Renal phenotype in Bardet-Biedl Syndrome: a combined defect of urinary concentration and dilution is associated with defective urinary AQP2 and UMOD excretion.
Abstract The renal phenotype in Bardet-Biedl syndrome (BBS) is highly variable. The present study describes renal findings in 41 BBS patients and analyzes the pathogenesis of hyposthenuria, the most common renal dysfunction. 5/41 patients (12%) showed an estimated glomerular filtration rate
Source: Am J Physiol Renal P... - August 3, 2016 Category: Urology & Nephrology Authors: Zacchia M, Zacchia E, Zona E, Capolongo G, Raiola I, Rinaldi L, Trepiccione F, Ingrosso D, Perna A, Di Iorio V, Simonelli F, Moe OW, Capasso G Tags: Am J Physiol Renal Physiol Source Type: research

Bench to Bedside: The next steps for biomarkers in acute kidney injury.
Abstract No new biomarker of Acute Kidney Injury (AKI) has entered routine clinical practice after a decade of promise, although L-FABP, NGAL, and the combination of TIMP2 and IGFBY-7 are approved for use in some jurisdictions. Acceptance of creatinine as a surrogate of not just GFR but also renal injury, changes in nephrologist work loads, failure to establish the added value of each biomarker to current clinical variables across multiple clinical settings, the lack of treatment options, and simply an insufficient passage of time, have all contributed to the lack of progress. Future studies should establish refer...
Source: Am J Physiol Renal P... - July 27, 2016 Category: Urology & Nephrology Authors: Pickering JW, Endre ZH Tags: Am J Physiol Renal Physiol Source Type: research

Aging-associated Renal Disease in Mice is Fructokinase Dependent.
Abstract Aging-associated kidney disease is usually considered a degenerative process associated with aging. Recently, it has been shown that animals can produce fructose endogenously, and that this can be a mechanism for causing kidney damage in diabetic nephropathy and in association with recurrent dehydration. We therefore hypothesized that low level metabolism of endogenous fructose might play a role in aging-associated kidney disease. Wild-type and fructokinase knockout mice were fed a normal diet for 2 years that had minimal (
Source: Am J Physiol Renal P... - July 27, 2016 Category: Urology & Nephrology Authors: Roncal-Jimenez CA, Ishimoto T, Lanaspa MA, Milagres T, Andres-Hernando A, Jensen T, Miyazaki M, Doke T, Hayasaki T, Nakagawa T, Maruyama S, Long DA, Kuwabara M, Sanchez-Lozada LG, Kang DH, Johnson RJ Tags: Am J Physiol Renal Physiol Source Type: research

Urothelial purine release during filling of murine and primate bladders.
Abstract During urinary bladder filling the bladder urothelium releases chemical mediators which in turn transmit information to the nervous and muscular systems to regulate sensory sensation and detrusor muscle activity. Defects in release of urothelial mediators may cause bladder dysfunctions that are characterized with aberrant bladder sensation during bladder filling. Previous studies have demonstrated release of adenosine 5'-triphosphate (ATP) from the bladder urothelium during bladder filling and ATP remains the most studied purine mediator that is released from the urothelium. However, the micturition cycle...
Source: Am J Physiol Renal P... - July 27, 2016 Category: Urology & Nephrology Authors: Durnin L, Hayoz S, Corrigan R, Yanez A, Koh SD, Mutafova-Yambolieva VN Tags: Am J Physiol Renal Physiol Source Type: research

EP3 receptor regulates water excretion in response to high salt intake.
Abstract The mechanisms by which prostanoids contribute to the maintenance of whole body water homeostasis are complex and not fully understood. The present study demonstrates that an EP3-dependent feedback mechanism contributes to the regulation of water homeostasis under high salt conditions. Rats on a normal diet and tap water were placed in metabolic cages and given either sulprostone (20 µg/kg/day) or vehicle for 3 days to activate EP3 receptors in thick ascending limb (TAL). Treatment was continued for another 3 days in rats given either 1% NaCl in the drinking water or tap water. Sulprostone decreased...
Source: Am J Physiol Renal P... - July 27, 2016 Category: Urology & Nephrology Authors: Hao S, DelliPizzi A, Quiroz-Munoz M, Jiang H, Ferreri NR Tags: Am J Physiol Renal Physiol Source Type: research

Early development of podocyte injury independent of hyperglycemia and elevations in arterial pressure in non-diabetic obese Dahl SS leptin receptor mutant rats.
Abstract The current study examined the effect of obesity on the development of renal injury within the genetic background of the Dahl salt-sensitive rat with a dysfunctional leptin receptor derived from Zinc-finger nucleases (SSLepRmutant strain). At 6 weeks of age, body weight was 35% higher in the SSLepRmutant strain compared to SSWT rats and remained elevated throughout the entire study. The SSLepRmutant strain exhibited impaired glucose tolerance and increased plasma insulin levels at 6 weeks of age suggesting insulin resistance while SSWT rats did not. However, blood glucose levels were normal throughout the...
Source: Am J Physiol Renal P... - July 27, 2016 Category: Urology & Nephrology Authors: McPherson KC, Taylor L, Johnson AC, Didion SP, Geurts AM, Garrett MR, Williams JM Tags: Am J Physiol Renal Physiol Source Type: research

Delayed treatment with fenofibrate protects against high-fat diet-induced kidney injury in mice: the possible role of AMPK-autophagy.
Abstract Fenofibrate activates not only peroxisome proliferator-activated receptor α (PPARα) but also adenosine monophosphate-activated protein kinase (AMPK). AMPK-mediated cellular responses protect kidney from high-fat diet (HFD)-induced injury, and autophagy resulting from AMPK activation has been regarded as a stress-response mechanism. Thus, the present study examined the role of AMPK and autophagy in the renotherapeutic effects of fenofibrate. C57BL/6J mice were divided into 3 groups: normal diet (ND), HFD, and HFD+fenofibrate (HFD+FF). Fenofibrate was administered 4 weeks after the initiation of...
Source: Am J Physiol Renal P... - July 27, 2016 Category: Urology & Nephrology Authors: Sohn M, Kim K, Uddin MJ, Lee G, Hwang I, Kang H, Kim H, Lee JH, Ha H Tags: Am J Physiol Renal Physiol Source Type: research

Polyuria-associated hydronephrosis induced by xenobiotic chemical exposure in mice.
Abstract Hydronephrosis is a commonly found disease state characterized by the dilation of renal calices and pelvis, resulting in the loss of kidney function in the severest cases. A generally accepted etiology of hydronephrosis involves the obstruction of urine flow along the urinary tract. In the recent years, we have developed a mouse model of hydronephrosis induced by lactational exposure to dioxin and demonstrated a lack of anatomical obstruction in this model. We also showed that prostaglandin E2 synthesis system plays a critical role in the onset of hydronephrosis. In the present study, we found that neonat...
Source: Am J Physiol Renal P... - July 20, 2016 Category: Urology & Nephrology Authors: Yoshioka W, Kawaguchi T, Nishimura N, Akagi T, Fujisawa N, Yanagisawa H, Matsumura F, Tohyama C Tags: Am J Physiol Renal Physiol Source Type: research

(Pro)Renin Receptor Regulates Potassium Homeostasis through a Local Mechanism.
Abstract (Pro)renin receptor (PRR) is highly expressed in the distal nephron with unclear functional implication. The present study was conducted to explore a potential role of renal PRR during high K+ (HK) loading. In normal Sprague-Dawley rats, a 1-week HK intake increased renal expression of full-length PRR and urinary excretion of soluble PRR (sPRR). Administration of PRO20, a decoy peptide antagonist of PRR, to K+-loaded animals elevated plasma K+ level and decreased urinary K+ excretion, accompanied with suppressed aldosterone excretion. HK downregulated Na+-Cl- cotransporter (NCC) expression but upregulated...
Source: Am J Physiol Renal P... - July 20, 2016 Category: Urology & Nephrology Authors: Xu C, Lu A, Wang H, Fang H, Zhou L, Sun P, Yang T Tags: Am J Physiol Renal Physiol Source Type: research

Lack of Hepcidin Ameliorates Anemia and Improves Growth in an Adenine-induced Mouse Model of Chronic Kidney Disease.
Abstract Growth delay is common in children with chronic kidney disease (CKD), often associated with poor quality of life. The role of anemia in uremic growth delay is poorly understood. Here we describe an induction of uremic growth retardation by 0.2% adenine diet in wild type (WT) and hepcidin gene (Hamp) knock-out (KO) mice, compared with their respective littermates fed a regular diet. Experiments were started at weaning (3 weeks). After 8 weeks, blood was collected and mice were euthanized. Adenine-fed WT mice developed CKD (BUN 82.8±11.6 mg/dL, creatinine 0.57±0.07 mg/dL) and were 2.1 cm short...
Source: Am J Physiol Renal P... - July 20, 2016 Category: Urology & Nephrology Authors: Akchurin O, Sureshbabu A, Doty SB, Zhu YS, Patino E, Cunningham-Rundles S, Choi ME, Boskey AL, Rivella S Tags: Am J Physiol Renal Physiol Source Type: research

Inhibition of T-cell activation by CTLA4-Fc is sufficient to ameliorate proteinuric kidney disease.
In this study we used the soluble CTLA4-Fc fusion protein Abatacept to block cell surface B7-1, preventing the cellular interaction and inhibiting T-cell activation. When Abatacept was dosed in an animal model of diabetes-induced albuminuria, it reduced albuminuria in both prevention and intervention modes. The number of T-cells infiltrating the kidneys of DN animals correlated with the degree of albuminuria and treatment with Abatacept reduced the number of renal T-cells. As B7-1 induction has been recently proposed to underlie podocyte damage in DN, Abatacept could be efficacious in DN by protecting podocytes. However, t...
Source: Am J Physiol Renal P... - July 20, 2016 Category: Urology & Nephrology Authors: Herrera M, Söderberg M, Sabirsh A, Valastro B, Molne J, Santamaría B, Valverde AM, Guionaud S, Heasman S, Bigley A, Jermutus L, Rondinone C, Coghlan M, Baker D, Moreno Quinn C Tags: Am J Physiol Renal Physiol Source Type: research

Reducing mTOR Augments Parietal Epithelial Cell Density in a Model of Acute Podocyte Depletion and in Aged Kidneys.
Abstract Parietal epithelial cells (PEC) response to glomerular injury may underlie a common pathway driving fibrogenesis following podocyte loss that typifies several glomerular disorders. Although the mammalian target of rapamycin (mTOR) pathway is important in cell homeostasis, little is known of the biological role or impact of reducing mTOR activity on PECs response following podocyte depletion, nor in the aging kidney. The purpose of these studies was to determine the impact on PECs of reducing mTOR activity following abrupt experimental depletion in podocyte number, as well as in a model of chronic podocyte...
Source: Am J Physiol Renal P... - July 20, 2016 Category: Urology & Nephrology Authors: McNicholas BA, Eng DG, Lichtnekert J, Rabinovitch PS, Pippin JW, Shankland SJ Tags: Am J Physiol Renal Physiol Source Type: research

The function of SH2B3 (LNK) in the kidney.
Abstract Recent evidence indicates the adapter protein SH2B3 has a major role in the progression of renal diseases. SH2B3 is highly expressed by hematopoietic cells and regulates cytokine signaling, inducing cell specific effects. Additionally, its expression in other cell types suggests that SH2B3 may have a more extensive role within the kidney. Ex vivo studies have determined targets of SH2B3 cell-specific signaling while in vivo studies have observed the SH2B3 overall affects in the progression of renal diseases. This mini-review covers the function of SH2B3-expressing cell types that contribute to renal patho...
Source: Am J Physiol Renal P... - July 20, 2016 Category: Urology & Nephrology Authors: Blass G, Mattson DL, Staruschenko A Tags: Am J Physiol Renal Physiol Source Type: research

Role of Prostate Inflammation and Fibrosis in Benign Prostate Hyperplasia and Lower Urinary Tract Symptoms.
Abstract Lower urinary tract symptoms (LUTS) in aging men are extremely common. They have historically been attributed to benign prostatic hyperplasia (BPH), enlargement of the prostate and bladder outlet obstruction. However, recent studies have revealed acute and chronic inflammation to by highly associated with LUTS, correlated with prostatic enlargement and implicated prostate fibrosis as a contributing cause of bladder outlet obstruction. This review examines the evidence implicating inflammation and fibrosis in BPH/LUTS. It identifies potential mechanisms by which inflammation may drive nociceptive signaling...
Source: Am J Physiol Renal P... - July 20, 2016 Category: Urology & Nephrology Authors: Bushman WA, Jerde TJ Tags: Am J Physiol Renal Physiol Source Type: research

SREBP Inhibition Ameliorates Renal Injury after Unilateral Ureteral Obstruction.
Abstract Tubulointerstitial fibrosis is a major feature associated with declining kidney function in chronic kidney disease of diverse etiology. No effective means as yet exists to prevent the progression of fibrosis. We have shown that the transcription factor SREBP-1 is an important mediator of the profibrotic response to TGFβ and Angiotensin II, both key cytokines in the fibrotic process. Here we examined the role of SREBP in renal interstitial fibrosis in the unilateral ureteral obstruction (UUO) model. The two isoforms of SREBP (-1 and -2) were activated by 3 days after UUO, with SREBP-1 showing a more s...
Source: Am J Physiol Renal P... - July 6, 2016 Category: Urology & Nephrology Authors: Mustafa M, Wang TN, Chen X, Gao B, Krepinsky JC Tags: Am J Physiol Renal Physiol Source Type: research

4-PBA Improves Lithium-induced Nephrogenic Diabetes Insipidus by Attenuating ER Stress.
In conclusion, in experimental lithium-induced NDI, 4-PBA improved urinary concentrating defect and increased AQP2 expression, likely via attenuating ER stress in inner medullary collecting duct principal cells. PMID: 27385737 [PubMed - as supplied by publisher] (Source: Am J Physiol Renal P...)
Source: Am J Physiol Renal P... - July 6, 2016 Category: Urology & Nephrology Authors: Zheng P, Lin Y, Wang F, Luo R, Zhang T, Hu S, Feng P, Liang X, Li C, Wang W Tags: Am J Physiol Renal Physiol Source Type: research

High mobility group box 1 inhibits HCO3- absorption in medullary thick ascending limb through RAGE-Rho-ROCK-mediated inhibition of basolateral Na+/H+ exchange.
Abstract High mobility group box 1 (HMGB1) is a nuclear protein released extracellularly in response to infection or injury, where it activates immune responses and contributes to the pathogenesis of kidney dysfunction in sepsis and sterile inflammatory disorders. Recently we demonstrated that HMGB1 inhibits HCO3 (-) absorption in perfused rat medullary thick ascending limbs (MTAL) through a basolateral RAGE-dependent pathway that is additive to TLR4-ERK-mediated inhibition by LPS. Here, we examined signaling and transport mechanisms that mediate inhibition by HMGB1. Inhibition of HCO3 (-) absorption by HMGB1 was ...
Source: Am J Physiol Renal P... - June 29, 2016 Category: Urology & Nephrology Authors: Watts BA, George T, Badalamenti A, Good DW Tags: Am J Physiol Renal Physiol Source Type: research

A Model of Calcium Homeostasis in the Rat.
Abstract We developed a model of calcium homeostasis in the rat in order to better understand the impact of dysfunctions such as primary hyperparathyroidism and vitamin D deficiency on calcium balance. The model accounts for the regulation of calcium intestinal uptake, bone resorption, and renal reabsorption by parathyroid hormone (PTH), vitamin D3, and Ca2+ itself. It is the first such model to incorporate recent findings regarding the role of the calcium sensing receptor (CaSR) in the kidney, the presence of a rapidly exchangeable pool in bone, and the delayed response of vitamin D3 synthesis. Accounting for two...
Source: Am J Physiol Renal P... - June 29, 2016 Category: Urology & Nephrology Authors: Granjon D, Bonny O, Edwards A Tags: Am J Physiol Renal Physiol Source Type: research

The influence of altitude hypoxia on uroflowmetry parameters in women.
Abstract There is scientific evidence to suggest a correlation between hypoxia and physiology of micturition. During a Himalayan Scientific and Mountaineering Expedition, we performed tests to investigate the functional interactions between altitude hypoxia and uroflowmetry parameters in women. The tests were carried out in seven women (36.3±7.1 years) from normoxic (1340 m a.s.l.) to hypoxic conditions (up to 5050 m a.s.l.) and during the return descent. The following measures were determined: uroflowmetry parameters and saturation of peripheral oxygen (SpO2). As expected, SpO2 decreased from 97.7% to 77.8...
Source: Am J Physiol Renal P... - June 29, 2016 Category: Urology & Nephrology Authors: Verratti V, Paulesu L, Pietrangelo T, Doria C, Di Giulio C, Aloisi AM Tags: Am J Physiol Renal Physiol Source Type: research

The Epoxyeicosatrienoic Acid Analog, PVPA, Ameliorates Cyclosporine-Induced Hypertension and Renal Injury in Rats.
Abstract The introduction of calcineurin inhibitors (CNI) into clinical practice in the late 1970s transformed organ transplantation and led to significant improvement in acute rejection episodes. However, despite their significant clinical utility, the use of these agents is hampered by the development of hypertension and nephrotoxicity, which ultimately lead to end-stage kidney disease and overt cardiovascular outcomes. There are currently no effective agents to treat or prevent these complications. Importantly, CNI-free immunosuppressive regimens lack the overall efficacy of CNI-based treatments and put patient...
Source: Am J Physiol Renal P... - June 29, 2016 Category: Urology & Nephrology Authors: Yeboah MM, Khan MA, Chesnik MA, Sharma A, Paudyal MP, Falck JR, Imig JD Tags: Am J Physiol Renal Physiol Source Type: research

Altered urothelial ATP signalling in major subset of human overactive bladder patients with pyuria.
Abstract RATIONALE: Overactive Bladder (OAB) is an idiopathic condition, characterized by urgency, urinary frequency and urgency incontinence, in the absence of routinely traceable urinary infection. We have described microscopic pyuria (≥10 wbc μl-1) in patients suffering from the worst symptoms. It is established that inflammation is associated with increased ATP release from epithelial cells, and extracellular ATP originating from the urothelium following increased hydrostatic pressure, is a mediator of bladder sensation. OBJECTIVES: Here, using bladder-biopsy samples, we have investigated urothelial...
Source: Am J Physiol Renal P... - June 29, 2016 Category: Urology & Nephrology Authors: Contreras-Sanz A, Krska L, Balachandran AA, Curtiss NL, Khasriya R, Kelley S, Strutt M, Gill HS, Taylor KM, Mansfield KJ, Wu C, Peppiatt-Wildman CM, Malone-Lee J, Duckett J, Wildman SS Tags: Am J Physiol Renal Physiol Source Type: research

HMGB1/TLR4 signaling induces an inflammatory response following high-pressure renal pelvic perfusion in a porcine model.
In conclusion, this study has demonstrated that HMGB1/TLR4 signaling contributes to the inflammatory response following high-pressure renal pelvic perfusion in a porcine model and has implications for the management of inflammation after PCNL. PMID: 27358057 [PubMed - as supplied by publisher] (Source: Am J Physiol Renal P...)
Source: Am J Physiol Renal P... - June 29, 2016 Category: Urology & Nephrology Authors: Shao Y, Sha M, Chen L, Li D, Lu J, Xia S Tags: Am J Physiol Renal Physiol Source Type: research

Demonstration of the functional impact of vasopressin signalling in thick ascending limb by a targeted transgenic rat approach.
Abstract The antidiuretic hormone vasopressin (AVP) regulates renal salt and water reabsorption along the distal nephron and collecting duct system. These effects are mediated by V2 receptors (V2R) and release of intracellular Gs-mediated cAMP to activate epithelial transport proteins. Inactivating mutations in the V2R gene lead to the X-linked form of nephrogenic diabetes insipidus (NDI) which has chiefly been related with impaired aquaporin 2-mediated water reabsorption in the collecting ducts. Previous work also suggested the AVP-V2R-mediated activation of Na+-K+-2Cl--cotransporters (NKCC2) along the thick asce...
Source: Am J Physiol Renal P... - June 15, 2016 Category: Urology & Nephrology Authors: Mutig K, Borowski T, Boldt C, Borschewski A, Paliege A, Popova E, Bader M, Bachmann S Tags: Am J Physiol Renal Physiol Source Type: research

Senescence in chronic allograft nephropathy.
ez JA Abstract Despite increasing numbers of patients on dialysis, the numbers of renal transplants performed yearly have remained relatively static. During the last 50 years, there have been many advances in the pharmacology of prevention of organ rejection. However, most patients will suffer from a slow but steady decline in renal function leading to graft loss. The most common cause of long-term graft loss is chronic allograft nephropathy (CAN). Therefore, elucidating and understanding the mechanisms involved in CAN is crucial for achieving better post-transplant outcomes. It is thought that the development of ...
Source: Am J Physiol Renal P... - June 15, 2016 Category: Urology & Nephrology Authors: Sosa Peña MD, Lopez-Soler R, Melendez JA Tags: Am J Physiol Renal Physiol Source Type: research

Albumin: innocent bystander or culprit?
Abstract EF -F456-2015. PMID: 27306981 [PubMed - as supplied by publisher] (Source: Am J Physiol Renal P...)
Source: Am J Physiol Renal P... - June 15, 2016 Category: Urology & Nephrology Authors: Peired AJ, Bitzer M Tags: Am J Physiol Renal Physiol Source Type: research

Cln three-requiring 9 is a negative regulator of Th17 pathway-driven inflammation in anti-glomerular basement membrane glomerulonephritis.
Abstract T helper 17 (Th17) lymphocytes promote renal inflammation in anti-glomerular basement membrane glomerulonephritis (anti-GBM GN), and signal transducer and activator of transcription 3 (STAT3) mediates activation of Th17 lymphocytes by interleukin 6 (IL-6) and transforming growth factor beta (TGFβ). Cln three requiring 9 (Ctr9), a subunit of RNA polymerase-associated factor complex (PAFc), regulates the transcription of IL-6/STAT3-dependent genes. Here, we investigated the role of Ctr9 in regulating Th17-driven inflammation in anti-GBM GN. In mice, STAT3β or IL-17 knockout ameliorated anti-GBM au...
Source: Am J Physiol Renal P... - June 15, 2016 Category: Urology & Nephrology Authors: Lee H, Lee JW, Yoo KD, Yoo JY, Lee JP, Kim DK, Chin HJ, Kim YS, Yang SH Tags: Am J Physiol Renal Physiol Source Type: research

Am J Physiol Renal Physiol; +18 new citations
18 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 2016/06/10PubMed 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... - June 10, 2016 Category: Urology & Nephrology Tags: Report Source Type: research

Activation of purinergic receptors (P2) in the renal medulla promotes endothelin-dependent natriuresis in male rats.
Abstract Renal endothelin-1 (ET-1) and purinergic signaling systems regulate Na+ reabsorption in the renal medulla. A link between the renal (ET-1) and purinergic systems was demonstrated in-vitro, however, the in-vivo interaction between these systems has not been defined. To test whether renal medullary activation of purinergic (P2) receptors promotes ET-dependent natriuresis, we determined the effect of increased medullary NaCl loading on Na+ excretion and inner medullary ET-1 mRNA expression in anesthetized adult male Sprague Dawley rats in the presence and absence of purinergic receptor antagonism. Isosmotic ...
Source: Am J Physiol Renal P... - May 25, 2016 Category: Urology & Nephrology Authors: Gohar EY, Speed JS, Kasztan M, Jin C, Pollock DM Tags: Am J Physiol Renal Physiol Source Type: research

The Role of Nedd4-1 WW Domains in Binding and Regulating Human Organic anion Transporter 1.
In conclusion, this is the first demonstration that Nedd4-1 regulates hOAT1 ubiquitination, expression, and transport activity through its WW2 and WW3 domains. PMID: 27226107 [PubMed - as supplied by publisher] (Source: Am J Physiol Renal P...)
Source: Am J Physiol Renal P... - May 25, 2016 Category: Urology & Nephrology Authors: Xu D, Wang H, Gardner CR, Pan Z, Zhang PL, Zhang J, You G Tags: Am J Physiol Renal Physiol Source Type: research

ASK1: a new therapeutic target for kidney disease.
Abstract Stress-induced activation of p38 MAPK and JNK signaling is a feature of both acute and chronic kidney disease and is associated with disease progression. Inhibitors of p38 MAPK or JNK activation provide protection against inflammation and fibrosis in animal models of kidney disease; however, clinical trials of p38 MAPK and JNK inhibitors in other diseases (rheumatoid arthritis and pulmonary fibrosis) have been disappointing. Apoptosis signal-regulating kinase 1 (ASK1) acts as an upstream regulator for the activation of p38 MAPK and JNK in kidney disease. Mice lacking the Ask1 gene are healthy with normal ...
Source: Am J Physiol Renal P... - May 25, 2016 Category: Urology & Nephrology Authors: Tesch G, Ma FY, Nikolic-Paterson DJ Tags: Am J Physiol Renal Physiol Source Type: research

The Podocyte and the Proteoglycan.
Abstract EF- F-603-2015. PMID: 27226109 [PubMed - as supplied by publisher] (Source: Am J Physiol Renal P...)
Source: Am J Physiol Renal P... - May 25, 2016 Category: Urology & Nephrology Authors: Kasinath BS Tags: Am J Physiol Renal Physiol Source Type: research

Specific endothelial heparin-binding EGF-like growth factor deletion ameliorates renal injury induced by chronic angiotensin II infusion.
In conclusion, our results suggest that shedding of HB-EGF from endothelium plays an important role in Ang II-induced renal injury by linking Ang II-AT1R with EGFR transactivation. Inhibition of HB-EGF shedding could be a potential therapeutic strategy for chronic kidney disease. PMID: 27226110 [PubMed - as supplied by publisher] (Source: Am J Physiol Renal P...)
Source: Am J Physiol Renal P... - May 25, 2016 Category: Urology & Nephrology Authors: Zeng F, Kloepfer LA, Finney C, Diedrich A, Harris RC Tags: Am J Physiol Renal Physiol Source Type: research

High serum creatinine non-linearity: a renal vital sign?
Abstract Patients with chronic kidney disease (CKD) may have non-linear serum creatinine concentration (SC) trajectories, especially as CKD progresses. Variability in SC is associated with renal failure and death. However, current methods for measuring SC variability are unsatisfactory because they blend information about SC slope and variance. We propose an improved method for defining and calculating a patient's SC slope and variance so that they are mathematically distinct, and we test these methods in a large sample of US veterans, examining the correlation of SC slope and SC non-linearity (SCNL), and the asso...
Source: Am J Physiol Renal P... - May 18, 2016 Category: Urology & Nephrology Authors: Palant CE, Chawla LS, Faselis C, Li P, Pallone TL, Kimmel PL, Amdur RL Tags: Am J Physiol Renal Physiol Source Type: research

Pyridoxamine reduces post-injury fibrosis and improves functional recovery after acute kidney injury.
Abstract Acute kidney injury (AKI) is a common and independent risk factor for death and chronic kidney disease (CKD). Despite promising preclinical data, there is no evidence that anti-oxidants reduce the severity of injury, increase recovery, or prevent CKD in patients with AKI. Pyridoxamine (PM) is a structural analog of vitamin B6 that interferes with oxidative macromolecular damage via a number of different mechanisms, and is in a phase 3 clinical efficacy trial to delay CKD progression in patients with diabetic kidney disease. Since oxidative stress is implicated as one of the main drivers of renal injury af...
Source: Am J Physiol Renal P... - May 18, 2016 Category: Urology & Nephrology Authors: Skrypnyk NI, Voziyan P, Yang H, de Caestecker CR, Theberge MC, Drouin M, Hudson B, Harris RC, de Caestecker MP Tags: Am J Physiol Renal Physiol Source Type: research

The Proximal Tubule is the Primary Target of Injury and Progression of Kidney Disease: Role of the glomerulotubular junction.
Abstract There is an alarming global increase in the incidence of end-stage kidney disease, for which early biomarkers and effective treatment options are lacking. Largely based on the histology of the end-stage kidney and on the model of unilateral ureteral obstruction, current investigation is focused on the pathogenesis of renal interstitial fibrosis as a central mechanism in the progression of chronic kidney disease (CKD). It is now recognized that cumulative episodes of acute kidney injury (AKI) can lead to CKD and conversely, CKD is a risk factor for AKI. Based on recent and historic studies, this review shi...
Source: Am J Physiol Renal P... - May 18, 2016 Category: Urology & Nephrology Authors: Chevalier RL Tags: Am J Physiol Renal Physiol Source Type: research

Heat shock factor 1 induces Crystallin-αB to protect against cisplatin nephrotoxicityα.
Heat shock factor 1 induces Crystallin-αB to protect against cisplatin nephrotoxicityα. Am J Physiol Renal Physiol. 2016 May 18;:ajprenal.00201.2016 Authors: Lou Q, Hu Y, Ma Y, Dong Z Abstract Cisplatin, a wildly used chemotherapy drug, induces nephrotoxicity that is characterized by renal tubular cell apoptosis. In response to toxicity, tubular cells can activate cytoprotective mechanisms, such as heat shock response. However, the role and regulation of heat shock response in cisplatin-induced nephrotoxicity remain largely unclear. Here we demonstrate the induction of Heat shock factor 1 ...
Source: Am J Physiol Renal P... - May 18, 2016 Category: Urology & Nephrology Authors: Lou Q, Hu Y, Ma Y, Dong Z Tags: Am J Physiol Renal Physiol Source Type: research

Postischemic microvasculopathy and Endothelial Progenitor Cell-based therapy in ischemic AKI - update and perspectives.
GA Abstract Acute kidney injury (AKI) dramatically increases mortality of hospitalized patients. Incidences have been increased in recent years. The most frequent cause is transient renal hypoperfusion or ischemia which induces significant tubular cell dyfunction / damage. In addition, two further events take place: interstitial inflammation and microvasculopathy (MV). The latter evolves within minutes to hours post-ischemia and may results in permanent deterioration of the peritubular capillary network, ultimately increasing the risk for chronic kidney disease (CKD) in the long-term. In recent years, our underst...
Source: Am J Physiol Renal P... - May 18, 2016 Category: Urology & Nephrology Authors: Patschan D, Kribben A, Müller GA Tags: Am J Physiol Renal Physiol Source Type: research

Perioperative glutamine supplementation restores the disturbed renal arginine synthesis after open aortic surgery, a randomized controlled clinical trial.
Abstract BACKGROUND: Postoperative renal failure is a common complication after open repair of an abdominal aneurysm. The amino-acid arginine is formed in the kidneys from its precursor citrulline, citrulline from glutamine in the intestines. Arginine enhances the function of the immune and cardiovascular system, which is important for recovery after and during surgery. We hypothesized that renal arginine production is diminished after ischemia-reperfusion injury by clamping of the aorta during open abdominal aortic surgery and that parenteral glutamine supplementation may compensate this impaired arginine synthes...
Source: Am J Physiol Renal P... - May 18, 2016 Category: Urology & Nephrology Authors: Brinkmann SJ, Buijs N, Vermeulen MA, Oosterink E, Schierbeek H, Beishuizen A, de Vries JP, Wisselink W, van Leeuwen PA Tags: Am J Physiol Renal Physiol Source Type: research

Increased Angiotensinogen Expression, Urinary Angiotensinogen Excretion and Tissue Injury in Non-clipped Kidneys of 2-Kidney 1-Clip Hypertensive Rats.
Abstract In angiotensin II (Ang II) dependent hypertension, there is an AT1 receptor dependent amplification mechanism enhancing intrarenal angiotensinogen (AGT) formation and secretion into the tubular fluid. To evaluate the role of increased arterial pressure, AGT mRNA, protein expression, and urinary AGT (uAGT) excretion and tissue injury were assessed in both kidneys of 2-kidney, 1-clip (2K1C) Sprague Dawley hypertensive rats subjected to left renal arterial clipping (0.25 mm gap). By 18-21 days, systolic arterial pressure increased to 180±3 mmHg, and uAGT increased. Water intake, body weights, 24 hr ur...
Source: Am J Physiol Renal P... - May 18, 2016 Category: Urology & Nephrology Authors: Shao W, Miyata K, Katsurada A, Satou R, Seth DM, Rosales CB, Prieto MC, Mitchell KD, Navar LG Tags: Am J Physiol Renal Physiol Source Type: research

20-HETE and CYP4A2 ω-hydroxylase contribute to the elevated blood pressure in hyperandrogenemic female rats.
In this study we determined the roles of 20-HETE and CYP4A2 on the elevated BP in hyperandrogenemic female rats. Chronic dihydrotestosterone (DHT) increased mean arterial pressure (MAP) in female Sprague Dawley rats (96±2 vs 108±2 mmHg; p
Source: Am J Physiol Renal P... - May 18, 2016 Category: Urology & Nephrology Authors: Dalmasso C, Maranon RO, Patil CN, Moulana M, Romero DG, Reckelhoff JF Tags: Am J Physiol Renal Physiol Source Type: research

Hippo Signaling in the Kidney: The Good and the Bad.
Abstract The Hippo signaling pathway is an evolutionarily conserved kinase cascade, playing multiple roles in embryonic development that controls organ size, cell proliferation and apoptosis. At the center of this network lie the Hippo kinase target and downstream pathway effector Yes-associated protein (YAP) and its paralog TAZ. In its phosphorylated form, cytoplasmic YAP is sequestered in an inactive state. When it is dephosphorylated, YAP a potent oncogene, is activated and relocates to the nucleus to interact with a number of transcription factors and signaling regulators that promote cell growth, differentiat...
Source: Am J Physiol Renal P... - May 18, 2016 Category: Urology & Nephrology Authors: Wong J, Meliambro K, Ray J, Campbell K Tags: Am J Physiol Renal Physiol Source Type: research

Klotho/fibroblast growth factor 23- and PTH-Independent estrogen receptor α Mediated direct Downregulation of NaPi-IIa by Estrogen in the Mouse Kidney.
CONCLUSIONS: estrogen causes phosphaturia and hypophosphatemia in mice. These effects result from downregulation of NaPi-IIa and NaPi-IIc proteins in the proximal tubule through the activation of ERα. The downregulation of NaPi-IIa by estrogen involves 3'UTR of its mRNA and is independent of Klotho/fgf23 and PTH signaling pathways. PMID: 27194721 [PubMed - as supplied by publisher] (Source: Am J Physiol Renal P...)
Source: Am J Physiol Renal P... - May 18, 2016 Category: Urology & Nephrology Authors: Webster R, Sheriff S, Faroqui R, Siddiqui F, Hawse JR, Amlal H Tags: Am J Physiol Renal Physiol Source Type: research

Glucagon actions on the kidney revisited. Possible role in potassium homeostasis.
Abstract It is now recognized that the metabolic disorders observed in diabetes are not, or not only due to the lack of insulin or insulin resistance, but also to elevated glucagon secretion. Accordingly, selective glucagon receptor antagonists are now proposed as a novel strategy for the treatment of diabetes. However, besides its metabolic actions, glucagon also influences kidney function. The glucagon receptor is expressed in the thick ascending limb, distal tubule and collecting duct, and glucagon regulates the transepithelial transport of several solutes in these nephron segments. Moreover, it also influences...
Source: Am J Physiol Renal P... - May 18, 2016 Category: Urology & Nephrology Authors: Bankir L, Bouby N, Blondeau B, Crambert G Tags: Am J Physiol Renal Physiol Source Type: research

Intrauterine growth restriction programs accelerated age-related increased cardiovascular risk in male offspring.
INTRAUTERINE GROWTH RESTRICTION PROGRAMS ACCELERATED AGE-RELATED INCREASED CARDIOVASCULAR RISK IN MALE OFFSPRING. Am J Physiol Renal Physiol. 2016 May 4;:ajprenal.00123.2016 Authors: Dasinger JH, Intapad S, Backstrom MA, Carter AJ, Alexander BT Abstract Placental insufficiency programs an increase in blood pressure associated with a two-fold increase in serum testosterone in male growth-restricted offspring at 4 months of age. Population studies indicate that the inverse relationship between birth weight and blood pressure is amplified with age. Thus, we tested the hypothesis that intrauterine growth ...
Source: Am J Physiol Renal P... - May 4, 2016 Category: Urology & Nephrology Authors: Dasinger JH, Intapad S, Backstrom MA, Carter AJ, Alexander BT Tags: Am J Physiol Renal Physiol Source Type: research

Pathophysiology of gadolinium-associated systemic fibrosis.
Abstract Systemic fibrosis from gadolinium-based magnetic resonance imaging contrast is a scourge for the afflicted. Although gadolinium-associated systemic fibrosis is a rare condition, the threat of litigation has vastly altered clinical practice. Most theories concerning the etiology of the fibrosis are grounded in case reports rather than experiment. This has led to the widely-accepted conjecture that the relative affinity of certain contrast agents for the gadolinium ion inversely correlates with the risk of succumbing to the disease. How gadolinium-containing contrast agents trigger widespread and site-speci...
Source: Am J Physiol Renal P... - May 4, 2016 Category: Urology & Nephrology Authors: Wagner B, Drel VR, Gorin Y Tags: Am J Physiol Renal Physiol Source Type: research

Recent Advances in Renal Hypoxia: Insights from Bench Experiments and Computer Simulations.
Abstract The availability of oxygen in renal tissue is determined by the complex interactions among a host of processes, including renal blood flow, glomerular filtration, arterial-to-venous oxygen shunting, medullary architecture, Na$^+$ transport, and oxygen consumption. When this delicate balance is disrupted, the kidney may become susceptible to hypoxic injury. Indeed, renal hypoxia has been implicated as one of the major causes of acute kidney injury and chronic kidney diseases. This review highlights recent advances in our understanding of renal hypoxia; some of these studies were published in response to a ...
Source: Am J Physiol Renal P... - May 4, 2016 Category: Urology & Nephrology Authors: Layton AT Tags: Am J Physiol Renal Physiol Source Type: research

The Evolving Field of Salt Transport Regulation in the Steve Hebert Lecture.
PMID: 27147671 [PubMed - as supplied by publisher] (Source: Am J Physiol Renal P...)
Source: Am J Physiol Renal P... - May 4, 2016 Category: Urology & Nephrology Authors: Gamba G Tags: Am J Physiol Renal Physiol Source Type: research

Novel therapeutic approaches for chronic kidney disease due to glomerular disorders.
gh SS Abstract Improved understanding of glomerular disease mechanisms over the past decade has led to the emergence of new and targeted therapeutic strategies for chronic kidney disease (CKD). Most promising among these are the administration of recombinant mutated human Angiopoietin-like 4, sialic acid related sugars that induce sialylation in vivo, compounds related to Bis-T-23, and immune-depletion of the soluble urokinase receptor from the circulation. Taking these therapeutic strategies into clinical trials will be the first step away from repurposed and relatively toxic drugs currently used for treating kid...
Source: Am J Physiol Renal P... - May 4, 2016 Category: Urology & Nephrology Authors: Del Nogal-Avila M, Donoro-Blazquez H, Saha MK, Marshall CB, Clement LC, Macé CE, Chugh SS Tags: Am J Physiol Renal Physiol Source Type: research

EF- 40-2016 Complement: An Unfinished Symphony.
Abstract The current issue reports that, when hypertension was induced in mice (using infusion of angiotensin II and with NaCl in the drinking water), the absence (knockout) of the first receptor for C5a (C5aR1) resulted in reduced albuminuria but increased amounts of interstitial collagen deposition in the heart. The role of the second C5a receptor (C5aR2) in responses to hypertension was not examined, but should be. Such patterns suggest that mice lacking C5aR1 express different outcomes during hypertension in the heart and in the kidneys. We review different strategies for blockade of complement activation prod...
Source: Am J Physiol Renal P... - May 4, 2016 Category: Urology & Nephrology Authors: Ward PA Tags: Am J Physiol Renal Physiol Source Type: research

Protein-bound uremic toxins: a long overlooked culprit in cardiorenal syndrome.
Abstract Protein-bound uremic toxins (PBUTs) accumulate once renal excretory function declines, and are not cleared by dialysis. There is increasing evidence that PBUTs exert toxic effects onmany vital organs including the kidney, blood vessels and heart. It has been suggested that PBUTs are likely to be a potential missing link in cardiorenal syndrome, based on the high incidence of cardiovascular events and mortality in the dialysis population which is dramatically reduced in successful kidney transplant recipients. These data have led the call for more effective dialysis or additional adjunctive therapy to erad...
Source: Am J Physiol Renal P... - May 4, 2016 Category: Urology & Nephrology Authors: Lekawanvijit S, Kompa AR, Krum H Tags: Am J Physiol Renal Physiol Source Type: research