Community Engagement to Improve Equity in Kidney Transplantation from the Ground Up: the Southeastern Kidney Transplant Coalition.

Purpose of review: The purpose of this review is to describe the Southeastern Kidney Transplant Coalition's mission, vision, goals, and Early Transplant Access registry as an example of a community/academic collaboration dedicated to improving access to transplantation and reducing inequities in transplant access. Recent findings: The barriers and facilitators to referral and evaluation for kidney transplantation are not necessarily the same as for waitlisting and transplantation. Recent findings suggest that inequities in transplant access are multilevel and multifactorial and require continued community engagement to improve access to kidney transplantation across patients, health systems, and populations. Summary: Community-engaged approaches are critical to ensuring that inequities in transplant access - which may vary across regions -- are not only described but are addressed in practice in a sustainable manner.

Racial disparities in preemptive referral for kidney transplantation in Georgia.

BACKGROUND: Racial disparities persist in access to kidney transplantation. Racial differences in preemptive referral, or referral prior to dialysis start, may explain this discrepancy. METHODS: Patient-level data on kidney transplant referrals (2005-2012) from all Georgia transplant centers were linked to the United States Renal Data System to examine racial disparities in preemptive referral, waitlisting, and living donor transplant. Adjusted logistic regression and Cox proportional hazard models determined the associations between race (African American vs white) and preemptive referral, and placement on the waitlist and receipt of a living donor kidney, respectively. RESULTS: Among 7752 adults referred for transplant evaluation, 20.38% (n = 1580) were preemptively referred. The odds of African Americans being preemptively referred for transplant evaluation were 37% (OR = 0.63; [95% CI: 0.55 0.71]) lower than white patients. Among preemptively referred patients, there was no racial difference (African Americans compared to white patients. HR = 0.96; [95% CI: 0.88, 1.04]) in waitlisting. However, African Americans were 70% less likely than white patients to receive a living donor transplant (HR = 0.30; [95% CI: 0.21, 0.42]). CONCLUSION: Racial disparities in transplant receipt may be partially explained by disparities in preemptive referral. Interventions to reduce racial disparities in kidney transplant access may need to be targeted earlier in the disease process.

Referral for Kidney Transplantation and Indicators of Quality of Dialysis Care: A Cross-sectional Study.

BACKGROUND: Dialysis facility performance measures to improve access to kidney transplantation are being considered. Referral of patients for kidney transplantation evaluation by the dialysis facility is one potential indicator, but limited data exist to evaluate whether referral is associated with existing dialysis facility quality indicators. STUDY DESIGN: Cross-sectional study. SETTING & PARTICIPANTS: 12,926 incident (July 2005 to September 2011) adult (aged 18-69 years) patients treated at 241 dialysis facilities with complete quality indicator information from US national registry data linked to transplantation referral data from all 3 Georgia kidney transplantation centers. FACTORS: Facility performance on dialysis quality indicators (high, intermediate, and low tertiles). OUTCOME: Percentages of patients referred within 1 year of dialysis therapy initiation at dialysis facility. RESULTS: Overall, a median of 25.4% of patients were referred for kidney transplantation within 1 year of dialysis therapy initiation. Higher facility-level referral was associated with better performance with respect to standardized transplantation ratio (high, 28.6%; intermediate, 25.1%; and low, 22.9%; P=0.001) and percentage waitlisted (high, 30.7%; intermediate, 26.8%; and low, 19.2%; P<0.001). Facility-level referral was not associated with indicators of quality of care associated with dialysis therapy initiation, including percentage of incident patients being informed of transplantation options. For most non-transplantation-related indicators of high-quality care, including those capturing mortality, morbidity, and anemia management, better performance was not associated with higher facility-level transplantation referral. LIMITATIONS: Potential ecologic fallacy and residual confounding. CONCLUSIONS: Transplantation referral among patients at dialysis facilities does not appear to be associated with overall quality of dialysis care at the facility. Quality indicators related to kidney transplantation were positively associated with, but not entirely correspondent with, higher percentages of patients referred for kidney transplantation evaluation from dialysis facilities. These results suggest that facility-level referral, which is within the control of the dialysis facility, may provide information about the quality of dialysis care beyond current indicators.

A Randomized Trial to Reduce Disparities in Referral for Transplant Evaluation.

Georgia has the lowest kidney transplant rates in the United States and substantial racial disparities in transplantation. We determined the effectiveness of a multicomponent intervention to increase referral of patients on dialysis for transplant evaluation in the Reducing Disparities in Access to kidNey Transplantation Community Study (RaDIANT), a randomized, dialysis facility-based, controlled trial involving >9000 patients receiving dialysis from 134 dialysis facilities in Georgia. In December of 2013, we selected dialysis facilities with either low transplant referral or racial disparity in referral. The intervention consisted of transplant education and engagement activities targeting dialysis facility leadership, staff, and patients conducted from January to December of 2014. We examined the proportion of patients with prevalent ESRD in each facility referred for transplant within 1 year as the primary outcome, and disparity in the referral of black and white patients as a secondary outcome. Compared with control facilities, intervention facilities referred a higher proportion of patients for transplant at 12 months (adjusted mean difference [aMD], 7.3%; 95% confidence interval [95% CI], 5.5% to 9.2%; odds ratio, 1.75; 95% CI, 1.36 to 2.26). The difference between intervention and control facilities in the proportion of patients referred for transplant was higher among black patients (aMD, 6.4%; 95% CI, 4.3% to 8.6%) than white patients (aMD, 3.7%; 95% CI, 1.6% to 5.9%; P<0.05). In conclusion, this intervention increased referral and improved equity in kidney transplant referral for patients on dialysis in Georgia; long-term follow-up is needed to determine whether these effects led to more transplants.

Variation in Dialysis Facility Referral for Kidney Transplantation Among Patients With End-Stage Renal Disease in Georgia.

IMPORTANCE: Dialysis facilities in the United States are required to educate patients with end-stage renal disease about all treatment options, including kidney transplantation. Patients receiving dialysis typically require a referral for kidney transplant evaluation at a transplant center from a dialysis facility to start the transplantation process, but the proportion of patients referred for transplantation is unknown. OBJECTIVE: To describe variation in dialysis facility-level referral for kidney transplant evaluation and factors associated with referral among patients initiating dialysis in Georgia, the US state with the lowest kidney transplantation rates. DESIGN, SETTING, AND PARTICIPANTS: Examination of United States Renal Data System data from a cohort of 15,279 incident, adult (18-69 years) patients with end-stage renal disease from 308 Georgia dialysis facilities from January 2005 to September 2011, followed up through September 2012, linked to kidney transplant referral data collected from adult transplant centers in Georgia in the same period. MAIN OUTCOMES AND MEASURES: Referral for kidney transplant evaluation within 1 year of starting dialysis at any of the 3 Georgia transplant centers was the primary outcome; placement on the deceased donor waiting list was also examined. RESULTS: The median within-facility percentage of patients referred within 1 year of starting dialysis was 24.4% (interquartile range, 16.7%-33.3%) and varied from 0% to 75.0%. Facilities in the lowest tertile of referral (<19.2%) were more likely to treat patients living in high-poverty neighborhoods (absolute difference, 21.8% [95% CI, 14.1%-29.4%]), had a higher patient to social worker ratio (difference, 22.5 [95% CI, 9.7-35.2]), and were more likely nonprofit (difference, 17.6% [95% CI, 7.7%-27.4%]) compared with facilities in the highest tertile of referral (>31.3%). In multivariable, multilevel analyses, factors associated with lower referral for transplantation, such as older age, white race, and nonprofit facility status, were not always consistent with the factors associated with lower waitlisting. CONCLUSIONS AND RELEVANCE: In Georgia overall, a limited proportion of patients treated with dialysis were referred for kidney transplant evaluation between 2005 and 2011, but there was substantial variability in referral among facilities. Variables associated with referral were not always associated with waitlisting, suggesting that different factors may account for disparities in referral.

The RaDIANT community study protocol: community-based participatory research for reducing disparities in access to kidney transplantation.

BACKGROUND: The Southeastern United States has the lowest kidney transplant rates in the nation, and racial disparities in kidney transplant access are concentrated in this region. The Southeastern Kidney Transplant Coalition (SEKTC) of Georgia, North Carolina, and South Carolina is an academic and community partnership that was formed with the mission to improve access to kidney transplantation and reduce disparities among African American (AA) end stage renal disease (ESRD) patients in the Southeastern United States. METHODS/DESIGN: We describe the community-based participatory research (CBPR) process utilized in planning the Reducing Disparities In Access to kidNey Transplantation (RaDIANT) Community Study, a trial developed by the SEKTC to reduce health disparities in access to kidney transplantation among AA ESRD patients in Georgia, the state with the lowest kidney transplant rates in the nation. The SEKTC Coalition conducted a needs assessment of the ESRD population in the Southeast and used results to develop a multicomponent, dialysis facility-randomized, quality improvement intervention to improve transplant access among dialysis facilities in GA. A total of 134 dialysis facilities are randomized to receive either: (1) standard of care or "usual" transplant education, or (2) the multicomponent intervention consisting of transplant education and engagement activities targeting dialysis facility leadership, staff, and patients within dialysis facilities. The primary outcome is change in facility-level referral for kidney transplantation from baseline to 12 months; the secondary outcome is reduction in racial disparity in transplant referral. DISCUSSION: The RaDIANT Community Study aims to improve equity in access to kidney transplantation for ESRD patients in the Southeast. TRIAL REGISTRATION: Clinicaltrials.gov number NCT02092727.

Cardiovascular disease in kidney donors: matched cohort study.

OBJECTIVE: To determine whether people who donate a kidney have an increased risk of cardiovascular disease. DESIGN: Retrospective population based matched cohort study. PARTICIPANTS: All people who were carefully selected to become a living kidney donor in the province of Ontario, Canada, between 1992 and 2009. The information in donor charts was manually reviewed and linked to provincial healthcare databases. Matched non-donors were selected from the healthiest segment of the general population. A total of 2028 donors and 20,280 matched non-donors were followed for a median of 6.5 years (maximum 17.7 years). Median age was 43 at the time of donation (interquartile range 34-50) and 50 at the time of follow-up (42-58). MAIN OUTCOME MEASURES: The primary outcome was a composite of time to death or first major cardiovascular event. The secondary outcome was time to first major cardiovascular event censored for death. RESULTS: The risk of the primary outcome of death and major cardiovascular events was lower in donors than in non-donors (2.8 v 4.1 events per 1000 person years; hazard ratio 0.66, 95% confidence interval 0.48 to 0.90). The risk of major cardiovascular events censored for death was no different in donors than in non-donors (1.7 v 2.0 events per 1000 person years; 0.85, 0.57 to 1.27). Results were similar in all sensitivity analyses. Older age and lower income were associated with a higher risk of death and major cardiovascular events in both donors and non-donors when each group was analysed separately. CONCLUSIONS: The risk of major cardiovascular events in donors is no higher in the first decade after kidney donation compared with a similarly healthy segment of the general population. While we will continue to follow people in this study, these interim results add to the evidence base supporting the safety of the practice among carefully selected donors.

Health insurance status of US living kidney donors.

BACKGROUND AND OBJECTIVES: Ensuring follow-up of living kidney donors (LKDs) is essential to long-term preventive care. We sought information on health insurance status of US LKDs, with particular attention to age, gender, and ethnicity. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The United Network for Organ Sharing/Organ Procurement Transplantation Network database was queried for associations among age at donation, race, gender, and health insurance status. We studied all US LKDs between July 2004 and September 2006. RESULTS: A total of 10,021 LKDs with known health insurance status were studied, 1765 (18%) of whom lacked health insurance at donation. There were 4852 donors without health insurance information. Younger kidney donors had higher rates of being uninsured (age 18 to 34: 26.2%; age 35 to 49: 15.2%; age 50 to 64: 11.2%; age >65: 3.8%; P < 0.0001), as did men (19.5 versus 16.3% for women; P < 0.0001), and ethnic minorities (white 13.4%, black 21%, Hispanic 35.6%, Asian 26.7%; P < 0.0001). CONCLUSIONS: This study confirms that younger patients, ethnic minorities, and men are less likely to have health insurance when donating a kidney, which could negatively affect adherence to long-term follow-up.

Race and renal function early after live kidney donation: an analysis of the United States Organ Procurement and Transplantation Network Database.

Among Americans, the risk for kidney disease is higher in individuals of African descent (AA) when compared with Caucasians. We considered whether there are similar racial differences in kidney function soon after donor nephrectomy. Of the 31,928 live kidney donors that donated between the years 2000 and 2005, 16,996 (53%) had post-donation serum creatinine recorded at a mean follow-up of 156 d (range 1-1410 d). A total of 14,525 (85%) were Caucasians and 2471 (15%) were AA. When compared with Caucasians, AA donors were more likely to be younger, heavier, and male, had a higher baseline serum creatinine and a shorter duration of follow-up. After accounting for these differences, the serum creatinine after donation and fractional rise in serum creatinine after donation were similar between the two groups (AA vs. Caucasian donors, 1.3 ± 0.3 vs. 1.2 ± 0.3 mg/dL; 53% vs. 45%) and the post-donation estimated glomerular filtration rate was also similar (57.2 ± 0.6 vs. 56.0 ± 0.2 mL/min per 1.73 m(2)). We observed no major clinical difference in glomerular filtration rate and ability to compensate for loss of renal mass soon after live kidney donation between Caucasian and AA donors.

Discovering misattributed paternity in living kidney donation: prevalence, preference, and practice.

When evaluating a living kidney donor and recipient with a father-child relationship, it may be discovered that the two are not biologically related. We analyzed data from the United Network for Organ Sharing and the Canadian Organ Replacement Registry to determine how frequently this occurs. We surveyed 102 potential donors, recipients, and transplant professionals for their opinion on whether such information should be disclosed to the donor-recipient pair. We communicated with transplant professionals from 13 Canadian centers on current practices for handling this information. In the United States and Canada, the prevalence of father-child living kidney donor-recipient pairs with less than a one-haplotype human leukocyte antigen match (i.e., misattributed paternity) is between 1% and 3%, or approximately 0.25% to 0.5% of all living kidney donations. Opinions about revealing this information were variable: 23% strongly favored disclosure; whereas, 24% were strongly opposed to it. Current practices are variable; some centers disclose this information, whereas others do not. Discovering misattributed paternity in living donation is uncommon but can occur. Opinions on how to deal with this sensitive information are variable. Discussion among transplant professionals will facilitate best practices and policies. Strategies adopted by some centers can be considered.

Cardiovascular disease and hypertension risk in living kidney donors: an analysis of health administrative data in Ontario, Canada.

BACKGROUND: Knowledge of any harm associated with living kidney donation guides informed consent and living donor follow-up. Risk estimates in the literature are variable, and most studies did not use a healthy control group to assess outcomes attributable to donation. METHODS: We observed a retrospective cohort using health administrative data for donations which occurred in Ontario, Canada between the years 1993 and 2005. There were a total of 1278 living donors and 6359 healthy adults who acted as a control group. Individuals were followed for a mean of 6.2 years (range, 1-13 years) after donation. The primary outcome was a composite of time to death or first cardiovascular event (myocardial infarction, stroke, angioplasty, and bypass surgery). The secondary outcome was time to a diagnosis of hypertension. RESULTS: There was no significant difference in death or cardiovascular events between donors and controls (1.3% vs. 1.7%; hazard ratio 0.7, 95% confidence interval 0.4-1.2). Donors were more frequently diagnosed with hypertension than controls (16.3% vs. 11.9%, hazard ratio 1.4, 95% confidence interval 1.2-1.7) but were also seen more often by their primary care physicians (median [interquartile range] 3.6 [1.9-6.1] vs. 2.6 [1.4-4.3] visits per person year, P<0.001). CONCLUSIONS: Based on administrative data, the risk of cardiovascular disease was unchanged in the first decade after kidney donation. The observed increase in diagnosed hypertension may be due to nephrectomy or more blood pressure measurements received by donors in follow-up and requires prospective study.

Gene expression patterns in deceased donor kidneys developing delayed graft function after kidney transplantation.

BACKGROUND: Delayed graft function (DGF) after kidney transplantation (KTx) ranges between 2% and 50%. The mechanisms leading to DGF deserve special interest because DGF exerts negative influences on long-term outcomes. We studied gene expression profiles in deceased donor kidney (DDK) biopsies with and without DGF. METHODS: Gene expression profiling was performed on donor kidney tissues from 33 DDK with the use of microarrays. DDK were classified as grafts with immediate function (non-DGF; n=21) and grafts with DGF (n=12). DGF was defined as a dialysis requirement in the first week after transplantation. Demographic donor and recipient information was collected. The robust-multiarray average method was used to estimate probe set expression summaries. Logistic regression was used to identify genes significantly associated with DGF development. RESULTS: Patients were followed for 3 months after KTx. Thirty-eight probe sets (n=36 genes) were univariably differentially expressed in DDK with DGF when compared with DDK with non-DGF (alpha=0.001). Sixty-nine probe sets (n=65 genes) were differentially expressed in DDK with DGF when compared with DDK with non-DGF after adjusting for cold ischemia time (alpha=0.001). Gene ontology terms classified the overexpressed genes in DDK with DGF as principally related to cell cycle/growth (e.g., IGFBP5, CSNK2A2), signal transduction (e.g., RASGRP3), immune response (e.g., CD83, BCL3, MX1), and metabolism (e.g., ENPP4, GBA3). TNFRSF1B was overexpressed in DDK with DGF. CONCLUSIONS: Cold ischemia time was a predictor of DGF independently of the preservation method. We identified a set of 36 genes candidates of DGF in DDK, with genes involved in the inflammatory response being the more important.

High prevalence of vitamin D deficiency in African American kidney transplant recipients.

Kidney transplant patients are at high risk for developing Vitamin D(3) deficiency. The prevalence rates of 25(OH) Vitamin D(3) deficiency and its association with parathyroid hormone (PTH) levels in African American kidney transplant recipients have not been examined. We measured 25(OH) Vitamin D(3) and intact PTH concentrations in 38 African American transplant patients at our center in October 2006. We collected various laboratory data including serum creatinine, calcium, phosphate, alkaline phosphatase, and glomerular filtration rate. Vitamin D(3) deficiency was present in 57.8% of the patients and 94.7% had insufficiency. Ten of 22 (45%) patients with chronic kidney disease stage 3 had intact PTH more than or equal to 70 pg/mL. On multivariate analysis, 25(OH) Vitamin D(3) level was negatively correlated with intact PTH (P<0.01) and alkaline phosphatase level was positively associated with intact PTH levels (P<0.002). Vitamin D(3) deficiency and insufficiency is present in most of the African American kidney transplant patients.

Molecular pathways involved in loss of kidney graft function with tubular atrophy and interstitial fibrosis.

Loss of kidney graft function with tubular atrophy (TA) and interstitial fibrosis (IF) causes most kidney allograft losses. We aimed to identify the molecular pathways involved in IF/TA progression. Kidney biopsies from normal kidneys (n = 24), normal allografts (n = 6), and allografts with IF/TA (n = 17) were analyzed using high-density oligonucleotide microarray. Probe set level tests of hypotheses tests were conducted to identify genes with a significant trend in gene expression across the three groups using Jonckheere-Terpstra test for trend. Interaction networks and functional analysis were used. An unsupervised hierarchical clustering analysis showed that all the IF/TA samples were associated with high correlation. Gene ontology classified the differentially expressed genes as related to immune response, inflammation, and matrix deposition. Chemokines (CX), CX receptor (for example, CCL5 and CXCR4), interleukin, and interleukin receptor (for example, IL-8 and IL10RA) genes were overexpressed in IF/TA samples compared with normal allografts and normal kidneys. Genes involved in apoptosis (for example, CASP4 and CASP5) were importantly overexpressed in IF/TA. Genes related to angiogenesis (for example, ANGPTL3, ANGPT2, and VEGF) were downregulated in IF/TA. Genes related to matrix production-deposition were upregulated in IF/TA. A distinctive gene expression pattern was observed in IF/TA samples compared with normal allografts and normal kidneys. We were able to establish a trend in gene expression for genes involved in different pathways among the studied groups. The top-scored networks were related to immune response, inflammation, and cell-to-cell interaction, showing the importance of chronic inflammation in progressive graft deterioration.

Quantitation of alloantibody concentration can predict patient sensitivity to intravenous immunoglobulin desensitization.

Despite the success of intravenous immunoglobulin (IVIg) desensitization to reduce anti-human leukocyte antigen antibodies, its high failure rate and expense limit its usefulness. We speculated that quantitation of alloantibody concentration could allow early identification of IVIg resistant patients. Patients were described as nonresponders (n=3) or responders (n=8). Panel reactive antibodies (PRA) were determined using Flowbeads and concentration calculated as molecules of equivalent soluble fluorochrome (MESF). PRA was equivalent between nonresponders and responders before (97+/-3% vs. 76+/-20%, P=NS) and after 3 IVIg/plasmapheresis (PP) treatments but lower among responders at end-of-treatment (76+/-20% vs. 44+/-15%, P<0.01). In contrast, pretreatment MESFs were higher (333,640+/-241,352 vs. 38,741+/-5,133, P=0.006) among nonresponders than responders. During treatment, MESFs decreased (P<0.05) in 0 of 3 nonresponders vs. 8 of 8 responders. Final MESFs were higher among nonresponders than responders. We report that quantitation of MESFs allows early identification of IVIg/PP resistant patients. This sensitive and inexpensive technique should allow more effective patient selection and reduce the costs associated with desensitization.

Living kidney donors requiring transplantation: focus on African Americans.

Risks of kidney donation include a poorly characterized risk of late kidney failure. We hypothesized that African Americans (AA) kidney donors were at greater risk for kidney failure. The United Network for Organ Sharing/Organ Procurement Transplantation Network database was searched for patients who previously donated a kidney and were subsequently placed on the kidney transplant waiting list. We then compared the race of donors listed for kidney transplant to the race of all living donors during the same time period. Between 1993 and 2005, 8889 donors (14.3%) were AA and 42,419 (68.1%) were Caucasian. During this same time period, 102 previous kidney donors developed kidney failure and were listed for kidney transplantation. Although AAs comprised 14.3% of all living kidney donors, they constituted 44% of donors reaching the waiting list (P<0.001). These data provide indirect evidence that the risk of kidney failure may be exaggerated in AA donors.

Evaluation of gene panel mRNAs in urine samples of kidney transplant recipients as a non-invasive tool of graft function.

Non-invasive monitoring may be useful after kidney transplantation (KT), particularly for predicting acute rejection (AR). It is less clear whether chronic allograft nephropathy (CAN) is also associated with changes in urine cells. To identify non-invasive markers of allograft function in kidney transplant patients (KTP), mRNA levels of AGT, TGF-beta1, EGFR, IFN-gamma, TSP-1, and IL-10 in urine (Ur) samples were studied using QRT-PCR. Ninety-five KTP and 111 Ur samples were evaluated. Patients (Pts) were divided as, within six months (N = 31), and with more than six months post-KT (N = 64). KTP with more than six months post-KT were classified as KTP with stable kidney function (SKF) (N = 32), KTP with SKF (creatinine < 2 mg/dL) and proteinuria > 500 mg/24 h (N = 18), and KTP with biopsy proven CAN (N = 14). F-test was used to test for equality of variances between groups. IL-10 mRNA was decreased in Ur samples from KTP with less than six months post-KT (P = 0.005). For KTR groups with more than six months post-KT, AGT and EGFR mRNA were statistically different among KTP with SKF, KTP with SKF and proteinuria, and CAN Pts (P = 0.003, and P = 0.01), with KTP with SKF having higher mean expression. TSP-1 mRNA levels also were significantly different among these three groups (P = 0.04), with higher expression observed in CAN Pts. Using the random forest algorithm, AGT, EGFR, and TGF-beta1 were identified as predictors of CAN, SKF, SKF with proteinuria. A characteristic pattern of mRNA levels in the different KTP groups was observed indicating that the mRNA levels in Ur cells might reflect allograft function.

Hepatitis C virus infection and kidney transplantation: predictors of patient and graft survival.

BACKGROUND: The effect of hepatitis C virus (HCV) infection on patients undergoing kidney transplantation (KTx) is uncertain. This study aimed to evaluate the outcomes of our HCV+/end-stage renal disease (ESRD) patient population based on the therapeutic option including KTx or continuation in dialysis. METHODS: KTx performed at Virginia Commonwealth University Hospital between January 2000 and December 2004 were tracked prospectively. Forty-three out of a total of 394 KTx patients included in the analysis were HCV+. A group of 52 contemporaneous HCV+/ESRD patients listed, but never transplanted, was also analyzed. HCV-negative transplanted patients were used as the control group. RESULTS: Patient survival posttransplantation was 81.4% and 68.5% at 1 and 3 years in the HCV+ group, and 97.1% and 92.9% at 1 and 3 years in the HCV- group, respectively (P=0.001). Graft survival was 81.2% and 64.1% at 1 and 3 years in the HCV+ group, and 93.2% and 84.1% at 1 and 3 years posttransplantation in the HCV- group (P=0.01). Univariate analysis identified Knodell score as a predictor of mortality in HCV+ patients (P=0.04). Cox proportional hazards multivariate analysis identified deceased donor (P=0.02), previous kidney transplant (P=0.007), pretransplant diabetes (P=0.05), and Knodell Score (P=0.012) as predictors of patient mortality. Patient survival was superior in HCV+ patients undergoing KTx versus remaining on dialysis. CONCLUSIONS: Patients with ESRD/HCV+ benefit from KTx without achieving the excellent survival of HCV-/ESRD patients. Liver biopsy is a useful tool to identify advanced liver disease at pretransplantation time.

Establishing the molecular pathways involved in chronic allograft nephropathy for testing new noninvasive diagnostic markers.

BACKGROUND: Chronic allograft nephropathy (CAN) is a cause of graft loss. The multistage processes that result in CAN are poorly understood. Noninvasive assays for detecting allograft dysfunction and predicting long-term outcomes are a priority in transplantation (Tx). METHODS: Renal tissue from kidney transplant patients (KTP) with CAN (n=11) and normal kidneys (NK; n=7) were studied using microarrays. Markers resulting from the microarray analysis (transforming growth factor [TGF]-beta, epidermal growth factor receptor [EGFR], angiotensinogen [AGT]) were tested in urine (Ur) and peripheral blood (PB) samples from the CAN patients (collected at the biopsy time) using reverse-transcriptase real-time polymerase chain reaction. Ur and PB samples from long-term KTP with stable renal function (SRF; n=20) were used as control. RESULTS: Assuming unequal variances between CAN and NK, using a false discovery rate of 0.005, and running 1,000 of all possible permutations, 728 probe sets were differentially expressed. Genes related to fibrosis and extracellular matrix deposition (i.e., TGF-beta, laminin, gamma 2, metalloproteinases-9, and collagen type IX alpha 3) were up-regulated. Genes related to immunoglobulins, B cells, T-cell receptor, nuclear factor of activated T cells, and cytokine and chemokines receptors were also upregulated. EGFR and growth factor receptor activity (FGFR)2 were downregulated in CAN samples. AGT, EGFR, and TGF-beta levels were statistical different in urine but not in blood samples of CAN patients when compared to KTP with SRF (P<0.001, P=0.04, and P<0.001, respectively). CONCLUSIONS: Genes related to fibrosis, extracellular matrix deposition, and immune response were found up-regulated in CAN. Markers resulting from the microarray analysis were differentially expressed in Ur samples of the CAN patients and in concordance with the microarray profiles.