American Journal of Physiology. Renal Physiology

Prenatal, perinatal, and adulthood exposure to chronic intermittent hypoxia (IH) increases blood pressure in rodents. Males exposed to chronic IH have higher blood pressure vs females. However, it is unknown if this same sex difference exists with acute perinatal IH. We tested the hypothesis that acute perinatal IH increases baseline blood pressure and enhances sensitivity to angiotensin II-induced hypertension in male Sprague Dawley rats. Male and female pups were randomized to control (room air) or IH (10 minutes of ~10% O2 three times/day) for the first 8 days of life...

Use of the immunosuppressants calcineurin inhibitors (CNIs) are limited by irreversible kidney damage, hallmarked by renal fibrosis. CNIs directly damage many renal cell types. Given the diverse renal cell populations, additional targeted cell types and signaling mechanisms warrant further investigation. We hypothesize that fibroblasts contribute to CNI-induced renal fibrosis and propagate profibrotic effects via the TGFβ/Smad signaling axis. To test this, kidney-damage resistant mice (C57BL/6) received tacrolimus (10mg/kg) or vehicle for 21 days...

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No abstract text is available yet for this article.

The thick ascending limb (TAL) is critical for the renal control of fluid and ion homeostasis. The function of the TAL depends on the activity of the bumetanide-sensitive Na-K-2Cl co-transporter NKCC2, which is highly abundant in the luminal membrane of TAL cells. TAL function is regulated by various hormonal and non-hormonal factors. However, many of the underlying signal transduction pathways remain elusive. Here, we describe and characterize a novel gene-modified mouse model for an inducible and specific Cre/Lox-mediated gene modification in the TAL...

No abstract text is available yet for this article.

Patients with chronic kidney disease (CKD) are at increased risk for adverse cardiovascular events. CKD is associated with increases in arterial stiffness while improvements of arterial stiffness, correlates with better survival. However, arterial stiffness is increased early in CKD suggesting there might be additional factors, unique to kidney disease, that increase arterial stiffness. Lysyl Oxidase (LOX) is a key mediator of collagen cross-linking and matrix remodeling. LOX is predominantly expressed in the cardiovascular system and its up regulation has been associated with increased tissue stiffening and extracellular matrix remodeling...

Measurement of total kidney volume (TKV) using magnetic resonance imaging (MRI) is a valuable approach for monitoring disease progression in autosomal dominant polycystic kidney disease (ADPKD) and is becoming more common in preclinical studies using animal models. Manual contouring of kidney MRI areas (i.e., manual method (MM)) is a conventional, but time-consuming, way to determine TKV. We developed a template-based semi-automatic image segmentation method (SAM) and validated it in three commonly used PKD models, Cys1cpk/cpk mice, Pkd1RC/RC mice, and Pkhd1pck/pck rats (n=10 per model)...

Inflammation that develops with the release of chemokines and cytokines during acute kidney injury (AKI) has been shown to participate in functional renal recovery. While a major research focus has been on the role of macrophages, the family of CXC motif chemokines that promote neutrophil adherence and activation also increase with kidney ischemia/reperfusion (I/R) injury. This study tested the hypothesis that intravenous delivery of endothelial cells that overexpress CXCR1 and CXCR2 improves outcomes in kidney I/R injury...

Polycystic kidney disease is a disorder of renal epithelial growth and differentiation. Transcription factor EB (TFEB), a master regulator of lysosome biogenesis and function, was studied for a potential role in this disorder. The nuclear translocation and functional responses to TFEB activation were studied in three murine models of renal cystic disease, including knockouts of folliculin, folliculin interacting proteins 1 and 2, and Pkd1 as well as in mouse embryonic fibroblasts lacking Pkd1 and 3-dimensional cultures of MDCK cells...

Postoperative acute kidney injury (AKI) is a common complication after surgery. The pathophysiology of postoperative AKI is complex. One potentially important factor is anesthetic modality. We therefore conducted a meta-analysis of the available literature regarding anesthetic modality and incidence of postoperative AKI. Records were retrieved until January 17, 2023, with the search terms ("propofol" OR "intravenous") AND ("sevoflurane" OR "desflurane" OR "isoflurane" OR "volatile" OR "inhalational") AND ("acute kidney injury" OR "AKI")...

Chronic kidney disease of uncertain etiology (CKDu) is a global health concern affecting tropical farming communities. CKDu is not associated with typical risk factors (e.g., diabetes) and strongly correlates with environmental drivers. To gain potential insights into disease etiology and diagnosis, here we report the first urinary proteome comparing CKDu patients and non-CKDu controls from Sri Lanka. We found 944 differentially abundant proteins (DAPs). In silico analyses identified 636 proteins of likely kidney and urogenital origin...

Activation of NADPH oxidase (NOX) enzymes and the generation of reactive oxygen species (ROS) and oxidative stress regulate vascular and renal function and contribute to the pathogenesis of hypertension. This study examined the role of NOXA1/NOX1 function in vascular reactivity of renal and mesenteric resistance arteries/arterioles of wild-type and Noxa1-/- mice. A major finding is that the renal blood flow (RBF) is less sensitive to acute stimulation by Ang II (Angiotensin II) in Noxa1-/- mice compared with wild-type mice, with a direct action on resistance arterioles independent of nitric oxide (NO) bioavailability...

The Na/K/2Cl cotransporter (NKCC2) in the thick ascending limb of the loop of Henle (TAL) mediates NaCl reabsorption. Cyclic guanosine monophosphate (cGMP), the second messenger of nitric oxide and atrial natriuretic peptide, inhibits NKCC2 activity by stimulating NKCC2 ubiquitination and decreasing surface NKCC2 levels. Among the E3-ubiquitin ligase families, the Cullin-RING E3 ubiquitin ligase (CRL) family is the largest. Cullins are molecular scaffold proteins that recruit multiple subunits to form the CRL complex...

Circadian variability in kidney function is well recognized but is often ignored as a potential confounding variable in physiological experiments. Here, we have created a data resource consisting of expression levels for mRNA transcripts in microdissected proximal tubule segments from mice as a function of the time of day. Small-sample RNA-sequencing (RNA-seq) was applied to microdissected S1 proximal convoluted tubules (PCTs) and S2 proximal straight tubules (PSTs). After stringent filtering, the data were analyzed using JTK-Cycle to detect periodicity...

BACKGROUND: Cancer patients represent a unique patient population with increased susceptibility to kidney disease. Drug-induced acute kidney injury (AKI) in cancer patients is a common problem. Cisplatin is a highly effective treatment used in many solid organ cancers and causes AKI in 30% of patients, increasing the risk of chronic kidney disease (CKD) development. Most preclinical cisplatin toxicity studies have been completed in mice without cancer. We believe the physiology of cancer patients is not adequately represented in preclinical models, and the objective of this study was to determine how lung cancer will alter cisplatin's nephrotoxicity...

Sex differences in renal function and blood pressure have been widely described across many species. Blood pressure dips during sleep and peaks in the early morning. Similarly, glomerular filtration rate, filtered electrolyte loads, urine volume, and urinary excretion all exhibit notable diurnal rhythms, which reflect, in part, the regulation of renal transporter proteins by circadian clock genes. That regulation is sexually dimorphic; as such, sex and time-of-day are not two independent regulators of kidney function and blood pressure...

This study aimed to clarify whether the down regulation of K+-Cl-co-transporter 2 (KCC2) in the sacral parasympathetic nucleus (SPN) of the lumbosacral spinal cord, from which the efferent pathway innervating the bladder originates, causes cellular hyperexcitability and triggers detrusor overactivity (DO) in spinal cord injury (SCI). SCI was produced by the Th8-9 spinal cord transection in female C57BL/6 mice. At 4 weeks after SCI, CLP290, a KCC2 activator, was administered, and cystometry was performed. Thereafter, neuronal activity with c-fos staining and KCC2 expression in the cholinergic preganglionic parasympathetic neurons in the SPN were examined using immunohistochemistry...

The bicarbonate-chloride exchanger, pendrin, in the kidney maintains acid-base balance and intravascular volume. Pendrin is upregulated in models associated with high circulating aldosterone concentration, such as dietary NaCl restriction or an aldosterone infusion. But it has not been established if pendrin is similarly regulated by aldosterone with high potassium diet because the effects of accompanying anions have not been considered. Here we explore how pendrin is modulated by different dietary potassium salts; wild-type (WT) and aldosterone synthase knockout mice (AS KO) randomized to control, high potassium bicarbonate or high potassium chloride diets...

The diverse functions of each nephron segment rely on the coordinated action of specialized cell populations that are uniquely defined by their transcriptional profile. In the collecting duct, there are two critical and distinct cell populations: principal cells and intercalated cells. Principal cells play key roles in the regulation of water, Na+ , and K+ , while intercalated cells are best known for their role in acid-base homeostasis. Currently, there are no in vitro systems that recapitulate the heterogeneity of the collecting ducts, which limits high-throughput and replicate investigations of genetic and physiological phenomena...