Clinical and Experimental Nephrology最新文献

Introduction: C3 glomerulopathy (C3G) is an ultra-rare, complex, under-recognized kidney disease with a challenging diagnosis and no approved treatment. Nephrologists were surveyed to understand the treatment and management of C3G. This study presents the diagnostic challenges and treatment patterns of Japanese patients with C3G.

Methods: Data from the Adelphi C3G Disease Specific Programme™, a multinational survey of nephrologists treating patients with C3G in 8 countries including Japan, were retrospectively analyzed. Nephrologists completed patient-record forms on patient demographics, diagnosis, clinical characteristics, and treatment approaches.

Results: Sixteen nephrologists from Japan responded to the survey for 36 patients with C3G. Mean age at diagnosis and at the time of the survey was 45.4 and 48.6 years, respectively. Common symptoms at diagnosis were proteinuria (100%) and hematuria (83%); 79% of patients had proteinuria of  ≥1 g/day, and 3% had an estimated glomerular filtration rate of <30 mL/min/1.73 m². Median time from initial examination by general practitioner to definitive diagnosis was 8.4 weeks; ~20% and 10% of patients had to wait for >4 and >8 months, respectively, to get a confirmed C3G diagnosis; and 69% of patients had an additional biopsy. Angiotensin receptor blockers (68%), corticosteroids (64%), and sodium-glucose cotransporter-2 inhibitors (25%) were the main treatments utilized. Physicians perceived 19% of patients to have a gradually deteriorating disease condition.

Conclusion: This survey analysis explored the current status in diagnosis and management of patients with C3G in Japan. The lack of specific treatments emphasizes the need for novel targeted therapies addressing the root cause of C3G.

Background: This study aimed to comparatively evaluate the prognostic value of the Japanese Renal Pathology Society (JRPS) classification for predicting diabetic kidney disease (DKD) progression in Chinese patients.

Methods: This retrospective cohort study included 124 patients diagnosed with DKD from 2014 to 2020. Patients were classified into four JRPS classification grades based on the J-score. Renal survival was assessed using Kaplan-Meier analysis and Cox regression, and predictive accuracy was compared with the RPS classification and total renal chronicity score using receiver operating characteristic (ROC) curve analysis and the DeLong test.

Results: Over a median follow-up of 37 months, 76.6% of patients reached renal outcomes, including 40.3% progressing to end-stage kidney disease (ESKD). Higher JRPS classification grades were independently associated with adverse renal outcomes. However, ROC analysis demonstrated that the JRPS classification exhibited inferior discriminative performance compared with the traditional RPS classification system.

Conclusion: The JRPS classification was independently associated with renal outcomes but showed inferior discriminatory performance compared with the RPS classification. These findings suggest that JRPS classification may provide complementary pathological information rather than serving as a primary prognostic tool.

Background: The clinical significance of the lactate-to-albumin ratio (LAR) in surgical patients with chronic kidney disease (CKD) remains underexplored. This research evaluated correlation between LAR and clinical prognosis in perioperative CKD patients.

Methods: Using data from the INSPIRE database (2011-2020), we retrospectively analyzed 1906 surgical CKD patients categorized by admission LAR tertiles. Multivariable Cox/logistic/linear regression and restricted cubic spline (RCS) models assessed outcomes, adjusting for demographics, comorbidities, and perioperative factors.

Results: The cohort (mean age 60.6 ± 14.7 years; 66.5% male) had a 6.7% in-hospital mortality rate. Elevated LAR was independently associated with in-hospital mortality (adjusted HR = 1.79, 95% CI 1.4-2.28, P < 0.001), with the highest tertile (T3) showing a 2.33-fold higher risk compared to T1 (P = 0.004). Secondary outcomes demonstrated similar trends: higher LAR correlated with increased 30-day mortality (adjusted HR = 2.02, 95% CI 1.49-2.73), ICU admission (adjusted OR = 2.35, 95% CI 1.57-3.53), CRRT use (adjusted OR = 3.01, 95% CI 2.06-4.39) and longer length of hospital stay (adjusted β = 5.28 days, 95% CI 0.64-9.93). Restricted cubic splines demonstrated a monotonically increasing risk of mortality and other adverse outcomes with rising LAR levels (all P for nonlinearity > 0.05).

Conclusion: Elevated LAR was associated with increased risk of in-hospital and 30-day mortality, ICU admission, CRRT use and longer length of hospital stay in surgical CKD patients. This ratio offers a practical biomarker for perioperative risk stratification in this clinical population.

Background: Fabry disease is a hereditary disorder that leads to the accumulation of glycolipids, such as globotriaosylceramide, because of the absence or decreased activity of the enzyme alpha-galactosidase A, causing various organ dysfunctions. Urinary mulberry bodies (MBs) are specific markers of Fabry disease and can be identified in urinary sediments through microscopic visual evaluation. However, MBs are present in small quantities in urine, and some are difficult to distinguish morphologically from other urinary components, necessitating a highly accurate and objective automated detection method. Here, we examined the detection of MBs using molecular imaging flow cytometry (MI-FCM).

Methods: Urine samples from patients with and without Fabry disease were analyzed by MI-FCM for MB detection. Microscopy was used as a control method to identify MBs.

Results: MI-FCM detected MBs in 33 of 36 Fabry disease patients (sensitivity: 91.7%) and did not detect MBs in any of the nine non-Fabry patients (specificity: 100%). In comparison, visual inspection under an optical microscope detected MBs in 23 of 36 Fabry disease patients (sensitivity: 63.9%), confirming that MI-FCM provided more accurate detection. MBs were detected by MI-FCM in 29 of 30 patients with negative urinary protein.

Conclusion: MI-FCM frequently detected MBs in Fabry disease patients, even before the onset of renal dysfunction. Screening for MBs may be useful for the early detection of Fabry disease.

This review series provided methodological guidance for clinical kidney research using real-world data, building on the "Hands-on R Seminar for Clinical Research: acute kidney injury (AKI) Detection and estimated glomerular filtration rate (eGFR) Slope Estimation from Creatinine Data," held at the 68th Annual Meeting of the Japanese Society of Nephrology in 2025. The seminar offered participants mock datasets, R scripts, and practical exercises to set up analysis environments and conduct data analyses, alongside brief lectures on conducting clinical research on AKI and eGFR decline. This series expands and complements the seminars. In Part 1, we provide an overview of the key components essential for successful clinical kidney research. First, formulating a robust research question is crucial, grounded in clinical experience and informed by up-to-date evidence. Common outcomes or exposures in clinical kidney studies include eGFR slope (as a marker of chronic kidney disease progression), AKI incidence, and initiation of kidney replacement therapy. Second, identifying appropriate data sources is necessary. In addition to primary data collection, routinely collected electronic health records and real-world databases (including disease registries) have become more accessible. Here, we summarize real-world databases in Japan, particularly those that include serum creatinine and urine test results. Finally, researchers require proper data handling and analytical skills. We highlight kidney research-specific techniques, such as AKI detection and eGFR slope calculation from longitudinal creatinine data. Subsequent articles in this series (Part 2 and beyond) will detail each specific method and include practical R commands.

Chronic kidney disease (CKD), a condition affecting over 850 million people worldwide, is a major global health issue. CKD leads to multimorbidities and disease complexity, expediting the aging process and increasing mortality rates-a phenomenon sometimes referred to as "renal senescence." The leading cause of death in patients with CKD is cardiovascular disease (CVD), accounting for one-third to one-half of all deaths, in stark contrast to cancer, which is the primary cause of death in the general population. While previous studies on kidney disease have focused extensively on urinary extracellular vesicles due to their potential as non-invasive diagnostic tools and their origin from kidney cells, our research highlighs the significance of circulating small extracellular vesicles (cEVs). We demonstrated that cEVs act as key mediators in the pathological intercellular and inter-organ communication between the kidneys and vascular smooth muscle cells (VSMCs). However, the biogenesis, cargo, and biological functions of cEVs remain incompletely understood under physiological and pathological conditions, including CKD. We identified microRNA (miRNA) transcriptomic signatures encapsulated in cEVs from CKD animal models, which were validated in human CKD samples. Notably, the depletion of specific miRNAs in CKD-derived cEVs promoted osteogenic differentiation of VSMCs and the deposition of calcium-phosphate crystals in vessels. In contrast, miRNAs enriched in cEVs from healthy individuals suppress these pathological processes, acting as a safeguard. These findings and future research could pave the way for the development of diagnostic and therapeutic platforms leveraging cEVs in nephrology.

Approximately, 1.2 million deaths occur each year from chronic kidney disease worldwide. The incidence is increasing and current treatments have limited efficacy. Many patients with kidney disease inevitably end up with kidney replacement therapy. mRNA has revolutionized the world of molecular therapy and spotlighted the attention of the medical community on its potential clinical application. Currently, mRNA-based therapies have started to emerge in the kidney field. In this review, we describe recent advances in renal mRNA-based therapies and discuss future possibilities for using mRNAs to treat kidney diseases.

Background: Proteinuria is often assessed by a single measurement, but persistent proteinuria has seldom been studied. Therefore, we investigated its association with cigarette smoking.

Methods: We prospectively followed 9,220 middle-aged Japanese men without renal dysfunction, proteinuria, diabetes, antihypertensive treatment, or cancer at baseline. Smoking status, daily cigarette consumption, and pack-years were assessed by questionnaire. Participants were grouped as nonsmokers, past smokers, or current smokers. Current smokers were classified by daily consumption (1-20 or ≥ 21) and cumulative exposure (0.1-40.0 or ≥ 40.1 pack-years). Persistent proteinuria was defined as proteinuria detected at ≥ 3 consecutive annual examinations. We used Cox proportional hazards models.

Results: There were 1972 nonsmokers, 2007 past smokers, and 5241 current smokers. During the 11-year follow-up, persistent proteinuria developed in 181 participants (28, 30, and 123 in each group), corresponding to incidence rates of 1.6, 1.7, and 2.6 per 1,000 person-years, respectively. In multivariate models, current smoking, daily cigarette consumption, and cumulative smoking consumption were significantly associated with the risk of persistent proteinuria, compared with nonsmoking. For daily cigarette consumption, multiple-adjusted HRs of persistent proteinuria for those who smoked 1-20, and ≥ 21 cigarettes per day were 1.59 (95% CI, 1.01-2.50), and 1.83 (1.15-2.91), respectively (P for trend = 0.011). For cumulative smoking exposure, the corresponding HRs for those with a pack-year of 0.1- 40.0, and ≥ 40.1 were 1.56 (1.00 -2.41), and 2.09 (1.26 -3.45), respectively (P for trend = 0.003).

Conclusions: In middle-aged Japanese men, cigarette smoking was associated with persistent proteinuria, and the risk rose with daily and cumulative smoking.