Clinical and Experimental Nephrology最新文献

Background: Hepcidin-25 plays an important role in regulating iron metabolism; however, the association between hepcidin-25 levels and hyporesponsiveness to erythropoiesis-stimulating agents (ESAs) is controversial. We aimed to clarify the associations between serum hepcidin-25 levels and hyporesponsiveness to ESAs in Japanese patients receiving hemodialysis, and between hepcidin-25 levels and other factors.

Methods: This observational cross-sectional study included hemodialysis patients recruited at Heisei-Hidaka Clinic in Japan from August 2023 to June 2024. Serum hepcidin-25 levels were measured by latex immunoassay. Hyporesponsiveness to ESAs was determined by the ESA resistance index (ERI). The correlation between hepcidin-25 levels and ERI was evaluated using Pearson's correlation coefficient. We also investigated the patient characteristics associated with hepcidin-25 levels using multiple regression analysis.

Results: Hepcidin-25 levels were significantly negatively correlated with ERI (r = - 0.438, p = 0.0005). Hepcidin-25 levels also showed significant positive correlations with serum iron, transferrin saturation (TSAT), serum ferritin, and high sensitive C-reactive protein (hs-CRP), and significant negative correlations with hematocrit, unsaturated iron-binding capacity, total iron-binding capacity, and serum erythropoietin levels. Hepcidin-25 levels were significantly higher in the patients who received oral iron-containing preparations than in those without these preparations. Multiple regression analysis showed significant partial regression coefficients for ERI, hematocrit, TSAT, serum ferritin, hs-CRP, and the administration of oral iron-containing preparations.

Conclusion: Serum hepcidin-25 levels were significantly negatively correlated with the ERI. The results suggest that hepcidin-25 levels might be associated with ERI, hematocrit, TSAT, serum ferritin, hs-CRP, and the administration of oral iron-containing preparations.

Background: The initiation of hemodialysis exhibits winter-peak seasonal variations, possibly associated with increased cardiac events during winter. The season of cardiac disease onset affects prognosis; however, the relationship between the season of hemodialysis initiation and subsequent cardiac outcomes remains unclear. We aimed to evaluate this association to determine whether the season of hemodialysis initiation could influence subsequent cardiac events.

Methods: We used data from a Japanese multicenter prospective dialysis initiation cohort. We divided the patients into four groups based on the season of hemodialysis initiation: Spring, Summer, Autumn, and Winter. The outcome was 3-year cardiac events defined as a composite of ischemic heart disease, heart failure, and sudden death. Considering the competing risks, we compared the incidence of subsequent cardiac events with the hemodialysis initiation season.

Results: Among the 1396 eligible patients, hemodialysis was initiated in 402 (29%), 346 (25%), 270 (19%), and 378 (27%) patients in Spring, Summer, Autumn, and Winter, respectively. Total fluid removal, heart failure symptoms, and fluid overload during the first hemodialysis session were more frequent in Autumn and Winter. During the 3-year follow-up, 264 patients (19%) developed cardiac events. Autumn was associated with a higher risk of developing cardiac events than Summer. Compared with Summer, the adjusted subdistribution hazard ratios (95% confidence intervals) were 1.40 (0.97-2.02) in Spring, 1.50 (1.02-2.21) in Autumn, and 1.15 (0.80-1.67) in Winter.

Conclusion: Hemodialysis initiation in autumn may be a potential indicator of subsequent cardiac events. Further studies are required to elucidate the underlying pathophysiological mechanisms.

Background: The role of Janus kinase (JAK) 2 in chronic kidney disease (CKD) remains unreported. This Mendelian randomisation (MR) study investigates the causal associations of JAK2 with CKD and provides references for the identification of possible therapeutic targets and the prevention of renal dysfunction.

Methods: Summary data for JAK2 and various CKD endpoints are extracted from genome-wide association study findings provided by the MRC Integrative Epidemiology Unit and FinnGen. The causal relationships are assessed using inverse variance weighted estimates, weighted median and MR-Egger regression. To ensure rigour, reverse MR, radial MR and leave-one-out approaches are employed for sensitivity analyses, with Cochran's Q used to assess heterogeneity.

Results: Inverse variance weighted estimates indicate potential two-way causal associations between JAK2 and membranous nephropathy (MN) (odds ratio [OR] = 1.138, 95% confidence interval [CI]: 1.073-1.206; reverse causal association: OR = 1.040, 95% CI: 1.002-1.079). Sensitivity analyses demonstrate that these relationships are relatively robust. An underlying causal relationship between JAK2 and estimated glomerular filtration rate is identified (OR = 0.996, 95%CI 0.993-1.000); however, this becomes non-significant after the radial MR test (P > 0.05). In addition, polycystic kidney disease exhibits a potential causal relationship with JAK2 (OR = 1.066, 95%CI 1.009-1.127).

Conclusions: Elevated relative expression of JAK2 may represent a potential risk factor for the occurrence of MN. Conversely, patients with MN may exhibit high relative expression of JAK2. These two-way causal associations may inform future efforts aimed at the prevention of CKD and the identification of possible therapeutic targets.

Background: The role of peripheral vascular smooth muscle cells (VSMCs) in vascular calcification has been overlooked compared with that of the major VSMCs. This study aimed to investigate the differentially expressed genes (DEGs) of peripheral VSMCs in patients with critical limb ischemia (CLI) results from peripheral arterial disease and Chronic Kidney disease (CKD).

Methods: We isolated peripheral VSMCs from the posterior tibial artery of 6 patients with CKD who underwent below-knee amputation for CLI. Using normal human aortic VSMCs as a control, we cultured all samples in normal and high phosphate media for 10 days. Total RNA was extracted and analyzed using mRNA sequencing. Expression levels of genes related to contractile and synthetic phenotypes were examined. Bioinformatics analysis of the DEGs was performed.

Results: All four genes (ACTA2, CALD1, CNN1, and TAGLN) related to the contractility phenotype increased only in the control group. The expression of all four genes (ICAM1, SPP1, MMP3, and TIMP1) related to the synthetic phenotype showed no significant changes or decreases in all samples. Several genes (SERTAD4, ITGA11, SPRN, IGFBP6, BCL2A1, APOE, TRABD2A, and FAM13B) showed significant changes under calcifying conditions. Only UNC5B expression showed an opposite pattern between normal human aortic VSMC and pathological peripheral VSMCs.

Conclusions: UNC5B was overexpressed only in pathologic peripheral VSMCs under calcifying conditions, whereas downregulated in normal aortic VSMCs. Further research on the effect of UNC5B on peripheral VSMC is warranted. (IRB number: H-1711-022-897).

Background: Cardiogenic shock (CS) after myocardial infarction remains associated with high mortality. Acute kidney injury (AKI), a common complication, substantially impacts outcomes. We investigated the prognostic relevance of AKI and renal replacement therapy (RRT) in CS.

Methods: In this retrospective study, 369 patients with infarct-related CS admitted to a tertiary center were analyzed. AKI was defined by KDIGO criteria. Clinical, laboratory, and hemodynamic data, including RRT use and in-hospital outcomes, were evaluated. Multivariable logistic regression identified independent predictors of AKI and RRT. Discriminatory power was assessed using AUC.

Results: AKI occurred in 42.8% of patients (n = 143), with 60.1% developing AKI within 48 h and 35.0% classified as stage 3. AKI patients were older (70.5 vs. 67.2 years; p = 0.010), had more pre-existing CKD (100 vs. 83.3%; p = 0.002), and required longer ventilation (168 vs. 65.5 h; p < 0.001). Inflammatory, renal, and perfusion markers were significantly elevated from day 2 onward. RRT was initiated in 8.9% overall and 23.1% of AKI patients, with 60.6% mortality. Predictors of AKI included age (OR 2.40; 95% CI 1.10-5.12) and norepinephrine dose (OR 1.001 per µg/kg; p = 0.042; AUC = 0.71). Predictors of RRT were admission creatinine (OR 2.05 per mg/dL; p = 0.003) and absence of CPR (OR 0.22; p = 0.008; AUC = 0.75). Overall mortality was 57.7%, higher in women (66.4% vs. 53.4%; p = 0.021).

Conclusions: AKI is common in infarct-related CS and linked to poor outcomes. Early identification of high-risk patients may enable timely renoprotective strategies.

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.