Clinical and Experimental Nephrology最新文献

Background: In 2011, the Great East Japan Earthquake hit the Futaba District on the northeast coast of Japan, followed by a tsunami and a nuclear power plant accident. In this study, we investigated the impact of post-earthquake life on the onset of chronic kidney disease (CKD) among the residents of the Futaba District.

Methods: Data on 17,859 residents of the Futaba District (7333 men, 10,526 women; mean age: 61.0 ± 10.2 years; mean follow-up period: 3.42 ± 1.51 years) who underwent health checkups and completed self-administered questionnaires in the Fukushima Mental Health and Lifestyle Survey were analyzed. These residents were confirmed to be CKD-free in 2012. Hence, they were assessed for the onset of CKD from 2013 to 2017.

Results: Univariate analysis results showed significant differences between residents with and without CKD. Differences in age, diabetes mellitus, body mass index (BMI), dyslipidemia, hypertension, hyperuricemia, Kessler 6 Psychological Distress Scale (K6) score, smoking habit, alcohol drinking history, exercise habit, history of job change, history of job loss, and evacuation experience were observed. Multivariate analysis was conducted to adjust for multiple factors, and age, BMI, dyslipidemia, hypertension, hyperuricemia, and K6 score were identified as significant promotional factors for CKD onset.

Conclusion: Among the well-recognized risk factors, severe stress reflected by a high K6 score was established to be correlated with CKD onset among residents originally without CKD. Stress management may be another treatment strategy for treating CKD.

Background: Although proteinuria is a key prognostic marker in immunoglobulin A nephropathy (IgAN), the optimal post-biopsy timing for its assessment remains uncertain, particularly given variability in treatment type and timing. Using longitudinal data from the Japan IgA Nephropathy Prospective Cohort Study (J-IGACS), we sought to identify the post-biopsy time point at which proteinuria most reliably predicts kidney outcomes.

Methods: Proteinuria was assessed at baseline and at 6, 12, 18, and 24 months after biopsy. The primary outcome was defined as a ≥ 50% increase in serum creatinine or initiation of kidney replacement therapy in adults (≥ 20 years) and as a ≥ 25% decline in eGFR or initiation of kidney replacement therapy in patients aged < 20 years. Model performance was compared using the corrected Akaike Information Criterion.

Results: Among 588 patients (median age 38 years; mean eGFR 76.5 mL/min/1.73 m²; median proteinuria 0.64 g/day), 43 (7.3%) reached the primary outcome during a median 78-month follow-up. Proteinuria at all time points was independently associated with kidney outcomes, with the 18-month measurement providing the best model fit. A threshold of 0.44 g/day (or g/gCr) yielded 79% sensitivity and 81% specificity, and patients with proteinuria ≥ 0.44 g/day at 18 months had significantly worse outcomes. Cox regression confirmed a robust association for 18-month proteinuria, irrespective of treatment type or timing.

Conclusions: Proteinuria measured 18 months post-biopsy showed the strongest association with long-term kidney outcomes in IgAN, supporting its use as a universal treatment target across heterogeneous post-biopsy clinical courses.

Background: The risk of mortality and cardiovascular disease (CVD) may be higher among some super-older adults with chronic kidney disease (CKD). We assessed outcomes across CKD stages in an aging Japanese population.

Methods: This retrospective cohort study using nationwide health examination and insurance claims database enrolled individuals aged 75-90 years whose renal function was measured > 2 times during the observation period. CKD stages were classified using eGFR and urinary protein levels. We used a Cox proportional hazards model to evaluate all-cause mortality and CVD events by CKD stage and a logistic regression model to assess dialysis initiation by renal function and proteinuria among patients with advanced CKD.

Results: Of 365,664 individuals aged 75-90 years, > 30% met the CKD diagnosis criteria, mostly the CKD G3aA1 category. During follow-up, 18,238 deaths and 48,937 CVD events occurred. Mortality and CVD incidence increased with advancing CKD stages. Mortality risk was elevated only among G3a patients with urinary protein (A2/3: HR 1.64 [95% CI 1.53-1.76]), but not without (A1: HR 1.01 [0.97-1.05]). CVD risk increased significantly across all A2/3 stages, but not in A1. Dialysis was initiated in 9.5% of patients with CKD G4/5, with an earlier risk observed in the A2/3 group.

Conclusion: In older adults, CKD prognosis varies according to stage and proteinuria. Most individuals with early-stage, proteinuria-negative CKD do not experience adverse outcomes, whereas trace or greater proteinuria indicates higher risk. Outcome-based CKD management in a super-older population is essential to avoid overtreatment and ensure appropriate care.

Background: Proteinuria reduction is an established surrogate endpoint for IgA nephropathy (IgAN) progression in international trials, but evidence in Japanese populations is scarce. We aimed to assess the association between early changes in proteinuria and long-term kidney outcomes in a large, real-world cohort of Japanese patients with IgAN.

Methods: This nationwide, multicenter cohort study utilized the Japan Chronic Kidney Disease Database (J-CKD-DB) data. We analyzed 1,039 IgAN patients (mean age 48.8 years; 46.0% women), categorized by dipstick proteinuria change at 9 ± 1 months from baseline: a reduction group (≥1-step improvement) and a non-reduction group (stable or worsened). The primary outcome was total eGFR slope; secondary was a composite kidney event (≥40% eGFR decline or eGFR < 15 mL/min/1.73 m²).

Results: The mean baseline eGFR was 56.8 (±27.7) mL/min/1.73 m². During a median follow-up of 1,357 days, the mean annual eGFR slope in the reduction group was -0.13 mL/min/1.73 m² (95% CI, -0.37 to 0.11), compared to -2.73 mL/min/1.73 m² (95% CI, -2.96 to -2.49) in the non-reduction group. In multivariable adjustment for baseline covariates, the hazard ratio for the composite kidney event in the reduction group was significantly lower compared to the non-reduction group was 0.79 (95% CI, 0.63-0.99).

Conclusions: In this large, real-world Japanese cohort, early dipstick proteinuria reduction was significantly associated with both a slower long-term eGFR decline and a lower risk of major kidney events. These findings may support the use of early proteinuria reduction as a surrogate endpoint for clinical trials and regulatory evaluation of IgA nephropathy in Japan.

Background: Renal involvement, occurring in approximately -1% to 5% of patients with sarcoidosis, is characterized mainly by granulomatous interstitial nephritis. Angiotensin-converting enzyme (ACE) reflects the presence of granuloma; accordingly, serum ACE (sACE) and tubular injury markers are measured in renal sarcoidosis (RS). However, these markers possess low diagnostic accuracy; therefore, we hypothesized that urinary ACE (uACE) could reflect granuloma in the kidneys and be a disease-specific marker for RS.

Methods: In this single-center retrospective study, the sACE and uACE levels were measured and the creatinine-corrected ratio of uACE and sACE (u/s ACE ratio) was calculated. Additionally, patients with sarcoidosis without renal insufficiency (RI), sarcoidosis with RI, and tubulointerstitial nephritis (TIN) without a sarcoidosis etiology were included as controls.

Results: This study included 18, 18, 14, and 10 patients in the RS, sarcoidosis without RI, sarcoidosis with RI, and TIN without sarcoidosis etiology groups, respectively. uACE and u/s ACE ratio in the RS group were higher than those in the control groups. In the RS group, u/s ACE ratio was positively correlated with the degree of tubulointerstitial injury (r = 0.69, P = 0.0045); the cutoff value of u/s ACE ratio for diffuse tubulointerstitial injury was 0.39%, with a sensitivity and specificity of 100.0% each. Furthermore, obvious positive correlations were observed among u/s ACE ratio, inflammatory cell infiltrates (r = 0.53, P = 0.044), and interstitial fibrosis (r = 0.56, P = 0.029) in the RS group.

Conclusion: u/s ACE ratio and sACE could be useful biomarkers for diagnosing RS in sarcoidosis and TIN, respectively. A simple uACE assay could help diagnose and assess disease severity in patients with RS.

Background: Pediatric kidney failure carries high cardiovascular risk. Kidney transplantation is the preferred therapy, yet residual endothelial dysfunction contributes to post-transplant morbidity. The current study determines whether pre-transplant hemodialysis versus peritoneal dialysis affects post-transplant levels of soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular adhesion molecule-1 (sVCAM-1), P-selectin, and nitric oxide (NO) in pediatric kidney transplant recipients.

Methods: In a cross-sectional study, we assessed 53 children 6-24 months after kidney transplantation. Fourteen had received peritoneal dialysis and 39 hemodialysis pre-transplant. Serum sICAM-1, sVCAM-1, and P-selectin were measured using a Luminex-based assay and NO by chemiluminescence.

Results: Baseline demographic characteristics were similar between groups. Peritoneal dialysis was associated with lower sICAM-1 (p= 0.028) and sVCAM-1 (p= 0.006) and higher NO (p< 0.001), whereas P-selectin did not differ (p= 0.308). sICAM-1 correlated positively with P-selectin (r= 0.286, p= 0.038) and dialysis duration (r= 0.303, p= 0.028) and inversely with glomerular filtration rate (r=-0.328, p= 0.016). sVCAM-1 correlated positively with dialysis exposure time (r= 0.340, p= 0.013) and negatively with NO (r=-0.393, p= 0.004). Dialysis type and duration predicted sVCAM-1 (R²=0.199), dialysis exposure time-predicted sICAM-1 (R²=0.203), and modality-predicted NO (R²=0.252).

Conclusions: In pediatric kidney transplant recipients, pre-transplant peritoneal dialysis is associated with reduced endothelial activation and enhanced NO bioavailability compared with hemodialysis, suggesting a vascular benefit that could inform dialysis selection prior to transplantation.

Background: Proteinuria is a key marker of chronic kidney disease, notably in diabetic nephropathy (DN) and IgA nephropathy (IgAN). This study examined urinary IgG fragmentation and its link to disease progression.

Methods: Urinary IgG fragments were analyzed via western blot in diabetic mice and human subjects (controls: n = 7; diabetics: n = 14; IgAN: n = 15). Mouse and human IgG cleavage with renal tubular and glomerular fractions was performed in the presence or absence of protease inhibitors. Urinary cathepsin B activity was also measured.

Results: In diabetic mice, a 31-kDa IgG fragment appeared in the urine before the onset of albuminuria. This process was mediated by cathepsin D in the tubular fraction. Analysis of human subjects showed that fragmented IgG, especially the 47 kDa fragment, was increased in the urine of diabetic patients and correlated with elevated glycated hemoglobin (HbA1c) levels, but not in IgAN patients. Cathepsin B generated the IgG fragment by the tubular fraction, and its urinary activity was lower in IgAN patients than in diabetics.

Conclusion: Distinct patterns of IgG fragmentation and cathepsin B activity in DN versus IgAN suggest urinary IgG fragments may serve as early biomarkers and reflect disease-specific proteolytic pathways.

Background: The phenotype of autosomal recessive polycystic kidney disease (ARPKD) can be quite variable: some patients progress to end-stage kidney disease (ESKD) in infancy, while others may not require kidney replacement therapy (KRT) until later childhood or adolescence. This study aimed to evaluate clinical, biochemical, imaging, and genetic findings that may influence kidney prognosis in pediatric patients with ARPKD.

Methods: The patients diagnosed before birth or in the first month were classified as perinatal presenters and later than 1 month as non-perinatal presenters. Additionally, groups were formed based on estimated glomerular filtration rate (eGFR) at the last visit and variant types.

Results: Seventeen patients (8 male, 9 female) were enrolled in the study. Kidney survival rates at 5 years was 71.4% in the perinatal group, whereas it was 100% in the non-perinatal group. The early height-adjusted kidney dimension (haKD) was positively correlated with perinatal presentation and antenatal diagnosis. At the last follow-up, the mean eGFR was significantly lower in the truncating group with four patients (23.5%) progressing to stage-5 chronic kidney disease (CKD).

Conclusions: The kidney survival rate is lower in patients with early presentation. Initial low eGFR and severe variants are important predictors of kidney survival. Additionally, early high haKD may be associated with poor kidney outcome. Further studies with larger patient populations and long-term follow-up are necessary to better understand the prognosis of pediatric patients with ARPKD.

Background: Cognitive impairment is a prevalent comorbidity in patients with chronic kidney disease (CKD). While hemodialysis (HD) and peritoneal dialysis (PD) are established renal replacement therapies, their relative effects on cognitive outcomes remain unclear. This meta-analysis compared cognitive outcomes between HD and PD in CKD patients.

Methods: The protocol was prospectively registered on PROSPERO (CRD42024602533). PubMed, CENTRAL, Embase, Medline, Web of Science, PsychInfo, and CINAHL were searched from January 2000 to January 2025. Eligible studies included cohort studies of adult patients undergoing HD versus PD. Primary outcomes were cognitive function and dementia incidence. A random-effects meta-analysis model was used. Risk of bias was assessed using ROBINS-I, and evidence quality was evaluated using GRADE. Methodological rigor was benchmarked against previous reviews using AMSTAR 2.0.

Results: The search identified 1489 studies, of which 26, involving 326,216 patients, were included. There was a statistically significant difference in overall cognitive function between HD and PD (SMD: -0.46; 95% CI: -0.62 to -0.29; p < 0.00001; I² = 49%), and dementia incidence (OR: 1.68; 95% CI: 1.25 to 2.25; p = 0.0006; I² = 94%). Subgroup and qualitative analyses suggested PD offers advantages in executive function, verbal memory, and cognitive stability.

Conclusions: Quantitative analyses revealed significant evidence, and qualitative trends suggest PD may be associated with better cognitive outcomes in select domains. These findings underscore the need to individualize dialysis modality decisions based on cognitive risk profiles and conduct further standardized research.

Background: Zinc-α2-glycoprotein (ZAG) is an adipokine, which may act locally to regulate adipocyte metabolism. Downregulation of ZAG expression in obesity has been reported in obesity in both mice and humans. In contrast, other studies revealed that serum ZAG levels were positively associated with renal dysfunction. We investigated whether serum ZAG levels serve as a biomarker for renal impairment in a general population, both cross-sectionally and longitudinally.

Methods: A total of 223 residents (85 men and 138 women, mean age 67.1 ± 9.7 years old) underwent health examinations in 2011. Baseline fasting blood samples were collected, including measurement of serum ZAG. Participants were followed annually for 13 years.

Results: Mean serum ZAG levels were 49.2 ± 13.7 μg/mL in males, and 41.7 ± 9.0 μg/mL in females. In univariate analysis, ZAG levels were significantly associated with male gender (p = 0.005), estimated glomerular filtration rate (eGFR p = 0.004, inversely), smoking habit (p = 0.031), and medication for hyperlipidemia (p = 0.024 inversely). In multiple logistic regression analysis, eGFR (p = 0.002, inversely), male gender (p = 0.003), and medication for hyperlipidemia (p = 0.038 inversely) remained significantly and independently associated with serum ZAG at baseline. During follow-up, 31 subjects developed chronic kidney diseases (CKD). However, baseline ZAG was not significantly associated with incident CKD over 13 years.

Conclusions: Serum ZAG levels were independently associated with renal function and may represent a novel biomarker of renal dysfunction in a general population. However, ZAG did not predict long-term CKD development.