Autologous hematopoietic stem cell transplantation (AHSCT)-based immune system reset (ISR) is conceptually distinct from donor-hematopoietic chimerism: recipient immunity is deeply depleted and rebuilt from recipient-derived hematopoietic stem/progenitor cells, without intended donor hematopoiesis. This review evaluates whether that platform could support kidney-allograft acceptance under reduced immunosuppression and, in exceptional responders, justify later testing of operational tolerance. We separate four evidence levels: mechanistic observations after AHSCT for autoimmune disease, preclinical hematopoietic-rescue models without intended donor chimerism, human partial-reset/minimization studies, and true drug-free tolerance. Autoimmune-disease data establish repertoire renewal and regulatory rebalancing, but do not prove alloantigen-specific tolerance. Experimental and early clinical transplant evidence remains limited and heterogeneous. We refine the proposed immune reconstitution-window model as a falsifiable framework in which continuous graft-derived donor-antigen exposure must coincide with a transient period of heightened immune plasticity. Donor antigen may enter this window through kidney transplantation during reconstitution after pretransplant ISR, or may already be present when ISR is applied to a stable recipient with an established allograft. Antigen presence is hypothesized to be necessary, but not sufficient, for donor-specific hyporesponsiveness. The model is linked to measurable targets: reduction of circulating and memory lymphocytes, turnover of donor-reactive clones, recovery of thymic output and naive repertoires, HLA-antibody trajectories interpreted against pretransplant donor-specific antibody status and specificity, absence of molecular or histologic graft injury, and reduced immunosuppression requirements. We also address resistant plasma cells, tissue-resident memory, pathogen-specific immunity, natural-killer-cell missing-self responses, age-dependent thymic recovery, stem-cell source, organ- and donor-type constraints, and kidney-specific safety. Current evidence supports biomarker-gated mechanistic testing in highly selected patients, not routine AHSCT or unmonitored immunosuppression withdrawal.

Due to the easier availability of transgenic mice and reagents, the mouse orthotopic liver transplantation model offers significant advantages in liver transplantation research. However, technical challenges have limited its broader application. The most challenging steps of the procedure include manual anastomosis of the suprahepatic vena cava, cuff anastomosis of the portal vein, and maintaining the anhepatic phase within 20 minutes. This study aims to provide detailed solutions to overcome these bottlenecks and introduces a modified magnetic device to facilitate safer and more efficient cuff anastomosis. We also describe the learning curve for beginners to achieve a 30-day survival rate exceeding 90% in mouse orthotopic liver transplantation. We demonstrate that mouse orthotopic liver transplantation can be mastered within 8 months of continuous practice, with 7-day and 30-day survival rates improving from 0% to 96.7% and 0% to 93.3%, respectively. The entire procedure can be completed within 80 minutes. We believe these technical improvements will provide more practical guidance for mouse liver transplantation.

Pediatric donor kidneys show rapid compensatory development in morphology and function after being transplanted into adult recipients. Establishing an animal model that can simulate clinical pediatric‐to‐adult (P→A) kidney transplantation is important for studying the characteristics and potential mechanisms related to this rapid graft growth. In the P→A group, kidneys harvested from 3‐ to 4‐week‐old Sprague–Dawley (SD) rats weighing <50 g were transplanted into adult SD rats (300‐400 g). Novel techniques were employed using recipient common iliac vessels for vascular anastomosis and ureter graft drag‐in connection to the recipient bladder. As a control group, conventional kidney transplantation was performed between adult SD rats (A→A group). A total of 11 transplants were performed in the P→A group. Eight recipients survived to 28 days without obvious complications and were euthanized for graft harvesting and analysis. Ultrasonography showed that the renal grafts grew significantly faster in the P→A group than in the A→A group during the first 7 days after transplantation, and the size of the renal grafts in the two groups was similar on day 28. Histology revealed significant glomerular enlargement and cell proliferation in the pediatric donor kidneys, with signs of hyperfiltration injury but without podocyte proliferation. Proximal tubular epithelial cells (PTECs) in the P→A group showed significant cell proliferation and hypertrophy. This study has successfully established an animal model in rats with similar characteristics to clinical P→A kidney transplantation, providing a new tool for studying the pathophysiological changes and potential mechanisms of early rapid compensatory growth of the grafts after small pediatric donor kidneys were transplanted into size‐mismatched large adult recipients.

BackgroundLaparoscopic living donor nephrectomy (LLDN) is the preferred technique for living donor kidney transplantation, but multiple renal arteries pose challenges due to increased surgical complexity. While cases with up to seven renal arteries have been reported, the occurrence of kidneys with more than three renal arteries is extremely rare. This report presents a successful retroperitoneoscopic nephrectomy in a living donor with five renal arteries, a case not previously detailed in the literature.Case reportA 65-year-old female donor with five left renal arteries underwent retroperitoneoscopic LLDN. The kidney was reconstructed ex vivo using the recipient's internal iliac artery trunk and its branches. Vascular reconstruction was achieved by anastomosing the donor's renal arteries to the recipient's iliac artery branches, forming a single arterial ostium, which was then anastomosed to the recipient's external iliac artery. The recipient, a 33-year-old male, also underwent concurrent repair of a left inguinal hernia. Postoperative outcomes were excellent, with immediate graft function, no dialysis requirement, and stable renal function at 60 days post-transplant.ConclusionThis case demonstrates that retroperitoneoscopic LLDN for kidneys with five renal arteries is technically feasible and safe. It highlights the utility of the recipient's internal iliac artery for ex vivo reconstruction, expanding the potential for successful transplantation in complex anatomical scenarios.

Effective treatment of late antibody-mediated rejection (late AMR) is still an unmet medical need. Clearing donor-specific antibody (DSA) and preventing its rebound is the ideal goal of treatment. We have summarized the clinical data from seven patients with late or chronic active AMR after renal transplantation who received daratumumab (Dara)-based treatment first (Phase 1) and then tocilizumab (TCZ) therapy (Phase 2). Phase 1 consisted of an intensive treatment period (Dara plus PP/IVIG) and a maintenance treatment period (Dara alone). The main clinical indicators were DSA, Banff scores and renal function. After 4 to 17 weeks of intensive treatment, the MFI values of DSA in five of the seven patients fell below 5,000. During Dara maintenance treatment, only one patient’s DSA became negative, and the remaining six patients’ DSAs remained relatively stable or showed rebound. However, after TCZ treatment was begun, the DSA eventually became negative in three patients and decreased to low levels (< 3,500) in the other three patients. Also, our treatment stabilized renal function in all patients. At 24–28 months after treatment, renal biopsy showed partial remission of microvascular inflammation in four of six patients. In addition, capillary C4d deposition became negative in all patients (P = 0.001), and the mean score of i-IFTA was significantly reduced (P = 0.012). Other chronic injury scores did not change significantly. This new therapy combining Dara and TCZ achieved a good desensitization effect, providing an important reference point for designing better-optimized treatment of late or chronic active AMR in the future. This retrospectively study was approved by the Ethics Committee of Tongji Hospital, Wuhan, China (TJ-IRB20230729).

the most ef fi cacious desensitization strategy is to

Background. Renal ischemia-reperfusion injury (RIRI) plays an important role in the poor prognosis of patients with renal transplants. However, the potential targets and mechanism of IRI are still unclear. Method. Differential gene expression (DEG) analysis and weighted correlation network analysis (WGCNA) were performed on the GSE27274 dataset. Pathway enrichment analysis on the DEGs was performed. To identify the hub DEGs, we constructed a protein-protein interaction (PPI) network. Finally, the hub genes were verified, and candidate drugs were screened from the DsigDB database. Results. A hundred DEGs and four hub genes (Atf3, Psmb6, Psmb8, and Psmb10) were screened out. Pathway enrichment analysis revealed that 100 DEGs were mainly enriched in apoptosis and the TNF signaling pathway. The four hub genes were verified in animal models and another dataset (GSE148420). Thereafter, a PPI network was used to identify the four hub genes (Atf3, Psmb6, Psmb8, and Psmb10). Finally, eight candidate drugs were identified as potential drugs. Conclusion. Three hub genes (Psmb6, Psmb8, and Psmb10) were associated with RIRI and could be potential novel biomarkers for RIRI.

Focal segmental glomerular sclerosis (FSGS) tends to recur after kidney transplantation, particu-larly when genetic testing is negative. Once the recurrence happens, the renal graft function can rapidly become impaired, following a massive urine protein loss. Despite intensive plasmaphere-sis and high-dose rituximab treatment, the complete remission rate remains below 50%. The Kunxian capsule, representing a new generation of tripterygium preparation, has shown promis -ing results in controlling proteinuria in patients with IgA nephropathy. It is unclear whether Kun-xian capsule treatment would also produce a favorable response in cases of FSGS recurrence. Here we report favorable results with this approach in a patient with early recurrent FSGS after kidney transplantation; we treated this patient successfully with a Kunxian capsule, a low dose of rituximab (200 mg), and reduced sessions of plasmapheresis. Complete remission, with a 90% reduction in total urine protein (0.81 g/24 h vs 8.3 g/24 h), was achieved within 2 weeks post-treatment. Of interest, the complete remission state in this patient has been maintained over 20 months with continuous administration of Kunxian capsules after the cessation of plasmaphere-sis. The potential mechanisms involved here include direct podocyte protection and the anti-inflammatory and immunosuppressive properties of triptolide in the Kunxian capsule. Our case may offer a new reference option for treating recurrent FSGS in the future.

Objective:To summarize the incidence of acute rejection (AR) after pediatric kidney transplantation (KT) at a single center and examine its impact on graft/patient survival and risk factors for AR.Methods:This is a retrospective cohort study including pediatric recipients who underwent kidney transplantation in past 8 years.After excluding recipients of graft thrombosis within a week post-transplant and lost to follow-ups, a total of 143 cases were ultimately recruited and assigned into two groups of AR (n=29) and non-AR (n=114).Basic profiles of both donors and recipients and graft/patient survival rate were compared between two groups.Relative risk factors for AR episodes were also examined by Logistic regression.Results:Renal grafts for 130/143 cases (90.9%) were harvested from deceased donors and 120(83.9%) cases from children.Twenty-seven transplants (18.9%) were performed in infants and young recipients aged < 3 years.During a median follow-up of 33 months, 34 AR episodes occurred in 29(20.3%) patients.Rate of re-transplantation (27.6% vs. 7.9%), pediatric donor (96.5% vs. 80.7%) and rabbit anti-human thymocyte globulin (rATG) induction (79.3% vs. 36%) were significantly higher in AR group than non-AR group ( P=0.007, P=0.046, P<0.001).Multivariate regression analysis indicated that basiliximab induction caused a significant reduction in the risk of AR incidence as compared with rATG induction (odds ratio 0.13, 95% confidence interval 0.04-0.43, P<0.001).The median time of AR incidence was 1.3 months post-transplantation and 23 episodes (67.6%) were confirmed by biopsy.After anti-rejection treatment, 52.9%(n=18) of the cases achieved a full recovery and 38.3% (n=13) had improved graft function.However, 3 cases (8.8%) developed irreversible graft failure.The 1/3-year graft survival rates were significantly lower in AR group than those in non-AR group (75.3% vs. 95.2%, 68.4% vs. 90.4%, P=0.01), and there was no significant difference in 1-and 3-year patient survival rates between two groups. Conclusions:The incidence of AR is relatively high in pediatric renal transplantation, which has an impact on graft survival.Basiliximab induction can effectively reduce the risk of AR.

Background Late or chronic active antibody-mediated rejection (AMR) associated with de novo donor-specific antibodies (dnDSA) after renal transplantation is a great clinical challenge because it is often resistant to conventional therapies. Daratumumab, an anti-CD38 monoclonal antibody that can deplete plasma cells, may be effective for the treatment of late or chronic active AMR. Methods We designed a novel regimen that included early intensive therapy with daratumumab plus plasmapheresis (PP)/intravenous immunoglobulins (IVIG) and later maintenance therapy with daratumumab alone, and used this regimen to treat late or chronic active AMR in two kidney transplant recipients with extremely high levels of anti-DQ7 dnDSA. Results Both patients had a limited clinical response to the early treatment with rituximab and PP/IVIG (with or without splenic irradiation); however, they had a remarkable decrease in anti-DQ7 DSA (MFI value from ~20,000 to ~5,000) after 2-3 months of intensive therapy with daratumumab plus PP/IVIG. Over 20 months of follow-up, patient 1 maintained a low DSA (as low as 1,572) and normal renal function on daratumumab maintenance therapy. Patient 2 retained a low DSA and improved renal function and pathological lesions within one year after treatment but then deteriorated because of acute T cell-mediated rejection. Conclusions Our daratumumab-based regimen has shown promising results in the treatment of refractory late active or chronic active AMR in renal transplant recipients with high-level dnDSA. This may provide a reference for better use of daratumumab in the treatment of late or chronic active AMR.

Background:Renal transplantation in HLA-presensitized recipients entails an increased risk of antibody-mediated rejection (AMR) and graft loss. There is currently no accepted standard treatment protocol that can help transplant surgeons safely perform deceased donor (DD) kidney transplantation in presensitized patients without pretransplant desensitization.Methods:Fifty-one panel-reactive antibody (PRA)-positive recipients and 62 PRA-negative retransplant recipients (control) who received DD renal transplantation were included. Patients in the presensitized group (donor-specific antibody [DSA]-positive, n=25; DSA-negative, n=26) without desensitization received a modified perioperative treatment starting on day 0 or -1 with rituximab, thymoglobulin, and low daily doses of intravenous immunoglobulin (IVIG, 10-20 g/d, for 14 days). Plasmapheresis was performed once before surgery in DSA-positive recipients.Results:The median follow-up time was 51 months in the presensitized group and 41 months in the control group. The incidence of early acute rejection (AR) and AMR (including mixed rejection) was 35.3% and 13.7% in the presensitized group, respectively, significantly higher than in the control group (14.5% and 1.6%, respectively). Within the presensitized group, the DSA-positive subgroup had more AMR than the DSA-negative subgroup (24.0% vs. 3.8%), but the incidence of T cell-mediated rejection was comparable (20.0% vs. 23.4%). In the presensitized group, all rejections were successfully reversed, and graft function remained stable during follow-up. The 1-year and 3-year survival rates of the grafts and recipients in this group were 98.0%.Conclusion:With a modified IVIG-based perioperative regimen, excellent intermediate-term graft and recipient survival outcomes can be achieved in presensitized patients who received DD kidney transplantation without prior desensitization.

Clear cell renal cell carcinoma (ccRCC) is an immunogenic tumor, and investigating the immunorelated genes is essential. To investigate the immunoprognostic genes of ccRCC, we analyzed the data assimilated from a public database (The Cancer Genome Atlas (TCGA) database and the gene expression omnibus (GEO) database) using bioinformatics. Then, an immunoprognosis model was constructed to identify four hub genes with moderate predictive values for the prognosis of ccRCC patients. These four genes were associated with the prognosis of ccRCC patients based on Oncomine and Gena Expression Profiling Interactive Analysis (GEPIA) databases. The correlation analysis between the immune infiltrate, immune checkpoints, and immunotherapy and this immunoprognosis model showed that immune infiltration could predict the immunotherapy effects. We also conducted a quantitative real-time polymerase chain reaction analysis and found that the expressions of three hub genes were associated with tumor progression (P<0.1). In conclusion, four genes that may serve as potential biomarkers in ccRCC were identified with respect to prognosis.

Objective:To summarize the clinical characteristics and treatment of cytomegalovirus(CMV)infection in pediatric kidney transplant patients.Methods:From May 2014 to July 2021, a total of 9 cases(8.65%)of 104 pediatric kidney transplant recipients were diagnosed with CMV infection in our centre.Retrospective data was collected for these 9 paediatric recipients.The clinical characteristics of the disease, treatment data and outcomes were summarized.Results:The median age of the 9 children was 10 years(0.25-15 years), 6 of whom were treated with polyclonal antibody for immunity induction.CMV IgG was negative in 4 children before renal transplantation.Only one patient received anti-CMV prophylaxis.The median time from transplant to the diagnosis of CMV infection was 22(7-15)days.Among the 9 children, 7 had fever, pneumonia and diarrhea, 2 had no typical symptoms, three patients were complicated with viral, bacterial or fungal infections.Acute rejection occurred in 3 patients at the same time as CMV infection or after CMV DNA turned negative.Nine patients were cured and discharged after ganciclovir or valganciclovir treatment.Median time of CMV DNA negative transformation was 32(17-90)days.Conclusions:Pediatric transplant recipients are at particularly elevated risk of CMV disease.Antiviral prophylaxis should be initiated early after transplantation.

ABO blood group antibodies have not been generated or are at low titer during early infancy. Therefore, in theory, ABO-incompatible kidney transplantation (ABOi KT) may be successfully achieved in small infants without any pre-transplant treatment. We report here the first ABO-incompatible deceased donor kidney transplantation (ABOi DDKT) in an infant. The recipient infant was ABO blood group O, and the donor group A. The recipient was diagnosed with a Wilms tumor gene 1 (WT1) mutation and had received peritoneal dialysis for 4 months prior to transplant. At 7 months and 27 days of age, the infant underwent bilateral native nephrectomy and single-kidney transplantation from a 3-year-old brain-dead donor. No pre- or post-transplantation antibody removal treatment was performed, since the recipient's anti-iso-hemagglutinin-A Ig-M/G antibody titers were both low (1:2) before transplantation and have remained at low levels or undetectable to date. At 11 months post-transplant, the recipient is at home, thriving, with normal development and graft function. This outcome suggests that ABOi DDKT without antibody removal preparatory treatment is feasible in small infants, providing a new option for kidney transplantation in this age range.

Obesity-driven cardiac lipid accumulation can progress to lipotoxic cardiomyopathy. Soluble epoxide hydrolase (sEH) is the major enzyme that metabolizes epoxyeicosatrienoic acids (EETs), which have biological activity of regulating lipid metabolism. The current study explores the unknown role of sEH deficiency in lipotoxic cardiomyopathy and its underlying mechanism. Wild-type and Ephx2 knock out (sEH KO) C57BL/6 J mice were fed with high-fat diet (HFD) for 24 weeks to induce lipotoxic cardiomyopathy animal models. Palmitic acid (PA) was utilized to induce lipotoxicity to cardiomyocytes for in vitro study. We found sEH KO, independent of plasma lipid and blood pressures, significantly attenuated HFD-induced myocardial lipid accumulation and cardiac dysfunction in vivo. HFD-induced lipotoxic cardiomyopathy and dysfunction of adenosine 5'-monophosphate-activated protein kinase-mammalian target of rapamycin complex (AMPK-mTORC) signaling mediated lipid autophagy in heart were restored by sEH KO. In primary neonatal mouse cardiomyocytes, both sEH KO and sEH substrate EETs plus sEH inhibitor AUDA treatments attenuated PA-induced lipid accumulation. These effects were blocked by inhibition of AMPK or autophagy. The outcomes were supported by the results that sEH KO and EETs plus AUDA rescued HFD- and PA-induced impairment of autophagy upstream signaling of AMPK-mTORC, respectively. These findings revealed that sEH deficiency played an important role in attenuating myocardial lipid accumulation and provided new insights into treating lipotoxic cardiomyopathy. Regulation of autophagy via AMPK-mTORC signaling pathway is one of the underlying mechanisms.

Objective:To explore the efficacy and safety of a novel Tripterygium preparation (Kunxian Capsules)in kidney transplant recipients developing refractory proteinuria after transplantation.Methods:A total of 59 kidney transplant recipients received regular follow-ups from August 2018 to July 2021.Severity of proteinuria, kidney graft function and adverse effects were retrospectively recorded before and at Month 1/2/3/6 months after Kunxian treatment.They were divided into two groups of effective and void to explore the potential effect-related factors.Results:Six-month treatment was completed in 57 patients except for 2 cases of discontinued treatment due to severe adverse effects.A significant reduction in amount of proteinuria was observed at Month 1 [1.09(0.42, 2.59 g/24 h)vs 1.82(1, 2.7 g/24 h, P<0.01)]and the trend continued during subsequent follow-ups.Twenty-nine patients(50.9%)responded remarkably.Eighteen patients(31.6%)showed no response.The overall effective rate was 68.4%.Inter-group comparison revealed strong correlations between treatment efficacy and baseline serum creatinine levels, early initiation of treatment and symptom duration from onset to treatment.Kidney graft IgA nephropathy demonstrated the highest effective rate(11/13, 84.6%). Furthermore, elevated blood concentration of tacrolimus hinted at a potential drug interaction. Conclusions:Kunxian Capsules is efficacious and safe for renal transplant recipients developing moderate-severe proteinuria and not responding to traditional medications.Early initiation of treatment before graft function decline is recommended.Reducing tacrolimus dose cautiously in advance and monitoring adverse events are also essential.

Objective:To summarize the clinical characteristics and therapeutic drug selection of post-transplantation diabetes mellitus(PTDM)after kidney transplantation in children.Methods:From May 2014 to March 2021, a total of 5 cases(5.38%)of 93 paediatric kidney transplant recipients with a median follow-up period of 34 months were diagnosed with PTDM in our centre.Retrospective data analysis was performed for these 5 paediatric recipients.The characteristics of the disease, treatment data and outcomes were summarized.Among the five paediatric recipients, one was male and four patients were female, ranging the age from 12 to 17 years.All recipients received a tacrolimus-based immunosuppressive regimen with prednisone discontinued no later than 3 months after kidney transplant.Results:The onset of PTDM ranged from 1 month to 46 months(median: 17 months)after transplantation.The blood glucose of two children returned to normal gradually after tacrolimus conversion to cyclosporine, with one of them was given insulin temporarily.Three children received oral hypoglycaemic agents, including one received acarbose, one received metformin, and one received metformin combined with acarbose.After a median follow-up of 6 months, the levels of blood glucose in five children were stable, and there was no significant change in serum creatinine and urine protein.Conclusions:The treatment of PTDM in children should be individualized with considering of age, gender and immunosuppressive regimen. Switch from tacrolimus to cyclosporine is effective. Metformin or other hypoglycemic agentsis helpful when tacrolimus is maintained.

Background: Blood purification therapy has not been applied in the detoxification of germanium compounds. This report described a case of germanium poisoning with renal failure, liver dysfunction, and acute pancreatitis which was successfully treated by continuous venovenous hemodiafiltration (CVVHDF) combined with plasmapheresis. Case report: A 58-year-old male was admitted to a local hospital due to polydipsia, polyuria, and weight loss for 2 months. The patient was definitely diagnosed with germanium poisoning and was treated with blood purification therapy, CVVHDF combined with plasmapheresis. The blood and urinary germanium concentrations decreased rapidly during the first week after the combined blood purification therapy. The blood germanium concentration gradually reduced to within the normal range within the next three weeks and fluctuated at a normal level. However, the urinary germanium concentration exceeded the normal level after three months, indicating an accumulation of germanium in the organs and tissues. The patient's clinical symptoms ameliorated and the functions of kidney, liver and pancreatitis gradually recovered. Conclusion: Combined CVVHDF with plasmapheresis is an effective treatment for germanium poisoning and the associated multiple organ dysfunctions.