The latest medical research on Kidney Cancer

Nutrition and physical activity are two major issues in the management of CKD patients who are often older, have comorbidities and are prone to malnutrition and physical inactivity, conditions that cause loss of quality of life and increase the risk of death. We performed a multidimensional assessment of nutritional status and of physical performance and activity in CKD patients on conservative therapy in order to assess the prevalence of sedentary behaviour and its relationship with body composition.

115 consecutive stable CKD patients aged 45-80 years were included in the study. They had no major skeletal, muscular or neurological disabilities. All patients underwent a multidimensional assessment of body composition, physical activity and exercise capacity.

Sedentary patients, as defined by mean daily METs < 1.5 were older and differed from non-sedentary patients in terms of body composition, exercise capacity and nutrient intake, even after adjusting for age. Average daily METs were positively associated with lean body mass, muscle strength, 6-MWT performance, but negatively associated with fat body mass, body mass index and waist circumference. In addition, a sedentary lifestyle may have negative effects on free fat mass, muscle strength and exercise capacity, and may increase fat body mass. Conversely, s decrease in muscle mass and/or an increase in fat mass may lead to a decrease in physical activity and exercise capacity.

There is a clear association and potential interrelationship between nutritional aspects and exercise capacity in older adults with CKD: they are really the two sides of the same coin.

Both hypoxia and fibroblast growth factor-23 (FGF-23) are key factors in ischemia-reperfusion (I/R)-induced acute kidney injury (AKI). This study aimed to explore the relationship between hypoxia and FGF-23 in AKI.

An I/R-AKI animal model was established using male BALB/c mice. HK-2 cells, a part of the human proximal tubular epithelial cell line, were subjected to hypoxia/reoxygenation (H/R). qPCR was used to measure FGF-23 and HIF-1α, ELISA was used to measure inflammatory and oxidative stress cytokines. Western blotting used to measure the phosphorylation of ERK level.

In I/R mice, the levels of interleukin-6 (IL-6), tumor necrosis factor (TNF-α), malondialdehyde (MDA), and the phosphorylation of extracellular signal-regulated kinase (ERK) were increased, whereas the levels of interleukin-10 (IL-10), superoxide dismutase (SOD), glutathione peroxidase (GPx), and klotho were decreased, compared to the sham operated mice. Silencing the FGF-23 expression in I/R mice normalized the levels of IL-6, IL-10, TNF-α, MDA, SOD, Gpx, and ERK phosphorylation (p-ERK). In HK-2 cells, hypoxia-reperfusion (H/R) elevated the levels of IL-6, TNF-α, MDA, and ERK phosphorylation, but reduced IL-10, SOD, GPx, and klotho levels. Hypoxia induced apoptosis in HK-2 cells but silencing of FGF-23 expression blocked the effects of hypoxia on cell apoptosis, proinflammatory factors levels, oxidative stress response, and p-ERK levels.

FGF-23 is a key molecule in AKI, and hypoxia plays a crucial role in AKI by inducing cell apoptosis; however, its role is regulated by FGF-23. FGF-23 affects oxidative stress and the inflammatory response of kidney tissues by activating the ERK/mitogen-activated protein kinase (MAPK) signaling pathway.

Sodium Glucose Co-transporter 2 inhibitors (SGLT2i) have been shown to provide effective cardiorenal protection, reducing mortality in conditions such as heart failure (HF) and chronic kidney disease (CKD). While several mechanisms have been identified, recent research has shed light on the drug's ability to attenuate sympathetic nervous system (SNS) activity. However, controversy exists on whether this is due to the extra-renal effects of the drug, or simply due to its renoprotective effects. However, recent trials have highlighted the persistent efficacy of SGLT2i despite declining renal function. Therefore, investigating the ability of SGLT2i to attenuate the SNS independently of the kidney could lead to more insight into its mechanism of action. So far, there has been limited research done on investigating the extra-renal effects of SGLT2i in human subjects on dialysis where the glucosuric renal effects of SGLT2i are negligible. This current study therefore aims to investigate the effects of SGLT2i on the SNS in anuric haemodialysis patients.

We developed a protocol for a mechanistic study to investigate the extra-renal effects of SGLT2i on the SNS. The study will be an investigator-led, open-label, prospective study involving 20 adult (aged ≥18 years) haemodialysis patients with a residual urine output of (RUO) of ≤250 mL/day. Participants will be administered empagliflozin 25 mg/day for 6 weeks. Baseline SNS activity will be measured before and after administration by microneurography to assess central SNS outflow. Secondary outcomes such as changes from baseline in SNS stressor response, heart rate variability, and endothelial function will also be examined. We hypothesize that the use of empagliflozin will result in reduced sympathetic drive in anuric haemodialysis patients.

This will be the first study evaluating the effects of SGLT2i on the sympathetic nervous system in haemodialysis subjects. This study aims to enhance our understanding of the potential role of SGLT2i-induced SNS reduction in the setting of markedly reduced renal function. The study has received ethics approval from the Royal Perth Hospital Human Research Ethics Committee. Australian New Zealand Clinical Trials Registry (ANZCTR) ID: ACTRN12623001237673.