Clinical and Experimental Nephrology最新文献

Background: The trajectory of the ankle-brachial index (ABI) over time in relation to death has not been fully described in patients undergoing hemodialysis. We modeled ABI trajectory pattern before death in patients undergoing maintenance hemodialysis.

Methods: Patients undergoing hemodialysis in a dialysis facility were retrospectively enrolled and categorized into two groups, deceased and surviving groups, based on their status at the end of the observation period. Linear mixed-effect model and a backward timescale from the year of death or study end date were used to compare ABI trajectory between the deceased and surviving groups during the observation period.

Results: A total of 442 patients (median age, 65 years; 60.2%, men) were included. During the observation period (median, 5.3 years; maximum, 8.5 years), 130 deaths were observed. Differences in ABI between the deceased and survivors were detected in the early stages (difference at 7 years before death, 0.08; p = 0.01), with the differences between these groups becoming more pronounced at 1 year before death (difference at 1 year before death, 0.11; p < 0.001).

Conclusions: Differences in ABI trajectory between the deceased and survivors were detected from the early stages to just before death.

Renal ischemia-reperfusion injury (RIRI) is a major cause of acute kidney failure. Recent studies have shown that RIRI mechanism is closely related to abnormal mitochondrial biogenesis, fusion, fission, and autophagy. Maintaining normal mitochondrial function is essential for RIRI treatment. Therefore, it is important to explore molecular mechanisms of RIRI and relevant therapeutic targets. This review describes the role of mitochondria in RIRI and summarises information about potential drugs that regulate mitochondrial function, with the aim of providing ideas for clinical targeting of mitochondria to prevent and treat RIRI.

Background: Contrast agents are known to increase the risk of radiocontrast-induced nephropathy (CIN), particularly in elderly, diabetic, or dehydrated patients. However, the exact molecular mechanisms leading to renal injury in CIN remain unclear. Probenecid (PBN), an organic anion transport inhibitor that also inhibits Pannexin1 channels, has been suggested as a potential therapeutic agent in certain nephropathy models. This study aimed to examine the protective effects of PBN in CIN. Additionaly, considering the roles of small RhoGTPases and Pannexin1 in nephropathy and their interactions, we investigated the relationship between these molecules in the same CIN rat model.

Methods: CIN was induced in male Wistar rats by a single intraperitoneal (ip.) injection of iohexol. The animals were treated with either saline (i.p) or PBN (150 mg/kg or 300 mg/kg, i.p) twice daily for 5 days following iohexol (3 g iodine/kg) administration. Kidney tissue samples were stained with hematoxylin and eosin to assess tubular injury. Immunohistochemical analysis was also performed to evaluate the expression of RhoA, Rac1, Pannexin1, and active Caspase-3.

Results: Iohexol caused tubular necrosis, dilatation, vacuolization and brush border loss, while high-dose PBN significantly reduced these changes. Rac1, Pannexin1 and active-Caspase 3 expressions were increased in CIN, while RhoA expression was decreased compared to control. High-dose PBN ameliorated these changes, but significant improvement was observed in RhoA expression.

Conclusions: These results indicate that PBN may protect against CIN through modulation of small Rho GTPases (increasing RhoA expressions or altered balance between RhoA and Rac1) and Pannexin1 channels in Wistar rats.

Background: Increased serum anti-nephrin antibody titers and co-localization of nephrin and IgG in kidney tissues have been reported in minimal change disease (MCD) and post-transplant recurrent focal segmental glomerulosclerosis (FSGS). These results indicate an association of anti-nephrin antibodies with nephrotic syndrome (NS); however, the exact relationship remains unclear. Herein, we evaluated nephrin/IgG co-localization in the glomeruli of patients with various kidney diseases, including monogenic NS, to clarify the association between idiopathic nephrotic syndrome (INS) and anti-nephrin antibodies.

Methods: IgG and nephrin co-localization was investigated in 52 kidney tissue biopsy samples, comprising INS in the active phase (n = 26; MCD, n = 19; FSGS, n = 7) and remission (n = 6), monogenic NS (n = 3), and other kidney diseases (n = 17). Double-immunofluorescence staining for nephrin/IgG was performed in unfixed frozen sections for 2 h at room temperature with Alexa Fluor-labeled nephrin/IgG cocktail antibodies. Nephrin/IgG co-localization was assessed using optical sectioning under a fluorescence microscope.

Results: Nephrin/IgG co-localization was observed in 81% (21/26, children: 15/17, adults: 6/9) of active INS cases, 84% (16/19) of MCD cases, and 71% (5/7) of FSGS cases. No co-localization was observed in NS with monogenic variants or other kidney diseases.

Conclusion: Nephrin/IgG co-localization in the kidney tissue is finding observed in active INS, strongly indicating an association between anti-nephrin antibodies and INS onset. The nephrin/IgG cocktail antibody is a rapid and effective approach for investigating INS pathogenesis that facilitates the differential diagnosis of immune-mediated NS from other kidney diseases, including monogenic NS.

Background: T50 calciprotein crystallization test (serum calcification propensity, T50) is a blood test which assesses the resistance of the serum to calcification stress in vitro. Because of its limited availability in clinical practice of chronic kidney disease, we aimed to develop equations for estimated T50 (eT50).

Methods: This was an observational study in 1,651 hemodialysis patients whose T50 was measured by the method Pasch et al. The data sets were divided into two groups for the derivation (N = 1,003) and validation (N = 648) of the equations. Logarithmically transformed values of measured T50 were regressed by relevant variables selected from 36 candidates based on the Akaike's Information Criteria.

Results: Because the initial model A included 19 variables, we developed simpler models B and C with 10 and 5 variables, respectively, for clinical use. All these models included serum phosphate, magnesium, sodium, chloride, and total ion binding capacity. When these equations were validated, the intercept, slope, and R² values were 1.130, 0.770, 0.596 for model A, 1.093, 0.782, and 0.597 for model B, and 0.979, 0.806, and 0.573 for model C, respectively. Multivariable-adjusted Fine-Gray analysis showed that a lower eT50 value by model A, B, or model C was an independent predictor of a higher risk of new cardiovascular events in the total cohort as the measured T50 was.

Conclusions: We developed three equations for eT50 from clinically available variables. These eT50 values may be useful if measured T50 is not available.

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.

This article is part of a review series on water and electrolyte disorders, based on the annual "Electrolyte Winter Seminar" for early-career nephrologists in Japan. The seminar features interactive case-based discussions, some of which are included as self-assessment questions. The fifth installment addresses the management of hyperkalemia. Hyperkalemia frequently occurs in patients with chronic kidney disease (CKD) and can become life-threatening when severe, necessitating prompt treatment regardless of its underlying cause. Renin-angiotensin system inhibitors (RASi) are a recognized risk factor for hyperkalemia in CKD; however, discontinuing RASi in response to elevated potassium levels may adversely affect patient outcomes. Although there are no formal criteria distinguishing acute from chronic hyperkalemia, symptoms presentation and potassium levels offer a practical guide for clinical management. This review covers standard treatment strategies for severe (symptomatic or acute) hyperkalemia in emergency and inpatient settings and discusses how to manage mild-to-moderate (asymptomatic or chronic) cases in CKD patients while continuing RASi therapy.