Albumin contributes to kidney disease progression in Alport syndrome.
Abstract Alport syndrome is a familial kidney disease caused by defects in the collagen IV network of the glomerular basement membrane. The lack of collagen α3α4α5(IV) changes the glomerular basement membrane morphologically and functionally, rendering it leaky to albumin and other plasma proteins. Filtered albumin has been suggested to be a cause of the glomerular and tubular injuries observed at advanced stages of Alport syndrome. To directly investigate the role albumin plays in progression of disease in Alport syndrome, we generated albumin knockout (Alb-/-) mice to use as a tool for removing...
Source: Am J Physiol Renal P... - May 4, 2016 Category: Urology & Nephrology Authors: Jarad G, Knutsen RH, Mecham RP, Miner JH Tags: Am J Physiol Renal Physiol Source Type: research

Does Pharmacological Activation of 5-HT1A Receptors Improve Urine Flow Rate in Female Rats?
This study examined the effects of 5-HT1A receptors on regulating urethral functions in female rats, and investigated underlying modulatory mechanisms. Intravesical pressure (IVP), external urethral sphincter-electromyography (EUS-EMG), and UFR were simultaneously recorded during continuous transvesical infusion to examine the effects of a 5-HT1A receptor agonist (8-OH-DPAT) and antagonist (WAY-100635) on bladder and urethral functions. In addition, this study evaluated the independent roles of urethral striated and smooth muscles in the UFR in rats after the neuromuscular blockade (NMB) treatment and the bilateral hypogas...
Source: Am J Physiol Renal P... - May 4, 2016 Category: Urology & Nephrology Authors: Chen SC, Hsieh TH, Fan WJ, Lai CH, Peng CW Tags: Am J Physiol Renal Physiol Source Type: research

Activation of soluble guanylyl cyclase by BAY 58-2667 improves bladder function in cyclophosphamide-induced cystitis in mice.
This study aimed to evaluate the effects of the sGC activator BAY 58-2667 on voiding dysfunction, protein expressions of α1 and β1 sGC subunits and cGMP levels in the bladder tissues after cyclophosphamide (CYP) exposure. Female C57BL/6 mice (20-25 g) were injected with CYP (300 mg/kg, i.p) to induce cystitis. Mice were pretreated or not with BAY 58-2667 (1 mg/kg, gavage), given 1 h prior to CYP injection. The micturition patterns and in vitro bladder contractions were evaluated at 24 h. In freely-moving mice, CYP injection produced reduced the micturition volume and increased the number of urine spots. Cystomet...
Source: Am J Physiol Renal P... - April 27, 2016 Category: Urology & Nephrology Authors: de Oliveira MG, Calmasini FB, Alexandre EC, De Nucci G, Mónica FZ, Antunes E Tags: Am J Physiol Renal Physiol Source Type: research

Glomerular pathology and the progression of chronic kidney disease.
Abstract Structural studies of the glomerulus, largely undertaken in animal models, have informed our understanding of the progression of chronic kidney disease (CKD) for decades. A fundamental tenet of that understanding is that a loss of podocytes underlies progression in many or most cases of progressive CKD. Recent attempts have been made to reconcile earlier findings from glomerular physiology (the primacy of glomerular capillary hypertension in causation of secondary glomerular sclerosis) with structural findings and have suggested a more detailed model of the mechanisms underlying podocyte detachment as via...
Source: Am J Physiol Renal P... - April 27, 2016 Category: Urology & Nephrology Authors: Lemley KV Tags: Am J Physiol Renal Physiol Source Type: research

The expression, regulation and function of Kir4.1 (Kcnj10) in the mammalian kidney.
Abstract Kir.4.1 is an inwardly-rectifying potassium (K+) channel and is expressed in the brain, inner ear and kidney. In the kidney, Kir4.1 is expressed in the basolateral membrane of the late thick ascending limb (TAL), the distal convoluted tubule (DCT) and the connecting tubule (CNT)/ cortical collecting duct (CCD). It plays a role in K+ recycling across the basolateral membrane in corresponding nephron segments and in generating negative membrane potential. The renal phenotypes of the loss-function-mutations of Kir4.1 include mild salt wasting, hypomagnesemia, hypokalemia, and metabolic alkalosis, suggesting ...
Source: Am J Physiol Renal P... - April 27, 2016 Category: Urology & Nephrology Authors: Su XT, Wang WH Tags: Am J Physiol Renal Physiol Source Type: research

Wnt6 regulates epithelial cell differentiation and is dysregulated in renal fibrosis.
Abstract Diabetic nephropathy is the most common microvascular complication of diabetes mellitus, manifesting as mesangial expansion, glomerular basement membrane thickening, glomerular sclerosis and progressive tubulointerstitial fibrosis leading to end-stage renal disease. Here we describe the functional characterization of Wnt6, whose expression is progressively lost in diabetic nephropathy and animal models of acute tubular injury and renal fibrosis. We have shown prominent Wnt6 and FzD7 expression in the mesonephros of the developing mouse kidney, suggesting a role for Wnt6 in epithelialization. Importantly, ...
Source: Am J Physiol Renal P... - April 27, 2016 Category: Urology & Nephrology Authors: Beaton H, Andrews D, Parsons M, Murphy M, Gaffney A, Kavanagh D, McKay GJ, Maxwell AP, Taylor CT, Cummins EP, Godson C, Higgins DF, Murphy P, Crean J Tags: Am J Physiol Renal Physiol Source Type: research

What we need to know about the effect of lithium on the kidney.
Abstract Lithium has been a valuable treatment for bipolar affective disorders for decades. Clinical use of lithium, however, has been problematic due to its narrow therapeutic index and concerns for its toxicity in various organ systems. Renal side effects associated with lithium include polyuria, nephrogenic diabetes insipidus, proteinuria, distal renal tubular acidosis and reduction in glomerular filtration rate. Histologically, chronic lithium nephrotoxicity is characterized by interstitial nephritis with microcyst formation and occasional focal segmental glomerulosclerosis. Nevertheless, this type of toxicity...
Source: Am J Physiol Renal P... - April 27, 2016 Category: Urology & Nephrology Authors: Gong R, Wang P, Dworkin LD Tags: Am J Physiol Renal Physiol Source Type: research

Par3A is dispensable for the function of the glomerular filtration barrier of the kidney.
In conclusion, Par3A function is either dispensable for slit diaphragm integrity or compensatory mechanisms and a high redundancy of the different polarity proteins including Par3B, Lgl or PALS1 maintain the function of the glomerular filtration barrier even in the absence of Par3A. PMID: 27122542 [PubMed - as supplied by publisher] (Source: Am J Physiol Renal P...)
Source: Am J Physiol Renal P... - April 27, 2016 Category: Urology & Nephrology Authors: Koehler S, Tellkamp F, Niessen CM, Bloch W, Kerjaschki D, Schermer B, Benzing T, Brinkkoetter PT Tags: Am J Physiol Renal Physiol Source Type: research

Collecting Duct (Pro)Renin Receptor Targets ENaC to Mediate Angiotensin II-Induced Hypertension.
Abstract (Pro)renin receptor (PRR) is abundantly expressed in the collecting duct (CD) and the expression is further induced by angiotensin II (AngII). The present study was conducted to investigate the role of CD PRR during AngII-induced hypertension and to further explore the underlying mechanism. Radiotelemetry demonstrated that a 1-wk AngII infusion gradually and significantly induced hypertensive response in floxed mice and this response was significantly attenuated in mice lacking PRR in the CD (termed CD PRR KO). AngII infusion in floxed mice increased urinary renin activity and selectively induced renal me...
Source: Am J Physiol Renal P... - April 27, 2016 Category: Urology & Nephrology Authors: Peng K, Lu X, Wang F, Nau A, Chen R, Zhou SF, Yang T Tags: Am J Physiol Renal Physiol Source Type: research

50 Years of Renal Physiology from One Man and the Perfused Tubule: Maurice B. Burg.
In this study, we have taken a scientific visualization approach to study the scientific contributions of Dr. Burg and the isolated perfused tubule preparation as determining research impact by the number of research students, postdoctoral fellows, visiting scientists, and national and international collaborators. Additionally, we have examined the research collaborations (1st and 2nd generation scientists), established the migrational visualization of the 1st generation scientists who worked directly with Dr. Burg, quantified the metrics indices, identified and quantified the network of co-authorship of the 1st generation...
Source: Am J Physiol Renal P... - April 27, 2016 Category: Urology & Nephrology Authors: Hamilton KL, Moore TB Tags: Am J Physiol Renal Physiol Source Type: research

MAD2B-mediated SnoN Downregulation Is Implicated in Fibroblast Activation and Tubulointerstitial Fibrosis.
In conclusion, our observation proposes that besides cell cycle management MAD2B has a profibrotic role during fibroblast activation and TIF by suppressing SnoN expression. Targeting MAD2B-SnoN pathway is a promising intervention for TIF. PMID: 27122545 [PubMed - as supplied by publisher] (Source: Am J Physiol Renal P...)
Source: Am J Physiol Renal P... - April 27, 2016 Category: Urology & Nephrology Authors: Tang H, Su H, Fan D, Ye C, Lei CT, Jiang HJ, Gao P, He FF, Zhang C Tags: Am J Physiol Renal Physiol Source Type: research

The complement receptor C5aR1 contributes to renal damage but protects the heart in angiotensin II-induced hypertension.
UO Abstract Adaptive and innate immune responses contribute to hypertension and hypertensive end-organ damage. Here we determined the role of the anaphylatoxin C5a, a major inflammatory effector of the innate immune system that is generated in response to complement activation, in hypertensive end-organ damage. For this pupose we assessed the phenotype of C5a receptor 1 (C5aR1)-deficient mice in in angiotensin II (Ang II)-induced renal and cardiac injury. Expression of the C5aR1 on infiltrating and resident renal as well as on cardiac cells was determined using a GFP-C5aR1 reporter knock-in mouse. Flow cytometric...
Source: Am J Physiol Renal P... - April 6, 2016 Category: Urology & Nephrology Authors: Weiss S, Rosendahl A, Czesla D, Meyer-Schwesinger C, Stahl RA, Ehmke H, Kurts C, Zipfel PF, Köhl J, Wenzel UO Tags: Am J Physiol Renal Physiol Source Type: research

Renal tubular epithelial cell prorenin receptor regulates blood pressure and sodium transport.
Abstract The physiological significance of the renal tubular prorenin receptor (PRR) has been difficult to elucidate due to developmental abnormalities associated with global or renal-specific PRR knockout (KO). We recently developed an inducible renal tubule-wide PRR KO using the Pax8/LC1 transgenes and demonstrated that disruption of renal tubular PRR at 1 month of age caused no renal histological abnormalities. Here, we examined the role of renal tubular PRR in blood pressure (BP) regulation and Na(+)excretion and investigated the signaling mechanisms by which PRR regulates Na(+)balance. No detectable differenc...
Source: Am J Physiol Renal P... - April 6, 2016 Category: Urology & Nephrology Authors: Ramkumar N, Stuart D, Mironova E, Bugay V, Wang S, Abraham N, Ichihara A, Stockand JD, Kohan DE Tags: Am J Physiol Renal Physiol Source Type: research

C-reactive protein exacerbates renal ischemia-reperfusion injury: are myeloid derived suppressor cells to blame?
Abstract Myeloid derived suppressor cells (MDSC) are a CD11b(+)Gr1(+)population in mice that can be separated into granulocytic (g-MDSC) and monocytic (m-MDSC) subtypes based on their expression of Ly6G and Ly6C. Both MDSC subtypes are potent suppressors of T cell immunity and their contribution has been investigated in a plethora of diseases including renal cancer, renal transplant, and chronic kidney disease. Whether MDSCs contribute to the pathogenesis of acute kidney injury (AKI) remains unknown. Herein, using human CRP transgenic (CRPtg) and CRP deficient mice (CRP(-/-)) subjected to bilateral renal ischemia-...
Source: Am J Physiol Renal P... - April 6, 2016 Category: Urology & Nephrology Authors: Pegues MA, McWilliams IL, Szalai AJ Tags: Am J Physiol Renal Physiol Source Type: research

Distribution of the organic anion transporters NaDC3 and OAT1-3 along the human nephron.
Abstract The initial step in renal secretion of organic anions (OA) is mediated by transporters in the basolateral membrane (BLM). Contributors to this process are the primary-active Na+/K+-ATPase (EC 3.6.3.9), the secondary-active sodium-dicarboxylate cotransporter 3 (NaDC3/SLC13A3), and the tertiary-active OA transporters OAT1/SLC22A6, OAT2/SLC22A7 and OAT3/SLC22A8. In human kidneys we analyzed the localization of these transporters by immunochemical methods in tissue cryosections and isolated membranes. The specificity of antibodies was validated with HEK293 cells stably transfected with functional OA transport...
Source: Am J Physiol Renal P... - April 6, 2016 Category: Urology & Nephrology Authors: Breljak D, Ljubojević M, Hagos Y, Micek V, Balen Eror D, Vrhovac Madunić I, Brzica H, Karaica D, Radovic N, Kraus O, Anzai N, Koepsell H, Burckhardt G, Burckhardt BC, Sabolić I Tags: Am J Physiol Renal Physiol Source Type: research

Therapeutic effects and mechanism of conditioned media from human mesenchymal stem cells on anti-GBM glomerulonephritis in WKY rats.
Abstract Recent studies have demonstrated that conditioned media derived from mesenchymal stem cells (MSCs-CM) have therapeutic effects in various experimental diseases. However, the therapeutic mechanism is not fully understood. Here we investigated the therapeutic effects and mechanism of MSCs-CM in experimental anti-glomerular basement membrane (GBM) glomerulonephritis (GN). We administered either MSCs-CM or vehicle from day 0 up to day 10 following induction of nephrotoxic serum nephritis in Wistar-Kyoto rats. In vitro, we analyzed the effects of MSCs-CM on TNF-α-mediated cytokine production in cultured ...
Source: Am J Physiol Renal P... - April 6, 2016 Category: Urology & Nephrology Authors: Iseri K, Iyoda M, Ohtaki H, Matsumoto K, Wada Y, Suzuki T, Yamamoto Y, Saito T, Hihara K, Tachibana S, Honda K, Shibata T Tags: Am J Physiol Renal Physiol Source Type: research

Differential effects of superoxide and hydrogen peroxide on myogenic signaling, membrane potential and contractions of mouse renal afferent arterioles.
Abstract Myogenic contraction is the principal component of renal autoregulation that protects the kidney from hypertensive barotrauma. Contractions are initiated by a rise in perfusion pressure that signals a reduction in membrane potential (Em) of vascular smooth muscle cells to activate voltage operated calcium channels (VOCCs). Since reactive oxygen species (ROS) have variable effects on myogenic tone, we investigated the hypothesis that superoxide (O2 (.-)) and hydrogen peroxide (H2O2) differentially impact myogenic contractions. The myogenic contractions of mouse isolated and perfused single afferent arterio...
Source: Am J Physiol Renal P... - April 6, 2016 Category: Urology & Nephrology Authors: Li L, Lai EY, Wellstein A, Welch WJ, Wilcox CS Tags: Am J Physiol Renal Physiol Source Type: research

Am J Physiol Renal Physiol; +17 new citations
17 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: Am J Physiol Renal Physiol These pubmed results were generated on 2016/04/01PubMed comprises more than 24 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites. (Source: Am J Physiol Renal P...)
Source: Am J Physiol Renal P... - April 1, 2016 Category: Urology & Nephrology Tags: Report Source Type: research

2016 Young Investigator Award of the American Physiological Society Renal Section.
PMID: 26984952 [PubMed - as supplied by publisher] (Source: Am J Physiol Renal P...)
Source: Am J Physiol Renal P... - March 16, 2016 Category: Urology & Nephrology Authors: Navar LG Tags: Am J Physiol Renal Physiol Source Type: research

Measuring the intra-renal distribution of glomerular volumes from histologic sections.
Abstract Glomerular volume is an important metric reflecting glomerular filtration surface area within the kidney. Glomerular hypertrophy, or increased glomerular volume, may be an important marker for renal stress. Current stereologic techniques report the average glomerular volume (AVglom) within the kidney. These techniques cannot assess the spatial or regional heterogeneity common in developing renal pathology. Here, we report a novel "Unfolding" technique to measure the actual distribution of individual glomerular volumes from the 2D glomerular profiles observed by optical microscopy. The Unfolding ...
Source: Am J Physiol Renal P... - March 16, 2016 Category: Urology & Nephrology Authors: Hann BD, Baldelomar EJ, Charlton JR, Bennett KM Tags: Am J Physiol Renal Physiol Source Type: research

The C-terminal tail of polycystin-1 regulates complement factor B expression by Signal Transducer and Activator of Transcription 1.
In conclusion, our study reveals possible mechanisms of CFB up-regulation in ADPKD and a novel role of PC1-CTT on ADPKD associated inflammation. Furthermore our study suggests that targeting STAT1 may be a new strategy to prevent inflammation in the kidney of patients with ADPKD. PMID: 26984954 [PubMed - as supplied by publisher] (Source: Am J Physiol Renal P...)
Source: Am J Physiol Renal P... - March 16, 2016 Category: Urology & Nephrology Authors: Wu M, Chen M, Jing Y, Gu J, Mei S, Yao Q, Zhou J, Yang M, Sun L, Wang W, Hu H, Wüthrich RP, Mei C Tags: Am J Physiol Renal Physiol Source Type: research

COX-2 gene dosage dependent defects in kidney development.
sing RM Abstract Deletion of cyclooxygenase-2 (COX-2) causes impairment of kidney development including hypothrophic glomeruli and cortical thinning. A critical role for COX-2 is seen 4 to 8 days postnatally. The present study was aimed at answering whether different COX-2 gene dosage and partial pharmacological COX-2 inhibition impairs kidney development. We studied kidney development in COX-2(+/+), COX-2(+/-), and COX-2(-/-) mice as well as in C57Bl6 mice treated postnatally with low (5 mg/kg/d) and high doses (10 mg/kg/d) of selective COX-2 inhibitor SC-236. COX-2(+/-) mice exhibit impaired kidney development l...
Source: Am J Physiol Renal P... - March 16, 2016 Category: Urology & Nephrology Authors: Slattery P, Frölich S, Schreiber Y, Nüsing RM Tags: Am J Physiol Renal Physiol Source Type: research

Effects of exercise training on urinary tract function after spinal cord injury.
Abstract Spinal cord injury (SCI) causes dramatic changes in quality of life including coping with bladder dysfunction which requires repeated daily and nightly catheterizations. Our lab has recently demonstrated in a rat SCI model that repetitive sensory information generated through task-specific stepping and/or loading can improve non-locomotor functions, including bladder function. To target potential underlying mechanisms, the current study included a forelimb-only exercise group to ascertain whether improvements may be attributed to general activity effects that impacts target organ-neural interactions or to...
Source: Am J Physiol Renal P... - March 16, 2016 Category: Urology & Nephrology Authors: Hubscher CH, Montgomery LR, Fell JD, Armstrong JE, Poudyal P, Herrity AN, Harkema SJ Tags: Am J Physiol Renal Physiol Source Type: research

Monomeric C-reactive protein inhibits renal cell-directed complement activation mediated by properdin.
ten C Abstract Earlier studies have shown that complement activation on renal tubular cells is involved in induction of interstitial fibrosis and cellular injury. Evidence suggests that the tubular cell damage is initiated by the alternative pathway (AP) of complement with properdin having an instrumental role. Properdin is a positive regulator of the AP, which can bind necrotic cells as well as viable proximal tubular epithelial cells (PTEC), inducing complement activation. Various studies have indicated that in circulation there is an unidentified inhibitor of properdin. We investigated the ability of CRP, both ...
Source: Am J Physiol Renal P... - March 16, 2016 Category: Urology & Nephrology Authors: O Flynn J, van der Pol P, Dixon KO, Prohászka Z, Daha MR, van Kooten C Tags: Am J Physiol Renal Physiol Source Type: research

Hyperaldosteronism following decreased renal K+ excretion in KCNMB2 knock-out mice.
Abstract The kidney is the primary organ ensuring K(+) homeostasis. K(+) is secreted into the urine in the distal tubule by two mechanisms; by the ROMK channel (Kir1.1) by the KCa1.1 channel. Here we report a novel knock-out mouse of the β2 subunit (KCNMB2) of the KCa1.1 channel, which displays hyperaldosteronism following decreased renal K(+) excretion. KCNMB2(-/-) mice displayed hyperaldosteronism, normal plasma [K(+)] and produced dilute urine with decreased [K(+)]. The normokalemia indicated that hyperaldosteronism did not result from primary aldosteronism. Activation of the RAAS was also ruled out as ren...
Source: Am J Physiol Renal P... - March 9, 2016 Category: Urology & Nephrology Authors: Larsen CK, Jensen IS, Sorensen MV, de Bruijn PI, Bleich M, Praetorius HA, Leipziger J Tags: Am J Physiol Renal Physiol Source Type: research

Metformin, an AMPK activator, stimulates the phosphorylation of Aquaporin 2 and Urea Transporter A1 in Inner Medullary Collecting Ducts.
Abstract Nephrogenic diabetes insipidus (NDI) is characterized by production of very large quantities of dilute urine due to an inability of the kidney to respond to vasopressin. Congenital NDI results from mutations in the type 2 vasopressin receptor (V2R) in approximately 90% of families. These patients do not have mutations in aquaporin-2 (AQP2) or urea transporter UT-A1 (UT-A1). We tested adenosine monophosphate kinase (AMPK) since it is known to phosphorylate another vasopressin-sensitive transporter, NKCC2 (Na-K-2Cl cotransporter). We found AMPK expressed in rat inner medulla (IM). AMPK directly phosphorylat...
Source: Am J Physiol Renal P... - March 9, 2016 Category: Urology & Nephrology Authors: Klein JD, Wang Y, Blount MA, Molina PA, LaRocque LM, Ruiz JA, Sands JM Tags: Am J Physiol Renal Physiol Source Type: research

Renal Blood Flow Autoregulation What are the contributions for nitric oxide and superoxide to modulate the myogenic response.
Abstract EF- F416-2015. PMID: 26962100 [PubMed - as supplied by publisher] (Source: Am J Physiol Renal P...)
Source: Am J Physiol Renal P... - March 9, 2016 Category: Urology & Nephrology Authors: Imig JD Tags: Am J Physiol Renal Physiol Source Type: research

Berliner Announcement.
PMID: 26962101 [PubMed - as supplied by publisher] (Source: Am J Physiol Renal P...)
Source: Am J Physiol Renal P... - March 9, 2016 Category: Urology & Nephrology Authors: Caplan MJ Tags: Am J Physiol Renal Physiol Source Type: research

EF- F-231-2015 ACTH action on podocytes: mystery solved?
Abstract Podocytes are the key target cell for injury in proteinuric kidney disorders such as focal segmental glomerulosclerosis (FSGS), minimal change disease and membranous nephropathy. Sadly, advances in elucidating the molecular architectural details of the podocyte actin cytoskeleton, cell body and intervening slit diaphragm have not yet translated into targeted therapeutic agents for clinical use. For over 60 years nephrologists have been treating glomerular diseases with repurposed, non-specific immunosuppressive drugs, such as steroids and alkylating agents. Clinical responses have been variable with wide ...
Source: Am J Physiol Renal P... - March 9, 2016 Category: Urology & Nephrology Authors: Cravedi P, Campbell K Tags: Am J Physiol Renal Physiol Source Type: research

RAS and sex differences in diabetic nephropathy.
Abstract The incidence and progression of kidney diseases are influenced by sex. The renin-angiotensin system (RAS) is an important regulator of cardiovascular and renal function. Sex differences in the renal response to RAS blockade have been demonstrated. Circulating and renal RAS has been shown to be altered in type 1 and type 2 diabetes; this enzymatic cascade plays a critical role in the development of diabetic nephropathy (DN). Angiotensin converting enzyme (ACE) and ACE2 are differentially regulated depending on its localization within the diabetic kidney. Furthermore, clinical and experimental studies have...
Source: Am J Physiol Renal P... - March 9, 2016 Category: Urology & Nephrology Authors: Clotet S, Riera M, Pascual J, Soler MJ Tags: Am J Physiol Renal Physiol Source Type: research

Renovascular remodeling and renal injury after extended angiotensin II infusion.
Abstract Chronic angiotensin II (Ang II) infusion for one or two weeks leads to progressive hypertension and induces inward hypertrophic remodeling in preglomerular vessels, which is associated with increased renal vascular resistance (RVR) and decreased glomerular perfusion. Considering the ability of preglomerular vessels to exhibit adaptive responses, the present study was performed to evaluate glomerular perfusion and renal function after six weeks of Ang II infusion. To address this study, male Wistar rats were submitted to fictitious surgery (control) or osmotic minipump insertion (Ang II 200 ng/kg/min, 42 d...
Source: Am J Physiol Renal P... - March 9, 2016 Category: Urology & Nephrology Authors: Casare FA, Thieme K, Costa-Pessoa JM, Rossoni LV, Couto GK, Fernandes FB, Casarini DE, Oliveira-Souza M Tags: Am J Physiol Renal Physiol Source Type: research

Mass spectrometric imaging of metabolites in kidney tissues from rats treated with furosemide.
Abstract In the kidney, metabolic processes are different among the cortex (COR), outer medulla (OM), and inner medulla (IM). Using matrix-assisted laser desorption/ionization (MALDI) and imaging mass spectrometry (IMS), we examined the change of metabolites in the COR, OM, and IM of the rat kidney after furosemide treatment, compared with vehicle-treated controls. Osmotic minipumps were implanted in male Sprague-Dawley rats to deliver 12 mg/d/rat of furosemide. Vehicle-treated- (n = 14) and furosemide-treated- (furosemide rats, n = 15) rats in metabolic cages received a fixed amount of rat chow (15 g/220 g bw/day...
Source: Am J Physiol Renal P... - March 9, 2016 Category: Urology & Nephrology Authors: Jung JW, Lee MS, Choi HJ, Jung S, Lee YJ, Hwang GS, Kwon TH Tags: Am J Physiol Renal Physiol Source Type: research

Tetrahydrobiopterin Ameliorates the Exaggerated Exercise Pressor Response in Patients with Chronic Kidney Disease: A Randomized Controlled Trial.
Abstract Chronic kidney disease (CKD) patients have an exaggerated increase in blood pressure (BP) during rhythmic (RHG 20%) and static (SHG 30%) handgrip exercise. Nitric Oxide (NO) levels increase during exercise and help prevent excessive hypertension by both increasing vasodilation and reducing sympathetic nerve activity (SNA). Therefore, we hypothesized that tetrahydrobiopterin (BH4), an essential cofactor for nitric oxide synthase (NOS), would ameliorate the exaggerated exercise pressor response in CKD patients. In a randomized, double-blinded, placebo-controlled trial, we tested the effects of 12 weeks of s...
Source: Am J Physiol Renal P... - March 9, 2016 Category: Urology & Nephrology Authors: Lin A, Liao P, Millson EC, Quyyumi AA, Park J Tags: Am J Physiol Renal Physiol Source Type: research

Bridging translation for acute kidney injury with better pre-clinical modeling of human disease.
Abstract The current lack of effective therapeutics for patients with acute kidney injury (AKI) represents an important and unmet medical need. Given the importance of the clinical problem it is time for us to take a few steps back and reexamine current practices. The focus of this review is to explore the extent to which failure of therapeutic translation from animal studies to human studies stems from deficiencies in the pre-clinical models of AKI. We will evaluate whether the pre-clinical models of AKI that are commonly used recapitulate the known pathophysiologies of AKI that are being modeled in humans, focus...
Source: Am J Physiol Renal P... - March 9, 2016 Category: Urology & Nephrology Authors: Skrypnyk NI, Siskind LJ, Faubel S, de Caestecker MP Tags: Am J Physiol Renal Physiol Source Type: research

The anti-inflammatory peptide Ac-SDKP is released from thymosin β4 by renal meprin α and prolyl oligopeptidase.
The anti-inflammatory peptide Ac-SDKP is released from thymosin β4 by renal meprin α and prolyl oligopeptidase. Am J Physiol Renal Physiol. 2016 Mar 9;:ajprenal.00562.2015 Authors: Kumar N, Nakagawa P, Janic B, Romero CA, Worou ME, Monu SR, Peterson EL, Shaw J, Valeriote F, Ongeri EM, Niyitegeka JV, Rhaleb NE, Carretero OA Abstract N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) is a natural tetra-peptide with anti-inflammatory and anti-fibrotic properties. We have previously shown that prolyl-oligopeptidase (POP) is involved in the Ac-SDKP release from thymosin β4 (Tβ4). However,...
Source: Am J Physiol Renal P... - March 9, 2016 Category: Urology & Nephrology Authors: Kumar N, Nakagawa P, Janic B, Romero CA, Worou ME, Monu SR, Peterson EL, Shaw J, Valeriote F, Ongeri EM, Niyitegeka JV, Rhaleb NE, Carretero OA Tags: Am J Physiol Renal Physiol Source Type: research

Delivery of interleukin-10 via injectable hydrogels improves renal outcomes and reduces systemic inflammation following ischemic acute kidney injury in mice.
Abstract Injectable hydrogels can be used to deliver drugs in situ over a sustained period of time. We hypothesized that sustained delivery of interleukin-10 (IL-10) following acute kidney injury (AKI) would mitigate the local and systemic pro-inflammatory cascade induced by AKI and reduce subsequent fibrosis. Wild-type C57BL/6 mice underwent ischemia-reperfusion AKI with avertin anesthesia. Three days later, mice were treated with either hyaluronic acid injectable hydrogel with or without IL-10, or IL-10 suspended in saline, injected under the capsule of the left kidney, or hydrogel with IL-10 injected subcutaneo...
Source: Am J Physiol Renal P... - March 9, 2016 Category: Urology & Nephrology Authors: Soranno DE, Rodell CB, Altmann C, Duplantis J, Andres-Hernando A, Burdick JA, Faubel S Tags: Am J Physiol Renal Physiol Source Type: research

Pronounced kidney hypoxia precedes albuminuria in type-1 diabetic mice.
In conclusion, intrarenal tissue hypoxia in diabetes precedes albuminuria thereby being a plausible cause for the onset and progression of diabetic nephropathy. PMID: 26936871 [PubMed - as supplied by publisher] (Source: Am J Physiol Renal P...)
Source: Am J Physiol Renal P... - March 2, 2016 Category: Urology & Nephrology Authors: Franzén S, Pihl L, Khan N, Gustafsson H, Palm F Tags: Am J Physiol Renal Physiol Source Type: research

The Rebirth of Interest in Renal Tubular Function.
Abstract The measurement of glomerular filtration rate by the clearance of inulin or creatinine has evolved over the past fifty years into an estimated value (eGFR) based solely on plasma creatinine concentration. We have examined some of the misconceptions and misunderstanding of the classification of renal disease and its course which have followed this evolution. Further, renal plasma flow and tubular function, which in the past were estimated by the clearance of the exogenous aryl amine, para amino hippurate, are no longer measured. Over the past decade, studies in experimental animals with reduced nephron mas...
Source: Am J Physiol Renal P... - March 2, 2016 Category: Urology & Nephrology Authors: Lowenstein J, Grantham JJ Tags: Am J Physiol Renal Physiol Source Type: research

Neuroanatomical and behavioral correlates of urinary dysfunction induced by vaginal distension in rats.
MS, Cruz Y Abstract The aim of the present study was to use a model of simulated human childbirth in rats to determine the damage to genitourinary structures and behavioral signs of urinary dysfunction induced by VD in female rats. In Experiment 1, the length of the genitourinary tract and the nerves associated with it were measured immediately after simulated human delivery induced by vaginal distension (VD) or sham (SH) procedure. Electroneurograms of the dorsal nerve of the clitoris (DNC) was also recorded. In Experiment 2, histological characteristics of the bladder and major pelvic ganglion (MPG) of VD and S...
Source: Am J Physiol Renal P... - March 2, 2016 Category: Urology & Nephrology Authors: Palacios JL, Juárez M, Morán C, Xelhuantzi N, Damaser MS, Cruz Y Tags: Am J Physiol Renal Physiol Source Type: research

Spontaneous One-Kidney Rats are More Susceptible to Develop Hypertension by DOCA-NaCl and Subsequent Kidney Injury Compared to Uninephrectomized Rats.
Abstract There is little clinical data of how hypertension may influence individuals with nephron deficiency in the context of being born with a single kidney. We recently developed a new rat model (the HSRA rat) that is born with a single kidney and exhibits progressive kidney injury and decline in kidney function with age. We hypothesized that deoxycorticosterone acetate (DOCA)-salt would induce a greater increase in blood pressure and therefore accelerate progression of kidney injury in rats born with a solitary kidney compared to rats that have undergone unilateral nephrectomy. Time course evaluation of blood ...
Source: Am J Physiol Renal P... - March 2, 2016 Category: Urology & Nephrology Authors: Wang X, Johnson AC, Sasser JM, Williams JM, Solberg Woods LC, Garrett MR Tags: Am J Physiol Renal Physiol Source Type: research

N-sulfation of heparan sulfate is critical for syndecan-4 mediated podocyte cell-matrix interactions.
Abstract Previous work showed that podocytes unable to assemble heparan sulfate on cell surface proteoglycan core proteins have compromised cell-matrix interactions. This present report further explores the role of N-sulfation of intact heparan chains in podocyte-matrix interactions. For the purposes of this study, a murine model in which the enzyme, N-deacetylase/N-sulfotransferase 1 (NDST1) was specifically deleted in podocytes and immortalized podocyte cell lines lacking NDST1 were developed and used to explore the effects of such a mutation on podocyte behavior in vitro. NDST1 is a bifunctional enzyme, ultimat...
Source: Am J Physiol Renal P... - March 2, 2016 Category: Urology & Nephrology Authors: Sugar T, Wassenhove-McCarthy DJ, Orr AW, Green J, van Kuppevelt TH, McCarthy KJ Tags: Am J Physiol Renal Physiol Source Type: research

Melanocortin 1 Receptor Agonist Protects Podocytes Through Catalase and RhoA Activation.
aldsson B Abstract Drugs containing adrenocorticotropic hormone (ACTH) have been used as therapy for patients with nephrotic syndrome. We have previously shown that ACTH and a selective agonist for the melanocortin 1 receptor (MC1R) exert beneficial actions in experimental membranous nephropathy with reduced proteinuria, reduced oxidative stress, improved glomerular morphology and function. Our hypothesis is that MC1R activation in podocytes elicits beneficial effects by promoting stress fibers and maintaining podocyte viability. To test the hypothesis, we cultured podocytes and used highly specific agonists for t...
Source: Am J Physiol Renal P... - February 17, 2016 Category: Urology & Nephrology Authors: Elvin J, Buvall L, Lindskog Jonsson A, Granqvist A, Lassén E, Bergwall L, Nyström J, Haraldsson B Tags: Am J Physiol Renal Physiol Source Type: research

Loss of diacylglycerol kinase epsilon in mice causes endothelial distress and impairs glomerular Cox-2 and PGE2 production.
Abstract Thrombotic microangiopathy (TMA) is a disorder characterized by microvascular occlusion that can lead to thrombocytopenia, hemolytic anemia and glomerular damage. Complement activation is the central event in most cases of TMA. Primary forms of TMA are caused by mutations in genes encoding components of the complement or regulators of the complement cascade. Recently, we and others have described a genetic form of TMA caused by mutations in the gene diacylglycerol kinase epsilon (DGKE) that encodes the lipid kinase DGKε. DGKε is unrelated to the complement pathway, which suggests that unid...
Source: Am J Physiol Renal P... - February 17, 2016 Category: Urology & Nephrology Authors: Zhu J, Chaki M, Lu D, Ren C, Wang SS, Rauhauser AA, Li B, Zimmerman S, Jun B, Du Y, Vadnagara K, Wang H, Elhadi S, Quigg RJ, Topham MK, Mohan C, Ozaltin F, Zhou XJ, Marciano DK, Bazan NG, Attanasio M Tags: Am J Physiol Renal Physiol Source Type: research

Angiotensin II-mediated hypertension impairs nitric oxide-induced NKCC2 inhibition in thick ascending limbs.
Abstract In thick ascending limbs (THALs) NO decreases NaCl reabsorption via cGMP-mediated inhibition of Na/K/2Cl cotransporter (NKCC2). In angiotensin (Ang II)-induced hypertension, endothelin-1 (ET-1)-induced NO production by THALs is impaired. However, whether this alters NO's natriuretic effects and the mechanisms involved are unknown. In other cell types, Ang II augments phosphodiesterase 5 (PDE5)-mediated cGMP degradation. We hypothesized that NO-mediated inhibition of NKCC2 activity and stimulation of cGMP synthesis are blunted via PDE5 in Ang II-induced hypertension. Sprague Dawley rats were infused with v...
Source: Am J Physiol Renal P... - February 17, 2016 Category: Urology & Nephrology Authors: Ramseyer VD, Ortiz PA, Carretero OA, Garvin JL Tags: Am J Physiol Renal Physiol Source Type: research

NLRP3 Deletion Protects against Renal Fibrosis and Attenuates Mitochondrial Abnormality in Mouse with 5/6 Nephrectomy.
Abstract Progressive fibrosis in chronic kidney disease (CKD) is the well-recognized cause leading to the progressive loss of renal function. Emerging evidence indicated a pathogenic role of NLRP3 inflammasome in mediating kidney injury. However, the role of NLRP3 in remnant kidney disease model is still undefined. The present study is undertaken to evaluate the function of NLRP3 in modulating renal fibrosis in a CKD model of 5/6 nephrectomy (5/6 Nx) and the potential involvement of mitochondrial dysfunction in the pathogenesis. Employing NLRP3+/+ and NLRP3-/- mice with or without 5/6 Nx, we examined renal fibroti...
Source: Am J Physiol Renal P... - February 17, 2016 Category: Urology & Nephrology Authors: Gong W, Mao S, Yu J, Song J, Jia Z, Huang S, Zhang A Tags: Am J Physiol Renal Physiol Source Type: research

The disruption of KCNJ10 (Kir4.1) stimulates the expression of ENaC in the collecting duct.
Abstract Kcnj10 encodes the inwardly rectifying K(+) channel 4.1 (Kir4.1) and is expressed in the basolateral membrane of late TAL, DCT, CNT and CCD. In the present study, we perform experiments in p9 WT and Kcnj10(-/-) mice to examine the role of Kir.4.1 in contributing to the basolateral K(+) conductance in the CNT and CCD, and to investigate whether disruption of Kir4.1 up-regulates ENaC expression. Immunostaining shows that Kir4.1 and Kir5.1 are expressed in the basolateral membrane of CNT and CCD. The patch-clamp studies detect three types of K(+) channels (23 pS, 40 pS and 60 pS) in the basolateral membrane ...
Source: Am J Physiol Renal P... - February 17, 2016 Category: Urology & Nephrology Authors: Su XT, Zhang C, Wang L, Gu R, Lin DH, Wang WH Tags: Am J Physiol Renal Physiol Source Type: research

Mechanism of increased clearance of glycated albumin by Proximal tubule cells.
Abstract Serum albumin is the most abundant plasma protein and has a long half-life due to neonatal Fc receptor (FcRn) mediated transcytosis by many cell types including proximal tubule cells of the kidney. Albumin also interacts with, and is modified by, many small and large molecules. Therefore, the focus of this study was to address the impact of specific known biologic albumin modifications on albumin-FcRn binding and cellular handling. Binding at pH 6.0 and 7.4 was performed since FcRn binds albumin strongly at acidic pH and releases it following transcytosis at physiological pH. Equilibrium dissociation cons...
Source: Am J Physiol Renal P... - February 17, 2016 Category: Urology & Nephrology Authors: Wagner MC, Myslinski J, Pratap S, Flores B, Rhodes GJ, Sandoval R, Kumar S, Patel M, Ashish A, Molitoris BA Tags: Am J Physiol Renal Physiol Source Type: research

TGF-β, Notch, and HGF weave a tangled web of kidney repair.
TGF-β, Notch, and HGF weave a tangled web of kidney repair. Am J Physiol Renal Physiol. 2016 Feb 10;:ajprenal.00050.2016 Authors: Sussman CR PMID: 26864936 [PubMed - as supplied by publisher] (Source: Am J Physiol Renal P...)
Source: Am J Physiol Renal P... - February 10, 2016 Category: Urology & Nephrology Authors: Sussman CR Tags: Am J Physiol Renal Physiol Source Type: research

Augmentation of angiotensinogen expression in the proximal tubule by intracellular angiotensin II via AT1a/MAPK/NF-кB signaling pathways.
Abstract Long-term angiotensin II (ANG II) infusion significantly increases ANG II levels in the kidney through two major mechanisms; AT1 receptor-mediated augmentation of angiotensinogen (AGT) expression and uptake of circulating ANG II by the proximal tubules. However, it is not known whether intracellular ANG II stimulates AGT expression in the proximal tubule. In the present study, we overexpressed an intracellular cyan fluorescent ANG II fusion protein (Ad-sglt2-ECFP/ANG II) selectively in the proximal tubule of rats and mice using the sodium and glucose co-transporter 2 (sglt2) promoter. AGT mRNA and protein...
Source: Am J Physiol Renal P... - February 10, 2016 Category: Urology & Nephrology Authors: Zhuo JL, Kobori H, Li XC, Sato R, Katsurada A, Navar LG Tags: Am J Physiol Renal Physiol Source Type: research

FGF23 from Bench to Bedside.
Abstract There is a strong association between elevated circulating Fibroblast Growth Factor-23 (FGF23) levels and adverse outcomes in patients with chronic kidney disease (CKD) of all stages. Initially discovered as a regulator of phosphate and vitamin D homeostasis, FGF23 has now been implicated in several pathophysiological mechanisms that may negatively impact the cardiovascular and renal systems. FGF23 is purported to have direct (off-target) effects in the myocardium, as well as canonical effects on FGF receptor/ -klotho receptor complexes in the kidney to activate the renin-angiotensin-aldosterone system, m...
Source: Am J Physiol Renal P... - February 10, 2016 Category: Urology & Nephrology Authors: Kovesdy CP, Quarles LD Tags: Am J Physiol Renal Physiol Source Type: research