ABSTRACT
Using the Scientific Registry of Transplant Recipients, we examined the association between donor-recipient biologic relationship and long-term recipient and allograft survival among glomerulonephritis (GN) patients. Four GN types were studied: membranous nephropathy, IgA, lupus-associated nephritis, and focal segmental glomerulosclerosis (FSGS). We identified all adult primary living-donor recipients between 2000 and 2018 (n = 19,668): related (n = 10,437); unrelated (n = 9,231). Kaplan-Meier curves were generated for the recipient, death-censored graft survival and death with functioning graft through ten years post-transplant. Multivariable Cox proportional hazard models were used to examine the association between the donor-recipient relationship and outcomes of interest. There was an increased risk for acute rejection by 12 months post-transplant among the unrelated compared to the related group in IgA (10.1% vs. 6.5%, p<0.001), FSGS (12.1% vs. 10%, p-0.016), and lupus nephritis (11.8% vs. 9.2%; p-0.049). The biological donor-recipient relationship was not associated with a worse recipient or graft survival or death with functioning graft in the multivariable models. These findings are consistent with the known benefits of living-related-donor kidney transplants and counter the reports of the potential adverse impact of the donor-recipient biologic relationship on allograft outcomes.
Subject(s)
Biological Products , Glomerulonephritis , Glomerulosclerosis, Focal Segmental , Kidney Transplantation , Adult , Humans , Kidney Transplantation/adverse effects , Living Donors , Glomerulosclerosis, Focal Segmental/surgery , Glomerulonephritis/complications , Glomerulonephritis/surgery , Graft Survival , Graft Rejection/etiology , Allografts , Immunoglobulin A , Transplant Recipients , Risk FactorsABSTRACT
BACKGROUND: The HIV Organ Policy Equity (HOPE) act afforded transplantation of organs from donors who have HIV. Herein we compared the long-term outcomes of recipients with HIV by donor HIV testing status. METHODS: Using the Scientific Registry of Transplant Recipients, we identified all primary adult kidney transplant recipients who were HIV-positive between 1/1/16-12/31/21. Recipients were grouped into three cohorts according to the donor HIV status based on antibody (Ab) and nucleic acid testing (NAT): Donor Ab-/NAT- (n = 810), Donor Ab+ /NAT- (n = 98), and Donor Ab+/NAT+ (n = 90). We compared recipient and death-censored graft survival (DCGS) by donor HIV testing status using Kaplan-Meier curves and Cox proportional hazards regression, censored at 3 years posttransplant. Secondary outcomes were delayed graft function (DGF) and the following 1-year outcomes: acute rejection, re-hospitalization, and serum creatinine. RESULTS: In Kaplan-Meier analyses, patient survival and DCGS were similar by donor HIV status (log rank p = .667; log rank p = .388). DGF occurred more frequently in donors with HIV Ab-/NAT- testing compared with Ab+/NAT- or Ab+/NAT+ testing (38.0% vs. 28.6% vs. 26.7%, p = .028). Average dialysis time before transplant was twice as long for recipients who received organs from donors with Ab-/NAT- testing (p < .001). Acute rejection, re-hospitalization and serum creatinine at 12 months did not differ between the groups. CONCLUSIONS: Patient and allograft survival for recipients living with HIV remains comparable irrespective of donor HIV testing status. Utilizing kidneys from deceased donors with HIV Ab+/NAT- or Ab+/NAT+ testing shortens dialysis time prior to transplant.
Subject(s)
HIV Infections , HIV , Adult , Humans , United States/epidemiology , Creatinine , Tissue Donors , Kidney , Graft Survival , Graft Rejection/prevention & controlABSTRACT
The long-term outcomes of positive crossmatch (+XM) simultaneous liver-kidney (SLK) transplantations are conflicting. We examined the association between crossmatch status and SLK outcomes in recipients discharged on tacrolimus and mycophenolate with or without steroids. We analyzed the Scientific Registry of Transplant Recipients for all primary SLK recipients between 2003 and 2020 with available crossmatch and induction data. We grouped recipients according to the crossmatch status: negative crossmatch (-XM; n = 3040) and +XM (n = 407). Kaplan-Meier curves were generated to examine recipient, death-censored liver, and death-censored kidney survival by crossmatch status. Cox proportional hazard models were used to investigate the association between crossmatch status and outcomes of interest with follow-up censored at 10 years. Models were adjusted for recipient age, sex, diabetes mellitus, Model for End-Stage Liver Disease score, duration on the liver waiting list, induction immunosuppression, steroid maintenance, hepatitis C infection, donor age and sex, local vs. shared organ, cold ischemia time, and previous liver transplantation status. In the univariable analysis, crossmatch status was not associated with recipient survival (log-rank p = 0.63), death-censored liver graft survival (log-rank p = 0.05), or death-censored kidney graft survival (log-rank p = 0.11). Compared with -XM, +XM recipients had a similar 1-year liver rejection rate, but higher kidney rejection rate (4.6% vs. 8.9%, p = 0.002). In the multivariable models, +XM status was not associated with deleterious long-term recipient, liver, or kidney grafts survival. -XM and +XM SLK transplantations have comparable long-term recipient, liver graft, and kidney survival with a slightly increased risk of early kidney allograft rejection in the +XM group. Crossmatch positivity in SLK transplantations should not influence the decision to use organs from a specific donor.
Subject(s)
End Stage Liver Disease , Kidney Transplantation , Liver Transplantation , End Stage Liver Disease/etiology , Graft Rejection/epidemiology , Graft Survival , Humans , Kidney , Kidney Transplantation/adverse effects , Liver Transplantation/adverse effects , Retrospective Studies , Severity of Illness Index , United States/epidemiologyABSTRACT
There are several choices for induction immunosuppression in kidney-after-liver transplantation. We used the Scientific Registry of Transplant Recipients database. We assessed all kidney-after-liver transplant recipients in the United States between 1/1/2000 and 7/31/2017 to study kidney graft and patient outcomes by induction type. We only included patients discharged on tacrolimus and mycophenolate with or without steroids and had a negative crossmatch before kidney engraftment. We grouped recipients by kidney induction type into the following 3 groups: depletional (n = 550), nondepletional (n = 434), and no antibody induction (n = 144). We studied patient and kidney allograft survival using Cox proportional hazard regression, with transplant center included as a random effect. Models were adjusted for liver induction regimen, recipient and donor age, sex, human leukocyte antigen mismatches, payor type, living donor kidney transplantation, dialysis status, time from liver engraftment, hepatitis C virus status, and the presence of diabetes mellitus at time of kidney transplantation and transplantation year. The 6-month and 1-year rejection rates did not differ between groups. Compared with no induction, neither depletional nor nondepletional induction was associated with an improved recipient or graft survival in the multivariable models. Depletional induction at the time of liver transplantation was associated with worse patient survival after kidney transplantation (hazard ratio [HR], 1.7; 95% confidence interval [CI], 1.09-2.67; P = 0.02). Living donor kidney transplantation was associated with a 48.1% improved graft survival (HR, 0.52; 95% CI, 0.33-0.82; P = 0.00). In conclusion, in the settings of a negative cross-match and maintenance with tacrolimus and mycophenolate, induction use was not associated with a patient or graft survival benefit in kidney-after-liver transplantations.
Subject(s)
Kidney Transplantation , Liver Transplantation , Allografts , Graft Rejection/epidemiology , Graft Rejection/prevention & control , Graft Survival , Humans , Immunosuppressive Agents/therapeutic use , Kidney , Kidney Transplantation/adverse effects , Liver Transplantation/adverse effects , United States/epidemiologyABSTRACT
BACKGROUND: We studied the association of induction immunosuppression and pediatric deceased-donor kidney recipient and graft survival. METHODS: We utilized the SRTR to evaluate all primary pediatric deceased-donor kidney transplants from January 1st, 2000, through December 2018. We included only recipients who were maintained on tacrolimus and mycophenolate. Recipients were grouped by induction type: alemtuzumab n = 320, r-ATG n = 2091 and IL-2RA n = 2165. Recipient and allograft survival, and their predictors, were examined. Models were adjusted for age, sex, ethnicity, HLA-antigen mismatches, transplant year, steroid maintenance, pre-emptive transplantation and payor type, with the transplant center included as a random effect. RESULTS: Rejection rates at 6 months (alemtuzumab 8.6% vs r-ATG 7.8% vs IL2-RA 9.2%; P = .30) and 12 months (alemtuzumab 17.2% vs r-ATG 15.7% vs IL2-RA 16.5%; P = .70) were not significantly different between induction groups. In the multivariable models, compared to IL-2RA neither alemtuzumab nor r-ATG was associated with improved recipient [alemtuzumab (HR 1.06, P = .88); r-ATG (HR 1.03, P = .84)] or graft survival [alemtuzumab (HR 1.18, P = .32); r-ATG (HR 1.10, P = .21)]. CONCLUSION: In this large cohort of standard immunological risk primary pediatric deceased-donor kidney recipients on tacrolimus and mycophenolate maintenance, depletional induction regimens were not associated with better rejection rates, recipient, or graft survival compared to IL-2RA induction. Racial, payor type, and sex-related outcome disparities were significant in this group independent of the induction choice.
Subject(s)
Immunosuppressive Agents/administration & dosage , Kidney Transplantation , Adolescent , Alemtuzumab/administration & dosage , Antilymphocyte Serum/administration & dosage , Child , Child, Preschool , Female , Graft Rejection , Graft Survival , Humans , Infant , Interleukin-2 Receptor alpha Subunit/administration & dosage , Male , Mycophenolic Acid/administration & dosage , Risk Factors , Tacrolimus/administration & dosage , United StatesABSTRACT
OBJECTIVE: We examined the association between induction type and outcomes of live-donor pediatric kidney recipients on tacrolimus and mycophenolate maintenance. MATERIAL AND METHODS: We analyzed the SRTR standard analysis file to evaluate primary live-donor pediatric kidney recipients between 2000 and 2018. Recipients were grouped by induction type into three groups: alemtuzumab n = 289, anti-thymocyte n = 1197, and IL-2RA n = 1625. Kaplan-Meier curves were generated for recipient and death-censored graft survival. Predictors of recipient and allograft survival were examined using Cox proportional hazards models. Models were adjusted for age, sex, ethnicity, renal failure etiology, HLA-mismatches, transplant year, steroid maintenance, preemptive transplantation, payor type, and donor factors such as age, sex, and donor-recipient relationship. The transplant center was included as a random effect to account for inter-center variability. RESULTS: Rejection rates at 6 months (Alemtuzumab 9.5% vs. r-ATG 5.7% vs. IL2-RA 5.3%; P: .023) and 12 months (Alemtuzumab 14.5% vs. r-ATG 10.8% vs. IL2-RA 9%; P: .028) were significantly higher in the alemtuzumab group. PTLD rate (Alemtuzumab 0.8% vs. r-ATG 2.2% vs. IL2-RA 1%; P: .028) was significantly higher in the anti-thymocyte group. In the multivariable models, induction type did not influence patient or death-censored graft survival within ten years post-transplant. CONCLUSION: In this large cohort of standard immunological risk primary pediatric live-donor kidney recipients, as compared to IL-2RA, neither alemtuzumab nor anti-thymocyte globulin was associated with improved long-term graft or recipient survival. In the first year post-transplant, recipients of alemtuzumab induction had a higher rejection rate, while PTLD was more frequently observed in the anti-thymocyte recipients.
Subject(s)
Immunosuppressive Agents/administration & dosage , Kidney Transplantation , Living Donors , Transplant Recipients , Adolescent , Alemtuzumab/administration & dosage , Antilymphocyte Serum/administration & dosage , Child , Child, Preschool , Female , Graft Rejection , Graft Survival , Humans , Infant , Interleukin-2 Receptor alpha Subunit/administration & dosage , Male , Mycophenolic Acid/administration & dosage , Tacrolimus/administration & dosage , United StatesABSTRACT
In the general population, obesity is associated with an increased risk of developing hypertension (HTN), type 2 diabetes mellitus (DM), and end-stage renal disease (ESRD). Therefore, most transplant centers have a body mass index (BMI) threshold for accepting living kidney donors. But there have been no studies of postdonation weight gain trends and any associated risks. We tracked serial BMIs in 940 donors for a median (IQ range) follow-up of 22.3 (15.4-35.8) years. We studied the impact of postdonation weight gain in a model adjusted for family history of HTN or DM. Donor characteristics included age, sex, smoking, fasting blood glucose, eGFR, systolic and diastolic BP, and BMI at time of donation and time postdonation. Postdonation weight gain was associated with a significant increase in the relative risk of developing HTN RR 1.93 (95% CI 1.51-2.46) (P < 0.001) and/or DM RR 4.18 (95% CI 2.05-8.5) (P < 0.0001), but not (to date) cardiovascular disease (CVD), reduced eGFR or death. Like the general population, donors gained weight as they aged; a higher BMI was associated with higher incidence of DM and HTN. Postdonation care should include ongoing counseling on the risks of substantial weight gain.
Subject(s)
Diabetes Mellitus, Type 2/etiology , Hypertension/etiology , Living Donors/supply & distribution , Nephrectomy/adverse effects , Obesity/etiology , Tissue and Organ Harvesting/adverse effects , Weight Gain , Adult , Body Mass Index , Female , Follow-Up Studies , Humans , Kidney Transplantation , Male , Middle Aged , Prognosis , Risk FactorsSubject(s)
Galactose , Glomerulonephritis, IGA , Humans , Immunoglobulin A , Kidney Glomerulus , Tissue DonorsABSTRACT
BACKGROUND: Heart transplantation remains the most definitive therapy for qualified candidates with end-stage heart failure. Concomitant kidney disease is common in this population prompting an increase in simultaneous heart-kidney (SHK) transplantation in recent years. The goal of our study was to explore the effects of the 2018 heart allocation policy (HAP) change on candidate listing characteristics and compare survival rates at 1 y in patients that were supported with a left ventricular assist device (LVAD) pretransplant and underwent SHK or heart alone transplant (HAT). METHODS: We used data from the Scientific Registry of Transplant Recipients and identified all adults who underwent primary SHK or HAT between January 2010 and March 2022. Recipients supported with a durable LVAD and estimated glomerular filtration rate <60 mL/min/1.73 m 2 were selected (n = 309 SHK; 217 pre- and 92 post-HAP and n = 3,324 HAT; 2738 pre- and 586 post-HAP). RESULTS: Difference in survival at 1 y did not reach statistical significance. Comparing the 1-y survival of SHK and HAT recipients who were bridged with LVAD pre-HAP, we found no significant difference ( P = 0.694). Adjusting for the same covariates in a multivariable model did not affect the results (SHK versus HAT hazard ratio 0.84 [0.51, 1.37]; P = 0.48). In contrast, SHK recipients supported with an LVAD who were listed and transplanted post-HAP change had significantly lower 1-y survival, when compared with HAT ( P = 0.037). CONCLUSIONS: Our findings suggest that the HAP change had a potentially negative impact on the survival of select patients undergoing SHK transplant. Further research is warranted in this area.
Subject(s)
Heart Failure , Heart Transplantation , Heart-Assist Devices , Kidney Transplantation , Renal Insufficiency, Chronic , Adult , Humans , Kidney Transplantation/methods , Treatment Outcome , Retrospective Studies , Kidney , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/diagnosis , Renal Insufficiency, Chronic/surgery , Heart Failure/diagnosis , Heart Failure/surgeryABSTRACT
Most calcineurin inhibitor (CNI)-based protocols reduce blood trough goals approximately 2-3 months post-transplant in clinically stable kidney transplant recipients. The CNI target trough level to prevent rejection, after reduction, is unknown. Using a multivariate Cox proportional hazards model, we determined the association of time-varying tacrolimus (TAC) trough levels with acute rejection (AR) occurring in the first 6 months post-transplant, but specifically we assessed this association after 3 months. A total of 1930 patients received TAC-based immunosuppression prior to AR in a prospective study. Of the 151 (7.8%) who developed AR, 47 developed AR after 3 months post-transplant. In an adjusted time-varying multivariate model, each 1 ng/ml decrease in TAC trough levels was associated with a 7.2% increased risk of AR [hazards ratio (HR) = 1.07, 95% confidence interval (CI) (1.01, 1.14) P = 0.03] in the first 6 months. There was an additional 23% increased risk of AR with each 1 ng/ml decrease in the TAC trough levels in months 3-6 [HR = 1.23, 95% CI (1.06, 1.43) P = 0.008]. In conclusion, lower TAC trough levels were significantly associated with increased risk of AR in the first 6 months post-transplant with additional risk of AR between months 3 and 6 post-transplant. The timing and practice of TAC dose reduction should be personalized based on the individual's risk factors.
Subject(s)
Graft Rejection/diagnosis , Graft Rejection/immunology , Immunosuppressive Agents/blood , Immunosuppressive Agents/therapeutic use , Kidney Transplantation/methods , Renal Insufficiency/blood , Renal Insufficiency/therapy , Tacrolimus/blood , Tacrolimus/therapeutic use , Adult , Age Factors , Calcineurin Inhibitors , Clinical Trials as Topic , Cohort Studies , Female , Humans , Immunosuppression Therapy/methods , Male , Middle Aged , Multivariate Analysis , Pancreas Transplantation/methods , Proportional Hazards Models , Prospective Studies , Reproducibility of Results , Risk FactorsABSTRACT
BACKGROUND: We examined the association between induction type for a second kidney transplant in dialysis-dependent recipients and the long-term outcomes. METHODS: Using the Scientific Registry of Transplant Recipients, we identified all second kidney transplant recipients who returned to dialysis before re-transplantation. Exclusion criteria included: missing, unusual, or no-induction regimens, maintenance regimens other than tacrolimus and mycophenolate, and positive crossmatch status. We grouped recipients by induction type into 3 groups: the anti-thymocyte group (N = 9899), the alemtuzumab group (N = 1982), and the interleukin 2 receptor antagonist group (N = 1904). We analyzed recipient and death-censored graft survival (DCGS) using the Kaplan-Meier survival function with follow-up censored at 10 years post-transplant. We used Cox proportional hazard models to examine the association between induction and the outcomes of interest. To account for the center-specific effect, we included the center as a random effect. We adjusted the models for the pertinent recipient and organ variables. RESULTS: In the Kaplan-Meier analyses, induction type did not alter recipient survival (log-rank P = .419) or DCGS (log-rank P = .146). Similarly, in the adjusted models, induction type was not a predictor of recipient or graft survival. Live-donor kidneys were associated with better recipient survival (HR 0.73, 95% CI [0.65, 0.83], P < .001) and graft survival (HR 0.72, 95% CI [0.64, 0.82], P < .001). Publicly insured recipients had worse recipient and allograft outcomes. CONCLUSION: In this large cohort of average immunologic-risk dialysis-dependent second kidney transplant recipients, who were discharged on tacrolimus and mycophenolate maintenance, induction type did not influence the long-term outcomes of recipient or graft survival. Live-donor kidneys improved recipient and graft survival.
Subject(s)
Kidney Transplantation , Tacrolimus , Humans , United States , Tacrolimus/pharmacology , Kidney Transplantation/adverse effects , Renal Dialysis , Immunosuppressive Agents/adverse effects , Kidney , Treatment Outcome , Graft Survival , Graft Rejection , Transplant Recipients , Retrospective StudiesABSTRACT
BACKGROUND: Steroid avoidance in kidney transplantation has been proven noninferior. Long-term outcome data on steroid avoidance in simultaneous pancreas-kidney (SPK) remains scant. METHODS: Utilizing the Scientific Registry of Transplant Recipients between 2000 and 2020, we studied all primary crossmatch negative SPK recipients (N = 5683) who received antithymocyte globulin induction and were discharged alive with functioning grafts on tacrolimus and mycophenolate ± steroid maintenance. Recipients were grouped according to steroid use into 2 groups: steroid maintenance (n = 4191) and steroid avoidance (n = 1492). Kaplan-Meier curves censored at 10 y were generated for recipient and allograft survival by steroid maintenance. Predictors for recipient and graft survival were examined using Cox Proportional Hazards. Models were adjusted for age, body mass index, ethnicity, diabetes type, human leukocyte-antigen mismatches, cold ischemia time, transplant era, preemptive transplantation, and pancreas donor risk index with the transplant center included as a random effect. RESULTS: Steroid avoidance gained popularity over time, accounting for over one-fourth of the studied cohort. One-year acute rejection rates by steroid avoidance were comparable for kidney (8.6% versus 9%, P = 0.783); however, the pancreas rejection rate was lower in the steroid avoidance group (7.9% versus 10%; P = 0.035). After adjustment, steroid avoidance did not influence recipient survival (lower level of confidence interval, adjusted hazard ratio, upper level of confidence interval: 0.94, 1.15, 1.39), pancreas (0.75, 0.93, 1.16), or kidney (0.95, 1.18, 1.45) death-censored survival, compared with steroid maintenance. CONCLUSIONS: Accounting for the recipient and graft characteristics, steroid avoidance is associated with similar recipient, pancreas, and kidney graft outcomes compared with steroid maintenance in SPK recipients after antithymocyte globulin induction with tacrolimus and mycophenolate maintenance.
Subject(s)
Kidney Transplantation , Pancreas Transplantation , Humans , United States , Kidney Transplantation/adverse effects , Tacrolimus/therapeutic use , Pancreas Transplantation/adverse effects , Antilymphocyte Serum/therapeutic use , Immunosuppressive Agents/adverse effects , Steroids/adverse effects , Kidney , Graft Survival , Graft RejectionABSTRACT
BACKGROUND: The use of temporary mechanical circulatory support (tMCS) devices (intra-aortic balloon pump; Impella 2.5, CP, 5.0; venoarterial extracorporeal membrane oxygenation) increased significantly across the United States for heart transplant candidates after the allocation policy change. Whether this practice change also affected simultaneous heart-kidney (SHK) candidates and recipient survival is understudied. METHODS: We used the Scientific Registry of Transplant Recipients database to identify adult SHK recipients between January 2010 and March 2022. The population was stratified into pre- and post-heart allocation change cohorts. Kaplan-Meier curves were generated to compare 1-y survival rates. A Cox proportional hazards model was used to investigate the effect of allocation period on patient survival. Recipient outcomes bridged with eligible tMCS devices were compared in the post-heart allocation era. In a separate analysis, SHK waitlist mortality was evaluated between the allocation eras. RESULTS: A total of 1548 SHK recipients were identified, and 1102 were included in the final cohort (534 pre-allocation and 568 post-allocation change). tMCS utilization increased from 17.9% to 51.6% after the allocation change, with venoarterial extracorporeal membrane oxygenation use rising most significantly. However, 1-y post-SHK survival remained unchanged in the full cohort (log-rank P = 0.154) and those supported with any of the eligible tMCS devices. In a separate analysis (using a larger cohort of all SHK listings), SHK waitlist mortality at 1 y was significantly lower in the current allocation era ( P = 0.002). CONCLUSIONS: Despite the remarkable increase in tMCS use in SHK candidates after the heart allocation change, 1 y posttransplant survival remained unchanged. Further studies with larger cohorts and longer follow-ups are needed to confirm these findings.
Subject(s)
Heart Failure , Heart Transplantation , Heart-Assist Devices , Kidney Transplantation , Adult , Humans , United States , Kidney Transplantation/adverse effects , Heart Transplantation/adverse effects , Proportional Hazards Models , Kidney , Policy , Retrospective Studies , Heart Failure/diagnosis , Heart Failure/surgery , Waiting ListsABSTRACT
Background: Focal segmental glomerulosclerosis (FSGS) is a common cause of end-stage kidney disease requiring kidney transplantation and can recur in the allograft in 30-80% of recipients resulting in reduced graft survival. Plasmapheresis has shown efficacy in treating some cases of recurrent FSGS but isolated plasmapheresis has not demonstrated efficacy in preventing recurrent FSGS. Rituximab has had anecdotal success in preventing recurrence in a single center study but has not been studied in combination with plasmapheresis for preventing FSGS recurrence. Methods: We are conducting a randomized, controlled, multicenter clinical trial of adult and pediatric kidney transplant recipients with primary FSGS to assess whether plasmapheresis in combination with rituximab prevents recurrent disease post-transplantation. Discussion: Rituximab combined with plasmapheresis is a promising, novel therapy to prevent recurrent FSGS, a disease with limited therapeutic options and no consensus guidelines for prevention or treatment. Clinical trial registration: https://clinicaltrials.gov/ct2/show/NCT03763643, identifier NCT03763643.
ABSTRACT
BACKGROUND: Induction choices for kidney-after-heart transplant recipients are variable. We examined the impact of kidney induction types on kidney graft and patient survival in heart transplant recipients. METHODS: We analyzed the Scientific Registry of Transplant Recipient database from inception through the end of 2018 to study kidney and patient outcomes in the United States after heart transplantation. We only included recipients who were discharged on tacrolimus and mycophenolate maintenance. We grouped recipients by induction type into 3 groups: depletional (N = 307), nondepletional (n = 253), and no-induction (steroid only) (n = 57). We studied patients and kidney survival using Cox PH regression, with transplant centers included as a random effect. We adjusted the models for heart induction, recipient and donor age, gender, time between heart and kidney transplant, heart transplant indication, HLA mismatches, payor, live-donor kidney, transplant year, dialysis status, and diabetes mellitus at the time of kidney transplant. RESULTS: The 1-y kidney rejection rates and creatinine levels were similar in all groups. The 1-y rehospitalization rate was higher in the depletional group (51.7%) and nondepletional group (50.7%) than in the no-induction group (39.1%) although this was not statistically significant. There were no differences in recipient or kidney survival by kidney induction type. Live-donor kidney was associated with improved patient (hazard ratio, 0.74; 95% confidence interval, 0.54-1.0; P = 0.05) and kidney survival (hazard ratio, 0.45; 95% confidence interval, 0.24-0.84; P = 0.012]. CONCLUSIONS: Type of kidney induction did not influence patient or kidney graft survival in heart transplant recipients. No-induction may be the preferred choice due to the lack of clinical benefits associated with induction use.
Subject(s)
Graft Rejection , Heart Transplantation , Allografts , Graft Survival , Heart Transplantation/adverse effects , Humans , Kidney , Living Donors , United States/epidemiologyABSTRACT
BACKGROUND: The role of induction in preemptive second kidney recipients is unclear. We examined the association between induction therapy and the long-term graft and recipient survival in the settings of tacrolimus and mycophenolate maintenance. METHODS: We identified all preemptive second kidney transplant recipients between 2000 and 2020 in the Scientific Registry of Transplant Recipients. We excluded those with missing or mixed induction regimens and positive crossmatch. We grouped recipients by induction type into 3 groups: anti-thymocyte globulin (n = 1442), alemtuzumab (n = 362), and interleukin-2 receptor antagonist (IL-2RA; n = 481). We generated Kaplan-Meier curves of the recipient and death-censored graft survival (DCGS) with follow-up censored at 10 years. We used multivariable Cox proportional hazards models to examine the association between induction and the above outcomes. We adjusted the models for recipient and donor variables. RESULTS: Rates of delayed graft function, rejection, hospitalization, and post-transplant lymphoproliferative disorder at one year were not statistically different. Recipient survival did not vary by induction type in the Kaplan-Meier analysis (log-rank P = .189) or in the multivariable model. However, DCGS was the lowest in the Alemtuzumab group (log-rank P = .01). In the multivariable models, alemtuzumab was associated with a 57% increased risk of graft loss (1.57, 95% confidence interval (1.08, 2.30), P = .019) compared to anti-thymocyte. Live-donor kidneys were associated with significantly better recipient survival and DCGS. CONCLUSIONS: Compared to anti-thymocyte induction, alemtuzumab, but not IL-2RA, was associated with inferior graft survival in preemptive second transplant recipients discharged on tacrolimus and mycophenolate.
Subject(s)
Kidney Transplantation , Tacrolimus , Humans , United States , Tacrolimus/adverse effects , Alemtuzumab/adverse effects , Kidney Transplantation/adverse effects , Graft Rejection/etiology , Graft Rejection/prevention & control , Receptors, Interleukin-2 , Antibodies, Monoclonal, Humanized , Immunosuppressive Agents/adverse effects , Graft Survival , KidneyABSTRACT
Long-term outcome data by induction type in simultaneous pancreas-kidney (SPK) is limited. Methods: Utilizing the Scientific Registry of Transplant Recipients, we examined all primary SPK transplants between 2000 and 2020, excluding crossmatch-positive recipients. We grouped recipients according to induction regimen into 3 groups: rabbit anti-thymocyte globulin (r-ATG) (n = 5678), alemtuzumab (n = 1199), and interleukin-2 receptor antagonist (IL-2RA; n = 1593). We analyzed the 10-y recipient and composite (kidney and pancreas) graft survival using the Kaplan-Meier survival function. Cox-proportion hazard models were generated to examine the association between induction type, the 10-y recipient, and graft survival. Models were adjusted for recipient age, sex, ethnicity, HLA-mismatch, diabetes type, dialysis dependency, cold-ischemia time, local versus imported organs, panel reactive antibody, steroid maintenance, and Pancreas Donor Risk Index. Results: r-ATG was associated with the lowest 1-y kidney and pancreas rejection rates compared with other agents (P < 0.001). In the univariable analysis, induction type was not associated with recipient (log-rank P = 0.11) or graft survival (log-rank P = 0.36). In the multivariable model for the composite graft survival, alemtuzumab use was associated with 22% increased kidney or pancreas graft loss compared with r-ATG (adjusted hazard ratio, 1.22; 95% confidence interval, 1.05-1.42), whereas IL-2RA use was not a predictor of graft survival. Induction type did not influence recipient survival in the adjusted model. Conclusions: r-ATG use was associated with the lowest SPK rejection rates. Compared with r-ATG, alemtuzumab but not IL-2RA was associated with worse long-term death-censored SPK graft outcome. Our analysis supports the common use of r-ATG for induction in US primary SPK recipients.
ABSTRACT
Introduction. Solid organ transplant graft-versus-host disease (SOT-GVHD) is a rare phenomenon in which recipients of solid organ transplant develop GVHD due to the presence of donor lymphocytes in the graft. SOT-GVHD most often occurs in patients receiving small bowel or liver transplants. Diagnosis is typically via identification of lymphocytic infiltration on histopathology and molecular demonstration of donor T cell chimerism in the target organ. The gastrointestinal (GI) system is the most common target of SOT-GVHD, and one estimate places long-term survival of patients with SOT-GVHD at 20% at 5 years. In this report, we present the case of a patient with sequential kidney and pancreas transplant who developed SOT-GVHD targeting host lymphocytes, skin, and liver, with a long period of stability before treatment with antithymocyte globulin. Peripheral blood chimerism testing was used to track response to therapy. Remarkably, he survived 1.5 years despite recurrent infections before dying of unrelated causes.
ABSTRACT
Particularly large acetaminophen overdoses, termed massive, create a therapeutic challenge given the standardized, N-acetylcysteine-based treatment. One consideration in addition to N-acetylcysteine is the initiation of hemodialysis due to the dialyzable nature of acetaminophen, though encumbered by the concurrent removal of the antidote, N-acetylcysteine. Such cases of large acetaminophen overdose, along with possible concomitant ingestions of other drugs or inactive ingredients, can be complicated by challenging-to-interpret clinical signs and laboratory findings. We describe a case of a 46-year-old man for whom we were consulted regarding consideration of dialysis treatment 7 hours after ingestion of 125 g of acetaminophen. The patient developed multiple early signs and laboratory findings consistent with a significant acetaminophen overdose. He also developed a rarely described, likely acetaminophen-interference-induced laboratory abnormality. Finally, he possibly had toxicity from an "inactive" ingredient. He was treated with a single session of prolonged hemodialysis (9.5 hours) and increased dosing of N-acetylcysteine with a positive outcome. Herein, we discuss the decision making and interpretation of clinical data pertaining to dialysis treatment and other therapies after a massive acetaminophen overdose.