Myltykbay Rysmakhanov, Aibolat Smagulov, Nadiar Mussin, Asset Kaliyev, Bazylbek Zhakiyev, Yerlan Sultangereyev, Gani Kuttymuratov. Korean J Transplant 2022;36:253-8. https://doi.org/10.4285/kjt.22.0053

Kidney transplantation is the preferred treatment for end-stage renal disease (ESRD), yet challenges persist in long-term graft survival and post-transplant complications. Genomic profiling, especially whole-exome sequencing (WES), offers new opportunities to personalize donor-recipient matching and predict transplant outcomes. This study aimed to explore the genetic landscape of both transplant recipients and donors using WES. This prospective cohort study included 64 kidney transplant recipients (51 adults, 13 pediatric) and 61 donors in Kazakhstan. WES was performed to identify monogenic causes of ESRD, evaluate rejection-associated immune polymorphisms (31 SNPs), and screen for post-transplant risk using a 355-gene Transplant Morbidity Panel. Variants were classified following ACMG/AMP guidelines, and allele frequencies were compared to global reference datasets. Among recipients, pathogenic/likely pathogenic variants were found in 15.4% of pediatric and 9.1% of adult cases, with additional variants of uncertain significance detected in 23.1% and 23.6%, respectively. WES identified monogenic nephropathies including Alport syndrome, cystinuria, and polycystic kidney disease. In donors, 13.1% carried variants associated with latent renal or systemic conditions despite no clinical manifestation at donation. The APOE p.Cys130Arg variant, linked to lipid dysregulation, was observed more frequently in recipients (allele frequency 0.17) than donors (0.09), though not statistically significant. Among the 31 SNPs evaluated, significant associations with acute rejection were observed for IL1B rs1143634 and TP53 rs1625895 under dominant models. IL1B carriers showed increased rejection risk (OR = 4.62, p = 0.039), whereas TP53 carriers appeared protected (OR = 0.058, p = 0.027). Given the limited number of rejection cases, these findings should be considered exploratory and require validation in larger cohorts. Additionally, 44.3% of recipients carried at least one pathogenic or likely pathogenic variant in the Transplant Morbidity Panel, particularly in genes related to malignancy, cardiomyopathy, and monogenic diabetes. This study provides one of the first applications of WES in a Central Asian kidney transplant population. Findings highlight the prevalence of monogenic and comorbid risk variants in both recipients and donors and support the use of genomic screening for improving pre- and post-transplant care. The identification of immune-related SNPs and extra-renal findings further underscores the utility of WES for personalized transplant management. Integration of genomics into transplant workflows may help address the ongoing gap between clinical need and transplant outcomes, particularly in low-resource settings.

Background: The comparative effects of pharmacological treatment, bariatric surgery, and diet on insulin resistance (IR) remain unclear. Aim: To study the comparative effects of the methods on IR: pharmacologic, bariatric surgery, and very-low-calorie diet (VLCD) in patients with type 2 diabetes mellitus (T2DM) and hypertension. Methods: Design: a 90-day prospective, multicenter, comparative clinical trial including 130 adult patients divided into three groups: Drug, Surgery, and VLCD. Endpoints: HOMA-IR; weight loss; and HbA1c, systolic/diastolic blood pressure (SBP/DBP). Results: At 90 days, weight loss in the Surgery (−19.8%) and VLCD groups (−17.4%) was significant (p < 0.0001), while in the Drug group, the loss was insignificant (−6.5%; p = 0.06). SBP/DBP in the Drug group decreased by −9.5% (p = 0.0002) and −4.1% (p = 0.09), respectively. SBP/DBP in the Surgery group decreased by −13.6% and −10.6%, respectively (p < 0.001), and in the VLCD group, by −23.3% and 21.3%, respectively (p < 0.0001). HOMA-IR in Drug, Surgery, and VLCD groups decreased by −42.2% (p = 0.004), −87.6% (p < 0.0001), and −88.7% (p < 0.0001), respectively. In the Drug group, HOMA-IR did not reach the normal level. Correlation-regression analysis revealed a direct correlation between weight loss and a decrease in HOMA-IR (r = 0.526; F = 33.2, p < 0.0001). HOMA-IR decreases by 65% if weight decreases by 10%; if weight decreases by 25%, then HOMA-IR decreases by 83%. Conclusions: HOMA-IR was associated with weight loss: the greater the weight loss, the lower the HOMA-IR. Weight loss leads to a reduction in the need for antidiabetic/antihypertensive drugs in patients with T2DM and hypertension.

Введение: Несмотря на достаточное количество трансплантационных центров, наличие квалифицированных специалистов, современное техническое оснащение клиник, государственное финансирование, количество трансплантаций органов от посмертных доноров в Казахстане остается катастрофически низким. Одной из причин отказов граждан от участия в программе органного донорства являются религиозные убеждения. Цель – осветить роль исламской религии и тенгрианства в развитии посмертного донорства, а также изучить текущее положение в трансплантационной деятельности в Республике Казахстан. Стратегия поиска: с целью сбора информации о роли исламской религии и тенгрианства в донорстве органов, был проведен обзор литературы в Scopus, PubMed, National Library of Medicine, Embase, MedLine, Google Academic, проанализированы данные Республиканского центра по координации трансплантации и высокотехнологических медицинских услуг Министерства здравоохранения Республики Казахстан по вопросам трансплантационной деятельности в Казахстане. Результаты: Текущее состояние в отношении посмертного донорства и трансплантационной деятельности в Казахстане в целом показало неоднородный вид. Полученные данные показали, что трансплантация органов, в особенности посмертное донорство, требует радикальных изменений. Была выявлена неоднозначная роль исламской религии, а также концепции тенгрианства на развитие посмертного донорства. Законодательная база, информированность и стереотип мышления общества в отношении донорства, инфраструктура, оснащение необходимым и связанное с этим образование для развития трансплантации нуждаются в улучшениях. Вывод: Развитие посмертного донорства любой страны во многом зависит от уровня экономического развития самой страны, достаточной поддержки правительства, правильного понимания и информированности общества, самих медицинских работников о посмертном донорстве и его пользы для граждан, нуждающихся в трансплантации органов. Introduction: despite a sufficient number of transplantation centers, the presence of qualified specialists, modern technical equipment of the clinic, state financing, the number of organs from posthumous donors in Kazakhstan remains catastrophically low. One of the reasons for the failures of citizens to participate in the program of organ donation is religious beliefs. The goal is to highlight the role of Islamic religion and tengrism in the development of posthumous donation, as well as study the current position in transplantation in the Republic of Kazakhstan. Search strategy: In order to collect information about the role of Islamic religion and Tengrism in the donation of the organs, a review of literature was carried out in Scopus, Pubmed, National Library of Medicine, Embase, Medline, Google Academic, analyzed data from the Republican Center for Coordination of Transplantation and High-Tech Medical Services of the Ministry of Health of the Republic of Kazakhstan on issues of transplantation activities in Kazakhstan. Results: The current state in relation to deceased organ donation and transplantation in Kazakhstan as a whole showed a heterogeneous form. The data obtained showed that the transplantation of organs, especially posthumous donation, requires radical changes. The ambiguous role of the Islamic religion, as well as the concept of tengrism on the development of deceased organ donation, was revealed. The legislative framework, awareness and stereotype of the thinking of society regarding donation, infrastructure, equipping the necessary and related education for the development of transplantation need improvements. Conclusion: the development of the deceased organ donation of any country largely depends on the level of economic development of the country, sufficient support for the government, the correct understanding and awareness of society, the medical workers themselves about deceased organ donation and its benefits for citizens who need transplantation of organs. Кіріспе: Трансплантация орталықтарының жеткілікті санына, білікті мамандардың болуына, клиникалардың заманауи техникалық жарақтандырылуына, мемлекеттік қаржыландыруға қарамастан, Қазақстанда қайтыс болған донорлардан...

Ischemia-reperfusion injury (IRI) is a complex pathophysiological process that can lead to severe and irreversible consequences, including the complete loss of renal function. While standardized strategies for preventing IRI during "back-table" and cold preservation are available, various intraoperative prevention methods have been proposed to mitigate the harmful effects of warm ischemia and reperfusion of the kidney. These methods include pharmacological agents, mechanical interventions, and surgical techniques such as renal capsulotomy, ischemic preconditioning, venous blood reperfusion, renal perfusion, and the use of tissue engineering techniques like mesenchymal stromal/stem cells and/or decellularization. In this comprehensive analysis, we provide a detailed overview of pharmacological agents and intraoperative methods and approaches for the prevention and treatment of renal IRI. We begin by discussing the mechanisms of IRI and the challenges of preventing it during surgery. Then using a bibliometric analysis and molecular docking of brand-new legends we showed eplerenone have the most binding affinity to Aldehyde dehydrogenase (AD), Estrogen receptor (ER), Klotho protein, Mineralocorticoid receptor (MR), and Toll-like receptor 4 (TLR4) for preventing IRI comparing with other available therapeutics, Benzodioxole, Hydrocortisone, Indoles, Nicotinamide adenine dinucleotide, and Niacinamide. Next, we provide a comprehensive analysis of the potential benefits and limitations of various prevention strategies, including an in-depth discussion of the mechanisms of action of pharmacological agents, mechanical interventions, and surgical techniques. Furthermore, we introduce a novel scoring system for the prevention methods of kidney IRI, which takes into account the effectiveness, feasibility, and safety of each method. We then analyze the current state of clinical research in this area and discuss the implications of these methods for future clinical practice. Overall, this article provides a valuable resource for clinicians and researchers seeking to prevent and treat renal IRI in surgical settings, and introduces a new scoring system that can be used to guide the selection of the most effective and safe prevention methods.