Background: Catheter-related infections, such as exit-site infection and tunnel infection, are major complications in peritoneal dialysis (PD) patients, affecting their prognosis. This study investigates the association between skin conditions and catheter-related infections.Methods: Data from two distinct sources were analyzed: (1) 626 PD patients in the Korean arm of the Peritoneal Dialysis Outcomes and Practice Patterns Study (PDOPPS) and (2) skin microbiome data from 76 dialysis patients at Soonchunhyang University Cheonan Hospital. The relationship between catheter-related infection and self-reported xerosis and pruritus severity was assessed by Cox regression. Risk factors for xerosis and pruritus were evaluated by logistic regression. Furthermore, we discovered the relationship between the severity of pruritus and the relative abundance of Staphylococcus aureus on the skin.Results: The risk of catheter-related infections in PD patients increased with xerosis (hazard ratio [HR], 2.71; 95% confidence interval [CI], 1.19–6.18) and pruritus (HR, 2.57; 95% CI, 1.27–5.22), particularly increasing the risk of S. aureus-associated catheter-related infections (xerosis: HR, 5.66; 95% CI, 1.97–16.30; pruritus: HR, 5.93; 95% CI, 2.18–16.15). The relative abundance of S. aureus was notably higher in patients with severe pruritus. Moreover, patients were more likely to exhibit severe xerosis if they owned pets, had higher serum creatinine levels, and elevated calcium-phosphorus product levels.Conclusion: Xerosis and pruritus significantly increase the risk of catheter-related infections, especially those caused by S. aureus. Instead of relying solely on prophylactic antibiotics for infection prevention, this study highlights the need for new preventive strategies in PD patients, focusing specifically on effective skin management.

With rising pet ownership, concerns regarding pet-related infections during peritoneal dialysis (PD) have increased. This retrospective study analyzed the characteristics of PD-related infections according to pet ownership. A total of 162 PD patients treated at Soonchunhyang University Cheonan Hospital between 2016 and 2023 were reviewed. Patients were grouped by pet ownership and pet type (dog or cat) based on data obtained from PD nurse home visits. Peritonitis, exit-site infection (ESI), and tunnel infection (TI) were defined according to the International Society of Peritoneal Dialysis guidelines, and data on causative organisms and clinical outcomes were collected. Zoonotic microorganism-associated peritonitis episodes were identified in patients with pets. Staphylococcus-associated ESIs (55.6 vs. 16.2%, p = 0.006) were more frequently observed in patients with pets than in those without pets. However, the overall incidence of peritonitis and ESI did not differ significantly between patients with and without pets, and pet ownership was not associated with mortality or PD catheter removal. These findings suggest that while pet ownership may influence the microbial characteristics of PD-related infections, it does not appear to increase overall infection incidence or adverse clinical outcomes.

Background:The independent impact of type 2 diabetes mellitus (T2DM) on kidney outcomes beyond albuminuria remains unclear. We evaluated whether T2DM affects kidney outcomes in individuals with normal kidney function without albuminuria. Methods:Data from the National Health Insurance Service-National Sample Cohort of Korea (2009-2015) were analyzed. Individuals with normal kidney function were stratified by T2DM status. The primary outcome was a composite kidney outcome consisting of initiation of kidney replacement therapy and a sustained decline in estimated glomerular filtration rate (eGFR) of ≥40% from baseline. Results:Among 77,267 individuals with normal kidney function without albuminuria, patients with T2DM (n = 11,957) showed significantly steeper annual decline in eGFR than non-T2DM individuals (-0.113 mL/min per 1.73 m2 per year; 95% confidence interval [CI], -0.222 to -0.003). T2DM was associated with a 57% higher risk of composite kidney outcome (adjusted hazard ratio, 1.57; 95% CI, 1.28-1.92), independent of traditional risk factors. This association was strongest in individuals with glomerular hyperfiltration and longer T2DM duration (≥6 years). Conclusion:Normal kidney function T2DM was associated with accelerated kidney function decline and a 1.5-fold increased risk of adverse kidney outcomes compared with normal kidney function non-T2DM, particularly in individuals with glomerular hyperfiltration and longer duration.

In 1990 R. Curto introduced the notion of n-hyponormality which provides a bridge between subnormal and hyponormal operators. The study of n-hyponormal weighted shifts has been well developed by several mathematicians. In this paper we introduce a property CP(n) for weighted shifts related to (n + 1) x (n + 1) conditionally positive definite matrices, which generalizes n-hyponormality for weighted shifts. First the flatness of a weighted shift with properties CP (2) and CP (3) is considered, yielding a result which generalizes previous work. A formula for property CP(n) is constructed, which distinguishes the classes of weighted shifts with property CP(n). We introduce an algorithm to construct weighted shifts with property CP(n) and detect the structure related to property CP(n). Finally, we discuss property CP(n) of a homographic-type weighted shift with a constraint condition. (c) 2025 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.

BACKGROUND:Chronic kidney disease (CKD)-associated pruritus is a severe distressing condition that frequently occurs in patients undergoing dialysis. In this study, the profile of the skin microbiome was analyzed to understand the underlying etiology and potential treatments. METHODS:Seventy-six end-stage kidney disease (ESKD) patients (hemodialysis, 40; peritoneal dialysis, 36) and 15 healthy controls were enrolled and swabbed at three sites: back, antecubital fossa, and shin. The pruritus severity of the enrolled subjects was validated by the Worst Itch Numeric Rating Scale (WI-NRS), 5-D itch scale, and Uremic Pruritus in Dialysis Patients (UP-Dial). The 16S genebased metagenomics method was applied to skin microbiome analysis. RESULTS:In the comparison of bacterial communities of ESKD patients and the control group, there was a significant difference on back. Specifically, the average composition ratio of the Cutibacterium in the back samples was significantly lower in ESKD patients than in healthy controls (p < 0.01). In further analysis of ESKD patients, Cutibacterium was significantly lower in the high pruritus group than in the low pruritus group (p < 0.05), even though other clinical parameters such as age, calcium-phosphorus product, and intact parathyroid hormone showed no significance difference between the groups. CONCLUSION:In ESKD patients, the skin microbiome of the back was significantly altered, and the severity of itching was related to the reduction of Cutibacterium. This research reveals the relationship between skin microbiota and CKD-associated pruritus in multiple skin sites for the first time. The results of this study suggest a potential data basis for the diagnosis and treatment of CKD-associated pruritus.

Rationale: Peritonitis caused by Pantoea agglomerans is a rare occurrence in patients undergoing peritoneal dialysis. Cases potentially linked to pet dogs are even rarer, and there is limited literature available. Patient concerns: A patient undergoing peritoneal dialysis presented with symptoms of peritonitis, including abdominal pain and cloudy dialysis fluid. Diagnoses: Microbiological analysis identified P agglomerans as the causative organism. Interventions: The patient was treated with targeted antibiotic therapy and showed a positive response. Outcomes: During a subsequent medical interview, it was revealed that the patient had close contact with their pet dog, raising the possibility that the infection may have been associated with this exposure. Lessons: This case highlights the importance of considering zoonotic transmission as a potential source of infection in peritoneal dialysis patients, particularly when there is close contact with pets. Healthcare providers should educate patients about the potential risks posed by pets and implement preventive strategies to mitigate such risks.

BACKGROUND:Receptor-interacting protein kinase (RIPK)3 is an essential molecule for necroptosis and its role in kidney fibrosis has been investigated using various kidney injury models. However, the relevance and the underlying mechanisms of RIPK3 to podocyte injury in albuminuric diabetic kidney disease (DKD) remain unclear. Here, we investigated the role of RIPK3 in glomerular injury of DKD. METHODS:We analyzed RIPK3 expression levels in the kidneys of patients with biopsy-proven DKD and animal models of DKD. Additionally, to confirm the clinical significance of circulating RIPK3, RIPK3 was measured by ELISA in plasma obtained from a prospective observational cohort of patients with type 2 diabetes, and estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR), which are indicators of renal function, were followed up during the observation period. To investigate the role of RIPK3 in glomerular damage in DKD, we induced a DKD model using a high-fat diet in Ripk3 knockout and wild-type mice. To assess whether mitochondrial dysfunction and albuminuria in DKD take a Ripk3-dependent pathway, we used single-cell RNA sequencing of kidney cortex and immortalized podocytes treated with high glucose or overexpressing RIPK3. RESULTS:RIPK3 expression was increased in podocytes of diabetic glomeruli with increased albuminuria and decreased podocyte numbers. Plasma RIPK3 levels were significantly elevated in albuminuric diabetic patients than in non-diabetic controls (p = 0.002) and non-albuminuric diabetic patients (p = 0.046). The participants in the highest tertile of plasma RIPK3 had a higher incidence of renal progression (hazard ratio [HR] 2.29 [1.05-4.98]) and incident chronic kidney disease (HR 4.08 [1.10-15.13]). Ripk3 knockout improved albuminuria, podocyte loss, and renal ultrastructure in DKD mice. Increased mitochondrial fragmentation, upregulated mitochondrial fission-related proteins such as phosphoglycerate mutase family member 5 (PGAM5) and dynamin-related protein 1 (Drp1), and mitochondrial ROS were decreased in podocytes of Ripk3 knockout DKD mice. In cultured podocytes, RIPK3 inhibition attenuated mitochondrial fission and mitochondrial dysfunction by decreasing p-mixed lineage kinase domain-like protein (MLKL), PGAM5, and p-Drp1 S616 and mitochondrial translocation of Drp1. CONCLUSIONS:The study demonstrates that RIPK3 reflects deterioration of renal function of DKD. In addition, RIPK3 induces diabetic podocytopathy by regulating mitochondrial fission via PGAM5-Drp1 signaling through MLKL. Inhibition of RIPK3 might be a promising therapeutic option for treating DKD.

Toxin- and drug-induced tubulointerstitial nephritis (TIN), characterized by interstitial infiltration of immune cells, frequently necessitates dialysis for patients due to irreversible fibrosis. However, agents modulating interstitial immune cells are lacking. Here, we addressed whether the housekeeping enzyme glutamyl-prolyl-transfer RNA synthetase 1 (EPRS1), responsible for attaching glutamic acid and proline to transfer RNA, modulates immune cell activity during TIN and whether its pharmacological inhibition abrogates fibrotic transformation. The immunological feature following TIN induction by means of an adenine-mixed diet was infiltration of EPRS1high T cells, particularly proliferating T and γδ T cells. The proliferation capacity of both CD4+ and CD8+ T cells, along with interleukin-17 production of γδ T cells, was higher in the kidneys of TIN-induced Eprs1+/+ mice than in the kidneys of TIN-induced Eprs1+/- mice. This discrepancy contributed to the fibrotic amelioration observed in kidneys of Eprs1+/- mice. TIN-induced fibrosis was also reduced in Rag1-/- mice adoptively transferred with Eprs1+/- T cells compared to the Rag1-/- mice transferred with Eprs1+/+ T cells. The use of an EPRS1-targeting small molecule inhibitor (bersiporocin) under clinical trials to evaluate its therapeutic potential against idiopathic pulmonary fibrosis alleviated immunofibrotic aggravation in TIN. EPRS1 expression was also observed in human kidney tissues and blood-derived T cells, and high expression was associated with worse patient outcomes. Thus, EPRS1 may emerge as a therapeutic target in toxin- and drug-induced TIN, modulating the proliferation and activity of infiltrated T cells.

Proton pump inhibitors (PPIs) are widely used to treat acid-related disorders. However, PPI use may be associated with an increased risk of osteoporosis and fractures. Therefore, this study aimed to investigate the association between PPI use and the risk of osteoporosis and fractures using national data. Two nested case-control studies were conducted using nationwide population cohort data. The first study included patients with osteoporosis and controls while the second included patients with fractures and controls. Associations between PPI use and the risk of osteoporosis and fractures were analyzed using propensity score overlap-weighted odds ratios (ORs). The results showed that current PPI use was associated with a higher risk of osteoporosis than non-use (overlap-weighted OR = 37.4, 95% confidence interval: 33.3–42.1, P < 0.001). This association was stronger with a longer duration of PPI use. Similar associations were observed for distal radius, hip, and spinal fractures in the patient group. However, no significant associations were observed between PPI use and fractures in the PPI-treated group. Here, PPI use was associated with a higher risk of osteoporosis and fractures, particularly with a longer duration of use. Therefore, clinicians should consider the potential risks associated with PPIs when prescribing them to patients with acid-related disorders.

The specific impact of type 2 diabetes mellitus (T2D) on renal outcomes, independent of albuminuria, is not fully understood. This study aimed to investigate the renal outcomes in non-albuminuric T2D subjects compared to non-albuminuric non-T2D subjects. Data from the National Health Insurance Service-National Sample Cohort of Korea from 2009 to 2015 were analyzed. The non-albuminuric T2D group was compared with the non-albuminuric non-T2D group. The primary outcome was a composite renal outcome consisting of the initiation of renal replacement therapy and a decline of ≥ 40% in eGFR from baseline. Of 587,339 subjects, 77,267 were analyzed: 11,957 in the T2D group and 65,310 in the non-T2D group. The T2D group demonstrated a greater annual decline in eGFR of -0.113 ml/min/1.73 m2 (95% CI: -0.222 – -0.003, p = 0.044). The adjusted hazard ratio for the primary outcome was 1.57 (95% CI: 1.28¬–1.92, p < 0.001). The steeper decline in eGFR was particularly evident in patients with glomerular hyperfiltration (eGFR ≥ 120 ml/min/1.73 m2) and a duration of T2D exceeding 6 years. Non-albuminuric T2D was associated with a greater annual decline in renal function and had a 1.5-fold increased risk of adverse renal outcomes compared to non-albuminuric non-T2D.

Background: Chronic kidney disease is a significant health burden worldwide, with increasing incidence. Although several genome- wide association studies (GWAS) have investigated single nucleotide polymorphisms (SNP) associated with kidney trait, most studies were focused on European ancestry. Methods: We utilized clinical and genetic information collected from the Korean Genome and Epidemiology Study (KoGES). Results: More than five million SNPs from 58,406 participants were analyzed. After meta-GWAS, 1,360 loci associated with estimated glomerular filtration rate (eGFR) at a genome-wide significant level (p = 5 × 10–8) were identified. Among them, 399 loci were validated with at least one other biomarker (blood urea nitrogen [BUN] or eGFRcysC) and 149 loci were validated using both markers. Among them, 18 SNPs (nine known ones and nine novel ones) with 20 putative genes were found. The aggregated effect of genes estimated by MAGMA gene analysis showed that these significant genes were enriched in kidney-associated pathways, with the kidney and liver being the most enriched tissues. Conclusion: In this study, we conducted GWAS for more than 50,000 Korean individuals and identified several variants associated with kidney traits, including eGFR, BUN, and eGFRcysC. We also investigated functions of relevant genes using computational methods to define putative causal variants.

Background Chronic kidney disease (CKD) poses a significant health challenge, yet early detection remains difficult. Resting heart rate (RHR) has been shown to be a reliable indicator of type 2 diabetes, prompting interest in its potential as an independent predictor of CKD. This study aimed to investigate the association between RHR and CKD prevalence, as well as explore potential interactions between RHR and other risk factors for CKD in a sample of 25,246 adults. Methods Data from the Korean National Health and Nutrition Examination Survey (2011–2014) were utilized for this study, with 19,210 participants included after screening. Logistic regression analysis was employed to examine the relationship between RHR and CKD prevalence. Stratified analyses were conducted based on known risk factors for CKD. Results Participants with an RHR ≥ 90 bpm exhibited a 2.07-fold [95% confidence interval (CI): 1.28–3.34] and 2.22-fold (95% CI: 1.42–3.48) higher prevalence of CKD in men and women, respectively, compared to those with an RHR < 60 bpm. The association between RHR and CKD prevalence was particularly pronounced in younger participants (40–59 years vs. ≥ 60 years), individuals with diabetes (yes vs. no), and those with a longer duration of diabetes (≥ 7 years vs. < 7 years). Conclusion Elevated RHR was found to be significantly associated with a higher prevalence of CKD in both men and women, independent of demographic, lifestyle, and medical factors. These findings suggest that RHR could serve as a valuable predictor for undiagnosed CKD.

In response to the increase in the prevalence of chronic kidney disease (CKD) in Korea, the growth of patients requiring renal replacement therapy and the subsequent increase in medical costs, the rapid expansion of patients with end-stage kidney disease (ESKD), and the decrease in patients receiving home therapy, including peritoneal dialysis, the Korean Society of Nephrology has proclaimed the new policy, Kidney Health Plan 2033 (KHP 2033). KHP 2033 would serve as a milestone to bridge the current issues to a future solution by directing the prevention and progression of CKD and ESKD, particularly diabetic kidney disease, and increasing the proportion of home therapy, thereby reducing the socioeconomic burden of kidney disease and improving the quality of life. Here, we provide the background for the necessity of KHP 2033, as well as the contents of KHP 2033, and enlighten the Korean Society of Nephrology's future goals. Together with patients, healthcare providers, academic societies, and national policymakers, we need to move forward with goal-oriented drive and leadership to achieve these goals.

Since the seminal success of Edmonton protocol in 2000, pancreatic islet transplantation has been very actively pursued worldwide1. This breakthrough has provided considerable encouragement to patients affected with type 1 diabetes, particularly those experiencing severe hypoglycemia and poor glycemic control, as well as healthcare professionals dedicated to their treatment. As of the latest report, over 1,300 patients have undergone pancreatic islet transplantation2. Notably, several recent studies have presented long-term follow-up results extending beyond 10 or even 20 years2. Despite these advancements, the field faces a significant challenge stemming from the diverse criteria employed across studies for assessing graft survival and transplantation success. This challenge is exacerbated by disparate transplantation protocols and confinement of studies to specific countries or institutions, hindering a comprehensive assessment of transplantation responses and the identification of prognostic factors. To integrate and compile data from islet transplantation, the Collaborative Islet Transplant Registry (CITR) was established in 2001, with participation from more than 39 centers across over 10 countries to date2. Over the past two decades, this expansive registry has played a crucial role in aggregating islet transplantation data, significantly advancing our understanding of this therapeutic approach. This year, the CITR has reported three pivotal studies based on the accumulation and long-term analysis of this extensive dataset (Table 1)2-4. Primary outcome Secondary outcome High predictability of C-peptide for primary outcome The higher the C-peptide level, the greater the likelihood of achieving each outcome Cut-off value of C-peptide for optimal graft function: ≥1.0 ng/mL Outperformance of the mixed-meal tolerance test-stimulated C-peptide-to-glucose ratio in predictive ability for all primary outcomes except absence of SHEs, compared with both fasting and stimulated C-peptide First, Bernhard Hering and colleagues4 provided important clinical insights into transplantation protocols and post-transplant management by proposing a common set of four favorable factors. This study involved an extensive and thorough exploration, encompassing various affecting factors such as recipient/donor characteristics, islet graft properties, and immunosuppression methods. Four factors were identified with the highest predictive power, including recipient age of 35years or older, total infused islets of 325,000 islet equivalents or more, induction of immunosuppression with T cell depletion and/or tumor necrosis factor-alpha (TNF-α) inhibition, and maintenance with both the mechanistic target of rapamycin (mTOR) and a calcineurin inhibitor with the highest predictive power. Importantly, with the exception of age, these factors are modifiable and amenable to intervention. Secondly, David Baidal et al.3 observed a robust correlation between clinical outcomes and concurrent measurements of fasting and stimulated C-peptide levels, along with the C-peptide-to-glucose ratio. This finding implies that retention of C-peptide function should be regarded as another potential goal of islet transplantation. Lastly, in The Lancet Diabetes & Endocrinology, Mikaël Chetboun et al.2 reported the primary graft function (PGF; islet graft function after islet the last islet infusion) and 5 year outcome results. They utilized the BETA-2 score (derived from fasting C-peptide, fasting plasma glucose, HbA1c, and insulin dose expressed as continuous variables), based on 28 days after last islet transplantation, as an indicator to predict the 5 year success rate of islet transplantation2. This is significant as it introduces an indicator for predicting the success rate of transplantation, which, until now, either did not exist or was challenging to apply in practice due to diverse standards in various studies. Notably, the correlation analysis between PGF and long-term outcome considered all possible confounding factors, enhancing the reliability and verification power of the study, given its multi-center nature involving more than 1,000 transplants. It is important to note that the PGF was evaluated at 28 days after the last islet infusion. As the authors have already mentioned2, this timeframe is considered appropriate, taking into account graft engraftment and vascularization. Additionally, it could allow sufficient time for stabilizing glucose homeostasis after transplantation. Previous studies have measured the BETA-2 score at 3 months or continuously after islet transplantation to analyze its relationship with transplantation outcomes5. However, given the rapid decline in graft function during the first month after transplantation and a gradual decrement thereafter5, the 1-month time point suggested in this study appears to be appropriate for evaluating graft function to predict clinical outcomes. Lastly, they are unveiling a prediction model based on the results of this study (accessible on http://pgf.diabinnov.com/), providing crucial information for predicting the prognosis after islet transplantation, determining the need for additional islet transplantation, and offering valuable guidance to healthcare professionals and patients before and after islet transplantation. It is imperative to emphasize that the BETA-2 score at 28 days after transplantation is derived from the composite outcomes of various donor and recipient factors, encompassing islet number and function, immune responses, metabolic factors, and even unknown or poorly measured elements. Therefore, considering a multivariate analysis incorporating PGF in the model, it is necessary to reevaluate their conclusion that the number of islet infusions and the transplanted islet mass had no significant impact on major clinical outcomes. While the BETA-2 score can serve as a useful indicator for assessing graft function and predicting long-term outcomes, successful islet transplantation still requires meticulous preparation and vigilant post-transplant management, addressing factors ranging from islet number, mass, and function to post-transplant immunosuppressants1, 3. Chetboun et al.2 applied the Igls 2.0 criteria (revised from the original version), which distinguishes clinical outcomes based on glucose regulation from beta cell graft function using C-peptide and insulin requirement. Consequently, they excluded insulin dependence from the category of unsuccessful islet transplantation but considered fasting C-peptide as low as 0.2 ng/mL as a favorable outcome. This aspect warrants careful attention when interpreting their findings. As noted in another CITR report this year, the retention of C-peptide is closely tied to outcomes such as metabolic restoration, loss of severe hypoglycemic events (defined as hypoglycemia associated with loss of consciousness or requiring third-party assistance for recovery), and achieving insulin independence3. Despite the use of more lenient criteria for defining unsuccessful islet transplantation, the 5 year transplant success rate in this integrated registry remains below 30%. If more stringent parameters, such as insulin independence or a significant reduction in insulin requirement as suggested in the initial Igls criteria (a consensus definition for outcomes of beta cell replacement therapy in the treatment of diabetes from the international pancreas and islet transplantation association (IPITA)/European pancreas and islet transplantation (EPITA), consisting of four factors: HbA1c, severe hypoglycemia, insulin requirement, and C-peptide), and a higher C-peptide level (at least 0.3 ng/mL or more) are employed, the success rate could be anticipated to be even lower. This underscores that, despite significant progress in pancreatic islet transplantation, there is still considerable more room for improvement in achieving successful islet transplantation in the future. Over the past two decades, remarkable advancements have transpired in islet transplantation. The outcomes delineated by the CITR, spanning this period and involving more than 30 centers, provide valuable insights that could significantly contribute to the broader adoption of islet transplantation. We are now able to systematically address common favorable factors associated with successful transplantation outcomes, and there is a growing recognition that maintaining C-peptide levels after transplantation may be another critical goal for successful outcomes. Furthermore, it is now pertinent to deliberate the utilization of the BETA-2 score, measured at 28 days after islet transplantation, as a pivotal tool for guiding re-transplantation decisions in patients. Prospective clinical trials are warranted to explore the BETA-2 score threshold at 28 days, guiding re-transplantation decisions, assessing the target goal of graft function, and validating these findings across diverse ethnic groups including Asian populations. In addition to benefiting from this extensive registry data, the development of modalities capable of assessing islet function before transplantation, such as islets-on-chip, along with the advancement of innovative immunomodulatory approaches, may pave the way for more successful islet transplantation in the future. This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (No. 2021R1C1C1013016) to E.Y.L.; by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health &Welfare, Republic of Korea (grant number: HI13C0954) and Cooperative Research Program for Agriculture Science and Technology Development (Project No. PJ01345301) Rural Development Administration, Republic of Korea to K.H.Y. Editorial services were provided by Caron Modeas, Evolved Editing, LLC. Kun-Ho Yoon is an Editorial Board member of Journal of Diabetes Investigation and a co-author of this article. To minimize bias, they were excluded from all editorial decision-making related to the acceptance of this article for publication.

Abstract Aims/Introduction To investigate the long‐term efficacy of various encapsulated xenogeneic islet transplantation, and to explore the impact of different donor porcine genetic traits on islet transplantation outcomes. Materials and Methods Donor porcine islets were obtained from wild‐type, α1,3‐galactosyltransferase knockout (GTKO) and GTKO with overexpression of membrane cofactor protein genotype. Naked, alginate, alginate‐chitosan (AC), alginate‐perfluorodecalin (A‐PFD) and AC‐perfluorodecalin (AC‐PFD) encapsulated porcine islets were transplanted into diabetic mice. Results In vitro assessments showed no differences in the viability and function of islets across encapsulation types and donor porcine islet genotypes. Xenogeneic encapsulated islet transplantation with AC‐PFD capsules showed the most favorable long‐term outcomes, maintaining normal blood glucose levels for 180 days. A‐PFD capsules showed comparable results to AC‐PFD capsules, followed by AC capsules and alginate capsules. Conversely, blood glucose levels in naked islet transplantation increased to >300 mg/dL within a week after transplantation. Naked islet transplantation outcomes showed no improvement based on donor islet genotype. However, alginate or AC capsules showed delayed increases in blood glucose levels for GTKO and GTKO with overexpression of membrane cofactor protein porcine islets compared with wild‐type porcine islets. Conclusion The AC‐PFD capsule, designed to ameliorate both hypoxia and inflammation, showed the highest long‐term efficacy in xenogeneic islet transplantation. Genetic modifications of porcine islets with GTKO or GTKO with overexpression of membrane cofactor protein did not influence naked islet transplantation outcomes, but did delay graft failure when encapsulated.