Nonadherence to immunosuppressants is recognized to occur after renal transplantation, but the size of its impact on transplant survival is not known. A systematic literature search identified 325 studies (in 324 articles) published from 1980 to 2001 reporting the frequency and impact of nonadherence in adult renal transplant recipients. Thirty-six studies meeting the inclusion criteria for further review were grouped into cross-sectional and cohort studies and case series. Meta-analysis was used to estimate the size of the impact of nonadherence on graft failure. Only two studies measured adherence using electronic monitoring, which is currently thought to be the most accurate measure. Cross-sectional studies (n=15) tended to rely on self-report questionnaires, but these were poorly described; a median (interquartile range) of 22% (18%-26%) of recipients were nonadherent. Cohort studies (n=10) indicated that nonadherence contributes substantially to graft loss; a median (interquartile range) of 36% (14%-65%) of graft losses were associated with prior nonadherence. Meta-analysis of these studies showed that the odds of graft failure increased sevenfold (95% confidence interval, 4%-12%) in nonadherent subjects compared with adherent subjects. Standardized methods of assessing adherence in clinical populations need to be developed, and future studies should attempt to identify the level of adherence that increases the risk of graft failure. However, this review shows nonadherence to be common and to have a large impact on transplant survival. Therefore, significant improvements in graft survival could be expected from effective interventions to improve adherence.

Frequency and impact of nonadherence to immunosuppressants after renal transplantation: a systematic review.

This literature review summarizes the evidence on the prevalence, determinants, clinical and economic consequences of nonadherence with immunosuppressive drugs in renal transplant patients. A literature search yielded 38 articles measuring nonadherence by self-report, collateral report, assay, refill prescriptions or electronic monitoring. The weighted mean prevalence of self-reported nonadherence was 28%. Nonadherence is associated with poor clinical outcomes, contributing to 20% of late acute rejection episodes and 16% of the graft losses (weighted means). In addition, nonadherence results in lower lifetime costs because of shorter survival, yet also in a lower number of quality adjusted life years. Consistent determinants of nonadherence were younger age, social isolation, and cognitions (e.g. low self-efficacy, certain health beliefs). Determinants concerning the health care system/team seem to be under-investigated. Because the evidence summarized in this review is based on older immunosuppressive regimens, further research should focus on prevalence, determinants and consequences of nonadherence with newer immunosuppressive regimens.

https://onlinelibrary.wiley.com/doi/epdf/10.1111/j.1432-2277.2005.00176.x

Prevalence, consequences, and determinants of nonadherence in adult renal transplant patients: a literature review.

Current methods for predicting graft recovery after kidney transplantation are not reliable. We performed a prospective, multicenter, observational cohort study of deceased-donor kidney transplant patients to evaluate urinary neutrophil gelatinase-associated lipocalin (NGAL), IL-18, and kidney injury molecule-1 (KIM-1) as biomarkers for predicting dialysis within 1 wk of transplant and subsequent graft recovery. We collected serial urine samples for 3 d after transplant and analyzed levels of these putative biomarkers. We classified graft recovery as delayed graft function (DGF), slow graft function (SGF), or immediate graft function (IGF). Of the 91 patients in the cohort, 34 had DGF, 33 had SGF, and 24 had IGF. Median NGAL and IL-18 levels, but not KIM-1 levels, were statistically different among these three groups at all time points. ROC curve analysis suggested that the abilities of NGAL or IL-18 to predict dialysis within 1 wk were moderately accurate when measured on the first postoperative day, whereas the fall in serum creatinine (Scr) was not predictive. In multivariate analysis, elevated levels of NGAL or IL-18 predicted the need for dialysis after adjusting for recipient and donor age, cold ischemia time, urine output, and Scr. NGAL and IL-18 quantiles also predicted graft recovery up to 3 mo later. In summary, urinary NGAL and IL-18 are early, noninvasive, accurate predictors of both the need for dialysis within the first week of kidney transplantation and 3-mo recovery of graft function.

IL-18 and Urinary NGAL Predict Dialysis and Graft Recovery after Kidney Transplantation

A systematic review of kidney transplantation from expanded criteria donors.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/ajt.12955

Novel Once-Daily Extended-Release Tacrolimus (LCPT) Versus Twice-Daily Tacrolimus in De Novo Kidney Transplants: One-Year Results of Phase III, Double-Blind, Randomized Trial

AIMS to analyze the frequency of transplants using expanded donor criteria (EDC) and the incidence of delayed graft function, acute rejection and the patient and graft survival compared to ideal donors (ID). PATIENTS retrospective analysis of the 582 cadaver renal transplants performed from Jun 1988 to Mar 2003 in adult recipients. The expanded donor criteria were considered as history of hypertension or evidence of atherosclerosis, diabetes, age less than 5 or more than 55 years old, serum creatinine higher than 2.0 mg/dL, shock and retrieval in cardiac arrest. The statistical analysis used was Student t test, Chi-square test, and Kaplan-Meier method as indicated. RESULTS 25.4% of our transplants used expanded criteria donor. Comparing, respectively, the EDC and ID we found: the incidence of delayed graft function of 63.9% vs 50.4% (P: 0.007); incidence of acute rejection of 66.1% vs 72.3% (P: 0.203). The patient survival at 1 and 5 years was 87% vs 92% and 81% vs 79%, respectively (P: 0.6809). The graft survival at 1 and 5 year was 74% vs 82% and 57% vs 59% (P: 0.2072), respectively for EDC and ID. CONCLUSIONS One fourth of our cadaver transplants fulfilled the extended donor criteria. The incidence of delayed graft function was higher in these transplants, but the prevalence of rejection episodes was similar to ideal donors. The patient and graft survival were not statistically different at 1 and 5 year.

Renal transplants using expanded cadaver donor criteria.

Patient noncompliance as a cause of late kidney graft failure.

RENAL transplantation is the treatment of choice for end-stage renal failure. However, the recipient needs a lifelong intake of immunosuppressive medication for the long-term success of the transplantation. There is a growing awareness of patient noncompliance with immunosuppression, which can result in rejection and graft loss. Recent data show rates of noncompliance ranging from less than 5% to more than 45%; it depends on time posttransplant and evaluation method. Noncompliance is one of the major causes of graft failure among renal transplant recipients. The objective of this study was to evaluate the present rate of graft loss due to noncompliance among our patients and to identify factors associated with noncompliance.

Kidney graft failure due to noncompliance.

From 1977 to July 2002, 1,376 renal transplants were performed at Santa Casa of Porto Alegre. The number of transplants and the patient and graft survival rates have been rising each year since 1987. The overall one-year graft survival rates were 90% for living donor recipients and 80% for cadaver donor recipients, respectively; however, the patient and graft survival rates increased significantly between the early (1977-1995) and more recent (1996-2002) periods. Pediatric patients (less than 18 years old) accounted for 15.8% of the transplants that were performed, most of them from living related donors. The patient and graft survival rates did not differ statistically when we compared recipients of transplants from "ideal" and marginal cadaver donors, even when we considered only those risk factors that affected graft function in assigning a marginal donor. During the 25-year observation period, 537 grafts have been lost (39%), including those patients who died with functioning graft. We are currently following 834 patients with a functioning graft, with an average follow-up of 67+54 months.

Twenty-five year experience with renal transplantation at Santa Casa Hospital, Porto Alegre.

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Renal transplants using expanded cadaver donor criteria.

Patient noncompliance as a cause of late kidney graft failure.

Kidney graft failure due to noncompliance.

Twenty-five year experience with renal transplantation at Santa Casa Hospital, Porto Alegre.