Xanthine oxidase (XO) is an important source of reactive oxygen species. This study investigated whether XO inhibition exerts renoprotective effects by inhibiting vascular endothelial growth factor (VEGF) and NADPH oxidase (NOX) in diabetic kidney disease (DKD). Febuxostat (5 mg/kg) was administered to streptozotocin (STZ)-treated 8-week-old male C57BL/6 mice via intraperitoneal injection for 8 weeks. The cytoprotective effects, its mechanism of XO inhibition, and usage of high-glucose (HG)-treated cultured human glomerular endothelial cells (GECs) were also investigated. Serum cystatin C, urine albumin/creatinine ratio, and mesangial area expansion were significantly improved in febuxostat-treated DKD mice. Febuxostat reduced serum uric acid, kidney XO levels, and xanthine dehydrogenase levels. Febuxostat suppressed the expression of VEGF mRNA, VEGF receptor (VEGFR)1 and VEGFR3, NOX1, NOX2, and NOX4, and mRNA levels of their catalytic subunits. Febuxostat caused downregulation of Akt phosphorylation, followed by the enhancement of dephosphorylation of transcription factor forkhead box O3a (FoxO3a) and the activation of endothelial nitric oxide synthase (eNOS). In an in vitro study, the antioxidant effects of febuxostat were abolished by a blockade of VEGFR1 or VEGFR3 via NOX-FoxO3a-eNOS signaling in HG-treated cultured human GECs. XO inhibition attenuated DKD by ameliorating oxidative stress through the inhibition of the VEGF/VEGFR axis. This was associated with NOX-FoxO3a-eNOS signaling.

Several studies reported the effect of obesity on the progression of IgA nephropathy (IgAN). However, the impact of obesity on the clinicopathologic presentation of IgAN remains uncertain. This is a retrospective cross-sectional study from eight university hospitals in South Korea. Patients were categorized into three groups using the Asia-Pacific obesity classification based on body mass index (BMI). Clinical and histopathologic data at the time of renal biopsy were analyzed. Among 537 patients with IgAN, the obese group was more hypertensive and had lower estimated glomerular filtration rate and more proteinuria than other groups. The histologic scores for mesangial matrix expansion (MME), interstitial fibrosis, tubular atrophy, and mesangial C3 deposition differed significantly between the three groups. Among these histopathologic parameters, BMI was independently positively associated with MME score on multivariable linear regression analysis (p = 0.028). Using multivariable logistic regression analysis, the obese group was independently associated with higher MME scores compared to the normal weight/overweight group (p = 0.020). However, BMI was not independently associated with estimated glomerular filtration rate or proteinuria on multivariable analysis. Obesity was independently associated with severe MME in patients with IgAN. Obesity may play an important pathogenetic role in mesangial lesions seen in IgAN.

Hyperuricemia is a significant risk factor for cardiovascular morbidity and chronic kidney disease progression. IgA nephropathy (IgAN) is a well-known primary glomerular nephropathy. Hyperuricemia is associated with a poor prognosis in IgAN patients. We evaluated the association of hyperuricemia with the histopathological severity of IgAN in male and female patients; 658 patients diagnosed with IgAN via kidney biopsy were initially included. Baseline patient data were collected by eight university hospitals affiliated with the College of Medicine of the Catholic University of Korea. Pathological features were independently evaluated by eight expert pathologists working in the hospitals, and the consensus was reached. Of the initial 658 patients, 517 were finally included (253 males and 264 females). Hyperuricemia was defined as a serum uric acid (UA) level >7.0 mg/dL for males and >5.6 mg/dL for females; 108 (42.7%) males and 95 (35.9%) females exhibited hyperuricemia. Compared to the patients with normal UA levels, the global glomerulosclerosis, segmental sclerosis, mesangial matrix expansion (MME), endocapillary proliferation (ECP), interstitial fibrosis (IF), and tubular atrophy (TA) scores were higher in hyperuricemic males and females. In multivariable linear regression, the serum UA level correlated significantly with the MME, ECP, IF, and TA scores of female IgAN patients only.

IgA nephropathy (IgAN) is a globally well-known primary glomerular nephropathy. Hypertriglyceridemia (HTG) is one factor contributing to atherosclerosis and is a common complication of renal failure. HTG is a significant risk factor for decreased renal function in patients with IgAN. We evaluated the association of HTG with the histopathological features of IgAN patients. A total of 480 patients diagnosed with IgAN via kidney biopsy from eight university hospitals affiliated with the College of Medicine of the Catholic University of Korea were included in the final cohort. Pathological features were evaluated by eight expert pathologists with hospital consensus. HTG was defined as a serum triglyceride (TG) level of ≥150 mg/dL. In the study population analysis, the HTG group was older, with more males; higher body mass index (BMI), low-density lipoprotein cholesterol (LDL-C) and spot urine protein ratio; and lower estimated glomerular filtration rate (eGFR). In the lipid profile analysis, eGFR was negatively correlated with TGs/ high-density lipoprotein cholesterol (HDL) and triglyceride-glucose index (TyG). Proteinuria positively correlated with TGs/HDL, non-HDL/HDL, LDL/HDL, TyG, TGs and LDL. The percentages of global sclerosis (GS), segmental sclerosis (SS) and capsular adhesion (CA), and the scores for mesangial matrix expansion (MME) and mesangial cell proliferation (MCP), were more elevated in the HTG group compared to the normal TG group. Multivariable linear regression analysis showed that the percentages of global sclerosis, segmental sclerosis and capsular adhesion, as well as the scores for mesangial matrix expansion and mesangial cell proliferation, were positively associated with TG level. In binary logistic regression, the HTG group showed a higher risk for global sclerosis and segmental sclerosis. In conclusion, HTG is a significant risk factor for glomerulosclerosis in IgAN.

Objective: Osteoporosis is prevalent in patients with chronic kidney disease (CKD), with risk increasing as CKD progresses, subsequently elevating fracture risk. While previous studies have shown a link between low skeletal muscle mass and osteoporosis in the general population, there is limited research exploring this relationship in patients with advanced CKD (stages 3-5D). This study aimed to evaluate whether skeletal muscle area (SMA), as measured by abdominal CT, is correlated with bone mineral density (BMD) in advanced CKD patients beginning hemodialysis. Methods: This single-center, retrospective cohort study included patients who started maintenance hemodialysis at Daejeon St. Mary’s Hospital from January 2018 to September 2021. Patients who underwent abdominal CT and BMD assessments within three months of dialysis initiation were enrolled, resulting in a sample of 87 individuals. Baseline characteristics were analyzed, with patients stratified by sex and SMA quartiles. Pearson’s correlation and multivariate regression analyses were conducted to the relationship between SMA and BMD T-scores. Results: The study cohort had an average age of 65.4 years, with 52.9% of participants being male. Male patients exhibited significantly higher SMA and BMD T-scores in both the lumbar spine and femur compared to female patients. SMA showed the strongest positive correlation with BMD at both sites (lumbar spine, r = 0.424; femur, r = 0.514; p < 0.001). Multivariate analysis identified SMA as an independent positive predictor of BMD, while alkaline phosphatase (ALP) was independently associated with lower femur BMD. In the SMA-based subgroup analysis, patients with lower SMA had significantly lower BMD T-scores and a higher risk of osteoporosis. Logistic regression indicated that patients in the lowest SMA quartile had substantially increased odds of osteoporosis compared to those in the highest quartile, with an adjusted odds ratio of 30.59 (p = 0.008). Conclusions: Lower skeletal muscle mass is significantly associated with lower bone density and a higher risk of osteoporosis in advanced CKD patients initiating hemodialysis. SMA, as measured by abdominal CT, may serve as a useful marker for identifying patients at elevated osteoporosis risk in this population.

Obesity and adipose tissue are commonly regarded as detrimental factors linked to adverse outcomes, including cardiovascular and metabolic diseases. However, the obesity paradox is obesity that may provide survival benefits for chronic diseases including patients undergoing hemodialysis. Fat mass can be a surrogate marker for nutrition status in patients undergoing hemodialysis. Thus, this study evaluated subcutaneous fat and all-cause mortality in patients initiating hemodialysis. A total of 123 patients initiating hemodialysis were included in this study. MATLAB (version R2014a) was used to identify subcutaneous fat area (SFA) and visceral fat area (VFA) in computed tomography images for the analysis of body composition. The survival rate was calculated using Cox regression analysis. The Kaplan–Meier survival rates were 70.0% and 85.7% in the low and high subcutaneous fat area (SFA) groups, respectively (log rank, p = 0.021). In Cox analysis, the low SFA group showed high risk for all-cause mortality than the high SFA group (hazard ratio (HR) 3.541, 95% CI 1.358–9.235, p = 0.010). In subgroup univariate analysis, the risk for all-cause mortality was higher in patients with low SFA and diabetes than those with high SFA and diabetes (HR 3.541, 95% CI 1.358–9.235, p = 0.010). In multivariate analysis, the risk for all-cause mortality was higher in patients with low SFA and diabetes than those with high SFA and diabetes (HR 4.615, 95% CI 1.484–14.351, p = 0.008). Conclusively, low SFA increases the risk of 2-year all-cause mortality, and SFA analysis can provide information for risk evaluation for patients initiating hemodialysis.