scholarly journals Early renal function trajectories, cytomegalovirus serostatus and long-term graft outcomes in kidney transplant recipients

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Jonathan P. Law ◽  
Richard Borrows ◽  
David McNulty ◽  
Adnan Sharif ◽  
Charles J. Ferro
Keyword(s):  
Kidney Transplant ◽  
Graft Survival ◽  
Hazard Analysis ◽  
Graft Loss ◽  
Smooth Curve ◽  
Mortality Data ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Rapid Deterioration

Abstract Background Improved recognition of factors influencing graft survival has led to better short-term kidney transplant outcomes. However, efforts to prevent long-term graft decline and improve graft survival have seen more modest improvements. The adoption of electronic health records has enabled better recording and identification of donor-recipient factors through the use of modern statistical techniques. We have previously shown in a prevalent renal transplant population that episodes of rapid deterioration are associated with graft loss. Methods Estimated glomerular filtration rates (eGFR) between 3 and 27 months after transplantation were collected from 310 kidney transplant recipients. We utilised a Bayesian approach to estimate the most likely eGFR trajectory as a smooth curve from an average of 10,000 Monte Carlo samples. The probability of having an episode of rapid deterioration (decline greater than 5 ml/min/1.73 m2 per year in any 1-month period) was calculated. Graft loss and mortality data was collected over a median follow-up period of 8 years. Factors associated with having an episode of rapid deterioration and associations with long-term graft loss were explored. Results In multivariable Cox Proportional Hazard analysis, a probability greater than 0.8 of rapid deterioration was associated with long-term death-censored graft loss (Hazard ratio 2.17; 95% Confidence intervals [CI] 1.04–4.55). In separate multivariable logistic regression models, cytomegalovirus (CMV) serostatus donor positive to recipient positive (Odds ratio [OR] 3.82; 95%CI 1.63–8.97), CMV donor positive (OR 2.06; 95%CI 1.15–3.68), and CMV recipient positive (OR 2.03; 95%CI 1.14–3.60) were associated with having a greater than 0.8 probability of an episode of rapid deterioration. Conclusions Early episodes of rapid deterioration are associated with long-term death-censored graft loss and are associated with cytomegalovirus seropositivity. Further study is required to better manage these potentially modifiable risks factors and improve long-term graft survival.

P1638EARLY RENAL FUNCTION TRAJECTORIES, CYTOMEGALOVIRUS SEROSTATUS AND LONG-TERM GRAFT OUTCOMES IN KIDNEY TRANSPLANT RECIPIENTS: A BAYESIAN ANALYSIS STUDY

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Jonathan Law ◽  
Richard Borrows ◽  
David McNulty ◽  
Adnan Sharif ◽  
Charles Ferro
Keyword(s):  
Kidney Transplant ◽  
Graft Loss ◽  
Smooth Curve ◽  
Rapid Progression ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Short Term ◽  
Allograft Function

Abstract Background and Aims Despite significant improvements in short-term kidney transplant survival, long-term graft survival has not improved to the same degree with transplant failure being a top four cause of end-stage renal disease. We previously showed in a prevalent kidney transplant population that most patients do not experience linear renal function trajectories1. Many, instead, have periods of stability whilst others experience rapid progression. We also showed that episodes of rapid progression are associated with graft loss. Understanding trajectories of kidney allograft function is, therefore, key to defining the mechanisms underpinning allograft dysfunction. In this study, we evaluated the allograft function trajectories and associated factors, in an unselected, incident population of kidney allograft recipients in the early period post-transplantation. We also investigate whether episodes of rapid progression or non-progression are associated with graft loss in an extended follow-up period Method Demographic and clinical data were obtained from electronic health records. We used Bayesian smoothing techniques1 to create 10,000 Monte Carlo sample curves for 310 kidney transplant recipients for estimated glomerular filtration rates from 3-27 months after transplantation. This technique produces a smooth curve for each patient that reflects the gradual, longer term changes in eGFR values, rather than the rapid, short-term changes because of clinical and biologic variation as well as other interference including measurement error. The estimated trajectory is a smooth curve, allowing its slope to be calculated month by month. The probability of having an episode of rapid progression (decline greater than 5 ml/min/1.73m2/year in any 1-month period) and non-progression (decline no greater than -1ml/min/1.73m2/year) were calculated. Overall follow-up period was 8 years. Factors associated with having an episode of rapid progression, non-progression, and associations with long-term graft loss were explored. Results A median of 54 eGFR measurements per patient were available from 3-27 months for analysis. 65 patients (21%) had a probability of rapid progression greater than 0.8. During the follow-up period, 34 patients (11%) lost their graft. In multivariable Cox Proportional Hazard analysis, a probability greater than 0.8 of rapid progression was associated with long-term death-censored graft loss (Hazard ratio, 2.17; 95% CI, 1.04-4.55). In separate multivariable logistic regression models, cytomegalovirus serostatus donor positive to recipient positive (Odds ratio [OR], 3.82; 95% CI 1.63-8.97), CMV donor positive (OR 2.06; 95% CI 1.15-3.68), and CMV recipient positive (OR 2.03; 95% CI 1.14-3.60) were associated with having a greater than 0.8 probability of an episode of rapid progression. Having a probability greater than 0.8 of non-progression was not associated graft loss. Conclusion Early episodes of rapid progression are associated with long-term death-censored graft loss and are associated with cytomegalovirus seropositivity. Possible mechanisms include adverse cytomegalovirus-related immunomodulatory effects resulting in increased infections, glomerular injury and allograft vasculopathy. Further investigation into these factors may yield potentially modifiable risk factors and improve graft survival.

scholarly journals Living Donor Kidney Transplantation Improves Graft and Recipient Survival in Patients with Multiple Kidney Transplants

2020 ◽  
Vol 9 (7) ◽  
pp. 2118 ◽  
Author(s):  
Maria Irene Bellini ◽  
Aisling E Courtney ◽  
Jennifer A McCaughan
Keyword(s):  
Kidney Transplantation ◽  
Renal Replacement Therapy ◽  
Replacement Therapy ◽  
Kidney Transplant ◽  
Graft Survival ◽  
Living Donor ◽  
Patient Survival ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients

Background: Failed kidney transplant recipients benefit from a new graft as the general incident dialysis population, although additional challenges in the management of these patients are often limiting the long-term outcomes. Previously failed grafts, a long history of comorbidities, side effects of long-term immunosuppression and previous surgical interventions are common characteristics in the repeated kidney transplantation population, leading to significant complex immunological and technical aspects and often compromising the short- and long-term results. Although recipients’ factors are acknowledged to represent one of the main determinants for graft and patient survival, there is increasing interest in expanding the donor’s pool safely, particularly for high-risk candidates. The role of living kidney donation in this peculiar context of repeated kidney transplantation has not been assessed thoroughly. The aim of the present study is to analyse the effects of a high-quality graft, such as the one retrieved from living kidney donors, in the repeated kidney transplant population context. Methods: Retrospective analysis of the outcomes of the repeated kidney transplant population at our institution from 1968 to 2019. Data were extracted from a prospectively maintained database and stratified according to the number of transplants: 1st, 2nd or 3rd+. The main outcomes were graft and patient survivals, recorded from time of transplant to graft failure (return to dialysis) and censored at patient death with a functioning graft. Duration of renal replacement therapy was expressed as cumulative time per month. A multivariate analysis considering death-censored graft survival, decade of transplantation, recipient age, donor age, living donor, transplant number, ischaemic time, time on renal replacement therapy prior to transplant and HLA mismatch at HLA-A, -B and -DR was conducted. In the multivariate analysis of recipient survival, diabetic nephropathy as primary renal disease was also included. Results: A total of 2395 kidney transplant recipients were analysed: 2062 (83.8%) with the 1st kidney transplant, 279 (11.3%) with the 2nd graft, 46 (2.2%) with the 3rd+. Mean age of 1st kidney transplant recipients was 43.6 ± 16.3 years, versus 39.9 ± 14.4 for 2nd and 41.4 ± 11.5 for 3rd+ (p < 0.001). Aside from being younger, repeated kidney transplant patients were also more often males (p = 0.006), with a longer time spent on renal replacement therapy (p < 0.0001) and a higher degree of sensitisation, expressed as calculated reaction frequency (p < 0.001). There was also an association between multiple kidney transplants and better HLA match at transplantation (p < 0.0001). A difference in death-censored graft survival by number of transplants was seen, with a median graft survival of 328 months for recipients of the 1st transplant, 209 months for the 2nd and 150 months for the 3rd+ (p = 0.038). The same difference was seen in deceased donor kidneys (p = 0.048), but not in grafts from living donors (p = 0.2). Patient survival was comparable between the three groups (p = 0.59). Conclusions: In the attempt to expand the organ donor pool, particular attention should be reserved to high complex recipients, such as the repeated kidney transplant population. In this peculiar context, the quality of the donor has been shown to represent a main determinant for graft survival—in fact, kidney retrieved from living donors provide comparable outcomes to those from single-graft recipients.

scholarly journals P1706THE GRAFT SURVIVAL OF KIDNEY TRANSPLANTATION ACCORDING TO ETHNICITY IN KIDNEY TRANSPLANT RECIPIENTS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Yeonsoon Jung ◽  
Jisu Kim ◽  
Haesu Jeon ◽  
Ye Na Kim ◽  
Ho Sik Shin ◽  
...  
Keyword(s):  
African American ◽  
Kidney Transplantation ◽  
Kidney Transplant ◽  
Graft Survival ◽  
Cox Regression ◽  
Patient Survival ◽  
Graft Loss ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Data Set

Abstract Background African American kidney transplant recipients experience disproportionately high rates of graft loss. The aim of this analysis was to use a UNOS data set that contains detailed baseline and longitudinal clinical data to establish and quantify the impact of the current overall graft loss definition on suppressing the true disparity magnitude in US AA kidney transplant outcomes. Methods Longitudinal cohort study of kidney transplant recipients using a data set created by United Network for Organ Sharing (UNOS), including 266,128 (African American 70,215, Non-African American 195,913) transplant patient between 1987 and December 2016. Multivariable analysis was conducted using 2-stage joint modeling of random and fixed effects of longitudinal data (linear mixed model) with time to event outcomes (Cox regression). Results 195,913 non-African American (AA) (73.6%) were compared with 70,215 AA (26.4%) recipients. 10-year-graft survival of AA in all era is lower than that of non-AA (31% in deceased kidney transplants (DKT) AA recipient and 42% in living kidney transplantation (LKT) non-AA recipient). 10-year-patient survival of AA with functioning graft in all era is similar that of non-AA. Multivariate Cox regression of factors associated with patient survival with functioning graft are acute rejection within 6 months, DM, hypertension and etc. Pre-transplant recipient BMI in AA show the trend as a protective factor in patient survival with functioning graft although not significantly in statistics Conclusions African American kidney transplant recipients experience a substantial disparity in graft loss, but not patient death with functioning graft.

Immunological biomarkers and long term graft survival. Prospective follow-up of 457 kidney transplant recipients

2017 ◽  
Author(s):  
Michał Ciszek ◽  
Krzysztof Mucha ◽  
Bartosz Foroncewicz ◽  
Dorota Żochowska ◽  
Maciej Kosieradzki ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Graft Survival ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients

scholarly journals Long-Term Outcomes in 831 Kidney Transplant Recipients with 20 Years of Graft Function

2021 ◽  
Vol 8 ◽  
Author(s):  
Varvara Kirchner ◽  
Kristen Gillingham ◽  
Oscar Serrano ◽  
Srinath Chinnakotla ◽  
Ty Dunn ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Graft Survival ◽  
Interstitial Fibrosis ◽  
Graft Loss ◽  
Graft Function ◽  
Solid Organ ◽  
Kidney Transplant Recipients ◽  
Long Term Outcomes ◽  
Tubular Atrophy

An understanding of long-term outcomes for kidney transplant(KTx) recipients who survive with graft function beyond a specific time posttransplant is the first step in creating protocols to optimize care for current and improve outcomes for future recipients. We studied 831KTx recipients-580 living donor(LD); 251 deceased donor(DD)—with graft survival(GS) >20 years.  For primary LD recipients, 25-year patient survival(PS) was 83%; 35-year, 59%.  Their 25-year death-censored graft survival(DCGS) was 89%; 35-year, 72%.   DD recipients had lower PS(P<0.01), DCGS(P<0.01).   After 20 years, two major causes of graft loss(GL) were death with function(DwF)(58%, LD; 58%, DD) and interstitial fibrosis and tubular atrophy(IFTA)(22%, LD; 23%, DD).  Two major causes of DwF were cancer(31%, LD; 31%, DD) and cardiovascular disease(CVD)(19%, LD;17%, DD).  Per multivariate analysis(MVA), risk factors for GL after 20 years in pre–calcineurin inhibitor(CNI) era were human leukocyte antigen(HLA) mismatches >3 antigens, pretransplant type 1 diabetes mellitus(DM1); in CNI era, a history of rejection, female gender.  New comorbidities after 20 years were common: CVD(13%, non-DM1;18%, DM1), infections(27%, non-DM1;37%, DM1), 20-29 years posttransplant.  Cancer after 20 years included: nonmelanotic skin cancer,22%; solid organ,7%; post-transplant lymphoproliferative disease(PTLD),2%.  To improve long-term outcomes, clinical trials on prevention, recognition, and treatment of new comorbidities are needed.

scholarly journals Trends in the Causes of Death among Kidney Transplant Recipients in the United States (1996–2014)

2018 ◽  
Vol 48 (6) ◽  
pp. 472-481 ◽  
Author(s):  
Ahmed A. Awan ◽  
Jingbo Niu ◽  
Jenny S. Pan ◽  
Kevin F. Erickson ◽  
Sreedhar Mandayam ◽  
...  
Keyword(s):  
United States ◽  
Kidney Transplant ◽  
Cardiovascular Mortality ◽  
Causes Of Death ◽  
Graft Loss ◽  
Graft Function ◽  
The United States ◽  
Mortality Data ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients

Background: Death with graft function remains an important cause of graft loss among kidney transplant recipients (KTRs). Little is known about the trend of specific causes of death in KTRs in recent years. Methods: We analyzed United States Renal Data System data (1996–2014) to determine 1- and 10-year all-cause and cause-specific mortality in adult KTRs who died with a functioning allograft. We also studied 1- and 10-year trends in the various causes of mortality. Results: Of 210,327 KTRs who received their first kidney transplant from 1996 to 2014, 3.2% died within 1 year after transplant. Cardiovascular deaths constituted the majority (24.7%), followed by infectious (15.2%) and malignant (2.9%) causes; 40.1% of deaths had no reported cause. Using 1996 as the referent year, all-cause as well as cardiovascular mortality declined, whereas mortality due to malignancy did not. For analyses of 10-year mortality, we studied 94,384 patients who received a first kidney transplant from 1996 to 2005. Of those, 22.1% died over 10 years and the causative patterns of their causes of death were similar to those associated with 1-year mortality. Conclusions: Despite the downtrend in mortality over the last 2 decades, a significant percentage of KTRs die in 10-years with a functioning graft, and cardiovascular mortality remains the leading cause of death. These data also highlight the need for diligent collection of mortality data in KTRs.

High Regulatory T-Cell Levels at 1 Year Posttransplantation Predict Long-Term Graft Survival Among Kidney Transplant Recipients

2012 ◽  
Vol 44 (9) ◽  
pp. 2538-2541 ◽  
Author(s):  
D. San Segundo ◽  
G. Fernández-Fresnedo ◽  
E. Rodrigo ◽  
J.C. Ruiz ◽  
M. González ◽  
...  
Keyword(s):  
T Cell ◽  
Kidney Transplant ◽  
Graft Survival ◽  
Regulatory T Cell ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients

scholarly journals Induction Immunosuppression in Pediatric Kidney Transplant Recipients Under the Age of 11 with Rabbit Anti-Thymocyte Globulin

2020 ◽  
Vol 3 ◽  
Author(s):  
William Goggins ◽  
Richard Mangus ◽  
Burcin Ekser ◽  
William Goggins
Keyword(s):  
Kidney Transplant ◽  
Graft Survival ◽  
Lymphoproliferative Disorder ◽  
Graft Loss ◽  
Bk Virus ◽  
P Value ◽  
Induction Agent ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Post Transplant

Background:     At the time of kidney transplantation (KT), induction immunosuppression is used to reduce the incidence of early rejection and avoid the use of chronic corticosteroids in maintenance immunosuppression. There is currently no standard of care for induction immunosuppression in the pediatric recipient, instead it is based on institutional preference. In this study, we compare our current induction immunosuppression, rabbit anti-thymocyte globulin (rATG), to our previous induction immunosuppression, Daclizumab in patients under the age of 11.     Methods:     From 07/2004 to 08/2019, 79 patients under the age of 11 have received a KT. 7 patients were excluded from analysis due to Basiliximab induction (n=3), graft loss within 10 days (n=3) and patient death (n=1). 72 patients were analyzed, of which 39 patients (54%) with rATG induction were compared to 33 patients (46%) with daclizumab induction. All patients were maintained on steroid-free immunosuppression regimen after transplant. More than 20 variables were followed, along with rejection, graft failure, and any prevalence of post-transplant lymphoproliferative disorder (PTLD) was recorded (Figure 1).    Results:     Patients demographics were similar in both groups. Graft survival was good and statistically similar up to 5 years. In both groups, serum creatinine levels were similar up to 1 year follow up. Although CMV infection was similar in both groups, BK viremia and BK virus in the urine were more frequent in rATG group. Post-transplant lymphoproliferative disorder was significantly higher in the Daclizumab group (p=0.022), but less acute rejection was observed in the Daclizumab group (Figure 1).     Potential Impact:     Our study suggests that rATG is a safe and effective induction agent in pediatric kidney transplant recipients under the age of 11. Recipients have excellent patient and graft survival. It is associated with strong kidney function and low PTLD. Screening for BK virus in the urine is essential with rATG induction.     Table 1:     Induction Agent  Daclizumab  rATG  p value  Demographics        Number  33  39  N.S.  Sex  15M, 18F  27M, 12F  0.042  Age (years)  5.5 ± 2.7  6.1 ± 2.7  N.S.  Height (m)  1.02 ± 0.23  1.06 ± .21  N.S.  Weight (kg)  18.75 ± 9.93  19.08 ± 6.42  N.S.  Outcomes        Cr 1 month (mg/dL)  0.56 ± .31  0.45 ± .17  0.056  Cr 6 months (mg/dL)  0.54 ± .22  0.52 ± .18  N.S.  Cr 1 year (mg/dL)  0.63 ± .27  0.59 ± .17  N.S.  eGFR 1 month (ml/min/1.73m2)  84.81 ± 27.95  107.08 ± 30.09  0.0019  eGFR 6 months (ml/min/1.73m2)  85.04 ± 27.60  92.48 ± 28.07  N.S.  eGFR 1 year (ml/min/1.73m2)  74.31 ± 26.8  79.3 ± 22.01  N.S.  Rejection 6 months  1 (3.03%)  8 (20.51%)  0.0188  Rejection 1 year  2 (6.06%)  8 (20.51%)  0.0682  Graft Survival 1 year  100% (33/33)  100% (39/39)  N.S.  Graft Survival 3 years  96.97% (32/33)  100% (25/25)  N.S.  Graft Survival 5 years  96.88 (31/32)  100% (22/22)  N.S.  Cases of PTLD  5 (18.18%)  0 (0%)  0.022  Chronic steroid use  2 (6.06%)  2 (5.13%)  N.S.  BK Urine only 1 year  0% (0/33)*  10.26% (4/39)  0.0439  BK Viremia 1 year  3.03% (1/33)*  17.95% (7/39)  0.0356  CMV Viremia 1 year  0% (0/33)  5.13% (2/39)  N.S.  N.S.= Not statistically significant.  *BK screening was not routine during time of daclizumab induction 

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