Despite recent progresses in microbiome and infection, the role of multi-kingdom gut microbiome in kidney transplantation (KT) infection remains unexplored. Here we performed a longitudinal and integrative multi-omics analysis of the gut microbiome, fecal metabolome and plasma metabolome in 169 KT recipients across 5 different transplantation centers, comprising discovery and validation cohorts. We observed KT-specific four kingdom microbiome dysbiosis, including bacteria, fungi, archaea and viruses, with the most pronounced shifts in bacterial and fungal communities. Furthermore, we identified 6 infection-associated co-abundance groups (CAGs) composed of 23 bacterial and 3 fungal species, highlighting extensive bacterial-fungal interactions. Interestingly, infection-associated fecal metabolomic pattern F1, enriched in N-acetylputrescine and hydroxyproline, was positively correlated with Enterococcus-, Citrobacter- and Lactococcus-dominated CAGs, as well as the plasma metabolite signature, represented by phenylacetyl-l-glutamine, indoxyl sulfate and leukotriene. In contrast, cholesterol sulfate and menadione in plasma were aligned with fecal indoleacetic acid and stachyose, a metabolic signature more characteristic of non-infected recipients. Finally, the combinatorial biomarkers of fungal and bacterial species achieved powerful diagnosis ability of KT infection in an independent validation cohort (area under the receiver operating characteristic curve (AUROC) = 0.80) with the fecal metabolites achieving high accuracy (AUROC = 0.83). Collectively, our findings not only uncovered the postoperative infection-specific multi-kingdom microbial network dynamics, but also revealed the microbial and its metabolic biomarkers with powerful diagnostic ability for postoperative infection in kidney transplantation.
Opportunistic infections after organ transplantation require frequent monitoring over years. However, current diagnostic tests are inaccessible to patients in resource-limited settings. Here, we present a microfluidic-enhanced nucleic acid test for on-site reporting (MONITOR), a fully integrated, sample-in-answer-out platform for point-of-care (POC) detection of opportunistic infections. MONITOR employs a gene-specific DNAzyme that, upon integration with recombinase polymerase amplification, enables CRISPR-like trans-cleavage signal amplification with single-molecule sensitivity. It further incorporates a rapid, extraction-free protocol for processing the urine sample, lyophilized assay reagents for cold-chain-free storage and transportation, and a 3D-printed microfluidic cartridge for self-contained, contamination-free fluid handling. A portable real-time fluorescence reader and smartphone application are further developed to enable on-site quantification. Clinical validation showed complete concordance with qPCR across the tested cohorts and a field trial identified high-risk patients with systemic BK polyomavirus infection. MONITOR fulfills ideal criteria for POC testing, offering a practical solution for decentralized, quantitative viral monitoring in low-resource settings. Opportunistic infections are among the leading causes of graft loss for organ transplant recipients. Here authors introduce a protein-free CRISPR-like assay platform called MONITOR, which, when combined with pre-amplification, achieves single-molecule sensitivity, enabling sample-in-answer-out quantification of post-transplant infections in resource-limited settings.
ABSTRACT Cell‐specific detection of aberrant mRNA in blood is essential for diagnosing and treating hematological malignancies. However, current sensors are unable to function in unprocessed whole blood due to limitations in chemical stability and cell‐targeting capability. Here, we engineer a cell‐resolved ultrastable sensor for hematology (CRUSH) via spherical‐nucleic‐acid (SNA) technology, which enables live‐cell detection of leukemia fusion transcripts in unprocessed whole blood. CRUSH employs stoichiometrically controlled thiol protector to achieve a defect‐free thiol monolayer on AuNPs. This design feature endows CRUSH with a record‐breaking stability, withstanding 0.1 M dithiothreitol, a 10,000‐fold improvement over conventional SNAs. We also demonstrate that the phagocytic bias of myeloid cells over lymphoid cells drives selective internalization of CRUSH in myeloid lineages in whole blood. Leveraging cellular selectivity and engineered stability, CRUSH offers a mixed‐and‐read diagnostic test, where lyophilized sensors are directly mixed with whole blood samples, followed by standard flow cytometry analysis. This one‐step test detects BCR‐ABL1 fusions in living myeloid cells with high specificity and robustness, enabling accurate discrimination of multilineage acute lymphoblastic leukemia within 1 h. Our study bridges biosensing innovation with urgent diagnostic needs, offering a rapid, specific, and robust tool for accurate diagnosis and treatment of hematologic malignancies.
Background: The use of hepatitis B surface antigen-positive (HBsAg+) kidneys may expand the donor pool for transplantation. This study evaluated the incidence, risk factors, complications, organ function, and survival outcomes of transplants from HBsAg+ donors to HBsAg- recipients. Methods: A systematic search of five databases was conducted through 20 August 2023. Incidence was expressed with 95% confidence intervals (CIs); odds ratios (ORs) and hazard ratios (HRs) assessed risk factors and survival. Results: Sixteen studies were included. Donor-derived HBV infection occurred in 3.60% (21/583). Risk was higher in HBsAb-negative (OR: 6.67, 95% CI: 1.08-41.10) and HBcAb-negative recipients (OR: 12.96, 95% CI: 2.06-81.69). Abnormal liver function occurred in 35.18%, hepatitis in 3.07%, and hepatic failure in 0.84%. Liver and kidney function at 1-3 years were comparable between HBsAg+ and HBsAg- kidney recipients. Five- and ten-year graft survival (85.2%, 82.7%) and patient survival (93.0%, 91.4%) were similar to controls (p > 0.05). Conclusions: HBsAg+ kidneys can achieve acceptable long-term outcomes with appropriate antiviral prophylaxis and cautious recipient selection, though infection risk requires careful assessment. These findings supports the cautious and selective use of HBsAg-positive kidneys in appropriately selected recipients use and standardized HBV prophylaxis.
The use of single-cell combinatorial indexing sequencing via droplet microfluidics presents an attractive approach for balancing cost, scalability, robustness and accessibility. However, existing methods often require tailored protocols for individual modalities, limiting their automation potential and clinical applicability. To address this, we introduce UDA-seq, a universal workflow that integrates a post-indexing step to enhance throughput and systematically adapt existing droplet-based single-cell multimodal methods. UDA-seq was benchmarked across various tissue and cell types, enabling several common multimodal analyses, including single-cell co-assay of RNA and VDJ, RNA and chromatin, and RNA and CRISPR perturbation. Notably, UDA-seq facilitated the efficient generation of over 100,000 high-quality single-cell datasets from three dozen frozen clinical biopsy specimens within a single-channel droplet microfluidics experiment. Downstream analysis demonstrated the robustness of this approach in identifying rare cell subpopulations associated with clinical phenotypes and exploring the vulnerability of cancer cells. UDA-seq incorporates a post-indexing step to enhance the throughput of droplet-based single-cell multimodal sequencing, enabling efficient large-scale single-cell analysis.
OBJECTIVE:This study aims to comprehensively evaluate the safety profile of belatacept administration in real-world clinical settings. METHODS:Disproportionality analysis methodologies, including Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-Item Gamma Poisson Shrinker (MGPS) algorithms, were utilized to quantify real-world adverse event (AE) signals associated with belatacept. RESULTS:A total of 4631 adverse event reports were extracted from the FDA Adverse Event Reporting System (FAERS) database, of which 2337 adverse events were identified as "primary suspect" (PS) attributed to belatacept. Belatacept-related adverse events involved 27 system organ classes (SOCs). Common adverse reaction preferred terms (PTs) consistent with the FDA label for belatacept identified in FAERS analysis included anemia (PT: 10019281), diarrhea (PT: 10012736), and urinary tract infection (PT: 10046577). Notably, several potential novel or off-label adverse event signals were detected in the analysis, including multiple organ transplant rejection (ROR = 976.42), tertiary syphilis (ROR = 901.31), removal of renal transplant (ROR = 857.72), perinephric fluid collection (ROR = 563.03), graft loss (ROR = 549.26), polyomavirus positive (ROR = 548), subcapsular renal hematoma (ROR = 475.53), renal transplant rejection (ROR = 293.73), renal transplant failure (ROR = 204.27), polyomavirus viremia (ROR = 203.62), renal vein thrombosis (ROR = 171), renal transplant infection (ROR = 168.26), injection (ROR = 154.2), and graft hemorrhage (ROR = 152.17). The distribution of adverse event reports varied across populations. Most reports were submitted by consumers (P = .0099), and females were predominantly represented. There was a significant age difference between female and male patients (P = .035). CONCLUSION:This study identifies potential novel adverse event signals for belatacept within the FAERS database, and highlights age, sex differences, and comorbidity complexity in adverse event distribution, providing essential references for clinical drug safety and subsequent mechanistic research.
ABO-incompatible kidney transplantation is widely used to meet the escalating need for organs. Current recipient-centric desensitization protocols involving antibody depletion through plasmapheresis increase the risk of infections, perioperative bleeding events and costs. Here we present a donor-centric desensitization protocol, converting type-A kidneys into enzyme-converted O kidneys during hypothermic perfusion to remove the A antigen from the kidneys. An ex vivo model resulted in no antibody-mediated injury. Encouraged by this, an enzyme-converted O kidney was transplanted into a type-O brain-dead recipient with a high titre of anti-A antibody, and no hyperacute rejection was observed. The graft was well tolerated with no evidence of antibody-mediated rejection for 2 days. Antibody-mediated lesions and complement deposition were found starting 3 days post-transplant, coinciding with A-antigen regeneration, and later higher Banff scores, suggesting an immune-mediated response. Single-cell sequencing confirms the elevated expression of accommodation-related genes, suggesting the potential for longer-term tolerance. This study provides a donor-centric organ engineering strategy and has the potential to broaden the reach of ABO-incompatible kidney transplantation, improving the fairness of and access to organ allocation. An ex vivo model and pre-clinical study in a brain-dead recipient provide enzyme-converted O organs to avoid hyperacute rejection in ABO-incompatible kidney transplant patients.
PURPOSE:Whether robot-assisted kidney transplantation (RAKT) using grafts with multiple arteries (GMAs) is feasible has rarely been examined. This study shares our experience with RAKT using GMAs from living donors, focusing on assessing the technical feasibility and early postoperative outcomes. MATERIALS AND METHODS:Between July 2020 and January 2024, we prospectively collected data from consecutive patients undergoing living donor RAKT in our center. We retrospectively analyzed the clinical data of patients who underwent RAKT using grafts with a single artery (GSA) or GMAs. All vascular reconstructions of grafts with multiple arteries were performed ex vivo on the bench in iced slush, followed by robotic anastomosis of the single reconstructed artery to the external iliac artery. RESULTS:A total of 212 living donor RAKT procedures were performed by two experienced surgeons at a single institution. Using propensity score analysis, 125 recipients of grafts with a single artery (the GSA group) were selected and compared with 25 recipients of grafts with multiple renal arteries (the GMA group). There were no significant differences in the perioperative parameters or graft function outcomes between the GMA and GSA groups. Although the median operative time and revascularization ischemia times were higher in the GMA cohort, the differences were not statistically significant (200 versus 190 min, p = 0.5, and 60 versus 55 min, p = 0.8, respectively). No major intra- or postoperative complications were recorded in the GMA cohort. Additionally, there were no instances of graft loss or mortality during the follow-up period in either group. CONCLUSIONS:This study, the largest single-center study of RAKT from living donors utilizing GMAs, demonstrates the technical feasibility of this approach, achieving optimal perioperative and early functional outcomes. TRIAL REGISTRATION:ClinicalTrials.gov identifier: NCT06577805.
Matching ABO blood group antigens between donors and recipients is critical to prevent hyperacute rejection in kidney transplantation. Enzymatic conversion of blood group antigens to the universal O type presents a promising strategy to overcome barriers in ABO-incompatible kidney transplantation. In this study, we employ α-galactosidase from Bacteroides fragilis to convert type B kidneys to type O during hypothermic machine perfusion. After 3 hours of perfusion with enzyme, more than 95% of blood group B antigens in the kidney endothelium are effectively removed. Subsequently, enzyme-treated kidneys are protected from antibody-mediated injuries in an ex vivo simulation of ABO-incompatible kidney transplantation. Encouraged by these results, a discarded type B kidney, following enzymatic conversion, is transplanted into a type O brain-dead recipient with high titer of anti-B antibody. The allograft survives for 63 hours without hyperacute rejection. Blood group B antigens re-express within 48 hours, with histopathological analyses indicating no evidence of antibody-mediated rejection. This enzymatic conversion approach holds the potential to broaden the practice of ABO-incompatible kidney transplantation, decrease waiting times and facilitate equitable organ allocation. The complexity of matching ABO blood groups presents a formidable barrier to successful transplantation. Here, the authors show that an enzymatic converted type B kidney was transplanted into a type O brain-dead recipient without hyperacute rejection.
Background:Kidney transplant recipients continue to face a significant long-term risk of death-censored allograft failure (DCGF). We aimed to evaluate early donor renal function recovery following living-donor nephrectomy and investigate their relationship with long-term allograft outcomes. Methods:We conducted a longitudinal cohort and machine learning study by including consecutive living-donor kidney transplantations between January 1, 2007, and December 31, 2022 from West China Hospital. Early renal function recovery was defined as the donor creatinine relative change (dCRC), calculated as the ratio of the difference between pre-donation creatinine and post-donation creatinine to the pre-donation creatinine. We examined the risk of 10-year DCGF from electronic medical records. We employed Cox regression, XGBoost, and Random Forest models to determine whether dCRC could enhance the predictive value of the established iBOX score. Model performance was assessed using Area Under the Receiver Operating Characteristic (ROC) curve (AUC). Findings:Among 3241 transplantations screened, 2575 cases were included (mean recipient age 32.5 years). After a median follow-up of 85.5 months after transplantation, 113 recipients (4.4%) experienced DCGF. The median dCRC were 21.1% (IQR: 7.1%-36.8%). Receiver Operator curves reported stronger associations between dCRC and DCGF compared with predonation creatinine (AUC: 0.689 vs. 0.504, P = 0.0082). Each 10% increase in dCRC corresponded to 36.7% higher DCGF risk (HR 1.367, 95% CI 1.262-1.479, P < 0.0001), with a J-shaped dose-response relationship. This association persisted across pre-donation eGFR and post-donation eGFR (<90 vs. ≥ 90 mL/min/1.73 m2). Last, incorporating dCRC significantly improved the prediction of 10-year DCGF beyond the iBOX alone by multivariable Cox analysis (AUC: 0.868 [95% CI: 0.816-0.920] vs. 0.765 [95% CI: 0.682-0.848], P = 0.0017), XGBoost (AUC: 0.840 [95% CI: 0.765-0.914] vs. 0.727 [95% CI: 0.632-0.822], P = 0.0029), and Random Forest (AUC: 0.857 [95% CI: 0.792-0.921] vs. 0.701 [95% CI: 0.608-0.794], P < 0.0001) in the testing cohort. Interpretation:Early donor renal function recovery represents an alternative predictor of death-censored graft failure after living-donor kidney transplantation. This index may enhance risk prediction when integrated with established models. The predominantly young recipient population may limit generalizability to older transplant candidates. Funding:None.
BACKGROUND:Weight management was recommended to have more access to transplantation and improve transplant outcomes after liver transplantation (LT). However, the dose-response relationship between body mass index (BMI) and transplant outcomes has not been clearly defined. METHODS:PubMed, Embase, Web of Science, and Cochrane Library databases were searched up to October 20th, 2019. Dose-response meta-analyses was conducted to establish the dose-response relationship pattern. RESULTS:Twenty-three observational studies were eligible. In the pair-wise analysis, compared with normal BMI, HRs in underweight, overweight, obesity-I, obesity-II, and obesity-III were 2.13, 0.96, 1.06, 1.36, and 1.97 for patient death, and 3.08, 1.02, 1.25, 1.58, and 2.90, for graft loss. In the dose-response analysis, U-shaped relationships were observed between BMI and both patient and graft survival (P < .001, P < .001). Referring to 17.5kg/m2, the patient death risk decreased to 0.72 (95% CI: 0.62-0.84) in 27kg/m2 and then increased to 1.44 (95% CI:1.09-1.90) in 28.7-42kg/m2. Comparing to 17.5kg/m2, individuals in 26.7-28.0kg/m2 had the least risk of graft loss with HR of 0.62 (95% CI:0.48-0.80) and increased to 1.64 (95% CI:1.03-2.61) in 42kg/m2. Subgroup analyses by age, sex, sample size, duration of follow-up, location, publication year, and study type presented similar results. CONCLUSION:Underweight and severe obesity are associated with a significantly increased risk of graft loss and patient death after liver transplantation. Overweight, especially BMI of 26-28 kg/m2, may have extra survival benefit. Weight management before liver transplantation may be necessary.
Background: Human umbilical cord mesenchymal stem cells derived extracellular vesicles (HUMSC-EVs) have drawn much interest in kidney transplantation, mainly because of their renoprotection by alleviating cell injury and stimulating tissue repair. Cellular senescence has been proven to play a dual regulatory role in kidney ischemia-reperfusion injury (IRI), and the regulation of HUMSC-EVs on tubular epithelial cell senescence may be a potential therapeutic target. Materials and methods: In vitro, the hypoxia-reoxygenation of human kidney-2 cells was used to simulate kidney IRI, and the regulation of HUMSC-EVs on human kidney-2 cells was detected. Transcriptome sequencing of human kidney-2 cells was used to explore the potential regulatory mechanism. In vivo, adult male mice were divided into five groups: control group, IRI group, HUMSC-EVs treatment group, senolytics treatment group (dasatinib + quercetin), and combined treatments group (HUMSC-EVs and senolytics). Kidney function, senescent features of tubular epithelial cells, acute kidney injury, and chronic interstitial fibrosis in mice were detected to explore the renoprotection effects of HUMSC-EVs. Results: Kidney IRI significantly up-regulated expressions of LaminB1, p53, p21, p16, senescence-associated beta-galactosidase, and apoptosis of tubular epithelial cells. In the mouse kidney IRI model, kidney subcapsular injection of HUMSC-EVs significantly improved kidney function, reducing the senescent features of tubular epithelial cells and alleviating acute kidney injury and chronic interstitial fibrosis. HUMSC-EVs mainly achieved renoprotection by regulating Bax/Bcl-2-dependent apoptosis during acute kidney injury and mostly reduced tubular atrophy and kidney interstitial fibrosis by regulating Ras-pERK-Ets1-p53 pathway-dependent cell senescence. Oral administration of senolytics also alleviated kidney injury induced by IRI, while the combined treatments of HUMSC-EVs and senolytics had better renoprotection effects. Conclusions: The combination of HUMSC-EVs and senolytics alleviated acute kidney injury and chronic interstitial fibrosis by dynamic regulation of cell senescence and apoptosis, which provides a therapeutic potential strategy for organ preservation and tissue repair in kidney transplantation.
In our investigation, we aimed to shed light on the role of senescent cells in renal fibrosis, considering the observed correlation between renal tubular epithelial cell senescence and the presence of renal fibrosis. Our findings confirm the manifestation of senescence characteristics in renal tubular epithelial cells during renal fibrosis and establish their capacity to trigger a transition from macrophages to myofibroblasts, known as macrophage-myofibroblast transition (MMT). Additionally, our study uncovered that extracellular vesicles released by senescent HK-2 cells (sHK-2) play a pivotal role in facilitating MMT. Subsequently, we investigated the miRNA profile in sHK-2-derived extracellular vesicles (sHK-2-EVs) and confirmed the elevated abundance of specific miRNAs, including miR-20a-5p and miR-21-5p, compared to normal HK-2-EVs. Notably, these miRNAs possess the capability to induce M2-like polarization in macrophages and enhance the expression of TGF-β. Moreover, TGF-β can stimulate macrophages to produce miR-20a-5p and miR-21-5p, establishing a positive feedback loop that amplifies the TGF-β/Smad pathway and facilitates the process of macrophage-myofibroblast transition.
Background: Robot-assisted kidney transplantation (RAKT) surgery is an advanced minimally invasive technique, albeit with extended surgical and kidney ischemia time. To safeguard kidney function, the authors have devised a continuous surface cooling method (CSCT) for intraoperative kidney cooling. Materials and methods: Patients receiving RAKT were divided into CSCT group and conventional group. The CSCT is a custom-designed apparatus composed of a single-layer plastic bag, featuring an inflow and an outflow that create a closed circuit for the continuous flow of cooling saline. The conventional group utilized ice slush for kidney graft cooling (Vattikuti Urology Institute-Medanta Technique, VUIMT). Patients who underwent open renal transplantation during the same period were also included in the study. All patients were subject to a minimum 2-month follow-up. And 1:3 propensity score matching was used to minimize selection bias. Results: A total of 144 patients underwent CSCT, 47 underwent VUIMT, and 196 underwent open surgery were included in the study, while after matching, 129, 43, 129 patients were included in the three groups, respectively. The median follow-up time was 19 months. None of the patients experienced delayed graft function, patient mortality, or graft loss. After introducing the kidney into the abdominal cavity for 20 minutes, the surface temperature of the kidney in the CSCT group was notably lower compared to the VUIMT group (15.42 +/- 0.88 vs. 21.74 +/- 2.53 degrees C, P=0.001). This temperature disparity became more pronounced at 65 min (19.74 +/- 1.61 vs. 29.82 +/- 1.63 degrees C, P<0.001). At both 3 and 7 days post-transplantation, creatinine levels in the VUIMT group were significantly higher than those in the CSCT and open surgery groups (at 3 days, 244.13 +/- 45.61 vs. 182.51 +/- 55.47 in CSCT group, P<0.001, or vs. 182.77 +/- 61.32 in the open surgery group, P<0.001; at 7 days, 162.42 +/- 54.86 vs. 143.11 +/- 44.32 in the CSCT group, P<0.001, or vs. 135.23 +/- 45.27 in the open surgery group, P<0.001). No differences were observed in blood creatinine, estimated glomerular filtration rate, and perioperative complications between the CSCT and open surgery groups. Conclusion: The CSCT presents a significant advantage over the traditional VUIMT method in terms of kidney cooling and early postoperative kidney function preservation. Additional research is required to ascertain whether the CSCT can enhance the long-term prognosis of kidney transplant recipients.
We aim to establish diagnostic thresholds of sarcopenia and myosteatosis based on CT measurements, and to validate their prognostic value in a large cohort of kidney transplant recipients. Local healthy population with abdominal CT between 2010 and 2022, and patients underwent kidney transplantation between 2015 and 2019 at our center were retrospectively included. The skeletal muscle index and muscle attenuation of abdominal muscles were calculated based on CT image at the middle of the third lumbar vertebra. Primary endpoints included all-cause mortality and death censored allograft survival. Age- and sex-specific thresholds for sarcopenia and myosteatosis were established based on 1598 healthy local population. The final patient cohort consisted of 992 kidney transplant recipients (median age 34 years, interquartile range 28–44 years; 694 males), including 33 (3.3
BACKGROUND:The potential of Tocilizumab (TCZ) in preventing the cytokine storm caused by COVID-19 infection has been observed, while the survival benefits were inconclusive in solid-organ transplant recipients. We aimed to explore whether the timing of TCZ administration holds significance in the clinical course of COVID-19 infection and identify predicative factors of TCZ efficacy. METHODS:We conducted a prospective cohort study between December 2022, and January 2023. Early TCZ use referred to administration within 6 days after symptoms onset, while late TCZ use indicated administration after 6 days. The primary endpoint was 30-day mortality. RESULTS:Twenty-seven kidney transplant recipients with severe COVID-19 infection were enrolled, with 10 in the early use group and 17 in the late use group. In the early use group, ferritin, lactate dehydrogenase (LDH), C-reactive protein (CRP) and brain natriuretic peptide(BNP) levels had shown significant inhibitions comparing to the late use group, and those inflammatory cytokines demonstrated a noticeable decreasing trend after TCZ administration, whereas only CRP levels decreased in the late use group. The Kaplan-Meier survival curve demonstrated that the early use group had a higher likelihood of survival (P = 0.0078). Receiver Operating Characteristic (ROC) analyses revealed that the time from symptoms to TCZ use (AUC: 0.645), LDH (AUC: 0.803), CRP (AUC: 0.787), and IL-6 (AUC: 0.725) were potential predictive factors of TCZ efficacy. TCZ use within 6 days from symptoms onset, with CRP < 73.5 mg/L, LDH < 435.5 IU/L, and IL-6 < 103.5 pg/mL, had higher survival rates (P = 0.008, P = 0.009, P < 0.001, P < 0.001). CONCLUSION:This study highlights the survival benefits of early TCZ use and the predicative role of cytokines levels in predicting TCZ efficacy in kidney transplant recipients with severe COVID-19 infection.
Background:The impact of different pretransplant dialysis modalities on post-transplant outcomes for pancreas-kidney transplantation is currently unclear. This study aims to assess the association between pretransplant dialysis modalities [hemodialysis (HD) and peritoneal dialysis] and outcomes following pancreas-kidney transplantation.Methods:The authors searched PubMed, EMBASE, and the Cochrane Library for relevant studies published from inception until 1 December 2023. The authors included studies that examined the relationship between pretransplant dialysis modalities and clinical outcomes for pancreas-kidney transplantation. The primary outcomes considered were patient, pancreas and kidney graft survival, and intra-abdominal infection.Results:A total of 13 studies involving 1503 pancreas-kidney transplant recipients were included. Pretransplant HD was associated with improved pancreas graft survival (hazard ratio = 0.71, 95% confidence interval: 0.51-0.99, I-2=12%) and a decreased risk of intra-abdominal infection [odds ratio (OR)=0.69, 95% CI: 0.51-0.93, I-2=5%). However, no significant association was found between the dialysis modalities and patient or kidney graft survival. Furthermore, pretransplant HD was linked to a reduced risk of anastomotic leak (OR=0.32, 95% CI: 0.161-0.68, I-2=0%) and graft thrombosis (OR=0.56, 95% CI: 0.33-0.96, I-2=20%).Conclusion:Pretransplant HD is the preferred dialysis modality while awaiting pancreas-kidney transplantation, although well-designed prospective studies are needed to confirm these findings.