Death-censored Graft Failure Research Articles

The relative importance of donor age in deceased and living donor kidney transplantation

In deceased donor kidney transplantation donor age is known to influence graft survival. The influence of living donor age on graft survival is questioned. We compared the influence of living and deceased donor age on the outcome of renal transplantation. All 1821 transplants performed in our center between 1990 and 2009 were included in the analysis. Observation was until April 2012. A total of 941 patients received a deceased donor kidney and 880 a living donor kidney. In multivariate Cox analysis, recipient age, maximum and current panel reactive antibodies, transplant year, HLA-mismatches, donor age, donor gender, donor type, delayed graft function, and calcineurin inhibitor (CNI) and prednisone as initial immunosuppression were found to have a significant influence on death-censored graft failure. The influence of both living and deceased donor age followed a J-shaped curve, above 30 years the risk increased with increasing age. Donor type and donor age had an independent influence. The graft failure risk of deceased donor transplantation is almost twice that of living donor transplantation so that a 60-year-old living donor kidney has the same graft failure risk as a 20-year-old deceased donor kidney.

Depression Diagnoses After Living Kidney Donation

Limited data exist on correlates of psychological outcomes after kidney donation. We used a database integrating Organ Procurement and Transplantation Network registrations for 4650 living kidney donors from 1987 to 2007 with administrative data of a U.S. private health insurer (2000-2007 claims) to identify depression diagnoses among prior living donors. The burden and demographic correlates of depression after enrollment in the insurance plan were estimated by Cox regression. Graft failure and death of the donor's recipient were examined as time-varying exposures. After start of insurance benefits, the cumulative frequency of depression diagnosis was 4.2% at 1 year and 11.5% at 5 years, and depression among donors was less common than among age- and gender-matched general insurance beneficiaries (rate ratio, 0.70; 95% confidence intervals [CI], 0.60-0.81). Demographic and clinical correlates of increased likelihood of depression diagnoses among the prior donors included female gender, white race, and some perioperative complications. After adjustment for donor demographic factors, recipient death (adjusted hazard ratio (aHR), 2.23; 95% CI, 1.11-4.48) and death-censored graft failure (aHR, 3.30; 95% CI, 1.49-7.34) were associated with two to three times the relative risk of subsequent depression diagnosis among nonspousal unrelated donors. There were trends toward increased depression diagnoses after recipient death and graft failure among spousal donors but no evidence of associations of these recipient events with the likelihood of depression diagnosis among related donors. Recipient death and graft loss predict increased depression risk among unrelated living donors in this privately insured sample. Informed consent and postdonation care should consider the potential impact of recipient outcomes on the psychological health of the donor.

Human leukocyte antigen mismatches associated with increased risk of rejection, graft failure, and death independent of initial immunosuppression in renal transplant recipients

Human leukocyte antigen (HLA) mismatches have been shown to adversely affect renal allograft outcomes and remain an important component of the allocation of deceased donor (DD) kidneys. The ongoing importance of HLA mismatches on transplant outcomes in the era of more potent immunosuppression remains debatable. Using Australia and New Zealand Dialysis and Transplant Registry, live and DD renal transplant recipients between 1998 and 2009 were examined. The association between the number of HLA mismatches and HLA-loci mismatches and outcomes were examined. Of the 8036 renal transplant recipients, 59% had between 2 and 4 HLA mismatches. Compared with 0 HLA mismatch, increasing HLA mismatches were associated with a higher risk of graft failure and patient death in the adjusted models. HLA mismatches were associated with an incremental risk of rejection although the relative risk was higher for live donor kidney transplants. Increasing HLA-AB and HLA-DR mismatches were associated with a greater risk of acute rejection, graft failure, death-censored graft failure, and/or death. There was no consistent association between initial immunosuppressive regimen and outcomes. Our results corroborate and extend the previous registry analyses demonstrating that HLA mismatches are associated with poorer transplant outcomes independent of immunosuppression and transplant era.

Association of pre-transplant erythropoiesis-stimulating agent responsiveness with post-transplant outcomes

The role of pre-transplant erythropoiesis-stimulating agent (ESA) responsiveness in affecting post-transplant outcomes is not clear. Linking the 5-year patient data of a large dialysis organization to the 'Scientific Registry of Transplant Recipients', we identified 8795 hemodialyzed patients who underwent first kidney transplantation. Mortality or graft failure, delayed graft function (DGF) and acute rejection risks were estimated by Cox regression [hazard ratio (HR)] and logistic regression, respectively. Patients were 48 ± 14 years old and included 38% women and 36% diabetics. Compared to renal allograft recipients who were in the first quartile of pre-transplant ESA responsiveness index (ERI), i.e. ESA dose divided by hemoglobin and weight, recipients in second, third and fourth quartiles had higher adjusted graft-censored death HR (and 95% confidence intervals) of 1.7 (1.0-2.7), 1.8 (1.1-2.9) and 2.3 (1.4-3.9) and higher death-censored graft failure HR of 1.6 (1.0-2.5), 2.0 (1.2-3.1) and 1.6 (0.9-2.6), respectively. No significant association between pre-transplant ERI and post-transplant DGF or acute rejection was detected. Higher pre-transplant ERI during the hemodialysis treatment period was associated with worse post-transplant long-term outcomes including increased all-cause death and higher risk of graft failure.

Serum Phosphate Measured at 6 and 12 Months After Successful Kidney Transplant Is Independently Associated With Subsequent Graft Loss

Serum phosphate concentrations have been shown to predict graft loss in prevalent, but not incident, kidney transplant populations. The reasons for this are unknown. We investigated whether serum phosphate at 6 or 12 months posttransplant was associated with graft loss in the same cohort. Data were collected for 325 patients transplanted and followed up at a single center (1996-2004). The association between serum phosphate at 6 and 12 months posttransplant and graft failure was analyzed. Univariable associations with death-censored graft failure were seen for serum phosphate at 6 and 12 months (hazard ratio [HR] 1.33; 95% confidence interval [CI] 1.20-1.48; P < .001, and HR 1.40; CI 1.27-1.54; P < .001). On bivariable analysis (phosphate at 6 vs 12 mo), a significant association remained for both variables and increased graft failure rate (HR 1.19; CI 1.07-1.34; P = .002, and HR 1.37; CI 1.21-1.55; P < .001). These associations persisted in multivariable models (HR 1.27; CI 1.07-1.51; P = .007, and HR 1.34; CI 1.14-1.57; P < .001 for phosphate at 6 and 12 mo). Serum phosphate at 6 and 12 months posttransplant is an independent predictor of graft loss. Any future trial designed to investigate the benefits of phosphate lowering should consider recruiting patients as early as 6 months posttransplant.

Effects of Antibody Induction on Transplant Outcomes in Human Leukocyte Antigen Zero-Mismatch Deceased Donor Kidney Recipients

We aimed to investigate the impact of antibody induction on outcomes in human leukocyte antigen (HLA) 0-mismatched deceased donor kidney recipients. Using the Organ Procurement and Transplant Network/United Network of Organ Sharing database as of November 2009, we identified 44,008 adult deceased donor kidney recipients who received primary kidney transplants alone between 2003 and 2008 (HLA 0 mismatch, n = 6274; ≥ 1 mismatch, n=37,734; median follow-up: 834 days). The impact of induction (thymoglobulin, interleukin-2 receptor antagonists [IL-2RA], or alemtuzumab; vs. no induction) on rejection (initial hospitalization, 6 months, first year), death-censored graft failure, and mortality were analyzed using multivariate logistic and Cox regression in the two groups. The impact of individual agents on outcomes was further analyzed in 0-mismatch recipients. There was a decreased risk of rejection over the first 6 months for HLA 0-mismatch recipients of antibody induction (adjusted odds ratio=0.71, P=0.003), but this effect was not observed at 1 year; in comparison, induction was associated with a reduced risk of rejection over the first year for HLA-mismatched recipients (0.87, P<0.001). The use of thymoglobulin (0.72, P=0.02) and IL-2RA (0.67, P=0.004) was associated with a decreased risk of rejection compared with no-induction at 6 months but was not different at 1 year (thymoglobulin: 0.77, P=0.05; IL-2RA:0.81, P=0.11) in HLA 0-mismatched recipients. Induction was not associated with improved graft or patient survival in HLA 0-mismatch recipients. In HLA 0-mismatch deceased donor recipients, antibody induction was associated with a decreased risk of rejection at 6 months posttransplant. Its use did not improve graft and patient survival over the follow-up period.

Lack of impact of donor age on patient survival for renal transplant recipients ≥60 years

There has been an increase in the number of older patients on the transplant waiting list and acceptance of older donor kidneys. Although kidneys from older donors have been associated with poorer graft outcomes, whether there is a differential impact of donor age on outcomes in older recipients remains unclear. The aim of this study was to evaluate the effect of donor age on graft and patient survival in renal transplant (RT) recipients ≥60years. Using the Australia and New Zealand Dialysis and Transplant Registry, outcomes of 1,037 RT recipients ≥60years between 1995 and 2009 were analyzed. Donor age groups were categorized into 0-20, >20-40, >40-60, and >60years. Compared with recipients receiving donor kidneys >60years, those receiving donor kidneys >20-40years had lower risk of acute rejection (odds ratio 0.46, 95% CI 0.27, 0.79; P<0.01) and death-censored graft failure (HR 0.37, 95% CI 0.19, 0.72; P<0.01). There was no association between donor age groups and death. With a corresponding growth in the availability of older donor kidneys and the observed lack of association between donor age and patient survival in RT recipients ≥60years, preferential allocation of older donor kidneys to RT recipients ≥60years may not disadvantage the life expectancy of these patients.

Pretransplant serum phosphate levels and outcomes after kidney transplantation

The relation between serum phosphate control while on dialysis and kidney transplant outcomes is uncertain. Our study assessed the effect of pretransplant serum phosphate levels (PTxP) on kidney transplant outcomes. Hemodialysis patients included in the Dialysis Morbidity and Mortality Study of the US Renal Data System, undergoing kidney transplantation were studied (n=801). Delayed graft function (DGF) and graft failure as a function of PTxP, were assessed using multivariable logistic and Cox regression models. The within-quartile medians (interquartile range) of PTxP were 4.2 (3.7-4.5), 5.4 (5.1-5.7), 6.4 (6.1-6.8) and 8.5 (7.7-9.7) mg/dL. The adjusted odds ratio (OR) for DGF was significantly elevated for the fourth vs. first PTxP quartiles (OR=1.68; 95% confidence interval [95% CI], 1.05-2.71). Restricting the cohort to patients transplanted prior to the publication of the KDOQI bone metabolism and disease guidelines, PTxP measured within 1-year of transplant, or deceased donor recipients generally showed similar results. The adjusted hazard ratios for death-censored graft failure increased across PTxP quartiles (p for trend = 0.015). Higher PTxP is associated with an increased risk of adverse kidney allograft outcomes including DGF and death-censored graft failure. This suggests an important additional benefit of optimizing phosphate control in patients awaiting kidney transplantation while on dialysis.

Renal function following living, standard criteria deceased and expanded criteria deceased donor kidney transplantation: impact on graft failure and death

We examined United States Renal Data System (USRDS) data for adult kidney transplant recipients in 1995-2003 (n = 87 575) to investigate associations of 12-month renal function with long-term clinical outcomes. Estimated glomerular filtration rate (eGFR) was computed by the Modification of Diet in Renal Disease (MDRD) equation. Associations of eGFR at the first transplant anniversary with graft and patient-survival in years 1-9 post-transplant were evaluated by multivariate nonlinear regression with spline forms, adjusted for recipient, donor, and transplant factors. Regardless of donor type, the likelihood of graft failure and death increased significantly with lower eGFR. The impact of poor eGFR was more pronounced for graft failure than death. Relative effects were similar across donor types, but were strongest among living-donor recipients. For example, compared with reference eGFR of 80 ml/min/1.73 m2, 1-year eGFR of 20 ml/min/1.73 m2 was associated with adjusted hazards ratios for subsequent death-censored graft failure of 9.2 in living, 8.9 in standard criteria deceased, and 5.9 in expanded criteria deceased-donor recipients. First-year renal function after kidney transplantation has strong, nonlinear associations with subsequent allograft and patient survival regardless of donor type. Post-transplant eGFR may be a useful end-point for discriminating benefits of care strategies that differentially affect renal function.

Association Between Age and Graft Failure Rates in Young Kidney Transplant Recipients

Age at transplant and graft failure risk are associated in young kidney transplant recipients. The risk of graft failure may also vary by current age, irrespective of age at transplant. We sought to estimate age-specific graft failure rates in young kidney transplant recipients and to estimate the relative hazards of graft failure at different ages, compared with at the age of 25 to 29 years. We evaluated 90,689 patients recorded in the United States Renal Data System database who received a first transplant when younger than 40 years (1988-2009); 18,310 were younger than 21 years at transplant. Time-dependent Cox models with time-varying covariates were used to estimate the association between age (time-dependent) and death-censored graft failure risk, adjusted for time since transplant and other potential confounders. There were 31,857 graft failures over a median follow-up of 5.9 years (interquartile range, 2.5-10.5 years; maximum, 21.8 years). Crude age-specific graft failure rates were highest in 19 year olds (6.6 per 100 person-years). Compared with individuals with the same time since transplant observed at 25 to 29 years of age, death-censored graft failure rates were highest in 17 to 24 year olds (hazard ratio, 1.20; [95% confidence interval 1.13, 1.27] for 17-20 year olds and 1.20 [1.13, 1.26] for 21-24 year olds; both P<0.0001) and lowest in 5 to 12 year olds (hazard ratio, 0.60; [0.53, 0.68] for 5-9 year olds and 0.56 [0.49, 0.64] for 10-12 year olds; both P<0.0001). Among first kidney transplant recipients younger than 40 years, older adolescents and young adults (17-24 years) have the highest risk of graft failure, irrespective of age at transplant.

Dialysis Modality and Outcomes in Kidney Transplant Recipients

The influence of pretransplant dialysis modality on post-transplant outcomes is not clear. This study examined associations of pretransplant dialysis modality with post-transplant outcomes in a large national cohort of kidney transplant recipients. Linking the 5-year patient data of a large dialysis organization to the Scientific Registry of Transplant Recipients, 12,416 hemodialysis and 2092 peritoneal dialysis patients who underwent first kidney transplantation were identified. Mortality or graft failure and delayed graft function risks were estimated by Cox regression (hazard ratio) and logistic regression (odds ratio), respectively. Recipients treated with peritoneal dialysis pretransplantation had lower (21.9/1000 patient-years [95% confidence interval: 18.1-26.5]) crude all-cause mortality rate than those recipients treated with hemodialysis (32.8/1000 patient-years [30.8-35.0]). Pretransplant peritoneal dialysis use was associated with 43% lower adjusted all-cause and 66% lower cardiovascular death. Furthermore, pretransplant peritoneal dialysis use was associated with 17% and 36% lower unadjusted death-censored graft failure and delayed graft function risk, respectively. However, after additional adjustment for relevant covariates, pretransplant peritoneal dialysis modality was not a significant predictor of death-censored graft failure delayed graft function, respectively. Similar trends were noted on analyses using a propensity score matched cohort of 2092 pairs of patients. Compared with hemodialysis, patients treated with peritoneal dialysis before transplantation had lower mortality but similar graft loss or delayed graft function. Confounding by residual selection bias cannot be ruled out.

Association of Pretransplant Glycemic Control With Posttransplant Outcomes in Diabetic Kidney Transplant Recipients

OBJECTIVEObservational studies have yielded inconsistent findings regarding the association of hemoglobin A1c (HbA1c) with survival in diabetic patients on dialysis. The association between pretransplant glycemic control and short- and long-term posttransplant outcomes in kidney transplant recipients is not clear.RESEARCH DESIGN AND METHODSLinking the 5-year patient data of a large dialysis organization (DaVita) to the Scientific Registry of Transplant Recipients, we identified 2,872 diabetic dialysis patients who underwent first kidney transplantation. Mortality or graft failure and delayed graft function (DGF) risks were estimated by Cox regression (hazard ratio [HR]) and logistic regression (odds ratio), respectively.RESULTSPatients were 53 ± 11 years old and included 36% women and 24% African Americans. In our fully adjusted model, allograft failure–censored, all-cause death HR and 95% CI for time-averaged pretransplant HbA1c categories of 7 to <8%, 8 to <9%, 9 to 10%, and ≥10%, compared with 6 to <7% (reference), were 0.89 (0.59–1.36), 2.06 (1.31–3.24), 1.41 (0.73–2.74), and 3.43 (1.56–7.56), respectively; and graft failure–censored cardiovascular death HR was 0.38 (0.13–1.05), 1.78 (0.69–4.55), 1.59 (0.44–5.76), and 4.28 (0.85–21.64), respectively. We did not find any difference in risk of death-censored graft failure or DGF with different pretransplant HbA1c levels.CONCLUSIONSPoor pretransplant glycemic control appears associated with decreased posttransplant survival in kidney transplant recipients, whereas allograft outcomes may not be affected.

Long‐Term Outcomes of Patients Treated with Primary Stenting for Transplant Renal Artery Stenosis: A 10‐year Case Cohort Study

The purpose of the present study was to evaluate graft and patient survival and long-term outcomes of primary endoluminal stenting (PES) as an initial treatment for transplant renal artery stenosis (TRAS). From December 1999 to March 2010, 744 consecutive patients undergoing renal transplantation were enrolled. Patients were divided into one of two groups: the study group, comprised of 18 patients who underwent PES for TRAS > 60%, and a control group, including the remaining 726 recipients who did not develop TRAS post-transplantation. Primary outcome measures were death-censored graft failure and all-cause mortality. The immediate and long-term effects of PES were evaluated by assessing blood pressure (BP) control and biochemical graft function. The technical success rate for PES was 100%, and minor complication occurred in only one case (5.6% of the study group). With a mean follow-up of 7.1 ± 3.7 and 6.9 ± 2.4 years in the study and control groups, respectively, 4 patients in the study group and 113 patients in the control group reached the primary outcome (log rank P = 0.418). The reduction in stenosis resulted in immediate improvement in BP control and graft function, which persisted throughout the 6 year follow-up period. Restenosis occurred in only one patient (5.6%), but restenosis was not the cause of graft failure. This study indicated that both the long-term graft and patient survival were as good in TRAS patients treated with PES as in patients without TRAS. The data also supported the use of PES as an initial treatment for TRAS.

Long‐Term Impact of Pretransplant and Posttransplant Diabetes Mellitus on Kidney Transplant Outcomes

The aim of this study was to compare the impact of preexisting diabetes mellitus (pre-DM), posttransplant DM (PTDM), and non-DM on the long-term outcomes of renal transplant recipients (RTRs). This is a retrospective observational cohort study of 427 RTRs who underwent transplantation from 1999 to 2008. Patients were divided into non-DM, pre-DM, and PTDM groups. The primary outcome was the composite of doubling of the serum creatinine (SCr) level, graft failure, or death. Secondary outcomes were biopsy-proven acute rejection (BPAR), biopsy-proven interstitial fibrosis and/or tubular atrophy (IF/TA), and individual components of the primary outcome. A total of 70 patients (16.4%) had pre-DM, 104 (24.2%) had PTDM, and 253 (59.3%) had non-DM. Kaplan–Meier analysis indicated significant differences in the development of the primary outcome: p = 0.003 (log rank test). Relative to the non-DM group, the pre-DM group had a 6.36-fold increased risk [95% confidence interval (CI) 2.43–16.33; p < 0.001), and the PTDM group had a 2.00-fold increased risk (95% CI 1.08–3.73; p = 0.029) for development of the primary outcome. Patients in the pre-DM group had 6.73-fold (95% CI 2.46–18.42; p < 0.001), 4.56-fold (95% CI 1.77–11.78; p = 0.002), and 13.95-fold (95% CI 2.96–65.75; p < 0.001) increased risks for the development of SCr doubling, biopsy-proven IF/TA, and death-censored graft failure, respectively. Patients in the PTDM group had a 2.09-fold (95% CI 1.10–3.99; p = 0.025), increased risk for the development of SCr doubling. The presence of pre-DM or PTDM significantly impaired kidney allograft outcome.

Uromodulin in Renal Transplant Recipients: Elevated Urinary Levels and Bimodal Association with Graft Failure

Background: Urinary uromodulin (UMOD) predicts renal prognosis in native kidneys, but data are conflicting. We investigated its prognostic impact for graft failure (GF) in renal transplant recipients (RTR; n = 600). Methods: UMOD concentration was measured cross-sectionally in RTR at 6.0 years [2.6–11.4] post-transplant, in matched patients with native chronic kidney disease (CKD) and healthy subjects. In 59 cases, RTR allograft biopsies were reviewed. Results: During a follow-up of 5.3 years [4.5–5.7], GF had occurred in 7% of RTR. Median UMOD excretion (mg/24 h) was 20.4 in RTR, 11.6 in CKD and 5.7 in controls (p < 0.001). There was a curvilinear association between UMOD excretion and baseline renal function (p < 0.003) and death-censored GF, with 5.5, 11.5 and 4.0% of the cases in subsequent UMOD excretion tertiles, respectively (p = 0.002). On multivariate Cox regression analysis, hazard ratios for GF for the 1st and 3rd tertiles were 0.37 (p = 0.01) and 0.21 (p = 0.001), respectively. Interstitial fibrosis and tubular atrophy were more severe in the middle tertile (p = 0.007). Conclusions: Urinary UMOD is elevated in RTR and associated with graft function, morphology and outcome in a bimodal fashion. Dissection of the disparate mechanisms of GF prediction by urinary UMOD might provide new clues for its alleged pathogenetic significance in progressive renal function loss.

Lymphoproliferative Disorders After Adult Kidney Transplant: Epidemiology and Comparison of Registry Report With Claims-Based Diagnoses

Posttransplant lymphoproliferative disorder (PTLD) is a major complication of kidney transplant. Retrospective cohort study comparing PTLD incidence rates using US Medicare claims and Organ Procurement and Transplantation Network (OPTN) data, examining risk factors for PTLD in OPTN data, and studying recipient and graft survival after PTLD diagnosis. All adult first-transplant patients who underwent deceased or living donor kidney-only transplants in 2000-2006 (n = 89,485) followed up through 3 years posttransplant. Recipient and donor characteristics, HLA mismatches, viral serologic test results, and initial immunosuppression. OPTN-reported or Medicare claims-based PTLD diagnosis, recipient and graft survival after OPTN-reported PTLD diagnosis. Adjusted HRs for PTLD diagnosis estimated using a Cox proportional hazards model; probability of survival free of all-cause graft failure estimated using the Kaplan-Meier method. The incidence rate of PTLD during the first posttransplant year was 2-fold higher in Medicare claims (0.46/100 patient-years; 95% CI, 0.39-0.53) than in OPTN data (0.22/100 patient-years; 95% CI, 0.17-0.27). Factors associated with increased rates of PTLD included older age, white race (vs African American), induction with T-cell-depleting antibodies, Epstein-Barr virus seronegativity at the time of transplant, and cytomegalovirus seronegativity at the time of transplant. The adjusted risk of death with graft function was 17.5 (95% CI, 14.3-21.4) times higher after a report of PTLD, and the risk of death-censored graft failure was 5.5 (95% CI, 3.9-7.7) times higher. Shortcomings inherent in large databases, including inconsistencies in patient follow-up, reporting, and coding practices by transplant centers; insufficient registry data to analyze acute rejection episodes and antirejection treatment; no available data for potential effects of different types of PTLD treatment on patient outcomes. Despite the limitations of data collected by registries, PTLD clearly is an important complication; both mortality and death-censored graft failure increase after PTLD.

Associations of Renal Function at 1-Year After Kidney Transplantation With Subsequent Return to Dialysis, Mortality, and Healthcare Costs

Improved early kidney transplant outcomes limit the contemporary utility of standard clinical endpoints. Quantifying the relationship of renal function at 1 year after transplant with subsequent clinical outcomes and healthcare costs may facilitate cost-benefit evaluations among transplant recipients. Data for Medicare-insured kidney-only transplant recipients (1995-2003) were drawn from the United States Renal Data System. Associations of estimated glomerular filtration rate (eGFR) level at the first transplant anniversary with subsequent death-censored graft failure and patient death in posttransplant years 1 to 3 and 4 to 7 were examined by parametric survival analysis. Associations of eGFR with total health care costs defined by Medicare payments were assessed with multivariate linear regression. Among 38,015 participants, first anniversary eGFR level demonstrated graded associations with subsequent outcomes. Compared with patients with 12-month eGFR more than or equal to 60 mL/min/1.73 m, the adjusted relative risk of death-censored graft failure in years 1 to 3 was 31% greater for eGFR 45 to 59 mL/min/1.73 m (P<0.0001) and 622% greater for eGFR 15 to 30 mL/min/1.73 m (P<0.0001). Associations of first anniversary eGFR level with graft failure and mortality remained significant in years 4 to 7. The proportions of recipients expected to return to dialysis or die attributable to eGFR less than 60 mL/min/1.73 m over 10 years were 23.1% and 9.4%, respectively, and were significantly higher than proportions attributable to delayed graft function or acute rejection. Reduced eGFR was associated with graded and significant increases in health care spending during years 2 and 3 after transplant (P<0.0001). eGFR is strongly associated with clinical and economic outcomes after kidney transplantation.

Albuminuria, Proteinuria, and Novel Urine Biomarkers as Predictors of Long-term Allograft Outcomes in Kidney Transplant Recipients

Proteinuria is an established marker of decreased kidney function after kidney transplant. It recently has been suggested that albuminuria might be a more reliable marker. Although albuminuria often is regarded as a marker of glomerular damage, because chronic renal allograft damage is believed to be predominantly an interstitial process, albuminuria in this case might reflect tubular damage. Accordingly, we investigated the value of albuminuria, proteinuria, and tubular damage markers (KIM-1 [kidney injury molecule 1], NAG [N-acetyl-β-d-glucosaminidase], NGAL [neutrophil gelatinase-associated lipocalin], and H-FABP [heart fatty acid binding protein]) in predicting graft outcome in kidney transplant recipients. Prospective observational cohort study. 606 patients visiting our outpatient kidney transplant clinic in 2001-2003 were included and used in the analysis for death-censored graft failure. Median follow-up was 4.7 (25th-75th percentile, 3.8-5.2) years. 577 patients had follow-up longer than 1 year and were included in the analysis for estimated glomerular filtration rate (eGFR) decrease. Median follow-up was 3.2 (25th-75th percentile, 2.7-3.7) years. Urine protein, albumin, and tubular damage markers in 24-hour urine samples. Death-censored graft failure and decrease in eGFR. There were 42 patients with graft failure; mean eGFR change was -0.46 ± 3.7 (standard deviation) mL/min/1.73 m(2)/y. The area under the receiver operating characteristic curve for death-censored graft failure showed that albuminuria (0.78; 95% CI, 0.59-0.76) was significantly higher than proteinuria (0.67; 95% CI, 0.59-0.76; P = 0.001), NGAL (0.63; 95% CI, 0.52-0.74; P = 0.02), and H-FABP (0.62; 95% CI, 0.53-0.73; P = 0.005) and not significantly different from KIM-1 (0.74; 95% CI, 0.66-0.82) and NAG (0.75; 95% CI, 0.67-0.83). Results were similar for the eGFR decrease outcome. Single-center observational study. Measuring albuminuria may provide superior predictions for long-term renal outcomes after kidney transplant than total proteinuria. Additional assessment of urinary excretion of tubular damage markers may have limited value.

Blood transfusions in kidney transplant candidates are common and associated with adverse outcomes

Surprisingly, there are no data regarding transfusion frequency, factors associated with transfusion administration in patients on the kidney transplant waiting list, or transfusion impact on graft and recipient outcomes. We used United States Renal Data System data to identify 43,025 patients added to the waiting list in 1999-2004 and followed through 2006 to assess the relative risk of post-listing transfusions. In 69,991 patients who underwent transplants during the same time period, we assessed the association between pre-transplant transfusions and level of panel-reactive antibody (PRA) at the time of transplant, and associations between PRA and patient outcomes. The three-yr cumulative incidence of transfusions was 26% for patients added to the waiting list in 1999, rising to 30% in 2004. Post-listing transfusions were associated with a 28% decreased likelihood of undergoing transplant, and a more than fourfold increased risk of death. There was a graded association between percent PRA at the time of transplant and adjusted risk of death-censored graft failure, death with function, and the combined event of graft failure and death. These data demonstrate that transfusions remain common and confirm the adverse association between transfusions and PRA, and high PRA and inferior graft and patient outcomes.

The Relationship Between Kidney Function and Long-term Graft Survival After Kidney Transplant

Whether chronic kidney disease (CKD) staging provides a useful framework for predicting outcomes after kidney transplant is unclear. Retrospective cohort study. We used data from the Patient Outcomes in Renal Transplantation (PORT) Study, including 13,671 transplants from 12 centers during 10 years of follow-up. Estimated glomerular filtration rate (eGFR; in milliliters per minute per 1.73 m(2)) at 12 months posttransplant. All-cause graft failure (a composite end point consisting of return to dialysis therapy, pre-emptive retransplant, or death with function), death-censored graft failure, and death with a functioning graft. The relationship between 12-month eGFR and subsequent graft outcomes through 10 years posttransplant was assessed using Cox proportional hazards analyses. Stage 3 included 63% of patients and was subdivided into stages 3a (eGFR, 45-59 mL/min/1.73 m(2); 34%) and 3b (eGFR, 30-44 mL/min/1.73 m(2); 29%). Compared with stage 2 (eGFR, 60-89 mL/min/1.73 m(2); 24%), adjusted Cox proportional HRs for graft failure were 1.12 (95% CI, 1.01-1.24; P = 0.04) for stage 3a, 1.50 (95% CI, 1.35-1.66; P < 0.001) for stage 3b, 2.86 (95% CI, 2.53-3.22; P < 0.001) for stage 4 (eGFR, 15-29 mL/min/1.73 m(2); 9%), and 13.2 (95% CI, 10.7-16.4; P < 0.001) for stage 5 (eGFR <15 mL/min/1.73 m(2); 1%). For stage 1 (eGFR ≥ 90 mL/min/1.73 m(2); 3%), risk of graft failure was increased (1.41 [95% CI, 1.13-1.75]; P < 0.001), likely due to serum creatinine associations independent of kidney function. Similar associations were seen between CKD stages and mortality. Retrospective study; lack of gold-standard measurements of true GFR; lack of measures of comorbidity, inflammation, muscle mass, proteinuria, and other noncreatinine markers of eGFR. CKD stages validated in the general population provide a useful framework for predicting outcomes after kidney transplant.