Serum granulosa cell-derived TNF-α promotes inflammation and apoptosis of renal tubular cells and PCOS-related kidney injury through NF-κB signaling.

Polycystic ovary syndrome (PCOS) is a disorder with endocrinal and metabolic problems in reproductive aged women. Evidence shows that PCOS is in a high prone trend to develop kidney diseases. In this study, we investigated the mediators responsible for PCOS-related kidney injury. We found that tumor necrosis factor (TNF-α) levels were significantly increased in serum and primary cultured granulosa cells (GCs) from PCOS patients. Serum TNF-α levels were positively correlated with serum testosterone and luteinizing hormone (LH)/follicle-stimulating hormone (FSH) ratio, suggesting its positive role in the severity of PCOS. Serum TNF-α levels were also positively correlated with the levels of urinary KapU, LamU, α1-MU and ß2-MU, the markers for renal tubular cell-derived proteinuria. We established a PCOS mouse model by resection of the right kidney, followed by daily administration of dihydrotestosterone (DHT, 27.5 µg, i.p.) from D7 for 90 days. We found that TNF-α levels were significantly increased in the ovary and serum of the mice, accompanied by increased renal tubular cell apoptosis, inflammation and fibrosis in kidneys. Furthermore, the receptor of TNF-α, tumor necrosis factor receptor 1 (TNFR1), was significantly upregulated in renal tubular cells. We treated human ovarian granulosa-like tumor cells (KGN) with DHT (1 µg/ml) in vitro, the conditioned medium derived from the granulosa cell culture greatly accelerated apoptotic injury in human proximal tubular epithelial cells (HKC-8), which was blocked after knockdown of TNF-α in KGN cells. Furthermore, knockdown of TNFR1 in renal tubular epithelial cells greatly ameliorated cell injury induced by granulosa cell-derived conditioned medium. These results suggest that serum TNF-α plays a key role in mediating inflammation and apoptosis in renal tubular cells associated with PCOS-related kidney injury.

Prevalence and determinants of parathyroid dysfunction in elderly patients on hemodialysis.

BACKGROUND: The goal of this study was to investigate underlying factors of parathyroid dysfunction in elderly patients undergoing maintenance hemodialysis. METHODS: A total of 286 patients on maintenance hemodialysis were included. Hemoglobin, serum creatinine (Scr), blood urea nitrogen (BUN), serum calcium, serum phosphorus (P), intact parathyroid hormone (iPTH), and serum albumin (Alb) were measured and analyzed both before and after dialysis. RESULTS: A higher incidence of low iPTH level (<150 pg/l) was observed in the elderly group than that in the non-elderly group (55.8 vs. 36.7%, p < 0.05). Elderly patients had a shorter dialysis duration, lighter dry weight, lower concentrations of BUN, Scr, P, iPTH, Alb and standard protein nitrogen present rate (nPNA) compared to that of non-elderly group patients (p < 0.05). CONCLUSIONS: Low iPTH level occurs more frequently in elderly hemodialysis patients. Furthermore, age, serum P, serum Alb and nPNA were independently associated with a low iPTH level.

Associaton of Retinol Binding Protein 4 (RBP4) Levels With Hyperuricemia: A Cross-Sectional Study in a Chinese Population.

Background: There are few studies on predictive biomarkers for hyperuricemia, and the predictive value of these biomarkers tends to be poor. Additionally, no reports have described the predictive value of retinol binding protein 4 (RBP4) for hyperuricemia. Purpose: This study was performed to evaluate the value of RBP4 for predicting the risk of hyperuricemia in a general population, determine whether RBP4 could be used alone or in combination with other factors to predict the risk of hyperuricemia in the general population, and establish an optimum predictive model. Methods: We conducted a population-based cross-sectional survey in 2018, involving a questionnaire, physical examination, and laboratory testing. We enrolled 2303 individuals by stratified random sampling, and 2075 were included in the data analysis after applying the eligibility criteria. Results: Serum RBP4 level had a highly significant association with hyperuricemia (P<0.001). After adjusting for potential confounders, logistic regression indicated that the risk of hyperuricemia was highest in the highest RBP4 quartile (odds ratio: 7.9, 95% confidence interval [CI]: 4.18-14.84, compared to the lowest quartile). The area under the receiver operating characteristic (ROC) curve (AUC) for RBP4 was 0.749 (95% CI: 0.725-0.774, P<0.001), which was higher than that for all the other predictors assessed. The optimum model for predicting hyperuricemia in the general population consisted of RBP4, sex (male), body mass index, serum creatinine, high-sensitivity C-reactive protein, fasting blood glucose, insulin, and alcohol consumption. The AUC was 0.804 (95% CI: 0.782-0.826, P<0.001). Conclusions: RBP4 is strongly associated with hyperuricemia, and its predictive value was higher than that of traditional predictors.

High-Sensitivity C-Reactive Protein Leads to Increased Incident Metabolic Syndrome in Women but Not in Men: A Five-Year Follow-Up Study in a Chinese Population.

PURPOSE: Metabolic syndrome (MetS), characterized by a constellation of insulin resistance, central obesity, hypertension, and hyperlipidemia, is a global health threat. High-sensitivity C-reactive protein (hs-CRP) has been shown to be associated with type 2 diabetes and cardiovascular disease; however, its association with incident MetS is less known. Therefore, the aim of this study was to examine the prospective association between hs-CRP and MetS among a Chinese population in a 5-year follow-up study. PATIENTS AND METHODS: The levels of hs-CRP were measured using serum samples collected at baseline recruitment in 2012 from 886 participants without MetS. Follow-up interviews were conducted in 2018, and MetS was diagnosed by 2017 criteria from the Chinese Diabetes Society. Multivariate logistic regression models were used to assess the overall and sex-specific associations between hs-CRP and incident MetS. The odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were computed with adjustment for demographic, socioeconomic, clinical, and lifestyle factors. RESULTS: After a mean follow-up duration of 5.40 ± 0.56 years, 116 (13.3%) participants developed MetS. In the total study population, increased hs-CRP levels were associated with a higher risk of MetS (OR comparing extreme quartiles of hs-CRP: 4.06 [95% CI: 1.91-8.65]) in the fully-adjusted model. When stratified by sex, the positive association was only observed in women (OR: 4.82 [1.89-12.3]) but not in men (OR: 3.15 [0.82-12.1]; P-interaction = 0.039). CONCLUSION: In this study of a Chinese population, a positive association between hs-CRP and incident MetS was found only in women and not in men. Sex-specific prediction and intervention of MetS using hs-CRP as a target should be further evaluated.

Protective Effects of Bu-Shen-Huo-Xue Formula against 5/6 Nephrectomy-Induced Chronic Renal Failure in Rats.

Chronic renal failure (CRF) is a serious disease related to increasing incidence and prevalence as well as decline in quality of life. Bu-Shen-Huo-Xue formula (BSHX), one of traditional herbal formulations, has been clinically employed to treat CRF for decades, but the mechanisms involved have not been investigated. In the present study, we investigated the effects of BSHX on some closely related parameters in 5/6 nephrectomy CRF rats. Rats with CRF were divided into five groups, namely, one control group, one enalapril group, and three BSHX treatment groups (0.25, 0.5, and 1 g/kg·d). The rats subjected to sham operation were used as a normal control. After eight weeks of treatment, BSHX significantly decreased the levels of Scr and BUN, downregulated the mRNA expression levels of TGF-ß 1, CTGF, NF-κB, TNF-α, and OPN, upregulated the mRNA expression of PPARγ, and reduced in situ expression of fibronectin and laminins. Histological findings also showed significant amelioration of the damaged renal tissue. BSHX protects 5/6 nephrectomy rats against chronic renal failure probably via regulating the expression of TNF-α, NF-κB, TGF-ß 1, CTGF, PPARγ, OPN, fibronectin, and laminins and is useful for therapy of CRF.