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Renal proximal tubule

Istvan Arany, Anthony Carter, Samuel Hall, Tibor Fulop, Mehul Dixit
Chronic nicotine exposure (via smoking, E-cigarettes) increases oxidative stress in the kidney that sensitizes it to additional injury in experimental models and in the renal patient. The pro-apoptotic p66(shc) protein-via serine36 phosphorylation that facilitates its mitochondrial translocation and therein cytochrome c binding-generates oxidative stress that leads to injury of renal proximal tubule cells during chronic nicotine exposure. Coenzyme Q10-a clinically safe antioxidant-has been used against nicotine/smoke extract-associated oxidative stress in various non-renal cells...
October 22, 2016: Apoptosis: An International Journal on Programmed Cell Death
Min Shi, Liang Ma, Li Zhou, Ping Fu
Aristolochic acid nephropathy (AAN) is a progressive kidney disease caused by a Chinese herb containing aristolochic acid. Excessive death of renal tubular epithelial cells (RTECs) characterized the acute phase of AAN. Therapies for acute AAN were limited, such as steroids and angiotensin-receptor blockers (ARBs)/angiotensin-converting enzyme inhibitors (ACEIs). It was interesting that, in acute AAN, female patients showed relative slower progression to renal failure than males. In a previous study, female hormone 17β-estradiol (E2) was found to attenuate renal ischemia-reperfusion injury...
October 18, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Grazyna Nowak, Diana Takacsova Bakajsova, Judit Megyesi
Previously, we documented that activation of protein kinase C-ε (PKC-ε) mediates mitochondrial dysfunction in cultured renal proximal tubule cells (RPTC). This study tested whether deletion of the PKC-ε decreases dysfunction of renal cortical mitochondria and improves kidney function after renal ischemia. PKC-ε levels in mitochondria of ischemic kidneys increased 24h after ischemia. Complex I- and complex II-coupled state 3 respirations were reduced 44% and 27%, respectively, in wild-type (WT) but unchanged and increased in PKC-ε-deficient (KO) mice after ischemia...
October 19, 2016: American Journal of Physiology. Renal Physiology
Richard W Naylor, Rachel C Dodd, Alan J Davidson
The nephron is the functional unit of the kidney and is divided into distinct proximal and distal segments. The factors determining nephron segment size are not fully understood. In zebrafish, the embryonic kidney has long been thought to differentiate in situ into two proximal tubule segments and two distal tubule segments (distal early; DE, and distal late; DL) with little involvement of cell movement. Here, we overturn this notion by performing lineage-labelling experiments that reveal extensive caudal movement of the proximal and DE segments and a concomitant compaction of the DL segment as it fuses with the cloaca...
October 19, 2016: Scientific Reports
Masahiro Ono, Atsumi Baden, Hiroyuki Okudaira, Masato Kobayashi, Keiichi Kawai, Shuntaro Oka, Hirokatsu Yoshimura
[(18)F]Fluciclovine (trans-1-amino-3-[(18)F]fluorocyclobutanecarboxylic acid; anti-[(18)F]FACBC), a positron emission tomography tracer used for the diagnosis of recurrent prostate cancer, is transported via amino acid transporters (AATs) with high affinity (Km: 97-230 μM). However, the mechanism underlying urinary excretion is unknown. In this study, we investigated the involvement of AATs and drug transporters in renal [(18)F]fluciclovine reuptake. [(14)C]Fluciclovine (trans-1-amino-3-fluoro[1-(14)C]cyclobutanecarboxylic acid) was used because of its long half-life...
October 14, 2016: International Journal of Molecular Sciences
Zhiming Zhu
Management of hypertension in diabetes is critical for reducing cardiovascular mortality and morbidity. Dietary approaches for controlling high blood pressure have historically focused on sodium. Thus, many guidelines recommend that patients with type 2 diabetes reduce high sodium intake. Nonetheless, the potential benefits of sodium reduction are debatable. The kidney has a crucial role in glucose filtration and reabsorption in addition to its regulation of fluid and electrolyte homeostasis. A key factor linking sodium uptake and glucose transport is the sodium-glucose cotransporter 2 (SGLT2) in renal proximal tubular cells...
September 2016: Journal of Hypertension
Hirokazu Muraoka, Kazuhiro Hasegawa, Shu Wakino
OBJECTIVE: Nicotinamide phosphoribosyltransferase (Nampt) cooperates with a longevity gene, Sirt1, to exert the potentiation of stress resistance. We have reported that the high expression level of Nampt in PTs contributes to the sufficient supply of NMN to glomeruli. We also showed that downregulation of Nampt and NMN in PT in DN leads to glomerular damages (Nature Medicine 2013). However, the regulation mechanisms of Nampt expression remain unknown. DESIGN AND METHOD: We investigated how Nampt expression is consistently retained at high levels in PTs under normal conditions and how Nampt levels are decreased in DN...
September 2016: Journal of Hypertension
Johanne Tremblay, Carole G Campion, Thomas Verissimo, Suzanne Cossette, Hiroyuki Matsuda, Pavel Hamet
OBJECTIVE: Epidermal growth factor receptor (EGFR) signaling plays a dual role in hypertension-induced kidney damage. EGFR is critically involved in angiotensin II-induced renal lesions and fibrosis but is also engaged in kidney tissue repair. Consequently, targeting EGFR in renal diseases is complex because even if inhibition of EGFR activity would be beneficial, a minimal EGFR activity is needed to recover from harmful insults. Our group has identified HCaRG (Hypertension-related, Calcium-Regulated Gene) whose expression is increased in kidneys of hypertensive rats and mice...
September 2016: Journal of Hypertension
Markus Schlaich, Rosemary Elliott, Caroline Rudnicka, Vance Matthews
OBJECTIVE: Sympathetic nervous system activation is a common feature in various metabolic disorders such as obesity, metabolic syndrome, and type-2 diabetes. The sodium glucose co-transporter 2 (SGLT-2) mediates re-absorption of glucose from the renal proximal tubules. SGLT-2 inhibitors have attracted substantial attention due to their glucose and blood pressure lowering effects. Furthermore, the SGLT-2 inhibitor empagliflozin has recently been associated with improved cardiovascular outcomes in patients with type 2 diabetes...
September 2016: Journal of Hypertension
Hiroaki Kitamura, Daisuke Nakano, Zhang Yifan, Akira Nishiyama
OBJECTIVE: Carperitide, alpha-human atrial natriuretic peptide, is used in expectation of protecting the kidney during sepsis in internal care unit; however, the detailed mechanism of action has not been clarified yet. As septic acute kidney injury (AKI) does not induce characteristic histological damage, we aimed assess the effects of carperitide treatment on the decline of renal function during lipopolysaccharide-induced AKI by using real-time intravital imaging technique. DESIGN AND METHOD: The renal function was analyzed by the bolus-shot FITC-inulin kinetics method that visualizes the tubular flow after free filtration from glomeruli...
September 2016: Journal of Hypertension
John Chan, Chao-Sheng Lo, Yixuan Shi, Isabelle Chenier, Shao-Ling Zhang
OBJECTIVE: We aimed to investigate whether overexpression of heterogeneous nuclear ribonucleoprotein F (HnRNP F, a transcription factor) in renal proximal tubular cells (RPTCs) prevents systemic hypertension and kidney injury in type 2 diabetic db/db transgenic (Tg) mice and study its underlying mechanism (s) of action. DESIGN AND METHOD: Db/db hnRNP F-Tg mice (BKS strain) were generated by cross-breeding of db/m + mice with Tg mice specifically overexpressing HnRNP F in their RPTCs using kidney-specific androgen-regulated protein promoter (KAP2)...
September 2016: Journal of Hypertension
Resham Poudel
The kidneys maintain glucose homeostasis through its utilization, gluconeogenesis, and reabsorption. Glucose is freely filtered and reabsorbed in order to retain energy essential between meals. The amount of glucose reabsorbed by the kidneys is equivalent to the amount entering the filtration system. With a daily glomerular filtration rate of 180 L, approximately 180 g (180 L/day × 100 mg/dL) of glucose must be reabsorbed each day to maintain an average fasting plasma glucose concentration of 5.6 mmol/L (100 mg/dL)...
September 2016: Journal of Hypertension
Ana Vrdoljak, Vanja Ivković, Sandra Karanović, Živka Dika, Ivana Vuković, Jelena Kos, Mario Laganović, Tajana Željković Vrkić, Margareta Fištrek Prlić, Ivan Pećin, Bojan Jelaković
OBJECTIVE: It was observed that glomerular hyperfiltration (GHF) is associated with progression of kidney disease in diabetics, patients in stage 1 hypertension (HT), and we found previously that eGFR decreased faster also in prehypertensives (PHT) with GHF. Here we analyzed whether GHF in PHT is associated with other biomarkers of early renal impairment. DESIGN AND METHOD: From 954 subjects enrolled in ENAH follow-up study, 371(137 m;mean age = 46years) were eligible for further analysis:100 with optimal,72 with normal BP,70 with PHT(high normal BP),and 129 with newly diagnosed untreated HT...
September 2016: Journal of Hypertension
Ranga M Weerakkody, Pushpa N Lokuliyana, Ruchika D Lanerolle
Hump-nosed viper (Hypnale hypnale; HNV) is one of the six major snake species in Sri Lanka that cause envenomation. Nephrotoxicity, coagulopathy, and neurotoxicity are wellrecognized features of its envenomation. Type 4 renal tubular acidosis (RTA4) has only once been described previously in this condition, and we report two further cases. Two patients aged 53 and 51 presented following HNV bites with acute kidney injury and microangiopathic hemolytic anemia. Both underwent multiple cycles of hemodialysis until the polyuric phase was reached...
September 2016: Saudi Journal of Kidney Diseases and Transplantation
Vasilios Tsimihodimos, Theodosios D Filippatos, Sebastian Fillippas-Ntekouan, Moses S Elisaf
Sodium-glucose co-transporter 2 inhibitors (SGLT-2) inhibitors) represent a new class of antidiabetic drugs that act through the inhibition of glucose and sodium reabsorption at proximal tubules. It has been shown that tThese substances may exhibit renonephroprotective properties, since they expressed clinically as a prevention of the deterioration of the glomerular filtration rate and a reductionreduce in the degree of albuminuria in patients with established diabetes-associated kidney disease. In this review we present in detail the pathophysiologic mechanisms that have been recently implicated in the rennephroprotective properties of SGLT-2 inhibitors...
October 7, 2016: Current Vascular Pharmacology
Suman Pradhan, Christine Pellino, Kayleigh MacMaster, Dennis Coyle, Alison A Weiss
Seizures and neurologic involvement have been reported in patients infected with Shiga toxin (Stx) producing E. coli, and hemolytic uremic syndrome (HUS) with neurologic involvement is associated with more severe outcome. We investigated the extent of renal and neurologic damage in mice following injection of the highly potent form of Stx, Stx2a, and less potent Stx1. As observed in previous studies, Stx2a brought about moderate to acute tubular necrosis of proximal and distal tubules in the kidneys. Brain sections stained with hematoxylin and eosin (H&E) appeared normal, although some red blood cell congestion was observed...
2016: Frontiers in Cellular and Infection Microbiology
Ming-Zhi Zhang, Xin Wang, Yinqiu Wang, Aolei Niu, Suwan Wang, Chenhang Zou, Raymond C Harris
Cytokines IL-4 and IL-13 play important roles in polarization of macrophages/dendritic cells to an M2 phenotype, which is important for recovery from acute kidney injury. Both IL-4 and IL-13 activate JAK3/STAT6 signaling. In mice with diphtheria toxin receptor expression in proximal tubules (selective injury model), a relatively selective JAK3 inhibitor, tofacitinib, led to more severe kidney injury, delayed recovery from acute kidney injury, increased inflammatory M1 phenotype markers and decreased reparative M2 phenotype markers of macrophages/dendritic cells, and development of more severe renal fibrosis after diphtheria toxin administration...
October 10, 2016: Kidney International
Marianne Uteng, Andreas Mahl, Nicolau Beckmann, Alessandro Piaia, David Ledieu, Valerie Dubost, Elaine Tritto, Armin Wolf, Pierre Moulin, Li Li, Salah-Dine Chibout, Francois Pognan
The aim of this study was to determine the relative safety of four antiviral drugs (telbivudine, tenofovir, adefovir, entecavir) against hepatitis B virus with respect to kidney function and toxicity in male Spraque-Dawley rats. The antiviral drugs were administered once daily for four weeks by oral gavage at about 10 and 25-40 times the human equivalent dose. Main assessments included markers of renal toxicity in urine, magnetic resonance imaging (MRI) of kidney function, histopathology and electron microscopic examination...
October 13, 2016: Toxicological Sciences: An Official Journal of the Society of Toxicology
Blythe D Shepard, Lydie Cheval, Zita Peterlin, Stuart Firestein, Hermann Koepsell, Alain Doucet, Jennifer L Pluznick
Olfactory receptors (ORs) are G protein-coupled receptors which serve important sensory functions beyond their role as odorant detectors in the olfactory epithelium. Here we describe a novel role for one of these ORs, Olfr1393, as a regulator of renal glucose handling. Olfr1393 is specifically expressed in the kidney proximal tubule, which is the site of renal glucose reabsorption. Olfr1393 knockout mice exhibit urinary glucose wasting and improved glucose tolerance, despite euglycemia and normal insulin levels...
October 14, 2016: Scientific Reports
Jessica Ann Dominguez Rieg, Samantha de la Mora Chavez, Timo Rieg
The Na(+)/H(+) exchanger isoform 3 (NHE3) facilitates Na(+) absorption and H(+) secretion and is expressed in the intestine, proximal tubule and thick ascending limb of the kidney. While the function of NHE3 for Na(+) and HCO3(-) (re)absorption has been defined using conventional NHE3 knockout mice (NHE3(-/-)), the recent generation of conditional NHE3 knockout mice started to give critical new insight into the role of this protein by allowing for temporal and spatial control of NHE3 expression. For example, in contrast to NHE3(-/-) mice, knockout of NHE3 in the S1 and S2 segments of the proximal tubule or along the entire tubule/collecting duct does not cause any lethality...
October 12, 2016: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
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