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Oxidative stress plays a key role in chronic kidney disease (CKD) development and progression, inducing kidney cell damage, inflammation, and fibrosis. However, effective therapeutic interventions to slow down CKD advancement are currently lacking. The multifaceted pharmacological effects of molecular hydrogen (H2) have made it a promising therapeutic avenue. H2 is capable of capturing harmful •OH and ONOO- while maintaining the crucial reactive oxygen species (ROS) involved in cellular signaling. The NRF2-KEAP1 system, which manages cell redox balance, could be used to treat CKD. H2 activates this pathway, fortifying antioxidant defenses and scavenging ROS to counteract oxidative stress. H2 can improve NRF2 signaling by using the Wnt/β-catenin pathway and indirectly activate NRF2-KEAP1 in mitochondria. Additionally, H2 modulates NF-κB activity by regulating cellular redox status, inhibiting MAPK pathways, and maintaining Trx levels. Treatment with H2 also attenuates HIF signaling by neutralizing ROS while indirectly bolstering HIF-1α function. Furthermore, H2 affects FOXO factors and enhances the activity of antioxidant enzymes. Despite the encouraging results of bench studies, clinical trials are still limited and require further investigation. The focus of this review is on hydrogen's role in treating renal diseases, with a specific focus on oxidative stress and redox signaling regulation, and it discusses its potential clinical applications.

Abstract Background Membranous glomerulonephritis is the most common primary etiology for the nephrotic syndrome in adults. Beyond the clinical hallmark of nephrotic syndrome such as fluid overloading, dyslipidemia and hypoalbuminemia, the dysregulated homeostasis of potassium and its possible mechanism is seldomly discussed, and its association with the clinical course of membranous GN is lacking. Case presentation A 65 year-old female attended to our emergent department for progressive lower leg edema after taking 15-h of flight. Hypoalbuminemia and hyperlipidemia were both noted, and 24-h urinary total protein was up to 17,950 mg/day. Elevated creatin-phospho-kinase developed at the initial presentation with hypokalemia due to excressive renal excretion. Glycosuria without elevated glycated Hemoglobin occurred. The pathology of kidney biopsy revealed subepithelial immunocomplex deposits with spike formation in the electron microscopy and the positive anti-Phosphlipase A2 receptor antibodies(PLA-2R) with hallmark of membranous glomerulonephritis. In the light microscopy, the vacuolization of proximal tubules was noted, which contributed to the potassium wasting. After 1 year following up duration, the patient’s proteinuria persisted after maintenance treatment with calcineurin inhibitor. Conclusion Hypokalemia is a neglected issue in the membranous glomerulonephritis. Unlike the previous literature, our patient had the vacuolization of proximal tubule at the initial presentation with hypokalemia, which might contribute the potassium wasting. The proximal tubular damage with hypokalemia might be a predictive factor for membranous glomerulonephritis.

Abstract Subjects with comorbidities are at risk for neurodegeneration. There is a lack of a direct relationship between comorbidities and neurodegeneration. In this study, immunomagnetic reduction (IMR) assays were utilized to assay plasma Aβ1–42 and total tau protein (T-Tau) levels in poststroke (PS, n = 27), family history of Alzheimer’s disease (ADFH, n = 35), diabetes (n = 21), end-stage renal disease (ESRD, n = 41), obstructive sleep apnea (OSA, n = 20), Alzheimer’s disease (AD, n = 65). Thirty-seven healthy controls (HCs) were enrolled. The measured concentrations of plasma Aβ1–42 were 14.26 ± 1.42, 15.43 ± 1.76, 15.52 ± 1.60, 16.15 ± 1.05, 16.52 ± 0.59, 15.97 ± 0.54 and 20.06 ± 3.09 pg/mL in HC, PS, ADFH, diabetes, ESRD, OSA and AD groups, respectively. The corresponding concentrations of plasma T-Tau were 15.13 ± 3.62, 19.29 ± 8.01, 17.93 ± 6.26, 19.74 ± 2.92, 21.54 ± 2.72, 20.17 ± 2.77 and 41.24 ± 14.64 pg/mL. The plasma levels of Aβ1–42 and T-Tau in were significantly higher in the PS, ADFH, diabetes, ESRD and OSA groups than controls (Aβ1–42 in PS: 15.43 ± 1.76 pg/mL vs. 14.26 ± 1.42 pg/mL, p

Background and aimsSarcopenia has a higher occurrence rate in patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD) than in the general population. Low handgrip strength—and not sarcopenia per se—is associated with clinical outcomes in patients with CKD, including cardiovascular mortality and hospitalization. The factors contributing to low handgrip strength are still unknown. Accordingly, this study aimed to determine whether uremic toxins influence low handgrip strength in patients with CKD.Materials and methodsThis cohort study lasted from August 2018 to January 2020. The participants were divided into three groups: the control group [estimated glomerular filtration rate (eGFR) ≥ 60 ml/min], an advanced CKD group (eGFR = 15–60 ml/min), and an ESRD group (under maintenance renal replacement therapy). All participants underwent handgrip strength measurement, dual-energy X-ray absorptiometry, and blood sampling for myokines (irisin, myostatin, and interleukin 6) and indoxyl sulfate. Sarcopenia was defined according to the Asian Working Group for Sarcopenia consensus as low appendicular skeletal muscle index (appendicular skeletal muscle/height2 of < 7.0 kg/m2 in men and < 5.4 kg/m2 in women) and low handgrip strength (< 28 kg in men and < 18 kg in women).ResultsAmong the study participants (control: n = 16; CKD: n = 17; and ESRD: n = 42), the ESRD group had the highest prevalence of low handgrip strength (41.6 vs. 25% and 5.85% in the control and CKD groups, respectively; p < 0.05). The sarcopenia rate was similar among the groups (12.5, 17.6, and 19.5% for the control, CKD, and ESRD groups, respectively; p = 0.864). Low handgrip strength was associated with high hospitalization rates within the total study population during the 600-day follow-up period (p = 0.02). The predictions for cardiovascular mortality and hospitalization were similar among patients with and without sarcopenia (p = 0.190 and p = 0.094). The serum concentrations of indoxyl sulfate were higher in the ESRD group (227.29 ± 92.65 μM vs. 41.97 ± 43.96 μM and 6.54 ± 3.45 μM for the CKD and control groups, respectively; p < 0.05). Myokine concentrations were similar among groups. Indoxyl sulfate was associated with low handgrip strength in univariate and multivariate logistic regression models [univariate odds ratio (OR): 3.485, 95% confidence interval (CI): 1.372–8.852, p = 0.001; multivariate OR: 8.525, 95% CI: 1.807–40.207, p = 0.007].ConclusionHandgrip strength was lower in the patients with ESRD, and low handgrip strength was predictive of hospitalization in the total study population. Indoxyl sulfate contributed to low handgrip strength and counteracted the benefits of myokines in patients with CKD.

Introduction: Indoxyl sulfate (IS), a protein-bound uremic toxin, is associated with kidney function and chronic kidney disease (CKD)-related complications. Currently, serum IS levels are primarily quantified using mass spectrometry-based methods, which are not feasible for routine clinical examinations. Methods: The efficiencies of three commercial ELISA kits in determination of serum IS were validated by comparing with ultra-performance liquid chromatography (UPLC)-MS/MS-based method using Bland-Altman analysis. The associations between kidney parameters and serum IS levels determined by ELISA kit from Leadgene and UPLC-MS/MS were evaluated by Spearman correlation coefficient in a CKD validation cohort. Results: ELISA kit from Leadgene showed clinical agreement with UPLC-MS/MS in the determination of serum IS levels (p = 0.084). In patients with CKD, Spearman's correlation analysis revealed a perfect correlation between the IS levels determined using the Leadgene ELISA kit and UPLC-MS/MS (r = 0.964, p < 0.0001). IS levels determined using the Leadgene ELISA kit were associated with the estimated glomerular filtration rate (r = -0.772, p < 0.0001) and serum creatinine concentration (r = 0.824, p < 0.0001) in patients with CKD, and on dialysis (r = 0.557, p = 0.006). Conclusions: The Leadgene ELISA kit exhibits comparable efficacy to UPLC-MS/MS in quantifying serum IS levels, supporting that ELISA would be a personalized method for monitoring the dynamic changes in serum IS levels in dialysis patients to prevent the progression of CKD.

IntroductionDiabetes mellitus (DM) is a pathological hyperglycemic state related to the dysregulation of insulin. Chronic kidney disease (CKD) is a common chronic complication in diabetic patients. A vegetarian diet could be one of the preventive strategies for the occurrence of CKD in patients with diabetes mellitus. However, it is still unknown whether a vegetarian diet lowers the occurrence of CKD in DM patients.Research Design and MethodsThis retrospective study was conducted at Taipei Tzu Chi Hospital from 5 September 2005 to 31 December 2016. Subjects with an HbA1c level > 6.5% or previous history of diabetes mellitus elder than 40 years were grouped based on self-reported dietary habits (vegetarians, lacto-ovo vegetarians and omnivores) in the structured questionnaire. Structural equation modeling (SEM) was applied to estimate the direct and indirect effects of variables on the occurrence of chronic kidney disease.ResultsAmong these 2,797 subjects, the participants were grouped into dietary habits as vegans (n = 207), lacto-ovo vegetarians (n = 941) and omnivores (n = 1,649). The incidence of overall CKD was higher in the omnivore group [36.6% vs 30.4% (vegans) and 28.5% (lacto-ovo vegetarian), p < 0.001]. In the SEM model, after adjusting for age and sex, the lacto-ovo vegetarian [OR: 0.68, 95% confidence interval (CI): 0.57–0.82] and vegan groups (OR 0.68, 95% CI: 0.49–0.94) were both associated with a lower risk of CKD occurrence than the omnivore group. The vegan diet and lacto-ovo diet lowered the risk related to a high BMI (OR: 0.45, p < 0.001, OR: 0.58, p < 0.001) and hyperuricemia (OR: 0.53, p < 0.001; OR: 0.55, p < 0.001) for the occurrence of CKD.ConclusionVegetarian dietary habits were associated with a lower occurrence of CKD in DM patients.

Background and aims: Vaccination for severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) is strongly recommended. The efficacy of SARS-CoV-2 vaccine for patients with end-stage renal disease is low. Indoxyl sulfate (IS) is a representative protein bound uremic toxin arousing immune dysfunction in CKD patients. It is unknown whether IS impairs the efficacy of vaccines for SARS-CoV-2. Materials and Methods: From 1 June 2021, to 31 December 2021, hemodialysis patients (n = 358) and a control group (n = 59) were eligible to receive the first dose of the ChAdOx1 COVID-19 vaccine. Titer measurements indicative of the humoral response (anti-S1 IgG and surrogate virus neutralization test (sVNT) results) and indoxyl sulfate concentration measurement were performed 4 weeks after ChAdOx1 vaccine injection. Results: The serum concentrations of anti-S1 IgG were 272 ± 1726 AU/mL and 2111 ± 4424 AU/mL in hemodialysis patients and control group (p < 0.05), respectively. The sVNT values were 26.8 ± 21.1% and 54.0 ± 20.2% in the hemodialysis and control groups (p < 0.05), respectively. There was a decreasing trend for the anti-S1 IgG titer from the lowest to highest quartile of IS (p < 0.001). The patients with higher concentrations of IS had lower sVNT (p for trend < 0.001). Conclusion: Hemodialysis patients had weaker humoral immunity after the first dose of the ChAdOx1 vaccine. Higher concentration of IS altered the development of anti-S1 antibodies and sVNT-measured neutralization.

Renal osteodystrophy is common in patients with chronic kidney disease and end-stage renal disease and leads to the risks of fracture and extraosseous vascular calcification. Secondary hyperparathyroidism (SHPT) is characterized by a compensatory increase in parathyroid hormone (PTH) secretion in response to decreased renal phosphate excretion, resulting in potentiating bone resorption and decreased bone quantity and quality. Calcium-sensing receptors (CaSRs) are group C G-proteins and negatively regulate the parathyroid glands through (1) increasing CaSR insertion within the plasma membrane, (2) increasing 1,25-dihydroxy vitamin D3 within the kidney and parathyroid glands, (3) inhibiting fibroblast growth factor 23 (FGF23) in osteocytes, and (4) attenuating intestinal calcium absorption through Transient Receptor Potential Vanilloid subfamily member 6 (TRPV6). Calcimimetics (CaMs) decrease PTH concentrations without elevating the serum calcium levels or extraosseous calcification through direct interaction with cell membrane CaSRs. CaMs reduce osteoclast activity by reducing stress-induced oxidative autophagy and improving Wnt-10b release, which promotes the growth of osteoblasts and subsequent mineralization. CaMs also directly promote osteoblast proliferation and survival. Consequently, bone quality may improve due to decreased bone resorption and improved bone formation. CaMs modulate cardiovascular fibrosis, calcification, and renal fibrosis through different mechanisms. Therefore, CaMs assist in treating SHPT. This narrative review focuses on the role of CaMs in renal osteodystrophy, including their mechanisms and clinical efficacy.

Vitamin D has been described as an essential nutrient and hormone, which can cause nuclear, non-genomic, and mitochondrial effects. Vitamin D not only controls the transcription of thousands of genes, directly or indirectly through the modulation of calcium fluxes, but it also influences the cell metabolism and maintenance specific nuclear programs. Given its broad spectrum of activity and multiple molecular targets, a deficiency of vitamin D can be involved in many pathologies. Vitamin D deficiency also influences mortality and multiple outcomes in chronic kidney disease (CKD). Active and native vitamin D serum levels are also decreased in critically ill patients and are associated with acute kidney injury (AKI) and in-hospital mortality. In addition to regulating calcium and phosphate homeostasis, vitamin D-related mechanisms regulate adaptive and innate immunity. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections have a role in excessive proinflammatory cell recruitment and cytokine release, which contribute to alveolar and full-body endothelial damage. AKI is one of the most common extrapulmonary manifestations of severe coronavirus disease 2019 (COVID-19). There are also some correlations between the vitamin D level and COVID-19 severity via several pathways. Proper vitamin D supplementation may be an attractive therapeutic strategy for AKI and has the benefits of low cost and low risk of toxicity and side effects.