Day-Time Declamping Is Associated with Better Outcomes in Kidney Transplantation: The Circarein Study.
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ABSTRACT:
SUBMITTER: Montaigne D
PROVIDER: S-EPMC8198093 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Background: The aim of the present study was to investigate the impact of time in therapeutic range TTR on long-term outcomes of living kidney transplants. Methods: We included 1,241 living kidney transplants and randomized them into development and validation cohorts with a ratio of 2:1. The tacrolimus TTR percentage was calculated by linear interpolation with a target range (5-10 ng/ml months 0-3, 4-8 ng/ml months 4-12). The optimal TTR cutoff was estimated by the receiver operating characteristic curve analysis on the basis of acute rejection (AR) within 12 months in the development cohort. Outcomes were analyzed between patients with high TTR and low TTR in the development and validation cohorts, respectively. The TTR was also compared with other tacrolimus measures. Results: The optimal TTR cutoff value was 78%. In the development cohort, patients with TTR > 78% had significantly higher rejection- and infection-free survival. TTR < 78% was an independent risk factor for AR (OR: 2.97, 95%CI: 1.82-4.84) and infection (OR: 1.55, 95%CI: 1.08-2.22). Patient and graft survival were significantly higher in those with TTR>78%, and TTR<78% was associated with graft loss (OR: 3.2, 95%CI: 1.38-7.42) and patient death (OR: 6.54, 95%CI: 1.34-31.77). These findings were confirmed in the validation cohort. Furthermore, we divided all included patients into a high and low TTR group. TTR was more strongly associated with patient and graft survival than mean level, standard deviation, and intrapatient variability (IPV). Conclusions: Increasing the TTR of tacrolimus in the first year was associated with improved long-term outcomes in living kidney transplants, and TTR may be a novel valuable strategy to monitor tacrolimus exposure.
| S-EPMC6933438 | biostudies-literature
Project description:Background and objectivesModern immunosuppressant regimens have significantly decreased acute rejection rates, but may have increased the risk of graft loss driven by adverse drug reactions (ADRs) and medication errors (MEs). The objectives of this study were to determine the incidence and risk factors for MEs and ADRs and determine the association between transplant outcomes and these events.Design, setting, participants, & measurementsThis was a post hoc analysis of a prospective, randomized trial that included patients aged>18 years that received a solitary renal transplant at an academic medical center recruited between March 2009 and July 2011. Patients were divided into groups based on developing a clinical significant ME (CSME), defined as a significant ME that contributed to a hospital admission.ResultsThe mean study follow-up was 2.5 ± 0.7 years. There were a total of 233 MEs and 327 ADRs in the 200 patients included in the analysis, with 64% of the cohort experiencing at least one ME and 87% experiencing an ADR; 23 patients (12%) experienced a CSME. Patients that experienced CSMEs had a trend toward more post-transplant readmissions (median 1 [interquartile range (IQR), 0-5] versus 0 [0-2]; P=0.06), higher costs for readmissions (median $18,091 [IQR, $3023-$56,268] versus $0 [$0-$15,991]; P<0.01), and overall length of stay (median 5.0 days [IQR, 2.0-14.0] versus 0.0 days [IQR, 0.0-5.5]; P<0.01) after the CSME event. CSME patients were also more likely to experience graft failure (22% versus 10%; P=0.05).ConclusionsSignificant MEs commonly occur in renal transplant recipients and are associated with an increased risk of deleterious clinical outcomes, including subsequent hospital days, costs, and graft loss.
| S-EPMC4011453 | biostudies-literature
Project description:Background and objectivesHistorically, length of pretransplant dialysis was associated with premature graft loss and mortality after kidney transplantation, but with recent advancements in RRT it is unclear whether this negative association still exists.Design, setting, participants, &measurementsThis is a retrospective cohort study evaluating 6979 first kidney allograft recipients from the Austrian Registry transplanted between 1990 and 2013. Duration of pretransplant dialysis treatment was used as categoric predictor classified by tertiles of the distribution of time on dialysis. A separate category for pre-emptive transplantation was added and defined as kidney transplantation without any dialysis preceding the transplant. Outcomes were death-censored graft loss, all-cause mortality, and the composite of both.ResultsMedian duration of follow-up was 8.2 years, and 1866 graft losses and 2407 deaths occurred during the study period. Pre-emptive transplantation was associated with a lower risk of graft loss (hazard ratio, 0.76; 95% confidence interval, 0.59 to 0.98), but not in subgroup analyses excluding living transplants and transplants performed since 2000. The association between dialysis duration and graft loss did not depend on the year of transplantation (P=0.40) or donor source (P=0.92). Longer waiting time on dialysis was not associated with a higher rate of graft loss, but the rate of death was higher in patients on pretransplant dialysis for >1.5 years (hazard ratio, 1.62; 95% confidence interval, 1.43 to 1.83) compared with pretransplant dialysis for <1.5 years.ConclusionsOur findings support the evidence that pre-emptive transplantation is associated with superior graft survival compared with pretransplant dialysis, although this association was weaker in transplants performed since 2000. However, our analysis shows that length of dialysis was no longer associated with a higher rate of graft loss, although longer waiting times on dialysis were still associated with a higher rate of death.
| S-EPMC5220655 | biostudies-literature
Project description:Disturbances in calcium-phosphate homeostasis are common after kidney transplantation. We aimed to assess the relationship between deregulations in plasma calcium and phosphate over time and mortality and death-censored graft failure (DCGF). In this prospective cohort study, we included kidney transplant recipients with ≥2 plasma calcium and phosphate measurements. Data were analyzed using time-updated Cox regression analyses adjusted for potential confounders including time-updated kidney function. We included 2769 patients (mean age 47 ± 14 years, 42.3% female) with 138 496 plasma calcium and phosphate levels (median [IQR] 43 [31-61] measurements per patient). During follow-up of 16.3 [8.7-25.2] years, 17.2% developed DCGF and 7.9% died. Posttransplant hypercalcemia was associated with an increased risk of mortality (1.63 [1.31-2.00], p < 0.0001), but not with DCGF. Hyperphosphatemia was associated with both DCGF (2.59 [2.05-3.27], p < .0001) and mortality (3.14 [2.58-3.82], p < .0001). Only the association between hypercalcemia and mortality remained significant in sensitivity analyses censored by a simultaneous eGFR <45 mL/min/1.73 m2 . Hypocalcemia and hypophosphatemia were not consistently associated with either outcome. Posttransplant hypercalcemia, even in the presence of preserved kidney function, was associated with an increased mortality risk. Associations of hyperphosphatemia with DCGF and mortality may be driven by eGFR.
| S-EPMC8359271 | biostudies-literature
Project description:IntroductionThe Renal Healthcare Program Uruguay (NRHP-UY) is a national, multidisciplinary program that provides care to chronic kidney disease (CKD) patients. In this study, we report the global results of CKD patient outcomes and a comparison between those treated at the NRHP-UY Units, with those patients who were initially included in the program but did not adhere to follow up.MethodsA cohort of not-on dialysis CKD patients included prospectively in the NRHP-UY between October 1st 2004 and September 30th 2017 was followed-up until September 30th 2019. Two groups were compared: a) Nephrocare Group: Patients who had at least one clinic visit during the first year on NRHP-UY (n = 11174) and b) Non-adherent Group: Patients who were informed and accepted to be included but had no subsequent data registered after admission (n = 3485). The study was approved by the Ethics Committee and all patients signed an informed consent. Outcomes were studied with Logistic and Cox´s regression analysis, Fine and Gray competitive risk and propensity-score matching tests.Results14659 patients were analyzed, median age 70 (60-77) years, 56.9% male. The Nephrocare Group showed improved achievement of therapeutic goals, ESKD was more frequent (HR 2.081, CI 95%1.722-2.514) as planned kidney replacement therapy (KRT) start (OR 2.494, CI95% 1.591-3.910), but mortality and the combined event (death and ESKD) were less frequent (HR 0.671, CI95% 0.628-0.717 and 0.777, CI95% 0.731-0.827) (p = 0.000) compared to the Non-adherent group. Results were similar in the propensity-matched group: ESKD (HR 2.041, CI95% 1.643-2.534); planned kidney replacement therapy (KRT) start (OR 2.191, CI95% 1.322-3.631) death (HR 0.692, CI95% 0.637-0.753); combined event (HR 0.801, CI95% 0.742-0.865) (p = 0.000).ConclusionMultidisciplinary care within the NRHP-UY is associated with timely initiation of KRT and lower mortality in single outcomes, combined analysis, and propensity-matched analysis.
| S-EPMC9565398 | biostudies-literature
Project description:History of psychosis or mania, if uncontrolled, both represent relative contraindications for kidney transplantation. We examined 3680 US veterans who underwent kidney transplantation. The diagnosis of history of psychosis/mania was based on a validated algorithm. Measured confounders were used to create a propensity score-matched cohort (n = 442). Associations between pretransplantation psychosis/mania and death with functioning graft, all-cause death, graft loss, and rejection were examined in survival models and logistic regression models. Post-transplant medication nonadherence was assessed using proportion of days covered (PDC) for tacrolimus and mycophenolic acid in both groups. The mean ± SD age of the cohort at baseline was 61 ± 11 years, 92% were male, and 66% and 27% of patients were white and African-American, respectively. Compared to patients without history of psychosis/mania, patients with a history of psychosis/mania had similar risk of death with functioning graft [subhazard ratio (SHR) (95% confidence interval (CI)): 0.94(0.42-2.09)], all-cause death [hazard ratio (95% CI): 1.04 (0.51-2.14)], graft loss [SHR (95% CI): 1.07 (0.45-2.57)], and rejection [odds ratio(95% CI): 1.23(0.60-2.53)]. Moreover, there was no difference in immunosuppressive drug PDC in patients with and without history of psychosis/mania (PDC: 76 ± 21% vs. 78 ± 19%, P = 0.529 for tacrolimus; PDC: 78 ± 17% vs. 79 ± 18%, P = 0.666 for mycophenolic acid). After careful selection, pretransplantation psychosis/mania is not associated with adverse outcomes in kidney transplant recipients.
| S-EPMC5903964 | biostudies-literature
Project description:ObjectiveSpending at least 90% of hospital admission in a stroke unit (SU) is a recommended indicator of receiving high-quality stroke care. However, whether this makes a difference to patient outcomes is unknown. We aimed to investigate outcomes and factors associated with patients with acute stroke spending at least 90% of their admission in an SU, compared with those having less time in the SU.DesignObservational study using cross-sectional data.SettingData from hospitals which participated in the 2015 Stroke Foundation National Audit: Acute Services (Australia) and had an SU. This audit includes an organisational survey and retrospective medical record audit of approximately 40 admissions from each hospital.ParticipantsPatients admitted to an SU during their acute admission were included.Outcome measuresHospital-based patient outcomes included length of stay, independence on discharge, severe complications and discharge destination. Patient, organisational and process indicators were included in multilevel logistic modelling to determine factors associated with spending at least 90% of their admission in an SU.ResultsEighty-eight hospitals with an SU audited 2655 cases (median age 76 years, 55% male). Patients who spent at least 90% of their admission in an SU experienced: a length of stay that was 2 days shorter (coefficient -2.77, 95% CI -3.45 to -2.10), fewer severe complications (adjusted OR (aOR) 0.60, 95% CI 0.43 to 0.84) and were less often discharged to residential aged care (aOR 0.59, 95% CI 0.38 to 0.94) than those who had less time in the SU. Patients admitted to an SU within 3 hours of hospital arrival were three times more likely to spend at least 90% of their admission in an SU.ConclusionSpending at least 90% of time in an SU is a valid measure of stroke care quality as it results in improved patient outcomes. Direct admission to SUs is warranted.
| S-EPMC6252690 | biostudies-literature
Project description:The outcomes of kidney transplantation and immunosuppression in people infected with human immunodeficiency virus (HIV) are incompletely understood.We undertook a prospective, nonrandomized trial of kidney transplantation in HIV-infected candidates who had CD4+ T-cell counts of at least 200 per cubic millimeter and undetectable plasma HIV type 1 (HIV-1) RNA levels while being treated with a stable antiretroviral regimen. Post-transplantation management was provided in accordance with study protocols that defined prophylaxis against opportunistic infection, indications for biopsy, and acceptable approaches to immunosuppression, management of rejection, and antiretroviral therapy.Between November 2003 and June 2009, a total of 150 patients underwent kidney transplantation; survivors were followed for a median period of 1.7 years. Patient survival rates (±SD) at 1 year and 3 years were 94.6±2.0% and 88.2±3.8%, respectively, and the corresponding mean graft-survival rates were 90.4% and 73.7%. In general, these rates fall somewhere between those reported in the national database for older kidney-transplant recipients (?65 years) and those reported for all kidney-transplant recipients. A multivariate proportional-hazards analysis showed that the risk of graft loss was increased among patients treated for rejection (hazard ratio, 2.8; 95% confidence interval [CI], 1.2 to 6.6; P=0.02) and those receiving antithymocyte globulin induction therapy (hazard ratio, 2.5; 95% CI, 1.1 to 5.6; P=0.03); living-donor transplants were protective (hazard ratio, 0.2; 95% CI, 0.04 to 0.8; P=0.02). A higher-than-expected rejection rate was observed, with 1-year and 3-year estimates of 31% (95% CI, 24 to 40) and 41% (95% CI, 32 to 52), respectively. HIV infection remained well controlled, with stable CD4+ T-cell counts and few HIV-associated complications.In this cohort of carefully selected HIV-infected patients, both patient- and graft-survival rates were high at 1 and 3 years, with no increases in complications associated with HIV infection. The unexpectedly high rejection rates are of serious concern and indicate the need for better immunotherapy. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT00074386.).
| S-EPMC3028983 | biostudies-literature
Project description:Recent advances in surgical, immunosuppressive and monitoring protocols have led to the significant improvement of overall one-year kidney allograft outcomes. Nonetheless, there has not been a significant change in long-term kidney allograft outcomes. In fact, chronic and acute antibody-mediated rejection (ABMR) and non-immunological complications following kidney transplantation, including multiple incidences of primary kidney disease, as well as complications such as cardiovascular diseases, infections, and malignancy are the major factors that have contributed to the failure of kidney allografts. The use of molecular techniques to enhance histological diagnostics and noninvasive surveillance are what the latest studies in the field of clinical kidney transplant seem to mainly focus upon. Increasingly innovative approaches are being used to discover immunosuppressive methods to overcome critical sensitization, prevent the development of anti-human leukocyte antigen (HLA) antibodies, treat chronic active ABMR, and reduce non-immunological complications following kidney transplantation, such as the recurrence of primary kidney disease and other complications, such as cardiovascular diseases, infections, and malignancy. In the present era of utilizing electronic health records (EHRs), it is strongly believed that big data and artificial intelligence will reshape the research done on kidney transplantation in the near future. In addition, the utilization of telemedicine is increasing, providing benefits such as reaching out to kidney transplant patients in remote areas and helping to make scarce healthcare resources more accessible for kidney transplantation. In this article, we discuss the recent research developments in kidney transplants that may affect long-term allografts, as well as the survival of the patient. The latest developments in living kidney donation are also explored.
| S-EPMC7230851 | biostudies-literature
Project description:Kidney transplantation is the treatment of choice for patients with kidney failure. Priority on the waiting list and optimal donor-recipient matching are guided by mathematical scores, clinical variables and macroscopic observation of the donated organ. Despite the increasing rates of successful kidney transplantation, maximizing the number of available organs while ensuring the optimum long-term performance of the transplanted kidney remains both key and challenging, and no unequivocal markers are available for clinical decision making. Moreover, the majority of studies performed thus far has focused on the risk of primary non-function and delayed graft function and subsequent survival and have mainly analysed recipients' samples. Given the increasing use of donors with expanded criteria and/or cardiac death, predicting whether grafts will provide sufficient kidney function is increasingly more challenging. Here we compile the available tools for pre-transplant kidney evaluation and summarize the latest molecular data from donors that may predict short-term (immediate or delayed graft function), medium-term (6 months) and long-term (≥12 months) kidney function. The use of liquid biopsy (urine, serum, plasma) to overcome the limitations of the pre-transplant histological evaluation is proposed. Novel molecules and approaches such as the use of urinary extracellular vesicles are also reviewed and discussed, along with directions for future research.
| S-EPMC9972840 | biostudies-literature