Whole body acid-base modeling revisited
The textbook account of whole body acid-base balance in terms of endogenous acid production, renal net acid excretion, and gastrointestinal alkali absorption, which is the only comprehensive model around, has never been applied in clinical practice or been formally validated. To improve understanding of acid-base modeling, we managed to write up this conventional model as an expression solely on urine chemistry. Renal net acid excretion and endogenous acid production were already formulated in terms of urine chemistry, and we could from the literature also see gastrointestinal alkali absorption in terms of urine excretions...
Source: AJP: Renal Physiology - April 1, 2017 Category: Urology & Nephrology Authors: Ring, T., Nielsen, S. Tags: REVIEW Source Type: research
Mononuclear phagocyte subpopulations in the mouse kidney
Mononuclear phagocytes are the most common cells in the kidney associated with immunity and inflammation. Although the presence of these cells in the kidney has been known for decades, the study of mononuclear phagocytes in the context of kidney function and dysfunction is still at an early stage. The purpose of this review is to summarize the present knowledge regarding classification of these cells in the mouse kidney and to identify relevant questions that would further advance the field and potentially lead to new opportunities for treatment of acute kidney injury and other kidney diseases. (Source: AJP: Renal Physiology)
Source: AJP: Renal Physiology - April 1, 2017 Category: Urology & Nephrology Authors: George, J. F., Lever, J. M., Agarwal, A. Tags: REVIEW Source Type: research
Determination of renal function and injury using near-infrared fluorimetry in experimental cardiorenal syndrome
Cardiorenal syndrome type 1 causes acute kidney injury but is poorly understood; animal models and diagnostic aids are lacking. Robust noninvasive measurements of glomerular filtration rate are required for injury models and clinical use. Several have been described but are untested in translational models and suffer from biologic interference. We developed a mouse model of cardiorenal syndrome and tested the novel near-infrared fluorophore ZW800-1 to assess renal and cardiac function. We performed murine cardiac arrest and cardiopulmonary resuscitation followed by transthoracic echocardiography, 2 and 24 h later. Transcut...
Source: AJP: Renal Physiology - April 1, 2017 Category: Urology & Nephrology Authors: Ikeda, M., Wakasaki, R., Schenning, K. J., Swide, T., Lee, J. H., Miller, M. B., Choi, H. S., Anderson, S., Hutchens, M. P. Tags: INNOVATIVE METHODOLOGY Source Type: research
Liver X receptor {beta} increases aquaporin 2 protein level via a posttranscriptional mechanism in renal collecting ducts
Liver X receptors (LXRs) including LXRα and LXRβ are nuclear receptor transcription factors and play an important role in lipid and glucose metabolism. It has been previously reported that mice lacking LXRβ but not LXRα develop a severe urine concentrating defect, likely via a central mechanism. Here we provide evidence that LXRβ regulates water homeostasis through increasing aquaporin 2 (AQP2) protein levels in renal collecting ducts. LXRβ–/– mice exhibited a reduced response to desmopressin (dDAVP) stimulation, suggesting that the diabetes insipidus phenotype is of both central...
Source: AJP: Renal Physiology - April 1, 2017 Category: Urology & Nephrology Authors: Su, W., Huang, S.-Z., Gao, M., Kong, X.-M., Gustafsson, J.-A., Xu, S.-J., Wang, B., Zheng, F., Chen, L.-H., Wang, N.-P., Guan, Y.-F., Zhang, X.-Y. Tags: RESEARCH ARTICLE Source Type: research
Fgfr2 is integral for bladder mesenchyme patterning and function
While urothelial signals, including sonic hedgehog (Shh), drive bladder mesenchyme differentiation, it is unclear which pathways within the mesenchyme are critical for its development. Studies have shown that fibroblast growth factor receptor 2 (Fgfr2) is necessary for kidney and ureter mesenchymal development. Our objective was to determine the role of Fgfr2 in bladder mesenchyme. We used Tbx18cre mice to delete Fgfr2 in bladder mesenchyme (Fgfr2BM–/–). We performed three-dimensional reconstructions, quantitative real-time PCR, in situ hybridization, immunolabeling, ELISAs, immunoblotting, void stain on paper,...
Source: AJP: Renal Physiology - April 1, 2017 Category: Urology & Nephrology Authors: Ikeda, Y., Zabbarova, I., Schaefer, C. M., Bushnell, D., De Groat, W. C., Kanai, A., Bates, C. M. Tags: RESEARCH ARTICLE Source Type: research
Influence of sex on hyperfiltration in patients with uncomplicated type 1 diabetes
In conclusion, female T1D-H patients had higher RE and FF and lower ERPF than their male counterparts with no associated sex differences in RA. Prospective intervention studies should consider sex as a modifier of renal hemodynamic responses to renal protective therapies. (Source: AJP: Renal Physiology)
Source: AJP: Renal Physiology - April 1, 2017 Category: Urology & Nephrology Authors: Skrtic, M., Lytvyn, Y., Bjornstad, P., Reich, H. N., Scholey, J. W., Yip, P., Sochett, E. B., Perkins, B., Cherney, D. Z. I. Tags: RESEARCH ARTICLE Source Type: research
MicroRNA-30e targets BNIP3L to protect against aldosterone-induced podocyte apoptosis and mitochondrial dysfunction
MicroRNAs are essential for the maintenance of podocyte homeostasis. Emerging evidence has demonstrated a protective role of microRNA-30a (miR-30a), a member of the miR-30 family, in podocyte injury. However, the roles of other miR-30 family members in podocyte injury are unclear. The present study was undertaken to investigate the contribution of miR-30e to the pathogenesis of podocyte injury induced by aldosterone (Aldo), as well as the underlying mechanism. After Aldo treatment, miR-30e was reduced in a dose-and time-dependent manner. Notably, overexpression of miR-30e markedly attenuated Aldo-induced apoptosis in podoc...
Source: AJP: Renal Physiology - April 1, 2017 Category: Urology & Nephrology Authors: Guo, Y., Deng, X., Chen, S., Yang, L., Ni, J., Wang, R., Lin, J., Bai, M., Jia, Z., Huang, S., Zhang, A. Tags: RESEARCH ARTICLE Source Type: research
Parallel microarray profiling identifies ErbB4 as a determinant of cyst growth in ADPKD and a prognostic biomarker for disease progression
Autosomal dominant polycystic kidney disease (ADPKD) is the fourth most common cause of end-stage renal disease. The disease course can be highly variable and treatment options are limited. To identify new therapeutic targets and prognostic biomarkers of disease, we conducted parallel discovery microarray profiling in normal and diseased human PKD1 cystic kidney cells. A total of 1,515 genes and 5 miRNA were differentially expressed by more than twofold in PKD1 cells. Functional enrichment analysis identified 30 dysregulated signaling pathways including the epidermal growth factor (EGF) receptor pathway. In this paper, we ...
Source: AJP: Renal Physiology - April 1, 2017 Category: Urology & Nephrology Authors: Streets, A. J., Magayr, T. A., Huang, L., Vergoz, L., Rossetti, S., Simms, R. J., Harris, P. C., Peters, D. J. M., Ong, A. C. M. Tags: RESEARCH ARTICLE Source Type: research
RACK1 regulates angiotensin II-induced contractions of SHR preglomerular vascular smooth muscle cells
The preglomerular microcirculation of spontaneously hypertensive rats (SHR) is hypersensitive to angiotensin (ANG) II, and studies have shown that this is likely due to enhanced coincident signaling between G protein subunits αq (Gαq; released by ANG II) and β (Gβ; released by Gi-coupled receptors) to active phospholipase C (PLC). Here we investigated the molecular basis for the enhanced coincident signaling between Gβ and Gαq in SHR preglomerular vascular smooth muscle cells (PGVSMCs). Because receptor for activated C kinase 1 (RACK1; a scaffolding protein) organizes interactions between G...
Source: AJP: Renal Physiology - April 1, 2017 Category: Urology & Nephrology Authors: Zhu, X., Jackson, E. K. Tags: RESEARCH ARTICLE Source Type: research
NLRP3 inflammasome activation contributes to aldosterone-induced podocyte injury
Aldosterone (Aldo) has been shown as an important contributor of podocyte injury. However, the underlying molecular mechanisms are still elusive. Recently, the pathogenic role of NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome in mediating renal tubular damage was identified while its role in podocyte injury still needs evidence. Thus the present study was undertaken to investigate the role of NLRP3 inflammasome in Aldo-induced podocyte damage. In vitro, exposure of podocytes to Aldo enhanced NLRP3, caspase-1, and IL-18 expressions in dose- and time-dependent manners, indicating an activation of NL...
Source: AJP: Renal Physiology - April 1, 2017 Category: Urology & Nephrology Authors: Bai, M., Chen, Y., Zhao, M., Zhang, Y., He, J. C.-J., Huang, S., Jia, Z., Zhang, A. Tags: RESEARCH ARTICLE Source Type: research
DNA repair in ischemic acute kidney injury
Ischemia-reperfusion injury (IRI) is a common cause of acute kidney injury leading to an induction of oxidative stress, cellular dysfunction, and loss of renal function. DNA damage, including oxidative base modifications and physical DNA strand breaks, is a consequence of renal IRI. Like many other organs in the body, a redundant and highly conserved set of endogenous repair pathways have evolved to selectively recognize the various types of cellular DNA damage and combat its negative effects on cell viability. Severe damage to the DNA, however, can trigger cell death and elimination of the injured tubular epithelial cells...
Source: AJP: Renal Physiology - April 1, 2017 Category: Urology & Nephrology Authors: Pressly, J. D., Park, F. Tags: REVIEW Source Type: research
Corrigendum
(Source: AJP: Renal Physiology)
Source: AJP: Renal Physiology - March 8, 2017 Category: Urology & Nephrology Tags: CORRIGENDA Source Type: research
A simple method to ensure homogeneous drug distribution during intrarenal infusion
Intrarenal drug infusion plays an important role in renal experimental research. Laminar flow of the blood can cause streaming and inhomogeneous intrarenal distribution of infused drugs. We suggest a simple method to achieve a homogeneous intravascular distribution of drugs infused into the renal artery of anesthetized rats. The method employs a multiple sidehole catheter inserted into the renal artery, which enables an efficient drug mixing with the arterial blood. To verify the efficiency of this method, we use laser speckle imaging and renal artery flowmetry. The results show that, compared with the conventional single-...
Source: AJP: Renal Physiology - March 8, 2017 Category: Urology & Nephrology Authors: Postnov, D. D., Salomonsson, M., Sorensen, C. M., Sosnovtseva, O. Tags: RESEARCH ARTICLE Source Type: research
From 20th century metabolic wall charts to 21st century systems biology: database of mammalian metabolic enzymes
The organization of the mammalian genome into gene subsets corresponding to specific functional classes has provided key tools for systems biology research. Here, we have created a web-accessible resource called the Mammalian Metabolic Enzyme Database (https://hpcwebapps.cit.nih.gov/ESBL/Database/MetabolicEnzymes/MetabolicEnzymeDatabase.html) keyed to the biochemical reactions represented on iconic metabolic pathway wall charts created in the previous century. Overall, we have mapped 1,647 genes to these pathways, representing ~7 percent of the protein-coding genome. To illustrate the use of the database, we apply it to th...
Source: AJP: Renal Physiology - March 8, 2017 Category: Urology & Nephrology Authors: Corcoran, C. C., Grady, C. R., Pisitkun, T., Parulekar, J., Knepper, M. A. Tags: RESEARCH ARTICLE Source Type: research
Pericytes and immune cells contribute to complement activation in tubulointerstitial fibrosis
We have examined the pathogenic role of increased complement expression and activation during kidney fibrosis. Here, we show that PDGFRβ-positive pericytes isolated from mice subjected to obstructive or folic acid injury secrete C1q. This was associated with increased production of proinflammatory cytokines, extracellular matrix components, collagens, and increased Wnt3a-mediated activation of Wnt/β-catenin signaling, which are hallmarks of myofibroblast activation. Real-time PCR, immunoblots, immunohistochemistry, and flow cytometry analysis performed in whole kidney tissue confirmed increased expression of C1q,...
Source: AJP: Renal Physiology - March 8, 2017 Category: Urology & Nephrology Authors: Xavier, S., Sahu, R. K., Landes, S. G., Yu, J., Taylor, R. P., Ayyadevara, S., Megyesi, J., Stallcup, W. B., Duffield, J. S., Reis, E. S., Lambris, J. D., Portilla, D. Tags: RESEARCH ARTICLE Source Type: research
