Raising serum uric acid with a uricase inhibitor worsens PKD in rat and mouse models
Am J Physiol Renal Physiol. 2024 Apr 18. doi: 10.1152/ajprenal.00372.2023. Online ahead of print.ABSTRACTHumans 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 ox...
Source: Am J Physiol Renal P... - April 18, 2024 Category: Urology & Nephrology Authors: Anjana Chaudhary Zhibin He Daniel J Atwood Makoto Miyazaki Ozgur A Oto Allen Davidoff Charles L Edelstein Source Type: research

Keratin 5 Basal Cells are Temporally Regulated Developmental and Tissue Repair Progenitors in Bladder Urothelium
Am J Physiol Renal Physiol. 2024 Apr 18. doi: 10.1152/ajprenal.00378.2023. Online ahead of print.ABSTRACTUrothelium 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 prev...
Source: Am J Physiol Renal P... - April 18, 2024 Category: Urology & Nephrology Authors: Brian Becknell Mohammad El-Harakeh Felipe Rodriguez-Tirado Kelly M Grounds Birong Li Macie Kercsmar Xin Wang Ashley R Jackson Source Type: research

Cannabinoid Receptor Type 1 Activation Causes a Water Diuresis by Inducing an Acute Central Diabetes Insipidus in Mice
Am J Physiol Renal Physiol. 2024 Apr 18. doi: 10.1152/ajprenal.00320.2022. Online ahead of print.ABSTRACTCannabis 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. As the ...
Source: Am J Physiol Renal P... - April 18, 2024 Category: Urology & Nephrology Authors: Joshua L Rein Ken Mackie Thomas R Kleyman Lisa M Satlin Source Type: research

JAK inhibition during the early phase of SARS-CoV-2 infection worsens kidney injury by suppressing endogenous antiviral activity in mice
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. Serum creatinine levels and the urinary albumin/creatinine ratio increased on day 4 after MA10 infection. Measurement of the urinary neutrophil gelatinase-associated lipocalin/creatinine ratio and hematoxylin and eosin staining revealed tubular damage in MA10-infected murine kidneys, indicating kidney injury in the murine COVID-19 model. Interferon (IFN)-γ and interleukin-6 upregulation in the sera of MA10-infecte...
Source: Am J Physiol Renal P... - April 18, 2024 Category: Urology & Nephrology Authors: Hibiki Sakai Hiroyasu Kamuro Nagisa Tokunoh Takeshi Izawa Shigeyuki Tamiya Ayaha Yamamoto Shota Tanaka Daisuke Okuzaki Chikako Ono Yoshiharu Matsuura Yoshiaki Okada Yasuo Yoshioka Yasushi Fujio Masanori Obana Source Type: research

Effect of the DASH diet on the sodium-chloride cotransporter and aquaporin-2 in urinary extracellular vesicles
Am J Physiol Renal Physiol. 2024 Apr 18. doi: 10.1152/ajprenal.00274.2023. Online ahead of print.ABSTRACTThe 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 d...
Source: Am J Physiol Renal P... - April 18, 2024 Category: Urology & Nephrology Authors: Dana Bielopolski Luca Musante Ewout J Hoorn Henrik Molina Douglas Barrows Thomas Carroll Michael A Harding Samantha Upson Adam Qureshi Max M Weder Jonathan N Tobin Rhonda G Kost U Erdbr ügger Source Type: research

Influence of Proteolytic Cleavage of ENaC's Gamma Subunit upon Na < sup > + < /sup > and K < sup > + < /sup > Handling
Am J Physiol Renal Physiol. 2024 Apr 18. doi: 10.1152/ajprenal.00027.2024. Online ahead of print.ABSTRACTThe 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 (143RKRR146, 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 143RKRR146 mutation to 143QQQQ146 (γQ4) in 129/Sv mice ...
Source: Am J Physiol Renal P... - April 18, 2024 Category: Urology & Nephrology Authors: Evan C Ray Andrew Nickerson Shaohu Sheng Rolando Carrisoza-Gayt án Tracey Lam Allison Marciszyn Lei Zhang Alexa Jordahl Chunming Bi Aaliyah Winfrey Zhaohui Kou Sebastien Gingras Annet Kirabo Lisa M Satlin Thomas R Kleyman Source Type: research

Double-negative T cells have a reparative role after experimental severe ischemic acute kidney injury
Am J Physiol Renal Physiol. 2024 Apr 18. doi: 10.1152/ajprenal.00376.2023. Online ahead of print.ABSTRACTT 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...
Source: Am J Physiol Renal P... - April 18, 2024 Category: Urology & Nephrology Authors: Kyungho Lee Sepideh Gharaie Johanna T Kurzhagen Andrea M Newman-Rivera Lois J Arend Sanjeev Noel Hamid Rabb Source Type: research

Commensal Microbiota Regulate Aldosterone
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. In addition, we examined urinary aldosterone. Our findings demonstrated that when the gut microbiota is suppressed following antibiotic treatment, there is an increase in plasma and urinary aldosterone in both female and male mice. In contrast, an increase in PRA is seen only in males. We also found that when gut microbiota are absent (germ-...
Source: Am J Physiol Renal P... - April 18, 2024 Category: Urology & Nephrology Authors: Brittni N Moore Alexandra D Medcalf Rachel Q Muir Chudan Xu Francine Z Marques Jennifer L Pluznick Source Type: research

Animal models to study cognitive impairment of chronic kidney disease
Am J Physiol Renal Physiol. 2024 Apr 18. doi: 10.1152/ajprenal.00338.2023. Online ahead of print.ABSTRACTMild 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 ...
Source: Am J Physiol Renal P... - April 18, 2024 Category: Urology & Nephrology Authors: Pedro H Imenez Silva Marion Pepin Andreja Figurek Eugenio Guti érrez-Jiménez Micka ël Bobot Anna Iervolino Francesco Mattace-Raso Ewout J Hoorn Matthew A Bailey Lucie H énaut Rikke Nielsen Sebastian Frische Francesco Trepiccione Gaye Hafez Hande O Alt Source Type: research

Podocyte-Specific Silencing of Acid Sphingomyelinase Gene to Abrogate Hyperhomocysteinemia-Induced NLRP3 Inflammasome Activation and Glomerular Inflammation
In conclusion, our findings suggest that ASM in podocytes plays a crucial role in the control of NLRP3 inflammasome activation and exosome release.PMID:38634138 | DOI:10.1152/ajprenal.00195.2023 (Source: Am J Physiol Renal P...)
Source: Am J Physiol Renal P... - April 18, 2024 Category: Urology & Nephrology Authors: Dandan Huang Jason M Kidd Yao Zou Xiaoyuan Wu Ningjun Li Todd W B Gehr Pin-Lan Li Guangbi Li Source Type: research

Raising serum uric acid with a uricase inhibitor worsens PKD in rat and mouse models
Am J Physiol Renal Physiol. 2024 Apr 18. doi: 10.1152/ajprenal.00372.2023. Online ahead of print.ABSTRACTHumans 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 ox...
Source: Am J Physiol Renal P... - April 18, 2024 Category: Urology & Nephrology Authors: Anjana Chaudhary Zhibin He Daniel J Atwood Makoto Miyazaki Ozgur A Oto Allen Davidoff Charles L Edelstein Source Type: research

Keratin 5 Basal Cells are Temporally Regulated Developmental and Tissue Repair Progenitors in Bladder Urothelium
Am J Physiol Renal Physiol. 2024 Apr 18. doi: 10.1152/ajprenal.00378.2023. Online ahead of print.ABSTRACTUrothelium 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 prev...
Source: Am J Physiol Renal P... - April 18, 2024 Category: Urology & Nephrology Authors: Brian Becknell Mohammad El-Harakeh Felipe Rodriguez-Tirado Kelly M Grounds Birong Li Macie Kercsmar Xin Wang Ashley R Jackson Source Type: research

Cannabinoid Receptor Type 1 Activation Causes a Water Diuresis by Inducing an Acute Central Diabetes Insipidus in Mice
Am J Physiol Renal Physiol. 2024 Apr 18. doi: 10.1152/ajprenal.00320.2022. Online ahead of print.ABSTRACTCannabis 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. As the ...
Source: Am J Physiol Renal P... - April 18, 2024 Category: Urology & Nephrology Authors: Joshua L Rein Ken Mackie Thomas R Kleyman Lisa M Satlin Source Type: research

JAK inhibition during the early phase of SARS-CoV-2 infection worsens kidney injury by suppressing endogenous antiviral activity in mice
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. Serum creatinine levels and the urinary albumin/creatinine ratio increased on day 4 after MA10 infection. Measurement of the urinary neutrophil gelatinase-associated lipocalin/creatinine ratio and hematoxylin and eosin staining revealed tubular damage in MA10-infected murine kidneys, indicating kidney injury in the murine COVID-19 model. Interferon (IFN)-γ and interleukin-6 upregulation in the sera of MA10-infecte...
Source: Am J Physiol Renal P... - April 18, 2024 Category: Urology & Nephrology Authors: Hibiki Sakai Hiroyasu Kamuro Nagisa Tokunoh Takeshi Izawa Shigeyuki Tamiya Ayaha Yamamoto Shota Tanaka Daisuke Okuzaki Chikako Ono Yoshiharu Matsuura Yoshiaki Okada Yasuo Yoshioka Yasushi Fujio Masanori Obana Source Type: research

Effect of the DASH diet on the sodium-chloride cotransporter and aquaporin-2 in urinary extracellular vesicles
Am J Physiol Renal Physiol. 2024 Apr 18. doi: 10.1152/ajprenal.00274.2023. Online ahead of print.ABSTRACTThe 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 d...
Source: Am J Physiol Renal P... - April 18, 2024 Category: Urology & Nephrology Authors: Dana Bielopolski Luca Musante Ewout J Hoorn Henrik Molina Douglas Barrows Thomas Carroll Michael A Harding Samantha Upson Adam Qureshi Max M Weder Jonathan N Tobin Rhonda G Kost U Erdbr ügger Source Type: research