Risk Of Graft Failure Research Articles

Oxalate Nephropathy After Kidney Transplantation: Risk Factors and Outcomes of Two Phenotypes.

Describing risk factors and outcomes in kidney transplant recipients with oxalate nephropathy (ON) may help elucidate the pathogenesis and guide treatment strategies. We used a large single-center database to identify patients with ON and categorized them into delayed graft function with ON (DGF-ON) and late ON. Incidence density sampling was used to select controls. A total of 37 ON cases were diagnosed between 1/2011 and 1/2021. DGF-ON (n=13) was diagnosed in 1.05% of the DGF population. Pancreatic atrophy on imaging (36.4% vs. 2.9%, p=0.002) and gastric bypass history (7.7% vs. 0%; p=0.06) were more common in DGF-ON than with controls with DGF requiring biopsy but without evidence of ON. DGF-ON was not associated with worse graft survival (p=0.98) or death-censored graft survival (p=0.48). Late ON (n=24) was diagnosed after a mean of 78.2 months. Late ON patients were older (mean age 55.1 vs. 48.4 years; p=0.02), more likely to be women (61.7% vs. 37.5%; p=0.03), have gastric bypass history (8.3% vs. 0.8%; p=0.02) and pancreatic atrophy on imaging (38.9% vs. 13.3%; p=0.02). Late ON was associated with an increased risk of graft failure (HR 2.0; p=0.07) and death-censored graft loss (HR 2.5; p=0.10). We describe two phenotypes of ON after kidney transplantation: DGF-ON and late ON. Our study is the first to our knowledge to evaluate DGF-ON with DGF controls without ON. Although limited by small sample size, DGF-ON was not associated with adverse outcomes when compared with controls. Late ON predicted worse allograft outcomes.

The impact of the OPTN policy change on patients with a durable left ventricular assist device and chronic kidney disease: Analysis of the UNOS database.

The Organ Procurement and Transplantation Network (OPTN) implemented modifications in 2018 to the adult heart transplant allocation system to better stratify the most medically urgent transplant candidates. We evaluated the impact of these changes on patients supported by a durable left ventricular assist device (LVAD) with chronic kidney disease (CKD). To evaluate the impact of the OPTN policy change on patients supported by durable left ventricular assist devices (LVAD) with chronic kidney disease (CKD). We performed an analysis of patients from the United Network of Organ Sharing Database supported by durable LVAD listed for a heart transplant (HT) between October 17, 2016 and September 30, 2021. Patients were divided into two groups: pre- and postpolicy, depending on whether they were listed on or prior to October 17, 2018. Patients who were on dialysis prior to surgery or discharge were excluded from the analysis. Patients with simultaneous heart and kidney transplants were excluded. Patients who were listed for transplant prepolicy change but transplanted postpolicy change were excluded. This cohort was then subdivided into degrees of CKD based on estimated glomerular filtration rate (eGFR), which resulted in 678 patients (23.7%) in Stage 1 (GFR ≥89.499) (Prepolicy: 345, Postpolicy: 333), 1233 (43.1%) in Stage 2 (89.499 > GFR ≥ 59.499) (Prepolicy: 618, Postpolicy: 615), 613 (21.4%) in Stage 3a (59.499 > GFR ≥ 44.499) (Prepolicy: 291, Postpolicy: 322), 294 (10.3%) in Stage 3b (44.499 > GFR ≥ 29.499) (Prepolicy: 143, Postpolicy: 151), 36 (1.3%) in Stage 4 (29.499 > GFR ≥ 15) (Prepolicy: 21, Postpolicy: 15), and 9 (0.3%) in Stage 5 (15 > GFR) (Prepolicy: 4, Postpolicy: 5). The primary outcome was 1-year and 2-year post-HT survival. There were 2863 patients who met the study criteria (1422 prepolicy, 1441 postpolicy). Overall survival, regardless of CKD stage, was lower following the policy change (p < 0.01). There was a similar risk of primary graft failure (PGF) in the pre- and postpolicy period (1.8% vs. 1.2%, p = 0.26). 1-year overall survival was 93% (91, 94) and 89% (87, 91) in the pre- and postpolicy periods, respectively. 2-year overall survival was 89% (88, 91) and 85% (82, 87) in the pre- and postpolicy periods, respectively. For CKD Stages 1, 2, 3a, 3b, 4, and 5, 1 -year survival was 93% (91, 95), 92% (90,93), 89% (86, 91), 89% (86, 93), 80% (68, 94), and 100% (100, 100), respectively. For CKD Stages 1, 2, 3a, 3b, 4, and 5, 2-year survival was 91% (88, 93), 88% (86, 90), 84% (81, 88), 84% (80, 89), 73% (59, 90), and 100% (100, 100), respectively. Patients with CKD 1 and 2 had better survival compared to those with CKD 3 (p < 0.01) and CKD 4 and 5 (p = 0.03) in the pre- and postpolicy periods. Patients with CKD 3 did not have a survival advantage over those with CKD 4 and 5 (p = 0.25). On cox regression analysis, advancing degrees of CKD were associated with an increased risk of mortality. Patients with LVAD support had decreased overall survival after the OPTN policy change. Patients with more advanced CKD had lower survival than patients without advanced CKD, though they were not impacted by the OPTN policy change.

Effect of Lateral Extra-Articular Procedures Combined With ACL Reconstruction on the Rate of Graft Rupture in Patients Aged Older Than 30 Years: A Matched-Pair Analysis of 1102 Patients From the SANTI Study Group

Background: Clinical studies have demonstrated significant advantages of combined anterior cruciate ligament (ACL) reconstruction (ACLR) and lateral extra-articular procedures (LEAPs) over isolated ACLR in terms of reducing graft rupture and reoperation rates. However, most of the published studies have included young patients, and no studies have focused on patients aged >30 years. Purpose/Hypothesis: The purpose of this study was to compare the outcomes of isolated ACLR versus ACLR + LEAP at midterm follow-up in patients aged >30 years. The hypothesis was that patients who underwent combined procedures would experience significantly lower rates of graft rupture. Study Design: Cohort study; Level of evidence, 3. Methods: Patients >30 years of age who underwent primary ACLR + LEAP between January 2003 and December 2020 were propensity matched at a 1:1 ratio to patients who underwent isolated ACLR. A retrospective analysis of prospectively collected data was performed to determine graft rupture rates, knee stability, reoperation rates, and complications. Graft survivorship was assessed using the Kaplan-Meier method. Risk factors associated with the occurrence of graft failure were analyzed using a Cox proportional hazards model. Results: Two groups of 551 patients each were included in the study, and the mean follow-up was 97.19 ± 47.23 months. The overall mean age was 37.01 ± 6.24 years. The LEAP group consisted of 503 (91.3%) patients who had anterolateral ligament reconstruction and 48 (8.7%) patients who had a Lemaire procedure. Overall, 19 (1.7%) patients had graft failure: 15 (2.7%) in the no-LEAP group and 4 (0.7%) in the LEAP group (P = .0116). The risk of graft failure was significantly associated with the absence of LEAP (31 vs 12; hazard ratio, 3.309; 95% CI, 1.088-10.065; P = .0350) and age between 30 and 35 years (hazard ratio, 4.533; 95% CI, 1.484-13.841; P = .0080). A higher rate of reoperation for secondary meniscectomy was found in the no-LEAP group (5.6% vs 2.2%; P = .0031). Conclusion: Patients aged >30 years who underwent combined ACLR and LEAP experienced a >3-fold lower risk of ACL graft failure compared with those who underwent isolated ACLR. Furthermore, the group without LEAP experienced a higher rate of secondary meniscectomy.

A multimodal aftercare intervention improves the outcome after kidney transplantation – results of the KTx360° aftercare program using claims data

The after-care treatment project KTx360° aimed to reduce graft failure and mortality after kidney transplantation (KTx). The study was conducted in the study centers Hannover, Erlangen and Hannoversch Muenden from May 2017 to October 2020 under the trial registration ISRCTN29416382. The program provided a multimodal aftercare program including specialized case management, telemedicine support, psychological and exercise assessments, and interventions. For the analysis of graft failure, which was defined as death, re-transplantation or start of long-term dialysis, we used longitudinal claims data from participating statutory health insurances (SHI) which enabled us to compare participants with controls. To balance covariate distributions between these nonrandomized groups we used propensity score methodology, in particular the inverse probability of treatment weighting (IPTW) approach. In total, 930 adult participants were recruited at three different transplant centres in Germany, of whom 320 were incident (enrolled within the first year after KTx) and 610 prevalent (enrolled >1 year after KTx) patients. Due to differences in the availability of the claims data, the claims data of 411 participants and 418 controls could be used for the analyses. In the prevalent group we detected a significantly lower risk for graft failure in the study participants compared to the matched controls (HR=0.13, 95% CI=0.04-0.39, p=0.005, n=389 observations), whereas this difference could not be detected in the incident group (HR=0.92, 95% CI=0.54-1.56, p=0.837, n=440 observations). Our findings suggest that a multimodal and multidisciplinary aftercare intervention can significantly improve outcome after KTx, specifically in patients later after KTx. For evaluation of effects on these outcome parameters in patients enrolled within the first year after transplantation longer observation times are necessary. The study was funded by the Global Innovation fund of the Joint Federal Committee of the Federal Republic of Germany, grant number 01NVF16009.

Incidence of Cytomegalovirus Infection After Repeat Keratoplasty and Associated Rate of Graft Failure.

The aim of this work was to compare the prognosis and characteristics of patients with Cytomegalovirus (CMV) infection (CMV+) with those of patients without virus infection (Virus-) undergoing repeat keratoplasty. This prospective propensity score-matched cohort study enrolled patients who underwent repeat keratoplasty for graft failure at the Peking University Third Hospital between January 2016 and May 2022. Patients with prior viral keratitis before the first keratoplasty were excluded. The primary outcome measure was the graft failure rate. The secondary outcome measures included the anterior segment characteristics, intraocular pressure (IOP), and endothelial cell density. Ninety-four matched patient pairs were included. The graft failure rate in the CMV+ group (71%) was higher than that in the Virus- group (29%) (P < 0.001). CMV infection in the cornea increased the risk of repeat graft failure and shortened the median survival time (hazard ratio, 3.876; 95% confidence intervals, 2.554-5.884; P < 0.001). The characteristics of graft failure included exacerbation of ocular surface inflammation, neovascularization, and opacification. Epithelial defects, high IOP, and endothelial decompensation were observed at an increased frequency in the CMV+ group (all P < 0.005). Recurrent CMV infection presented as early endothelial infection in the CMV+ group. Recurrence of CMV infection was confined to the graft endothelium without involving the stroma and epithelium post-repeat endothelial keratoplasty. CMV infection post-keratoplasty leads to persistent endothelial damage and graft opacification and significantly increases the risk of repeat graft failure. Localized recurrence of CMV infection in the endothelial grafts underscores the importance of monitoring and treatment. Chictr.org.cn, ChiCTR1800014684.

#1713 Blood pressure goals in kidney transplant recipients: an analysis of the collaborative transplant study

Abstract Background and Aims Hypertension is an independent risk factor for cardiovascular disease, the leading cause of death in kidney transplant recipients. Because there is no “one size fits all” approach to blood pressure targets, particularly in the heterogenous group of kidney transplant recipients, identification of subgroup-specific targets, considering factors like age and sex, may be appropriate. However, currently available studies are limited because of sample sizes, and no subgroup analyses have been performed examining the effects of different blood pressure targets on allograft and patient survival. The aim of our study was to investigate the impact of different ACC/AHA blood pressure categories on graft survival and patient mortality and to identify subgroup-specific targets. Method This large-scale retrospective study included 1-year blood pressure data from 62, 556 kidney transplant recipients reported to the Collaborative Transplant Study from 209 centers in 39 countries. Hypertension was categorized according to 2017 ACC/AHA guidelines. The primary outcomes were death-censored graft failure and patient mortality during post-transplant year 1 to 6. Multivariable Cox regression analysis was performed to control for immunologic and nonimmunologic confounders. Results One year after transplantation, 77% of kidney transplant recipients had hypertension. Hypertension stages 1 (130–139/80–89 mmHg), 2a (140–159/90–99 mmHg), and 2b (≥160/≥100 mmHg) were associated with an 8%, 34%, and 102% increased risk of death-censored graft failure, respectively, whereas elevated blood pressure levels (120–129/&amp;lt;80 mmHg) did not significantly increase the risk. Patient mortality was only significantly higher in those with hypertension stage 2b with a Hazard Ratio of 1.21 (95% CI, 1.08–1.36; P &amp;lt; .001). In addition, the impact of hypertension stages on death-censored graft failure varied in different subpopulations (Fig. 1). Female recipients, younger recipients, recipients who received kidneys from donors younger than 60 years, re-transplanted recipients, and recipients with pre-transplant HLA antibodies had a significantly increased risk of death-censored graft failure associated with higher blood pressure levels (Fig. 1). Kidney transplant recipients with hypertension stage 2 continued to have an increased risk of graft failure one year after transplantation, even when they achieved normal blood pressure in the second year. Conclusion This study highlights the importance of treating hypertension early after kidney transplantation to improve long-term graft and patient survival. Attention should be paid to female, younger, and sensitized recipients, who may particularly benefit from optimal blood pressure control.

#623 One-year outcome of kidney transplant recipients harbouring complement regulatory gene mutation

Abstract Background and Aims Thrombotic Microangiopathy (TMA) is associated with genetic abnormalities in complement regulatory pathways. The impact of complement regulatory gene (CRG) mutation on post-transplant TMA in Indian kidney transplant recipients (KTR) is unknown. This study was conducted to ascertain an association between post-transplant renal limited TMA and the risk of graft failure in KTRs harbouring mutations in genes encoding complement-regulatory proteins. Method A Single Centre, Prospective Cohort Study was undertaken to assess the incidence of post-transplant renal limited TMA in KTRs with mutations in genes encoding complement regulatory proteins. Patients enrolled over one year were followed up for one-year post-transplantation. Genetic testing was performed with MLPA and Clinical exome sequencing. Results 138 KTRs with a mean age of 36.39 ± 12.39 years were enrolled. CRG mutation was seen in 96/138 (69.6%) KTRs. Duplication of the CFHR gene (n = 72) was most prevalent followed by mutations in CFH (n = 6), CFI (n = 2), MCP (n = 2), and DGKE (n = 1). Mutations in CFB, C3, and THBD genes were not detected. The Incidence of Post transplant renal limited TMA in KTRs with CRG mutations is 9.37% (9/96). Mutation related to aHUS was seen in 9 out of 11 patients who developed TMA. There was no significant difference in eGFR of patients with or without CRG mutation at the end of 1 year. Conclusion The prevalence of CRG mutation in KTRs is high and the majority of patients with post-transplant de novo TMA had CRG mutations. The graft functions at the end of 1 year were similar in patients with or without CRG gene mutation. This study suggests that the presence of CRG mutation should not preclude the option of Kidney transplantation in a patient with ESRD.

#2300 Validation study of the 4-variable kidney failure risk equation for prediction of allograft loss in a group of pediatric kidney transplant recipients

Abstract Background and Aims Emerging evidence suggests that the 4-variable Kidney Failure Risk Equation (KFRE) can be used to predict the risk of graft failure in adult transplant recipients. However, research studies in pediatric patients are lacking. This study aimed to validate the 4-variable KFRE (age, sex, estimated glomerular filtration rate [eGFR], and urine albumin-to-creatinine ratio [uACR]) for prediction of the 2- and 5-year risk of graft failure in a group of pediatric transplant patients. Method A retrospective observational study involving 59 pediatric patients who underwent kidney transplant between January 2007 and December 2017 was conducted. The KFRE risk scores were calculated with data collected at 1-year post-transplantation. The area under the receiver operating characteristic curves (AUC) and calibration plots were used to assess the discrimination and calibration properties of the 4-variable KFRE in predicting the risk of graft failure at 2 and 5 years from the point of the 1-year post-transplantation measurements. Results Among the 59 patients, 41 (69.5%) were male, with median age of 12.8 years (interquartile range 9.2-15.7) at the time of the kidney transplant. Eleven (18.6%) were living donor recipients. Median eFGR at 1-year post-transplantation was 62.0 mL/min/1.73 m2 (50.0-76.5); 1 (1.7%) and 3 (5.1%) patients developed graft failure within 2 and 5 years from the point of the 1-year post-transplantation measurements, respectively. The 4-variable KFRE showed excellent discrimination for the 2-year risk (AUC 0.966, 95% confidence interval [CI] 0.914-1.000) and very good discrimination for the 5-year risk (AUC 0.887, 95% CI 0.732-1.000). Calibration plots however showed imprecise calibration. A discernible trend was apparent in this sample, suggesting that living donor recipients have increased probability of experiencing graft failure in the first 5 years (p = 0.069). Conclusion The 4-variable KFRE may be of interest in predicting kidney failure progression in pediatric kidney transplant recipients using data at 1-year post-transplant, however to substantiate these findings and ensure the robustness of conclusions, larger-scale studies should be conducted.

#2414 Hypertension resolution after kidney transplantation is associated with better kidney transplant outcomes in patients with pre-transplant hypertension

Abstract Background and Aims Hypertension is prevalent in patients with advanced chronic kidney disease (CKD), and kidney transplantation (KT) can potentially improve hypertension. Although hypertension is expected to be resolved after KT in many recipients with pre-transplant hypertension, little is known about the hypertension resolution rate and its prognostic role in KT outcomes. Method We retrospectively identified KT recipients (between 2006 and 2015) who had pre-transplant hypertension using Health Insurance Review &amp; Assessment Service and Korea National Health Insurance System. The recipients were categorized into two groups based on their post-KT hypertension status: “persistent hypertension” and “resolved hypertension”. Cox proportional hazard analyses were performed to assess the risk of death-censored graft failure and all-cause mortality with adjusting various clinical, immunological risk factors, and socioeconomic status. Results Among 11,342 KT recipients with pre-transplant hypertension, 8,233 (73%) remained hypertensive, while 3,109 (27%) experienced hypertension resolution after KT. Recipients with resolved hypertension had lower rates of delayed graft function and major comorbidities, including diabetes mellitus, ischemic heart disease, and stroke compared to recipients who remained hypertensive. After adjusting for multiple covariates, the resolved hypertension group had 0.59-fold (95% confidence interval [CI] 0.49–0.73) lower risk for graft failure and 0.59-fold (95% CI 0.48–0.73) lower risk for all-cause mortality compared to the persistent hypertension group. Subgroup analyses revealed that the protective effect of resolved hypertension on graft survival was more pronounced in females (P for interaction = 0.045), and on overall survival was weaker in recipients with diabetes (P for interaction = 0.033). Conclusion A significant proportion of patients experienced hypertension resolution after KT, which is associated with improved graft survival and overall patient survival. The post-KT hypertension status can be used as a prognostic indicator for predicting better outcomes in KT recipients with pre-transplant hypertension.

#910 Pharmacometabolomics identified nonactivated metabolites of azathioprine and mycophenolate mofetil in urine of kidney transplant recipients

Abstract Background and Aims Metabolomics is employed frequently in clinical research with the aim of identifying disease-related mechanisms, biomarkers, and druggable targets. This technique is also used increasingly to obtain molecular evidence of chemical exposures, including dietary (e.g. caffeine, ethanol), lifestyle (e.g. tobacco smoke, illicit drugs), and medical exposures (e.g. therapeutic drugs). The latter opportunity recently led to the development of the subfield of ‘pharmacometabolomics’ that aims to yield insights into real-world patterns of drug metabolism, which may not always be in agreement with published (consensus) metabolic patterns. These insights are particularly relevant for drugs having narrow therapeutic windows, such as immunosuppressive drugs, and could contribute to more personalized evaluations of drug efficacy and safety. In this work, we applied pharmacometabolomics to study the real-world metabolism of the immunosuppressive drugs azathioprine and mycophenolate mofetil in kidney transplant recipients (KTR). In addition, we used the same data to obtain molecular evidence for the use of various prescribed, contraindicated, and illicit drugs. Method Untargeted ‘SWATH’ pharmacometabolomics was applied to 24-hour urine samples of 1258 kidney transplant recipients included in the TransplantLines Food and Nutrition Biobank and Cohort Study (NCT02811835) and the TransplantLines Biobank and Cohort Study (NCT03272841). Corresponding data were evaluated in order to assess whether observed metabolite profiles of azathioprine and mycophenolate mofetil are in agreement with consensus metabolic patterns. In addition, data were evaluated to validate self-reported drug use and to detect illicit (e.g. cocaine) and contraindicated drugs (e.g. NSAIDs after kidney transplantation). Results We unveiled disagreements between the consensus and real-world metabolism of both azathioprine and mycophenolate mofetil by discovering previously unreported drug metabolites. Importantly, our data suggest that considerable portions of these two prodrugs are not converted to their active forms. Based on several therapeutic drug classes, we furthermore demonstrated the capability of pharmacometabolomics to validate self-reported drug use, with both data sources being in good agreement (Cohen's kappa ≥0.90). Pharmacometabolomics also proved to be useful in the study of underreported exposures, as we identified cocaine and varying cocaine adulterants in the urine of 5 (0.4%) KTR. Moreover, we found NSAIDs in the urine of 49 (4%) KTR, for which the latter drugs are contraindicated. Conclusion Our work provides new insights into the metabolic fate of azathioprine and mycophenolate mofetil. Notably, we found the parent prodrugs as well as multiple nonactivated drug metabolites which warrant further investigations to rule out potential underdosing, as is associated with an increased risk of graft failure and morbidity. In addition, we could use the same data to obtain molecular evidence of prescribed, contraindicated, and illicit drugs, as are frequently studied using data retrieved through anamnesis and questionnaires. This application thus allows for reducing information bias in subsequent pharmacoepidemiological studies. Furthermore, it may have a signaling function for certain risky lifestyle habits and for inappropriate drug use.

#2831 A randomised controlled study of a Combined Home-based ExERcISe and Nutritional ApproacH to improve frailty in kidney transplant recipients (CHERISH)

Abstract Background and Aims Post-transplantation frailty is common, with a prevalence of up to 52% in kidney transplant recipients (KTRs), and is associated with increased mortality, recurrent hospitalisation and inferior quality of life (QoL). Resistance exercise training (RET) was found to improve frailty in this patient group. Both high and low protein intakes were associated with potential risk of graft failure. To date, no studies have evaluated the safety and efficacy of RET combined with protein supplementation (RETPS) in KTRs. The objectives of this study were to investigate the effect of RETPS on kidney function and frailty status in KTRs, and assess its impact on QoL. Method Forty clinically stable KTRs ≥1 year post-transplantation [mean age = 54 ± 14 years; 50% male, median time post-transplantation = 7 years] were enrolled and randomised to either RET (n = 20) or RETPS (n = 20). All participants completed a 30-minute home-based progressive RET regimen 2-3 times weekly for 12 weeks, guided by an exercise worksheet and a study-specific video link. Participants received weekly telephone call to ensure safety and compliance of the interventions. The RETPS group received additional body-weight adjusted whey protein supplementation 1-hour post exercise. Total daily dietary protein intake did not exceed 1.40 g/kg/day to confine to a safe level of protein consumption in KTRs. Kidney function was measured by estimated glomerular filtration rate (eGFR), creatinine, and albumin-creatinine ratio (ACR). Frailty was evaluated using Fried Frailty Phenotype (FFP), Short Performance Physical Battery (SPPB), 60-second Sit-to-Stand test (60s-STST), handgrip- (HG) and back-leg-chest- (BLC) derived muscle strength, bioimpedance-derived lean tissue index (LTI), and ultrasound-derived thigh muscle thickness (TMT). QoL was assessed using Short Form (SF) -36 questionnaire. All measurements were performed at baseline and at week 12. Results Kidney function did not differ significantly between baseline and week 12 in both RET [eGFR: 62.1 vs 59.7 ml/min; creatinine: 107.3 vs 111.5 μmol/L; ACR: 12.8 vs 10.4 mg/mmol] and RETPS [eGFR: 61.2 vs 60.7 ml/min; creatinine: 101.1 vs 102.2 μmol/L; ACR: 17.6 vs 20.9 mg/mmol] groups. Frailty status assessed by FFP and SPPB improved in both RET [FFP: 2.5 vs 1.3, P &amp;lt; .001; SPPB: 7.2 vs 11.6, P &amp;lt; .001] and RETPS [FFP: 2.8 vs 1.1, P &amp;lt; .001; SPPB: 6.4 vs 10.9, P &amp;lt; .001] groups, but the improvements did not differ significantly between groups (P &amp;gt; 0.23). Improvements in 60s-STST, HG-derived muscle strength, BLC-derived muscle strength, and ultrasound-derived TMT were observed in both RET [60s-STST: 23 vs 27, P &amp;lt; .001; HG-derived muscle strength: 24 vs 30 kg, P &amp;lt; .001; BLC-derived muscle strength: 62 vs 71 kg, P &amp;lt; .001; ultrasound-derived TMT: 15 vs 19 mm, P &amp;lt; .001] and RETPS [60s-STST: 20 vs 29, P &amp;lt; .001; HG-derived muscle strength: 24 vs 32 kg, P &amp;lt; .001; BLC-derived muscle strength: 57 vs 80 kg, P &amp;lt; .001; ultrasound-derived TMT: 14 vs 21 mm, P &amp;lt; .001] groups, with greater improvements in RETPS group for 60s-STST (P &amp;lt; .01), HG-derived muscle strength (P &amp;lt; .05), BLC-derived muscle strength (P &amp;lt; .05), and ultrasound-derived TMT (P &amp;lt; .001). For bioimpedance-derived LTI, improvement was observed only in RETPS group [12.8 vs 14.8 kg/m2, P &amp;lt; .05]. SF-36-derived overall-, physical- and mental- related QoL improved in both groups (P &amp;lt; .05 for all), with RETPS group reporting a greater improvement in physical-related QoL (P &amp;lt; .05). Conclusion This represents the first study demonstrating RET combined with protein supplementation is safe and effective in improving frailty and QoL in KTRs. Protein supplementation augments increased muscle mass and strength beyond RET effect, further enhancing improvement in physical-related QoL.

#1847 Pregnancy impact on kidney transplant outcome

Abstract Background and Aims Renal transplantation improves the fertility of women of childbearing age. The possibility of a term pregnancy is one of the benefits of solid organ transplantation for women. Studies have also shown an increase in graft loss during and after pregnancy among sensitized patients and a higher risk of graft failure due to rejection in pregnancies occurring in the first and second-year post-transplantation. Most of these observations were found in studies using controls of non-pregnant recipients, but most did not match the study group in several critical clinical parameters, such as the gender of the controls, the creatinine level prepregnancy, or the cause of native kidney failure. The aim of our study is to investigate the long-term effects of pregnancy on graft function in female renal transplant recipients at Mansoura Urology and Nephrology center who experienced pregnancy after kidney transplantation. Method Retrospective cohort study conducted on 236 patients out of 3000 kidney transplant recipient who underwent renal transplantation (RT) at Mansoura Urology and Nephrology Centre between March 1976 and December 2019. divided into group I; 118 kidney transplant female's recipient experienced pregnancy at any time after kidney transplant and Group II; 118 kidney transplant female's recipients who didn`t experience pregnancy after renal transplantation, they were matched according to age and duration of renal transplantation and comparable in primary immunosuppressant drugs. all kidney recipients were reviewed for preoperative &amp; operative and post-operative details also we record maternal and fetal complication. Results Our study included 118 kidney transplant recipients who got pregnant 191 times, 64 kidney transplant recipients got pregnant for the second time, while 9 of them got pregnant for the third time. We retrospectively evaluated the maternal, fetal complications and evolution of graft function after each pregnancy. Main maternal complications were gestational hypertension developed in 87 pregnancy cases out of 191 (45.5%), preeclampsia (25.1%), UTI (18.8%), gestational DM (9.9%), and graft rejection during pregnancy (4.1%). Longer hemodialysis duration (OR: 0.45, p value: 0.05), Calcineurin-based immunosuppressive protocols (Tacrolimus; OR: 2.3, p value: 0.02; Cyclosporine; OR: 0.36, p value: 0.007), Proteinuria more than or equal to 0.5 g/day (OR: 5.4, p value: 0.001) and/or serum creatinine more than or equal to 1.3 mg/dl (OR: 3.75, p value: 0.001) before pregnancy and rising of serum creatinine and/or proteinuria (Proteinuria; OR: 20.84, p value: 0.001; serum creatinine ≥1.3 mg/dl; OR: 4.3, p value: 0.001) are important risk factors associated with gestational hypertension. The mean serum creatinine level pre-pregnancy (mean ± SD) was (0.9 ± 0.2) mg/dL and 24-hour urinary protein mean ± SD before pregnancy was (0.4 ± 0.2) g/day. Serum creatinine and 24-hour urinary protein were higher during and after pregnancy with a statistically significant difference when compared to before pregnancy data (P-value: 0.001), (P- value: 0.04) retrospectively. At last follow-up, the majority of patients were alive with functioning graft with no statistically significant difference between two groups (P-value: 0.07), also no significant difference as regard graft failure incidence (p-value: 0.52). Conclusion Although the outcome of live births is favourable, the risks of maternal and fetal complications are high in kidney transplant recipients including pregnancy-induced hypertension, increased rates of preeclampsia, gestational diabetes, and caesarean section rates. The risk of miscarriage, prematurity, and low birth rate is also high. Serum creatinine and 24-hour urinary protein tend to increase during and after pregnancy which may impair the graft outcome. pregnancy counselling is necessary to avoid high-risk or unwanted pregnancies.

The Potential Utilization of Machine Perfusion to Increase Transplantation of Macrosteatotic Livers.

The demand for liver transplantation has led to the utilization of marginal grafts including moderately macrosteatotic livers (macrosteatosis ≥30% [Mas30]), which are associated with an elevated risk of graft failure. Machine perfusion (MP) has emerged as a technique for organ preservation and viability testing; however, little is known about MP in Mas30 livers. This study evaluates the utilization and outcomes of Mas30 livers in the era of MP. The Organ Procurement and Transplantation Network database was queried to identify biopsy-proven Mas30 deceased donor liver grafts between June 1, 2016, and June 23, 2023. Univariable and multivariable models were constructed to study the association between MP and graft utilization and survival. The final cohort with 3317 Mas30 livers was identified, of which 72 underwent MP and were compared with 3245 non-MP livers. Among Mas30 livers, 62 (MP) and 1832 (non-MP) were transplanted (utilization of 86.1% versus 56.4%, P < 0.001). Donor and recipient characteristics were comparable between MP and non-MP groups. In adjusted analyses, MP was associated with significantly increased Mas30 graft utilization (odds ratio, 7.89; 95% confidence interval [CI], 3.76-16.58; P < 0.001). In log-rank tests, MP was not associated with 1- and 3-y graft failure (hazard ratio, 0.49; 95% CI, 0.12-1.99; P = 0.319 and hazard ratio 0.43; 95% CI, 0.11-1.73; P = 0.235, respectively). The utilization rate of Mas30 grafts increases with MP without detriment to graft survival. This early experience may have implications for increasing the available donor pool of Mas30 livers.

Long-Term Graft and Patient Survival After Re-Transplantation.

BACKGROUND Kidney transplant recipients have higher life expectancy but may require subsequent transplantations, raising ethical concerns regarding organ allocation. We assessed the safety of multiple kidney transplants through long-term follow-up. MATERIAL AND METHODS A retrospective cohort study was conducted at a single center, categorizing patients based on the number of kidney transplantations received. The primary outcome was the composite of death-censored graft failure and overall mortality. The secondary outcome was death-censored graft failure. RESULTS Between 2000 and 2019, our center performed 2152 kidney transplantations. Patients were divided into 3 groups: A (1 transplant; n=1850), B (2 transplants; n=285), and C (3 or more transplants; n=75). Group C patients were younger, had fewer comorbidities, and received more aggressive induction therapy. The primary outcomes, including death-censored graft loss and overall mortality, showed similar rates across groups (A: 21.3%, B: 25.2%, C: 21.7%, p=0.068). However, the secondary outcome of death-censored graft failure alone was significantly lower in group A compared to the other groups. No significant difference was observed between groups B and C (8% vs 16% and 13%, respectively, p=0.001, p=0.845). Multivariate analysis identified having a living donor as the strongest predictor of patient and graft survival in all study groups. CONCLUSIONS Graft and patient survival rates were similar between first and multiple transplant recipients. Multiple transplant recipients had lower death-censored graft failure risk compared to first transplant recipients. However, the risk did not differ among second and subsequent transplant recipients. Younger patients, especially those with a living donor, should be considered for repeat kidney transplantation.

Socioeconomic deprivation is associated with worse patient and graft survival following adult liver transplantation.

The impact of social determinants of health (SDOH) on adult liver transplant recipient outcomes is not clear at a national level. Further understanding of the impact of SDOH on patient outcomes can inform effective equitable healthcare delivery. Unadjusted and multivariable models were used to analyze the Scientific Registry of Transplant Recipients to evaluate the association between the Social Deprivation Index (SDI) based on liver transplant recipient's residential location and patient and graft survival. We included adult recipients between 1/1/2008-12/1/2021. Patient and graft survival were lower in adults living in areas with deprivation scores above the median. Five-year patient and graft survival were 78.7% and 76.5% respectively in the cohort above median SDI compared to 80.5% and 78.3% below median SDI. Compared to the recipients in low deprivation residential areas, recipients residing in highest deprivation (SDI quintile=5) cohort had 6% higher adjusted risk of mortality (Adjusted Hazard Ratio [AHR]=1.06,95%C.I. 1.01-1.13) and 6% higher risk of graft failure (AHR=1.06,95% C.I. 1.001-1.11). The increased risks for recipients residing in more vulnerable residential areas were higher (AHR=1.11,95% CI 1.03-1.20 for both death and graft loss) following the first-year post-transplantation. Importantly, overall risk for graft loss associated with SDI was not linear but instead accelerated above the median level of deprivation. In the United States, SDOH, as reflected by residential distress, significantly impact 5-year patient and graft survival. The overall effect of residential deprivation are modest, but importantly, results illustrate they are more strongly associated with longer-term follow up and accelerate at higher deprivation levels. Further research is needed to evaluate effective interventions and policies to attenuate disparities in outcomes among recipients in highly disadvantaged areas.

Oral Glucose Tolerance Test as a Risk Marker for Developing Post-Transplant Diabetes Mellitus

IntroductionThe incidence of post-transplant diabetes mellitus (PTDM) can reach 30% during the first 6 months after kidney transplantation (KT), increasing the risk of graft failure and mortality. There is no well-established biomarker for predicting PTDM occurrence. This study evaluated the association between the abnormal 2-hour oral glucose tolerance test (OGTT) and the PTDM incidence. MethodsA retrospective single-center study, including adult kidney transplant recipients from deceased donors, was performed between March 2021 and June 2022. Exclusion criteria: age <18 years; pretransplant diabetes mellitus (DM); death with a functioning graft; loss of follow-up and/or graft failure before 6 months post-transplant. The results of pretransplant OGTT, fasting (FPG), and afternoon plasma glucose levels at hospitalization and FPG in the first, second, and third months post-transplant were evaluated. For analysis, patients were grouped according to the PTDM diagnosis: PTDM and non-PTDM. ResultsFrom 164 KT performed in the period, 50 (30%) were included, most male (n = 34, 68%), with a mean age of 48.3 ± 12.5 years. Nine patients (18%) developed PTDM, 44% between 3 and 6 months. General characteristics and immunosuppressive therapy were similar between the groups. The mean FPG in the pretransplant OGTT was significantly higher in the PTDM group compared with the non-PTDM group (85.7 ± 7.9 vs 79.1 ± 8.2, P = .03). The number of patients classified as impaired glucose tolerance (IGT) on the pre-transplant OGTT was significantly higher in the PTDM group. ConclusionIGT in the pretransplant OGTT was associated with PTDM cases in kidney transplant recipients without a previous diagnosis of DM.

Influence of induction therapy and antiretroviral regimen on outcomes in kidney transplant recipients living with human immunodeficiency.

Kidney transplantation has a survival benefit for people with human immunodeficiency virus (HIV) and end-stage kidney disease, however increased rates of rejection remain an issue. Questions remain regarding the impact of induction immunosuppression therapy and antiretroviral (ARV) choice on long-term outcomes. We performed a multicenter retrospective analysis of outcomes in recipients with HIV who received kidneys from donors without HIV transplanted between 2004 and 2019. The association between induction and ARV regimens and long-term outcomes including rejection, graft, and recipient survival over 5 years was investigated using Cox regression modeling. Seventy-eight kidney transplants (KT) performed in 77 recipients at five US transplant centers were included, with median follow up of 7.1 (4.3-10.7) years. Overall recipient and graft survival were 83% and 67%, respectively. Rejection occurred in 37% (29/78). Recipients with rejection were more likely to be younger, recipients of deceased donor organs, and Black. Receipt of rabbit anti-thymocyte globulin (rATG) induction without protease-inhibitor (PI)-based ARVs was associated with 83% lower risk of rejection (adjusted hazard ratio (aHR) 0.17 (95% CI 0.05-0.63), p =.007) and a non-statistically significantly lower risk of graft failure (aHR 0.18 (0.03-1.16), p =.07) when compared to those who received other induction and ARV combinations. In this multicenter retrospective study, we found a trend toward lower rejection and improved graft survival among those who received both rATG for induction and PI-sparing ARVs.

Outcomes with allogeneic stem cell transplant using cryopreserved versus fresh hematopoietic progenitor cell products

BackgroundAllogeneic hematopoietic stem cell transplant (alloHSCT) is a mainstay of treatment for hematologic malignancies such as acute leukemias and aggressive lymphomas. Historically, fresh hematopoietic progenitor cell (HPC) products have been preferred to cryopreserved products (cryo-HPC) due to concerns of loss of stem cell viability and number with the cryopreservation procedure. ObjectiveWe aimed to analyze the outcomes of patients who received cryo-HPCs during the COVID-19 pandemic and compare this against historical cohorts that received fresh HPC. Study DesignA retrospective chart review was conducted on all adult patients who received a peripheral blood alloHSCT in British Columbia, Canada between June 2017 and November 2021. Baseline characteristics, Kaplan-Meier (KM) overall survival (OS), engraftment, and incidences of acute and chronic graft versus host disease were compared between patients who received cryo-HPCs and fresh HPCs. Univariable analysis followed by multivariable analysis was performed using a backward stepwise selection procedure to generate predictors of OS, cumulative incidence of relapse (CIR), nonrelapse mortality (NRM), and primary and secondary graft failure. ResultsThree hundred eighty-three patients were included in the analysis, with cryo-HPC representing 40%. Median viability was higher in the fresh-HPC group at 99.2% (IQR 98.3–99.5) versus cryo-HPCs at 97.0% (96.0, 98.6) (P < 0.01). The 12-month actuarial survivals were 77% in the fresh HPC and 75% in the cryo-HPC groups (P = 0.21). There were no differences between cryo-HPCs and fresh HPCs on univariable analysis of OS, CIR, or NRM. There was a shorter median time to platelet engraftment in patients receiving fresh HPC at 17 days (IQR 16, 20) versus cryo-HPC at 21 days (IQR 18, 29), P < 0.001. There was a shorter median time to neutrophil engraftment in the fresh HPC group at 17 days (IQR 14, 20) versus 20 days (17, 23), P < 0.001. Cryo-HPC accounted for 5 out of 6 cases of primary graft failure (P = 0.04), and 3 out of five cases of secondary graft failure (P = 0.39). There were no significant differences in acute GVHD between the fresh HPC and cryo-HPC groups (P = 0.34). The incidence of moderate or severe chronic GVHD was 32% in the fresh-HPC group and 17% in the cryo-HPC group (P < 0.001).In multivariable analysis, cryopreservation did not emerge as an independent predictor of OS, CIR, NRM, primary GF or secondary GF. However, viability <90% on arrival at our center was a significant predictor of OS (HR 5.3, 2.3–12.3, P < 0.01), primary graft failure (OR 36.3, 5.4–210.2, P < 0.01), and secondary graft failure (OR 18.4, 1.7–121.1, P < 0.01). ConclusionsPatients who received cryo-HPCs had similar OS and relapse rates to those who received fresh-HPCs but typically took 2–3 days longer to achieve engraftment of platelets or neutrophils and were associated increased primary graft failure. However, after accounting for multiple variables, cryopreservation was no longer a significant predictor of survival or engraftment while viability <90% emerged as an important predictor of OS, primary graft failure, and secondary graft failure. If confirmed, this suggests that viability on arrival at the infusion center may be a good quality control indicator used to identify HPC products that may warrant recollection if the risk of graft failure is sufficiently increased.

Association of Posterior Tibial Slope With Outcomes After Multiligamentous Knee Reconstruction for Knee Dislocation Grades 2 to 4.

Patients with isolated anterior cruciate ligament (ACL) reconstruction have demonstrated an increased risk of ACL graft failure and lower patient-reported outcome (PRO) scores when increased posterior tibial slope (PTS) is present. However, there is a paucity of literature evaluating the effect of PTS on outcomes after combined bicruciate multiligamentous knee reconstruction. To determine whether differences exist for graft failure rates or PRO scores based on PTS after combined bicruciate multiligamentous knee reconstruction. Cohort study; Level of evidence, 3. All patients who underwent combined ACL and posterior cruciate ligament (PCL) reconstruction between 2000 and 2020 at our institution were identified. Exclusion criteria were age <18 years, knee dislocation grade 5 injuries, concomitant osteotomy procedures, and <2 years of clinical follow-up. Demographic and outcomes data were collected from our prospectively gathered multiligamentous knee injury database. Lysholm and International Knee Documentation Committee (IKDC) scores were analyzed in relation to PTS. Outcomes were compared for patients with a PTS above and below the mean for the total cohort, PTS >12° versus <12°, positive versus negative Lachman test at follow-up, and positive versus negative posterior drawer test at follow-up. A total of 98 knees in 98 patients were included in the study, with a mean clinical follow-up of 5.1 years (median, 4.6 years; range, 2-16 years). The mean PTS was 8.7° (range, 0.4°-16.9°). Linear regression analysis showed no significant correlation between PTS and IKDC or Lysholm scores. Patients with a PTS above the mean of 8.7° trended toward lower IKDC (P = .08) and Lysholm (P = .06) scores. Four patients experienced ACL graft failure and 5 patients experienced PCL graft failure. There were no differences in graft failure rates or PRO scores for patients with a PTS >12°. Patients with a positive Lachman test trended toward higher PTS (9.6° vs 8.5°, P = .15). In this series of bicruciate multiligamentous knee reconstructions at midterm follow-up, no differences in graft failures, complications, reoperations, revisions, or PRO scores based on PTS were identified. Patients with a positive Lachman test were found to have a slightly higher PTS, although this did not reach statistical significance.

Treatment of Medial Patellar Instability With Bipolar Patellofemoral Cartilage Lesions: Staged De-rotational Distal Femoral Osteotomy Followed by Bipolar Osteochondral Allograft Transplantation and Tibial-Tubercle Osteotomy

Background: Patellar instability with symptomatic cartilage lesions in young patients is a challenging problem to treat. The use of osteotomies to correct malalignment and fresh osteochondral allograft transplantation (OCA) to address cartilage lesions and patellofemoral dysplasia is a viable treatment option for carefully selected patients. Indications: The patient is a 22-year-old woman with medial patellar instability caused by iatrogenic distal femoral external rotation and uncontained grade IV patellofemoral lesions. The patient was indicated for OCA because the lesions were too large for an osteochondral autograft transfer system (OATS) and were uncontained and not amenable to autologous chondrocyte implantation. Bipolar OCA also addresses the patient’s patellofemoral dysplasia by restoring a more morphologically normal patellofemoral joint. The external rotation and mild varus deformity are corrected with a biplanar distal femoral osteotomy. Correction of malalignment is necessary prior to OCA transplantation to avoid abnormal graft loading and thereby decrease the risk of graft failure. Technique Description: (1) Diagnostic arthroscopy and fluoroscopic examination under anesthesia. (2) Lateral closing wedge de-rotational distal femoral osteotomy. (3) Bipolar OCA with tibial tubercle osteotomy and removal of hardware. Results: In this case, the patient had significant improvement in her symptoms and had full knee range of motion with a normal gait at 3 months after surgery. Depending on a patient’s preoperative function and the specific pathology, full recovery can take considerably longer. A successful outcome is considered return to activities of daily living without significant pain. Return to higher level athletic activities is significantly more unpredictable. Graft survival of bipolar patellofemoral OCA is variable, and the literature is limited by the small number of procedures performed, but published series range from 60% to 85% at 5 years. Discussion/Conclusion: A successful outcome in these unique, complex cases depends on good patient selection, preoperative planning, and surgical execution. Patellar instability can be reliably treated when the predisposing anatomical factors are appropriately corrected. Bipolar OCA can provide significant improvement in pain and function, but continues to have the highest rate of graft failure compared with other sites within the knee, and should be considered a salvage operation for patients with significant limitations in activities of daily living. Patient Consent Disclosure Statement: The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form of approval from the patient(s) with this submission for publication.