Background: Biliary complications remain a major source of morbidity after living-donor livertransplantation (LDLT), particularly in recipients with marked donor-recipient duct size disparity. Weevaluated the feasibility and short-term clinical performance of an intraoperatively placed biodegradableinternal biliary stent in adult LDLT recipients with duct-to-duct mismatch greater than 50%. Methods:This prospective, single-centre pilot study enrolled 12 consecutive adult LDLT recipients between August2024 and August 2025. Eligibility required primary LDLT, duct-to-duct biliary reconstruction, andintraoperative confirmation of marked duct mismatch, defined as a donor duct diameter more than50% smaller than the recipient duct diameter. A biodegradable Archimedes (R) stent with an 11-weekdegradation profile was placed entirely within the bile duct across the anastomosis and secured with a6-0 polydioxanone suture. Outcomes were compared with a frequency-matched historical cohort of 12adult LDLT recipients transplanted between 2018 and 2023 without stent placement. Matching variableswere right-lobe graft use, recipient age band, mismatch category, and biliary reconstruction complexity.The primary endpoint was technical feasibility. Secondary endpoints included anastomotic stricture,bile leak, biliary cast material, cholangitis, endoscopic retrograde cholangiopancreatography (ERCP)requirement, stent migration, and graft loss through 12 months. Results: Technical success was achievedin all 12 stented recipients (100%). Median recipient age was 52 years (interquartile range [IQR], 42-60),and median duct mismatch was 65% (IQR, 58-72). No anastomotic strictures occurred in the stentedcohort at 12 months, compared with 5/12 (41.7%) in historical controls (p = 0.037, two-sided Fisher'sexact test). One bile leak (8.3%) resolved with drainage alone. Biliary cast material occurred in 2/12recipients (16.7%); one required ERCP and one resolved without intervention. ERCP was required in1/12 stented recipients (8.3%) versus 6/12 controls (50.0%;p = 0.069). No stent migration, cholangitis,pancreatitis, or graft loss occurred in the stented cohort. Conclusions: In adult LDLT recipients withmarked duct mismatch, biodegradable internal biliary stenting was technically feasible and demonstratedan acceptable safety profile. Compared with a frequency-matched historical cohort, stented recipientshad fewer anastomotic strictures and numerically fewer ERCPs, although comparative inference remainslimited by the pilot design and small sample size. Prospective multicentre evaluation is warranted
Background: Pregnancy after living kidney donation is increasingly common, but the dominant obstetricphenotype remains unclear. Prior work focused on hypertension, yet placental dysfunction and fetalgrowth impairment may be more informative. We investigated whether post-donation pregnancies areassociated with increased risks of placental dysfunction and fetal growth restriction versus matchednon-donor and pre-donation pregnancies. Methods: Nationwide Swedish registry-based cohort study(1995-2018) including women <= 45 years at living kidney donation. Singleton pre- and post-donationpregnancies were identified. Post-donation pregnancies were compared 1:10 with matched generalobstetric controls (age, parity, year, region) and with pre-donation pregnancies. Primary outcome:placental dysfunction (pre-eclampsia or SGA <10th percentile). Co-primary: SGA as proxy for fetalgrowth restriction. Adjusted regression models accounted for maternal clustering. Results: 642 donorscontributed 987 pre-donation and 1,013 post-donation pregnancies; 10,130 controls were included.Placental dysfunction occurred in 21.4% (post-donation) vs. 15.2% (pre-donation) vs. 16.8% (controls).Adjusted ORs: 1.38 (95% CI 1.19-1.60) vs. controls and 1.45 (1.21-1.74) vs. pre-donation. SGA occurred in17.6%, 12.4%, and 13.7%, respectively (ORs 1.41 and 1.49). Mean birth weight was 92 g lower post-donation(95% CI -118 to -66). Pre-eclampsia alone showed modest association (OR 1.25, 1.04-1.50), suggesting afetal growth phenotype. Conclusions: Post-donation pregnancies had higher risks of placental dysfunctionand impaired fetal growth, with weaker association for pre-eclampsia alone. The absolute risk increasewas modest ( 5 percentage points), supporting targeted antenatal surveillance focused on fetal growthalongside maternal hypertension.
Background: Chronic lung allograft dysfunction remains the leading barrier to long-term graft survival after lung transplantation. Therapeutic options are limited once lung function begins to decline rapidly, and the role of anti-thymocyte globulin in this setting remains incompletely defined. This study evaluated the clinical effectiveness and safety of anti-thymocyte globulin in patients with rapidly progressive chronic lung allograft dysfunction. Methods: We performed a retrospective single-center cohort study of adult lung transplant recipients diagnosed with chronic lung allograft dysfunction between 2013 and 2023. Rapidly progressive chronic lung allograft dysfunction was defined a priori as a decline in FEV1 exceeding 100 mL/month over the 3-month period preceding treatment or index-date assessment, confirmed by at least 3 spirometric measurements. Patients treated with anti-thymocyte globulin for progressive chronic lung allograft dysfunction were compared with contemporaneous patients with rapidly progressive chronic lung allograft dysfunction who did not receive anti-thymocyte globulin. The primary effectiveness endpoint was change in the rate of FEV1 decline during the 6 months before and after anti-thymocyte globulin administration. Secondary endpoints included partial response, complete response, post-chronic lung allograft dysfunction graft survival, and treatment-related safety outcomes. Propensity-score matching was used for survival comparison between treated and untreated groups. Results: Of 187 lung transplant recipients reviewed, 168 developed chronic lung allograft dysfunction and 112 met criteria for rapidly progressive disease. Among these, 64 received anti-thymocyte globulin and 48 did not. After exclusion for inadequate spirometric follow-up, 58 anti-thymocyte globulin-treated patients were included in the effectiveness analysis. The mean pre-anti-thymocyte globulin FEV1 slope was -1.78 mL/day, improving to -1.49 mL/day after treatment (mean difference 0.29 mL/day, 95% CI 0.01-0.57, p=0.04). A partial response was observed in 69.0%, while a complete response was observed in 8.6%. In propensity-matched analysis (40 pairs), median graft survival was 28.4 months in the anti-thymocyte globulin group versus 19.2 months in the control group. The hazard ratio for graft failure was 0.71 (95% CI 0.46-1.09, p=0.12), which did not reach statistical significance. Infectious complications within 6 months of anti-thymocyte globulin occurred in 27.6%, with bacterial pneumonia as the most common event. Conclusions: In patients with rapidly progressive chronic lung allograft dysfunction, anti-thymocyte globulin was associated with modest attenuation of FEV1 decline. However, no statistically significant survival benefit was detected. The substantial burden of infectious complications (27.6%) and hematologic toxicity (36.2%) underscores the need for careful patient selection. These findings are hypothesis-generating rather than definitive. Prospective randomized trials are needed to determine whether any survival benefit exists and to establish the optimal risk-benefit profile for this therapy.
Background: Prior work identified preoperative fibrinogen <125 mg/dL as a predictor of transfusion in living donor liver transplantation (LDLT), but external validation is lacking. This study provides external validation of this threshold. Objective: To externally validate the association between fibrinogen <125 mg/dL and major transfusion in adult LDLT recipients, and evaluate its relationship with early recovery. Methods: Consecutive adult LDLT recipients (Jan 2022-Dec 2023) were analyzed. The 125 mg/dL threshold was pre-specified from prior ROC analysis (AUC 0.638). Primary outcome: major transfusion (>= 4 units PRBC, prespecified as upper quartile). Multivariable logistic regression adjusted for MELD-Na, INR, platelets, bilirubin, hemoglobin, albumin, cold ischemia time, and surgery duration. Model discrimination (AUC) and calibration (Hosmer-Lemeshow) were assessed. Results: Among 219 recipients, 70 (32.0%) had fibrinogen <125 mg/dL. Low fibrinogen patients had higher platelet counts (79.6 vs. 52.2, p = 0.047), greater blood loss (1850 vs. 1050 mL, p < 0.001), more PRBC (5.5 vs. 2.5 units, p < 0.001), and more FFP (6.0 vs. 3.0 units, p < 0.001). Major transfusion occurred in 51.4% vs. 16.8% (p < 0.001). On multivariable analysis, fibrinogen <125 mg/dL remained independently associated with major transfusion (aOR 7.84, 95% CI 1.98-31.02, p = 0.003). The model showed good discrimination (AUC 0.784) and calibration (p = 0.342). Each 50-mg/dL decrease in fibrinogen increased transfusion odds (aOR 1.38, p = 0.008). Low fibrinogen patients required longer ventilation (30 vs. 18 h, p = 0.002) and vasopressor support (28 vs. 16 h, p = 0.008). Conclusion: This validation study confirms fibrinogen <125 mg/dL predicts increased transfusion and delayed recovery after LDLT. However, the modest discriminative ability (prior AUC 0.638) suggests fibrinogen should be used with other markers, not alone. Multicenter validation is needed before clinical implementation.
Background: Durable operational tolerance after kidney transplantation remains uncommon. Most immunosuppression-withdrawal strategies have relied on calendar-based tapering rather than biologically informed decision-making. We tested whether biomarker-guided immunosuppression withdrawal could improve the safety and feasibility of minimization after living-donor kidney transplantation. Methods: This prospective, single-arm, open-label pilot study enrolled 22 adult, low-immunologic-risk recipients of primary living-donor kidney allografts between January 2021 and June 2022. All participants received induction with rabbit antithymocyte globulin and rituximab, followed by tacrolimus-, sirolimus-, and short-course mycophenolate-based maintenance without chronic corticosteroids. Withdrawal was initiated only after a predefined biomarker gate was satisfied, incorporating stable graft function, absence of donor-specific HLA antibodies, reassuring protocol histology, and a favorable composite immune-reconstitution profile. The primary endpointwas successful complete withdrawal of maintenance immunosuppression for 52 consecutive weeks without biopsy-proven acute rejection, donor-specific antibody development, recurrent disease, graft loss, death, or sustained graft dysfunction. Results: Fourteen of 22 recipients (63.6%) met biomarker eligibility for tacrolimus withdrawal at a median of 34 weeks (IQR 31-37) after transplantation, and 10 (45.5%) subsequently met eligibility for full withdrawal and discontinued all maintenance immunosuppression. Seven recipients (31.8%) met the primary endpoint. Overall biopsy-proven acute rejection occurred in 3 of 22 recipients (13.6%), all T cell-mediated; no antibody-mediated rejection occurred. De novo donor-specific HLA antibodies developed in 2 recipients (9.1%). There were no cases of patient death or graft loss. In exploratory analyses, recipients who met the primary endpoint showed higher transitional B-cell fractions (18.4% vs. 11.5%), higher naive-to-memory B-cell ratios (2.6 vs. 1.4), lower CD8(+) TEMRA frequencies (21.7% vs. 31.9%), higher Treg/CD4 ratios (0.079 vs. 0.058), and lower serum BLyS concentrations (1.6 vs. 3.1 ng/mL) at the prewithdrawal biomarker assessment than recipients who failed to achieve durable withdrawal. Conclusions: In this pilot study, biomarker-guided immunosuppression withdrawal was associated with a subset of low-risk living-donor kidney transplant recipients in whom complete immunosuppression withdrawal appeared feasible with acceptable short-term safety. These hypothesis-generating findings support further prospective validation of immune-state-guided minimization strategies in larger cohorts.
Murine kidney transplantation is a powerful platform for mechanistic transplant research, but sensitive longitudinal measurement of graft function remains challenging. Conventional serum creatinine and blood urea nitrogen often fail to detect modest yet biologically important differences in renal injury and recovery. We evaluated whether serial transdermal glomerular filtration rate (tGFR) measurement could identify early functional benefit from peri-transplant costimulation blockade in a murine allogeneic kidney transplant model. Twelve-week-old BALB/c and C57BL/6J mice of both sexes underwent orthotopic kidney transplantation using sex-matched donor-recipient pairs. Recipients underwent bilateral native nephrectomy, making survival dependent on allograft function. Animals were assigned to syngeneic transplantation, untreated allogeneic transplantation, or allogeneic transplantation with short-course peri-transplant anti-CD154 costimulation blockade. Renal function was assessed serially by tGFR, serum creatinine, and blood urea nitrogen. Histologic injury was evaluated at prespecified time points. Baseline renal function was comparable among recipient groups before transplantation. Following allogeneic transplantation, untreated recipients developed a marked decline in tGFR with incomplete recovery by day 28. In contrast, costimulation blockade significantly attenuated the early nadir and improved recovery through day 28. These functional differences were larger and more consistent when assessed by tGFR than by serum creatinine or blood urea nitrogen. Treated recipients also demonstrated prolonged survival and reduced glomerulitis, tubulitis, and peritubular capillaritis on histologic analysis. Sex-stratified analysis showed benefit in both males and females, with slightly greater late functional recovery among treated females. These findings show that serial tGFR is a sensitive primary endpoint for detecting early therapeutic benefit in murine kidney transplantation. Peri-transplant costimulation blockade improved graft function, survival, and histologic injury, and these effects were captured most clearly by direct longitudinal measurement of glomerular filtration rate.
Background: Molecular HLA mismatch has shown greater biologic precision than conventional antigen mismatch for estimating alloimmune risk after kidney transplantation. Prior work in an ethnically diverse steroid-sparing cohort demonstrated that increasing molecular mismatch was associated with early de novo donor-specific antibody (dnDSA) development, but follow-up was limited to the early post-transplant period. We performed a longitudinal extension study to evaluate whether the same mismatch framework remains associated with cumulative dnDSA development and rejection through 24 months. Methods: We analyzed a patient-level cohort of 630 kidney transplant recipients generated as a scaled longitudinal extension of a published 3-month study. Baseline variables included sex, recipient ethnicity, transplant type, graft number, induction/maintenance regimen, total ABDR antigen mismatch, and three molecular mismatch metrics: HLA-Matchmaker antibody-verified (AbVer) eplet load, HLA-EMMA solvent-accessible (SolAcc) amino-acid mismatch load, and PIRCHE-II peptide mismatch load. Outcomes were cumulative dnDSA at 3, 6, 12, 18, and 24 months, biopsy occurrence, and cumulative rejection through 24 months. Logistic regression and receiver operating characteristic analysis were used to compare mismatch measures. Results: In the 630-patient cohort, cumulative dnDSA incidence rose from 77/630 (12.2%) at 3 months to 91/630 (14.4%) at 6 months, 119/630 (18.9%) at 12 months, 134/630 (21.3%) at 18 months, and 149/630 (23.7%) at 24 months. Cumulative rejection increased from 44/630 (7.0%) to 93/630 (14.8%) over the same intervals. At 3 months, 54 of 77 dnDSA events were persistent and 23 were transient. By 24 months, 72 additional late dnDSA events were modeled, most frequently between 6 and 12 months. Higher 24-month dnDSA burden was associated with higher median AbVer, SolAcc, and PIRCHE-II loads. In multivariable analysis, each mismatch metric remained associated with cumulative 24-month dnDSA: ABDR mismatch odds ratio (OR) 1.385, HLA-Matchmaker OR 1.152, HLA-EMMA OR 1.037, and PIRCHE-II OR 1.004 (all P < 0.001). HLA-EMMA showed the strongest single-metric discrimination for 24-month dnDSA(area under the curve [AUC] 0.761), compared with 0.733 for HLA-Matchmaker, 0.639 for PIRCHE-II, and 0.612 for ABDR mismatch. Rejection by 24 months occurred in 14.8% overall but was concentrated among recipients with persistent or late dnDSA. Conclusions: In this longitudinal extension, higher molecular mismatch burden remained strongly associated with cumulative dnDSA development and rejection through 24 months. HLA-EMMA and HLA-Matchmaker outperformed conventional antigen mismatch for dnDSA discrimination, supporting further prospective evaluation of molecular mismatch-informed surveillance and immunosuppression stratification in ethnically diverse steroid-sparing kidney transplant programs.
Background: Acute myeloid leukemia (AML) remains an aggressive hematologic malignancy in which resistance to apoptosis limits the efficacy of standard chemotherapy. MicroRNA-222 (miR-222) has been implicated in leukemic cell survival and proliferation, and its inhibition may sensitize AML cells to cytotoxic treatment. Objective: To evaluate whether inhibition of miR-222 enhances the anti-leukemic effect of cytarabine in HL-60 cells and to determine associated changes in apoptosis-related and AML-relevant gene expression. Methods: HL-60 cells were transfected with locked nucleic acid anti-miR-222 (LNA-anti-miR-222). Following pilot optimization of cytarabine concentration (IC50 1.8 mu M) and LNA dose (50 pmol selected from 10-100 pmol titration), cells were assigned to five groups: untreated control, scrambled LNA control, cytarabine alone (1 mu M), LNA-anti-miR-222 alone (50 pmol), and LNA-anti-miR-222 plus cytarabine. A 3x3 concentration-response matrix was also tested. Relative miR-222 expression was quantified by SYBR Green real-time PCR using U6 normalization. Cell viability was assessed by MTT assay at 72 hours. Apoptosis was evaluated by Annexin V/7-AAD flow cytometry at 48 hours. Expression of BAX, BCL-2, MCL-1, WT1, C-KIT, and CEBPA was measured by real-time PCR (GAPDH normalization). Statistical comparisons for qPCR were performed on.Ct values. Results: LNA-anti-miR-222 effectively suppressed miR-222 expression in HL-60 cells (by approx. 74%, p<0.01). Cytarabine alone reduced cell viability to 68.3% and induced 19.4% total apoptosis, whereas miR-222 inhibition alone reduced viability to 51.6% and induced 27.5% apoptosis. The combination of LNA-anti-miR-222 and cytarabine produced the greatest reduction in viability (29.8%) and the highest apoptotic fraction (48.6%, p<0.001 vs either alone). A 3x3 concentration matrix confirmed the robustness of the enhanced effect across multiple doses, and two-way ANOVA revealed a significant interaction between the two agents (p=0.008). Combination treatment was associated with marked upregulation of BAX (4.1-fold), downregulation of BCL-2 (0.31-fold) and MCL-1 (0.52-fold), and substantial suppression of C-KIT expression (0.23-fold). WT1 showed a modest decrease (0.71-fold), whereas CEBPA did not change significantly. Conclusion: Inhibition of miR-222 enhanced the cytotoxic and pro-apoptotic activity of cytarabine in HL-60 cells across a range of concentrations. These findings support miR-222 as a potential therapeutic target in AML and suggest that miR-222 blockade may improve chemosensitivity, pending protein-level validation of the proposed mechanisms.
Introduction: In higher immunologic-risk kidney transplant recipients, tacrolimus minimization may reduce nephrotoxicity but risks rejection and dnDSA. Renin-angiotensin system (RAS) blockade may offer anti-inflammatory benefits. We assessed 24-month outcomes of standard- versus low-dose prolonged-release tacrolimus with or without ACEi/ARB. Methods: In this multicenter, prospective, open-label trial, higher-risk de novo kidney transplant recipientswere randomized to low- or standard-dose tacrolimus and to ACEi/ARB or other antihypertensive therapy (OAHT). All received basiliximab, mycophenolate, and steroids. Outcomes included survival, BPAR, dnDSA, graft function, proteinuria, protocol biopsies, and safety. Results: 320 patients were randomized; 316 received treatment. At 24 months, patient survival was 98.1% overall. Graft survival was lowest with low-dose tacrolimus+OAHT (91.1%) versus other groups (96.2-98.7%). BPAR was highest with low-dose+OAHT (25.3%) versus others (12.7-16.5%). Class II dnDSA occurred in 13.9% of low-dose+OAHT versus 5.1-7.6% in others. eGFR was similar across groups; proteinuria was lower with ACEi/ARB. Protocol biopsies showed less inflammatory fibrosis progression with low-dose+ACEi/ARB versus low-dose+OAHT. Safety was comparable; ACEi/ARB recipients had slightly lower hemoglobin. Conclusion: In higher immunologic-risk recipients, low-dose tacrolimus with early RAS blockade achieved 24-month outcomes closer to standard-dose regimens than low-dose without RAS blockade. Minimization without RAS blockade increased rejection and dnDSA, supporting further study of risk-stratified minimization with early RAS blockade.
Background and Aims: Alcohol-associated liver disease (ALD) is a leading indication for liver transplantation (LT), and many ALD recipients present with substantial physiologic acuity, renal dysfunction, and infectious risk. Tacrolimus initiation is often delayed in this setting to limit nephrotoxicity or avoid intensifying active infection, but the clinical consequences remain incompletely defined. We evaluated whether delayed tacrolimus initiation after LTwas associated with biopsy-proven acute rejection (BPAR), infectious complications, graft loss, and mortality within 12 months after transplant. Methods: We performed a single-center retrospective cohort study of adult deceased-donor LT recipients transplanted for ALD at Virginia Commonwealth University Health System between November 1, 2015 and July 31, 2023. The primary exposure was tacrolimus initiation timing: early (detectable by day 7) versus delayed (after day 7). The primary endpoint was BPAR within 12 months. Secondary endpoints included CMV DNAemia, bloodstream infection, graft loss, and mortality. To address confounding by indication, we performed propensity score matching (1:1 nearest neighbor) based on pre-transplant illness severity. Sensitivity analyses included multivariable Cox regression and stratification by MELD-Na category. Results: Among 284 included recipients, 189 (67%) had early initiation and 95 (33%) had delayed initiation. Propensity score matching produced 82 well-balanced pairs. In the matched cohort, delayed tacrolimus initiation remained associated with significantly higher BPAR (39% vs 16%, p=0.001; adjusted HR = 2.84, 95% CI 1.58-5.12, p<0.001). CMV DNAemia (30% vs 18%, p=0.04) and bloodstream infection (24% vs 12%, p=0.03) were also higher in the delayed group. Delayed initiationwas associated with increased graft loss (HR = 2.21, 95% CI 1.12-4.36, p=0.02) and all-cause mortality (HR = 2.34, 95% CI 1.14-4.81, p=0.02) in Cox regression. Results were consistent across sensitivity analyses. Conclusions: Among LT recipients with ALD, delayed tacrolimus initiation beyond post-transplant day 7 was associated with higher risk of BPAR, CMV DNAemia, bloodstream infection, graft loss, and mortality, even after rigorous adjustment for confounding by indication. These findings suggest that when clinically feasible, minimizing tacrolimus delay may improve outcomes, and that delayed initiation should prompt heightened surveillance for rejection and infection.
Living donor liver transplantation expands access to transplant and may reduce waitlist mortality among patients with end-stage liver disease, yet its use remains limited and unevenly distributed across donor subgroups. While prior national work has shown that living liver donation varies by donor-recipient relationship and demographic characteristics, the role of donor educational attainment in shaping these trends remains insufficiently studied. We examined whether growth in living liver donation in the United States from 2012 to 2022 differed jointly by donor-recipient relationship and donor educational attainment. We conducted a national registry study of living liver donors in the United States between January 1, 2012 and December 31, 2022 using Scientific Registry of Transplant Recipients data. The primary outcome was change in the annual number of living liver donors over time. Donors were stratified by donor-recipient relationship (biologically related versus unrelated), educational attainment (high school or less, technical school, bachelor's/associate degree, and graduate degree), and age (< 40 versus >= 40 years). Negative binomial regression was used to estimate the incidence rate ratio for change in donor counts per 3-year increment. A total of 4,122 living liver donors were identified during the study period, including 2,845 biologically related donors and 1,277 unrelated donors. Growth in living liver donation was uneven across educational strata. Among biologically related donors, the greatest increase was observed in donors with graduate education (IRR 1.44, 95% CI 1.31-1.58), whereas among unrelated donors, the strongest rise also occurred in donors with graduate education (IRR 1.52, 95% CI 1.38-1.67). Lower-education donor groups demonstrated the smallest increase over time, with IRRs ranging from 1.00 to 1.15, compared with 1.31 to 1.62 in higher-education strata. Age-stratified analyses showed that the largest increase occurred among unrelated donors aged < 40 years in the graduate education group (IRR 1.62, 95% CI 1.45-1.81). Living liver donation in the United States increased over the past decade, but the increase was concentrated in donor subgroups with higher educational attainment, especially among unrelated donors. These findings identify unequal growth in completed donation across donor subgroups, but they do not establish the mechanisms responsible for that pattern. Additional studies incorporating donor evaluation pathways, socioeconomic measures, and center- or region-level data are needed to clarify the processes underlying these differences.
Background: The acceptance of living kidney donor candidates with nephrolithiasis varies across transplant programs. Although radiographic stone burden and prior symptomatic episodes frequently influence donor selection, the prognostic role of urinary metabolic abnormalities in predicting symptomatic stone recurrence after donor evaluation remains insufficiently characterized. Objective: To determine whether metabolic abnormalities identified during living donor evaluation are associated with symptomatic kidney stone events after evaluation among candidates with a personal history or radiographic evidence of nephrolithiasis. Methods: We designed a retrospective cohort study of adult living kidney donor candidates evaluated at a tertiary transplant center between 2012 and 2024. Eligible candidates had either a prior symptomatic kidney stone history, asymptomatic radiographic nephrolithiasis on donor imaging, or both. Baseline variables included demographics, body mass index, prior stone history, radiographic stone burden, laterality, maximum stone diameter, and 24-hour urine metabolic parameters. Donation outcome was classified as donated, not donated because of kidney stone-related concerns, or not donated for other reasons. The primary outcome was a symptomatic kidney stone event after donor evaluation. Univariable and multivariable logistic regression models were used to identify factors associated with non-donation due to stone disease and with post-evaluation symptomatic stone recurrence. Results: Among 284 donor candidates with nephrolithiasis, 146 (51.4%) donated, 68 (23.9%) did not donate due to kidney stone-related concerns, and 70 (24.6%) did not donate for other reasons. Low urine volume, hypocitraturia, hypercalciuria, and higher radiographic stone burden were more frequent among candidates who were declined because of stone-related risk. During a median follow-up of 5.2 years, 49 candidates (17.3%) experienced a symptomatic kidney stone event after donor evaluation. In multivariable analysis, younger age (aOR 0.94 per year, 95% CI 0.91-0.98, p=0.003), two or more stones on baseline imaging (aOR 2.84, 95% CI 1.52-5.31, p=0.001), hypocitraturia (aOR 2.67, 95% CI 1.39-5.12, p=0.003), and low urine volume (aOR 2.41, 95% CI 1.26-4.60, p=0.008) were independently associated with symptomatic recurrence, whereas donation itself was not independently associated with post-evaluation symptomatic stone events. Conclusions: In living kidney donor candidates with nephrolithiasis, urinary metabolic abnormalities appear to refine recurrence risk beyond radiographic stone burden alone. Standardized metabolic evaluation may improve donor risk stratification and support more consistent transplant committee decision-making.
Background: Obesity remains a major barrier to kidney transplantation despite the survival benefit of transplantation over dialysis. This study evaluated the cost-effectiveness of four strategies for adults with end-stage kidney disease and obesity undergoing kidney transplant evaluation in the United States. Methods: A state-transition Markov cohort model was developed from the health-sector perspective. Four strategies were compared: liberal waitlisting, bariatric surgery, glucagon-like peptide-1 receptor agonist therapy, and intensive lifestyle management. Inputs were drawn from publicly available evidence published between 2015 and 2023. The primary outcome was the incremental cost-effectiveness ratio per quality-adjusted life-year gained. Results: Over a 10-year horizon, liberal waitlisting had the lowest discounted cost ($246,100), whereas bariatric surgery had the highest discounted effectiveness (4.891 quality-adjusted life-years). Compared with liberal waitlisting, bariatric surgery increased cost by $35,400 and effectiveness by 0.079 quality-adjusted life-years, yielding an incremental cost-effectiveness ratio of $448,101 per quality-adjusted life-year gained, above conventional U.S. willingness-to-pay thresholds. Glucagon-like peptide-1 receptor agonist therapy improved outcomes versus lifestyle management but remained less efficient than bariatric surgery. Conclusions: Liberal waitlisting was the economically preferred strategy in the 10-year base-case analysis. Bariatric surgery produced the greatest health gain but was not cost-effective relative to liberal waitlisting, while glucagon-like peptide-1 receptor agonist therapy improved on lifestyle management without surpassing the other strategies in overall economic performance.
