Yosuke Hirakawa’s research while affiliated with University of Tokyo Hospital and other places

Aims/Introduction The impact of rare pathogenic variants on diabetic kidney disease (DKD) has not been investigated in detail. Previous studies have detected pathogenic variants in 22% of Caucasian patients with DKD; however, this proportion may vary depending on ethnicity and updates to the database. Therefore, we performed a whole‐genome analysis of patients with DKD in type 2 diabetes mellitus in Japan, utilizing a recent database to investigate the prevalence of kidney‐related pathogenic variants and describe the characteristics of these patients. Materials and methods Whole‐genome sequencing was performed, and variants were analyzed following the GATK Best Practices. We extracted data on 790 genes associated with Mendelian kidney and genitourinary diseases. Pathogenic variants were defined based on the American College of Medical Genetics criteria, including both heterozygous and homozygous variants classified as pathogenic or likely pathogenic. Results Among 79 participants, heterozygous pathogenic variants were identified in 27 (34.1%), a higher prevalence than previously reported. No homozygous pathogenic variants were detected. The identified heterozygous pathogenic variants were roughly divided into 23.7% related to glomerulopathy, 36.8% related to tubulointerstitial disease, 10.5% related to cystic disease/ciliopathy, and 28.9% related to others. Diagnostic variants were found in 10 patients (12.7%) in seven genes (ABCC6, ALPL, ASXL1, BMPR2, GCM2, PAX2, and WT1), all associated with autosomal dominant congenital disease. Conclusions This study identified a considerable number of patients with DKD in Japan who carried kidney‐related heterozygous pathogenic variants. These findings suggest potential ethnic differences and highlight the impact of database updates on variant detection.

Recent progress in gas‐sensing technology has enabled the rapid collection and highly sensitive analysis of skin gases associated with body odour. Skin gases can be collected less invasively, more continuously, and less consciously than blood or urine. Patients with end‐stage kidney disease (ESKD) have a characteristic uremic odour that fades after initiating kidney replacement therapy. We investigated the potential for objectively and quantitatively evaluating the factors underlying uraemia. Skin gases were collected using a passive flux sampler placed on the forearm, with peak intensities measured using gas chromatography–mass spectrometry (GC/MS). We investigated the changes in skin gases obtained from the haemodialysis (HD) group before and after the first HD session of patients undergoing incident dialysis and compared them between the ESKD groups (HD and non‐HD) and the healthy group. Thermal desorption enabled the collection of volatile molecules for 20 min using GC/MS preprocessing. Amongst 137 volatile molecules collected from the HD group ( N = 5), 16 were detected in all patients. Aldehydes and alkanes were detected more frequently, and four volatile molecules, including 6‐methyl‐5‐hepten‐2‐one, were detected in all participants in the ESKD ( N = 11) and healthy ( N = 7) groups. Benzaldehyde and undecanal showed significantly higher intensities in the ESKD group. Additionally, five unidentified volatile molecules were undetectable after dialysis, suggesting an association with the uremic odour. A comprehensive skin gas analysis technique has enabled the identification of volatile molecules related to ESKD. With a short sampling time, skin gas analysis has potential applications in clinical testing and telemedicine.

Post-transplant lymphoproliferative disorder (PTLD) affects from 0.8-2.5% of kidney transplant patients, with peaks in incidence within 1 year and 10-14 years post-transplant. Very late-onset PTLD (VL-PTLD) can occur over 10 years post-transplant, reportedly up to 30 years, but its characteristics remain unclear. A 61-year-old man developed PTLD 45 years after kidney transplant, presenting with fever and shortness of breath. Computed tomography revealed lung and liver masses and biopsy-confirmed stage IVB monomorphic PTLD. Despite obtaining an initial improvement, the patient died on day 66. VL-PTLD may differ from early- or late-onset PTLD, thus necessitating further research on both the associated risks and management.

Background Telemedicine involves medical, diagnostic, and treatment-related services using telecommunication technology. Not only does telemedicine contribute to improved patient quality of life and satisfaction by reducing travel time and allowing patients to be seen in their usual environment, but it also has the potential to improve disease management by making it easier for patients to see a doctor. Recently, owing to IT developments, research on telemedicine has been increasing; however, its usefulness and limitations in randomized controlled trials remain unclear because of the multifaceted effects of telemedicine. Furthermore, the specific metrics that can be used as cross-disciplinary indicators when comparing telemedicine and face-to-face care also remain undefined. Objective This review aimed to provide an overview of the general and cross-disciplinarity metrics used to compare telemedicine with in-person care in randomized controlled trials. In addition, we identified previously unevaluated indicators and suggested those that should be prioritized in future clinical trials. Methods MEDLINE and Embase databases were searched for publications that met the inclusion criteria according to PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analysis Extension for Scoping Reviews). Original, English-language articles on randomized controlled trials comparing some forms of telemedicine with face-to-face care from January 2019 to March 2024 were included, and the basic information and general metrics used in these studies were summarized. Results Of the 2275 articles initially identified, 79 were included in the final analysis. The commonly used metrics that can be used across medical specialties were divided into the following 3 categories: (1) patient-centeredness (67/79, 85%), including patient satisfaction, workload, and quality of life; (2) patient outcomes (57/79, 72%), including general clinical parameters such as death, admission, and adverse events; and (3) cost-effectiveness (40/79, 51%), including cost assessment and quality-adjusted life year. Notably, only 25 (32%) of 79 studies evaluated all the 3 categories. Other metrics, such as staff convenience, system usability, and environmental impact, were extracted as indicators in different directions from the three categories above, although few previous reports have evaluated them (staff convenience: 8/79, 10%; system usability: 3/79, 4%; and environmental impact: 2/79, 3%). Conclusions A significant variation was observed in the metrics used across previous studies. Notably, general indicators should be used to enhance the understandability of the results for people in other areas, even if disease-specific indicators are used. In addition, indicators should be established to include all three commonly used categories of measures to ensure a comprehensive evaluation: patient-centeredness, patient outcomes, and cost-effectiveness. Staff convenience, system usability, and environmental impact are important indicators that should be used in future trials. Moreover, standardization of the evaluation metrics is desired for future clinical trials and studies. Trial Registration Open Science Forum Registries YH5S7; https://doi.org/10.17605/OSF.IO/YH5S7

Biomarkers for the prediction of diabetic kidney disease are still unsatisfactory. Although D‐amino acids have been shown to reflect kidney conditions, their efficacy in treating diabetic kidney disease (DKD) has not been demonstrated. This study explored the potential role of D‐amino acids as progression markers for DKD, an aspect not addressed previously. We performed comprehensive D‐amino acid measurements and collected the longitudinal estimated glomerular filtration rate (eGFR) data of 135 patients. We defined fast decliners (FDs) as patients exhibiting > 10% decline from baseline eGFR per year and compared the D‐amino acid levels of FDs and non‐FDs. Then, we verified that D‐amino acids could predict FDs independent of creatinine levels. In patients with diabetic kidney disease, D‐serine, D‐alanine, and D‐proline were only detected in the blood, while 15 D‐amino acids were detected in the urine. Using supervised orthogonal partial least squares analysis, blood D‐serine and urine D‐amino acid levels were identified as features characterizing diabetic kidney disease. Baseline blood D‐serine levels and ratios did not differ between the FD and non‐FD groups; however, short‐term changes in blood D‐serine levels differed. This study emphasized the significance of D‐serine as a prognostic marker for DKD, an aspect not identified in previous research.

UNSTRUCTURED Not applicable

[This corrects the article DOI: 10.2196/64159.].

Telemedicine is a medical practice that uses electronic information and communication technologies. It is not exclusive to face-to-face care but complements face-to-face care and other forms of medical care. It has advantages such as facilitating home therapy, reducing patient travel time and costs, and empowering patients. This makes equitable access to care feasible. Clinical studies have been conducted on telemedicine in nephrology outpatient care, inpatient consultations and hemodialysis, indicating that telemedicine can improve patient satisfaction, leading to enhanced treatment owing to increased adherence and frequency of visits. However, it has not been sufficiently used in the kidney field. The key to spreading “telenephrology” (telemedicine in nephrology) is how physical examinations and laboratory/imaging/physiological tests, currently challenging to perform without face-to-face contact, can be substituted with methods optimized for the telemedicine framework. This paper describes the current status of telemedicine and telenephrology, along with advanced methods for collecting data equivalent to laboratory, imaging and physiological tests outside of hospitals, including estimation of serum creatinine levels from saliva or tear fluid, estimation of blood hemoglobin levels by taking pictures of the eyelid conjunctiva or nails with a smartphone and ultrasound of the kidneys using motion capture technology. With an understanding of the strengths and weaknesses of current telemedicine, we should make full use of it for better treatment and patient care. However, further telenephrology research is required.

UNSTRUCTURED Telemedicine, or online medical care, has gained considerable attention worldwide. However, it has not been widely adopted in Japan, and the detailed status of received and provided online medical care and the reasons for its lack of popularity remain unknown. This study aims to investigate the current status of online medical care in Japan and the factors limiting its adoption from the perspective of both patients receiving and medical professionals providing online medical care. In total, 2 nationwide questionnaire surveys were conducted. The first survey, targeting both patients and healthy individuals, screened approximately 40,000 participants among 13 million people. The participants were selected to match the age distribution of the Japanese population based on government data, and their online medical care experience and medical visit status were recorded. To further investigate online medical care use and satisfaction, a web-based survey was conducted with 15% (6000/40,000) of the screened participants. The second survey, targeting medical professionals, was administered to a physician, a nurse, and a member of the administrative staff in each of 4900 randomly selected medical facilities to inquire about their online medical care practices and impressions. In addition, both surveys investigated the factors limiting online medical care expansion in Japan. The response rates among patients and healthy individuals targeted for the screening and main surveys were 92.5% (36,998/40,000) and ˃80% (1312/1478, 88.77%; 1281/1522, 84.17%; 404/478, 84.5%; and 2226/2522, 88.26% in 4 survey groups), respectively. The survey of medical professionals yielded 1552 responses (n=618, 39.82% physicians; n=428, 27.58% nurses; n=506, 32.6% administrative staff). Although the facility-level response rate was low (794/4900, 16.2%), some facility categories had relatively high response rates. Only 5.29% (1956/36,998) of the patients and healthy individuals had online medical care experience. When there were more hospitals nearby and they felt it was more work to see a physician in person, they were more likely to use online medical care (more nearby hospitals: adjusted odds ratio [aOR] 1.33, 95% CI 1.18-1.50; more work: aOR 1.48, 95% CI 1.35-1.63 per survey response point in the patient group). Similarly, these factors were substantially associated with satisfaction (more nearby hospitals: aOR 1.40, 95% CI 1.14-1.73; more work: aOR 1.50, 95% CI 1.27-1.76 per survey response point in the patient group). In both surveys, the most frequently selected factor preventing the widespread use of online medical care was patients’ need to switch to face-to-face medical care for mandatory tests and procedures. Inadequate awareness of and education on online medical care were also frequently selected. Our nationwide surveys provided insights into the current status of online medical care in Japan and simultaneously identified several problems and issues related to it, which will be useful in promoting its wider adoption.