Congenital anomalies of the kidney and urinary tract (CAKUT) are the most common causes of end-stage renal disease (ESRD) in children. These anomalies are primarily caused by disruptions in kidney development due to genetic abnormalities or environmental factors. The genetic factors associated with CAKUT include single-gene mutations, copy number variants, and single nucleotide polymorphisms. Recent advancements in genetic analysis technologies have facilitated the integration of genetic testing into clinical practice for patients with CAKUT. However, genetic diagnosis does not always provide direct benefits in clinical decision-making for CAKUT patients. This is because genetic analysis is generally performed to confirm diagnoses, whereas CAKUT diagnoses are often established through imaging studies prior to genetic testing. Consequently, genetic testing may not contribute additional diagnostic information in many cases. On the other hand, CAKUT can present with extrarenal manifestations, and in some cases, identifying the causative gene may offer valuable insights for patient management. Thus, establishing standardized criteria for genetic testing in CAKUT remains challenging. A careful assessment of the benefits and limitations of genetic testing is necessary on a case-by-case basis to determine its utility in clinical care.

【Objective】 This paper investigates the incidence and genetic analysis of hereditary kidney diseases in adult patients, focusing on autosomal dominant tubulointerstitial kidney disease (ADTKD) and focal segmental glomerulosclerosis (FSGS) due to genetic mutations such as MUC1 and LAMA5. It aims to highlight the need to recognize atypical presentations of hereditary kidney diseases in adults and the importance of genetic testing in diagnosis and treatment planning.

【Methods】 The study utilized Whole Exome Sequencing (WES) to analyze patients with hereditary kidney diseases. This method selectively reads the exons of human genes to identify genetic mutations, particularly focusing on rare pathogenic variants. Analysis involved increasing the study cohort and comparing genetic expressions, such as those in podocytes, using single-cell data for accurate diagnosis.

【Results】 In the study, ADTKD was linked to mutations in genes like UMOD and MUC1. The research identified a Japanese family with a unique MUC1 mutation presenting with both kidney dysfunction and interstitial pneumonia. In terms of FSGS, the study documented the first global case of an LAMA5 gene heterozygous mutation causing progressive kidney dysfunction alongside lung structural changes. These findings highlight the variability and complexity of adult hereditary kidney diseases’ presentations.

【Conclusion】 The novel genetic mutations identified in MUC1 and LAMA5 not only emphasize the varying geographical prevalence of genetic diseases but also demonstrate the extensive systemic manifestations associated with these mutations. It is essential to remain vigilant for atypical presentations in adult hereditary kidney diseases, emphasizing the critical role of comprehensive genetic analysis in clinical practice to guide diagnosis and management.

Recent advances in genetic testing techniques have facilitated the diagnosis of inherited kidney diseases and made genetic testing accessible to any institution. Therefore, an approach to diagnosing inherited kidney diseases has become indispensable in the clinical setting of kidney diseases. The benefits brought about by such genomic medicine can be summarized in the following points. Genetic testing has many benefits, including 1) elucidation of clinical characteristics of inherited kidney diseases, 2) selection of treatment methods, and 3) prediction and diagnosis of extrarenal complications. Overseas, the concept of the Genetics-First Approach, which recommends genetic testing at an early stage, is well established. In this review, I will explain the significance of these genomic medicines in the treatment of pediatric renal disease.

Post-transplant recurrence of focal segmental glomerulosclerosis (FSGS) is a major challenge in the field of kidney transplantation, because it is a known risk factor of graft failure. The risk of recurrence is particularly high in patients with primary FSGS, which is supposed to be caused by circulating factors. By contrast, recipients with secondary (adaptive, viral, and drug-induced) FSGS and genetic FSGS have a very low risk of FSGS recurrence. Therefore, it is very important to determine the cause of FSGS before kidney transplantation. When secondary FSGS is excluded based on past histories and physical examinations, genetic testing should be considered. In our analysis of FSGS patients with an age 1-15 years at onset, patients who met all of the following criteria had no pathogenic variants in genes associated with FSGS: (i) nephrotic syndrome, (ii) complete or partial remission with initial steroid therapy and/or additional immunosuppressive therapies, and (iii) diffuse foot process effacement on electron microscopy in the native kidney biopsy. By contrast, >90% patients who failed to meet at least one of the criteria had pathogenic variants in FSGS-associated genes. Therefore, genetic testing is highly recommended in such patients. In summary, adequate assessment of post-transplant recurrence risk and genetic diagnosis can guide individualized strategies for FSGS patients undergoing kidney transplantation, including pre-transplant prophylactic treatment.

Atypical hemolytic uremic syndrome (aHUS) is a type of complement-mediated thrombotic microangiopathy; to date, causative genes including complement genes (CFH, CFI, CD46 (MCP), C3, CFB, THBD. DGKE, PLG, INF2, VTN) have been identified, and it has been reported that life outcomes, risk of disease recurrence, and prognosis of kidney transplantation differ depending on the presence and type of causative gene mutations. Recurrence of aHUS after kidney transplantation is a major risk for abolition of transplant kidney function The availability of anti-C5 monoclonal antibodies and prophylactic complement therapy with these drugs at the time of kidney transplantation has made it possible to perform kidney transplantation in combination with prophylactic complement therapy in patients classified as high risk for recurrence who could not undergo kidney transplantation due to high recurrence rate. In this article, we review the disease entity, epidemiology, pathophysiology, diagnosis and treatment of aHUS, as well as prophylactic treatment for kidney transplantation in patients with recurrence risk. We hope that future research will lead to more detailed risk assessments and decision-making on indications for prophylactic complement therapy.

Chronic kidney disease (CKD) often results from identifiable causes such as diabetes, hypertension, or glomerulonephritis. However, a significant proportion of patients progress to end-stage renal disease (ESRD) without a clear etiology. Recent advancements in genetic research, including gene panel testing, whole exome sequencing (WES), and whole genome sequencing (WGS), have enabled the identification of genetic mutations in previously unexplained CKD cases. This study presents a case of familial kidney disease in a 30-year-old woman with ESRD, exploring the diagnostic process and implications of genetic testing. Genetic analysis later confirmed a novel MYH9 mutation associated with focal segmental glomerulosclerosis (FSGS). This diagnosis highlighted the value of genetic testing in predicting disease recurrence, identifying complications, and guiding family risk assessments. The case underscores the importance of integrating genetic testing into clinical practice while addressing associated ethical and psychological challenges. Comprehensive genetic evaluation, coupled with multidisciplinary collaboration, enhances diagnostic accuracy and supports individualized patient care. Genetic counseling remains pivotal in navigating reproductive and social implications, promoting informed decision-making for patients and families.

【Background】 Simple cold storage (SCS) is commonly used to preserve kidney allografts from deceased donors. Randomized clinical trials in Europe and the USA have demonstrated that hypothermic machine perfusion (HMP) improves transplantation outcomes. This study reports the first multicenter clinical trial of HMP in Japan, comparing contralateral kidneys preserved with SCS and HMP from the same donors.

【Methods】 Sixteen consecutive deceased donors provided kidneys for this study. One kidney from each donor was assigned to HMP, while the other was preserved using SCS. All 32 recipients were followed for one year. The primary endpoint was to assess stable perfusion parameters and conditions in the HMP group. Secondary endpoints included the duration of delayed graft function (DGF), incidence of primary graft non-function, serum creatinine levels, and allograft survival.

【Results】 All 16 HMP-preserved kidneys maintained stable perfusion and were successfully transplanted. Compared with the SCS group, HMP relatively reduced DGF duration (6.1±12.2 days vs. 3.4±4.8 days). Primary non-function occurred in one SCS recipient. Serum creatinine levels showed a lower tendency in the HMP group (e.g., 2.0±0.9 mg/dL vs. 11.7±0.7 mg/dL at one month). One-year graft survival was 100% in the HMP group, compared to 93.8% in the SCS group. All these data showed no significantly difference.

【Conclusion】 Hypothermic machine perfusion demonstrated safe use in a clinical setting and the possibility of reduced delayed graft function, improved allograft function, and superior one-year survival, However, further study will be needed.

【Objective】 A Transplant Testing Center collaborates with the Japan Organ Transplant Network (JOT) to handle histocompatibility testing. In recent years, there has been an increasing trend of transplant testing centers withdrawing from testing services, resulting in an extremely challenging situation for the organ transplant testing infrastructure. Our hospital received a request from the JOT in 2022, and starting from 2023, we have been performing the duties of a Designated Transplant Testing Center.

【Methods】 Since 2015, our facility has been conducting histocompatibility testing. Anticipating the transition to a designated transplant testing center, we have simultaneously expanded and streamlined internal operations, invested in personnel development, upgraded equipment, and improved our working environment.

【Results】 The duties of a designated transplant testing center require 24-hour availability. Our hospital, having had sufficient preparation time, successfully initiated these responsibilities without any issues related to personnel or equipment. Regarding staffing, having multiple staff members capable of conducting tests allows for rotation and thus facilitates workload distribution and burden reduction. As for equipment, we have established backup systems to handle any potential issues, ensuring uninterrupted operation.

【Conclusion】 Despite our hospital having commenced the duties of a designated transplant testing center, the organ transplant testing infrastructure remains under stringent conditions. Leveraging our experience, we aim to support the expansion of testing facilities. Additionally, efforts to alleviate the burden of testing tasks, such as promoting virtual cross-matching, are essential.

This report explores the impact of two emerging preservation technologies—Normothermic Regional Perfusion (NRP) and Normothermic Machine Perfusion (NMP)—on liver transplantation outcomes in the United States, particularly for organs donated after circulatory death (DCD). The study highlights that NRP, first introduced in Europe in 2016, has significantly improved DCD liver transplant outcomes, making them comparable to those from brain-dead (BD) donors. In the U.S., following the FDA approval of NMP devices from TransMedics and OrganOx in November 2022, there has been a substantial increase in the acceptance of DCD livers across multiple transplant centers. This has led to a noticeable expansion of the donor pool as Organ Procurement Organizations (OPOs) have actively facilitated DCD donations. While the number of BD donors has slightly decreased, the overall number of transplants for all organs has increased. The adoption of these technologies has not only enhanced organ viability but has also expanded the donor pool, resulting in a notable increase in transplant numbers and helping to address the critical issue of organ shortages in the U.S.