Chronic kidney disease (CKD) is a significant comorbidity in patients with rheumatoid arthritis (RA). The relative contributions of inflammatory and traditional renal risk factors to CKD progression remain unclear. We retrospectively analyzed 601 RA patients. Renal function and urinary abnormalities were assessed using creatinine-based estimated glomerular filtration rate (eGFR) and urinary albumin. We examined the factors associated with high or very high CKD risk in KDIGO heatmap and progression of CKD stage over five years using two models: logistic regression and Cox proportional hazards models. Furthermore, Propensity score methods were used to assess the association between methotrexate (MTX) use and CKD stage progression. CKD stage progression occurred in 106 patients. Both inflammatory and traditional renal risk factors were associated with high or very high CKD risk. In Cox analyses, age, lower baseline eGFR, anemia, and CRP ≥0.5 mg/dL were associated with CKD stage progression. In patients with baseline eGFR ≥60 mL/min/1.73 m2, CRP ≥0.5 mg/dL was independently associated with progression, whereas proteinuria and albuminuria were more relevant in patients with baseline eGFR <60 mL/min/1.73 m2. After adjusting for confounding variables using propensity score matching, there was no association between MTX use and an increased risk of kidney stage progression. Risk factors for CKD progression in RA may differ according to baseline eGFR. In patients with preserved eGFR, residual inflammation appears to be a relevant factor. In contrast, proteinuria, albuminuria, and anemia are more significant in patients with reduced eGFR.
Longitudinal studies have not examined the associations between albuminuria and renal function and changes in brain volume. Therefore, we investigated it in a general Asian population after excluding individuals with antihypertensive medication use and accounting for loss to follow-up bias. We analyzed data from 114 participants aged ≥ 50 years without a history of ischemic heart disease, stroke, or antihypertensive treatment in Ohasama town, Japan. Brain volumes were measured using magnetic resonance imaging. Multiple linear regression was performed to assess the associations between urinary albumin-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) and annual symmetric percentage change (ASPC) in brain volume after adjusting for covariates. Dropout bias was adjusted using inverse probability weighting (IPW). The mean age of participants was 66.9 years, 72.8
Evidence regarding the renoprotective effects of angiotensin receptor–neprilysin inhibitor (ARNI) in patients with chronic kidney disease (CKD) remains limited. We investigated the association of ARNI initiation with changes in estimated glomerular filtration rate (eGFR) slope and home blood pressure in patients with non-dialysis CKD. This retrospective single-center study included 89 patients with non-dialysis CKD who were switched from renin–angiotensin system inhibitors to sacubitril/valsartan because of insufficient blood pressure control. Changes in eGFR slope before and after ARNI initiation were evaluated using linear mixed-effects models. Associations between post-treatment home systolic blood pressure (post-HSBP) and eGFR slope were also assessed. Mean age was 72 ± 11 years, and baseline eGFR was 29 ± 15 mL/min/1.73 m2. The eGFR slope changed from − 3.81 to − 1.28 mL/min/1.73 m2/year after ARNI initiation, corresponding to a slope difference of + 2.52 mL/min/1.73 m2/year (95
Exposure to foodborne mycotoxins such as ochratoxin A (OTA) and citrinin (CIT) causes severe oxidative stress-mediated nephropathy. This study investigated the protective potential of 5-hydroxy-1-methylhydantoin (NZ-419), an endogenous creatinine metabolite, against OTA- and CIT-induced toxicity in human proximal tubular epithelial (HK-2) cells. We evaluated the radical-scavenging activity of NZ-419 using cell-free assays, including electron spin resonance. In HK-2 cells, its effects on mycotoxin-induced cytotoxicity, reactive oxygen species (ROS) generation, mitochondrial membrane potential (MMP), and related signaling pathways were assessed using biochemical assays, Western blotting, and qPCR. The effects of NZ-419 on hypoxia-reoxygenation-induced cellular stress were also examined. NZ-419 selectively scavenged hydroxyl radicals and peroxynitrite. In HK-2 cells, it significantly attenuated OTA-induced cytotoxicity. While not fully restoring viability in CIT-treated cells, it effectively mitigated oxidative stress induced by both mycotoxins. NZ-419 prevented MMP depolarization and upregulated Bcl-2, indicating anti-apoptotic potential. It suppressed ROS overproduction and NADPH oxidase 4 (NOX4) expression while activating the Keap1-Nrf2 pathway, upregulating antioxidant genes (SOD1, CAT, and GPx). Furthermore, NZ-419 reduced HIF-1α and CTGF expression under both mycotoxin-induced and hypoxia-reoxygenation conditions. NZ-419 selectively scavenges toxic radicals and attenuates mycotoxin-induced oxidative stress and mitochondrial dysfunction in HK-2 cells. These findings provide mechanistic evidence for the protective effects of NZ-419 and support its potential as a renoprotective agent against oxidative stress-related kidney injury.
Gallstones and acute cholecystitis are not usually regarded as core nephrology problems, yet accumulating observational evidence suggests that their burden is increased in chronic kidney disease (CKD), particularly in advanced predialysis CKD and end-stage kidney disease (ESKD). Plausible contributors include impaired gallbladder motility related to uremia-associated autonomic dysfunction, shared metabolic risk clustering, and, in selected patients, hemodynamic vulnerability related to intradialytic hypotension or low-output states. The central clinical issue may be underrecognition. In CKD and dialysis, abdominal complaints are often nonspecific and may overlap with uremic or intercurrent illness-related symptoms. In addition, uncomplicated acute cholecystitis may present early with absent or only mild hepatobiliary enzyme abnormalities, whereas marked bilirubin elevation or a cholestatic pattern should prompt evaluation for choledocholithiasis or cholangitis. Ceftriaxone-associated pseudolithiasis and glucagon-like peptide-1 receptor agonist exposure may further complicate the diagnostic picture. Although evidence linking CKD itself to primary acute cholangitis is less robust than that linking CKD to gallstones and acute cholecystitis, biliary obstruction and endoscopic intervention remain relevant because advanced CKD and ESKD may increase procedure-related morbidity. Emerging data also caution against reflexive therapeutic nihilism: source control should not be deferred solely because a patient has advanced CKD or dialysis dependence, and gallbladder drainage may serve as a planned bridge or alternative in selected high-risk patients. This focused review summarizes the epidemiologic links, plausible mechanisms, diagnostic pitfalls, and practical management implications of gallstones and acute cholecystitis in CKD and dialysis, and highlights why biliary disease should be recognized as an underappreciated comorbidity in nephrology care.
Hyperuricemia was associated with faster progression of proteinuria in diabetic nephropathy. However, the underlying mechanisms remained largely unknown. Therefore, this study aimed to explore whether there was a tightly regulated process involved in susceptibility to hyperuricemia under diabetic conditions. We established a diabetes model with hyperuricemia superimposed both in vivo and in vitro. The urinary albumin: creatinine ratio, biomarkers of podocyte damage, markers of inflammasome activation, and autophagosome markers were assessed. In vivo, we found that hyperuricemia aggravated podocyte injury in a diabetic mouse model, manifested by significantly increased albuminuria levels and severe slit diaphragm abnormalities. In addition, significantly excessive inflammasome activation, which might initiate hyperinflammation resulting in podocyte injury, was also found in the glomeruli of the superposed model, accompanied by diminished staining of the autophagosome marker LC3. Accordingly, in vitro, we revealed that high glucose pretreatment induced autophagic deficiency, potentiating inflammasome activation in podocytes. Furthermore, we confirmed that 3-methylamphetamine (3-MA), an inhibitor of autophagy, could aggravate uric acid-induced inflammasome activation in a dose- and time-dependent manner, whereas rapamycin, an inducer of autophagy, could alleviate uric acid-induced inflammasome activation in a dose- and time-dependent manner. Collectively, our data suggested that autophagic deficiency occurring in diabetic kidney disease might sensitize podocytes to hyperuricemia-induced injury by amplifying inflammasome activation. Enhancement of autophagy might provide a promising avenue for ameliorating inflammasome activation and preventing podocyte injury in established diabetic nephropathy.
Roxadustat, a hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI), exerts pleiotropic effects beyond erythropoiesis, including modulation of inflammation and immune responses. Preliminary studies suggest Roxadustat may modulate inflammation to reduce peritoneal dialysis-associated peritonitis (PDAP) risk, but this requires further proof. Patients treated with Roxadustat or recombinant human erythropoietin (rhuEPO) at least three months from September 2014 and September 2024 were respectively enrolled. 1:1 propensity score matching (PSM) was performed based on age, sex, albumin, hemoglobin, lipid profiles, and initial urine volume. The primary outcome was PDAP incidence rate, expressed as episodes per person-year. Incidence rate ratios (IRRs) were estimated using Poisson regression models. Among 296 eligible patients, PSM yielded 136 well-balanced individuals (68 per group). Over 225.85 patient-years of follow-up, 41 peritonitis episodes were recorded. The Roxadustat group exhibited a significantly lower PDAP incidence rate than the rhuEPO group (0.131 vs. 0.212 episodes per patient-year). Multivariable Poisson regression, adjusted for age, potassium, and albumin, confirmed that Roxadustat was associated with lower PDAP risk (adjusted IRR 0.494, 95
Sodium–glucose cotransporter 2 (SGLT2) inhibitors provide cardiorenal protection; however, a transient decline in estimated glomerular filtration rate (eGFR), known as the ‘‘initial dip’’, is frequently observed after initiation. Although this phenomenon reflects changes in intraglomerular hemodynamics, excessive decline may be associated with worsening renal function. Angiotensin receptor–neprilysin inhibitors (ARNIs) have demonstrated renal protective effects in heart failure, but their impact on the initial dip after SGLT2 inhibitor initiation remains unclear. We retrospectively evaluated the effect of prior ARNI use on the initial dip following SGLT2 inhibitor initiation in 157 patients with chronic kidney disease who newly started SGLT2 inhibitors between 2022 and 2025. Patients were classified into an ARNI group and an angiotensin receptor blocker (ARB) group. The primary outcome was the incidence of an initial dip, defined as a ≥ 5
Although depression is common among patients with chronic kidney disease (CKD), its impact on the incidence of end-stage kidney disease (ESKD) and all-cause mortality remains unclear. This retrospective cohort study used Cox proportional hazards (CPH) models and CPH models with penalized splines to assess the association between depression severity and the incidence of ESKD and mortality in patients with CKD, drawing on data from the Chronic Kidney Disease Japan Cohort (CKD-JAC) Study. This study included 1,694 patients with CKD (median age 61 years; mean eGFR 29.0 ± 12.2 mL/min/1.73 m2; median Beck Depression Inventory-II (BDI-II) score 8). Depression severity was classified into four categories: normal (0–13), mild (14–19), moderate (20–28), and severe (≥ 29). In Multivariable CPH models, ESKD risk showed a stepwise elevation in hazard ratios (HRs) without reaching statistical significance, whereas, mortality risk increased significantly in the moderate and severe group: HR 3.11 (95
Eldecalcitol is an active vitamin D analogue used for osteoporosis in Japan. Its usual dose is 0.75 μg/day, but calcium-related adverse effects can become clinically important when reduced kidney reserve, frailty, low body weight, poor intake, dehydration risk, interacting medicines, or unreliable follow-up coexist. This narrative review synthesizes trial, post-marketing, pharmacovigilance, and real-world monitoring evidence to define a practical safety framework. Eldecalcitol reduces vertebral fractures compared with alfacalcidol, whereas hip-fracture protection has not been established; therefore, its role should be determined by the patient's fracture pattern, treatment objective, kidney function, and availability of alternatives with established hip-fracture efficacy. Before treatment, clinicians should confirm osteoporosis, measure total serum calcium with albumin (and use albumin-adjusted calcium where appropriate), and assess serum creatinine with reported eGFR. Primary hyperparathyroidism and other metabolic bone disorders should be considered when baseline findings are atypical. Creatinine-based eGFR is the pragmatic minimum standard; cystatin C is most useful when low muscle mass or discordance makes kidney reserve uncertain. A lower dose of 0.5 μg/day is a dose-adjustment or re-challenge option after calcium normalization; it does not remove the need for calcium surveillance and clinical reassessment, and long-term fracture-prevention efficacy at that dose is not established. Eldecalcitol should be withheld during poor intake, dehydration, or acute illness and reconsidered when calcium rises or kidney function deteriorates. Safe use therefore requires risk-based selection rather than passive routine-dose prescribing, planned biochemical follow-up, and explicit treatment reassessment.
Chronic kidney disease (CKD) is associated with dysregulated lipid metabolism, particularly in proximal kidney tubules, where fatty acid oxidation serves as the primary energy source. The proximal tubules’ reliance on fatty acid oxidation rather than glycolysis underscores their unique metabolic profile, consistent with the absence of key glycolytic enzymes. This dysregulation contributes to maladaptive hypertrophy in CKD, where surviving nephrons exhibit compensatory hypertrophy to maintain kidney function. Here, we focus on two key regulators of lipid metabolism: peroxisome proliferator–activated receptor alpha (PPARα) and adenosine monophosphate (AMP)-activated protein kinase (AMPK). Recent multi-omics studies have identified PPARα as an important determinant of proximal tubule cell size and a mediator of compensatory hypertrophy. In CKD models, AMPK activity decreases, impairing cellular responses to energy stress, as indicated by altered AMP/ATP ratios. This defective energy sensing may be exacerbated by uremic metabolites that diminish AMPK function. Unc-51-like autophagy activating kinase 1 (ULK1) has been identified as a regulator of AMPK activity through specific phosphorylation sites that enhance AMP sensitivity. Future research should assess whether targeting these pathways restores metabolic homeostasis and mitigates CKD progression by enhancing AMPK activity and lipid metabolism.
ARHGAP24, a GTPase-activating protein (GAP) for the Rho family small GTPase Rac1, is highly expressed in podocytes and is thought to contribute to maintaining glomerular filtration barrier. Variants in ARHGAP24 have been implicated in human kidney diseases. However, the physiological requirement of ARHGAP24 in podocytes remains unclear. Here, we generated an arhgap24 knockout (KO) zebrafish, a well-established model organism, to investigate the in vivo role of ARHGAP24 in podocytes. An arhgap24 KO zebrafish was generated using the CRISPR/Cas9 double-nicking method with paired CRISPR RNAs targeting sequences flanking an arginine residue essential for GAP activity to increase target specificity and minimize off-target effects. Glomerular and podocyte morphology in adult arhgap24-deficient zebrafish was examined by light, immunofluorescence, and electron microscopy. We obtained a homozygous arhgap24 KO mutant lacking the catalytic arginine residue. Microscopic observations of the glomerulus in arhgap24-deficient zebrafish revealed widening of podocyte foot processes and glomerular basement membrane structural changes, including thickening, lamellation, spike-like extensions, and small electron-dense granules, which are typical features of glomerular and podocyte injury associated with disrupted glomerular filtration barrier. arhgap24 deficiency altered glomerular ultrastructure in zebrafish. This study provides initial evidence for an in vivo role of ARHGAP24 and suggests a potential link to human kidney disease.
Serum zinc levels decline with chronic kidney disease (CKD) progression, and zinc deficiency has been linked to impaired urinary sodium excretion and hypertension. However, its clinical impact on hypertension management in end-stage kidney disease remains unclear. This study investigated the association between serum zinc deficiency and antihypertensive treatment intensity in patients with stage 5 CKD initiating dialysis. In this single-center cross-sectional study, 175 adults initiating hemodialysis or peritoneal dialysis between November 2021 and December 2024 were included. Serum zinc levels were measured at dialysis initiation, and zinc deficiency was defined as < 60 μg/dL. Logistic and ordered logistic regression analyses adjusted for demographic and hypertension-related factors were conducted to evaluate factors associated with zinc deficiency and its relationship with the number of prescribed antihypertensive agents. Zinc deficiency was present in 59.4
Despite the rise of cancer immunotherapy, cisplatin remains a cornerstone in chemotherapy. Hyponatremia is a common but under-recognized adverse event of cisplatin. Previous studies on cisplatin-induced hyponatremia (CIH) are limited and mostly focus on the initial administration. This study aimed to assess the overall incidence of CIH and identify significant predictive factors. We conducted a single-center, retrospective cohort study of patients who received intravenous cisplatin at Juntendo University Hospital between 2018 and 2020. The occurrence and severity of CIH were assessed across all administrations. Predictive factors were analyzed using multiple logistic regression and generalized linear mixed models. Among 706 patients, 340 (48.2
Anemia in chronic kidney disease (CKD) is associated with poor outcomes, including CKD progression, mortality, and cardiovascular events. Standard treatments include iron supplements and injectable erythropoiesis-stimulating agents (ESAs). Oral hypoxia-inducible factor–prolyl hydroxylase inhibitors (HIF–PHIs) have recently emerged as a new treatment option, providing easier accessibility for general practitioners. This real-world descriptive study used the Japan Medical Data Survey database to analyze the prevalence of anemia, anemia treatment, and treatment type in non-dialysis patients with CKD and treated in primary care clinics. Data from 1 January 2018 to 31 December 2023 were assessed and analyzed by subgroups (year, CKD stage, patient age, treatment setting, sex, and region). This study included 397,419 patients. Anemia treatment rates increased from 16.4
INTRODUCTION:Point-of-care ultrasound (POCUS) is increasingly incorporated into nephrology practice, yet comparative data on educational strategies and the durability of their effects remain limited. We conducted a questionnaire-based study to examine whether a structured workshop (WS) differs from on-the-job training (OJT) in shaping self-reported POCUS practice and confidence among early-career nephrologists. METHODS:In August 2025, nephrologists with fewer than 15 postgraduate years at a single academic center were surveyed. Participants were categorized into three cohorts: those who attended a structured WS program (didactic lectures and hands-on training) in 2023, those who received OJT only in 2024, and those who received OJT only in 2025. All assessments were retrospectively reported at a single survey time point. Outcomes included self-rated confidence in examination frequency, technical skill, image interpretation, and mentoring others using a 5-point Likert scale. RESULTS:Thirty-four respondents (79.1% of all eligible nephrologists) were analyzed. In recalled post-training assessments, the WS group demonstrated higher confidence in interpretation and mentoring compared with OJT cohorts, whereas no differences were observed in technical skill or examination frequency. At the time of the survey, no significant between-group differences persisted. Within the WS group, confidence scores declined across all domains over time. CONCLUSION:In this exploratory study, structured workshops were associated with greater recalled post-training confidence in interpretative and mentoring domains, but these gains attenuated without reinforcement. Sustainable integration of nephrology-specific POCUS may require longitudinal, organization-supported educational frameworks rather than isolated instructional interventions, such as OJT alone.
Infection is a major cause of death in patients undergoing maintenance hemodialysis (HD). We examined whether the high-sensitivity Glasgow prognostic score (hsGPS), derived from serum C-reactive protein (CRP) and albumin, is associated with infection-related mortality. This retrospective cohort study included 3529 patients undergoing maintenance HD enrolled between December 31, 2006 and December 31, 2007 and followed until December 31, 2016. We used a high-sensitivity Glasgow prognostic score (hsGPS), defined using a lower CRP threshold in a GPS-type manner as follows: score 0, CRP ≤ 0.3 mg/dL and albumin ≥ 3.5 g/dL; score 1, CRP > 0.3 mg/dL or albumin < 3.5 g/dL; and score 2, CRP > 0.3 mg/dL and albumin < 3.5 g/dL. Associations were evaluated using Kaplan–Meier analysis, Cox proportional hazards models, Fine–Gray competing-risk models, and restricted cubic spline analyses. During a median follow-up of 3199 days, 1748 deaths occurred, including 451 infection-related deaths. In descriptive Kaplan–Meier analysis, infection-related death-free survival was lower in higher hsGPS groups. In the multivariable-adjusted Cox model, hazard ratios for infection-related mortality were 1.79 (95
The relationship between kidney function and hyponatremia risk remains poorly defined, particularly in patients with well-preserved kidney function. We aimed to clarify this association in an outpatient population across the full spectrum of kidney function. We conducted a cross-sectional study of 130,194 outpatients in Japan between 2010 and 2020. Multivariable logistic regression assessed the association between estimated glomerular filtration rate (eGFR) and hyponatremia (serum sodium ≤ 135 mEq/L), adjusting for demographic, clinical, medication-related, and laboratory covariates. The relationship between eGFR and urine concentration in hyponatremic patients was also assessed using the urine-to-plasma osmolality ratio. The prevalence of hyponatremia was 4.3
Autosomal dominant polycystic kidney disease (ADPKD) is characterized by progressive cyst growth, kidney enlargement, and decline in renal function. Increasing evidence suggests that inflammatory processes may contribute to disease progression. This study aimed to evaluate the association between tolvaptan use, systemic inflammatory markers, and total kidney volume (TKV) progression in patients with ADPKD. This retrospective study included 67 patients with ADPKD, including 40 receiving tolvaptan and 27 untreated controls. Neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), estimated glomerular filtration rate (eGFR), and TKV were evaluated at baseline and after 24 months. Longitudinal changes were assessed using Wilcoxon signed-rank tests and linear mixed-effects models. Patients receiving tolvaptan were younger and had higher baseline TKV values than untreated patients. During follow-up, NLR, PLR, and SII decreased in the tolvaptan group, whereas these markers increased in untreated patients. eGFR declined in both groups but appeared less pronounced in patients receiving tolvaptan. TKV increased in both groups; however, the percentage increase in TKV was lower among patients receiving tolvaptan. Significant time × treatment interactions were observed for NLR, PLR, SII, and TKV. In the non-tolvaptan group, NLR at 24 months showed a significant positive association with TKV. Tolvaptan use was associated with differences in longitudinal changes in systemic inflammatory markers and kidney volume progression in ADPKD. Further prospective studies are needed to clarify the clinical relevance of these associations.
