there were 43,951 total patient deaths. Deceased donor transplantation was independently associated with lower mortality at each center performance level compared with remaining on the waiting list; adjusted hazard ratio was 0.24 (95% confidence interval, 0.21 to 0.27) among 11,972 patients listed at high-performing centers, adjusted hazard ratio was 0.32 (95% confidence interval, 0.31 to 0.33) among 203,797 patients listed at centers performing as expected, and adjusted hazard ratio was 0.40 (95% confidence interval, 0.35 to 0.45) among 8039 patients listed at low-performing centers. The survival benefit was significantly different by center performance (P value for interaction <0.001).

Conclusions

Findings indicate that measured center performance modifies the survival benefit of kidney transplantation, but the benefit of transplantation remains highly significant even at centers with low measured quality. Policies that concurrently emphasize improved center performance with access to transplantation should be prioritized to improve ESRD population outcomes.     

Evidence of BK Polyomavirus Infection in Urothelial but not Renal Tumors from a Single Center Cohort of Kidney Transplant Recipients

Emerging evidence indicates that reactivation of BK polyomavirus (BKPyV) in the kidney and urothelial tract of kidney transplant recipients (KTRs) may be associated with cancer in these sites. In this retrospective study of a single center cohort of KTRs (n = 1307), 10 clear cell renal cell carcinomas and 5 urinary bladder carcinomas were analyzed from 15 KTRs for the presence of BKPyV infection through immunohistochemistry and fluorescent in situ hybridization (FISH). Three of these patients had already exhibited biopsy-proven polyomavirus-associated nephropathies (PyVAN). Although the presence of BKPyV large-T antigen was evident in the urothelium from a kidney removed soon after PyVAN diagnosis, it was undetectable in all the formalin-fixed and paraffin-embedded (FFPE) blocks obtained from the 10 kidney tumors. By contrast, large-T antigen (LT) labeling of tumor cells was detected in two out of five bladder carcinomas. Lastly, the proportion of BKPyV DNA-FISH-positive bladder carcinoma nuclei was much lower than that of LT-positive cells. Taken together, our findings further strengthen the association between BKPyV reactivation and cancer development in KTRs, especially bladder carcinoma.