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Regulatory T-cell Number in Peripheral Blood at 1 Year Posttransplant as Predictor of Long-term Kidney Graft Survival.

ABSTRACT: Background:Regulatory T (Treg) cells play a role in limiting kidney transplant rejection and can potentially promote long-term transplant tolerance. There are no large prospective studies demonstrating the utility of peripheral blood Treg cells as biomarkers for long-term graft outcome in kidney transplantation. The aim of our study was to analyze the influence of the absolute number of peripheral blood Treg cells after transplantation on long-term death-censored graft survival. Methods:We monitored the absolute numbers of Treg cells by flow cytometry in nonfrozen samples of peripheral blood in 133 kidney transplant recipients, who were prospectively followed up to 2 years after transplantation. Death-censored graft survival was determined retrospectively in January 2017. Results:The mean time of clinical follow-up was 7.4 ± 2.9 years and 24.1% patients suffered death-censored graft loss (DCGL). Patients with high Treg cells 1 year after transplantation and above the median value (14.57 cells/mm3), showed better death-censored graft survival (5-year survival, 92.5% vs 81.4%, Log-rank P = .030). One-year Treg cells showed a receiver operating characteristic - area under curve of 63.1% (95% confidence interval, 52.9-73.2%, P = 0.026) for predicting DCGL. After multivariate Cox regression analysis, an increased number of peripheral blood Treg cells was a protective factor for DCGL (hazard ratio, 0.961, 95% confidence interval, 0.924-0.998, P = 0.041), irrespectively of 1-year proteinuria and renal function. Conclusions:Peripheral blood absolute numbers of Treg cells 1 year after kidney transplantation predict a better long-term graft outcome and may be used as prognostic biomarkers.

SUBMITTER: San Segundo D

PROVIDER: S-EPMC6411222 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Regulatory T-cell Number in Peripheral Blood at 1 Year Posttransplant as Predictor of Long-term Kidney Graft Survival.

San Segundo David D Galván-Espinoza Luis H LH Rodrigo Emilio E Irure Juan J Ruiz Juan C JC Fernández-Fresnedo Gema G Riesco Laura L Bada Jairo J Belmar Lara L Lopez-Hoyos Marcos M

Transplantation direct 20190208 3

<h4>Background</h4>Regulatory T (Treg) cells play a role in limiting kidney transplant rejection and can potentially promote long-term transplant tolerance. There are no large prospective studies demonstrating the utility of peripheral blood Treg cells as biomarkers for long-term graft outcome in kidney transplantation. The aim of our study was to analyze the influence of the absolute number of peripheral blood Treg cells after transplantation on long-term death-censored graft survival.<h4>Metho ...[more]

PMID: 30882031

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Project description:Key Points eGFR at 1 year post transplant is an established predictor of graft failure, but the effects of major intercurrent events are not fully known. We assessed the link between 12-month eGFR and long-term graft failure accounting for intercurrent events and competing mortality risks. Acute rejection, cardiovascular events, and infectious events were significant risks; 12-month eGFR remained the dominant driver of graft failure. Visual Abstract Background Estimated glomerular filtration rate (eGFR) at 1 year post transplantation has been shown to be a strong predictor of long-term graft survival. However, intercurrent events (ICEs) may affect the relationship between eGFR and failure risk. Methods The OPTN and USRDS databases on single-organ kidney transplant recipients from 2012 to 2016 were linked. Competing risk regressions estimated adjusted subhazard ratios (SHRs) of 12-month eGFR on long-term graft failure, considering all-cause mortality as the competing risk, for deceased donor (DD) and living donor (LD) recipients. Additional predictors included recipient, donor, and transplant characteristics. ICEs examined were acute rejection, cardiovascular events, and infections. Results Cohorts comprised 25,131 DD recipients and 7471 LD recipients. SHRs for graft failure increased rapidly as 12-month eGFR values decreased from the reference 60 ml/min per 1.73 m2. At an eGFR of 20 ml/min per 1.73 m2, SHRs were 13–15 for DD recipients and 12–13 for LD recipients; at an eGFR of 30 ml/min per 1.73 m2, SHRs were 5.0–5.7 and 5.0–5.5, respectively. Among first-year ICEs, acute rejection was a significant predictor of long-term graft failure in both DD (SHR=1.63, P<0.001) and LD (SHR=1.51, P=0.006) recipients; cardiovascular events were significant in DD (SHR=1.24, P<0.001), whereas non-CMV infections were significant in the LD cohort (SHR=1.32, P=0.03). Adjustment for ICEs did not significantly reduce the association of eGFR with graft failure. Conclusions Twelve-month eGFR is a strong predictor of long-term graft failure after accounting for clinical events occurring from discharge to 1 year. These findings may improve patient management and clinical evaluation of novel interventions.

Project description:BackgroundIn Ontario, kidney transplants have risen by 4% annually in recent years. An understanding of how this will affect the future annual number of posttransplant follow-up visits informs how to organize and deliver care.ObjectiveWe projected the required number of annual posttransplant follow-up nephrology visits to inform posttransplant care delivery.DesignPopulation-based retrospective cohort study.SettingLinked databases from Ontario, Canada (population 14 million).PatientsIncident kidney transplant recipients from years 2008 to 2013.MeasurementsFrequency, distance traveled, and current and projected visits for posttransplant follow-up.MethodsAssuming a graft survival of 13 years and using the mean number of posttransplant clinic visits in years 1, 2, and 3, we forecasted the number of clinic visits needed in the year 2027.ResultsUsing data from 2443 recipients, the mean (SD) number of clinic visits per recipient was 14.0 (9.2) in the first year after transplant, and 3.9 (6.2) and 3.0 (5.3) in the second and third year, respectively. If transplant rates rise by 4% per year until 2027, the estimated annual visits number will increase from 30 622 to 43 948. The median (25th, 75th percentile) distance between transplant center and patient's home was 30 (13, 65) km. The median round-trip travel distance for these visits in the first year after transplantation was 603 km per recipient, and median driving cost was Can$344 (2017).LimitationsRegarding patient expense, limitations include that distances traveled were calculated orthodromically, and we did not account for patient cost of follow-up beyond that of vehicular travel. Regarding follow-up projections, limitations include the assumption that graft life span will not change, follow-up patterns do not differ between donor kidney type, and we did not survey stakeholders as to their preferred method of follow-up.ConclusionWe quantified the increase in posttransplant visits when regional annual rates of transplantation rise. Strategies recognizing the burden of these visits may enhance patient-centered care, as it is unclear how some patients manage costs, nor how the current health care system will manage the demand.

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Regulatory T-cell Number in Peripheral Blood at 1 Year Posttransplant as Predictor of Long-term Kidney Graft Survival.

Publications

Regulatory T-cell Number in Peripheral Blood at 1 Year Posttransplant as Predictor of Long-term Kidney Graft Survival.

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