Clinical and Experimental Nephrology最新文献

Background: Exercise therapy is important for exercise tolerance, for the prevention of frailty or sarcopenia, and to improve quality of life (QOL). Previous studies, including systematic reviews, have shown the efficacy of exercise therapy for kidney transplant recipients (KTRs), but the optimal types of exercise remain unclear. Therefore, we aimed to synthesize the published evidence and compare the efficacy of types of exercise.

Methods: We systematically searched for randomized controlled trials of the efficacy of exercise therapy in KTRs on PubMed and Ichushi, then performed a meta-analysis. Exercise was categorized as aerobic training (AT), resistance training (RT), or AT + RT. The risk of bias was assessed using ROB2 and the certainty of the evidence was evaluated using the GRADE approach.

Results: Twenty-five studies were included in the study and 18 in the meta-analysis. Exercise was associated with significant improvements in QOL (SF-36 physical functioning score), cardiorespiratory function (VO₂peak), physical function (performance in the 6-min walk test (6MWT) and sit/stand test (STS)), and a metabolic index (triglyceride concentration). Kidney function tended to be superior in the exercise group, but the difference was not significant. Other indices of glucose and lipid metabolism and the incidence of hospitalization did not differ between the Exercise and Control groups. AT + RT significantly improved VO₂peak, 6MWT performance, and the triglyceride concentration, whereas AT alone did not improve VO₂peak and RT alone did not improve 6MWT performance or the triglyceride concentration. The certainty of the evidence was generally "low" or "very low".

Conclusion: Exercise therapy improved the QOL, cardiorespiratory function, physical function, and triglyceride concentration of KTRs. The AT + RT combination may be the most effective exercise therapy for such patients.

Background: Double J (DJ) stent encrustation is a common postoperative complication that can lead to severe infection, obstruction, or stent retention. Existing predictive models primarily focus on indwelling time and urinary pH but have largely excluded patients with chronic kidney disease (CKD), limiting their applicability. This multicenter study aimed to develop and externally validate a nomogram for individualized prediction of DJ stent encrustation, incorporating renal function status for the first time.

Methods: A total of 760 patients who underwent upper urinary tract stone surgery with postoperative DJ stent placement were retrospectively analyzed. Clinical, biochemical, and behavioral variables were evaluated. Multivariate logistic regression identified independent predictors, which were used to construct a predictive nomogram. External validation was performed using an independent cohort of 337 patients from another tertiary hospital. Model discrimination, calibration, and clinical benefit were assessed by receiver operating characteristic (ROC) curve analysis, bootstrap calibration, and decision curve analysis (DCA).

Results: Stent encrustation occurred in 121 patients (15.9%). Four variables-stent indwelling time, urine pH, daily water intake, and renal function stage-were independently associated with encrustation (p < 0.05 for all). The nomogram achieved excellent discrimination (AUC = 0.877) and maintained strong external performance (AUC = 0.884). CKD significantly increased risk in a dose-dependent manner, and interaction analysis revealed a synergistic effect between CKD and urine pH (p = 0.002), explaining the lack of independent significance of pH in CKD subgroups.

Conclusion: This study established and externally validated the first nomogram for predicting DJ stent encrustation that includes CKD as a systemic variable. The model demonstrates high accuracy and generalizability, offering a practical tool for early identification of high-risk patients, particularly those with renal impairment, to guide individualized stent management and prevent irreversible renal damage.

Kidney transplantation is usually the optimal treatment option for patients living with kidney failure given its associations with improved survival, quality of life outcomes and a reduction in the personal, economic, and societal burden of long-term dialysis. While advantages of kidney transplantation are recognized, post-transplant complications, such as graft rejection, ischemia-reperfusion injury, surgical-related complications, and long-term consequences of immunosuppressive therapies, are commonly observed. There has been increased research on developing non-invasive biomarkers for the monitoring of transplanted kidneys over recent decades. The potential of urinary biomarkers to identify graft rejection, post-transplant acute tubular necrosis, detect progression of epithelial-to-mesenchymal transition toward tubulointerstitial fibrosis, and to differentiate between causes of graft dysfunction is an attractive alternative to invasive transplant biopsy. Innovative urinary biomarkers, such as those derived from omics technologies allow for a more holistic assessment of graft status through multi-parametric molecular analysis, although there remain questions on the consistency, reliability, and practicality of utilizing omics-based urinary biomarkers. The international nephrology community has continued to make concerted efforts to improve the procedures and cost-effectiveness of kidney transplant monitoring. In this article, we review the evidence and limitations of currently available urinary biomarkers and propose the application of urine-derived exfoliated kidney cells such as urinary exfoliated proximal tubule cells to prognosticate kidney transplant outcomes and monitor for post-transplant complications. Artificial intelligence and the incorporation of machine learning analysis of proximal tubular cell characteristics may optimize the process of differentiating graft rejection from other forms of kidney dysfunction non-invasively following kidney transplantation.

Background: With regard to complications of portal vein (PV) and inferior vena cava (IVC) thrombosis in autosomal dominant polycystic kidney disease (ADPKD), several cases have been reported based on imaging findings. However, only one autopsy case has been described and no systematic analysis has been conducted to date. This retrospective study aimed to review autopsy cases from our department over the past 37 years to clarify the frequency and background factors of thrombosis formation in ADPKD.

Methods: Among 4001 autopsies performed at our institution from 1987 to 2023, 10 ADPKD cases were identified. We examined the presence of thrombus in these 10 cases and compared pleural effusion and ascites volumes, major organ weights, and clinicopathological factors between cases with thrombus and those without.

Results: Among 10 ADPKD cases, thrombi were identified in four cases in which autopsies were performed relatively recently. These thrombi were distributed in the PV, IVC, and their branches. Compared to non-thrombotic cases, those with thrombi showed a statistically significant increase in kidney weight and tended to have a higher frequency of complications such as sepsis and severe aortic atherosclerosis.

Conclusion: This study reports the first systematic autopsy-based investigation of PV and IVC thrombosis in ADPKD. Thrombosis was found at a high frequency of 40% and appears to have increased in recent years. Increased kidney weight was associated with thrombosis formation, and blood stasis due to compression by enlarged kidneys is considered the primary cause. Further case accumulation and elucidation of the pathophysiology involved are anticipated.

Infections at hemodialysis access sites remain a critical challenge in managing end-stage renal disease patients, significantly affecting morbidity and mortality. This comprehensive review synthesizes current knowledge on risk factors, surveillance methods, diagnostic approaches, treatment strategies, and preventive measures for these infections. Through systematic analysis of literature from major databases up to July 2024, we explore infection-related complications, pathogenic agents, and management strategies. Staphylococcus aureus emerges as a primary pathogen, with concerning increases in multidrug-resistant strains. The review emphasizes the superior safety profile of arteriovenous fistulas compared to central venous catheters, highlighting the importance of access type selection. Continuous monitoring and early detection through physical examinations and specialized tests are crucial. Diagnostic accuracy is optimized by combining clinical assessment with laboratory testing and imaging studies. Treatment strategies focus on empiric systemic antibiotic therapy, guided by local epidemiology and culture results, often necessitating catheter removal for persistent infections. Preventive measures, including strict adherence to aseptic techniques and targeted use of antimicrobial locks, are detailed. The study advocates for a multifaceted approach to infection management, emphasizing multidisciplinary collaboration and adherence to evidence-based guidelines. Promising future directions, such as novel antimicrobial surfaces and lock solutions, offer potential for further reducing infection risks. This review provides valuable insights for healthcare providers, aiming to improve long-term outcomes and quality of life for hemodialysis-dependent patients through enhanced infection control strategies.

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 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.

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.