Renal physiology

A new class of antidiabetic drugs - gliflozins (inhibitors of sodium glucose cotransporter-2; SGLT-2i) stimulate glucose and sodium excretion, thereby contributing to improved glycemic control, weight loss and blood pressure reduction in diabetic patients. Large clinical trials in patients with type 2 diabetes treated with empagliflozin, canagliflozin or dapagliflozin have demonstrated their excellent efficacy in improving many cardiovascular outcomes, including the reduction of death from cardiovascular diseases, non-fatal myocardial infarction or stroke, and hospitalization for heart failure...

We present modern data on the role of superoxide dismutase (SOD) in antioxidant protection and gene regulation in acute pancreatitis. Antioxidant enzymes are essential in pathogenesis of numerous diseases. SOD is one of the key enzymes of antioxidant system. In this review, we analyzed activity of this enzyme depending on various factors, mechanisms and role in physiological and pathological processes, in particular, acute pancreatitis. SOD is significantly less active in patients with severe acute pancreatitis accompanied by renal failure, severe circulatory disorders and high mortality...

Lack of data on drug secretion in human milk is a concern for safe use of drugs during postpartum.Clinical studies are often difficult to perform; despite substantial improvements in computational methodologies such as physiologically based pharmacokinetic modelling, there is limited clinical data to validate such models for many drugs.Various factors that are likely to impact milk to plasma ratio were identified. A literature search was performed to gather available data on milk composition, total volume of milk produced per day, milk pH, haematocrit, and renal blood flow and glomerular filtration rate in various animal models...

Acid Sphingomyelinase has been reported to increase tissue ceramide and thereby mediate hHcy-induced glomerular NLRP3 inflammasome activation, inflammation, and sclerosis. In the present study, we tested whether somatic podocyte-specific silencing of Smpd1 gene attenuates hHcy-induced NLRP3 inflammasome activation and associated exosome release in podocytes and thereby suppresses glomerular inflammatory response and injury. In vivo , somatic podocyte-specific Smpd1 gene silencing almost blocked hHcy-induced glomerular NLRP3 inflammasome activation in Podocre mice compared to control littermates...

Mild cognitive impairment (MCI) is common in people with chronic kidney disease (CKD) and its prevalence increases with progressive loss of kidney function. MCI is characterized by a decline in cognitive performance greater than expected for an individual age and education level but with minimal impairment of instrumental activities of daily living. Deterioration can affect one or several cognitive domains (attention, memory, executive functions, language, and perceptual motor or social cognition). Given the increasing prevalence of kidney disease, more and more people with CKD will also develop MCI causing an enormous disease burden for these individuals, their relatives and society...

The gut microbiome regulates many important host physiological processes associated with cardiovascular health and disease; however, the impact of the gut microbiome on aldosterone is unclear. Investigating whether gut microbiota regulate aldosterone can offer novel insights into how the microbiome affects blood pressure. In this study, we aimed to determine whether gut microbiota regulate host aldosterone. We employed enzyme-linked immunosorbent assays (ELISAs) to assess plasma aldosterone and plasma renin activity (PRA) in female and male mice in which gut microbiota are intact, suppressed, or absent...

T cells mediate organ injury and repair. A proportion of unconventional kidney T cells called double-negative (DN) T cells (TCR+ CD4- CD8- ), with anti-inflammatory properties, were previously demonstrated to protect from early injury in moderate experimental AKI. However, their role in repair after AKI has not been studied. We hypothesized that DN T cells mediate repair after severe AKI. C57B6 mice underwent severe (40min) unilateral ischemia-reperfusion injury (IRI). Kidney DN T cells were studied by flow cytometry and compared to gold-standard anti-inflammatory CD4+ Tregs...

The ENaC γ subunit is essential for homeostasis of Na+ , K+ , and body fluid. Dual γ subunit cleavage before and after a short inhibitory tract allows dissociation of this tract, increasing channel open probability (PO ), in vitro . Cleavage proximal to the tract occurs at a furin recognition sequence (143 RKRR146 , in the mouse γ subunit). Loss of furin-mediated cleavage prevents in vitro activation of the channel by proteolysis at distal sites. We hypothesized that 143 RKRR146 mutation to 143 QQQQ146 (γQ4 ) in 129/Sv mice would reduce ENaC PO , impair flow-stimulated flux of Na+ (JNa ) and K+ (JK ) in perfused collecting ducts, reduce colonic amiloride-sensitive short circuit current (ISC ), and impair Na+ , K+ , and body fluid homeostasis...

The Dietary Approach to Stop Hypertension (DASH) diet, with its low sodium and high potassium content, acts like a diuretic by reducing sodium reabsorption in the kidney's distal convoluted tubule but without the side effects. Previous studies based on animal models didn't explore changes in human ion channel proteins. Recent insights into urinary extracellular vesicles (uEVs) suggest they reflect kidney tissue and physiological modifications. In our inpatient study, we shifted hypertensive volunteers from an American diet to the DASH diet, examining changes in those with stage 1 untreated hypertension...

Coronavirus disease 2019 (COVID-19) induces respiratory dysfunction as well as kidney injury. Although the kidney is considered a target organ of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and affected by COVID-19-induced cytokine storm, the mechanisms of renal reaction in SARS-CoV-2 infection are unknown. In this study, a murine COVID-19 model was induced by nasal infection with mouse-adapted SARS-CoV-2 (MA10). MA10 infection induced body weight loss along with lung inflammation in mice four days after infection...

Cannabis and synthetic cannabinoid consumption is increasing worldwide. Cannabis contains numerous phytocannabinoids that act on the G-protein-coupled cannabinoid receptors type 1 (CB1R) and type 2 (CB2R) expressed throughout the body, including the kidney. Essentially every organ, including the kidney, produces endocannabinoids (ECs), endogenous ligands to these receptors. Cannabinoids acutely increase urine output in rodents and humans, thus potentially influencing total-body water and electrolyte homeostasis...

Urothelium forms a distensible yet impermeable barrier, senses and transduces stimuli, and defends the urinary tract from mechanical, chemical and bacterial injuries. Biochemical and genetic labeling studies support the existence of one or more progenitor populations with the capacity to rapidly regenerate the urothelium following injury, but slow turnover, a low mitotic index, and inconsistent methodologies obscure progenitor identity. The progenitor properties of basal Keratin 5 urothelial cells (K5-UC) have been previously investigated, but those studies focused on embryonic or adult bladder urothelium...

Humans are predisposed to gout because they lack uricase that converts uric acid to allantoin. Rodents have uricase, resulting in low basal serum uric acid. A uricase inhibitor raises serum uric acid in rodents. There were 2 aims of the study in polycystic kidney disease (PKD): 1) to determine whether increasing serum uric acid with the uricase inhibitor, oxonic acid, resulted in faster cyst growth and 2) to determine whether treatment with the xanthine oxidase inhibitor, oxypurinol, reduced the cyst growth caused by oxonic acid...

OBJECTIVE: To delineate the efficacy and safety profile of hemodiafiltration with endogenous reinfusion (HFR) for uremic toxin removal in patients undergoing maintenance hemodialysis (MHD). METHODS: Patients who have been on MHD for a period of at least 3 months were enrolled. Each subject underwent one HFR and one hemodiafiltration (HDF) treatment. Blood samples were collected before and after a single HFR or HDF treatment to test uremic toxin levels and to calculate clearance rate...

INTRODUCTION: The commonly used clinical indicators are not sensitive and comprehensive enough to evaluate the early staging of chronic kidney disease (CKD). This study aimed to evaluate the differences in arterial spin labeling (ASL) and blood oxygenation level-dependent functional magnetic resonance imaging (BOLD-MRI) parameter values among patients at various stages of chronic kidney disease and healthy individuals. METHODS: Electronic databases PubMed, Web of Science, Cochrane, and Embase were searched from inception to March 29, 2024, to identify relevant studies on ASL and BOLD in CKD...

Hypertension is a major adverse effect of calcineurin inhibitors, such as tacrolimus (FK506) and cyclosporine, used clinically as immunosuppressants. Calcineurin inhibitor-induced hypertension (CIH) is linked to augmented sympathetic output from the hypothalamic paraventricular nucleus (PVN). GluA2-lacking, Ca2+ -permeable AMPA receptors (CP-AMPARs) are a key feature of glutamatergic synaptic plasticity, yet their role in CIH remains elusive. Here, we found that systemic administration of FK506 in rats significantly increased serine phosphorylation of GluA1 and GluA2 in PVN synaptosomes...

Guidelines are lacking for patients with calciphylaxis on renal replacement therapy, often leading to difficulty optimally treating these patients. A 60-year-old male veteran receiving hemodialysis presented with calciphylaxis of the left lower extremity and intractable pain. His condition was complicated by chronic back pain, long-term opioid therapy, and psychological trauma history. He was ultimately transferred to a calciphylaxis treatment center but was unable to tolerate further treatments due to sepsis and hemodynamic instability...

PURPOSE: To evaluate, by quantitative and qualitative methods, the glomerular ultrastructure in Wistar rats fed a cafeteria diet. METHODS: Male Wistar rats were divided into two groups at 21 days of age: control (C, n = 10) and cafeteria diet (CAF, n = 8). The animals were followed up until 5 months of age, followed by euthanasia. The blood, kidneys, and fat deposits--epididymal, retroperitoneal, and subcutaneous--were extracted and analyzed. Data were analyzed by Student's t test, and p < 0...

Organic anions (OA) are compounds including drugs or toxicants that are negatively charged at physiological pH and are typically transported by Organic Anion Transporters (OATs). Human OAT4 (SLC22A11) is expressed in the apical membrane of renal proximal tubules. Although there is no rodent ortholog of hOAT4, rodents express Oat5 (Slc22a19), an anion exchanger that is also localized to the apical membrane of renal proximal tubule cells. The purpose of this study was to determine the functional similarity between mouse Oat5 and human OAT4...

In vitro models that can faithfully replicate critical aspects of kidney tubule function such as directional drug transport are in high demand in pharmacology and toxicology. Accordingly, development and validation of new models is underway. The objective of this study was to characterize physiological and transport functions of various sources of human renal proximal tubule epithelial cells (RPTECs). We tested TERT1-immortalized RPTEC, including OAT1-, OCT2- or OAT3-overexpressing variants, and primary RPTECs...