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Background The traditional definition of delayed graft function (DGF) rests on dialysis requirement during the first postoperative week. Subsequently, a more objective and "functional" definition of DGF (fDGF) has been proposed as an alternative to this dialysis-based definition of DGF (dDGF) and defined as a failure of the serum creatinine to decrease by at least 10% daily on 3 successive days during the first week posttransplantation, irrespective of dialysis requirement. However, an association between fDGF and long-term graft failure has not been fully established, and it is unknown whether fDGF is a better marker of subsequent outcomes than dDGF. Methods We studied 750 adult deceased donor kidney transplant recipients (1996-2006) and analyzed the association between these two DGF definitions and long-term graft outcome. Results Univariable associations with death-censored graft failure were seen for both dDGF and fDGF (hazard ratio [HR] 1.59; 95% confidence interval [CI] 1.16-2.18; P=0.004 and HR 1.72; 95% CI 1.26-2.36; P=0.001, respectively). On bivariable analysis (dDGF vs. fDGF), dDGF lost significance, whereas the effect of fDGF persisted (HR 1.52; 95%CI 1.03-2.25; P=0.04). This was also the case in a multivariable model, where fDGF but not dDGF was significantly associated with graft failure (HR 1.47; 95%CI 1.06-2.03; P=0.02). Results were similar for overall graft failure. Conclusions This study confirms the utility of fDGF as an early marker of subsequent inferior allograft outcomes, suggesting superiority over the traditional (often subjective) dialysis-based definition. Wider adoption of the fDGF definition should be considered, both as a risk-stratification tool in clinical practice and a clinical trial endpoint.

Background. The early identification of kidney allografts at risk of later dysfunction has implications for clinical practice. Donor quality scoring systems (preoperative) and measures of early allograft function (first week postoperative) have previously shown practical utility. This study aimed to determine the optimal parameter(s) (preoperative and postoperative) with greatest predictive power for the development of subsequent allograft dysfunction. Methods. Consecutive deceased donor renal transplants (n=217) were studied. In each, the following measures were assessed: Preoperative donor quality scores: expanded criteria donor status; Deceased Donor Score (Nyberg et al., Am J Transplant 2003;3:715); Donor Risk Score (Schold et al., Am J Transplant 2005; 5(4 pt 1): 757); and delayed graft function (DGF) Nomogram (Irish et al., J Am Soc Nephrol 2003; 14:2967). Postoperative early function measures: dialysis requirement and duration; extended DGF definition (Boom et al., Kidney Int 2000; 58:859); creatinine at day 5 and day 7; creatinine reduction ratios at day 2 and day 7; and urine output posttransplantation. Primary outcome measures were creatinine at 12 months and the development of chronic kidney disease stage 4T. Results. Of donor scoring systems, Donor Risk Score was best associated with subsequent allograft function. Of early function measures: the extended definition of DGF, creatinine at day 5, and dialysis duration showed greatest predictive power in the patient population overall, those not requiring postoperative dialysis, and those requiring dialysis, respectively. No scores or early function measures were associated with change in creatinine between 6 and 12 months. Conclusions. This study validates and identifies the optimal early predictive parameter available for kidney transplant recipients, with implications for refining early postoperative management and potential utility in organ allocation policy.

BACKGROUND Detailed modeling and analysis of renal (dys)function trajectories has not been undertaken in kidney transplant recipients. Although previous studies have assumed linear trajectories, this likely represents an oversimplification. METHODS In this study, a Bayesian smoothing technique was undertaken to create 10,000 Monte Carlo samples for each of 158 patients over a median of 88 months. Specific parameters investigated were the prevalence of nonlinear trajectories, periods of nonprogression, and of rapid progression. RESULTS Forty-five (28%) patients displayed high probability (>80%) for a nonlinear trajectory. Periods of nonprogression were also common, present in 110 (70%) patients. A substantial proportion of patients showed deviation from the classic paradigm of progressive linear loss of graft function with 137 (87%) patients displaying nonlinearity or nonprogression. Only nine (6%) patients demonstrated at least one episode of nonprogression after an episode of progression, that is, once progression occurred, a subsequent period of nonprogression was uncommon. Episodes of nonprogression were less common (P < 0.001) in patients whose grafts subsequently failed, whereas episodes of rapid progression were more common (P = 0.04). CONCLUSION This study highlights the often nonlinear and nonprogressive nature of renal function decline after transplantation. Heightened understanding of the factors influencing these trajectories should help inform patients and clinicians alike.

Limiting the exposure of kidney transplant recipients to calcineurin inhibitors (CNIs) has potential merit, but there is no clear consensus on the utility of current strategies. In an attempt to aid clarification, we conducted a systematic review and meta-analysis of randomized trials that assessed CNI sparing (minimization or elimination) with mycophenolate as sole adjunctive immunosuppression.The search strategy identified trials where CNI sparing was accompanied by the continuation of, or conversion to, mycophenolate and compared with standard or higher dose CNI therapy. Two investigators independently examined each trial for eligibility, quality, and outcome measures. Additional subgroup analyses were assessed: (1) de novo CNI sparing; (2) elective CNI sparing beyond 2 months posttransplantation; and (3) CNI sparing for transplant dysfunction.Nineteen randomized controlled trials met the inclusion criteria permitting analysis of 3312 renal transplant recipients with median follow-up of 12 months. CNI sparing significantly improved glomerular filtration rate (weighted mean difference 4.4 mL/min, 95% confidence interval [CI] 2.9-5.9, P0.001); with some evidence, albeit weak, of improved graft survival (odds ratio 0.72, 95% CI 0.52-1.01, P=0.06). Acute rejection rates were only increased after elective CNI elimination (odds ratio 2.23, 95% CI 1.57-3.17, P0.001). There were no significant differences in mortality, malignancy or incidence of infections.CNI sparing strategies with adjunctive mycophenolate may play an important role in kidney transplant recipients. Improvements in short-term graft function, and possibly graft survival, are achievable. Longer term studies are needed to substantiate the short-term benefits, and refining elective CNI elimination protocols may help to reduce the risk of rejection.

Background. To date, efforts have focused on assessing estimated glomerular filtration rate (eGFR) formulae against measured GFR. However, a more appropriate clinical gold standard is one conveying a defined clinical disadvantage. In renal transplantation, these measures are mortality and graft failure. Methods. The Long Term Efficacy and Safety Surveillance database was used to analyze 1344 renal transplant recipients. eGFR was assessed 6 months posttransplantation with the following formulae: Cockcroft-Gault; Walser; Nankivell; abbreviated modification of diet in renal disease (aMDRD); MDRD7; Rule's refitted MDRD; and Mayo Clinic. The outcome measures were mortality and graft failure. Results. Although eGFR was statistically associated with subsequent mortality and graft failure in the Cox model (irrespective of which eGFR formula was used), the clinical utility of eGFR was moderate at best in predicting subsequent mortality and graft failure. No clinically relevant or statistically significant difference was discernable between formulae, with a maximum area under the receiver operating characteristic curve of 0.63 and 0.61 for 3- and 5-year mortality, respectively, and 0.66 and 0.60 for 3- and 5-year graft failure, respectively. Serum creatinine used in isolation displayed similar predictive utility, and no improvement was seen by investigating the change in creatinine or eGFR between 6 and 12 months. Conclusions. In summary, seven eGFR equations showed similar and limited utility in predicting mortality and graft failure after renal transplantation. This has important implications for the management of renal transplant recipients and the use of an eGFR as a surrogate endpoint in clinical trials.

Background. It remains unclear whether low hemoglobin levels are associated with increased mortality or graft loss after renal transplantation. This study assessed the relationship of hemoglobin levels with patient and graft survival in 3859 patients with functioning renal transplants more than 6-months posttransplantation. Methods. Detailed data was prospectively collected as part of the pharmacovigilance Long Term Efficacy and Safety Surveillance project. Results. Lower hemoglobin levels were associated with graft loss on multivariate analysis adjusted for demographic characteristics, comorbidity, and biochemical variables; lower hemoglobin was associated with mortality on univariate, but not adjusted analysis; hemoglobin variability was associated with mortality and graft loss on univariate, but not multivariate analysis. Older recipient age, lower serum albumin, raised urea, increased comorbidity (Charlson Index), and angiotensin-converting enzyme inhibitor (ACEi)/angiotensin II receptor blocker (ARB) non-use were also associated with mortality. Younger recipients, male recipients and those with lower serum albumin, lower body mass index, higher systolic blood pressure, and impaired allograft function experienced higher graft failure rates. Conclusions. This study suggests that full correction of hemoglobin levels to improve mortality in renal transplant recipients is unjustified; further study is required to assess the effect of hemoglobin correction in delaying graft failure. It also highlights other nonimmunologic risk factors for adverse outcomes in renal transplant recipients.