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Am J Physiol Renal Physiol 2022 May 9. Epub 2022 May 9.

Heart and Kidney Institute, College of Pharmacy, University of Houston, Houston, Texas, United States.

Ischemia/reperfusion (I/R) is considered the primary cause of acute kidney injury and is higher among older individuals. While ischemic episodes are hard to predict and prevent, detrimental ischemic effects could be mitigated by exogenous intervention. This study aims to identify the protective role of angiotensin (ANG)1-7 against I/R-induced renal injury in adult vs. Read More

Am J Physiol Renal Physiol 2022 May 9. Epub 2022 May 9.

Department of Anesthesiology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States.

Introduction: Acute kidney injury is a common cause of morbidity after congenital heart disease surgery. Progress on diagnosis and therapy remains limited, however, in part due to poor mechanistic understanding and lack of relevant translational models. Metabolomic approaches could help identify novel mechanisms of injury and potential therapeutic targets. Read More

Am J Physiol Renal Physiol 2022 May 9. Epub 2022 May 9.

Division of Nephrology & Hypertension, Oregon Health & Science University, Portland, OR, United States.

Cullin-RING ligases (CRLs) are a family of E3 ubiquitin ligases that control cellular processes through regulated degradation. Cullin 3 (CUL3) targets with-no-lysine kinase 4 (WNK4), a kinase that activates the Na-Cl cotransporter (NCC) the main pathway for sodium reabsorption in the distal convoluted tubule (DCT). Mutations in CUL3 lead to familial hyperkalemic hypertension by increasing WNK4 abundance. Read More

Am J Physiol Renal Physiol 2022 May 2. Epub 2022 May 2.

Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, Brazil.

Caloric restriction (CR) prevents obesity and increases resilience against pathological stimuli in laboratory rodents. At the mitochondrial level, protection promoted by CR in the brain and liver is related to higher calcium uptake rates and capacities, avoiding Ca-induced mitochondrial permeability transition. Dietary restriction has also been shown to increase kidney resistance against damaging stimuli, but if these effects are related to similar mitochondrial adaptations has not been uncovered. Read More

Am J Physiol Renal Physiol 2022 May 2. Epub 2022 May 2.

Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, United States.

Disruption of the blood-urine barrier can result in acute or chronic inflammatory bladder injury. Activation of the oxygen-regulated hypoxia-inducible factor (HIF) pathway has been shown to protect mucosal membranes by increasing the expression of cytoprotective genes and by suppressing inflammation. The activity of HIF is controlled by prolyl hydroxylase domain (PHD) dioxygenases, which have been exploited as therapeutic targets for the treatment of anemia of chronic kidney disease. Read More

Am J Physiol Renal Physiol 2022 06 25;322(6):F692-F707. Epub 2022 Apr 25.

Department of Molecular Pharmacology and Physiology, University of South Florida, Tampa, Florida.

Na-glucose cotransporter-2 (SGLT2) inhibitors are the new mainstay of treatment for diabetes mellitus and cardiovascular diseases. Despite the remarkable benefits, the molecular mechanisms mediating the effects of SGLT2 inhibitors on water and electrolyte balance are incompletely understood. The goal of this study was to determine whether SGLT2 inhibition alters blood pressure and kidney function via affecting the renin-angiotensin-aldosterone system (RAAS) and Na channels/transporters along the nephron in Dahl salt-sensitive rats, a model of salt-induced hypertension. Read More

Am J Physiol Renal Physiol 2022 06 25;322(6):F680-F691. Epub 2022 Apr 25.

Department of Physiology, University of Arizona Health Sciences Center, Tucson, Arizona.

Polycystic kidney disease (PKD) is the most common inheritable cause of kidney failure, and the underlying mechanisms remain incompletely uncovered. Renal nerves contribute to hypertension and chronic kidney disease-frequent complications of PKD. There is limited evidence that renal nerves may contribute to cardiorenal dysfunction in PKD and no investigations of the role of sympathetic versus afferent nerves in PKD. Read More

Am J Physiol Renal Physiol 2022 05;322(5)

Am J Physiol Renal Physiol 2022 06 18;322(6):F667-F679. Epub 2022 Apr 18.

Department of Nephrology and Laboratory Medicine, Kanazawa University, Kanazawa, Japan.

Recent studies have revealed the connection between amino acid chirality and diseases. We have previously reported that the gut microbiota produces various d-amino acids in a murine acute kidney injury (AKI) model. Here, we further explored the pathophysiological role of d-alanine (d-Ala) in AKI. Read More

Am J Physiol Renal Physiol 2022 06 18;322(6):F655-F666. Epub 2022 Apr 18.

Department of Medicine, Joan C. Edwards School of Medicine, Marshall University, Huntington, West Virginia.

We have previously demonstrated that the Na-K-ATPase signaling-mediated oxidant amplification loop contributes to experimental uremic cardiomyopathy and anemia induced by 5/6th partial nephrectomy (PNx). This process can be ameliorated by systemic administration of the peptide pNaKtide, which was designed to block this oxidant amplification loop. The present study demonstrated that the PNx-induced anemia is characterized by marked decreases in red blood cell (RBC) survival as assessed by biotinylated RBC clearance and eryptosis as assessed by annexin V binding. Read More

Am J Physiol Renal Physiol 2022 May;322(5):F573-F574

Am J Physiol Renal Physiol 2022 06 11;322(6):F587-F588. Epub 2022 Apr 11.

Department of Molecular Pharmacology and Physiology, College of Medicine, University of South Florida, Tampa, Florida.

Am J Physiol Renal Physiol 2022 06 11;322(6):F611-F624. Epub 2022 Apr 11.

Department of Nephrology, 2nd Affiliated Hospital of Harbin Medical University, Harbin, People's Republic of China.

Promoting adaptive repair in acute kidney injury (AKI) is an effective strategy to prevent the progression from AKI to chronic kidney disease. However, the mechanisms involved in renal repair after AKI remain unclear. In this study, we investigated the role of hypoxia-inducible factor (HIF), an important regulator of ischemic and hypoxic injury, in AKI during the repair phase. Read More

Am J Physiol Renal Physiol 2022 06 4;322(6):F597-F610. Epub 2022 Apr 4.

Department of Medicine and Center for Immunity and Regenerative Medicine, University of Virginia, Charlottesville, Virginia.

We have previously reported that increased expression and activation of kidney cell complement components play an important role in the pathogenesis of renal scarring. Here, we used floxed green fluorescent protein (GFP)-C5a receptor 1 (C5aR1) knockin mice (GFP-) and the model of folic acid (FA)-induced kidney injury to define the cell types and potential mechanisms by which increased C5aR1 activation leads to fibrosis. Using flow cytometry and confocal microscopy, we identified macrophages as the major interstitial cell type showing increased expression of C5aR1 in FA-treated mice. Read More

Am J Physiol Renal Physiol 2022 06 4;322(6):F639-F654. Epub 2022 Apr 4.

Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin.

The 5/6 nephrectomy rat remnant kidney model is commonly used to study chronic kidney disease (CKD). This model requires the removal of one whole kidney and two-thirds of the other kidney. The two most common ways of producing the remnant kidney are surgical resection of poles, known as the polectomy model, or ligation of superior and inferior segmental renal arteries, resulting in pole infarction. Read More

Am J Physiol Renal Physiol 2022 06 4;322(6):F625-F638. Epub 2022 Apr 4.

Division of Nephrology, Kidney Research Institute, and Institute for Stem Cell and Regenerative Medicine, Department of Medicine, Department of Laboratory Medicine and Physiology (adjunct), and Department of Bioengineering (adjunct), University of Washington School of Medicine, Seattle, Washington.

Kidney organoids derived from human pluripotent stem cells constitute a novel model of disease, development, and regenerative therapy. Organoids are human, experimentally accessible, high throughput, and enable reconstitution of tissue-scale biology in a petri dish. Although gene expression patterns in organoid cells have been analyzed extensively, less is known about the functionality of these structures. Read More

Am J Physiol Renal Physiol 2022 06 4;322(6):F589-F596. Epub 2022 Apr 4.

Veterans Affairs San Diego Healthcare System, San Diego, California.

Acute kidney injury (AKI) is a systemic inflammatory disease that contributes to remote organ failures. Multiple organ failure is the leading cause of death due to AKI, and lack of understanding of the mechanisms involved has precluded the development of novel therapies. Mitochondrial injury in AKI leads to mitochondrial fragmentation and release of damage-associated molecular patterns, which are known to active innate immune pathways and systemic inflammation. Read More

Am J Physiol Renal Physiol 2022 04;322(4):i-ii

Am J Physiol Renal Physiol 2022 05 28;322(5):F575-F576. Epub 2022 Mar 28.

Department of Surgery, grid.17635.36University of Minnesota, Minneapolis, Minnesota.

Am J Physiol Renal Physiol 2022 05 28;322(5):F577-F586. Epub 2022 Mar 28.

Department of Nephrology, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan.

Acute kidney injury (AKI) is a life-threatening condition and often progresses to chronic kidney disease or the development of other organ dysfunction even after recovery. Despite the increased recognition and high prevalence of AKI worldwide, there has been no established treatment so far. The aim of this study was to investigate the renoprotective effect of Kyoto University substance 121 (KUS121), a novel valosin-containing protein modulator, on AKI. Read More

Am J Physiol Renal Physiol 2022 Mar 28. Epub 2022 Mar 28.

The Jared Grantham Kidney Institute, University of Kansas Medical Center, Kansas City, KS, United States.

Individuals with autosomal dominant polycystic kidney disease (ADPKD) have a higher incidence of stone formation than the general population. However, there are no cystic animal models known to develop stones. Cystic mice compound heterozygous for hypomorphic Pkd1 and Pkd1 alleles develop cystic kidneys within a few weeks of birth but live beyond twenty weeks of age, allowing for the study of cystic comorbidities including stone formation. Read More

Am J Physiol Renal Physiol 2022 05 21;322(5):F540-F552. Epub 2022 Mar 21.

First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan.

Acute kidney injury (AKI) contributes to the development of acute lung injury (ALI) via proinflammatory responses. We hypothesized that activation of a nicotinic acetylcholine receptor (nAChR), which exerts cholinergic anti-inflammatory effects on macrophages, could reduce ALI after AKI. We aimed to determine whether nAChR agonists could reduce ALI after AKI and which macrophages in the lung or spleen contribute to the improvement of ALI by nAChR agonists. Read More

Am J Physiol Renal Physiol 2022 05 21;322(5):F553-F572. Epub 2022 Mar 21.

Kidney Research Institute, Seoul National University, Seoul, Korea.

Signal transducer and activator of transcription 3 (STAT3) is a pivotal mediator of IL-6-type cytokine signaling. However, the roles of its full-length and truncated isoforms in acute kidney injury (AKI) and its transition to chronic kidney disease (CKD) remain elusive. Herein, the role of STAT3 isoforms in the AKI-to-CKD transition was characterized using an ischemia-reperfusion injury (IRI) mouse model. Read More

Am J Physiol Renal Physiol 2022 Apr;322(4):F468

Am J Physiol Renal Physiol 2022 05 14;322(5):F470-F472. Epub 2022 Mar 14.

Division of Nephrology, Department of Medicine, Nephrology Research and Training Center, University of Alabama at Birmingham, Birmingham, Alabama.

Am J Physiol Renal Physiol 2022 05 14;322(5):F498-F511. Epub 2022 Mar 14.

Department of Physiology and Biophysics and the Center for Excellence in Cardiovascular Renal Research, University of Mississippi Medical Center, Jackson, Mississippi.

In independent studies, our laboratory has shown the importance of the degenerin proteins β-epithelial Na channel (βENaC) and acid-sensing ion channel 2 (ASIC2) in pressure-induced constriction (PIC) in renal interlobar arteries. Most, but not all, of the PIC response is abolished in mice lacking normal levels of βENaC or in ASIC2-null mice, indicating that the functions of βENaC and ASIC2 cannot fully compensate for the loss of the other. Degenerin proteins are known to associate and form heteromeric channels in expression systems, but whether they interact biochemically and functionally in vascular smooth muscle cells is unknown. Read More

Am J Physiol Renal Physiol 2022 03;322(3)

Am J Physiol Renal Physiol 2022 05 7;322(5):F512-F526. Epub 2022 Mar 7.

College of Veterinary Medicine, China Agricultural University, Beijing, People's Republic of China.

Injury-induced fibroblast-to-myofibroblast differentiation is a key event of renal fibrosis. Yes-associated protein (YAP), a transcriptional coactivator, plays an important role in fibroblast activation and Smad transcriptional activity to promote transforming growth factor-β (TGF-β)-induced differentiation from fibroblasts to myofibrolasts. Macrophage stimulating 1/2 (MST1/2), a negative regulator of YAP, also increases in fibroblasts by TGF-β stimulation. Read More

Am J Physiol Renal Physiol 2022 05 28;322(5):F527-F539. Epub 2022 Feb 28.

Division of Nephrology and Hypertension, Department of Medicine, UNC Kidney Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.

Obesity is a risk factor for the development of kidney disease. The role of diet in this association remains undetermined, in part due to practical limitations in studying nutrition in humans. In particular, the relative importance of calorie excess versus dietary macronutrient content is poorly understood. Read More

Am J Physiol Renal Physiol 2022 04 28;322(4):F429-F436. Epub 2022 Feb 28.

Division of Hypertension and Vascular Research, Department of Internal Medicine, grid.413103.4Henry Ford Hospital, Detroit, Michigan.

Obesity increases the risk of renal damage, but the mechanisms are not clear. Normally, kidneys autoregulate to keep the glomerular capillary pressure (P), renal blood flow, and glomerular filtration rate in a steady state. However, in obesity, higher P, renal blood flow, and glomerular filtration rate are noted. Read More