Chronic kidney disease amplifies severe kidney injury and mortality in a mouse model of skin arsenical exposure.

In previously published work, we elucidated the role of cutaneous arsenical exposure in promoting acute kidney injury (AKI) in adult healthy mice. Here, we determine whether pre-existing chronic kidney disease (CKD) increases the severity of AKI. Following exposure to aristolochic acid (AA) (a nephrotoxic phytochemical in humans), mice manifested classical markers of CKD, including robust interstitial fibrosis and loss in kidney function.

Cognate antigen-independent differentiation of resident memory T cells in chronic kidney disease.

Resident memory T cells (Ts), which are memory T cells that are retained locally within tissues, have recently been described as antigen-specific frontline defenders against pathogens in barrier and nonbarrier epithelial tissues. They have also been noted for perpetuating chronic inflammation. The conditions responsible for T differentiation are still poorly understood, and their contributions, if any, to sterile models of chronic kidney disease (CKD) remain a mystery.

Sex Differences in Diurnal Sodium Handling During Diet-Induced Obesity in Rats.

Background: Emerging evidence over the past several years suggests that diurnal control of sodium excretion is sex dependent and involves the renal endothelin system. Given recent awareness of disruptions of circadian function in obesity, we determined whether diet-induced obesity impairs renal handling of an acute salt load at different times of day and whether this varies by sex and is associated with renal endothelin dysfunction.

Methods: Male and female Sprague-Dawley rats were placed on a high-fat diet for 8 weeks before assessing renal sodium handling and blood pressure.

Circadian Control of Sodium and Blood Pressure Regulation.

The attention for the control of dietary risk factors involved in the development of hypertension, includes a large effort on dietary salt restrictions. Ample studies show the beneficial role of limiting dietary sodium as a lifestyle modification in the prevention and management of essential hypertension. Not until the past decade or so have studies more specifically investigated diurnal variations in renal electrolyte excretion, which led us to the hypothesis that timing of salt intake may impact cardiovascular health and blood pressure regulation.

Evidence for G-Protein-Coupled Estrogen Receptor as a Pronatriuretic Factor.

Background The novel estrogen receptor, G-protein-coupled estrogen receptor (GPER), is responsible for rapid estrogen signaling. GPER activation elicits cardiovascular and nephroprotective effects against salt-induced complications, yet there is no direct evidence for GPER control of renal Na handling. We hypothesized that GPER activation in the renal medulla facilitates Na excretion.

Diurnal Control of Blood Pressure Is Uncoupled From Sodium Excretion.

The diurnal rhythms of sodium handling and blood pressure are thought to be regulated by clock genes, such as Bmal1. However, little is known about the regulation of these factors by Bmal1, especially in rats. Using a novel whole-body Bmal1 knockout rat model (), we hypothesized that time of day regulation of sodium excretion is dependent on Bmal1.

Greater natriuretic response to ENaC inhibition in male versus female Sprague-Dawley rats.

Genes for the epithelial sodium channel (ENaC) subunits are expressed in a circadian manner, but whether this results in time-of-day differences in activity is not known. Recent data show that protein expression of ENaC subunits is higher in kidneys from female rats, yet females are more efficient in excreting an acute salt load. Thus, our in vivo study determined whether there is a time-of-day difference as well as a sex difference in the response to ENaC inhibition by benzamil.

Loss of circadian gene in the collecting duct lowers blood pressure in male, but not female, mice.

Kidney function follows a 24-h rhythm subject to regulation by circadian genes including the transcription factor . A high-salt diet induces a phase shift in expression in the renal inner medulla that is dependent on endothelin type B (ET) receptors. Furthermore, ET receptor-mediated natriuresis is sex dependent.