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Background: The renal artery plays a central role in renal perfusion and is critical for proper renal function. Ageing is an independent risk factor for both impaired renal function and vascular disorders, and associated with an increase in the expression of the vasoconstrictor endothelin-1 (ET-1), and caloric restriction (CR) without malnutrition has been shown to be an effective inhibitor of renal dysfunction induced by ageing. The objective of this study was to determine whether CR-mediated alleviation of renal dysfunction is mediated by ET-1 expression.Methods: The young (2 months, 2 M) and old (12 months, 12 M) Sprague-Dawley male rats were used and fed ad libitum. The 12-month-old rats were further divided into 12 M and 12 M-caloric restriction (CR) (30% calorie restriction). After 8 weeks, the renal tissues were showed by PAS staining, and age-related metabolic parameters and renal functions were detected in each group of rats. The inflammatory cytokines of interleukin (IL)-6, IL-1β, tumor necrosis factor alpha (TNF-α), and transforming growth factor beta 1 (TGF-β1) were analyzed using ELISA. The mRNA and protein expression in the renal artery were analysis by qRT-PCR and Immunoblot analysis.Results: Ageing was associated with significant increases in 24 h urine protein content and serum triglyceride and cholesterol in 12 M rats, both of which were significantly inhibited in 12 M-CR. The mRNA expression and the secretion of IL-6, IL-1β, TNF-α, and TGF-β1 in the renal artery was significantly increased with ageing and inhibited by CR. CR also inhibited ageing-induced Edn1 (encoding ET-1) mRNA and protein expression in the renal artery. In addition, CR could regulate ET-1 expression by inhibiting the activation of NF-κB signaling and activation and induction in the expression of NF-E2-related factor 2 (Nrf2) and histone deacetylase and gene repressor sirtuin 1 (SIRT1), both of which play a central role in mitigating oxidative stress in young rats.Conclusions: Moderate CR can reverse the ageing related kidney dysfunction by reducing the ET-1 expression. CR might be used as an alternative to prevent the ageing induced renal artery dysfunction.

Objective Evidence has demonstrated that Ca 2+ /calmodulin-dependent protein kinase type IV (CaMKIV) contributes to altered cytokine production by promoting the production of inflammatory cytokines. This study aimed to explore the protective role and underlying mechanisms of CaMKIV inhibition in experimental nephrotic syndrome. Methods BALB/c mice received single intravenous injections of adriamycin (10 mg/kg) then were sacrificed at two, four and six weeks. In the second study, treatment with KN-93, a CaMKIV inhibitor, or vehicle administered via intraperitoneal injection was started five days after adriamycin injection. Functional and pathologic parameters, the presence of inflammatory infiltration and the expressions of pro-inflammatory cytokines were assessed. Results The CaMKIV protein expression levels were upregulated in the mice with adriamycin nephropathy, which was significantly inhibited by KN-93 (p<0.01). As compared with the vehicle-treated controls, KN-93 treatment resulted in marked suppression of proteinuria and serum creatinine at week 6 (p<0.01), but not at two weeks after induction of the disease. KN-93 inhibited glomerulosclerosis and the development of tubulointerstitial lesions. The renal alpha-smooth muscle actin (α-SMA) expression was also significantly suppressed by KN-93 treatment at week 6 (p<0.01). Moreover, KN-93 inhibited the renal monocyte chemoattractant protein-1 (MCP-1) expression, paralleled by a reduction in the interstitial infiltration of macrophages and T-cells (p<0.01). Conclusion Our findings suggest that activation of CaMKIV signaling is involved in the progression of glomerular diseases with a proteinuric state. Our data therefore justify the development of small molecule CaMKIV inhibitors for the treatment of clinical nephrotic syndrome.

Introduction: While patients with diabetes are at higher risk of developing acute kidney injury (AKI), there are few studies on the recurrence of AKI in older adult patients. This study therefore aimed to examine the impact of diabetes on AKI recurrence and long-term outcomes in older male patients. Methods: This retrospective cohort study included older male patients who experienced AKI during hospitalization from July 2007 to August 2011. Medical records of all patients were followed up for 10 years. Patients with AKI Xin Shen and Kunming Lv contributed equally to this work.

Objective: The aim of the study was to analyze the clinical features of elderly patients with coronavirus disease 2019 (COVID-19) and to explore the relationship between COVID-19 patients and kidney injury. Methods: A total of 188 elderly patients with confirmed COVID-19 enrolled in this study were hospitalized for at least 1 week in the Central Theater Command General Hospital of Chinese People's Liberation Army from January 3, 2020 to March 14, 2020. The recorded information included clinical data and results of kidney-related laboratory tests. Retrospective analysis was performed. Results: The median age of the patients was 69 years (interquartile range 65–78, range: 60–97 years); 31.4% were 60–74 years old, and 68.6% were over 75 years old. A total of 12.8% and 18.6% of the patients were in critical and severe stages of COVID-19, respectively. The proportions of patients using mechanical ventilators and deaths were 9.5% and 8.5%, respectively. A total of 26.1% and 8.5% of the patients showed mild elevation of blood urea nitrogen (BUN) and serum creatinine (SCr) levels at admission. A total of 18.6% and 5.9% of the patients had elevated BUN and SCr 1 week after admission, respectively. A total of 3.1% of the patients were diagnosed with acute kidney injury, and 75% of those patients had chronic kidney disease before admission. Compared with the patients aged 60–74 years, those over 75 years exhibited significantly increased proportions of elevated BUN levels, critical illness, use of mechanical ventilated, and death. Multivariate logistic regression analysis revealed that an elevated BUN level at admission and 1 week after admission were independent risk factors for death in the elderly patients with COVID-19. Conclusion: There were more critical cases and a high mortality in elderly patients with COVID-19. An increased BUN level was an independent risk factor for death in elderly patients with COVID-19.