Clinical and Experimental Nephrology最新文献

Background: The frontier of renal outcome modifications in Japan 10 (FROM-J10) study is a 10 year longitudinal cohort study evaluating the long-term outcomes of treatment according to the clinical guidelines for chronic kidney disease (CKD) by primary care physicians. This study aimed to identify distinctive trajectories of kidney function among patients with CKD and evaluate the patient characteristics associated with each trajectory using the FROM-J10 study data.

Method: This secondary study used 10 years of data from 2379 patients aged between 40 and 74 years with CKD stages from G1 to G5 in the FROM-J10 study. Group-based trajectory modeling was applied to the change in estimated glomerular filtration rate (eGFR) over time, and patients were classified into distinct groups that followed similar trajectories. Multivariate logistic analysis was performed for patient characteristics associated with each trajectory.

Results: In total, 2257 patients with at least three eGFR values were included in this study. Two distinct trajectories of eGFR decline were identified: progressive decline (n = 1240, 54.9%) and gradual decline (n = 1017, 45.1%). In multivariate logistic analysis with gradual eGFR decline as a reference, proteinuria was associated with progressive eGFR decline in CKD from G2 to G4 + 5; lower albumin in G2, G3a, and G4 + 5; and lower hemoglobin in G3a to G4 + 5.

Conclusions: In patients with CKD adequately treated by primary care physicians, kidney function declined very slowly over 10 years. We suggest that patient characteristics identified as progressive eGFR decline, proteinuria, and lower albumin and hemoglobin levels should be managed appropriately in clinical practice.

Background: Primary membranoproliferative glomerulonephritis (MPGN) is a rare progressive kidney disease that often leads to end-stage kidney disease. Our previous nationwide registry study (Report 1, 2015-2018) characterized initial demographics and treatment patterns. In this study (Report 2), we aimed to update these findings, focusing on newly registered cases (2017-2021).

Methods: Personal clinical records of patients with primary MPGN between 2017 and 2021 were obtained from the national registry organized by the Japanese Ministry of Health, Labour and Welfare. Characteristics of primary MPGN throughout Japan were investigated.

Results: A total of 210 patients (median age, 49 years; male, 51%) with newly registered primary MPGN were identified. Nephrotic syndrome was present in 83.8% of patients at enrollment. Initial treatment frequently included corticosteroids (63.8%), with a modest increase in intravenous methylprednisolone pulse therapy (41.4%) compared with that in Report 1. The incidence of hemodialysis was 7.1%. Compared with those in Report 1, the demographic patterns were similar; however, nephrotic presentations were more common. Cyclosporine and mizoribine usage were significantly higher in the pediatric group (< 18 years, n = 44) compared to the corresponding usage in the older adult group (≥ 65 years, n = 75). The mean dosage of oral prednisolone and other immunosuppressants during initial treatment did not differ among the four age groups.

Conclusion: Compared with the earlier report (Report 1), patients with newly registered primary MPGN presented with nephrotic syndrome more often, highlighting the continued risk of poor prognosis and the need for more refined therapeutic approaches.

Estimated glomerular filtration rate (eGFR) slope, which quantifies the annual change in kidney function using longitudinal measurements of eGFR, has emerged as a critical surrogate endpoint for chronic kidney disease progression in clinical trials. Accordingly, there is an increasing number of observational studies calculating the eGFR slope as an outcome or exposure of interest. To calculate the eGFR slope, linear mixed-effects models are considered statistically more efficient and therefore recommended over linear regression models constructed for each individual. Linear mixed-effects models can account for both fixed effects at the population level and random effects, which allow for subject-specific intercepts and slopes-e.g. individual-specific variation from the population mean. We introduce the practical implications of linear mixed-effects models using R programming: calculating an individual's eGFR slope and comparing mean eGFR slopes between groups. This article is based on the hands-on seminar at the annual meeting of the 68th Japanese Society of Nephrology in 2025.

Introduction: The clinical characteristics of patients with nephrotic syndrome undergoing in-hospital rehabilitation are not well-understood, and the effects of exercise on acute kidney injury (AKI) or venous thromboembolism (VTE) in this population remain unclear.

Methods: We conducted a retrospective cohort study using a nationwide Japanese administrative claims database. We examined the clinical background of patients aged ≥ 18 years with nephrotic syndrome who underwent in-hospital rehabilitation. In a subgroup analysis of patients with nephrotic syndrome hospitalized for 14-90 days, we assessed the associations between rehabilitation intensity or early initiation and the development of AKI and VTE, as well as changes in activities of daily living (ADL), using multivariate logistic regression. Several sensitivity analyses were performed to confirm the robustness of the results.

Results: Among the 6989 patients with nephrotic syndrome who were hospitalized for ≥ 7 days, 1447 (20.7%) received rehabilitation. Factors associated with rehabilitation included older age, female sex, AKI, cerebrovascular disease, use of intravenous corticosteroids, anticoagulants, diuretics, hypoglycemic drugs, and longer hospital stay. In the subgroup analysis, no statistically significant association was detected between rehabilitation intensity or early initiation and the development of VTE, AKI, or improvements in ADL during hospitalization.

Conclusions: We described the clinical characteristics of patients with nephrotic syndrome who received in-hospital rehabilitation. In patients with nephrotic syndrome, no statistically significant association was detected between rehabilitation intensity or early initiation and the risk of VTE or AKI. Further studies are warranted to evaluate the effectiveness and safety of rehabilitation in patients with nephrotic syndrome.

Background: Thrombin is a serine protease that plays an important role in blood coagulation and has been implicated in kidney diseases, particularly glomerular disorders. In this study, we aimed to evaluate urinary thrombin in different types of kidney disease and investigate whether it can be used as a biomarker for the presence of segmental sclerosis lesions in IgA nephropathy.

Methods: We enrolled 151 patients aged ≥ 18 years who underwent renal biopsy at Kumamoto University Hospital or two of its affiliate hospitals between November 2016 and September 2021. Urine samples were obtained from patients, and urinary thrombin antigen levels were measured using a previously established highly sensitive enzyme-linked immunosorbent assay. We evaluated urinary thrombin in different types of kidney disease, focusing on IgA nephropathy, and assessed the association between urinary thrombin and histological severity classification (Oxford classification), especially S lesions.

Results: Among the patients with kidney disease, thrombinuria was more prevalent in those with focal segmental glomerulosclerosis [60%; 9/15]. In 34 patients with IgA nephropathy, the logistic regression model, using the presence of S lesions as the outcome variable, demonstrated that the odds ratios for thrombinuria and proteinuria were 7.20 and 2.82, respectively. The areas under the receiver operating characteristic curve (AUROC) regarding the models for thrombinuria and proteinuria were 0.73 and 0.56, respectively, with both differences being significant (p = 0.04).

Conclusions: Our findings suggest that thrombinuria may be a novel biomarker for kidney disease, particularly for segmental sclerosis lesions in IgA nephropathy.

Background: Clinical practice guidelines do not recommend tonsillectomy combined with steroid pulse therapy (TSP) as the initial treatment of severe IgA nephropathy (IgAN) in children. Therefore, the long-term prognosis following TSP is unknown in IgAN children with heavy proteinuria.

Methods: This retrospective study aimed to determine the long-term outcome of children with IgAN and heavy proteinuria (urinary protein-to-creatinine ratio, ≥ 1.0 g/g) following TSP as the initial treatment. The primary endpoint was the probability of achieving treatment-free clinical remission (CR: disappearance of both hematuria and proteinuria) without developing kidney complications at the last follow-up.

Results: After initiating TSP in 43 patients (median age, 10.4 years), CR was achieved in 41 patients (95%) at a median of 9.6 months. During the observation period (median, 7.5 years), four patients experienced proteinuria recurrence that required additional therapy. At the last follow-up (median age, 18.2 years), 37 patients (86%) achieved treatment-free CR without developing kidney complications (favorable group), whereas six patients received a renin-angiotensin system inhibitor for persistent proteinuria (unfavorable group). The age and proportion of glomeruli with crescents at IgAN diagnosis were significantly lower in the favorable group than in the unfavorable group. Multivariable analysis showed that a younger age at IgAN diagnosis (< 12.2 years) was an independent predictive factor for favorable outcomes. There were no serious adverse events and no significant negative changes in the anthropometric outcomes.

Conclusions: Initial treatment with TSP may result in treatment-free CR in children with IgAN and heavy proteinuria, particularly in patients diagnosed at a young age.

Background: With prolonged waiting times for deceased-donor kidney transplantation (DDKT) in Japan, objective data on frailty among wait-listed patients are limited. We assessed frailty using body composition and nutritional measures to identify predictors of 1 year mortality or hospitalization.

Methods: We retrospectively analyzed 134 patients on the DDKT waiting list starting December 2023. Body composition was assessed using multifrequency bioelectrical impedance analysis. Nutritional indices, including Survival Index, Prognostic Nutritional Index, Geriatric Nutritional Risk Index, and Nutrition Risk Index for Japanese Hemodialysis Patients, were calculated. Handgrip strength was also measured. Death or hospitalization within 1 year was defined as an event. Random forest and SHapley Additive Explanation analyses were used to identify predictors of event occurrence.

Results: Among 134 patients (median age 58 years, 68% male), 40% had obesity, 24% had sarcopenia, and nearly 50% exhibited malnutrition. The median dialysis duration was 10 years. During 1 year, 34 events (25%) occurred: seven deaths and 27 hospitalizations secondary to infection, malignancy, or heart failure. The fat mass index/fat-free mass index (FMI/FFMI) ratio was the strongest event predictor, followed by low grip strength, reduced SMI, low Survival Index, and low phase angle. Age, comorbidity index, and several nutritional indices showed limited predictive contributions.

Conclusions: A significant number of Japanese DDKT candidates demonstrated frailty characterized by obesity, sarcopenia, and malnutrition. Objective indicators, particularly FMI/FFMI, may aid in evaluating vulnerability and eligibility during registration and renewal. Integrating these measures into standardized national criteria may improve equity and outcomes in DDKT candidate selection.

Background: Sepsis and acute kidney injury (AKI) are common, often co-occurring ICU syndromes with high mortality. Although illness severity scores such as the Simplified Acute Physiology Score II (SAPS II) are powerful prognostic tools, it is unclear whether baseline illness severity modifies the relationship between sepsis and mortality in AKI. We hypothesized that this association varies across the severity spectrum.

Methods: In a retrospective cohort of 35,926 adults with AKI, we examined the interaction between sepsis (Sepsis-3 criteria) and baseline illness severity (SAPS II) in relation to 30-day survival. We used multivariable logistic regression adjusted for demographics, comorbidities, and organ dysfunction.

Results: A significant interaction between sepsis and illness severity was observed (p < 0.001). At low severity (SAPS II = 20), sepsis was associated with a 4.3 percentage point reduction in 30-day survival, whereas at high severity (SAPS II = 90), it was associated with a 23.6 percentage point increase in survival, representing a net reversal of 27.9 percentage points. This pattern was robust in sensitivity analyses.

Conclusions: In critically ill patients with AKI, the impact of sepsis on survival is strongly modified by baseline illness severity, reversing from harm at low severity to improved survival at high severity. This paradox challenges the assumption of uniform sepsis risk and suggests that, in the sickest patients, sepsis may indicate a state of potentially reversible organ dysfunction. Incorporating illness severity into AKI prognostication may better capture recovery potential, as severity scores alone may underestimate the likelihood of recovery in severe septic AKI.

Background: This study investigated whether low-phosphate boiled-meat meals (LP meals), provided together with a fixed minimal dose of calcium carbonate (CaCO₃), could help maintain stable CKD-MBD and inflammatory indicators in maintenance hemodialysis (MHD) patients, compared with standard meals receiving the same CaCO₃ dose.

Methods: Participants completed an adaptation diet followed by 7 days of LP meals or standard control meals. Both groups received an identical minimal dose of CaCO₃ (1 tablet/meal) to ensure equivalent binder exposure. Blood CKD-MBD parameters, inflammatory markers, and dietary intake were assessed at baseline and after the intervention.

Results: Forty patients completed the study (LP group, n = 20; control group, n = 20). Serum phosphate levels increased significantly in the control group after the intervention but remained stable in the LP group (2nd 6.61 ± 2.04 mg/dL vs. 1st 5.61 ± 1.14 mg/dL; P < 0.05). Reductions in tumor necrosis factor-α and serum calcium from baseline were significantly greater in the LP group than in the control group (both P < 0.05).

Conclusion: The LP meals, when consumed with a controlled, minimal CaCO3 dose, helped prevent increases in blood phosphate, hypercalcemia, and inflammation compared with standard meals that received the same binder dose.

Background: Although the SARS-CoV-2 Omicron variant demonstrates lower mortality than previous variants in the general population, its impact on patients with end-stage kidney disease (ESKD) remains concerning. Substantial mortality has been reported in patients with ESKD during the Omicron period; however, comparing this with influenza mortality could provide insights into COVID-19's true impact in this high-risk population.

Methods: Using the National Database of Health Insurance Claims of Japan, we conducted a retrospective cohort study of hemodialysis patients diagnosed with COVID-19 during the Omicron period (January 2022-March 2023) or influenza (September 2017-March 2023). The primary outcome was 30-day all-cause mortality. Overlap weighting based on propensity scores balanced confounding factors.

Results: We identified 53,047 COVID-19 and 35,808 influenza cases. After overlap weighting, the 30-day mortality rates were 3.4% for COVID-19 and 1.8% for influenza (hazard ratio [HR] 1.61 [95% CI 1.47, 1.77]). In subgroup analyses stratified by age, HRs were comparable across all age groups (20-49 years: 1.59 [0.81, 3.13]; 50-59 years: 1.43 [0.94, 2.17]; 60-69 years: 1.45 [1.15, 1.84]; 70-79 years: 1.68 [1.43, 1.96]; ≥ 80 years: 1.66 [1.45, 1.89]). The absolute risk differences (per 1,000 patients) across age groups were 1.7, 2.6, 6.2, 16.2, and 28.9 deaths, respectively.

Conclusions: In this nationwide study, COVID-19 Omicron variant was associated with significantly higher mortality than influenza in hemodialysis patients. Age-stratified analyses showed consistent relative risks but progressively larger absolute risk differences in older patients.