Genetic testing in pediatric kidney transplant recipients to promote informed choice and improve individualized monitoring.

Background: The growing body of research on kidney disease in children has identified a broad spectrum of genetic etiologies.

Methods: We conducted a prospective study to evaluate the efficacy of an optimized genetic test and subclinical changes in a real-world context before kidney transplantation. All cases involved recipients under the age of 18 who underwent whole exome sequencing (ES) between 2013 and 2022.

Clinical characteristics of 15 cases of renal transplantation with preexsiting donorspecific antibody.

Objectives: Currently, patients with pre-exsiting donor-specific antibody (DSA) are prone to antibody-mediated rejection (AMR) after surgery and are at a relatively high risk of postoperative complications and graft failure. The risk of postoperative complications and graft failure is relatively high. This study aims to discuss the clinical outcome of DSA-positive kidney transplantation and analyze the role and safety of preoperative pretreatment in DSA-positive kidney transplantation, providing single-center treatment experience for DSA-positive kidney transplantation.

Early prediction of growth patterns after pediatric kidney transplantation based on height-related single-nucleotide polymorphisms.

Background: Growth retardation is a common complication of chronic kidney disease in children, which can be partially relieved after renal transplantation. This study aimed to develop and validate a predictive model for growth patterns of children with end-stage renal disease (ESRD) after kidney transplantation using machine learning algorithms based on genomic and clinical variables.

Methods: A retrospective cohort of 110 children who received kidney transplants between May 2013 and September 2021 at the First Affiliated Hospital of Zhengzhou University were recruited for whole-exome sequencing (WES), and another 39 children who underwent transplant from October 2021 to March 2022 were enrolled for external validation.

Exploration of the mechanism of NORAD activation of TGF-β1/Smad3 through miR-136-5p and promotion of tacrolimus-induced renal fibrosis.

Background: Tacrolimus is a potent immunosuppressant, but has various side effects, with nephrotoxicity being the most common. Renal fibrosis is an important process of tacrolimus nephrotoxicity. Therefore, it is important to identify the factors that contribute to renal fibrosis after tacrolimus nephrotoxicity, and control its development.

Bone marrow mesenchymal stem cells repress renal transplant immune rejection by facilitating the APRIL phosphorylation to induce regulation B cell production.

Bone marrow mesenchymal stem cells (BMSCs) exert pivotal roles in suppressing immune rejection in organ transplantation. However, the function of BMSCs on immune rejection in renal transplantation remains unclear. This study aimed to evaluate the effect and underlying mechanism of BMSCs on immune rejection in renal transplantation.

The N6-methyladenosine writer WTAP contributes to the induction of immune tolerance post kidney transplantation by targeting regulatory T cells.

N6-methyladenosine (m6A) modification is involved in diverse immunoregulation, while the relationship between m6A modification and immune tolerance post kidney transplantation remains unclear. Expression of Wilms tumor 1-associating protein (WTAP), an m6A writer, was firstly detected in tolerant kidney transplant recipients (TOL). Then the role of WTAP on regulatory T (Treg) cell differentiation and function in CD4 T cells from kidney transplant recipients with immune rejection (IR) was investigated.

Population Pharmacokinetics of Mycophenolic Acid in Renal Transplant Patients: A Comparison of the Early and Stable Posttransplant Stages.

Mycophenolic acid (MPA) is an antimetabolic immunosuppressive drug widely used in solid organ transplantation and autoimmune diseases. Pharmacokinetics (PK) of MPA demonstrates high inter- and intra-variability. The aim of this study was to compare the population PK properties of MPA in adult renal transplant patients in the early and stable post-transplant stages and to simulate an optimal dosing regimen for patients at different stages.

Super-Minimal Incision Technique in Pediatric Kidney Transplantation: A Paired Kidney Analysis.

Background: Recently, the demand for minimally invasive techniques in kidney transplantation (MIKT) has increased. However, there is only a limited number of studies on MIKT, especially in pediatric kidney transplants. Hence, we evaluated whether there is a difference between the super-minimal incision technique in pediatric kidney transplantation (SMIPKT) and conventional kidney transplantation (CKT).

Donor BMSC-derived small extracellular vesicles relieve acute rejection post-renal allograft through transmitting Loc108349490 to dendritic cells.

Bone marrow-derived mesenchymal stem cell (BMSC)-derived small extracellular vesicles (sEVs) are potent candidates for the suppression of acute rejection post-renal allograft and have been reported to halt dendritic cells (DCs) maturation. However, whether BMSC-derived sEVs mitigate acute rejection post-renal allograft by targeting DCs is still unclear. In this study, donor BMSC-derived sEVs (sEVs) relieved the inflammatory response and suppressed mature DCs (mDCs) location in kidney grafts, and increased regulatory T (Treg) cell population in the spleens of the rats that underwent kidney allograft.

Uterine Sensitization-Associated Gene-1 in the Progression of Kidney Diseases.

Uterine sensitization-associated gene-1 (USAG-1), originally identified as a secretory protein preferentially expressed in the sensitized rat endometrium, has been determined to modulate bone morphogenetic protein (BMP) and Wnt expression to play important roles in kidney disease. USAG-1 affects the progression of acute and chronic kidney damage and the recovery of allograft kidney function by regulating the BMP and Wnt signaling pathways. Moreover, USAG-1 has been found to be involved in the process of T cell immune response, and its ability to inhibit germinal center activity and reduce humoral immunity is of great significance for the treatment of autoimmune nephropathy and antibody-mediated rejection (AMR) after renal transplantation.

An accessible insight into genetic findings for transplantation recipients with suspected genetic kidney disease.

Determining the etiology of end-stage renal disease (ESRD) constitutes a great challenge in the context of renal transplantation. Evidence is lacking on the genetic findings for adult renal transplant recipients through exome sequencing (ES). Adult patients on kidney transplant waitlist were recruited from 2017 to 2019.

A prediction model of delayed graft function in deceased donor for renal transplant: a multi-center study from China.

Background: Kidneys obtained from deceased donors increase the incidence of delayed graft function (DGF) after renal transplantation. Here we investigated the influence of the risk factors of donors with DGF, and developed a donor risk scoring system for DGF prediction.

Methods: This retrospective study was conducted in 1807 deceased kidney donors and 3599 recipients who received donor kidneys transplants in 29 centers in China.

Elevated Circulating IL-10 Producing Breg, but Not Regulatory B Cell Levels, Restrain Antibody-Mediated Rejection After Kidney Transplantation.

Background: Antibody-mediated rejection (AMR) occupies a major position for chronic rejection after kidney transplantation. Regulatory B cell (Breg) has been reported to have an inhibitory immune function, which contributes to the resistance for AMR.

Methods: A nested case-control study for nine healthy donors, 25 stable (ST) patients, and 18 AMR patients was performed to determine the type of Breg in maintaining immune tolerance and preventing AMR.

Pediatric kidney transplantation in China: an analysis from the IPNA Global Kidney Replacement Therapy Registry.

Background: The International Pediatric Nephrology Association (IPNA) Global Kidney Replacement Therapy (KRT) Registry was established to evaluate the incidence and outcomes of kidney replacement therapy (dialysis and transplantation) provided to children worldwide. Analysis of registry data for separate regions is feasible.

Methods: Three centers located in Shanghai, Guangzhou, and Zhengzhou, which have the greatest number of pediatric kidney transplantation cases in China, participated in this analysis of transplant data.

Transplantation of a single kidney from pediatric donors less than 10 kg to children with poor access to transplantation: a two-year outcome analysis.

Background: Access to kidney transplantation by uremic children is very limited due to the lack of donors in many countries. We sought to explore small pediatric kidney donors as a strategy to provide transplant opportunities for uremic children.

Methods: A total of 56 cases of single pediatric kidney transplantation and 26 cases of en bloc kidney transplantation from pediatric donors with body weight (BW) less than 10 kg were performed in two transplant centers in China and the transplant outcomes were retrospectively analyzed.

miR-136 improves renal fibrosis in diabetic rats by targeting down-regulation of tyrosine kinase SYK and inhibition of TGF-β1/Smad3 signaling pathway.

To investigate the way that miR-136 regulated spleen tyrosine kinase (SYK) and transforming growth factor-β1 (TGF-β1)/Smad3 signaling pathways on renal fibrosis. 100 male SD (Sprague-Dawley) rats were randomly divided into diabetic nephropathy (DN) group, normal control (NC) group, miR-136 mimics group, and control group. The renal fibrosis model of diabetic rats was established by streptozotocin (STZ) method.

Immature dendritic cells derived exosomes promotes immune tolerance by regulating T cell differentiation in renal transplantation.

Objective: To investigate the mechanism of immature dendritic cells-derived exosomes (imDECs) in the regulation of T cell differentiation and immune tolerance in renal allograft model mice.

Results: imDECs significantly improved the percent of survival, relieved inflammatory response, and reduced CD4+T cell infiltration. In addition, imDECs reduced the rejection associated cytokines in allograft mice, and increased the percentage of Foxp3+CD4+T cells in spleen and kidney tissues.

Bortezomib ameliorates acute allograft rejection after renal transplant by inhibiting Tfh cell proliferation and differentiation via miR-15b/IRF4 axis.

Objective: The present study aimed to investigate the functional role of bortezomib in the development of acute allograft rejection (AR) after renal transplant.

Methods: The mouse model of AR was established by allograft kidney transplant followed by the treatment of bortezomib. The serum cytokines, renal function, and the percentage of T follicular helper (Tfh) cells in CD4 T cells were measured.

Incorporation of Gene-Environment Interaction Terms Improved the Predictive Accuracy of Tacrolimus Stable Dose Algorithms in Chinese Adult Renal Transplant Recipients.

The narrow therapeutic window of tacrolimus necessitates daily monitoring and predictive algorithms based on genetic and nongenetic factors. In this study, we constructed predictive algorithms for tacrolimus stable dose in a retrospective cohort of 1045 Chinese renal transplant recipients. All patients were genotyped for CYP3A4 20230T>C (rs2242480), CYP3A4 T>C (rs4646437), CYP3A5*3 6898A>G (rs776746), ABCB1 129T>C (rs3213619); ABCB1 c.

Inhibition of lncRNA MEG3 protects renal tubular from hypoxia-induced kidney injury in acute renal allografts by regulating miR-181b/TNF-α signaling pathway.

Early damage to transplanted organs initiates excess inflammation that deteriorates existing injury, which is a leading cause of graft loss. Long noncoding RNAs (lncRNAs) are recently thought to play a significant role in cellular homeostasis during pathological process of kidney diseases. The aim of this study was to assess the function and mechanism of lncRNA, maternally expressed gene 3 (MEG3), on early renal allografts pathogenesis.

Regulatory B cells and advances in transplantation.

The effects of B cell subsets with regulatory activity on the immune response to an allograft have evoked increasing interest. Here, we summarize the function and signaling of regulatory B cells (Bregs) and their potential effects on transplantation. These cells are able to suppress the immune system directly via ligand-receptor interactions and indirectly by secretion of immunosuppressive cytokines, particularly IL-10.

Over-expressed microRNA-181a reduces glomerular sclerosis and renal tubular epithelial injury in rats with chronic kidney disease via down-regulation of the TLR/NF-κB pathway by binding to CRY1.

Background: MicroRNAs (miRNAs) contribute to the progression of chronic kidney disease (CKD) by regulating renal homeostasis. This study explored the effects of miR-181a on CKD through the Toll-like receptor (TLR)/nuclear factor-kappa B (NF-κB) pathway by binding to CRY1.

Methods: Seventy male rats were selected and assigned into specific groups: miR-181a mimic, miR-181a inhibitor, and siRNA against CRY1, with each group undergoing different treatments to investigate many different outcomes.

Pharmacokinetics of Mycophenolate Mofetil and Development of Limited Sampling Strategy in Early Kidney Transplant Recipients.

The mycophenolate mofetil (MMF) dose management for optimization of post-transplant treatment especially the early postoperative phase has been well recognized. MMF is a pro-drug of mycophenolic acid (MPA) and is widely used in Chinese renal transplant patients. Until now, the pharmacokinetic (PK) characteristics and model for the area under the concentration-time curve for the 12-h (h) of exposure (AUC) of MPA (MPA-AUC) estimation were lacking for the new formulation of MMF dispersible tablet in renal transplant patients.