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1.
Transplant Direct ; 10(6): e1622, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38769987

ABSTRACT

Background: Cytomegalovirus (CMV) infects >60% of adults and can pose an independent risk factor for allograft loss and mortality in solid organ transplant recipients. The purpose of this study is to evaluate the impact of a nationwide implementation of CMV seromatching (donor/recipient: D-/R- and D+/R+) in the U.S. deceased donor kidney allocation system (KAS). Methods: Adult candidates on the U.S. kidney-only transplant waiting list and deceased donor kidneys offered to the U.S. transplant centers were considered. A discrete-event simulation model, simulating the pre-COVID-19 period from January 1, 2015, to January 1, 2018, was used to compare the performances of currently employed KAS-250 policy (without CMV matching) to various simulated CMV matching policies parameterized by calculated panel reactive antibody exception threshold. Outcomes included CMV serodistribution, waiting time, access to transplantation among various groups, transplant rate, graft survival, kidney discard rate, and antigen-mismatch distribution, stratified by CMV serostatus. Results: CMV matching policy with a calculated panel reactive antibody exception threshold of 50% (namely, the CMV">50%" policy) strikes a better balance between benefits and drawbacks of CMV matching. Compared with KAS-250, CMV">50%" reduced CMV high-risk (D+/R-) transplants (6.1% versus 18.1%) and increased CMV low-risk (D-/R-) transplants (27.2% versus 13.1%); increased transplant rate for CMV R- patients (11.54 versus 12.57) but decreased for R+ patients (10.68 versus 10.48), yielding an increase in aggregate (11.09 versus 10.94); and reduced mean time to transplantation (by 6 wk); and reduced kidney discard rate (25.7% versus 26.2%). Conclusions: Our findings underscore the feasibility and potential advantages of a nationwide CMV seromatching policy in kidney transplantation.

3.
Transplantation ; 106(10): 2006-2018, 2022 10 01.
Article in English | MEDLINE | ID: mdl-35765128

ABSTRACT

BACKGROUND: Nonalcoholic steatohepatitis (NASH) continues to increase in frequency as an indication for liver transplantation (LT). Data on long-term outcomes for these patients are limited. We aimed to compare long-term patient and graft survival in patients undergoing LT for NASH in the United States to other indications. METHODS: We analyzed data from the Scientific Registry of Transplant Recipients of adult patients who underwent primary deceased-donor LT from January 1, 2005, to December 31, 2019. RESULTS: NASH has increased as an indication for LT by 4.5-fold, from 5.2% in 2005 to 23.4% in 2019. Patient (61.2%) and graft survival (59.2%) at 10 y are significantly poorer for NASH than for all other indications other than alcohol. Patients transplanted for NASH have higher body mass index (32.2 versus 27.6) and greater frequency of diabetes (13% versus 11.6%) than any other indication ( P < 0.001). Portal vein thrombosis, location in intensive care unit, dialysis, and pre-LT diabetes ( P < 0.001 for all) are independently predictive of patient death and graft loss. Body mass index is not predictive. NASH patients undergoing simultaneous liver kidney have markedly worse 10-y patient and graft survival than liver-only (52.3% versus 62.1%). Graft loss was attributed to recurrence of NASH in <1% of patients. CONCLUSIONS: LT for NASH is associated with relatively poor long-term patient and graft survival when compared with patients transplanted for other indications, NASH patients undergoing simultaneous liver kidney have the worst long-term outcomes.


Subject(s)
Diabetes Mellitus , Liver Transplantation , Non-alcoholic Fatty Liver Disease , Adult , Diabetes Mellitus/etiology , Graft Survival , Humans , Liver Transplantation/adverse effects , Non-alcoholic Fatty Liver Disease/complications , Retrospective Studies , Risk Factors , Treatment Outcome , United States/epidemiology
5.
Transplant Proc ; 53(6): 1858-1864, 2021.
Article in English | MEDLINE | ID: mdl-34246476

ABSTRACT

BACKGROUND: The kidney is essential for glucose and insulin metabolism. Living kidney donors (LKDs) experience a reduction in glomerular filtration rate of 25 to 30 mL/min after donor nephrectomy. Little is known about the effect of glomerular filtration rate decline on insulin sensitivity in LKDs. METHODS: We conducted a prospective pilot study on 9 LKDs (N = 9) who underwent dynamic metabolic testing (mixed meal tolerance test) to measure proxies of insulin sensitivity (homeostatic model assessment of insulin resistance, the area under curve [AUC] for insulin/glucose ratio, and Matsuda insulin sensitivity index) before and 3 months after donor nephrectomy. The primary outcome was the change in insulin sensitivity indices (delta [post-nephrectomy - pre-nephrectomy]). RESULTS: Four of the donors had a body mass index (BMI) between 32.0 and 36.7 predonation. Post-donor nephrectomy, compared with prenephrectomy values, median insulin AUC increased from 60.7 to 101.7 hr*mU/mL (delta median 33.3, P = .04) without significant change in median glucose AUC levels from 228.9 to 209.3 hr*mg/dL (delta median 3.2, P = .77). There was an increase in the median homeostatic model assessment of insulin resistance from 2 to 2.9 (delta median 0.8, P = .03) and the AUC insulin/glucose ratio from 30.9 to 62.1 pmol/mmol (delta median 17.5, P = .001), whereas the median Matsuda insulin sensitivity index decreased from 5.9 to 2.9 (delta median -2, P = .05). The changes were more pronounced in obese (BMI >32) donors. CONCLUSION: LKDs appear to have a trend toward a decline in insulin sensitivity post-donor nephrectomy in the short term, especially in obese donors (BMI >32). Further investigation with a larger sample size and longer follow-up is needed.


Subject(s)
Insulin Resistance , Kidney Transplantation , Living Donors , Adult , Aged , Female , Humans , Kidney , Kidney Transplantation/adverse effects , Male , Middle Aged , Nephrectomy/adverse effects , Pilot Projects , Prospective Studies , Young Adult
6.
Hepatology ; 73(4): 1464-1477, 2021 04.
Article in English | MEDLINE | ID: mdl-32559317

ABSTRACT

BACKGROUND AND AIMS: There are more adults than children living with congenital heart disease (CHD) in the United States, with a growing proportion requiring heart-liver transplantation (HLT). Our aim was to ascertain the frequency, outcomes, and prognostic factors in this patient population. APPROACH AND RESULTS: United Network for Organ Sharing data on adult patients who underwent heart transplantation (HT) from 2009 through March 2020 were analyzed. The primary study outcome was patient survival. Cox proportional-hazards modeling assessed for mortality associations. There were 1,084 HT recipients: 817 (75.4%) CHD HTs only, 74 (6.8%) CHD HLTs, 179 (16.5%) non-CHD HLTs, and 14 (1.3%) heart-liver-kidney transplants. The number of CHD HLTs increased from a prior rate of 4/year to 21/year in 2019. Among patients with CHD, the 5-year survival rates were 74.1% and 73.6% in HTs only and HLTs, respectively (P = 0.865). There was a higher rate of allograft failure attributable to rejection in CHD HTs only compared with CHD HLTs (3.2% versus 0.4%; P = 0.014). Only 25 out of 115 HT-performing hospitals undertook CHD HLTs. Higher-volume centers (averaging one CHD HLT per year) had a 5-year patient survival rate of 83.0% compared with 61.3% in lower-volume centers (P = 0.079). Among HLT recipients, total bilirubin (hazard ratio [HR], 1.06; 95% confidence interval [CI], 1.01-1.12) and diabetes (HR = 2.97, 95% CI = 1.21-7.31) were independently associated with increased mortality risk, whereas CHD and age were not. CONCLUSIONS: The rate of HLT for adult CHD in the United States is rising dramatically. The survival outcomes between CHD HT only and CHD HLT groups are comparable; however, the HLT group had lower rates of acute rejection. Among HLT recipients, diabetes and elevated bilirubin are associated with increased posttransplant mortality risk. An average of one CHD HLT per year could be considered a minimum quality metric at transplant centers.


Subject(s)
Heart Defects, Congenital/surgery , Heart Transplantation/mortality , Heart Transplantation/methods , Liver Transplantation/mortality , Liver Transplantation/methods , Outcome Assessment, Health Care , Adult , Bilirubin/blood , Diabetes Complications/mortality , Female , Follow-Up Studies , Heart Defects, Congenital/blood , Heart Defects, Congenital/epidemiology , Heart Transplantation/trends , Humans , Liver Transplantation/trends , Male , Middle Aged , Prognosis , Prospective Studies , Survival Rate , Tissue Donors , Transplant Recipients , Transplantation, Homologous/methods , Transplantation, Homologous/mortality , Transplantation, Homologous/trends , United States/epidemiology , Young Adult
7.
Am J Transplant ; 21(3): 1039-1055, 2021 03.
Article in English | MEDLINE | ID: mdl-32531107

ABSTRACT

Medical-refractory severe alcoholic hepatitis (AH) has a high mortality. The national frequency, longer term outcomes and regional practices of AH liver transplantation (LT) in the United States are not well described, despite the increasing mortality from alcohol-associated liver disease. We analyzed the trends in frequency and outcomes of UNOS data on 39 455 adult patients who underwent LT from 2014 to 2019, including AH LT recipients. LTs for AH increased 5-fold, from 28 in 2014 to 138 in 2019, varying 8-fold between UNOS regions. Three transplant centers accounted for 50%-90% of AH LTs within each region. The number of transplant centers performing AH LTs increased from 14 in 2014 to 47 in 2019. AH patients were younger (mean = 39.4 years), had higher MELD scores (mean = 36.8), and were more often on dialysis (46.0%) and in ICU (38.4%), compared to other indications (all P < .05). One- and 5-year graft survivals for AH LT recipients were 91.7% and 81.9%, respectively. The frequency of AH LT is increasing rapidly, with excellent medium-term outcomes. An impact of AH recurrence on patient or graft survival is not apparent in this national analysis. There are marked geographic variations in practices, highlighting the lack of selection criteria standardization.


Subject(s)
Hepatitis, Alcoholic , Liver Diseases, Alcoholic , Liver Transplantation , Adult , Graft Survival , Hepatitis, Alcoholic/surgery , Humans , Patient Selection , United States/epidemiology
8.
Transpl Infect Dis ; 22(1): e13204, 2020 Feb.
Article in English | MEDLINE | ID: mdl-31677214

ABSTRACT

BACKGROUND: Kidneys from deceased donors infected with hepatitis C virus (HCV) are underutilized. Most HCV virus-infected donors are designated as Public Health Service increased donors (PHS-IR). Impact of PHS and HCV designations on discard is not well studied. METHODS: We queried the UNOS data set for all deceased donor kidneys between January 2015 and December 2018. The final study cohort donors (n = 38 702) were stratified into three groups based on HCV antibody (Ab) and NAT status: (a) Ab-/NAT- (n = 35 861); (b) Ab+/NAT- (n = 973); and (c) Ab±/NAT+ (n = 1868). We analyzed utilization/discard rates of these organs, the impact of PHS-IR and HCV designations on discard using multivariable two-level hierarchical logistic regression models, forecasted number of HCV viremic donors/kidneys by 2023. RESULTS: During the study period, (a) the number of viremic donor kidneys increased 2 folds; (b) the multilevel mixed-effects logistic regression models showed that, overall, the PHS labeling (OR 1.20, CI 95% CI 1.15-1.29) and HCV designation (OR 2.29; 95% CI 2.15-2.43) were independently associated with increased risk of discard; (c) contrary to the general perception, PHS-IR kidneys across all HCV groups, compared to PHS-IR kidneys were more likely to be discarded; (d) we forecasted that the number of kidneys from HCV viremic donor kidneys might increase from 1376 in 2019 to 2092 in 2023. CONCLUSION: Hepatitis C virus viremic kidneys might represent 10%-15% of deceased donor organ pool soon with the current rate of the opioid epidemic. PHS labeling effect on discard requires further discussion of the utility of this classification.


Subject(s)
Hepacivirus/isolation & purification , Kidney Transplantation/adverse effects , Kidney/virology , Tissue and Organ Procurement/trends , Adult , Cadaver , Donor Selection/standards , Female , Hepacivirus/genetics , Hepatitis C , Humans , Logistic Models , Male , Middle Aged , Retrospective Studies , Risk Assessment , Risk Factors , United States , United States Public Health Service , Viremia , Young Adult
9.
Am J Transplant ; 19(11): 3058-3070, 2019 11.
Article in English | MEDLINE | ID: mdl-31207073

ABSTRACT

The United States opioid use epidemic over the past decade has coincided with an increase in hepatitis C virus  (HCV) positive donors. Using propensity score matching, and the Organ Procurement Transplant Network data files from January 2015 to June 2019, we analyzed the short-term outcomes of adult deceased donor kidney transplants of HCV uninfected recipients with two distinct groups of HCV positive donors (HCV seropositive, nonviremic n = 352 and viremic n = 196) compared to those performed using HCV uninfected donors (n = 36 934). Compared to the reference group, the transplants performed using HCV seropositive, nonviremic and viremic donors experienced a lower proportion of delayed graft function (35.2 vs 18.9%; P < .001 [HCV seropositive, nonviremic donors] and 36.2 vs 16.8% ;  P < .001[HCV viremic donors]). The recipients of HCV viremic donors had better allograft function at 6 months posttransplant (eGFR [54.1 vs 68.3 mL/min/1.73 m2; P = .004]. Furthermore, there was no statistical difference in the overall graft failure risk at 12 months posttransplant by propensity score matched multivariable Cox proportional analysis (HR =  0.60, 95% CI  0.23 to  1.29 [HCV seropositive, nonviremic donors] and HR =  0.85, 95% CI 0.25 to  2.96 [HCV viremic donors]). Further studies are required to determine the long-term outcomes of these transplants and address unanswered questions regarding the use of HCV viremic donors.


Subject(s)
Graft Survival , Hepatitis C/transmission , Kidney Failure, Chronic/surgery , Kidney Transplantation/methods , Tissue Donors/supply & distribution , Transplant Recipients/statistics & numerical data , Viremia/transmission , Adult , Aged , Antiviral Agents/therapeutic use , Female , Follow-Up Studies , Glomerular Filtration Rate , Hepacivirus/isolation & purification , Hepatitis C/drug therapy , Hepatitis C/virology , Humans , Male , Middle Aged , Prognosis , Retrospective Studies , Risk Factors , Tissue and Organ Procurement/methods , Viremia/drug therapy , Viremia/virology
10.
Liver Transpl ; 25(4): 598-609, 2019 04.
Article in English | MEDLINE | ID: mdl-30716208

ABSTRACT

Highly effective direct-acting antiviral (DAA) therapy has transformed outcomes of liver transplantation in hepatitis C virus (HCV) patients. We examined longer-term outcomes in HCV-positive recipients in the DAA era and analyzed the Scientific Registry of Transplant Recipients for primary adult, single-organ, nonfulminant liver transplant recipients in the United States from January 1, 2008 to June 30, 2018. Graft loss was compared among HCV-positive liver transplant recipients who received either an HCV-negative or HCV-positive donor (donor [D]-/recipient [R]+; D+/R+) and HCV-negative liver transplant recipients who received a HCV-negative donor (D-/R-). The groups were further divided between the pre-DAA and DAA eras. There were 52,526 patients included: 31,193 were D-/R- patients; 18,746 were D-/R+ patients; and 2587 were D+/R+ patients. The number of D-/R+ transplants decreased from 2010 in 2008 to 1334 in 2017, with this decline particularly noticeable since 2015. D-/R+ patients in the DAA era (n = 7107) were older, had higher rates of hepatocellular carcinoma, and lower Model for End-Stage Liver Disease scores than those in the pre-DAA era. Graft survival improved for all recipients in the DAA era but improved most dramatically in HCV-positive recipients: D-/R+ 1-year survival was 92.4% versus 88.7% and 3-year survival was 83.7% versus 77.7% (DAA versus pre-DAA era, respectively) compared with D-/R- 1-year survival of 92.7% versus 91.0% and 3-year survival of 85.7% versus 84.0% (DAA versus pre-DAA era, respectively). The magnitude of improvement in 3-year graft survival was almost 4-fold greater for D-/R+ patients. The 3-year survival for D+/R+ patients was similar to HCV-negative patients. In conclusion, the number of liver transplants for HCV has decreased by more than one-third over the past decade. Graft survival among HCV-positive recipients has increased disproportionately in the DAA era with HCV-positive recipients now achieving similar outcomes to non-HCV recipients.


Subject(s)
Antiviral Agents/administration & dosage , End Stage Liver Disease/surgery , Graft Rejection/epidemiology , Hepatitis C, Chronic/drug therapy , Liver Transplantation/adverse effects , Adult , Aged , Allografts/drug effects , Allografts/virology , End Stage Liver Disease/diagnosis , End Stage Liver Disease/mortality , End Stage Liver Disease/virology , Female , Graft Rejection/virology , Graft Survival/drug effects , Hepacivirus/isolation & purification , Hepatitis C, Chronic/transmission , Hepatitis C, Chronic/virology , Humans , Kaplan-Meier Estimate , Liver/drug effects , Liver/virology , Liver Transplantation/statistics & numerical data , Male , Middle Aged , Prospective Studies , Registries/statistics & numerical data , Severity of Illness Index , Survival Rate , Treatment Outcome , United States/epidemiology , Young Adult
11.
Hepatology ; 69(6): 2381-2395, 2019 06.
Article in English | MEDLINE | ID: mdl-30706517

ABSTRACT

Direct-acting antiviral (DAA) therapy has altered the frequency and outcome of liver transplantation (LT) for hepatitis C virus (HCV). The high efficacy and tolerability of DAA therapy has also created a rationale for utilizing HCV-viremic (HCV-RNA-positive) donors, including into HCV-negative recipients. We examined trends in frequency of organ utilization and graft survival in recipients of HCV-viremic donors (HCV-RNA positive as measured by nucleic acid testing [NAT]). Data were collected from the Scientific Registry of Transplant Recipients (SRTR) on adult patients who underwent a primary, single-organ, deceased donor LT from January 1, 2008 to January 31, 2018. Outcomes of HCV-negative transplant recipients (R- ) who received an allograft from donors who were HCV-RNA positive (DNAT+ ) were compared to outcomes for R- patients who received organs from donors who were HCV-RNA negative (DNAT- ). There were 11,270 DNAT- /R- ; 4,748 DNAT- /R+ ; 87 DNAT+ /R- ; and 753 DNAT+ /R+ patients, with 2-year graft survival similar across all groups: DNAT- /R- 88%; DNAT- /R+ 88%; DNAT+ /R- 86%; and DNAT+ /R+ 90%. Additionally, there were 2,635 LTs using HCV antibody-positive donors (DAb+ ): 2,378 DAb+ /R+ and 257 DAb+ /R- . The annual number of DAb+ /R- transplants increased from seven in 2008 to 107 in 2017. In the post-DAA era, graft survival improved for all recipients, with 3-year survival of DAb+ /R- patients and DAb+ /R+ patients increasing to 88% from 79% and to 85% from 78%, respectively. Conclusion: The post-DAA era has seen increased utilization of HCV-viremic donor livers, including HCV-viremic livers into HCV-negative recipients. Early graft outcomes are similar to those of HCV-negative recipients. These results support utilization of HCV-viremic organs in selected recipients both with and without HCV infection.


Subject(s)
Hepatitis C, Chronic/drug therapy , Liver Transplantation/methods , Liver/virology , Registries , Transplant Recipients/statistics & numerical data , Viremia/surgery , Adult , Antiviral Agents/therapeutic use , Cohort Studies , Female , Follow-Up Studies , Graft Rejection , Graft Survival , Hepacivirus/isolation & purification , Hepatectomy/methods , Hepatitis C, Chronic/pathology , Humans , Incidence , Kaplan-Meier Estimate , Liver Transplantation/mortality , Male , Middle Aged , Proportional Hazards Models , Retrospective Studies , Risk Assessment , Tissue and Organ Procurement/methods , Tissue and Organ Procurement/statistics & numerical data
12.
Kidney Int Rep ; 1(4): 221-229, 2016 11.
Article in English | MEDLINE | ID: mdl-27942610

ABSTRACT

BACKGROUND: The survival benefit from simultaneous liver-kidney transplantation (SLK) over liver transplant alone (LTA) in recipients with moderate renal dysfunction is not well understood. Moreover, the impact of deceased donor organ quality in SLK transplant survival has not been well described in the literature. METHODS: The Scientific Registry of Transplant Recipients was studied for adult recipients receiving LTA (N=2,700) or SLK (N=1,361) transplantation with moderate renal insufficiency between 2003 and 2013. The study cohort was stratified into four groups based on serum creatinine (Scr< 2 mg/dL versus Scr≥ 2 mg/dL) and dialysis status at listing and at transplant. The patients with end-stage renal disease and requiring acute dialysis more than three months before transplantation were excluded. A propensity score (PS)-matching was performed in each stratified groups to factor out imbalances between the SLK and LTA regarding covariates distribution and to reduce measured confounding. Donor quality was assessed with liver-donor risk index (L-DRI). The primary outcome of interest was post-transplant mortality. RESULTS: On multivariable PS-matched Cox proportional hazard models, SLK led to decrease in post-transplant mortality compared to LTA across all four groups, but only reached statistical significance (HR 0.77; 95% CI, 0.62-0.96) in the recipients not exposed to dialysis and Scr≥ 2 mg/dL at transplant (mortality incidence rate per patient-year 5.7% in SLK vs. 7.6% in LTA, p=0.005). The decrease in mortality was observed among SLK recipients with better quality donors (L-DRI<1.5). CONCLUSIONS: Exposure to pre-transplantation dialysis and donor quality affected overall survival among SLK recipients.

13.
Clin J Am Soc Nephrol ; 11(9): 1650-1661, 2016 09 07.
Article in English | MEDLINE | ID: mdl-27364616

ABSTRACT

BACKGROUND AND OBJECTIVES: IL-2 receptor antagonist (IL2-RA) is recommended as a first-line agent for induction therapy in renal transplantation. However, this remains controversial in deceased donor renal transplantation (DDRT) maintained on tacrolimus (TAC)/mycophenolic acid (MPA) with or without steroids. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We studied the United Network for Organ Sharing Registry for patients receiving DDRT from 2000 to 2012 maintained on TAC/MPA at transplantation hospital discharge (n=74,627) to compare outcomes of IL2-RA and other induction agents. We initially divided the cohort into two groups on the basis of steroid use at the time of discharge: steroid (n=59,010) versus no steroid (n=15,617). Each group was stratified into induction categories: IL2-RA, rabbit antithymocyte globulin (r-ATG), alemtuzumab, and no induction. The main outcomes were incidence of acute rejection within the first year and overall graft failure (defined as graft failure and/or death) post-transplantation. Propensity score (PS), specifically inverse probability of treatment weight, analysis was used to minimize selection bias caused by nonrandom assignment of induction therapies. RESULTS: Median (25th, 75th percentiles) follow-up times were 3.9 (1.1, 5.9) and 3.2 (1.1, 4.9) years for steroid and no steroid groups, respectively. Acute rejection within the first year and overall graft failure within 5 years of transplantation were more common in the no induction category (13.3%; P<0.001 and 28%; P=0.01, respectively) in the steroid group and the IL2-RA category (11.1%; P=0.16 and 27.4%; P<0.001, respectively) in the no steroid group. Compared with IL2-RA, PS-weighted and covariate-adjusted multivariable logistic and Cox analyses showed that outcomes in the steroid group were similar among induction categories, except that acute rejection was significantly lower with r-ATG (odds ratio [OR], 0.68; 95% confidence interval [95% CI], 0.62 to 0.74). In the no steroid group, compared with IL2-RA, odds of acute rejection with r-ATG (OR, 0.80; 95% CI, 0.60 to 1.00) and alemtuzumab (OR, 0.68; 95% CI, 0.53 to 0.88) were lower, and r-ATG was associated with better graft survival (hazard ratio, 0.86; 95% CI, 0.75 to 0.99). CONCLUSIONS: In DDRT, compared with IL2-RA induction, no induction was associated with similar outcomes when TAC/MPA/steroids were used. r-ATG seems to offer better graft survival over IL2-RA in steroid avoidance protocols.


Subject(s)
Alemtuzumab/therapeutic use , Antilymphocyte Serum/therapeutic use , Graft Rejection/epidemiology , Immunosuppressive Agents/therapeutic use , Induction Chemotherapy/methods , Kidney Transplantation/methods , Steroids/therapeutic use , Adolescent , Adult , Aged , Female , Follow-Up Studies , Graft Rejection/prevention & control , Graft Survival , Humans , Incidence , Maintenance Chemotherapy/methods , Male , Middle Aged , Mycophenolic Acid/therapeutic use , Propensity Score , Receptors, Interleukin-2/antagonists & inhibitors , Registries , Tacrolimus/therapeutic use , Young Adult
14.
Clin J Am Soc Nephrol ; 10(6): 1041-9, 2015 Jun 05.
Article in English | MEDLINE | ID: mdl-25979971

ABSTRACT

BACKGROUND AND OBJECTIVES: Induction therapy with IL-2 receptor antagonist (IL2-RA) is recommended as a first line agent in living donor renal transplantation (LRT). However, use of IL2-RA remains controversial in LRT with tacrolimus (TAC)/mycophenolic acid (MPA) with or without steroids. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The Organ Procurement and Transplantation Network registry was studied for patients receiving LRT from 2000 to 2012 maintained on TAC/MPA at discharge (n=36,153) to compare effectiveness of IL2-RA to other induction options. The cohort was initially divided into two groups based on use of maintenance steroid at time of hospital discharge: steroid (n=25,996) versus no-steroid (n=10,157). Each group was further stratified into three categories according to commonly used antibody induction approach: IL2-RA, rabbit anti-thymocyte globulin (r-ATG), and no-induction in the steroid group versus IL2-RA, r-ATG and alemtuzumab in the no-steroid group. The main outcomes were the risk of acute rejection at 1 year and overall allograft failure (graft failure or death) post-transplantation through the end of follow-up. Propensity score-weighted regression analysis was used to minimize selection bias due to non-random assignment of induction therapies. RESULTS: Multivariable logistic and Cox analysis adjusted for propensity score showed that outcomes in the steroid group were similar between no-induction (odds ratio [OR], 0.96; 95% confidence interval [95% CI], 0.86 to 1.08 for acute rejection; and hazard ratio [HR], 0.99; 95% CI, 0.90 to 1.08 for overall allograft failure) and IL2-RA categories. In the no-steroid group, odds of acute rejection with r-ATG (OR, 0.73; 95% CI, 0.59 to 0.90) and alemtuzumab (OR, 0.53; 95% CI, 0.42 to 0.67) were lower; however, overall allograft failure risk was higher with alemtuzumab (HR, 1.27; 95% CI, 1.03 to 1.56) but not with r-ATG (HR, 1.19; 95% CI, 0.97 to 1.45), compared with IL2-RA induction. CONCLUSIONS: Compared with no-induction therapy, IL2-RA induction was not associated with better outcomes when TAC/MPA/steroids were used in LRT recipients. r-ATG appears to be an acceptable and possibly the preferred induction alternative for IL2-RA in steroid-avoidance protocols.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Antilymphocyte Serum/therapeutic use , Calcineurin Inhibitors/therapeutic use , Immunosuppressive Agents/therapeutic use , Kidney Transplantation/methods , Living Donors , Mycophenolic Acid/therapeutic use , Steroids/therapeutic use , Tacrolimus/therapeutic use , Acute Disease , Adult , Alemtuzumab , Antibodies, Monoclonal, Humanized/adverse effects , Antigens, CD/immunology , Antigens, Neoplasm/immunology , Antilymphocyte Serum/adverse effects , CD52 Antigen , Calcineurin Inhibitors/adverse effects , Drug Therapy, Combination , Female , Glycoproteins/antagonists & inhibitors , Glycoproteins/immunology , Graft Rejection/immunology , Graft Rejection/prevention & control , Graft Survival/drug effects , Humans , Immunosuppressive Agents/adverse effects , Kaplan-Meier Estimate , Kidney Transplantation/adverse effects , Logistic Models , Male , Middle Aged , Multivariate Analysis , Mycophenolic Acid/adverse effects , Odds Ratio , Propensity Score , Proportional Hazards Models , Receptors, Interleukin-2/antagonists & inhibitors , Receptors, Interleukin-2/immunology , Registries , Retrospective Studies , Risk Factors , Steroids/adverse effects , Tacrolimus/adverse effects , Time Factors , Tissue and Organ Procurement , Treatment Outcome
15.
Transplantation ; 99(8): e66-74, 2015 Aug.
Article in English | MEDLINE | ID: mdl-25719258

ABSTRACT

BACKGROUND: Relationship between live donor renal anatomic asymmetry and posttransplant recipient function has not been studied extensively. METHODS: We analyzed 96 live kidney donors, who had anatomical asymmetry (>10% renal length and/or volume difference calculated from computerized tomography angiograms) and their matching recipients. Split function differences (SFD) were quantified with technetium-dimercaptosuccinic acid renography. Implantation biopsies at time 0 were semiquantitatively scored. A comprehensive model using donor renal volume adjusted to recipient weight (Vol/Wgt), SFD, and biopsy score was used to predict recipient estimated glomerular filtration rate (eGFR) at 1 year. Primary analysis consisted of a logistic regression model of outcome (odds of developing eGFR>60 mL/min/1.73 m(2) at 1 year), a linear regression model of outcome (predicting recipient eGFR at one-year, using the chronic kidney disease-epidemiology collaboration formula), and a Monte Carlo simulation based on the linear regression model (N=10,000 iterations). RESULTS: In the study cohort, the mean Vol/Wgt and eGFR at 1 year were 2.04 mL/kg and 60.4 mL/min/1.73 m(2), respectively. Volume and split ratios between 2 donor kidneys were strongly correlated (r = 0.79, P < 0.001). The biopsy scores among SFD categories (<5%, 5%-10%, >10%) were not different (P = 0.190). On multivariate models, only Vol/Wgt was significantly associated with higher odds of having eGFR > 60 mL/min/1.73 m (odds ratio, 8.94, 95% CI 2.47-32.25, P = 0.001) and had a strong discriminatory power in predicting the risk of eGFR less than 60 mL/min/1.73 m(2) at 1 year [receiver operating curve (ROC curve), 0.78, 95% CI, 0.68-0.89]. CONCLUSIONS: In the presence of donor renal anatomic asymmetry, Vol/Wgt appears to be a major determinant of recipient renal function at 1 year after transplantation. Renography can be replaced with CT volume calculation in estimating split renal function.


Subject(s)
Kidney Transplantation/methods , Kidney/diagnostic imaging , Kidney/surgery , Living Donors , Tomography, X-Ray Computed , Adult , Computer Simulation , Female , Glomerular Filtration Rate , Humans , Kidney/physiopathology , Kidney Function Tests , Kidney Transplantation/adverse effects , Linear Models , Logistic Models , Male , Middle Aged , Models, Biological , Monte Carlo Method , Multivariate Analysis , New York City , Odds Ratio , Organ Size , Postoperative Complications/etiology , Postoperative Complications/physiopathology , Predictive Value of Tests , Retrospective Studies , Risk Factors , Time Factors , Treatment Outcome
16.
Transplant Direct ; 1(10)2015 Nov.
Article in English | MEDLINE | ID: mdl-26949736

ABSTRACT

BACKGROUND: Hemolytic uremic syndrome (HUS) accounts for <1% of renal transplants in the US. There are limited data on the characteristics and outcomes of HUS in pediatric and adult kidney transplant recipients in the US. METHODS: This study included all renal transplant recipients identified with HUS (N=1,233) as a cause of end-stage renal disease between 1987 and 2013 using the UNOS/OPTN database. The cohort was divided into two age groups: pediatric (N=447) and adult (N=786). Main outcomes were acute rejection rate at one-year, allograft and patient survival, and recurrence of HUS post-transplant. Both age groups were then compared with a propensity score (1:2 ratio) matched control group with an alternative primary kidney disease (non-HUS cohort: pediatric [N= 829] and adult [N=1,547]). RESULTS: In pediatric cohort, when compared to the PS matched controls, acute rejection, death censored allograft and patient survival was similar in the HUS group. However, in the adult cohort, the graft and patient survivals were significantly worse in the HUS group. HUS was associated with allograft loss (HR=1.40, 95%CI 1.14-1.71) in adult recipients. Patients with HUS recurrence had significantly lower allograft and patient survival rates compared to the non-recurrent group in both age groups. Acute rejection was one of the major predictor of HUS recurrence in adults (OR=2.64, 95%CI 1.25-5.60). Calcineurin inhibitors (CNI) were not associated HUS recurrence in both age groups. CONCLUSION: Pediatric HUS-patients, unlike adult recipients, have similar outcomes compared to the PS matched controls. Recurrence of HUS is associated with poor allograft and patient survival in pediatric and adult patients. Use of CNIs seem to be safe as a part of maintenance immunosuppression post-transplantation. A comprehensive national registry is urgently needed.

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