Slit2 ameliorates renal inflammation and fibrosis after hypoxia-and lipopolysaccharide-induced epithelial cells injury in vitro

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhou, Xiangjun; Yao, Qisheng, E-mail: yymcyqs@126.com; Sun, Xinbo

Hypoxic acute kidney injury (AKI) is often incompletely repaired and leads to chronic kidney disease (CKD), which is characterized by tubulointerstitial inflammation and fibrosis. The Slit2 family of secreted glycoproteins is expressed in the kidney, it has been shown to exert an anti-inflammatory activity and prevent ischemic renal injury in vivo. However, whether Slit2 reduces renal fibrosis and inflammation after hypoxic and inflammatory epithelial cells injury in vitro remains unknown. In this study, we aimed to evaluate whether Slit2 ameliorated fibrosis and inflammation in two renal epithelial cells line challenged with hypoxia and lipopolysaccharide (LPS). Renal epithelial cells were treatedmore » with hypoxia and LPS to induce cell injury. Hoechst staining and Western blot analysis was conducted to examine epithelial cells injury. Immunofluorescence staining and Western blot analysis was performed to evaluate tubulointerstitial fibrosis. Real-time polymerase chain reaction (PCR) tested the inflammatory factor interleukin (IL)−1β and tumor necrosis factor (TNF)-α, and Western blot analysis determined the hypoxia-inducible factor (HIF)−1α, Toll-like receptor 4 (TLR4) and nuclear factor (NF)-κB. Results revealed that hypoxia induced epithelial cells apoptosis, inflammatory factor IL-1β and TNF-α release and tubulointerstitial fibrosis. LPS could exacerbate hypoxia -induced epithelial cells apoptosis, IL-1β and TNF-α release and fibrosis. Slit2 reduced the expression of fibronectin, the rate of epithelial cell apoptosis, and the expression of inflammatory factor. Slit2 could also inhibit the expression of TLR4 and NF-κB, but not the expression of HIF-1α. Therefore, Slit2 attenuated inflammation and fibrosis after LPS- and hypoxia-induced epithelial cells injury via the TLR4/NF-κB signaling pathway, but not depending on the HIF-1α signaling pathway. - Highlights: • Slit2 ameliorates inflammation after hypoxia-and LPS-induced epithelial cells

Sida rhomboidea.Roxb leaf extract ameliorates gentamicin induced nephrotoxicity and renal dysfunction in rats.

PubMed

Thounaojam, Menaka C; Jadeja, Ravirajsinh N; Devkar, Ranjitsinh V; Ramachandran, A V

2010-10-28

Sida rhomboidea.Roxb (SR) known as "Mahabala" in Ayurveda and marketed as "Shahadeyi" is used in ethnomedicine to treat ailments such as dysuria and urinary disorders. To evaluate nephroprotective potential of SR against gentamicin (GM) induced nephrotoxicity and renal dysfunction. Nephrotoxicity was induced in rats with GM (100 mg/kg bodyweight (i.p.) for 8 days) and were treated with SR extract (200 and 400 mg/kg bodyweight (p.o.) for 8 days) or 0.5% carboxymethyl cellulose (vehicle). Plasma and urine urea and creatinine, renal enzymatic and non-enzymatic antioxidants along with lipid peroxidation were evaluated in various experimental groups. GM treatment induced significant elevation (p<0.05) in plasma and urine urea, creatinine, renal lipid peroxidation along with significant decrement (p<0.05) in renal enzymatic and non-enzymatic antioxidants. SR treatment to GM treated rats (GM+SR) recorded significant decrement (p<0.05) in plasma and urine urea and creatinine, renal lipid peroxidation along with significant increment (p<0.05) in renal enzymatic and non-enzymatic antioxidants. SR leaf extract ameliorates GM induced nephrotoxicity and renal dysfunction and thus validates its ethnomedicinal use. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Emodin ameliorates cisplatin-induced apoptosis of rat renal tubular cells in vitro by activating autophagy

PubMed Central

Liu, Hong; Gu, Liu-bao; Tu, Yue; Hu, Hao; Huang, Yan-ru; Sun, Wei

2016-01-01

Aim: A previous report shows that emodin extracted from the Chinese herbs rhubarb and giant knotweed rhizome can ameliorate the anticancer drug cisplatin-induced injury of HEK293 cells. In this study, we investigated whether and how emodin could protect renal tubular epithelial cells against cisplatin-induced nephrotoxicity in vitro. Methods: The viability and apoptosis of normal rat renal tubular epithelial cells (NRK-52E) were detected using formazan assay and flow cytometry analysis, respectively. The expression levels of cleaved caspase-3, autophagy maker LC3 I/II, and AMPK/mTOR signaling pathway-related proteins were measured with Western blot analysis. The changes of morphology and RFP-LC3 fluorescence were observed under microscopy. Results: Cisplatin (10-50 μmol/L) dose-dependently induced cell damage and apoptosis in NRK-52E cells, whereas emodin (10 and 100 μmol/L) significantly ameliorated cisplatin-induced cell damage, apoptosis and caspase-3 cleavage. Emodin dose-dependently increased LC3-II levels and induced RFP-LC3-containing punctate structures in NRK-52E cells. Furthermore, the protective effects of emodin were abolished by bafilomycin A1 (10 nmol/L), and mimicked by rapamycin (100 nmol/L). Moreover, emodin increased the phosphorylation of AMPK and suppressed the phosphorylation of mTOR. The AMPK inhibitor compound C (10 μmol/L) not only abolished emodin-induced autophagy activation, but also emodin-induced anti-apoptotic effects. Conclusion: Emodin ameliorates cisplatin-induced apoptosis of rat renal tubular cells in vitro through modulating the AMPK/mTOR signaling pathways and activating autophagy. Emodin may have therapeutic potential for the prevention of cisplatin-induced nephrotoxicity. PMID:26775661

Emodin ameliorates cisplatin-induced apoptosis of rat renal tubular cells in vitro by activating autophagy.

PubMed

Liu, Hong; Gu, Liu-bao; Tu, Yue; Hu, Hao; Huang, Yan-ru; Sun, Wei

2016-02-01

A previous report shows that emodin extracted from the Chinese herbs rhubarb and giant knotweed rhizome can ameliorate the anticancer drug cisplatin-induced injury of HEK293 cells. In this study, we investigated whether and how emodin could protect renal tubular epithelial cells against cisplatin-induced nephrotoxicity in vitro. The viability and apoptosis of normal rat renal tubular epithelial cells (NRK-52E) were detected using formazan assay and flow cytometry analysis, respectively. The expression levels of cleaved caspase-3, autophagy maker LC3 I/II, and AMPK/mTOR signaling pathway-related proteins were measured with Western blot analysis. The changes of morphology and RFP-LC3 fluorescence were observed under microscopy. Cisplatin (10-50 μmol/L) dose-dependently induced cell damage and apoptosis in NRK-52E cells, whereas emodin (10 and 100 μmol/L) significantly ameliorated cisplatin-induced cell damage, apoptosis and caspase-3 cleavage. Emodin dose-dependently increased LC3-II levels and induced RFP-LC3-containing punctate structures in NRK-52E cells. Furthermore, the protective effects of emodin were abolished by bafilomycin A1 (10 nmol/L), and mimicked by rapamycin (100 nmol/L). Moreover, emodin increased the phosphorylation of AMPK and suppressed the phosphorylation of mTOR. The AMPK inhibitor compound C (10 μmol/L) not only abolished emodin-induced autophagy activation, but also emodin-induced anti-apoptotic effects. Emodin ameliorates cisplatin-induced apoptosis of rat renal tubular cells in vitro through modulating the AMPK/mTOR signaling pathways and activating autophagy. Emodin may have therapeutic potential for the prevention of cisplatin-induced nephrotoxicity.

The unsuitability of implantable Doppler probes for the early detection of renal vascular complications – a porcine model for prevention of renal transplant loss

PubMed Central

Jespersen, Bente; Møldrup, Ulla; Keller, Anna K.

2017-01-01

Background Vascular occlusion is a rare, but serious complication after kidney transplantation often resulting in graft loss. We therefore aimed to develop an experimental porcine model for stepwise reduction of the renal venous blood flow and to compare an implantable Doppler probe and microdialysis for fast detection of vascular occlusion. Methods In 20 pigs, implantable Doppler probes were placed on the renal artery and vein and a microdialysis catheter was placed in the renal cortex. An arterial flowprobe served as gold standard. Following two-hour baseline measurements, the pigs were randomised to stepwise venous occlusion, complete venous occlusion, complete arterial occlusion or controls. Results All parameters were stable through baseline measurements. Glutamate and lactate measured by microdialysis increased significantly (p = 0.02 and p = 0.03 respectively) 30 minutes after a 2/3 (66%) reduction in renal blood flow. The implantable Doppler probe was not able to detect flow changes until there was total venous occlusion. Microdialysis detected changes in local metabolism after both arterial and venous occlusion; the implantable Doppler probe could only detect vascular occlusions on the vessel it was placed. Conclusions We developed a new model for stepwise renal venous blood flow occlusion. Furthermore, the first comparison of the implantable Doppler probe and microdialysis for detection of renal vascular occlusions was made. The implantable Doppler probe could only detect flow changes after a complete occlusion, whereas microdialysis detected changes earlier, and could detect both arterial and venous occlusion. Based on these results, the implantable Doppler probe for early detection of vascular occlusions cannot be recommended. PMID:28542429

Resveratrol, an Nrf2 activator, ameliorates aging-related progressive renal injury

PubMed Central

Kim, Eun Nim; Lim, Ji Hee; Kim, Min Young; Ban, Tae Hyun; Jang, In-Ae; Yoon, Hye Eun; Park, Cheol Whee; Chang, Yoon Sik

2018-01-01

Background. Two important issues in the aging kidney are mitochondrial dysfunction and oxidative stress. An Nrf2 activator, resveratrol, is known to have various effects. Resveratrol may prevent inflammation and oxidative stress by activating Nrf2 and SIRT1 signaling. We examined whether resveratrol could potentially ameliorate the cellular condition, such as renal injury due to cellular oxidative stress and mitochondrial dysfunction caused by aging. Methods. Male 18-month-old C57BL/6 mice were used. Resveratrol (40 mg/kg) was administered to aged mice for 6 months. We compared histological changes, oxidative stress, and aging-related protein expression in the kidney between the resveratrol-treated group (RSV) and the control group (cont). We performed experiments using small-interfering RNAs (siRNAs) for Nrf2 and SIRT1 in cultured HK2 cells. Results. Resveratrol improved renal function, proteinuria, histological changes and inflammation in aging mice. Also, expression of Nrf2-HO-1-NOQ-1 signaling and SIRT1-AMPK-PGC-1α signaling was increased in the RSV group. Transfection with Nrf2 and SIRT1 siRNA prevented resveratrol-induced anti-oxidative effect in HK2 cells in media treated with H2O2. Conclusions. Activation of the Nrf2 and SIRT1 signaling pathways ameliorated oxidative stress and mitochondrial dysfunction. Pharmacological targeting of Nrf2 signaling molecules may reduce the pathologic changes of aging in the kidney. PMID:29326403

Renal sympathetic denervation attenuates hypertension and vascular remodeling in renovascular hypertensive rats.

PubMed

Li, Peng; Huang, Pei-Pei; Yang, Yun; Liu, Chi; Lu, Yan; Wang, Fang; Sun, Wei; Kong, Xiang-Qing

2017-01-01

Li P, Huang P, Yang Y, Liu C, Lu Y, Wang F, Sun W, Kong X. Renal sympathetic denervation attenuates hypertension and vascular remodeling in renovascular hypertensive rats. J Appl Physiol 122: 121-129, 2017. First published October 14, 2016; doi:10.1152/japplphysiol.01019.2015-Sympathetic activity is enhanced in patients with essential or secondary hypertension, as well as in various hypertensive animal models. Therapeutic targeting of sympathetic activation is considered an effective antihypertensive strategy. We hypothesized that renal sympathetic denervation (RSD) attenuates hypertension and improves vascular remodeling and renal disease in the 2-kidney, 1-clip (2K1C) rat model. Rats underwent 2K1C modeling or sham surgery; then rats underwent RSD or sham surgery 4 wk later, thus resulting in four groups (normotensive-sham, normotensive-RSD, 2K1C-sham, and 2K1C-RSD). Norepinephrine was measured by ELISA. Echocardiography was used to assess heart function. Fibrosis and apoptosis were assessed by Masson and TUNEL staining. Changes in mean arterial blood pressure in response to hexamethonium and plasma norepinephrine levels were used to evaluate basal sympathetic nerve activity. The 2K1C modeling success rate was 86.8%. RSD reversed the elevated systolic blood pressure induced by 2K1C, but had no effect on body weight. Compared with rats in the 2K1C-sham group, rats in the 2K1C-RSD group showed lower left ventricular mass/body weight ratio, interventricular septal thickness in diastole, left ventricular end-systolic diameter, and left ventricular posterior wall thickness in systole, whereas fractional shortening and ejection fraction were higher. Right kidney apoptosis and left kidney hypertrophy were not changed by RSD. Arterial fibrosis was lower in animals in the 2K1C-RSD group compared with those in the 2K1C-sham group. RSD reduced plasma norepinephrine and basal sympathetic activity in rats in the 2K1C-RSD group compared with rats in the 2K1C-sham group. These

Analysis of the dynamics of renal vascular resistance and urine flow rate in the cat following electrical stimulation of the renal nerves.

PubMed

Celler, B G; Stella, A; Golin, R; Zanchetti, A

1996-08-01

In ten sino aortic denervated, vagotomized and aneasthetized cats, renal efferent nerves were stimulated for 30 s with trains of constant current pulses at frequencies in the range 5-30 Hz. The arterial pressure, heart rate, urine flow rate (electronic drop counter) and renal blood flow (electromagnetic technique) were recorded. Subsequent computer processing gave the true means of renal artery pressure (MRAP) and renal blood flow (MRBF) and hence the renal vascular resistance (MRVR), over each cardiac cycle. Recovery of MRVR after the end of stimulation exhibited two distinct time constants. The fast component had a time constant of 2.03 +/- 0.26 s and represented 60.2 +/- 1.71% of the recovery. The time constant of the slower component was 14.1 +/- 1.9 s and represented 36.0 +/- 1.6% of the recovery. The relationship between MRVR and stimulus frequency was sigmoidal with maximum sensitivity at stimulus frequencies of 12.6 +/- 0.76 Hz. Changes in urine flow rate, in contrast, followed a hyperbolic function with maximum response sensitivity occurring at very low stimulus frequencies. Changes in urine flow rate were 50% complete at stimulus frequencies of 5 Hz. Identification of two distinct components in the relaxation phase of renal vascular resistance leads to a reasonable hypothesis that 60% of total renal vascular resistance may lie proximal to the glomerulus, whereas 36% may be accounted for by the efferent arterioles.

The Presence of Vascular Mimicry Predicts High Risk of Clear Cell Renal Cell Carcinoma after Radical Nephrectomy.

PubMed

Zhou, Lin; Chang, Yuan; Xu, Le; Liu, Zheng; Fu, Qiang; Yang, Yuanfeng; Lin, Zongming; Xu, Jiejie

2016-08-01

Vascular mimicry is a type of tumor cell plasticity. The aim of this study was to determine the prognostic value of vascular mimicry in patients with clear cell renal cell carcinoma. We performed a retrospective cohort study in 387 patients with clear cell renal cell carcinoma who underwent radical nephrectomy at Zhongshan Hospital, Fudan University between 2008 and 2009. Pathological features, baseline patient characteristics and followup data were recorded. Vascular mimicry in clear cell renal cell carcinoma tissue was identified by CD31-periodic acid-Schiff double staining. Univariate and multivariate Cox regression models were used to analyze the impact of prognostic factors on recurrence-free survival. The concordance index and the Akaike information criterion were used to assess the predictive accuracy and sufficiency of different models. Positive vascular mimicry staining occurred in 25 of 387 clear cell renal cell carcinoma cases (6.5%) and it was associated with an increased risk of recurrence (log-rank p <0.001). Incorporating vascular mimicry into pT stage, Fuhrman grade and Leibovich score helped refine individual risk stratification. Moreover, vascular mimicry was identified as an independent prognostic factor (p = 0.001). It was entered into a nomogram together with pT stage, Fuhrman grade, tumor size and necrosis. In the primary cohort the Harrell concordance index for the established nomogram to predict recurrence-free survival was slightly higher than that of the Leibovich model (0.850 vs. 0.823), which failed to reach statistical significance (p = 0.158). Vascular mimicry could be a potential prognosticator for recurrence-free survival in patients with clear cell renal cell carcinoma after radical nephrectomy. Further external validation and functional analysis should be pursued to assess its potential prognostic and therapeutic values for clear cell renal cell carcinoma. Copyright © 2016 American Urological Association Education and Research

Early treatment with losartan effectively ameliorates hypertension and improves vascular remodeling and function in a prehypertensive rat model.

PubMed

He, De-Hua; Lin, Jin-Xiu; Zhang, Liang-Min; Xu, Chang-Sheng; Xie, Qiang

2017-03-15

Pharmacological treatment of prehypertension may ameliorate hypertension and improve vascular structure and function. This study investigated 1) whether early treatment with either losartan or amlodipine at the onset of prehypertension can prevent hypertension and 2) whether losartan and amlodipine equally improve vascular remodeling and function in a rat model of hypertension. Stroke-prone spontaneously hypertensive (SHRSP) rats were administered losartan, amlodipine or saline for 6 or 16weeks at the onset of prehypertension. Wistar-Kyoto rats were used as a control. All groups were observed for 40weeks. Systolic blood pressure was measured using the tail-cuff method. Vascular structure and function were determined by microscopy and vascular ring contractility assays, respectively. Angiotensin II (Ang II) and aldosterone (Aldo) were measured by radioimmunoassays. Angiotensin II type 1 receptor (AT1R) and angiotensin II type 2 receptor (AT2R) expression was measured by western blot. Losartan effectively reduced progression from prehypertension to hypertension as well as vascular remodeling and improved vascular contractility in SHRSP rats. Long-term losartan (16weeks) had greater benefits than short-term (6weeks) treatment. Losartan increased Ang II and decreased Aldo levels in the serum and vessel walls of resistance vessels in a time-dependent manner. Losartan significantly decreased AT1R and increased AT2R vascular expression. Amlodipine had no effect on vascular AT1R and AT2R expression. Losartan administered at the onset of prehypertension is more effective than amlodipine in ameliorating hypertension and improving vascular remodeling and function, which is likely mediated by the renin-angiotensin-aldosterone system. Copyright © 2017 Elsevier Inc. All rights reserved.

Reducing VEGF-B Signaling Ameliorates Renal Lipotoxicity and Protects against Diabetic Kidney Disease.

PubMed

Falkevall, Annelie; Mehlem, Annika; Palombo, Isolde; Heller Sahlgren, Benjamin; Ebarasi, Lwaki; He, Liqun; Ytterberg, A Jimmy; Olauson, Hannes; Axelsson, Jonas; Sundelin, Birgitta; Patrakka, Jaakko; Scotney, Pierre; Nash, Andrew; Eriksson, Ulf

2017-03-07

Diabetic kidney disease (DKD) is the most common cause of severe renal disease, and few treatment options are available today that prevent the progressive loss of renal function. DKD is characterized by altered glomerular filtration and proteinuria. A common observation in DKD is the presence of renal steatosis, but the mechanism(s) underlying this observation and to what extent they contribute to disease progression are unknown. Vascular endothelial growth factor B (VEGF-B) controls muscle lipid accumulation through regulation of endothelial fatty acid transport. Here, we demonstrate in experimental mouse models of DKD that renal VEGF-B expression correlates with the severity of disease. Inhibiting VEGF-B signaling in DKD mouse models reduces renal lipotoxicity, re-sensitizes podocytes to insulin signaling, inhibits the development of DKD-associated pathologies, and prevents renal dysfunction. Further, we show that elevated VEGF-B levels are found in patients with DKD, suggesting that VEGF-B antagonism represents a novel approach to treat DKD. Copyright © 2017 Elsevier Inc. All rights reserved.

Vascular and renal effects of dopamine during extracellular volume expansion: Role of nitric oxide pathway.

PubMed

Costa, María A; Elesgaray, Rosana; Loria, Analía; Balaszczuk, Ana María; Arranz, Cristina

2006-02-28

The aim of the study was to determine the possible role of NO-system activation in vascular and renal effects of the dopaminergic system and the probable interaction between both systems during acute volume expansion in rats. Expanded (10% bw) and non-expanded anaesthetized male Wistar rats were treated with haloperidol, a DA receptor antagonist (3 mg/kg bw, ip). Mean arterial pressure, diuresis, natriuresis, renal plasma flow, glomerular filtration rate, nitrites and nitrates excretion (NOx) were determined. NADPH diaphorase activity was measured using a histochemistry technique in kidney, aorta and renal arteries. NOS activity in kidney and aorta from expanded and non-expanded animals was determined with L-[U14C]-arginine substrate, in basal conditions and after DA (1 microM) administration. The hypotensive effect of L-arg and hypertension induced by L-NAME were not modified by haloperidol. This blocker reverted the increase in diuresis, natriuresis and RPF induced by L-arg in both groups. Dopaminergic blockade induced a decrease in NOx excretion and in NADPH-diaphorase activity in glomeruli, proximal tubule and medullar collecting duct and in endothelium and vascular smooth muscle of renal arteries. DA induced an increase in NOS activity in renal medulla and cortex in both groups, but no changes in the aorta were observed. Our results suggest that renal DA would be associated with the renal response induced by NO during extracellular volume expansion. NO-system activation would be one of the mechanisms involved in renal DA activity during saline load, but NO appears not to be involved in DA vascular effects.

The utility of 64 channel multidetector CT angiography for evaluating the renal vascular anatomy and possible variations: a pictorial essay.

PubMed

Kumar, Sheo; Neyaz, Zafar; Gupta, Archna

2010-01-01

The increased use of laparoscopic nephrectomy and nephron-sparing surgery has prompted the need for a more detailed radiological evaluation of the renal vascular anatomy. Multidetector CT angiography is a fast and accurate modality for assessing the precise anatomy of the renal vessels. In this pictorial review, we present the multidetector CT angiography appearances of the normal renal vascular anatomy and a spectrum of various anomalies that require accurate vascular depiction before undergoing surgical treatment.

Quercetin Attenuates Vascular Calcification through Suppressed Oxidative Stress in Adenine-Induced Chronic Renal Failure Rats.

PubMed

Chang, Xue-Ying; Cui, Lei; Wang, Xing-Zhi; Zhang, Lei; Zhu, Dan; Zhou, Xiao-Rong; Hao, Li-Rong

2017-01-01

This study investigated whether quercetin could alleviate vascular calcification in experimental chronic renal failure rats induced by adenine. 32 adult male Wistar rats were randomly divided into 4 groups fed normal diet, normal diet with quercetin supplementation (25 mg/kg·BW/d), 0.75% adenine diet, or adenine diet with quercetin supplementation. All rats were sacrificed after 6 weeks of intervention. Serum renal functions biomarkers and oxidative stress biomarkers were measured and status of vascular calcification in aorta was assessed. Furthermore, the induced nitric oxide synthase (iNOS)/p38 mitogen activated protein kinase (p38MAPK) pathway was determined to explore the potential mechanism. Adenine successfully induced renal failure and vascular calcification in rat model. Quercetin supplementation reversed unfavorable changes of phosphorous, uric acid (UA) and creatinine levels, malonaldehyde (MDA) content, and superoxide dismutase (SOD) activity in serum and the increases of calcium and alkaline phosphatase (ALP) activity in the aorta ( P < 0.05) and attenuated calcification and calcium accumulation in the medial layer of vasculature in histopathology. Western blot analysis showed that iNOS/p38MAPK pathway was normalized by the quercetin supplementation. Quercetin exerted a protective effect on vascular calcification in adenine-induced chronic renal failure rats, possibly through the modulation of oxidative stress and iNOs/p38MAPK pathway.

Quercetin Attenuates Vascular Calcification through Suppressed Oxidative Stress in Adenine-Induced Chronic Renal Failure Rats

PubMed Central

Chang, Xue-ying; Cui, Lei; Wang, Xing-zhi; Zhang, Lei; Zhu, Dan

2017-01-01

Background This study investigated whether quercetin could alleviate vascular calcification in experimental chronic renal failure rats induced by adenine. Methods 32 adult male Wistar rats were randomly divided into 4 groups fed normal diet, normal diet with quercetin supplementation (25 mg/kg·BW/d), 0.75% adenine diet, or adenine diet with quercetin supplementation. All rats were sacrificed after 6 weeks of intervention. Serum renal functions biomarkers and oxidative stress biomarkers were measured and status of vascular calcification in aorta was assessed. Furthermore, the induced nitric oxide synthase (iNOS)/p38 mitogen activated protein kinase (p38MAPK) pathway was determined to explore the potential mechanism. Results Adenine successfully induced renal failure and vascular calcification in rat model. Quercetin supplementation reversed unfavorable changes of phosphorous, uric acid (UA) and creatinine levels, malonaldehyde (MDA) content, and superoxide dismutase (SOD) activity in serum and the increases of calcium and alkaline phosphatase (ALP) activity in the aorta (P < 0.05) and attenuated calcification and calcium accumulation in the medial layer of vasculature in histopathology. Western blot analysis showed that iNOS/p38MAPK pathway was normalized by the quercetin supplementation. Conclusions Quercetin exerted a protective effect on vascular calcification in adenine-induced chronic renal failure rats, possibly through the modulation of oxidative stress and iNOs/p38MAPK pathway. PMID:28691026

Renal autotransplantation--a possibility in the treatment of complex renal vascular diseases and ureteric injuries.

PubMed

Hau, Hans Michael; Bartels, Michael; Tautenhahn, Hans-Michael; Morgul, Mehmet Haluk; Fellmer, Peter; Ho-Thi, Phuc; Benckert, Christoph; Uhlmann, Dirk; Moche, Michael; Thelen, Armin; Schmelzle, Moritz; Jonas, Sven

2012-12-31

We report our contemporary experiences with renal autotransplantation in patients with complicated renal vascular diseases and/or complex ureteral injuries. Since its first performance, renal autotransplantation has been steadily improved and become a safe and effective procedure. Between 1998 and 2006, 6 renal autotransplantations in 6 patients were performed at the University Medical Center of Leipzig. After nephrectomy and renal perfusion ex vivo, the kidney was implanted standardized in the fossa iliaca. The vessels were anastomized to the iliac vessels, the ureter was reimplanted in an extravesical tunneled ureteroneocystostomy technique according to Lich-Gregoir. Demographic, clinical, and laboratory data of the patients were collected and analyzed for pre-, intra-, and postoperative period. Indications for renal autotransplantation were complex renovascular diseases in 2 patients (1 with fibromuscular dysplasia and 1 with Takayasu's arteritis) and in 4 patients with complex ureteral injuries. The median duration of follow-up was 9.7 years (range: 5.6-13.3). The laboratory values of our 6 patients showed improvements of creatinine, urea and blood pressure levels in comparison to the preoperative status at the end of follow-up period. The present study reports excellent results of renal autotransplantation in patients with renovascular disease or complex ureteric injuries. After a median follow-up of 9.7 years all 6 patients present with stable renal function as well as normal blood pressure values. Postoperative complications were observed with a rate comparable to other studies.

Liver Metastases From Renal Oncocytoma With Vascular Extension.

PubMed

Cacciamani, Giovanni; Cima, Luca; Ficial, Miriam; Novella, Giovanni; Siracusano, Salvatore; Tedeschi, Umberto; Balzarro, Matteo; Montin, Umberto; Cerruto, Maria A; De Marco, Vincenzo; Porcaro, Antonio B; Hes, Ondrej; DʼErrico, Antonia; Martignoni, Guido; Ghimenton, Claudio; Zaza, Gianluigi; Artibani, Walter; Brunelli, Matteo; Eccher, Albino

2017-07-04

The 2016 World Health Organization Renal Tumor Classification defines renal oncocytoma (RO) as a benign epithelial tumor; however, malignant histopathologic features have been documented. Rare cases with metastases have been reported. We describe the case of a 62-year-old woman who was referred to the Urology Clinic for a routine work-up. Magnetic resonance imaging and computerized tomography showed a 7-cm mass in the middle and lower portions of the left kidney and 2 suspected liver metastases. The patient underwent surgery. Microscopically both renal and liver lesions presented solid, solid-nested, and microcystic architecture, composed predominantly of large eosinophilic cells without any worrisome pattern except the vascular extension. The cells were positive for S100A1, CD117, and PAX-8 and negative for CAIX, CK7, and AMACR. Fluorescence in situ hybridization showed a disomic profile for the chromosomes 1, 2, 6, 7, 10, 17. No mutation of coding sequence of the SDHB, SDHC, SDHD, VHL, and BHD genes and no loss of heterozygosity at 3p were found. The final diagnosis was "RO" according to the 2016 World Health Organization Renal Tumor Classification with "liver metastases." This report provides a wide clinical-pathologic, immunophenotypical and molecular documentation of a RO with liver metastases.

Erhuang Formula ameliorates renal damage in adenine-induced chronic renal failure rats via inhibiting inflammatory and fibrotic responses.

PubMed

Zhang, Chun-Yan; Zhu, Jian-Yong; Ye, Ying; Zhang, Miao; Zhang, Li-Jun; Wang, Su-Juan; Song, Ya-Nan; Zhang, Hong

2017-11-01

The present study aimed to evaluate the protective effects of Erhuang Formula (EHF) and explore its pharmacological mechanisms on adenine-induced chronic renal failure (CRF). The compounds in EHF were analyzed by HPLC/MS. Adenine-induced CRF rats were administrated by EHF. The effects were evaluated by renal function examination and histology staining. Immunostaining of some proteins related cell adhesion was performedin renal tissues, including E-cadherin, β-catenin, fibronectin and laminin. The qRT-PCR was carried out determination of gene expression related inflammation and fibrosis including NF-κB, TNF-α, TGF-β1, α-SMA and osteopontin (OPN). Ten compounds in EHF were identified including liquiritigenin, farnesene, vaccarin, pachymic acid, cycloastragenol, astilbin, 3,5,6,7,8,3',4'-heptemthoxyflavone, physcion, emodin and curzerene. Abnormal renal function and histology had significant improvements by EHF treatment. The protein expression of β-catenin, fibronectin and laminin were significantly increased and the protein expression of E-cadherin significantly decreased in CRF groups. However, these protein expressions were restored to normal levels in EHF group. Furthermore, low expression of PPARγ and high expression of NF-κB, TNF-α, TGF-β1, α-SMA and OPN were substantially restored by EHF treatment in a dose-dependent manner. EHF ameliorated renal damage in adenine-induced CRF rats, and the mechanisms might involve in the inhibition of inflammatory and fibrotic responses and the regulation of PPARγ, NF-κB and TGF-β signaling pathways. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Lycium chinense leaves extract ameliorates diabetic nephropathy by suppressing hyperglycemia mediated renal oxidative stress and inflammation.

PubMed

Olatunji, Opeyemi Joshua; Chen, Hongxia; Zhou, Yifeng

2018-06-01

Diabetic nephropathy is one of the most serious and most frequently encountered diabetic complication, accounting for the highest cause of end-stage renal disease. This present study was aimed at exploring the protective/attenuative effect of Lycium chinense leaf extract (MELC) on streptozotocin induced diabetic nephropathy in experimental Sprague Dawley rats. The oral administration of diabetic rats with MELC markedly ameliorated renal dysfunction as observed in the significant reduction in the serum levels of creatinine, blood urea nitrogen (BUN), albumin and TGF-β1 as compared to the untreated diabetic control rats. In addition, the elevated levels of renal oxidative stress markers and pro-inflammatory parameters (GSH, SOD, CAT, MDA, TNF-α, IL-6 and IL-1β) were significantly reduced in MELC treated diabetic rats. The results obtained in this study suggests that L. chinense leaf might have the potential as possible pharmacological agent against diabetic nephropathy by suppressing renal oxidative stress and inflammation. Copyright © 2018. Published by Elsevier Masson SAS.

Ameliorative Effect of Allopurinol on Vascular Complications of Insulin Resistance

PubMed Central

El-Bassossy, Hany M.; Elberry, Ahmed A.; Azhar, Ahmad; Ghareib, Salah A.; Alahdal, Abdulrahman M.

2015-01-01

The aim of the current study was to evaluate the possible protective effect of allopurinol (Allo) on experimentally induced insulin resistance (IR) and vascular complications. Rats were divided into four groups: control, IR, allopurinol-treated IR (IR-Allo), and allopurinol-treated control (Allo). IR was induced by adding fructose and high fat, high salt diet for 12 weeks. The results showed that Allo has alleviated the increased level of TNF-α and the systolic, diastolic, mean, and notch pressure observed in IR with no change in pulse pressure. In addition, Allo decreased the heart rate in the treated group compared to IR rats. On the other hand, it has no effect on increased levels of insulin, glucose, fructosamine, or body weight gain compared to IR group, while it increased significantly the insulin level and body weight without hyperglycemia in the control group. Moreover, Allo treatment ameliorated increased level of 4HNE, Ang II, and Ang R1. In conclusion, the results of the current study show that Allo has a protective effect on vascular complications of IR which may be attributed to the effect of Allo on decreasing the TNF-α, 4HNE, Ang II, and Ang R1 as well as increasing the level of insulin secretion. PMID:25785277

Critical role of renal dipeptidyl peptidase-4 in ameliorating kidney injury induced by saxagliptin in Dahl salt-sensitive hypertensive rats.

PubMed

Sakai, Mariko; Uchii, Masako; Myojo, Kensuke; Kitayama, Tetsuya; Kunori, Shunji

2015-08-15

Saxagliptin, a potent dipeptidyl peptidase-4 (DPP-4) inhibitor, is currently used to treat type 2 diabetes mellitus, and it has been reported to exhibit a slower rate of dissociation from DPP-4 compared with another DPP-4 inhibitor, sitagliptin. In this study, we compared the effects of saxagliptin and sitagliptin on hypertension-related renal injury and the plasma and renal DPP-4 activity levels in Dahl salt-sensitive hypertensive (Dahl-S) rats. The high-salt diet (8% NaCl) significantly increased the blood pressure and quantity of urinary albumin excretion and induced renal glomerular injury in the Dahl-S rats. Treatment with saxagliptin (14mg/kg/day via drinking water) for 4 weeks significantly suppressed the increase in urinary albumin excretion and tended to ameliorate glomerular injury without altering the blood glucose levels and systolic blood pressure. On the other hand, the administration of sitagliptin (140mg/kg/day via drinking water) did not affect urinary albumin excretion and glomerular injury in the Dahl-S rats. Meanwhile, the high-salt diet increased the renal DPP-4 activity but did not affect the plasma DPP-4 activity in the Dahl-S rats. Both saxagliptin and sitagliptin suppressed the plasma DPP-4 activity by 95% or more. Although the renal DPP-4 activity was also inhibited by both drugs, the inhibitory effect of saxagliptin was more potent than that of sitagliptin. These results indicate that saxagliptin has a potent renoprotective effect in the Dahl-S rats, independent of its glucose-lowering actions. The inhibition of the renal DPP-4 activity induced by saxagliptin may contribute to ameliorating renal injury in hypertension-related renal injury. Copyright © 2015 Elsevier B.V. All rights reserved.

Mid-Term Vascular Safety of Renal Denervation Assessed by Follow-up MR Imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schmid, Axel, E-mail: axel.schmid@uk-erlangen.de; Schmieder, Raphael; Lell, Michael

Background/AimsRenal denervation (RDN) emerged as a treatment option for reducing blood pressure (BP) in patients with treatment-resistant hypertension (TRH). However, concerns have been raised regarding the incidence of late renal artery stenosis or thromboembolism after RDN. The goal of the current study was, therefore, to conduct a prospective clinical trial on the mid-term vascular integrity of the renal arteries and the perfusion of the renal parenchyma assessed by magnetic resonance imaging (MRI) in the follow-up after catheter-based RDN.MethodsIn our single-centre investigator initiated study, 51 patients with true TRH underwent catheter-based RDN using the Symplicity Flex{sup TM} catheter (Medtronic Inc., Palomore » Alto, CA). Follow-up MRI was performed at a median of 11 months (interquartile range 6–18 months) after RDN on a 1.5T MR unit. High-resolution MR angiography (MRA) and MRI results were compared to the baseline digital angiography of renal arteries obtained at time of RDN. In case of uncertainties (N = 2) catheter angiography was repeated.ResultsBoth office and 24-h ambulatory BP were significantly reduced 6 and 12 months after RDN. Renal function remained unchanged 6 and 12 months after RDN. In all patients, MRA excluded new or progression of pre-existing low grade renal artery stenosis as well as focal aneurysms at the sites of radiofrequency ablation. In none of the patients new segmental perfusion deficits in either kidney were detected on MRI.ConclusionsNo vascular or parenchymal complications after radiofrequency-based RDN were detected in 51 patients followed up by MRI.« less

PO-60 - Renal tumors with extensive vascular disease: management challenges in a pediatric series from the Hospital for Sick Children.

PubMed

Zamperlini-Netto, G; Zanette, A; Wehbi, E; Williams, S; Grant, R M; Brandao, L R

2016-04-01

Venous thrombotic events (VTE) are becoming more and more common in children, particularly in the hospital setting. To date, 1 in 200 children admitted to tertiary pediatric hospitals are now being recognized to develop VTE. Amongst those patients with an identified thrombotic occlusion, pediatric patients diagnosed with renal tumors have long been recognized, but their ideal management in the instances of vascular invasion remains controversial. We describe the clinical behavior of patients diagnosed with renal tumors and extra renal vascular involvement at The Hospital for Sick Children in Toronto, Canada. A retrospective analysis was conducted in patients diagnosed from 1990 to 2012. Data collected included: age, gender, symptoms at presentation, staging, pathology report, radiological evidence of intravascular thrombus [i.e. renal veins (RV), inferior vena cava (IVC) and right atrium (RA)], intraoperative findings, therapeutic protocol implemented and anticoagulation; for outcomes, tumor and/or thrombus recurrence, thromboembolic phenomena [i.e. pulmonary embolism (PE)] and survival. Of 299 patients with renal tumors identified, 292 were included: Wilms (219), Renal Cell Carcinoma (RCC, 29), Clear Cell Sarcoma of the Kidney (CCSK, 12), others (32). The median age of the group was 4.53years (4days - 18 years). Extra renal vascular disease was identified in 29 patients, with a median age 7.05years (0.6-16 years; p=0.03), including Wilms tumors (22/219, 10%), RCC (2/29, 7%), CCSK (1/12, 8.3%) and others (4/32, 12.5%; p=0.01). Vascular involvement comprised exclusive evidence of RV disease (7), IVC disease (19; 15 infra-hepatic), RA disease (3) and PE (5).Treatment escalation because of vascular disease included neo-adjuvant chemotherapy (12; Wilms [11], RCC [1]), intraoperative cavectomy/ thrombectomy (1; Wilms), and cavotomies (11 Wilms [7], RCC [1], CCSK [1], PNET [1], sarcoma [1]). Four patients were placed under cardiopulmonary bypass. Anticoagulation was

Ex Vivo Resection and Renal Autotransplantation for the Treatment of a Large Renal Vein Aneurysm Causing Recurrent Pulmonary Embolism and a Coexisting Vascular Malformation: A Case Report.

PubMed

Özyüksel, Arda; Aktaş, Sema; Çalıs, Elif; Erol, Cengiz; Sevmiş, Şinasi

2016-08-01

A 36-year-old young woman with a medical history of recurrent pulmonary embolism and chronic pelvic pain was admitted to our hospital. Contrast-enhanced imaging techniques revealed a large left renal vein aneurysm with a coexisting vascular mass. The patient was operated on electively, and the left kidney was autotransplanted to the right ileac fossa following the ex vivo resection of the vascular mass and the left renal vein aneurysm. Herein, we report an unusual coexistence of a vascular mass and recurrent pulmonary embolism treated successfully with our surgical treatment strategy. © The Author(s) 2016.

Longitudinal Assessment of Vascular Function With Sunitinib in Patients With Metastatic Renal Cell Carcinoma.

PubMed

Catino, Anna B; Hubbard, Rebecca A; Chirinos, Julio A; Townsend, Ray; Keefe, Stephen; Haas, Naomi B; Puzanov, Igor; Fang, James C; Agarwal, Neeraj; Hyman, David; Smith, Amanda M; Gordon, Mary; Plappert, Theodore; Englefield, Virginia; Narayan, Vivek; Ewer, Steven; ElAmm, Chantal; Lenihan, Daniel; Ky, Bonnie

2018-03-01

Sunitinib, used widely in metastatic renal cell carcinoma, can result in hypertension, left ventricular dysfunction, and heart failure. However, the relationships between vascular function and cardiac dysfunction with sunitinib are poorly understood. In a multicenter prospective study of 84 metastatic renal cell carcinoma patients, echocardiography, arterial tonometry, and BNP (B-type natriuretic peptide) measures were performed at baseline and at 3.5, 15, and 33 weeks after sunitinib initiation, correlating with sunitinib cycles 1, 3, and 6. Mean change in vascular function parameters and 95% confidence intervals were calculated. Linear regression models were used to estimate associations between vascular function and left ventricular ejection fraction, longitudinal strain, diastolic function (E/e'), and BNP. After 3.5 weeks of sunitinib, mean systolic blood pressure increased by 9.5 mm Hg (95% confidence interval, 2.0-17.1; P =0.02) and diastolic blood pressure by 7.2 mm Hg (95% confidence interval, 4.3-10.0; P <0.001) across all participants. Sunitinib resulted in increases in large artery stiffness (carotid-femoral pulse wave velocity) and resistive load (total peripheral resistance and arterial elastance; all P <0.05) and changes in pulsatile load (total arterial compliance and wave reflection). There were no statistically significant associations between vascular function and systolic dysfunction (left ventricular ejection fraction and longitudinal strain). However, baseline total peripheral resistance, arterial elastance, and aortic impedance were associated with worsening diastolic function and filling pressures over time. In patients with metastatic renal cell carcinoma, sunitinib resulted in early, significant increases in blood pressure, arterial stiffness, and resistive and pulsatile load within 3.5 weeks of treatment. Baseline vascular function parameters were associated with worsening diastolic but not systolic function. © 2018 American Heart

Vascular Smooth Muscle-Specific EP4 Receptor Deletion in Mice Exacerbates Angiotensin II-Induced Renal Injury.

PubMed

Thibodeau, Jean-Francois; Holterman, Chet E; He, Ying; Carter, Anthony; Cron, Gregory O; Boisvert, Naomi C; Abd-Elrahman, Khaled S; Hsu, Karolynn J; Ferguson, Stephen S G; Kennedy, Christopher R J

2016-10-20

Cyclooxygenase inhibition by non-steroidal anti-inflammatory drugs is contraindicated in hypertension, as it may reduce glomerular filtration rate (GFR) and renal blood flow. However, the identity of the specific eicosanoid and receptor underlying these effects is not known. We hypothesized that vascular smooth muscle prostaglandin E2 (PGE2) E-prostanoid 4 (EP4) receptor deletion predisposes to renal injury via unchecked vasoconstrictive actions of angiotensin II (AngII) in a hypertension model. Mice with inducible vascular smooth muscle cell (VSMC)-specific EP4 receptor deletion were generated and subjected to AngII-induced hypertension. EP4 deletion was verified by PCR of aorta and renal vessels, as well as functionally by loss of PGE2-mediated mesenteric artery relaxation. Both AngII-treated groups became similarly hypertensive, whereas albuminuria, foot process effacement, and renal hypertrophy were exacerbated in AngII-treated EP4 VSMC-/- but not in EP4 VSMC+/+ mice and were associated with glomerular scarring, tubulointerstitial injury, and reduced GFR. AngII-treated EP4 VSMC-/- mice exhibited capillary damage and reduced renal perfusion as measured by fluorescent bead microangiography and magnetic resonance imaging, respectively. NADPH oxidase 2 (Nox2) expression was significantly elevated in AngII-treated EP4 -/- mice. EP4-receptor silencing in primary VSMCs abolished PGE2 inhibition of AngII-induced Nox2 mRNA and superoxide production. These data suggest that vascular EP4 receptors buffer the actions of AngII on renal hemodynamics and oxidative injury. EP4 agonists may, therefore, protect against hypertension-associated kidney damage. Antioxid. Redox Signal. 25, 642-656.

Protein kinase CK2α catalytic subunit ameliorates diabetic renal inflammatory fibrosis via NF-κB signaling pathway.

PubMed

Huang, Junying; Chen, Zhiquan; Li, Jie; Chen, Qiuhong; Li, Jingyan; Gong, Wenyan; Huang, Jiani; Liu, Peiqing; Huang, Heqing

2017-05-15

Activation of casein kinase 2 (CK2) is closely linked to the body disturbance of carbohydrate metabolism and inflammatory reaction. The renal chronic inflammatory reaction in the setting of diabetes is one of the important hallmarks of diabetic renal fibrosis. However, it remains unknown whether CK2 influences the process of diabetic renal fibrosis. The current study is aimed to investigate if CK2α ameliorates renal inflammatory fibrosis in diabetes via NF-κB pathway. To explore potential regulatory mechanism of CK2α, the expression and activity of CK2α, which were studied by plasmid transfection, selective inhibitor, small-interfering RNA (siRNA) and adenovirus infection in vitro or in vivo, were analyzed by means of western blotting (WB), dual luciferase reporter assay and electrophoretic mobility shift assay (EMSA). The following findings were observed: (1) Expression of CK2α was upregulated in kidneys of db/db and KKAy diabetic mice; (2) Inhibition of CK2α kinase activity or knockdown of CK2α protein expression suppressed high glucose-induced expressions of FN and ICAM-1 in glomerular mesangial cells (GMCs); (3) Inhibition of CK2α kinase activity or knockdown of CK2α protein expression not only restrained IκB degradation, but also suppressed HG-induced nuclear accumulation, transcriptional activity and DNA binding activity of NF-κB in GMCs; (4) Treatment of TBB or CK2α RNAi adenovirus infection ameliorated renal fibrosis in diabetic animals; (5) Treatment of TBB or CK2α RNAi adenovirus infection suppressed IκB degradation and NF-κB nuclear accumulation in glomeruli of diabetic animals. This study indicates the essential role of CK2α in regulating the diabetic renal pathological process of inflammatory fibrosis via NF-κB pathway, and inhibition of CK2α may serve as a promising therapeutic strategy for diabetic nephropathy. Copyright © 2017 Elsevier Inc. All rights reserved.

Structured DAG oil ameliorates renal injury in streptozotocin-induced diabetic rats through inhibition of NF-κB and activation of Nrf2 pathway.

PubMed

Das, Kankana; Ghosh, Mahua

2017-02-01

Accumulating evidence suggested that inflammatory processes are involved in the development of diabetic nephropathy (DN). Here, we have tested the hypothesis that Caprylic Acid (Cy)-diacylglycerol (DAG) oil (Cy-DAG), a novel structurally formulated lipid with high nutritional value, ameliorated DN in streptozotocin (STZ)-induced diabetic rats through the anti-inflammatory mechanisms. Basic hematological, biochemical parameters, immunoblotting, immunofluorescence and flow cytometry analysis were performed to observe the anti-inflammatory potential of Cy-DAG oil. The data revealed that STZ significantly increased the renal oxidative stress markers and decreased the levels of renal enzymatic and non-enzymatic antioxidants. Moreover, renal nitric oxide (NO), tissue necrosis factor-α (TNF-α), interleukin-6 (IL-6) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) were also increased in the renal tissue of STZ-treated rats. Further, DAG oil pretreatment produced a significant improvement in renal antioxidant status, reduced the lipid peroxidation and the levels of inflammatory markers in STZ-treated kidney. Similarly, results of protein expression showed that DAG oil pretreatment normalized the renal expression of Nrf2/Keap1 and its downstream regulatory proteins in STZ-treated condition. Immunohistochemical observations provided further evidence that DAG oil effectively protected the kidney from STZ-mediated oxidative damage. These results suggested that the DAG oil ameliorated STZ-induced oxidative renal injury by the activation of AKT/Nrf2/HO-1 pathway and the inhibition of ROS/MAPK/NF-κB pathway. Copyright © 2016 Elsevier Ltd. All rights reserved.

Taurine Ameliorates Renal Oxidative Damage and Thyroid Dysfunction in Rats Chronically Exposed to Fluoride.

PubMed

Adedara, Isaac A; Ojuade, Temini Jesu D; Olabiyi, Bolanle F; Idris, Umar F; Onibiyo, Esther M; Ajeigbe, Olufunke F; Farombi, Ebenezer O

2017-02-01

Excessive exposure to fluoride poses several detrimental effects to human health particularly the kidney which is a major organ involved in its elimination from the body. The influence of taurine on fluoride-induced renal toxicity was investigated in a co-exposure paradigm for 45 days using five groups of eight rats each. Group I rats received normal drinking water alone, group II rats were exposed to sodium fluoride (NaF) in drinking water at 15 mg/L alone, group III received taurine alone at a dose of 200 mg/kg group IV rats were co-administered with NaF and taurine (100 mg/kg), while group V rats were co-administered with NaF and taurine (200 mg/kg). Administration of taurine significantly reversed the fluoride-mediated decrease in absolute weight and organo-somatic index of the kidney in the exposed rats. Taurine significantly prevented fluoride-induced elevation in plasma urea and creatinine levels in the exposed rats. Moreover, taurine restored fluoride-mediated decrease in the circulatory concentrations of triiodothyronine, thyroxine, and the ratio of triiodothyronine to thyroxine. Taurine ameliorated fluoride-mediated decrease in renal antioxidant status by significantly enhancing the antioxidant enzyme activities as well as glutathione level in the exposed rats. Additionally, taurine inhibited fluoride-induced renal oxidative damage by markedly decreasing the hydrogen peroxide and malondialdehyde levels as well as improved the kidney architecture in the treated rats. Collectively, taurine protected against fluoride-induced renal toxicity via enhancement of thyroid gland function, renal antioxidant status, and histology in rats.

Use of computed tomography renal angiography for screening feline renal transplant donors.

PubMed

Bouma, Jennifer L; Aronson, Lillian R; Keith, Dennis G; Saunders, H Mark

2003-01-01

Preoperative knowledge of the renal vascular anatomy is important for selection of the appropriate feline renal donor. Intravenous urograms (IVUs) have been performed routinely to screen potential donors at the Veterinary Hospital of the University of Pennsylvania (VHUP), but the vascular phase views lack sufficient detail of the renal vascular anatomy. Computed tomography angiography (CTA), which requires a helical computed tomography (CT) scanner, has been found to provide superior renal vascular anatomic information of prospective human renal donors. The specific aims of this study were as follows: 1) develop the CTA technique for the feline patient; and 2) obtain preliminary information on feline renal vessel anatomy in potential renal donors. Ten healthy, potential feline renal donors were anesthetized and imaged using a third-generation helical CT scanner. The time delay between i.v. contrast medium injection and image acquisition, and other parameters of slice collimation, slice interval, pitch, exposure settings, and reconstruction algorithms were varied to maximize contrast medium opacification of the renal vascular anatomy. Optimal CTA acquisition parameters were determined to be: 1) 10-sec delay post-i.v. bolus of iodinated contrast medium; 2) two serially acquired (corresponding to arterial and venous phases) helical scans through the renal vasculature; 3) pitch of 2 (4 mm/sec patient translation, 2 mm slice collimation); and 4) 120-kVp, 160-mA, and 1-sec exposure settings. Retrospective reconstructed CTA transverse images obtained at a 2-mm slice width and a 1-mm slice interval in combination with two-dimensional reformatted images and three-dimensional reconstructed images were qualitatively evaluated for vascular anatomy; vascular anatomy was confirmed at surgery. Four cats had single renal arteries and veins bilaterally; four cats had double renal veins. One cat had a small accessory artery supplying the caudal pole of the left kidney. One cat had a

Determinants of impaired renal and vascular function are associated with elevated levels of procoagulant factors in the general population.

PubMed

Dekkers, I A; de Mutsert, R; de Vries, A P J; Rosendaal, F R; Cannegieter, S C; Jukema, J W; le Cessie, S; Rabelink, T J; Lamb, H J; Lijfering, W M

2018-03-01

Essentials Why venous thrombosis is more prevalent in chronic kidney disease is unclear. We investigated whether renal and vascular function are associated with hypercoagulability. Coagulation factors showed a procoagulant shift with impaired renal and vascular function. This suggests that renal and vascular function play a role in the etiology of thrombosis. Background Impaired renal and vascular function have been associated with venous thrombosis, but the mechanism is unclear. Objectives We investigated whether estimated glomerular filtration rate (eGFR), urinary albumin-creatinine ratio (UACR), and pulse wave velocity (PWV) are associated with a procoagulant state. Methods In this cross-sectional analysis of the NEO Study, eGFR, UACR, fibrinogen, and coagulation factors (F)VIII, FIX and FXI were determined in all participants (n = 6536), and PWV was assessed in a random subset (n = 2433). eGFR, UACR and PWV were analyzed continuously and per percentile: per six categories for eGFR (> 50 th [reference] to < 1st) and UACR (< 50 th [reference] to > 99th), and per four categories (< 50 th [reference] to > 95th percentile) for PWV. Linear regression was used and adjusted for age, sex, total body fat, smoking, education, ethnicity, total cholesterol, C-reactive protein (CRP) and vitamin K antagonists use (FIX). Results Mean age was 55.6 years, mean eGFR 86.0 (12SD) mL 1.73 m - ² and median UACR 0.4 mg mmol -1 (25th, 75th percentile; 0.3, 0.7). All coagulation factors showed a procoagulant shift with lower renal function and albuminuria. For example, FVIII was 22 IU dL -1 (95% CI, 13-32) higher in the eGFR < 1st percentile compared with the > 50th percentile, and FVIII was 12 IU dL -1 (95% CI, 3-22) higher in the UACR > 99th percentile compared with the < 50th percentile. PWV was positively associated with coagulation factors FIX and FXI in continuous analysis; per m/s difference in PWV, FIX was 2.0 IU dL -1 (95% CI, 0.70-3.2) higher

Renal vascular responses to static handgrip: role of muscle mechanoreflex

NASA Technical Reports Server (NTRS)

Momen, Afsana; Leuenberger, Urs A.; Ray, Chester A.; Cha, Susan; Handly, Brian; Sinoway, Lawrence I.

2003-01-01

During exercise, the sympathetic nervous system is activated, which causes vasoconstriction. The autonomic mechanisms responsible for this vasoconstriction vary based on the particular tissue being studied. Attempts to examine reflex control of the human renal circulation have been difficult because of technical limitations. In this report, the Doppler technique was used to examine renal flow velocity during four muscle contraction paradigms in conscious humans. Flow velocity was divided by mean arterial blood pressure to yield an index of renal vascular resistance (RVR). Fatiguing static handgrip (40% of maximal voluntary contraction) increased RVR by 76%. During posthandgrip circulatory arrest, RVR remained above baseline (2.1 +/- 0.2 vs. 2.8 +/- 0.2 arbitrary units; P < 0.017) but was only 40% of the end-grip RVR value. Voluntary biceps contraction increased RVR within 10 s of initiation of contraction. This effect was not associated with an increase in blood pressure. Finally, involuntary biceps contraction also raised RVR. We conclude that muscle contraction evokes renal vasoconstriction in conscious humans. The characteristic of this response is consistent with a primary role for mechanically sensitive afferents. This statement is based on the small posthandgrip circulatory arrest response and the vasoconstriction that was observed with involuntary biceps contraction.

Febuxostat ameliorates diabetic renal injury in a streptozotocin-induced diabetic rat model.

PubMed

Lee, Hong-Joo; Jeong, Kyung Hwan; Kim, Yang Gyun; Moon, Joo Young; Lee, Sang Ho; Ihm, Chun Gyoo; Sung, Ji Youn; Lee, Tae Won

2014-01-01

Oxidative stress and inflammation are known to play central roles in the development of diabetic nephropathy (DN). Febuxostat is a novel non-purine xanthine oxidase (XO)-specific inhibitor developed to treat hyperuricemia. In this study, we investigated whether febuxostat could ameliorate DN via renoprotective mechanisms such as alleviation of oxidative stress and anti-inflammatory actions. Male Sprague-Dawley rats were divided into three groups: a normal group, a diabetes group (DM group), and a febuxostat-treated diabetes group (DM+Fx group). We administered 5 mg/kg of febuxostat to experimental rats for 7 weeks and evaluated clinical and biochemical parameters and XO and xanthine dehydrogenase (XDH) activity in hepatic tissue. The degree of oxidative stress and extent of inflammation were evaluated from urine samples and renal tissue collected from each group. Diabetic rats (DM and DM+Fx groups) had higher blood glucose and kidney weight relative to body weight than normal rats. Albuminuria was significantly reduced in febuxostat-treated diabetic rats compared with untreated diabetic rats. Quantitative analysis showed that hepatic XO and XDH activities were higher in the DM groups, but decreased after treatment with febuxostat. Urinary 8-OHdG concentrations and renal cortical nitrotyrosine also indicated reduced oxidative stress in the DM+Fx group relative to the DM group. The number of ED-1-stained cells in the glomerulus and tubule of diabetic renal tissue decreased in febuxostat-treated diabetic rats relative to that of non-treated diabetic rats. Diabetic rats also expressed higher transcript levels of inflammatory genes (E-selectin and VCAM-1), an inflammation-induced enzyme (COX-2), and inflammatory mediators (ED-1 and NF-κB) than control rats; expression of these genes was significantly reduced by treatment with febuxostat. Febuxostat prevents diabetic renal injury such as albuminuria. This renoprotective effect appears to be due to attenuation of the

Congenital capillary proliferation of the kidney: a distinctive renal vascular lesion of childhood.

PubMed

Cajaiba, Mariana M; North, Paula E; Gong, Shunyou; Dickman, Paul S; Mroczek-Musulman, Elizabeth; Sauer, David A; Perlman, Elizabeth J

2017-08-01

Renal vascular lesions (RVL) are rare, and their morphological spectrum remains largely unknown, particularly in children. In this study, we characterize the clinicopathological features of RVL in a cohort of 12 children. Seven lesions were classified as previously recognized entities: vascular malformations (4), papillary endothelial hyperplasia (2), and pyogenic granuloma (lobular capillary hemangioma; 1). An eighth lesion showed nonspecific findings, which were interpreted as reactive during our review. The remaining 4 cases presented either prenatally, at birth, or shortly after birth and were morphologically similar. These were characterized by a peculiar pattern of capillary proliferation with entrapment of native renal structures, variable amounts of extramedullary hematopoiesis and reactive lymphocytes, foci of infarction and hemorrhage, and the presence of feeding and draining vessels at their periphery. To our knowledge, this represents a previously undescribed congenital vascular lesion involving the kidney, which we have descriptively and provisionally termed congenital capillary proliferation of the kidney (CCPK). While it is unclear whether CCPK represents a malformation or neoplastic proliferation, it shows overlapping features with congenital hemangioma of the liver (solitary congenital hepatic hemangioma) and congenital nonprogressive hemangioma (CNH) of the skin and soft tissue, suggesting a possible common pathogenesis among these 3 entities. Copyright © 2017 Elsevier Inc. All rights reserved.

Targeting of the pulmonary capillary vascular niche promotes lung alveolar repair and ameliorates fibrosis

PubMed Central

Cao, Zhongwei; Lis, Raphael; Ginsberg, Michael; Chavez, Deebly; Shido, Koji; Rabbany, Sina Y.; Fong, Guo-Hua; Sakmar, Thomas P.; Rafii, Shahin; Ding, Bi-Sen

2016-01-01

Although the lung can undergo self-repair after injury, fibrosis in chronically injured or diseased lungs can occur at the expense of regeneration. Here we study how a hematopoietic-vascular niche regulates alveolar repair and lung fibrosis. Using intratracheal injection of bleomycin or hydrochloric acid in mice, we show that repetitive lung injury activates pulmonary capillary endothelial cells (PCECs) and perivascular macrophages, impeding alveolar repair and promoting fibrosis. Whereas the chemokine receptor CXCR7, expressed on PCECs, acts to prevent epithelial damage and ameliorate fibrosis after a single round of treatment with bleomycin or hydrochloric acid, repeated injury leads to suppression of CXCR7 expression and recruitment of vascular endothelial growth factor receptor 1 (VEGFR1)-expressing perivascular macrophages. This recruitment stimulates Wnt/β-catenin–dependent persistent upregulation of the Notch ligand Jagged1 (encoded by Jag1) in PCECs, which in turn stimulates exuberant Notch signaling in perivascular fibroblasts and enhances fibrosis. Administration of a CXCR7 agonist or PCEC-targeted Jag1 shRNA after lung injury promotes alveolar repair and reduces fibrosis. Thus, targeting of a maladaptbed hematopoietic-vascular niche, in which macrophages, PCECs and perivascular fibroblasts interact, may help to develop therapy to spur lung regeneration and alleviate fibrosis. PMID:26779814

Targeting of the pulmonary capillary vascular niche promotes lung alveolar repair and ameliorates fibrosis.

PubMed

Cao, Zhongwei; Lis, Raphael; Ginsberg, Michael; Chavez, Deebly; Shido, Koji; Rabbany, Sina Y; Fong, Guo-Hua; Sakmar, Thomas P; Rafii, Shahin; Ding, Bi-Sen

2016-02-01

Although the lung can undergo self-repair after injury, fibrosis in chronically injured or diseased lungs can occur at the expense of regeneration. Here we study how a hematopoietic-vascular niche regulates alveolar repair and lung fibrosis. Using intratracheal injection of bleomycin or hydrochloric acid in mice, we show that repetitive lung injury activates pulmonary capillary endothelial cells (PCECs) and perivascular macrophages, impeding alveolar repair and promoting fibrosis. Whereas the chemokine receptor CXCR7, expressed on PCECs, acts to prevent epithelial damage and ameliorate fibrosis after a single round of treatment with bleomycin or hydrochloric acid, repeated injury leads to suppression of CXCR7 expression and recruitment of vascular endothelial growth factor receptor 1 (VEGFR1)-expressing perivascular macrophages. This recruitment stimulates Wnt/β-catenin-dependent persistent upregulation of the Notch ligand Jagged1 (encoded by Jag1) in PCECs, which in turn stimulates exuberant Notch signaling in perivascular fibroblasts and enhances fibrosis. Administration of a CXCR7 agonist or PCEC-targeted Jag1 shRNA after lung injury promotes alveolar repair and reduces fibrosis. Thus, targeting of a maladapted hematopoietic-vascular niche, in which macrophages, PCECs and perivascular fibroblasts interact, may help to develop therapy to spur lung regeneration and alleviate fibrosis.

Tongxinluo ameliorates renal structure and function by regulating miR-21-induced epithelial-to-mesenchymal transition in diabetic nephropathy.

PubMed

Wang, Jin-yang; Gao, Yan-bin; Zhang, Na; Zou, Da-wei; Xu, Li-ping; Zhu, Zhi-yao; Li, Jiao-yang; Zhou, Sheng-nan; Cui, Fang-qiang; Zeng, Xiang-jun; Geng, Jian-guo; Yang, Jin-kui

2014-03-01

Diabetic nephropathy (DN) is one of the most important diabetic microangiopathies. The epithelial-to-mesenchymal transition (EMT) plays an important role in DN. The physiological role of microRNA-21 (miR-21) was closely linked to EMT. However, it remained elusive whether tongxinluo (TXL) ameliorated renal structure and function by regulating miR-21-induced EMT in DN. This study aimed to determine the effect of TXL on miR-21-induced renal tubular EMT and to explore the relationship between miR-21 and TGF-β1/smads signals. Real-time RT-PCR, cell transfection, in situ hybridization (ISH), and laser confocal microscopy were used, respectively. Here, we revealed that TXL dose dependently lowered miR-21 expression in tissue, serum, and cells. Overexpression of miR-21 can enhance α-smooth muscle actin (SMA) expression and decrease E-cadherin expression by upregulating smad3/p-smad3 expression and downregulating smad7 expression. Interestingly, TXL also increased E-cadherin expression and decreased α-SMA expression by regulating miR-21 expression. More importantly, TXL decreased collagen IV, fibronectin, glomerular basement membrane, glomerular area, and the albumin/creatinine ratio, whereas it increased the creatinine clearance ratio. The results demonstrated that TXL ameliorated renal structure and function by regulating miR-21-induced EMT, which was one of the mechanisms to protect against DN, and that miR-21 may be one of the therapeutic targets for TXL in DN.

A novel angiotensin II type 1 receptor-associated protein induces cellular hypertrophy in rat vascular smooth muscle and renal proximal tubular cells.

PubMed

Guo, Deng-Fu; Tardif, Valerie; Ghelima, Karin; Chan, John S D; Ingelfinger, Julie R; Chen, XiangMei; Chenier, Isabelle

2004-05-14

Angiotensin II stimulates cellular hypertrophy in cultured vascular smooth muscle and renal proximal tubular cells. This effect is believed to be one of earliest morphological changes of heart and renal failure. However, the precise molecular mechanism involved in angiotensin II-induced hypertrophy is poorly understood. In the present study we report the isolation of a novel angiotensin II type 1 receptor-associated protein. It encodes a 531-amino acid protein. Its mRNA is detected in all human tissues examined but highly expressed in the human kidney, pancreas, heart, and human embryonic kidney cells as well as rat vascular smooth muscle and renal proximal tubular cells. Protein synthesis and relative cell size analyzed by flow cytometry studies indicate that overexpression of the novel angiotensin II type 1 receptor-associated protein induces cellular hypertrophy in cultured rat vascular smooth muscle and renal proximal tubular cells. In contrast, the hypertrophic effects was reversed in renal proximal tubular cell lines expressing the novel gene in the antisense orientation and its dominant negative mutant, which lacks the last 101 amino acids in its carboxyl-terminal tail. The hypertrophic effects are at least in part mediated via protein kinase B activation or cyclin-dependent kinase inhibitor, p27(kip1) protein expression level in vascular smooth muscle, and renal proximal tubular cells. Moreover, angiotensin II could not stimulate cellular hypertrophy in renal proximal tubular cells expressing the novel gene in the antisense orientation and its mutant. These findings may provide new molecular mechanisms to understand hypertrophic agents such as angiotensin II-induced cellular hypertrophy.

Apigenin and naringenin regulate glucose and lipid metabolism, and ameliorate vascular dysfunction in type 2 diabetic rats.

PubMed

Ren, Bei; Qin, Weiwei; Wu, Feihua; Wang, Shanshan; Pan, Cheng; Wang, Liying; Zeng, Biao; Ma, Shiping; Liang, Jingyu

2016-02-15

Vascular endothelial dysfunction is regarded as the initial step of vascular complications in diabetes mellitus. This study investigated the amelioration of apigenin and naringenin in type 2 diabetic (T2D) rats induced by high-fat diet and streptozotocin and explored the underlying mechanism. Apigenin or naringenin was intragastrically administered at 50 or 100mg/kg once a day for 6 weeks. Biochemical parameters including blood glucose, glycated serum protein, serum lipid, insulin, superoxide dismutase (SOD), malonaldehyde and intercellular adhesion molecule-1 (ICAM-1) were measured. Vascular reactivity in isolated thoracic aortic rings was examined. Pathological features of the thoracic aorta were further observed through optical microscopy and transmission electron microscopy. Lastly, we evaluated their effects on insulin resistance of palmitic acid (PA)-induced endothelial cells. Compared with diabetic control group, apigenin and naringenin significantly decreased the levels of blood glucose, serum lipid, malonaldehyde, ICAM-1 and insulin resistance index, increased SOD activity and improved impaired glucose tolerance. Apigenin and naringenin restored phenylephrine-mediated contractions and acetylcholine or insulin-induced relaxations in aortic tissues. Furthermore, pathological damage in the thoracic aorta of apigenin and naringenin groups was more remissive than diabetic control group. In vitro, apigenin and naringenin inhibited NF-κB activation and ICAM-1 mRNA expression in PA-treated endothelial cells and improved nitric oxide production in the presence of insulin. In conclusion, both apigenin and naringenin can ameliorate glucose and lipid metabolism, as well as endothelial dysfunction in T2D rats at least in part by down-regulating oxidative stress and inflammation. In general, apigenin showed greater potency than naringenin equivalent. Copyright © 2016 Elsevier B.V. All rights reserved.

Neural control of renal function: role of renal alpha adrenoceptors.

PubMed

DiBona, G F

1985-01-01

Adrenoceptors of various subtypes mediate the renal functional responses to alterations in efferent renal sympathetic nerve activity, the neural component, and renal arterial plasma catecholamine concentrations, the humoral component, of the sympathoadrenergic nervous system. Under normal physiologic as well as hypertensive conditions, the influence of the renal sympathetic nerves predominates over that of circulating plasma catecholamines. In most mammalian species, increases in efferent renal sympathetic nerve activity elicit renal vasoconstrictor responses mediated predominantly by renal vascular alpha-1 adrenoceptors, increases in renin release mediated largely by renal juxtaglomerular granular cell beta-1 adrenoceptors with involvement of renal vascular alpha-1 adrenoceptors only when renal vasoconstriction occurs, and direct increases in renal tubular sodium and water reabsorption mediated predominantly by renal tubular alpha-1 adrenoceptors. In most mammalian species, alpha-2 adrenoceptors do not play a significant role in the renal vascular or renin release responses to renal sympathoadrenergic stimulation. Although renal tubular alpha-2 adrenoceptors do not mediate the increases in renal tubular sodium and water reabsorption produced by increases in efferent renal sympathetic nerve activity, they may be involved through their inhibitory effect on adenylate cyclase in modulating the response to other hormonal agents that influence renal tubular sodium and water reabsorption via stimulation of adenylate cyclase.

Vascular calcification and cardiac function according to residual renal function in patients on hemodialysis with urination.

PubMed

Shin, Dong Ho; Lee, Young-Ki; Oh, Jieun; Yoon, Jong-Woo; Rhee, So Yon; Kim, Eun-Jung; Ryu, Jiwon; Cho, Ajin; Jeon, Hee Jung; Choi, Myung-Jin; Noh, Jung-Woo

2017-01-01

Vascular calcification is common and may affect cardiac function in patients with end-stage renal disease (ESRD). However, little is known about the effect of residual renal function on vascular calcification and cardiac function in patients on hemodialysis. This study was conducted between January 2014 and January 2017. One hundred six patients with residual renal function on maintenance hemodialysis for 3 months were recruited. We used residual renal urea clearance (KRU) to measure residual renal function. First, abdominal aortic calcification score (AACS) and brachial-ankle pulse wave velocity (baPWV) were measured in patients on hemodialysis. Second, we performed echocardiography and investigated new cardiovascular events after study enrollment. The median KRU was 0.9 (0.3-2.5) mL/min/1.73m2. AACS (4.0 [1.0-10.0] vs. 3.0 [0.0-8.0], p = 0.05) and baPWV (1836.1 ± 250.4 vs. 1676.8 ± 311.0 cm/s, p = 0.01) were significantly higher in patients with a KRU < 0.9 mL/min/1.73m2 than a KRU ≥ 0.9 mL/min/1.73m2. Log-KRU significantly negatively correlated with log-AACS (ß = -0.29, p = 0.002) and baPWV (ß = -0.19, P = 0.05) after factor adjustment. The proportion of left ventricular diastolic dysfunction was significantly higher in patients with a KRU < 0.9 mL/min/1.73m2 than with a KRU ≥ 0.9 mL/min/1.73m2 (67.9% vs. 49.1%, p = 0.05). Patients with a KRU < 0.9 mL/min/1.73m2 showed a higher tendency of cumulative cardiovascular events compared to those with a KRU ≥ 0.9 ml/min/1.73m2 (P = 0.08). Residual renal function was significantly associated with vascular calcification and left ventricular diastolic dysfunction in patients on hemodialysis.

Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) enhances vascular and renal damage induced by hyperlipidemic diet in ApoE-knockout mice.

PubMed

Muñoz-García, Begoña; Moreno, Juan Antonio; López-Franco, Oscar; Sanz, Ana Belén; Martín-Ventura, José Luis; Blanco, Julia; Jakubowski, Aniela; Burkly, Linda C; Ortiz, Alberto; Egido, Jesús; Blanco-Colio, Luis Miguel

2009-12-01

Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is a member of the tumor necrosis factor superfamily of cytokines. TWEAK binds and activates the Fn14 receptor, and may regulate apoptosis, inflammation, and angiogenesis, in different pathological conditions. We have evaluated the effect of exogenous TWEAK administration as well as the role of endogenous TWEAK on proinflammatory cytokine expression and vascular and renal injury severity in hyperlipidemic ApoE-knockout mice. ApoE(-/-) mice were fed with hyperlipidemic diet for 4 to 10 weeks, then randomized and treated with saline (controls), TWEAK (10 microg/kg/d), anti-TWEAK neutralizing mAb (1000 microg/kg/d), TWEAK plus anti-TWEAK antibody (10 microg TWEAK +1000 microg anti-TWEAK/kg/d), or nonspecific IgG (1000 microg/kg/d) daily for 9 days. In ApoE(-/-) mice, exogenous TWEAK administration in ApoE(-/-) mice induced activation of NF-kappaB, a key transcription factor implicated in the regulation of the inflammatory response, in vascular and renal lesions. Furthermore, TWEAK treatment increased chemokine expression (RANTES and MCP-1), as well as macrophage infiltration in atherosclerotic plaques and renal lesions. These effects were associated with exacerbation of vascular and renal damage. Conversely, treatment of ApoE(-/-) mice with an anti-TWEAK blocking mAb decreased NF-kappaB activation, proinflammatory cytokine expression, macrophage infiltration, and vascular and renal injury severity, indicating a pathological role for endogenous TWEAK. Finally, in murine vascular smooth muscle cells or tubular cells, either ox-LDL or TWEAK treatment increased expression and secretion of both RANTES and MCP-1. Furthermore, ox-LDL and TWEAK synergized for induction of MCP-1 and RANTES expression and secretion. Our results suggest that TWEAK exacerbates the inflammatory response associated with a high lipid-rich diet. TWEAK may be a novel therapeutic target to prevent vascular and renal damage associated with

Multidetector computed tomography for preoperative evaluation of vascular anatomy in living renal donors.

PubMed

Türkvatan, Aysel; Akinci, Serkan; Yildiz, Sener; Olçer, Tülay; Cumhur, Turhan

2009-04-01

Currently, multidetector computed tomographic (MDCT) angiography has become a noninvasive alternative imaging modality to catheter renal angiography for the evaluation of renal vascular anatomy in living renal donors. In this study, we investigated the diagnostic accuracy of 16-slice MDCT in the preoperative assessment of living renal donors. Fifty-nine consecutive living renal donors (32 men, 27 women) underwent MDCT angiography followed by open donor nephrectomy. All MDCT studies were performed by using a 16-slice MDCT scanner with the same protocol consisting of arterial and nephrographic phases followed by conventional abdominal radiography. The MDCT images were assessed retrospectively for the number and branching pattern of the renal arteries and for the number and presence of major or minor variants of the renal veins. The results were compared with open surgical results. The sensitivity and specificity of MDCT for the detection of anatomic variants of renal arteries including the accessory arteries (n = 9), early arterial branching (n = 7) and major renal venous anomalies including the accessory renal veins (n = 3), late venous confluence (n = 4), circumaortic (n = 2) or retroaortic (n = 3) left renal veins were 100%. However, the sensitivity for identification of minor venous variants was 79%. All of three ureteral duplications were correctly identified at excretory phase conventional abdominal radiography. Sixteen-slice MDCT is highly accurate for the identification of anatomic variants of renal arteries and veins. Dual-phase MDCT angiography including arterial and nephrographic phases followed by conventional abdominal radiography enables complete assessment of renal donors without significant increase of radiation dose. However, the evaluation of minor venous variants may be problematic because of their small diameters and poor opacification.

The 6-hydroxychromanol derivative SUL-109 ameliorates renal injury after deep hypothermia and rewarming in rats.

PubMed

Vogelaar, Pieter C; Roorda, Maurits; de Vrij, Edwin L; Houwertjes, Martin C; Goris, Maaike; Bouma, Hjalmar; van der Graaf, Adrianus C; Krenning, Guido; Henning, Robert H

2018-04-11

Mitochondrial dysfunction plays an important role in kidney damage in various pathologies, including acute and chronic kidney injury and diabetic nephropathy. In addition to the well-studied ischaemia/reperfusion (I/R) injury, hypothermia/rewarming (H/R) also inflicts acute kidney injury. Substituted 6-hydroxychromanols are a novel class of mitochondrial medicines that ameliorate mitochondrial oxidative stress and protect the mitochondrial network. To identify a novel 6-hydroxychromanol that protects mitochondrial structure and function in the kidney during H/R, we screened multiple compounds in vitro and subsequently assessed the efficacy of the 6-hydroxychromanol derivatives SUL-109 and SUL-121 in vivo to protect against kidney injury after H/R in rats. Human proximal tubule cell viability was assessed following exposure to H/R for 48/4 h in the presence of various 6-hydroxychromanols. Selected compounds (SUL-109, SUL-121) or vehicle were administered to ketamine-anaesthetized male Wistar rats (IV 135 µg/kg/h) undergoing H/R at 15°C for 3 h followed by rewarming and normothermia for 1 h. Metabolic parameters and body temperature were measured throughout. In addition, renal function, renal injury, histopathology and mitochondrial fitness were assessed. H/R injury in vitro lowered cell viability by 94 ± 1%, which was counteracted dose-dependently by multiple 6-hydroxychomanols derivatives. In vivo, H/R in rats showed kidney injury molecule 1 expression in the kidney and tubular dilation, accompanied by double-strand DNA breaks and protein nitrosylation. SUL-109 and SUL-121 ameliorated tubular kidney damage, preserved mitochondrial mass and maintained cortical adenosine 5'-triphosphate (ATP) levels, although SUL-121 did not reduce protein nitrosylation. The substituted 6-hydroxychromanols SUL-109 and SUL-121 ameliorate kidney injury during in vivo H/R by preserving mitochondrial mass, function and ATP levels. In addition, both 6-hydroxychromanols

Inhibition of SET Domain–Containing Lysine Methyltransferase 7/9 Ameliorates Renal Fibrosis

PubMed Central

Sasaki, Kensuke; Nakashima, Ayumu; Irifuku, Taisuke; Yamada, Kyoko; Kokoroishi, Keiko; Ueno, Toshinori; Doi, Toshiki; Hida, Eisuke; Arihiro, Koji; Kohno, Nobuoki

2016-01-01

TGF-β1 activity results in methylation of lysine 4 of histone H3 (H3K4) through SET domain–containing lysine methyltransferase 7/9 (SET7/9) induction, which is important for the transcriptional activation of fibrotic genes in vitro. However, in vivo studies utilizing an experimental model of renal fibrosis are required to develop therapeutic interventions that target SET7/9. In this study, we investigated the signaling pathway of TGF-β1-induced SET7/9 expression and whether inhibition of SET7/9 suppresses renal fibrosis in unilateral ureteral obstruction (UUO) mice and kidney cell lines. Among the SET family, SET7/9 was upregulated on days 3 and 7 in UUO mice, and the upregulation was suppressed by TGF-β1 neutralizing antibody. TGF-β1 induced SET7/9 expression via Smad3 in normal rat kidney (NRK)-52E cells. In human kidney biopsy specimens from patients diagnosed with IgA nephropathy and membranous nephropathy, SET7/9 expression was positively correlated with the degree of interstitial fibrosis (r=0.59, P=0.001 in patients with IgA nephropathy; and r=0.58, P<0.05 in patients with membranous nephropathy). In addition, small interfering RNA-mediated knockdown of SET7/9 expression significantly attenuated renal fibrosis in UUO mice. Sinefungin, an inhibitor of SET7/9, also suppressed the expression of mesenchymal markers and extracellular matrix proteins and inhibited H3K4 mono-methylation (H3K4me1) in kidneys of UUO mice. Moreover, sinefungin had an inhibitory effect on TGF-β1-induced α-smooth muscle actin expression and H3K4me1 in both NRK-52E and NRK-49F cells. In conclusion, sinefungin, a SET7/9 inhibitor, ameliorates renal fibrosis by inhibiting H3K4me1 and may be a candidate therapeutic agent. PMID:26045091

Role of quercetin and arginine in ameliorating nano zinc oxide-induced nephrotoxicity in rats.

PubMed

Faddah, Laila M; Abdel Baky, Nayira A; Al-Rasheed, Nouf M; Al-Rasheed, Nawal M; Fatani, Amal J; Atteya, Muhammad

2012-05-02

Nanoparticles are small-scale substances (<100 nm) with unique properties. Therefore, nanoparticles pose complex health risk implications. The objective of this study was to detect whether treatment with quercetin (Qur) and/or arginine (Arg) ameliorated nephrotoxicity induced by two different doses of nano zinc oxide (n-ZnO) particles. ZnO nanoparticles were administered orally in two doses (either 600 mg or 1 g/Kg body weight/day for 5 conscutive days) to Wister albino rats. In order to detect the protective effects of the studied antioxidants against n-ZnO induced nepherotoxicity, different biochemical parameters were investigated. Moreover, histopathological examination of kidney tissue was performed. Nano zinc oxide-induced nephrotoxicity was confirmed by the elevation in serum inflammatory markers including: tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6); and C-reactive protein (CRP). Moreover, immunoglobulin (IGg), vascular endothelium growth factor (VEGF), and nitric oxide (NO) were significantly increased in rat serum. Serum urea and creatinine levels were also significantly increased in rats intoxicated with n-ZnO particles compared with the control group. Additionally, a significant decrease in the non-enzymatic antioxidant reduced glutathione (GSH) was shown in kidney tissues and serum glucose levels were increased. These biochemical findings were supported by a histopathological examination of kidney tissues, which showed that in the animals that received a high dose of n-ZnO, numerous kidney glomeruli underwent atrophy and fragmentation. Moreover, the renal tubules showed epithelial desquamation, degeneration and necrosis. Some renal tubules showed casts in their lumina. Severe congestion was also observed in renal interstitium. These effects were dose dependent. Cotreatment of rats with Qur and/or Arg along with n-ZnO significantly improved most of the deviated tested parameters. The data show that Qur has a beneficial effect against

Baicalin ameliorates renal fibrosis via inhibition of transforming growth factor β1 production and downstream signal transduction

PubMed Central

Zheng, Long; Zhang, Chao; Li, Long; Hu, Chao; Hu, Mushuang; Sidikejiang, Niyazi; Wang, Xuanchuan; Lin, Miao; Rong, Ruiming

2017-01-01

Previous studies have demonstrated the potential antifibrotic effects of baicalin in vitro, via examination of 21 compounds isolated from plants. However, its biological activity and underlying mechanisms of action in vivo remain to be elucidated. The present study aimed to evaluate the effect of baicalin on renal fibrosis in vivo, and the potential signaling pathways involved. A unilateral ureteral obstruction (UUO)-induced renal fibrosis model was established using Sprague-Dawley rats. Baicalin was administrated intraperitoneally every 2 days for 10 days. The degree of renal damage and fibrosis was investigated by histological assessment, and detection of fibronectin and collagen I mRNA expression levels. Epithelial-mesenchymal transition (EMT) markers, transforming growth factor-β1 (TGF-β1) levels and downstream phosphorylation of mothers against decapentaplegic 2/3 (Smad2/3) were examined in vivo and in an NRK-52E rat renal tubular cell line in vitro. Baicalin was demonstrated to markedly ameliorate renal fibrosis and suppress EMT, as evidenced by reduced interstitial collagen accumulation, decreased fibronectin and collagen I mRNA expression levels, upregulation of N- and E-cadherin expression levels, and downregulation of α-smooth muscle actin and vimentin expression. Furthermore, baicalin decreased TGF-β1 expression levels in serum and kidney tissue following UUO, and suppressed Smad2/3 phosphorylation in rat kidney tissue. In vitro studies identified that baicalin may inhibit the phosphorylation of Smad2/3 under the same TGF-β1 concentration. In conclusion, baicalin may protect against renal fibrosis, potentially via inhibition of TGF-β1 production and its downstream signal transduction. PMID:28260014

Thalidomide ameliorates cisplatin-induced nephrotoxicity by inhibiting renal inflammation in an experimental model.

PubMed

Amirshahrokhi, Keyvan; Khalili, Ali-Reza

2015-04-01

Cisplatin is a platinum-based chemotherapy drug. However, its chemotherapeutic use is restricted by serious side effects, especially nephrotoxicity. Inflammatory mechanisms have a significant role in the pathogenesis of cisplatin-induced nephrotoxicity. Thalidomide is an immunomodulatory and anti-inflammatory agent and is used for the treatment of various inflammatory diseases. The purpose of this study was to investigate the potential nephroprotective effect of thalidomide in a mouse model of cisplatin-induced nephrotoxicity. Nephrotoxicity was induced in mice by a single injection of cisplatin (15 mg/kg, i.p.) and treated with thalidomide (50 and 100 mg/kg/day, orally) for 4 days, beginning 24 h prior to the cisplatin injection. Renal toxicity induced by cisplatin was demonstrated by increasing plasma levels of creatinine and blood urea nitrogen (BUN). Cisplatin increased the renal production of the proinflammatory cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and transforming growth factor (TGF)-β1. In addition, kidney levels of malondialdehyde (MDA), myeloperoxidase (MPO), and nitric oxide (NO) were increased by cisplatin. Biochemical results showed that thalidomide reduced cisplatin-induced increase in plasma creatinine and BUN. Thalidomide treatment also significantly reduced tissue levels of the proinflammatory cytokines, MDA, MPO, and NO and increased anti-inflammatory cytokine IL-10. Furthermore, histological examination indicated that thalidomide ameliorated renal damage caused by cisplatin. These data suggest that thalidomide attenuates cisplatin-induced nephrotoxicity possibly by inhibition of inflammatory reactions. Taken together, our findings indicate that thalidomide might be a valuable candidate for the prevention of nephrotoxicity in patients receiving cisplatin.

The para-aortic ridge plays a key role in the formation of the renal, adrenal and gonadal vascular systems

PubMed Central

Isogai, Sumio; Horiguchi, Mayuko; Hitomi, Jiro

2010-01-01

Renal, adrenal, gonadal, ureteral and inferior phrenic arteries vary in their level of origin and in their calibre, number and precise anatomical relationship to other structures. Studies of the origin and early development of these arteries have evoked sharp disputes. The ladder theory of Felix, which states that ‘All the mesonephric arteries may persist; from them are formed the phrenic, suprarenal, renal and internal spermatic arteries’ has been generally quoted in the anatomical textbooks without rigorous verification for 100 years. In this study, we re-examined this theory by performing micro-injection of dye and resin into rat (Rattus norvegicus) embryos. Our results revealed that most of the mesonephric arteries had degenerated before the metanephros started its ascent. The definitive renal, adrenal, gonadal, ureteral and inferior phrenic arteries appeared as new branches from the gonadal artery and/or directly from the abdominal aorta to the para-aortic ridge. Coincidental to this, the anatomical architecture of the inter-renal vascular cage, which consists of the interlobar and arcuate arteries and their collateral veins, was completed within the developing metanephros. We demonstrated that the delicate renal vascular cage switched from the primary renal artery to the definitive renal artery and that the route of venous drainage changed from the posterior cardinal vein to the inferior (caudal) vena cava. PMID:20579173

Successful microscopic renal autotransplantation for left renal aneurysm associated with segmental arterial mediolysis.

PubMed

Yoshioka, Takashi; Araki, Motoo; Ariyoshi, Yuichi; Wada, Koichiro; Tanaka, Noriyuki; Nasu, Yasutomo

2017-07-01

Segmental arterial mediolysis (SAM) is an uncommon, nonarteriosclerotic vascular disease. SAM is characterized by lysis of arterial media and can lead to aneurysm formation. The renal arteries are the third most common arteries associated with SAM. We report the case of a 32-year-old man with left renal artery aneurysm associated with SAM. We successfully performed left renal autotransplantation using microscopic vascular reconstruction. SAM is characterized by vascular fragility; therefore, microscopic surgery is favorable for treating aneurysms associated with SAM. Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

βENaC acts as a mechanosensor in renal vascular smooth muscle cells that contributes to renal myogenic blood flow regulation, protection from renal injury and hypertension.

PubMed

Drummond, Heather A; Stec, David E

2015-06-01

Pressure-induced constriction (also known as the "myogenic response") is an important mechanodependent response in small renal arteries and arterioles. The response is initiated by vascular smooth muscle cell (VSMC) stretch due to an increase in intraluminal pressure and leads to vasoconstriction. The myogenic response has two important roles as a mechanism of local blood flow autoregulation and protection against systemic blood pressure-induced microvascular damage. However, the molecular mechanisms underlying initiation of myogenic response are unresolved. Although several molecules have been considered initiators of the response, our laboratory has focused on the role of degenerin proteins because of their strong evolutionary link to mechanosensing in the nematode. Our laboratory has addressed the hypothesis that certain degenerin proteins act as mechanosensors in VSMCs. This article discusses the importance of a specific degenerin protein, β Epithelial Na + Channel (βENaC), in pressure-induced vasoconstriction, renal blood flow and susceptibility to renal injury. We propose that loss of the renal myogenic constrictor response delays the correction of renal blood flow that occurs with fluctuations in systemic pressure, which allows pressure swings to be transmitted to the microvasculature, thus increasing the susceptibility to renal injury and hypertension. The role of βENaC in myogenic regulation is independent of tubular βENaC and thus represents a non-tubular role for βENaC in renal-cardiovascular homeostasis.

Emblic Leafflower (Phyllanthus emblica L.) Fruits Ameliorate Vascular Smooth Muscle Cell Dysfunction in Hyperglycemia: An Underlying Mechanism Involved in Ellagitannin Metabolite Urolithin A

PubMed Central

Zhou, Junxuan; Zhang, Cong

2018-01-01

Ellagitannins in Phyllanthus emblica L. (emblic leafflower fruits) have been thought of as the beneficial constituents for ameliorating endocrinal and metabolic diseases including diabetes. However, the effect of emblic leafflower fruits on diabetic vascular complications involved in ellagitannin-derived urolithin metabolites is still rare. In this study, acetylcholine-induced endothelium-independent relaxation in aortas was facilitated upon emblic leafflower fruit consumption in the single dose streptozotocin-induced hyperglycemic rats. Emblic leafflower fruit consumption also suppressed the phosphorylation of Akt (Thr308) in the hyperglycemic aortas. More importantly, urolithin A (UroA) and its derived phase II metabolites were identified as the metabolites upon emblic leafflower fruit consumption by HPLC-ESI-Q-TOF-MS. Moreover, UroA reduced the protein expressions of phosphor-Akt (Thr308) and β-catenin in a high glucose-induced A7r5 vascular smooth muscle cell proliferation model. Furthermore, accumulation of β-catenin protein and activation of Wnt signaling in LiCl-triggered A7r5 cells were also ameliorated by UroA treatment. In conclusion, our data demonstrate that emblic leafflower fruit consumption facilitates the vascular function in hyperglycemic rats by regulating Akt/β-catenin signaling, and the effects are potentially mediated by the ellagitannin metabolite urolithin A. PMID:29692859

Rapamycin promotes podocyte autophagy and ameliorates renal injury in diabetic mice.

PubMed

Xiao, Tangli; Guan, Xu; Nie, Ling; Wang, Song; Sun, Lei; He, Ting; Huang, Yunjian; Zhang, Jingbo; Yang, Ke; Wang, Junping; Zhao, Jinghong

2014-09-01

The aim was to explore the effects of rapamycin on autophagy and injury of podocytes in streptozocin (STZ)-induced type 1 diabetic mice, and its role in delaying progression of diabetic nephropathy. In this study, male Balb/c mice were divided into three groups: control (n = 12), STZ-induced diabetic (n = 12), and rapamycin-treated diabetic (DM + Rapa) (n = 12), which received intraperitoneal injection of rapamycin (2 mg/kg/48 h) after induction of DM. Levels of urinary albumin (UA), blood urea nitrogen, serum creatinine, and kidney weight/body weight were measured at week 12. Renal pathologic changes, number of podocytes autophagy, and organelles injury were investigated by PAS staining, transmission electron microscopy, and immunofluorescence staining, respectively. Western blot was performed to determine the expression of LC3 (a podocyte autophagy marker), phosphorylated mammalian target of rapamycin, p-p70S6K, bax, and caspase-3 protein. Podocytes count was evaluated by immunofluorescence staining and Wilms tumor 1 immunohistochemistry, and Western blot of nephrin and podocin. The results indicated that rapamycin could reduce the kidney weight/body weight and UA secretion. It could alleviate podocyte foot process fusion, glomerular basement membrane thickening, and matrix accumulation, and increase the number of autophagosomes, and LC3-expressing podocytes. Down-regulation of bax and caspase-3 protein, and up-regulation of nephrin and podocin protein were observed in the glomeruli of diabetic mice after administration of rapamycin. In conclusion, rapamycin can ameliorate renal injury in diabetic mice by increasing the autophagy activity and inhibition of apoptosis of podocytes.

Ansys Fluent versus Sim Vascular for 4-D patient-specific computational hemodynamics in renal arteries

NASA Astrophysics Data System (ADS)

Mumbaraddi, Avinash; Yu, Huidan (Whitney); Sawchuk, Alan; Dalsing, Michael

2015-11-01

The objective of this clinical-need driven research is to investigate the effect of renal artery stenosis (RAS) on the blood flow and wall shear stress in renal arteries through 4-D patient-specific computational hemodynamics (PSCH) and search for possible critical RASs that significantly alter the pressure gradient across the stenosis by manually varying the size of RAS from 50% to 95%. The identification of the critical RAS is important to understand the contribution of RAS to the overall renal resistance thus appropriate clinical therapy can be determined in order to reduce the hypertension. Clinical CT angiographic data together with Doppler Ultra sound images of an anonymous patient are used serving as the required inputs of the PSCH. To validate the PSCH, we use both Ansys Fluent and Sim Vascular and compare velocity, pressure, and wall-shear stress under identical conditions. Renal Imaging Technology Development Program (RITDP) Grant.

Male sex and vascular risk factors affect cystatin C-derived renal function in older people without diabetes or overt vascular disease.

PubMed

Werner, Karin Birgitta; Elmståhl, Sölve; Christensson, Anders; Pihlsgård, Mats

2014-05-01

to explore the effect of ageing on renal function with cystatin C as the marker of glomerular filtration rate (GFR) in the general population without vascular disease or diabetes. a cross-sectional analysis of a healthy subset from the Good Aging in Skåne-cohort study representative of the Swedish general population. 1252 participants without vascular disease and diabetes (43.9% men) of whom 203 were over 80 years old were included from the original cohort of 2931. plasma cystatin C and plasma creatinine were used as markers for GFR. Estimated GFR (eGFR) was calculated with three chronic kidney disease epidemiology collaboration (CKD-EPI) formulas involving cystatin C, creatinine or both. the median for plasma cystatin C was 0.93 mg/l (60-69 years old), 1.04 (70-79 years old) and 1.24 (80+ years old). The difference in mg/l between the 5th and 95th percentile was 0.46, 0.62 and 0.90 for these age groups. Male sex increased the age effect on plasma cystatin C levels with 0.004 mg/l/year (P = 0.03), adjusted for vascular risk factors. Smoking, lower HDL and higher diastolic blood pressure were associated with higher cystatin C levels. 54.7% (CKD-EPI creatinine) to 73.9% (CKD-EPI cystatin C) of the 80+ had an eGFR < 60 ml/min/1.73 m2. non-diabetics without overt vascular disease exhibit an age related but heterogeneous decline in renal function. The ageing effect is more pronounced in men. At least half of healthy 80+ years old could be expected to have at least CKD Stage 3 with eGFR < 60 ml/min/1.73 m2.

Green Tea Polyphenols Ameliorate the Early Renal Damage Induced by a High-Fat Diet via Ketogenesis/SIRT3 Pathway

PubMed Central

Yi, Weijie; Xie, Xiao; Du, Miying; Bu, Yongjun; Wu, Nannan; Yang, Hui; Tian, Chong; Xu, Fangyi; Xiang, Siyun; Zhang, Piwei; Chen, Zhuo

2017-01-01

Scope Several reports in the literature have suggested the renoprotective effects of ketone bodies and green tea polyphenols (GTPs). Our previous study found that GTP consumption could elevate the renal expression of the ketogenic rate-limiting enzyme, which was decreased by a high-fat diet (HFD) in rats. Here, we investigated whether ketogenesis can mediate renoprotection by GTPs against an HFD. Methods and Results Wistar rats were fed a standard or HFD with or without GTPs for 18 weeks. The renal oxidative stress level, kidney function, renal expression, and activity levels of mitochondrial 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) synthase 2 (HMGCS2) and sirtuin 3(SIRT3) were detected. The increased renal oxidative stress and the loss of renal function induced by the HFD were ameliorated by GTPs. Renal ketogenesis and SIRT3 expression and activity levels, which were reduced by the HFD, were restored by GTPs. In vitro, HEK293 cells were transfected with the eukaryotic expression plasmid pcDNA HMGCS2. GTP treatment could upregulate HMGCS2 and SIRT3 expression. Although SIRT3 expression was not affected by HMGCS2 transfection, the 4-hydroxy-2-nonenal (4-HNE) level and the acetyl-MnSOD (K122)/MnSOD ratio were reduced in HMGCS2-transfected cells in the context of H2O2. Conclusion The ketogenesis/SIRT3 pathway mediates the renoprotection of GTPs against the oxidative stress induced by an HFD. PMID:28814987

Atorvastatin ameliorates arsenic-induced hypertension and enhancement of vascular redox signaling in rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sarath, Thengumpallil Sasindran; Waghe, Prashantkumar; Gupta, Priyanka

Chronic arsenic exposure has been linked to elevated blood pressure and cardiovascular diseases, while statins reduce the incidence of cardiovascular disease predominantly by their low density lipoprotein-lowering effect. Besides, statins have other beneficial effects, including antioxidant and anti-inflammatory activities. We evaluated whether atorvastatin, a widely used statin, can ameliorate arsenic-induced increase in blood pressure and alteration in lipid profile and also whether the amelioration could relate to altered NO and ROS signaling. Rats were exposed to sodium arsenite (100 ppm) through drinking water for 90 consecutive days. Atorvastatin (10 mg/kg bw, orally) was administered once daily during the last 30more » days of arsenic exposure. On the 91st day, blood was collected for lipid profile. Western blot of iNOS and eNOS protein, NO and 3-nitrotyrosine production, Nox-4 and p22Phox mRNA expression, Nox activity, ROS generation, lipid peroxidation and antioxidants were evaluated in thoracic aorta. Arsenic increased systolic, diastolic and mean arterial blood pressure, while it decreased HDL-C and increased LDL-C, total cholesterol and triglycerides in serum. Arsenic down-regulated eNOS and up-regulated iNOS protein expression and increased basal NO and 3-nitrotyrosine level. Arsenic increased aortic Nox-4 and p22Phox mRNA expression, Nox activity, ROS generation and lipid peroxidation. Further, arsenic decreased the activities of superoxide dismutase, catalase, and glutathione peroxidase and depleted aortic GSH content. Atorvastatin regularized blood pressure, improved lipid profile and attenuated arsenic-mediated redox alterations. The results demonstrate that atorvastatin has the potential to ameliorate arsenic-induced hypertension by improving lipid profile, aortic NO signaling and restoring vascular redox homeostasis. - Highlights: • Arsenic increased systolic, diastolic and mean arterial blood pressure and caused dyslipidemia. • Arsenic

Osthole ameliorates renal ischemia-reperfusion injury in rats.

PubMed

Zheng, Yi; Lu, Min; Ma, Lulin; Zhang, Shudong; Qiu, Min; Wang, Yunpeng

2013-07-01

Renal ischemia-reperfusion (I/R) injury is a major cause of acute kidney injury. The pathogenetic mechanisms underlying I/R injury involve oxidative stress and apoptosis. Osthole, a natural coumarin derivative, has been reported to possess antioxidant and antiapoptotic activities. This study aimed to investigate the potential effects of osthole on renal I/R injury in an in vivo rat model. We induced renal I/R injury by clamping the left renal artery for 45 min followed by reperfusion, along with a contralateral nephrectomy. We randomly assigned 54 rats to three groups (18 rats/group): sham-operated, vehicle-treated I/R, and osthole-treated I/R. We treated rats intraperitoneally with osthole (40 mg/kg) or vehicle (40 mg/kg) 30 min before renal ischemia. We harvested serum and kidneys at 1, 6, and 24 h after reperfusion. Renal function and histological changes were assessed. We also determined markers of oxidative stress and cell apoptosis in kidneys. Osthole treatment significantly attenuated renal dysfunction and histologic damage induced by I/R injury. The I/R-induced elevation in kidney malondialdehyde level decreased, whereas reduced kidney superoxide dismutase and catalase activities were markedly increased. Moreover, osthole-treated rats had a dramatic decrease in apoptotic tubular cells, along with a decrease in caspase-3 and an increase in the Bcl-2/Bax ratio. Osthole treatment protects murine kidney from renal I/R injury by suppressing oxidative stress and cell apoptosis. Thus, osthole may represent a novel practical strategy to prevent renal I/R injury. Copyright © 2013 Elsevier Inc. All rights reserved.

Renal Vascular Structure and Rarefaction

PubMed Central

Chade, Alejandro R.

2014-01-01

An intact microcirculation is vital for diffusion of oxygen and nutrients and for removal of toxins of every organ and system in the human body. The functional and/or anatomical loss of microvessels is known as rarefaction, which can compromise the normal organ function and have been suggested as a possible starting point of several diseases. The purpose of this overview is to discuss the potential underlying mechanisms leading to renal microvascular rarefaction, and the potential consequences on renal function and on the progression of renal damage. Although the kidney is a special organ that receives much more blood than its metabolic needs, experimental and clinical evidence indicates that renal microvascular rarefaction is associated to prevalent cardiovascular diseases such as diabetes, hypertension, and atherosclerosis, either as cause or consequence. On the other hand, emerging experimental evidence using progenitor cells or angiogenic cytokines supports the feasibility of therapeutic interventions capable of modifying the progressive nature of microvascular rarefaction in the kidney. This overview will also attempt to discuss the potential renoprotective mechanisms of the therapeutic targeting of the renal microcirculation. PMID:23720331

Honey Supplementation in Spontaneously Hypertensive Rats Elicits Antihypertensive Effect via Amelioration of Renal Oxidative Stress

PubMed Central

Erejuwa, Omotayo O.; Sulaiman, Siti A.; Ab Wahab, Mohd S.; Sirajudeen, Kuttulebbai N. S.; Salleh, Salzihan; Gurtu, Sunil

2012-01-01

Oxidative stress is implicated in the pathogenesis and/or maintenance of elevated blood pressure in hypertension. This study investigated the effect of honey on elevated systolic blood pressure (SBP) in spontaneously hypertensive rats (SHR). It also evaluated the effect of honey on the amelioration of oxidative stress in the kidney of SHR as a possible mechanism of its antihypertensive effect. SHR and Wistar Kyoto (WKY) rats were randomly divided into 2 groups and administered distilled water or honey by oral gavage once daily for 12 weeks. The control SHR had significantly higher SBP and renal malondialdehyde (MDA) levels than did control WKY. The mRNA expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and glutathione S-transferase (GST) were significantly downregulated while total antioxidant status (TAS) and activities of GST and catalase (CAT) were higher in the kidney of control SHR. Honey supplementation significantly reduced SBP and MDA levels in SHR. Honey significantly reduced the activities of GST and CAT while it moderately but insignificantly upregulated the Nrf2 mRNA expression level in the kidney of SHR. These results indicate that Nrf2 expression is impaired in the kidney of SHR. Honey supplementation considerably reduces elevated SBP via amelioration of oxidative stress in the kidney of SHR. PMID:22315654

Honey supplementation in spontaneously hypertensive rats elicits antihypertensive effect via amelioration of renal oxidative stress.

PubMed

Erejuwa, Omotayo O; Sulaiman, Siti A; Ab Wahab, Mohd S; Sirajudeen, Kuttulebbai N S; Salleh, Salzihan; Gurtu, Sunil

2012-01-01

Oxidative stress is implicated in the pathogenesis and/or maintenance of elevated blood pressure in hypertension. This study investigated the effect of honey on elevated systolic blood pressure (SBP) in spontaneously hypertensive rats (SHR). It also evaluated the effect of honey on the amelioration of oxidative stress in the kidney of SHR as a possible mechanism of its antihypertensive effect. SHR and Wistar Kyoto (WKY) rats were randomly divided into 2 groups and administered distilled water or honey by oral gavage once daily for 12 weeks. The control SHR had significantly higher SBP and renal malondialdehyde (MDA) levels than did control WKY. The mRNA expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and glutathione S-transferase (GST) were significantly downregulated while total antioxidant status (TAS) and activities of GST and catalase (CAT) were higher in the kidney of control SHR. Honey supplementation significantly reduced SBP and MDA levels in SHR. Honey significantly reduced the activities of GST and CAT while it moderately but insignificantly upregulated the Nrf2 mRNA expression level in the kidney of SHR. These results indicate that Nrf2 expression is impaired in the kidney of SHR. Honey supplementation considerably reduces elevated SBP via amelioration of oxidative stress in the kidney of SHR.

Kv channel subunits that contribute to voltage-gated K+ current in renal vascular smooth muscle.

PubMed

Fergus, Daniel J; Martens, Jeffrey R; England, Sarah K

2003-03-01

The rat renal arterial vasculature displays differences in K(+) channel current phenotypes along its length. Small arcuate to cortical radial arteries express a delayed rectifier phenotype, while the predominant Kv current in larger arcuate and interlobar arteries is composed of both transient and sustained components. We sought to determine whether Kvalpha subunits in the rat renal interlobar and arcuate arteries form heterotetramers, which may account for the unique currents, and whether modulatory Kvbeta subunits are present in renal vascular smooth muscle cells. RT-PCR indicated the presence of several different Kvalpha subunit isoform transcripts. Co-immunoprecipitation with immunoblotting and immunohistochemical evidence suggests that a portion of the K(+) current phenotype is a heteromultimer containing delayed-rectifier Kv1.2 and A-type Kv1.4 channel subunits. RT-PCR and immunoblot analyses also demonstrated the presence of both Kvbeta1.2 and Kvbeta1.3 in renal arteries. These results suggest that heteromultimeric formation of Kvalpha subunits and the presence of modulatory Kvbeta subunits are important factors in mediating Kv currents in the renal microvasculature and suggest a potentially critical role for these channel subunits in blood pressure regulation.

Beneficial Effects of Renal Denervation on Pulmonary Vascular Remodeling in Experimental Pulmonary Artery Hypertension.

PubMed

Qingyan, Zhao; Xuejun, Jiang; Yanhong, Tang; Zixuan, Dai; Xiaozhan, Wang; Xule, Wang; Zongwen, Guo; Wei, Hu; Shengbo, Yu; Congxin, Huang

2015-07-01

Activation of both the sympathetic nervous system and the renin-angiotensin-aldosterone system is closely associated with pulmonary arterial hypertension. We hypothesized that renal denervation decreases renin-angiotensin-aldosterone activity and inhibits the progression of pulmonary arterial hypertension. Twenty-two beagles were randomized into 3 groups. The dogs' pulmonary dynamics were measured before and 8 weeks after injection of 0.1mL/kg dimethylformamide (control dogs) or 2mg/kg dehydromonocrotaline (pulmonary arterial hypertension and pulmonary arterial hypertension + renal denervation dogs). Eight weeks after injection, neurohormone levels and pulmonary tissue morphology were measured. Levels of plasma angiotensin II and endothelin-1 were significantly increased after 8 weeks in the pulmonary arterial hypertension dogs and were higher in the lung tissues of these dogs than in those of the control and renal denervation dogs (mean [standard deviation] angiotensin II: 65 [9.8] vs 38 [6.7], 46 [8.1]; endothelin-1: 96 [10.3] vs 54 [6.2], 67 [9.4]; P < .01). Dehydromonocrotaline increased the mean pulmonary arterial pressure (16 [3.4] mmHg vs 33 [7.3] mmHg; P < .01), and renal denervation prevented this increase. Pulmonary smooth muscle cell proliferation was higher in the pulmonary arterial hypertension dogs than in the control and pulmonary arterial hypertension + renal denervation dogs. Renal denervation attenuates pulmonary vascular remodeling and decreases pulmonary arterial pressure in experimental pulmonary arterial hypertension. The effect of renal denervation may contribute to decreased neurohormone levels. Copyright © 2014 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Vascular Hyperactivity in the Rat Renal Aorta Participates in the Association between Immune Complex-Mediated Glomerulonephritis and Systemic Hypertension.

PubMed

Pérez-Torres, Israel; Moguel-González, Bernardo; Soria-Castro, Elizabeth; Guarner-Lans, Verónica; Avila-Casado, María Del Carmen; Goes, Teresa Imelda Fortoul Vander

2018-06-03

Introduction : systemic hypertension (SH) involving endothelial dysfunction contributes to immune complex-mediated glomerulonephritis (ICGN). Objective, we demonstrate a relationship between ICGN and SH by analyzing vascular reactivity in renal aortic rings. Methods : 48 male Wistar rats were divided into four groups: (a) control (C); (b) injected with bovine serum albumin (BSA); (c) receiving 200 mg/L NAME (an analog of arginine that inhibits NO production) in drinking water; and (d) receiving BSA and 200 mg/L NAME. Rats were pre-immunized subcutaneously with BSA and Freund's adjuvant. After 10 days, groups (b) and (c) received 1 mg/mL of BSA in saline intravenous (IV) daily for 35 days. The urine of 24 h was measured at days 0, 15, 30 and 45. Results : vascular reactivity to norepinephrine (NE), acetylcholine (Ach) and NAME were tested. Creatinine clearance, vasodilatation, eNOS and elastic fibers were diminished ( p ≤ 0.001). Blood pressure, vasoconstriction, iNOS were increased, and glomerular alterations were observed in groups (b), (c) and (d) when compared to group (a) ( p ≤ 0.001). Conclusions: SH contributes to the development of progressive renal disease in ICGN. Alterations of the vascular reactivity are mediated by the endothelium in the renal aorta. Thus, the endothelium plays a determinant role in the production of vasoactive substances such as NO during this process.

Effects of age and caloric restriction in the vascular response of renal arteries to endothelin-1 in rats.

PubMed

Amor, Sara; García-Villalón, Angel Luis; Rubio, Carmen; Carrascosa, Jose Ma; Monge, Luis; Fernández, Nuria; Martín-Carro, Beatriz; Granado, Miriam

2017-02-01

Cardiovascular alterations are the most prevalent cause of impaired physiological function in aged individuals with kidney being one the most affected organs. Aging-induced alterations in renal circulation are associated with a decrease in endothelium-derived relaxing factors such as nitric oxide (NO) and with an increase in contracting factors such as endothelin-1(ET-1). As caloric restriction (CR) exerts beneficial effects preventing some of the aging-induced alterations in cardiovascular system, the aim of this study was to analyze the effects of age and caloric restriction in the vascular response of renal arteries to ET-1 in aged rats. Vascular function was studied in renal arteries from 3-month-old Wistar rats fed ad libitum (3m) and in renal arteries from 8-and 24-month-old Wistar rats fed ad libitum (8m and 24m), or subjected to 20% caloric restriction during their three last months of life (8m-CR and 24m-CR). The contractile response to ET-1 was increased in renal arteries from 8m and 24m compared to 3m rats. ET-1-induced contraction was mediated by ET-A receptors in all experimental groups and also by ET-B receptors in 24m rats. Caloric restriction attenuated the increased contraction to ET-1 in renal arteries from 8m but not from 24m rats possibly through NO release proceeding from ET-B endothelial receptors. In 24m rats, CR did not attenuate the aging-increased response of renal arteries to ET-1, but it prevented the aging-induced increase in iNOS mRNA levels and the aging-induced decrease in eNOS mRNA levels in arterial tissue. In conclusion, aging is associated with an increased response to ET-1 in renal arteries that is prevented by CR in 8m but not in 24m rats. Copyright © 2016 Elsevier Inc. All rights reserved.

Ghrelin improves vascular autophagy in rats with vascular calcification.

PubMed

Xu, Mingming; Liu, Lin; Song, Chenfang; Chen, Wei; Gui, Shuyan

2017-06-15

This study aimed to investigate whether ghrelin ameliorated vascular calcification (VC) through improving autophagy. VC model was induced by nicotine plus vitamin D 3 in rats and β-glycerophosphate in vascular smooth muscle cell (VSMC). Calcium deposition was detected by von Kossa staining or alizarin red S staining. ALP activity was also detected. Western blot was used to assess the protein expression. Ghrelin treatment attenuated the elevation of calcium deposition and ALP activity in VC model both in vivo and in vitro. Interesting, the protein levels of autophagy markers, LC3 and beclin1 were significantly upregulated by ghrelin in VC model. An autophagy inhibitor, 3-methyladenine blocks the ameliorative effect of ghrelin on VC. Furthermore, protein expressions of phosphate-AMPK were increased by ghrelin treatment both in calcified aorta and VSMC. The effect of ghrelin on autophagy induction and VC attenuation was prevented by AMPK inhibitor, compound C. Our results suggested that ghrelin improved autophagy through AMPK activation, which was resulted in VC amelioration. These data maybe throw light on prevention and therapy of VC. Copyright © 2016 Elsevier Inc. All rights reserved.

Diagnostic accuracy of a volume-rendered computed tomography movie and other computed tomography-based imaging methods in assessment of renal vascular anatomy for laparoscopic donor nephrectomy.

PubMed

Yamamoto, Shingo; Tanooka, Masao; Ando, Kumiko; Yamano, Toshiko; Ishikura, Reiichi; Nojima, Michio; Hirota, Shozo; Shima, Hiroki

2009-12-01

To evaluate the diagnostic accuracy of computed tomography (CT)-based imaging methods for assessing renal vascular anatomy, imaging studies, including standard axial CT, three-dimensional volume-rendered CT (3DVR-CT), and a 3DVR-CT movie, were performed on 30 patients who underwent laparoscopic donor nephrectomy (10 right side, 20 left side) for predicting the location of the renal arteries and renal, adrenal, gonadal, and lumbar veins. These findings were compared with videos obtained during the operation. Two of 37 renal arteries observed intraoperatively were missed by standard axial CT and 3DVR-CT, whereas all arteries were identified by the 3DVR-CT movie. Two of 36 renal veins were missed by standard axial CT and 3DVR-CT, whereas 1 was missed by the 3DVR-CT movie. In 20 left renal hilar anatomical structures, 20 adrenal, 20 gonadal, and 22 lumbar veins were observed during the operation. Preoperatively, the standard axial CT, 3DVR-CT, and 3DVR-CT movie detected 11, 19, and 20 adrenal veins; 13, 14, and 19 gonadal veins; and 6, 11, and 15 lumbar veins, respectively. Overall, of 135 renal vascular structures, the standard axial CT, 3DVR-CT, and 3DVR-CT movie accurately detected 99 (73.3%), 113 (83.7%), and 126 (93.3%) vessels, respectively, which indicated that the 3DVR-CT movie demonstrated a significantly higher detection rate than other CT-based imaging methods (P < 0.05). The 3DVR-CT movie accurately provides essential information about the renal vascular anatomy before laparoscopic donor nephrectomy.

Multimodality Intra-Arterial Imaging Assessment of the Vascular Trauma Induced by Balloon-Based and Nonballoon-Based Renal Denervation Systems.

PubMed

Karanasos, Antonios; Van Mieghem, Nicolas; Bergmann, Martin W; Hartman, Eline; Ligthart, Jurgen; van der Heide, Elco; Heeger, Christian-H; Ouhlous, Mohamed; Zijlstra, Felix; Regar, Evelyn; Daemen, Joost

2015-07-01

Renal denervation is a new treatment considered for several possible indications. As new systems are introduced, the incidence of acute renal artery wall injury with relation to the denervation method is unknown. We investigated the acute repercussion of renal denervation on the renal arteries of patients treated with balloon-based and nonballoon-based denervation systems by quantitative angiography, intravascular ultrasound, and optical coherence tomography (OCT). Twenty-five patients (50 renal arteries) underwent bilateral renal denervation with 5 different systems, 3 of which balloon-based (Paradise [n=5], Oneshot [n=6], and Vessix V2 [n=5)]) and 2 nonballoon-based (Symplicity [n=6] and EnligHTN [n=3]). Analysis included quantitative angiography and morphometric intravascular ultrasound measurements pre and post procedure and assessment of vascular trauma (dissection, edema, or thrombus) by OCT after denervation. A significant reduction in lumen size by quantitative angiography and intravascular ultrasound was observed in nonballoon denervation but not in balloon denervation. By postdenervation OCT, dissection was seen in 14 arteries (32.6%). The percentage of frames with dissection was higher in balloon-based denervation catheters. Thrombus and edema were detected in 35 (81.4%) and 32 (74.4%) arteries, respectively. In arteries treated with balloon-based denervation that had dissection by OCT, the balloon/artery ratio was higher (1.24 [1.17-1.32] versus 1.10 [1.04-1.18]; P<0.01). A varying extent of vascular injury was observed after renal denervation in all systems; however, different patterns were identified in balloon-based and in nonballoon-based denervation systems. In balloon denervation, the presence of dissections by OCT was associated with a higher balloon/artery ratio. © 2015 American Heart Association, Inc.

Renal Vascular Clamp Placement: A Potential Cause of Incomplete Hilar Control during Partial Nephrectomy.

PubMed

Tryon, David; Myklak, Kristene; Alsyouf, Muhannad; Conceicao, Carol; Peplinski, Brandon; Arenas, Javier L; Faaborg, Daniel; Ruckle, Herbert C; Baldwin, D Duane

2016-03-01

Previous benchtop studies have shown that robotic bulldog clamps provide incomplete vascular control of a Penrose drain. We determined the efficacy of robotic and laparoscopic bulldog clamps to ensure hemostasis on the human renal artery. The effect of clamp position on vascular control was also examined. Fresh human cadaveric renal arteries were used to determine the leak point pressure of 7 bulldog clamps from a total of 3 manufacturers. Five trials were performed per clamp at 4 locations, including the fulcrum, proximal, middle and distal positions. Comparison was done using the Kruskal-Wallis test with p <0.05 considered significant. None of the bulldog clamps leaked at a pressure less than 215 mm Hg when applied at the proximal, middle or distal position. In general leak point pressure decreased as the artery was positioned more distal along the clamp. The exception was when the vessel was placed at the fulcrum position. At that position 80% to 100% of trials with the Klein laparoscopic, 100% with the Klein robotic (Klein Robotic, San Antonio, Texas) and 60% to 80% with the Scanlan robotic (Scanlan International, Saint Paul, Minnesota) clamp leaked at pressure below 215 mm Hg. Each vascular clamp adequately occluded flow at physiological pressure when placed at the proximal, middle or distal position. Furthermore, these results demonstrate that there is leakage at physiological pressure when the artery is placed at the fulcrum of certain clamp types. These results suggest that applying a bulldog clamp at the fulcrum could potentially lead to inadequate vessel occlusion and intraoperative bleeding. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Renal toxicity of anticancer agents targeting vascular endothelial growth factor (VEGF) and its receptors (VEGFRs).

PubMed

Cosmai, Laura; Gallieni, Maurizio; Liguigli, Wanda; Porta, Camillo

2017-04-01

Since angiogenesis plays a key role in tumor growth, progression and metastasization, anti-vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR) agents have been developed over the years as anticancer agents, and have changed, for the better, the natural history of a number of cancer types. In the present review, the renal safety profile of presently available agents targeting either VEGF or VEGFRs will be discussed, together with the peculiarities related to their clinical use in patients with impaired renal function, or even in dialysis. Indeed, renal toxicity (especially, but not exclusively, hypertension and proteinuria) are quite commonly observed with these agents, and may be increased by the concomitant use of cytoxic chemotherapeutics. Despite all the above, kidney impairment or dialysis must not be regarded di per se as reasons not to administer or to stop an active anticancer treatment, especially considering the possibility of a significant survival improvement in many cancer patients treated with these agents.

Renal responses to central vascular expansion are suppressed at night in conscious primates

NASA Technical Reports Server (NTRS)

Kass, D. A.; Sulzman, F. M.; Fuller, C. A.; Moore-Ede, M. C.

1980-01-01

The renal and hemodynamic responses of squirrel monkeys to central vascular volume expansion induced by lower body positive pressure (LBPP) during the day and night are investigated. Twelve unanesthetized animals trained to sit in a metabolism chair in which they were restrained only at the waist by a partition separating upper and lower body chambers were subjected to 4 h of continuous LBPP during the day and night, and hemodynamic, urinary and drinking data were monitored. LBPP during day and night is found to induce similar increases in central venous pressure, rises in heart rate and elevations in mean arterial blood pressure. However, although daytime LBPP induced a significant increase in urine flow and sodium excretion, a marked nocturnal inhibition of the renal response to LBPP is observed. Analysis of the time course and circadian regulation patterns of the urinary responses suggests that several separate efferent control pathways are involved.

Acute renal haemodynamic and renin-angiotensin system responses to graded renal artery stenosis in the dog.

PubMed Central

Anderson, W P; Johnston, C I; Korner, P I

1979-01-01

1. The acute renal haemodynamic and renin-angiotensin system responses to graded renal artery stenosis were studied in chronically instrumented, unanaesthetized dogs. 2. Stenosis was induced over 30 sec by inflation of a cuff around the renal artery to lower distal pressure to 60, 40 or 20 mmHg, with stenosis maintained for 1 hr. This resulted in an immediate fall in renal vascular resistance, but over the next 5--30 min both resistance and renal artery pressure were restored back towards prestenosis values. Only transient increases in systemic arterial blood pressure and plasma renin and angiotensin levels were seen with the two milder stenoses. Despite restoration of renal artery pressure, renal blood flow remained reduced at all grades of stenosis. 3. Pre-treatment with angiotensin I converting enzyme inhibitor or sarosine1, isoleucone8 angiotensin II greatly attenuated or abolished the restoration of renal artery pressure and renal vascular resistance after stenosis, and plasma renin and angiotensin II levels remained high. Renal dilatation was indefinitely maintained, but the normal restoration of resistance and pressure could be simulated by infusing angiotensin II into the renal artery. 4. The effective resistance to blood flow by the stenosis did not remain constant but varied with changes in the renal vascular resistance. PMID:219182

miR-21 Contributes to Xenon-conferred Amelioration of Renal Ischemia–Reperfusion Injury in Mice

PubMed Central

Jia, Ping; Teng, Jie; Zou, Jianzhou; Fang, Yi; Zhang, Xiaoyan; Bosnjak, Zeljko J.; Liang, Mingyu; Ding, Xiaoqiang

2015-01-01

Background MicroRNAs participate in the regulation of numerous physiological and disease processes. The in vivo role of microRNAs in anesthetics-conferred organoprotection is unknown. Methods Mice were exposed for 2 h to either 70% xenon, or 70% nitrogen, 24 h before the induction of renal ischemia-reperfusion injury. The role of microRNA, miR-21, in renal protection conferred by the delayed xenon preconditioning was examined using in vivo knockdown of miR-21 and analysis of miR-21 target pathways. Results Xenon preconditioning provided morphologic and functional protection against renal ischemia-reperfusion injury (n = 6), characterized by attenuation of renal tubular damage, apoptosis, and oxidative stress. Xenon preconditioning significantly increased the expression of miR-21 in the mouse kidney. A locked nucleic acid-modified anti–miR-21, given before xenon preconditioning, knocked down miR-21 effectively, and exacerbated subsequent renal ischemia-reperfusion injury. Mice treated with anti–miR-21 and ischemia-reperfusion injury showed significantly higher serum creatinine than antiscrambled oligonucleotides-treated mice, 24 h after ischemia-reperfusion (1.37 ± 0.28 vs. 0.81 ± 0.14 mg/dl; n = 5; P < 0.05). Knockdown of miR-21 induced significant up-regulation of programmed cell death protein 4 and phosphatase and tensin homolog deleted on chromosome 10, two proapoptotic target effectors of miR-21, and resulted in significant down-regulation of phosphorylated protein kinase B and increased tubular cell apoptosis. In addition, xenon preconditioning up-regulated hypoxia-inducible factor-1α and its downstream effector vascular endothelial growth factor in a time-dependent manner. Knockdown of miR-21 resulted in a significant decrease of hypoxia-inducible factor-1α. Conclusions These results indicate that miR-21 contributes to the renoprotective effect of xenon preconditioning. PMID:23681145

miR-21 contributes to xenon-conferred amelioration of renal ischemia-reperfusion injury in mice.

PubMed

Jia, Ping; Teng, Jie; Zou, Jianzhou; Fang, Yi; Zhang, Xiaoyan; Bosnjak, Zeljko J; Liang, Mingyu; Ding, Xiaoqiang

2013-09-01

MicroRNAs participate in the regulation of numerous physiological and disease processes. The in vivo role of microRNAs in anesthetics-conferred organoprotection is unknown. Mice were exposed for 2 h to either 70% xenon, or 70% nitrogen, 24 h before the induction of renal ischemia-reperfusion injury. The role of microRNA, miR-21, in renal protection conferred by the delayed xenon preconditioning was examined using in vivo knockdown of miR-21 and analysis of miR-21 target pathways. Xenon preconditioning provided morphologic and functional protection against renal ischemia-reperfusion injury (n = 6), characterized by attenuation of renal tubular damage, apoptosis, and oxidative stress. Xenon preconditioning significantly increased the expression of miR-21 in the mouse kidney. A locked nucleic acid-modified anti-miR-21, given before xenon preconditioning, knocked down miR-21 effectively, and exacerbated subsequent renal ischemia-reperfusion injury. Mice treated with anti-miR-21 and ischemia-reperfusion injury showed significantly higher serum creatinine than antiscrambled oligonucleotides-treated mice, 24 h after ischemia-reperfusion (1.37 ± 0.28 vs. 0.81 ± 0.14 mg/dl; n = 5; P < 0.05). Knockdown of miR-21 induced significant up-regulation of programmed cell death protein 4 and phosphatase and tensin homolog deleted on chromosome 10, two proapoptotic target effectors of miR-21, and resulted in significant down-regulation of phosphorylated protein kinase B and increased tubular cell apoptosis. In addition, xenon preconditioning up-regulated hypoxia-inducible factor-1α and its downstream effector vascular endothelial growth factor in a time-dependent manner. Knockdown of miR-21 resulted in a significant decrease of hypoxia-inducible factor-1α. These results indicate that miR-21 contributes to the renoprotective effect of xenon preconditioning.

Utility of 16-MDCT angiography for comprehensive preoperative vascular evaluation of laparoscopic renal donors.

PubMed

Raman, Steven S; Pojchamarnwiputh, Suwalee; Muangsomboon, Kobkun; Schulam, Peter G; Gritsch, H Albin; Lu, David S K

2006-06-01

Our objective was to determine the efficacy of 16-MDCT angiography in preoperative evaluation of vascular anatomy of laparoscopic renal donors. Fifty-five consecutive renal donors (25 men and 30 women) underwent 16-MDCT angiography followed by donor nephrectomy. In the arterial and nephrographic phases, images were acquired with 60% overlap and 0.6-mm reconstruction in both phases after 120 mL of iohexol was injected at 4 mL/sec. On a 3D workstation, images were evaluated retrospectively by two abdominal imagers blinded to surgical results with respect to number and branching pattern of renal arteries and major and minor renal veins. These CT angiography results were compared with surgical findings. The surgically confirmed sensitivity of both reviewers (1 and 2) using the MDCT data for detection of renal arteries was 98.5% (65 of 66), and accuracies were 97.0% for reviewer 1 and 95.5% for reviewer 2. Sensitivity and accuracy detection of renal veins was 97% (61 of 63) and 98% (62 of 63) for reviewer 1 and reviewer 2, respectively. Sensitivity and accuracy detection of early arterial bifurcation (< 2 cm from aorta) was 100% (14 of 14), and sensitivity in detection of late venous confluence (< 1.5 cm from aorta) was 100% (8 of 8). All major renal venous variants were identified; reviewer 1 identified 78% (18 of 23) minor venous variants, and reviewer 2 identified 83% (19 of 23) minor venous variants. There were no hemorrhagic complications at surgery. Excellent agreement between reviewers (kappa = 0.92-0.97) was achieved for detection of normal and variant anatomy. 16-MDCT angiography enabled excellent preoperative detection of arterial anatomy and venous laparoscopic donor nephrectomy.

Transarterial Embolization of a Renal Artery Aneurysm Concomitant With Renal Arteriovenous Fistula.

PubMed

Hongsakul, Keerati; Bannangkoon, Kittipitch; Boonsrirat, Ussanee; Kritpracha, Boonprasit

2018-01-01

Congenital renal artery aneurysm is uncommon. Moreover, renal artery aneurysm concomitant with a congenital renal arteriovenous fistula is extremely rare. Transarterial embolization is the first-line treatment for these conditions. We report a case of a patient with congenital renal artery aneurysm concomitant with a congenital renal arteriovenous fistula of the upper polar left renal artery which was successfully treated by transarterial embolization with coil, glue, and Amplatzer vascular plug.

COX-2 is involved in vascular oxidative stress and endothelial dysfunction of renal interlobar arteries from obese Zucker rats.

PubMed

Muñoz, Mercedes; Sánchez, Ana; Pilar Martínez, María; Benedito, Sara; López-Oliva, Maria-Elvira; García-Sacristán, Albino; Hernández, Medardo; Prieto, Dolores

2015-07-01

Obesity is related to vascular dysfunction through inflammation and oxidative stress and it has been identified as a risk factor for chronic renal disease. In the present study, we assessed the specific relationships among reactive oxygen species (ROS), cyclooxygenase 2 (COX-2), and endothelial dysfunction in renal interlobar arteries from a genetic model of obesity/insulin resistance, the obese Zucker rats (OZR). Relaxations to acetylcholine (ACh) were significantly reduced in renal arteries from OZR compared to their counterpart, the lean Zucker rat (LZR), suggesting endothelial dysfunction. Blockade of COX with indomethacin and with the selective blocker of COX-2 restored the relaxations to ACh in obese rats. Selective blockade of the TXA2/PGH2 (TP) receptor enhanced ACh relaxations only in OZR, while inhibition of the prostacyclin (PGI2) receptor (IP) enhanced basal tone and inhibited ACh vasodilator responses only in LZR. Basal production of superoxide was increased in arteries of OZR and involved NADPH and xanthine oxidase activation and NOS uncoupling. Under conditions of NOS blockade, ACh induced vasoconstriction and increased ROS generation that were augmented in arteries from OZR and blunted by COX-2 inhibition and by the ROS scavenger tempol. Hydrogen peroxide (H2O2) evoked both endothelium- and vascular smooth muscle (VSM)-dependent contractions, as well as ROS generation that was reduced by COX-2 inhibition. In addition, COX-2 expression was enhanced in both VSM and endothelium of renal arteries from OZR. These results suggest that increased COX-2-dependent vasoconstriction contributes to renal endothelial dysfunction through enhanced (ROS) generation in obesity. COX-2 activity is in turn upregulated by ROS. Copyright © 2015 Elsevier Inc. All rights reserved.

A bio-artificial renal epithelial cell system conveys survival advantage in a porcine model of septic shock.

PubMed

Westover, Angela J; Buffington, Deborah A; Johnston, Kimberly A; Smith, Peter L; Pino, Christopher J; Humes, H David

2017-03-01

Renal cell therapy using the hollow fiber based renal assist device (RAD) improved survival time in an animal model of septic shock (SS) through the amelioration of cardiac and vascular dysfunction. Safety and ability of the RAD to improve clinical outcomes was demonstrated in a Phase II clinical trial, in which patients had high prevalence of sepsis. Even with these promising results, clinical delivery of cell therapy is hampered by manufacturing hurdles, including cell sourcing, large-scale device manufacture, storage and delivery. To address these limitations, the bioartificial renal epithelial cell system (BRECS) was developed. The BRECS contains human renal tubule epithelial cells derived from adult progenitor cells using enhanced propagation techniques. Cells were seeded onto trabeculated disks of niobium-coated carbon, held within cryopreservable, perfusable, injection-moulded polycarbonate housing. The study objective was to evaluate the BRECS in a porcine model of SS to establish conservation of efficacy after necessary cell sourcing and design modifications; a pre-clinical requirement to move back into clinical trials. SS was incited by peritoneal injection of E. coli simultaneous to insertion of BRECS (n=10) or control (n=15), into the ultrafiltrate biofeedback component of an extracorporeal circuit. Comparable to RAD, prolonged survival of the BRECS cohort was conveyed through stabilization of cardiac output and vascular leak. In conclusion, the demonstration of conserved efficacy with BRECS therapy in a porcine SS model represents a crucial step toward returning renal cell therapy to the clinical setting, initially targeting ICU patients with acute kidney injury requiring continuous renal replacement therapy. Copyright © 2014 John Wiley & Sons, Ltd. Copyright © 2014 John Wiley & Sons, Ltd.

D-Saccharic acid 1,4-lactone protects diabetic rat kidney by ameliorating hyperglycemia-mediated oxidative stress and renal inflammatory cytokines via NF-κB and PKC signaling

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bhattacharya, Semantee; Manna, Prasenjit; Gachhui, Ratan

2013-02-15

Increasing evidence suggests that oxidative stress is involved in the pathogenesis of diabetic nephropathy (DN) and this can be attenuated by antioxidants. D-Saccharic acid 1,4-lactone (DSL) is known for its detoxifying and antioxidant properties. Our early investigation showed that DSL can ameliorate alloxan (ALX) induced diabetes mellitus and oxidative stress in rats by inhibiting pancreatic β-cell apoptosis. In the present study we, therefore, investigated the protective role of DSL against renal injury in ALX induced diabetic rats. ALX exposure (at a dose of 120 mg/kg body weight, i. p., once) elevated the blood glucose level, serum markers related to renalmore » injury, the production of reactive oxygen species (ROS), and disturbed the intra-cellular antioxidant machineries. Oral administration of DSL (80 mg/kg body weight) restored all these alterations close to normal. In addition, DSL could also normalize the aldose reductase activity which was found to increase in the diabetic rats. Investigating the mechanism of its protective activity, we observed the activation of different isoforms of PKC along with the accumulation of matrix proteins like collagen and fibronectin. The diabetic rats also showed nuclear translocation of NF-κB and increase in the concentration of inflammatory cytokines in the renal tissue. The activation of mitochondria dependent apoptotic pathway was observed in the diabetic rat kidneys. However, treatment of diabetic rats with DSL counteracted all these changes. These findings, for the first time, demonstrated that DSL could ameliorate renal dysfunction in diabetic rats by suppressing the oxidative stress related signalling pathways. - Highlights: ► Sustained hyperglycemia and oxidative stress lead to diabetic renal injury. ► D-saccharic acid 1,4-lactone prevents renal damage in alloxan-induced diabetes. ► It restores intra-cellular antioxidant machineries and kidney apoptosis. ► DSL reduces hyperglycemia-mediated oxidative

Eppur Si Muove: The dynamic nature of physiological control of renal blood flow by the renal sympathetic nerves.

PubMed

Schiller, Alicia M; Pellegrino, Peter Ricci; Zucker, Irving H

2017-05-01

Tubuloglomerular feedback and the myogenic response are widely appreciated as important regulators of renal blood flow, but the role of the sympathetic nervous system in physiological renal blood flow control remains controversial. Where classic studies using static measures of renal blood flow failed, dynamic approaches have succeeded in demonstrating sympathetic control of renal blood flow under normal physiological conditions. This review focuses on transfer function analysis of renal pressure-flow, which leverages the physical relationship between blood pressure and flow to assess the underlying vascular control mechanisms. Studies using this approach indicate that the renal nerves are important in the rapid regulation of the renal vasculature. Animals with intact renal innervation show a sympathetic signature in the frequency range associated with sympathetic vasomotion that is eliminated by renal denervation. In conscious rabbits, this sympathetic signature exerts vasoconstrictive, baroreflex control of renal vascular conductance, matching well with the rhythmic, baroreflex-influenced control of renal sympathetic nerve activity and complementing findings from other studies employing dynamic approaches to study renal sympathetic vascular control. In this light, classic studies reporting that nerve stimulation and renal denervation do not affect static measures of renal blood flow provide evidence for the strength of renal autoregulation rather than evidence against physiological renal sympathetic control of renal blood flow. Thus, alongside tubuloglomerular feedback and the myogenic response, renal sympathetic outflow should be considered an important physiological regulator of renal blood flow. Clinically, renal sympathetic vasomotion may be important for solving the problems facing the field of therapeutic renal denervation. Copyright © 2016 Elsevier B.V. All rights reserved.

Eppur Si Muove: The Dynamic Nature of Physiological Control of Renal Blood Flow by the Renal Sympathetic Nerves

PubMed Central

Schiller, Alicia M.; Pellegrino, Peter Ricci; Zucker, Irving H.

2016-01-01

Tubuloglomerular feedback and the myogenic response are widely appreciated as important regulators of renal blood flow, but the role of the sympathetic nervous system in physiological renal blood flow control remains controversial. Where classic studies using static measures of renal blood flow failed, dynamic approaches have succeeded in demonstrating sympathetic control of renal blood flow under normal physiological conditions. This review focuses on transfer function analysis of renal pressure-flow, which leverages the physical relationship between blood pressure and flow to assess the underlying vascular control mechanisms. Studies using this approach indicate that the renal nerves are important in the rapid regulation of the renal vasculature. Animals with intact renal innervation show a sympathetic signature in the frequency range associated with sympathetic vasomotion that is eliminated by renal denervation. In conscious rabbits, this sympathetic signature exerts vasoconstrictive, baroreflex control of renal vascular conductance, matching well with the rhythmic, baroreflex-influenced control of renal sympathetic nerve activity and complementing findings from other studies employing dynamic approaches to study renal sympathetic vascular control. In this light, classic studies reporting that nerve stimulation and renal denervation do not affect static measures of renal blood flow provide evidence for the strength of renal autoregulation rather than evidence against physiological renal sympathetic control of renal blood flow. Thus, alongside tubuloglomerular feedback and the myogenic response, renal sympathetic outflow should be considered an important physiological regulator of renal blood flow. Clinically, renal sympathetic vasomotion may be important for solving the problems facing the field of therapeutic renal denervation. PMID:27514571

Effect of healthy aging on renal vascular responses to local cooling and apnea

PubMed Central

Patel, Hardikkumar M.; Mast, Jessica L.; Sinoway, Lawrence I.

2013-01-01

Sympathetically mediated renal vasoconstriction may contribute to the pathogenesis of hypertension in older adults, but empirical data in support of this concept are lacking. In 10 young (26 ± 1 yr) and 11 older (67 ± 2 yr) subjects, we quantified acute hemodynamic responses to three sympathoexcitatory stimuli: local cooling of the forehead, cold pressor test (CPT), and voluntary apnea. We hypothesized that all stimuli would increase mean arterial blood pressure (MAP) and renal vascular resistance index (RVRI) and that aging would augment these effects. Beat-by-beat MAP, heart rate (HR), and renal blood flow velocity (from Doppler) were measured in the supine posture, and changes from baseline were compared between groups. In response to 1°C forehead cooling, aging was associated with an augmented MAP (20 ± 3 vs. 6 ± 2 mmHg) and RVRI (35 ± 6 vs. 16 ± 9%) but not HR. In older adults, there was a positive correlation between the cold-induced pressor response and forehead pain (R = 0.726), but this effect was not observed in young subjects. The CPT raised RVRI in both young (56 ± 13%) and older (45 ± 8%) subjects, but this was not different between groups. Relative to baseline, end-expiratory apnea increased RVRI to a similar extent in both young (46 ± 14%) and older (41 ± 9%) subjects. During sympathetic activation, renal vasoconstriction occurred in both groups. Forehead cooling caused an augmented pressor response in older adults that was related to pain perception. PMID:23640587

Aqueous extract of Boerhaavia diffusa root ameliorates ethylene glycol-induced hyperoxaluric oxidative stress and renal injury in rat kidney.

PubMed

Pareta, Surendra K; Patra, Kartik C; Mazumder, Papiya M; Sasmal, Dinakar

2011-12-01

Boerhaavia diffusa Linn. (Nyctaginaceae) is widely used in traditional Indian medicines against renal afflictions including calcium oxalate (CaOx) urolithiasis and is known for antioxidant activity. The present study was designed to investigate the ameliorating effect of aqueous extract of B. diffusa roots (BDE) in hyperoxaluric oxidative stress and renal cell injury. In vitro antioxidant activity of BDE was estimated in terms of total phenolic content and 1,1-diphenyl-2-picryl hydrazyl free radical scavenging activity. Wistar albino rats were given 0.75% v/v ethylene glycol in drinking water to induce chronic hyperoxaluria and simultaneously BDE was given to nephrolithiasic treated rats at the dose of 100 and 200 mg/kg b.w. orally for 28 days. Urinary volume, oxalate, serum creatinine, blood urea nitrogen (BUN), malondialdehyde (MDA) and antioxidant enzyme (SOD, CAT, GST, GPx) were evaluated. BDE extract was found to posses a high total phenolic content and exhibited significant free radicals scavenging activity. Oxalate excretion significantly increased in hyperoxaluric animals as compared to control which was protected in BDE-treated animals. BDE treatment significantly reduced level of MDA and improved the activity of antioxidant enzymes followed by reduction in BUN and serum creatinine. In addition, BDE reduced the number of CaOx monohydrate crystals in the urine. Histological analysis depicted that BDE treatment inhibited deposition of CaOx crystal and renal cell damage. The present study reveals that antioxidant activity of BDE significantly protects against hyperoxaluric oxidative stress and renal cell injury in urolithiasis.

Novel vascular endothelial growth factor blocker improves cellular viability and reduces hypobaric hypoxia-induced vascular leakage and oedema in rat brain.

PubMed

Saraswat, Deepika; Nehra, Sarita; Chaudhary, Kamal; CVS, Siva Prasad

2015-05-01

Vascular endothelial growth factor (VEGF) is an important cerebral angiogenic and permeability factor under hypoxia. There is a need to find effective molecules that may ameliorate hypoxia-induced cerebral oedema. In silico identification of novel candidate molecules that block VEGF-A site were identified and validated with a Ramachandran plot. The active site residues of VEGF-A were detected by Pocketfinder, CASTp, and DogSiteScorer. Based on in silico data, three VEGF-A blocker (VAB) candidate molecules (VAB1, VAB2, and VAB3) were checked for improvement in cellular viability and regulation of VEGF levels in N2a cells under hypoxia (0.5% O2 ). Additionally, the best candidate molecule's efficacy was assessed in male Sprague-Dawley rats for its ameliorative effect on cerebral oedema and vascular leakage under hypobaric hypoxia 7260 m. All experimental results were compared with the commercially available VEGF blocker sunitinib. Vascular endothelial growth factor-A blocker 1 was found most effective in increasing cellular viability and maintaining normal VEGF levels under hypoxia (0.5% oxygen) in N2a cells. Vascular endothelial growth factor-A blocker 1 effectively restored VEGF levels, decreased cerebral oedema, and reduced vascular leakage under hypobaric hypoxia when compared to sunitinib-treated rats. Vascular endothelial growth factor-A blocker 1 may be a promising candidate molecule for ameliorating hypobaric hypoxia-induced vasogenic oedema by regulating VEGF levels. © 2015 Wiley Publishing Asia Pty Ltd.

Retinoid agonist isotretinoin ameliorates obstructive renal injury.

PubMed

Schaier, Matthias; Jocks, Thomas; Grone, Hermann-Josef; Ritz, Eberhard; Wagner, Juergen

2003-10-01

Interstitial fibrosis is a major cause of end stage renal failure. Retinoids, which are involved in tissue repair and fibrosis, inhibit inflammatory and proliferative pathways. Therefore, we studied the dose dependent effects of the retinoid receptor agonist isotretinoin 13-cis retinoic acid in the unilateral ureteral obstruction model (UUO). Sham operated control rats were compared with UUO rats treated with vehicle (UUO-Veh), or low (5 mg/kg body weight (UUO-LD) or high (25 mg/kg) (UUO-HD) dose isotretinoin. Kidneys were evaluated using reverse transcriptase-polymerase chain reaction and immunohistology 7 days after UUO. Renal injury and fibrosis were quantified by immunostaining and expression measurements of the genes involved in renal fibrosis. In UUO-Veh kidneys the interstitial area was expanded 5-fold but only 3-fold in UUO-HD and 3.5-fold in UUO-LD rats. Interstitial cell counts were 3-fold higher in UUO-Veh rats but significantly less in UUO-HD or UUO-LD animals. Tubular and interstitial cell proliferation was significantly higher in UUO-Veh rats compared with sham operated control plus vehicle animals but less so in UUO-LD and UUO-HD rats. In UUO-Veh rats interstitial infiltration by monocytes/macrophages was higher compared with unobstructed controls. It was significantly less after isotretinoin treatment. In UUO-Veh rats mRNA for procollagen I, and transforming growth factor-beta1 and II receptor was significantly increased. It was significantly less after treatment with isotretinoin. Fibronectin and collagen I immunostaining was also decreased by isotretinoin. Since isotretinoin limits proliferation, inflammation and fibrosis after UUO, retinoids should be further investigated as potentially promising therapeutic agents for renal disease.

Cyclosporine A-induced nephrotoxicity is ameliorated by dose reduction and conversion to sirolimus in the rat.

PubMed

Sereno, J; Vala, H; Nunes, S; Rocha-Pereira, P; Carvalho, E; Alves, R; Teixeira, F; Reis, F

2015-04-01

Side-effect minimization strategies to avoid serious side-effects of cyclosporine A (CsA), such as nephrotoxicity, have been mainly based on dose reduction and conversion to other putatively less nephrotoxic drugs, such as sirolimus (SRL), an inhibitor of the mammalian target of rapamycin. This study intended to evaluate the impact of protocols based on CsA dose reduction and further conversion to SRL on kidney function and lesions, based on serum, urine and renal tissue markers. The following 3 groups (n=6) were tested during a 9-week protocol: control (vehicle); CsA (5 mg/kg/day) and Red + Conv (CsA 30 mg/kg/day during 3 weeks + 3 weeks with CsA 5 mg/kg/day + SRL 1 mg/kg/day during the last 3 weeks). The following parameters were analysed: blood pressure, heart rate and biochemical data; serum and urine contents and clearances of creatinine, urea and neutrophil gelatinase-associated lipocalin (NGAL), as well as, glomerular filtration rate; kidney lipid peroxidation and clearance; kidney lesions were evaluated and protein expression was performed by immunohistochemistry. After the first 3 weeks of CsA (30 mg/kg/day) treatment animals showed body weight loss, hypertension, tachycardia, as well as, increased serum levels of non-HDL cholesterol, glucose, triglycerides, creatinine and urea, accompanied by decreased GFR and insulin levels. In addition, a significant increase in the expression of connective tissue growth factor, kidney injury molecule-1 (KIM-1), mammalian target of rapamycin, nuclear factor-κβ1 and transforming growth factor-β was found in the kidney, accompanied by extensive renal damage. The following 3 weeks with CsA dose reduction revealed amelioration of vascular and glomerular lesions, but without significant tubular improvement. The last 3 weeks with the conversion to sirolimus revealed high serum and urine NGAL contents but the CsA-evoked renal damage was substantially ameliorated, by reduced of connective tissue growth factor, mammalian

Diabetes and Age-Related Differences in Vascular Function of Renal Artery: Possible Involvement of Endoplasmic Reticulum Stress.

PubMed

Matsumoto, Takayuki; Watanabe, Shun; Ando, Makoto; Yamada, Kosuke; Iguchi, Maika; Taguchi, Kumiko; Kobayashi, Tsuneo

2016-02-01

To study the time-course relationship between vascular functions and endoplasmic reticulum (ER) stress in type 2 diabetes, we investigated vascular function and associated protein expression, including cyclo-oxygenase (COX), ER stress, and apoptotic markers, in renal arteries (RA) from type 2 diabetic Otsuka Long-Evans Tokushima fatty (OLETF) rats at the young adult (4 months old) and aged (18 months old) stages. In the RA of aged OLETF (vs. young OLETF), we found: (1) Increased contractions induced by uridine adenosine tetraphosphate (Up4A) and phenylephrine, (2) decreased relaxation and increased contraction induced by acetylcholine (ACh) at lower and higher concentrations, respectively, and (3) increased expression of COX-1 and C/EBP-homologous protein (CHOP, a pro-apoptotic protein). In aged rats, the expression of COX-1, COX-2, PDI (an ER protein disulfide isomerase), Bax (a proapoptotic marker), and CHOP were increased in RA from OLETF rats (vs. age-matched control Long-Evans Tokushima Otsuka [LETO] rats). Up-regulation of PDI and Bax were seen in the RA from young OLETF (vs. young LETO) rats. No age-related alterations were apparent in the above changes in RA from LETO rats, excluding ACh-induced contraction. Short-term treatment with the ER stress inhibitor tauroursodeoxycholic acid (TUDCA, 100 mg/kg per day, intraperitoneally for 1 week) to OLETF rats at the chronic stage of the disease (12 months old) could suppress renal arterial contractions induced by Up4A and ACh. These results suggest that a long-term duration of disease may be important for the development of vascular dysfunction rather than aging per se. The early regulation of ER stress may be important against the development of diabetes-associated vascular dysfunction.

Comparison of the effects of levocetirizine and losartan on diabetic nephropathy and vascular dysfunction in streptozotocin-induced diabetic rats.

PubMed

Anbar, Hanan S; Shehatou, George S G; Suddek, Ghada M; Gameil, Nariman M

2016-06-05

This work was designed to investigate the effects of levocetirizine, a histamine H1 receptor antagonist, on diabetes-induced nephropathy and vascular disorder, in comparison to an angiotensin II receptor antagonist, losartan. Diabetes was induced in male Sprague Dawley rats by a single intraperitoneal injection of streptozotocin (50mg/kg). Diabetic rats were divided into three groups; diabetic, diabetic-levocetirizine (0.5mg/kg/day) and diabetic-losartan (25mg/kg/day). Treatments were started two weeks following diabetes induction and continued for additional eight weeks. At the end of the experiment, urine was collected and serum was separated for biochemical measurements. Tissue homogenates of kidney and aorta were prepared for measuring oxidative stress, nitric oxide (NO), transforming growth factor-β1 (TGF-β1) and tumor necrosis factor-α (TNF-α). Moreover, histological analyses were conducted and aortic vascular reactivity was investigated. Levocetirizine improved renal function in diabetic rats (evidenced by mitigation of diabetes-induced changes in kidney to body weight ratio, serum albumin, urinary proteins and creatinine clearance). Moreover, levocetirizine attenuated the elevated renal levels of TNF-α and TGF-β1, ameliorated renal oxidative stress and restored NO bioavailability in diabetic kidney. These effects were comparable to or surpassed those produced by losartan. Moreover, levocetirizine, similar to losartan, reduced the enhanced responsiveness of diabetic aorta to phenylephrine. Histological evaluation of renal and aortic tissues further confirmed the beneficial effects of levocetirizine on diabetic nephropathy and revealed a greater attenuation of diabetes-induced vascular hypertrophy by levocetirizine than by losartan. In conclusion, levocetirizine may offer comparable renoprotective effect to, and possibly superior vasculoprotective effects than, losartan in streptozotocin-diabetic rats. Copyright © 2016 Elsevier B.V. All rights reserved.

[Preoperative assessment of renal vascular anatomy for donor nephrectomy: Is CT superior to MRI?].

PubMed

Arvin-Berod, A; Bricault, I; Terrier, N; Skowron, O; Cadi, P; Boillot, B; Thuillier, C; Cluze, C; Descotes, J-L; Rambeaud, J-J; Long, J-A

2011-01-01

computed tomography angiography (CTA) and magnetic resonance angiography (MRA) are both used in the preoperative assessment of vascular anatomy before donor nephrectomy. Our objective was to determine retrospectively and to compare the sensitivity of CTA and MRA imaging in preoperative renal vascularisation in living kidney donors. between 1999 and 2007, 42 kidney donors were assessed in our center: 27 by MRA, 10 by CTA, and five by both techniques. Images were interpreted using multiplanar reconstructions. Results were compared retrospectively with peroperative findings; discordant cases were re-examined by an experienced radiologist. Numbers of vessels detected with imaging methods was compared with numbers actually found at the operating time. MRA showed 35/43 arteries (Se 81.4 %) and 33/34 veins (Se 97.1 %), and CTA showed 18/18 arteries (Se 100 %) and 15/16 veins (Se 93.8 %). The presence of multiple arteries was detected in only one third of cases (3/9) on MRI scans; this difference was statistically significant. The missed arteries were not detected on second examination of the MRI scans with the knowledge of peroperative findings. MRA is less sensitive than CTA for preoperative vascularisation imaging in living renal donors, especially in the detection of multiple renal arteries. 2010 Elsevier Masson SAS. All rights reserved.

14S,21R-dihydroxy-docosahexaenoic acid treatment enhances mesenchymal stem cell amelioration of renal ischemia/reperfusion injury.

PubMed

Tian, Haibin; Lu, Yan; Shah, Shraddha P; Wang, Quansheng; Hong, Song

2012-05-01

Bone marrow mesenchymal stem cells (MSCs) have shown potential to improve treatment of renal failure. The prohealing functions of MSCs have been found to be enhanced by treatment with the lipid mediator, 14S,21R-dihydroxy-docosa4Z,7Z,10Z,12E,16Z,19Z-hexaenoic acid (14S,21R-diHDHA). In this article, using a murine model of renal ischemia/reperfusion (I/R) injury, we found that treatment with 14S,21R-diHDHA enhanced MSC amelioration of renal I/R injury. Treated MSCs more efficiently inhibited I/R-induced elevation of serum creatinine levels, reduced renal tubular cell death, and inhibited infiltration of neutrophils, macrophages, and dendritic cells in kidneys. Conditioned medium from treated MSCs reduced the generation of tumor necrosis factor-α and reactive oxygen species by macrophages under I/R conditions. Infusion of treated MSCs more efficiently reduced I/R-damage to renal histological structures compared with untreated MSCs (injury score: 7.9±0.4 vs. 10.5±0.5). Treated MSCs were resistant to apoptosis in vivo when transplanted under capsules of I/R-injured kidneys (active caspase-3+ MSCs: 4.2%±2.8% vs. 11.7%±2.4% of control) and in vitro when cultured under I/R conditions. Treatment with 14S,21R-diHDHA promoted viability of MSCs through a mechanism involving activation of the phosphoinositide 3-kinase -Akt signaling pathway. Additionally, treatment of MSCs with 14S,21R-diHDHA promoted secretion of renotrophic hepatocyte growth factor and insulin growth factor-1. Similar results were obtained when 14S,21RdiHDHA was used to inhibit apoptosis of human MSCs (hMSCs) and to increase the generation of renotrophic cytokines from hMSCs. These findings provide a lead for new strategies in the treatment of acute kidney injury with MSCs.

Laparoscopic partial nephrectomy for renal tumor: Nagoya experience.

PubMed

Yoshikawa, Yoko; Ono, Yoshinari; Hattori, Ryohei; Gotoh, Momokazu; Yoshino, Yasushi; Katsuno, Satoshi; Katoh, Masashi; Ohshima, Shinichi

2004-08-01

To clarify the indication for a vascular clamp during laparoscopic partial nephrectomy, the clinical results of 17 patients who underwent the procedure for small renal tumors were reviewed. Seventeen patients with renal tumors were enrolled in our laparoscopic partial nephrectomy program between October 1999 and November 2003. During laparoscopy, a vascular clamp was used to remove the tumor mass and suture the incised renal parenchyma and urinary collecting system in 8 patients who had less-than-1-cm-thick renal parenchyma between the mass and the renal sinus or calices. In the remaining 9 patients, who had 1-cm-or-more-thick renal parenchyma between the mass and sinus or calices, renal bleeding was controlled using ultrasonic scissors, gauze tampon, argon beam coagulator, and fibrin glue. Sixteen patients were successfully treated with laparoscopy; one required conversion to open surgery because of uncontrollable bleeding. The average operative time was 4.5 hours, and average estimated bleeding volume was 301 mL. In the 8 patients requiring vascular clamping by forceps, the average ischemic time was 25 minutes. In all patients, the tumor mass was completely removed with negative surgical margins, and renal function was preserved. Three patients had prolonged urinary leakage for a mean of 21 days. Laparoscopic partial nephrectomy offers many advantages, including surgery that is both nephron sparing and minimally invasive. A vascular clamp was indicated for patients with less-than-1-cm-thick renal parenchyma between the tumor mass and renal sinus or calices.

Dynamic analysis of patterns of renal sympathetic nerve activity: implications for renal function.

PubMed

DiBona, Gerald F

2005-03-01

Methods of dynamic analysis are used to provide additional understanding of the renal sympathetic neural control of renal function. The concept of functionally specific subgroups of renal sympathetic nerve fibres conveying information encoded in the frequency domain is presented. Analog pulse modulation and pseudorandom binary sequence stimulation patterns are used for the determination of renal vascular frequency response. Transfer function analysis is used to determine the effects of non-renal vasoconstrictor and vasoconstrictor intensities of renal sympathetic nerve activity on dynamic autoregulation of renal blood flow.

Discordant effects of guanidines on renal structure and function and on regional vascular dysfunction and collagen changes in diabetic rats.

PubMed

Nyengaard, J R; Chang, K; Berhorst, S; Reiser, K M; Williamson, J R; Tilton, R G

1997-01-01

We examined the effects of aminoguanidine and methylguanidine on vascular dysfunction, glomerular structural changes, and indexes of early and late nonenzymatic glycation in 7-month streptozotocin-induced diabetic rats. Kidney weight, glomerular volume, fractional mesangial volume, glomerular capillary basement membrane width, and urinary albumin excretion were increased in diabetic rats. Diabetes also 1) increased vascular albumin permeation twofold in retina, sciatic nerve, aorta, skin, and kidney; 2) decreased renal collagenase-soluble collagen; 3) increased collagen-associated fluorescence in kidney and skin but not in aorta; and 4) increased glycated hemoglobin levels and aortic pentosidine levels. Aminoguanidine reduced albuminuria by 70% after 4 months, and both guanidines 1) normalized aortic pentosidine levels and renal collagenase-soluble collagen, 2) had no effect on glycated hemoglobin levels or collagen-associated fluorescence (in aorta, kidney, or skin), and 3) had little or no effect on regional albumin permeation. These discordant effects of aminoguanidine on diabetes-induced vascular changes versus parameters of nonenzymatic glycation are consistent with a multifactorial pathogenesis of diabetic complications, including roles for metabolic imbalances independent of nonenzymatic glycation. To the extent that glomerular matrix accumulation and increased regional albumin permeation in chronically diabetic rats are sequelae of nonenzymatic glycation, these findings point to an important role for early glycation reactions and products.

Renal Heme Oxygenase-1 Induction with Hemin Augments Renal Hemodynamics, Renal Autoregulation, and Excretory Function

PubMed Central

Botros, Fady T.; Dobrowolski, Leszek; Navar, L. Gabriel

2012-01-01

Heme oxygenases (HO-1; HO-2) catalyze conversion of heme to free iron, carbon monoxide, and biliverdin/bilirubin. To determine the effects of renal HO-1 induction on blood pressure and renal function, normal control rats (n = 7) and hemin-treated rats (n = 6) were studied. Renal clearance studies were performed on anesthetized rats to assess renal function; renal blood flow (RBF) was measured using a transonic flow probe placed around the left renal artery. Hemin treatment significantly induced renal HO-1. Mean arterial pressure and heart rate were not different (115 ± 5 mmHg versus 112 ± 4 mmHg and 331 ± 16 versus 346 ± 10 bpm). However, RBF was significantly higher (9.1 ± 0.8 versus 7.0 ± 0.5 mL/min/g, P < 0.05), and renal vascular resistance was significantly lower (13.0 ± 0.9 versus 16.6 ± 1.4 [mmHg/(mL/min/g)], P < 0.05). Likewise, glomerular filtration rate was significantly elevated (1.4 ± 0.2 versus 1.0 ± 0.1 mL/min/g, P < 0.05), and urine flow and sodium excretion were also higher (18.9 ± 3.9 versus 8.2 ± 1.0 μL/min/g, P < 0.05 and 1.9 ± 0.6 versus 0.2 ± 0.1 μmol/min/g, P < 0.05, resp.). The plateau of the autoregulation relationship was elevated, and renal vascular responses to acute angiotensin II infusion were attenuated in hemin-treated rats reflecting the vasodilatory effect of HO-1 induction. We conclude that renal HO-1 induction augments renal function which may contribute to the antihypertensive effects of HO-1 induction observed in hypertension models. PMID:22518281

Exercise training normalizes renal blood flow responses to acute hypoxia in experimental heart failure: role of the α1-adrenergic receptor.

PubMed

Pügge, Carolin; Mediratta, Jai; Marcus, Noah J; Schultz, Harold D; Schiller, Alicia M; Zucker, Irving H

2016-02-01

Recent data suggest that exercise training (ExT) is beneficial in chronic heart failure (CHF) because it improves autonomic and peripheral vascular function. In this study, we hypothesized that ExT in the CHF state ameliorates the renal vasoconstrictor responses to hypoxia and that this beneficial effect is mediated by changes in α1-adrenergic receptor activation. CHF was induced in rabbits. Renal blood flow (RBF) and renal vascular conductance (RVC) responses to 6 min of 5% isocapnic hypoxia were assessed in the conscious state in sedentary (SED) and ExT rabbits with CHF with and without α1-adrenergic blockade. α1-adrenergic receptor expression in the kidney cortex was also evaluated. A significant decline in baseline RBF and RVC and an exaggerated renal vasoconstriction during acute hypoxia occurred in CHF-SED rabbits compared with the prepaced state (P < 0.05). ExT diminished the decline in baseline RBF and RVC and restored changes during hypoxia to those of the prepaced state. α1-adrenergic blockade partially prevented the decline in RBF and RVC in CHF-SED rabbits and eliminated the differences in hypoxia responses between SED and ExT animals. Unilateral renal denervation (DnX) blocked the hypoxia-induced renal vasoconstriction in CHF-SED rabbits. α1-adrenergic protein in the renal cortex of animals with CHF was increased in SED animals and normalized after ExT. These data provide evidence that the acute decline in RBF during hypoxia is caused entirely by the renal nerves but is only partially mediated by α1-adrenergic receptors. Nonetheless, α1-adrenergic receptors play an important role in the beneficial effects of ExT in the kidney. Copyright © 2016 the American Physiological Society.

Renal artery and vein injury following blunt trauma.

PubMed Central

Sturm, J T; Perry, J F; Cass, A S

1975-01-01

Blunt injuries of the renal vascular pedicle occur infrequently. The experience with fourteen cases of blunt renal vascular trauma is presented. Most patients were injured in motor vehicle accidents. The diagnosis was made immediately after admission in 6 patients, delayed in 5, and at autopsy in 3. Most patients presented with gross or microscopic hematuria. The diagnosis of renal vascular injury was suggested by IVP in most instances. Surgical management was used in the 6 patients in whom the immediate diagnosis of renal pedicle injury was made; primary vascular repair was carried out in 4 patients and nephrectomy in two. Conservative management was used in 4 of the 5 patients with delayed diagnosis, and nephrectomy was required in the fifth. Three patients received no treatment as two were dead on arrival and one die during laparotomy. Seven patients died (50%). One of the 7 survivors has a functioning kidney following repair of a renal vein laceration. Three patients with devascularized kidneys have been followed long term and have not developed hypertension. An IVP should be mandatory following severe blunt trauma, especially when hematuria is present. Renal arteriography is indicated with distortion of calyces, extravasation or nonfunction seen on IVP and allows a definitive diagnosis of renal vessel injury to be made. PMID:1190872

Curative effect and safety of vascularized fibula grafting in renal transplant recipients with osteonecrosis of the femoral head: three case reports.

PubMed

Guo, Y J; Jin, D X; Zhang, C Q; Chen, S B; Sheng, J G; Lee, H S; Zhang, K G; Zeng, B F

2009-11-01

Osteonecrosis of the femoral head is a common and severe complication after renal transplantation. It is characterized by deterioration of hip joint function, which impairs quality of life. We present 3 renal transplant case reports of patients with osteonecrosis of the femoral head who underwent free vascularized fibular grafting at our hospital. Follow-up was from 1(1/2) to 2 years. All 3 patients exhibited good recovery with substantial improvement in joint function. Intraoperative and postoperative findings demonstrated the safety of this surgical procedure.

Origin of a common trunk for the inferior phrenic arteries from the right renal artery: a new anatomic vascular variant with clinical implications.

PubMed

Topaz, On; Topaz, Allyne; Polkampally, Pritam R; Damiano, Thomas; King, Christopher A

2010-01-01

The inferior phrenic arteries constitute a pair of important vessels, supplying multiple organs including the diaphragm, adrenal glands, esophagus, stomach, liver, inferior vena cava, and retroperitoneum. The vast majority (80-90%) of inferior phrenic arteries originate as separate vessels with near equal frequency from either the abdominal aorta or the celiac trunk. Infrequently, the right and left inferior phrenic arteries can arise in the form of a common trunk from the aorta or from the celiac trunk. We herein present three patients with a new anatomic vascular variant: a common trunk of the inferior phrenic arteries arising from the right renal artery. In one case, the left inferior phrenic branch of the common trunk provided collaterals connecting with a supra-diaphragmatic branch of the left internal mammary artery and in another with the lateral wall of the pericardium. Angiographic identification of a common trunk for the inferior phrenic arteries arising from the right renal artery is important for proper diagnosis and clinical management. The presence of this unique vascular variant can impact revascularization of the renal arteries. Published by Elsevier Inc.

The Effects of Renal Denervation on Renal Hemodynamics and Renal Vasculature in a Porcine Model

PubMed Central

Verloop, Willemien L.; Hubens, Lisette E. G.; Spiering, Wilko; Doevendans, Pieter A.; Goldschmeding, Roel; Bleys, Ronald L. A. W.; Voskuil, Michiel

2015-01-01

Rationale Recently, the efficacy of renal denervation (RDN) has been debated. It is discussed whether RDN is able to adequately target the renal nerves. Objective We aimed to investigate how effective RDN was by means of functional hemodynamic measurements and nerve damage on histology. Methods and Results We performed hemodynamic measurements in both renal arteries of healthy pigs using a Doppler flow and pressure wire. Subsequently unilateral denervation was performed, followed by repeated bilateral hemodynamic measurements. Pigs were terminated directly after RDN or were followed for 3 weeks or 3 months after the procedure. After termination, both treated and control arteries were prepared for histology to evaluate vascular damage and nerve damage. Directly after RDN, resting renal blood flow tended to increase by 29±67% (P = 0.01). In contrast, renal resistance reserve increased from 1.74 (1.28) to 1.88 (1.17) (P = 0.02) during follow-up. Vascular histopathology showed that most nerves around the treated arteries were located outside the lesion areas (8±7 out of 55±25 (14%) nerves per pig were observed within a lesion area). Subsequently, a correlation was noted between a more impaired adventitia and a reduction in renal resistance reserve (β: -0.33; P = 0.05) at three weeks of follow-up. Conclusion Only a small minority of renal nerves was targeted after RDN. Furthermore, more severe adventitial damage was related to a reduction in renal resistance in the treated arteries at follow-up. These hemodynamic and histological observations may indicate that RDN did not sufficiently target the renal nerves. Potentially, this may explain the significant spread in the response after RDN. PMID:26587981

Increased diuresis, renal vascular reactivity, and blood pressure levels in young rats fed high sodium, moderately high fructose, or their association: a comparative evaluation.

PubMed

Da Silva, Rita de Cássia Vilhena A F; de Souza, Priscila; da Silva-Santos, José Eduardo

2016-12-01

Excessive intakes of sodium or fructose have been described as risk factors for hypertension. We hypothesized that even a moderately high fructose diet (6% fructose), either alone or in combination with high sodium (4% NaCl), may impair diuresis and renal and systemic vascular reactivity, contributing to the onset of high blood pressure in rats. Male Wistar rats were fed chow containing 4% NaCl (HS), 6% fructose (MHF), or both 4% NaCl and 6% fructose (HSMHF) for 6 weeks and had their diuresis, plasma creatinine, vascular reactivity of perfused kidneys and systemic arterial pressure evaluated. We found no differences in augmented diuresis among animals given HS, MHF, or HSMHF diets. After 6 weeks both the HS and HSMHF groups had increased weight in their left kidneys, but only the HSMHF group showed augmented plasma creatinine. The effects of phenylephrine on renal vascular perfusion pressure were similarly enhanced in kidneys from the HS, MHF, and HSMHF groups, but not on the systemic arterial pressure. Although when evaluated in anesthetized rats, only the HSMHF group presented augmented blood pressure, evaluation in conscious animals revealed that both the MHF and HSMHF diets, but not the HS alone, were able to induce tachycardia and hypertension. In conclusion, a MHF diet containing 6% fructose was enough to render the renal vascular bed hyperreactive to phenylephrine and to induce both hypertension and tachycardia. The combination of 6% fructose with 4% NaCl led to plasma accumulation of creatinine and accelerated the development of tachycardia.

Morphological and clinical aspects of the occurrence of accessory (multiple) renal arteries

PubMed Central

Gulas, Ewelina; Wysiadecki, Grzegorz; Szymański, Jacek; Majos, Agata; Stefańczyk, Ludomir; Topol, Mirosław

2016-01-01

Renal vascularization variants vastly differ between individuals due to the very complex embryogenesis of the kidneys. Moreover, each variant may have implications for clinical and surgical interventions. The number of operating procedures continues to grow, and includes renal transplants, aneurysmorrhaphy and other vascular reconstructions. In any surgical technique, unawareness of the presence of multiple renal arteries may result in a fatal outcome, especially if laparoscopic methods are used. The aim of this review is to comprehensively identify the variation within multiple renal arteries and to highlight the connections between the presence of accessory renal arteries and the coexistence of other variants of vascularization. Another aim is to determine the potential clinical implications of the presence of accessory renal arteries. This study is of particular importance for surgeons, intervention radiologists, nephrologists and vascular surgeons. PMID:29593819

Vascular Disruption in Combination with mTOR Inhibition in Renal Cell Carcinoma

PubMed Central

Ellis, Leigh; Shah, Preeti; Hammers, Hans; Lehet, Kristin; Sotomayor, Paula; Azabdaftari, Gissou; Seshadri, Mukund; Pili, Roberto

2013-01-01

Renal cell carcinoma (RCC) is an angiogenesis-dependent and hypoxia-driven malignancy. As a result, there has been an increased interest in the use of antiangiogenic agents for the management of RCC in patients. However, the activity of tumor-vascular disrupting agents (tumor-VDA) has not been extensively examined against RCC. In this study, we investigated the therapeutic efficacy of the tumor-VDA ASA404 (DMXAA, 5,6-dimethylxanthenone-4-acetic acid, or vadimezan) in combination with the mTOR inhibitor everolimus (RAD001) against RCC. In vitro studies were carried out using human umbilical vein endothelial cells and in vivo studies using orthotopic RENCA tumors and immunohistochemical patient tumor-derived RCC xenografts. MRI was used to characterize the vascular response of orthotopic RENCA xenografts to combination treatment. Therapeutic efficacy was determined by tumor growth measurements and histopathologic evaluation. ASA404/everolimus combination resulted in enhanced inhibition of endothelial cell sprouting in the 3-dimensional spheroid assay. MRI of orthotopic RENCA xenografts revealed an early increase in permeability 4 hours posttreatment with ASA404, but not with everolimus. Twenty-four hours after treatment, a significant reduction in blood volume was observed with combination treatment. Correlative CD31/NG2 staining of tumor sections confirmed marked vascular damage following combination therapy. Histologic sections showed extensive necrosis and a reduction in the viable rim following combination treatment compared with VDA treatment alone. These results show the potential of combining tumor-VDAs with mTOR inhibitors in RCC. Further investigation into this novel combination strategy is warranted. PMID:22084164

Coexistence of pheochromocytoma with uncommon vascular lesions

PubMed Central

Kota, Sunil Kumar; Kota, Siva Krishna; Meher, Lalit Kumar; Jammula, Sruti; Panda, Sandip; Modi, Kirtikumar D.

2012-01-01

Background: Pheochromocytoma/paragangliomas have been described to be associated with rare vascular abnormalities like renal artery stenosis. Coexistence of physiologically significant renal artery lesions is a compounding factor that alters management and prognosis of pheochromocytoma patients. Apart from individual case reports, data on such association in Indian population is not available. The aim of this study is to find the nature and prevalence of associated vascular abnormalities. Materials and Methods: From 1990 to 2010, a total of 50 patients were diagnosed with pheochromocytoma/paragangliomas. Hospital charts of these patients were reviewed retrospectively to identify those with unusual vascular abnormalities. Available literature was also reviewed. Results: Of the 50 patients with pheochromocytoma, 7 (14%) had coexisting vascular lesions including renal artery stenosis in 4, aortoarteritis in 1, aortic aneurysm in 1 and inferior vena cava thrombosis in 1. Pheochromocytoma was adrenal in 42 and extra adrenal in 8. Laparoscopic adrenalectomy was done in the patients. One patient with renal artery stenosis due to intimal fibrosis was subjected to percutaneous balloon angioplasty; the other three improved after adrenalectomy and lysis of fibrous adhesive bands. The patient with aortoarteritos was treated with oral steroids. Inferior vena cava thrombosis was reversed with anticoagulants. The patient with abdominal aortic aneurysm was advised for annual follow-up on account of its size of 4.5 cm and asymptomatic presentation. Conclusion: There are multiple mechanisms that can lead to renal artery stenosis and other vascular abnormalities in a case of pheochromocytoma. A high index of suspicion is necessary to enable both entities to be diagnosed preoperatively and allow proper planning of surgical therapy. Incomplete diagnosis may lead to persistent hypertension postoperatively in a case of associated renal artery stenosis. PMID:23226643

Transcatheter Amplatzer vascular plug-embolization of a giant postnephrectomy arteriovenous fistula combined with an aneurysm of the renal pedicle by through-and-through, arteriovenous access

PubMed Central

Kayser, Ole; Schäfer, Philipp

2013-01-01

Although endovascular transcatheter embolization of arteriovenous fistulas is minimally invasive, the torrential flow prevailing within a fistula implies the risk of migration of the deployed embolization devices into the downstream venous and pulmonary circulation. We present the endovascular treatment of a giant postnephrectomy arteriovenous fistula between the right renal pedicle and the residual renal vein in a 63-year-old man. The purpose of this case report is to demonstrate that the Amplatzer vascular plug (AVP) can be safely positioned to embolize even relatively large arteriovenous fistulas (AVFs). Secondly, we illustrate that this occluder can even be introduced to the fistula via a transvenous catheter in cases where it is initially not possible to advance the deployment-catheter through a tortuous feeder artery. Migration of the vascular plug was ruled out at follow-up 4 months subsequently to the intervention. Thus, the Amplatzer vascular plug and the arteriovenous through-and-through guide wire access with subsequent transvenous deployment should be considered in similar cases. PMID:23326248

Naringin ameliorates sodium arsenite-induced renal and hepatic toxicity in rats: decisive role of KIM-1, Caspase-3, TGF-β, and TNF-α.

PubMed

Adil, Mohammad; Kandhare, Amit D; Visnagri, Asjad; Bodhankar, Subhash L

2015-01-01

Chronic exposure of a naturally occurring metal arsenic leads to renal and hepatic diseases. Naringin, a flavanone glycoside, possesses anti-inflammatory and anti-oxidant potential. The aim of this investigation was to evaluate the protective effect of naringin against arsenic-induced renal and hepatic toxicity in rats. Renal and hepatic toxicity was induced in rats by sodium arsenite (5 mg/kg, p.o.). Rats were treated orally with either vehicle or naringin (20, 40, and 80 mg/kg) or Coenzyme Q10 (10 mg/kg) for 28 days. Various biochemical, histological, and molecular biomarkers were assessed in kidney and liver. Treatment with naringin (40 and 80 mg/kg) significantly and dose-dependently restored (p < 0.01 and p < 0.001) altered levels of kidney (serum creatinine, urine creatinine, BUN, uric acid, and creatinine clearance) and liver function test (AST and ALT) induced by sodium arsenite. Elevated levels of oxido-nitrosative stress in renal and hepatic tissue was significantly and dose-dependently decreased (p < 0.01 and p < 0.001) by naringin (40 and 80 mg/kg) treatment. It significantly and dose-dependently down-regulated (p < 0.01 and p < 0.001) renal KIM-1, Caspase-3, TGF-β, and TNF-α mRNA expression. Histopathological alteration induced in kidney and liver by sodium arsenite was reduced by naringin (40 and 80 mg/kg) treatment. In conclusion, naringin treatment ameliorates arsenic-induced renal and hepatic damage in rats due its antioxidant and anti-inflammatory properties via down-regulation of elevated oxido-nitrosative stress, KIM-1, Caspase-3, TGF-β, and TNF-α levels.

Vascular Type 1A Angiotensin II Receptors Control BP by Regulating Renal Blood Flow and Urinary Sodium Excretion.

PubMed

Sparks, Matthew A; Stegbauer, Johannes; Chen, Daian; Gomez, Jose A; Griffiths, Robert C; Azad, Hooman A; Herrera, Marcela; Gurley, Susan B; Coffman, Thomas M

2015-12-01

Inappropriate activation of the type 1A angiotensin (AT1A) receptor contributes to the pathogenesis of hypertension and its associated complications. To define the role for actions of vascular AT1A receptors in BP regulation and hypertension pathogenesis, we generated mice with cell-specific deletion of AT1A receptors in smooth muscle cells (SMKO mice) using Loxp technology and Cre transgenes with robust expression in both conductance and resistance arteries. We found that elimination of AT1A receptors from vascular smooth muscle cells (VSMCs) caused a modest (approximately 7 mmHg) yet significant reduction in baseline BP and exaggerated sodium sensitivity in mice. Additionally, the severity of angiotensin II (Ang II)-dependent hypertension was dramatically attenuated in SMKO mice, and this protection against hypertension was associated with enhanced urinary excretion of sodium. Despite the lower BP, acute vasoconstrictor responses to Ang II in the systemic vasculature were largely preserved (approximately 80% of control levels) in SMKO mice because of exaggerated activity of the sympathetic nervous system rather than residual actions of AT1B receptors. In contrast, Ang II-dependent responses in the renal circulation were almost completely eliminated in SMKO mice (approximately 5%-10% of control levels). These findings suggest that direct actions of AT1A receptors in VSMCs are essential for regulation of renal blood flow by Ang II and highlight the capacity of Ang II-dependent vascular responses in the kidney to effect natriuresis and BP control. Copyright © 2015 by the American Society of Nephrology.

Renal Interstitial Arteriosclerotic Lesions in Lupus Nephritis Patients: A Cohort Study from China

PubMed Central

Qin, Dan-dan; Wu, Li-hua; Song, Yan; Yu, Feng; Wang, Su-xia; Liu, Gang; Zhao, Ming-hui

2015-01-01

Objective The aim of this study was to evaluate renal arteriosclerotic lesions in patients with lupus nephritis and investigate their associations with clinical and pathological characteristics, especially cardio-vascular features. Design A retrospective cohort study. Participants Seventy-nine patients with renal biopsy-proven lupus nephritis, diagnosed between January 2000 and June 2008 from Peking University First Hospital. Results In clinico-pathological data, patients with arteriosclerosis had higher ratio of hypertension and more severe renal injury indices compared with patients with no renal vascular lesions. More importantly, patients with renal arteriosclerosis had worse cardiac structure and function under transthoracic echocardiographic examination. Patients with renal arteriosclerosis tend to have higher ratios of combined endpoints compared with those of no renal vascular lesions, although the difference didn’t reach statistical meanings (P = 0.104). Conclusion Renal arteriosclerotic lesion was common and associated with vascular immune complex deposits in lupus nephritis. It might have a certain degree of association with poor outcomes and cardiovascular events, which needs further explorations. PMID:26544865

Inflammation in renal atherosclerotic disease.

PubMed

Udani, Suneel M; Dieter, Robert S

2008-07-01

The study of renal atherosclerotic disease has conventionally focused on the diagnosis and management of renal artery stenosis. With the increased understanding of atherosclerosis as a systemic inflammatory process, there has been increased interest in vascular biology at the microvasculature level. While different organ beds share some features, the inflammation and injury in the microvasculature of the kidney has unique elements as well. Understanding of the pathogenesis yields a better understanding of the clinical manifestations of renal atherosclerotic disease, which can be very subtle. Furthermore, identifying the molecular mechanisms responsible for the progression of kidney damage can also direct clinicians and scientists toward targeted therapies. Existing therapies used to treat atherosclerotic disease in other vascular beds may also play a role in the treatment of renal atherosclerotic disease.

Green Tea Polyphenols, Mimicking the Effects of Dietary Restriction, Ameliorate High-Fat Diet-Induced Kidney Injury via Regulating Autophagy Flux

PubMed Central

Xie, Xiao; Yi, Weijie; Zhang, Piwei; Wu, Nannan; Yan, Qiaoqiao; Yang, Hui; Tian, Chong; Xiang, Siyun; Du, Miying; Getachew Assefa, Eskedar; Zuo, Xuezhi; Ying, Chenjiang

2017-01-01

Epidemiological and experimental studies reveal that Western dietary patterns contribute to chronic kidney disease, whereas dietary restriction (DR) or dietary polyphenols such as green tea polyphenols (GTPs) can ameliorate the progression of kidney injury. This study aimed to investigate the renal protective effects of GTPs and explore the underlying mechanisms. Sixty Wistar rats were randomly divided into 6 groups: standard diet (STD), DR, high-fat diet (HFD), and three diets plus 200 mg/kg(bw)/day GTPs, respectively. After 18 weeks, HFD group exhibited renal injuries by increased serum cystatin C levels and urinary N-acetyl-β-d-glucosaminidase activity, which can be ameliorated by GTPs. Meanwhile, autophagy impairment as denoted by autophagy-lysosome related proteins, including LC3-II, Beclin-1, p62, cathepsin B, cathepsin D and LAMP-1, was observed in HFD group, whereas DR or GTPs promoted renal autophagy activities and GTPs ameliorated HFD-induced autophagy impairment. In vitro, autophagy flux suppression was detected in palmitic acid (PA)-treated human proximal tubular epithelial cells (HK-2), which was ameliorated by epigallocatechin-3-gallate (EGCG). Furthermore, GTPs (or EGCG) elevated phosphorylation of AMP-activated protein kinase in the kidneys of HFD-treated rats and in PA-treated HK-2 cells. These findings revealed that GTPs mimic the effects of DR to induce autophagy and exert a renal protective effect by alleviating HFD-induced autophagy suppression. PMID:28505110

Bilateral Renal Denervation Ameliorates Isoproterenol-Induced Heart Failure through Downregulation of the Brain Renin-Angiotensin System and Inflammation in Rat

PubMed Central

Li, Jian-Dong; Cheng, Ai-Yuan; Huo, Yan-Li; Fan, Jie; Zhang, Yu-Ping; Fang, Zhi-Qin; Sun, Hong-Sheng; Peng, Wei; Zhang, Jin-Shun

2016-01-01

Heart failure (HF) is characterized by cardiac dysfunction along with autonomic unbalance that is associated with increased renin-angiotensin system (RAS) activity and elevated levels of proinflammatory cytokines (PICs). Renal denervation (RD) has been shown to improve cardiac function in HF, but the protective mechanisms remain unclear. The present study tested the hypothesis that RD ameliorates isoproterenol- (ISO-) induced HF through regulation of brain RAS and PICs. Chronic ISO infusion resulted in remarked decrease in blood pressure (BP) and increase in heart rate and cardiac dysfunction, which was accompanied by increased BP variability and decreased baroreflex sensitivity and HR variability. Most of these adverse effects of ISO on cardiac and autonomic function were reversed by RD. Furthermore, ISO upregulated mRNA and protein expressions of several components of the RAS and PICs in the lamina terminalis and hypothalamic paraventricular nucleus, two forebrain nuclei involved in cardiovascular regulations. RD significantly inhibited the upregulation of these genes. Either intracerebroventricular AT1-R antagonist, irbesartan, or TNF-α inhibitor, etanercept, mimicked the beneficial actions of RD in the ISO-induced HF. The results suggest that the RD restores autonomic balance and ameliorates ISO-induced HF and that the downregulated RAS and PICs in the brain contribute to these beneficial effects of RD. PMID:27746855

Review of Surgical Techniques of Experimental Renal Transplantation in Rats.

PubMed

Shrestha, Badri; Haylor, John

2017-08-01

Microvascular surgical techniques of renal transplant in rats have evolved over the past 5 decades to achieve successful rat renal transplant; these modifications have included surgical techniques to address the anatomic variations in the renal blood vessels and those to reduce ischemic and operation durations. Here, we review the surgical techniques of renal transplant in rats and evaluate the advantages and disadvantages of individual techniques of vascular and ureteric anastomoses. For this review, we performed a systematic literature search using relevant medical subject heading terms and included appropriate publications in the review. Since the first description of a rat model of renal transplant by Bernard Fisher and his colleagues in 1965, which used end-to-side anastomosis between the renal vein and renal artery to the recipient inferior vena cava and aorta, several vascular and ureteric anastomosis techniques have been modified. Vascular anastomosis techniques now include end-to-end anastomosis, use of donor aortic and inferior vena cava conduits, sleeve and cuff anastomoses, and application of fibrin glue. Likewise, restoration of the urinary tract can now be achieved by direct anastomosis of the donor ureter to the recipient bladder, end-to-end anastomosis between the donor and recipient ureters, and donor bladder cuff to the recipient bladder. There are advantages and disadvantages attributable to individual techniques. The range of vascular and ureteric anastomosis techniques that has emerged reflects the need for mastering more than one technique to suit the vascular anatomy of individual animals and to reduce operating time for achieving successful outcomes after renal transplant.

Erythropoietin-enhanced endothelial progenitor cell recruitment in peripheral blood and renal vessels during experimental acute kidney injury in rats.

PubMed

Cakiroglu, Figen; Enders-Comberg, Sora Maria; Pagel, Horst; Rohwedel, Jürgen; Lehnert, Hendrik; Kramer, Jan

2016-03-01

Beneficial effects of erythropoietin (EPO) have been reported in acute kidney injury (AKI) when administered prior to induction of AKI. We studied the effects of EPO administration on renal function shortly after ischemic AKI. For this purpose, rats were subjected to renal ischemia for 30 min and EPO was administered at a concentration of 500 U/kg either i.v. as a single shot directly after ischemia or with an additional i.p. dose until 3 days after surgery. The results were compared with AKI rats without EPO application and a sham-operated group. Renal function was assessed by measurement of serum biochemical markers, histological grading, and using an isolated perfused kidney (IPK) model. Furthermore, we performed flow cytometry to analyze the concentration of endothelial progenitor cells (EPCs) in the peripheral blood and renal vessels. Following EPO application, there was only a statistically non-significant tendency of serum creatinine and urea to improve, particularly after daily EPO application. Renal vascular resistance and the renal perfusion rate were not significantly altered. In the histological analysis, acute tubular necrosis was only marginally ameliorated following EPO administration. In summary, we could not demonstrate a significant improvement in renal function when EPO was applied after AKI. Interestingly, however, EPO treatment resulted in a highly significant increase in CD133- and CD34-positive EPC both in the peripheral blood and renal vessels. © 2015 International Federation for Cell Biology.

Renal autotransplantation for vascular disease: late outcome according to etiology.

PubMed

Chiche, Laurent; Kieffer, Edouard; Sabatier, Jean; Colau, Alexandre; Koskas, Fabien; Bahnini, Amine

2003-02-01

The purpose of this study was to evaluate the early and late outcomes of renal autotransplantation (RAT) according to the etiology of the underlying renal artery disease. Between January 1985 and April 2001, we performed 68 RAT procedures in 57 patients. The surgical indications were fibromuscular dysplasia (FMD) for 34 RAT procedures in 30 patients (11 men, 19 women; mean age, 41.3 +/- 14.6 years), Takayasu's disease (TD) for 26 RAT procedures in 19 patients (five men, 14 women; mean age, 33.0 +/- 12.3 years), and atherosclerosis for eight RAT procedures in eight patients (seven men, one woman; mean age, 66.5 +/- 7.9 years). The incidence rate of hypertension was 87% in patients with FMD and 100% in patients with TD and atherosclerosis. The incidence rate of renal dysfunction was 75% in patients with atherosclerosis, 27% in patients with FMD, and 16% in patients with TD. Autotransplantation was isolated in 31 cases and was associated with another vascular procedure in 37 cases, including 22 thoracoabdominal aorta repairs and 11 abdominal aorta or iliac artery repairs. The technique used to achieve renal revascularization was direct reimplantation in 17 cases and indirect reimplantation in 51 cases. The conduit used for indirect reimplantation was an arterial autograft in 42 cases, a vein autograft in seven cases, and a prosthetic graft in two cases. Simultaneous revascularization of the contralateral kidney was performed in 21 patients and included nine RAT procedures. Contralateral nephrectomy was performed in five patients. In the FMD group, early segmental infarction was observed in four cases. Secondary nephrectomy was necessary in one case (at 88 months). Actuarial survival rates were 96.2% +/- 0.03% at 5 years and 84.1% +/- 0.11% at 10 years. Secondary patency rates were 100% at 5 years and 92% +/- 0.07% at 10 years. Hypertension normalized or improved in 96% of patients. Renal function improved in 50% of patients. In the TD group, one patient died of

Effect of microgravity on renal and femoral flows during LBNP & intravenous saline load

NASA Technical Reports Server (NTRS)

Arbeille, P.; Gaffney, F. A.; Beck, L.; Coulon, J.; Porcher, M.; Blomqvist, C. G.

1996-01-01

Renal and femoral hemodynamics were studied in crew members at rest and during lower body negative pressure before and after the D-2 Spacelab mission and with intravenous saline loading. Specific measurements included renal vascular resistance, femoral arterial flow, and vascular resistance, along with other cardiovascular parameters. Cardiovascular adaptation to microgravity is discussed with a focus on changes observed in femoral and renal vascular resistance.

[Vascular trombosis of renal graft: 9 cases].

PubMed

Kaaroud, Hayet; Béji, Soumaya; Ben Hamida, Fethi; Rais, Lamia; Ben Abdallah, Taieb; El Younsi, Fethi; Ben Moussa, Fatma; Abderrahim, Ezzedine; Bardi, Rafika; Ayed, Khaled; Chebil, Mohamed; Kheder, Adel

2008-04-01

Allograft renal thrombosis can occur in 1 to 6% of cases. Many predisposing factors has been identified especially alteration of coagulation. We analyzed in this study frequency and predisposing factors of renal graft thrombosis. We report a retrospective study including 319 renal transplant recipients. Nine patients (2.8%) presented veinous graft thrombosis in 5 cases and arterial thombosis in 4 cases. There were 6 men and 3 women aged of 30.6 years meanly (10-56) which developed the thrombosis 6 days (1-48) after the transplantation. All patients were detransplanted after 16.2 days and 1 patient died. Thrombosis constitute an important cause of graft loss. A perfect surgical technic and prophylactic treatment in high risk patients are necessary to reduce this complication.

Antibody and complement reduce renal hemodynamic function in isolated perfused rat kidney.

PubMed

Jocks, T; Zahner, G; Helmchen, U; Kneissler, U; Stahl, R A

1996-01-01

To evaluate the effect of antibody and complement on renal hemodynamic changes, glomerular injury was induced in isolated perfused kidneys by an anti-thymocyte antibody (ATS) and rat serum (RS). Glomerular filtration rate (GFR), renal vascular resistance (RVR), and renal perfusate flow (RPF) were assessed over an 80-min period. The possible role of thromboxane (Tx) was tested by the application of the Tx synthesis inhibitor UK-38485 and the Tx receptor blocker daltroban. Perfusion of kidneys with ATS and RS significantly reduced GFR at 10 min (control, 501 +/- 111; ATS + RS, 138 +/- 86 ml.g kidney-1.min-1, significance of F = 0.000) after RS. Similarly, RPF (ml.g kidney-1.min-1) fell from 19.2 +/- 1.8 to 6.1 +/- 2.0 (significance of F = 0.000), whereas RVR (mmHg.ml-1.g.min) increased threefold from 5.2 +/- 0.4 to 17.9 +/- 5.0 at 10 min. These changes were ameliorated by the pretreatment of the rats with daltroban and UK-38485. Addition of erythrocytes to the perfusate increased RVR and GFR, whereas RPF decreased compared with cell-free perfused kidneys. ATS and RS in this preparation also decrease GFR and RPF. The hemodynamic alterations appeared without changes in filtration fraction. Compared with untreated, perfused control kidneys, glomerular Tx formation was significantly increased in ATS and RS perfused kidneys. These data demonstrate that antibody and RS induce impairment of renal hemodynamics, which are mediated by increased Tx formation.

Klotho gene delivery ameliorates renal hypertrophy and fibrosis in streptozotocin-induced diabetic rats by suppressing the Rho-associated coiled-coil kinase signaling pathway.

PubMed

Deng, Minghong; Luo, Yumei; Li, Yunkui; Yang, Qiuchen; Deng, Xiaoqin; Wu, Ping; Ma, Houxun

2015-07-01

The present study aimed to investigate whether klotho gene delivery attenuated renal hypertrophy and fibrosis in streptozotocin-induced diabetic rats. A recombinant adeno-associated virus (rAAV) carrying mouse klotho full-length cDNA (rAAV.mKL), was constructed for in vivo investigation of klotho expression. Diabetes was induced in rats by a single tail vein injection of 60 mg/kg streptozotocin. Subsequently, the diabetic rats received an intravenous injection of rAAV.mKL, rAAV.green fluorescent protein (GFP) or phosphate-buffered saline (PBS). The Sprague-Dawley rat group received PBS and served as the control group. After 12 weeks, all the rats were sacrificed and ELISA, immunohistochemical and histological analyses, fluorescence microscopy, semi-quantitative reverse transcription-polymerase chain reaction and western blottin were performed. A single dose of rAAV.mKL was found to prevent the progression of renal hypertrophy and fibrosis for at least 12 weeks (duration of study). Klotho expression was suppressed in the diabetic rats, but was increased by rAAV.mKL delivery. rAAV.mKL significantly suppressed diabetes-induced renal hypertrophy and histopathological changes, reduced renal collagen fiber generation and decreased kidney hypertrophy index. In addition, rAAV.mKL decreased the protein expression levels of fibronectin and vimentin, while it downregulated the mRNA expression and activity of Rho-associated coiled-coil kinase (ROCK)I in the kidneys of the diabetic rats. These results indicated that klotho gene delivery ameliorated renal hypertrophy and fibrosis in diabetic rats, possibly by suppressing the ROCK signaling pathway. This may offer a novel approach for the long-term control and renoprotection of diabetes.

Naringin ameliorates gentamicin-induced nephrotoxicity and associated mitochondrial dysfunction, apoptosis and inflammation in rats: Possible mechanism of nephroprotection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sahu, Bidya Dhar; Tatireddy, Srujana; Koneru, Meghana

Gentamicin-induced nephrotoxicity has been well documented, although its underlying mechanisms and preventive strategies remain to be investigated. The present study was designed to investigate the protective effect of naringin, a bioflavonoid, on gentamicin-induced nephrotoxicity and to elucidate the potential mechanism. Serum specific renal function parameters (blood urea nitrogen and creatinine) and histopathology of kidney tissues were evaluated to assess the gentamicin-induced nephrotoxicity. Renal oxidative stress (lipid peroxidation, protein carbonylation, enzymatic and non-enzymatic antioxidants), inflammatory (NF-kB [p65], TNF-α, IL-6 and MPO) and apoptotic (caspase 3, caspase 9, Bax, Bcl-2, p53 and DNA fragmentation) markers were also evaluated. Significant decrease in mitochondrialmore » NADH dehydrogenase, succinate dehydrogenase, cytochrome c oxidase and mitochondrial redox activity indicated the gentamicin-induced mitochondrial dysfunction. Naringin (100 mg/kg) treatment along with gentamicin restored the mitochondrial function and increased the renal endogenous antioxidant status. Gentamicin induced increased renal inflammatory cytokines (TNF-α and IL-6), nuclear protein expression of NF-κB (p65) and NF-κB-DNA binding activity and myeloperoxidase (MPO) activity were significantly decreased upon naringin treatment. In addition, naringin treatment significantly decreased the amount of cleaved caspase 3, Bax, and p53 protein expression and increased the Bcl-2 protein expression. Naringin treatment also ameliorated the extent of histologic injury and reduced inflammatory infiltration in renal tubules. U-HPLS-MS data revealed that naringin co-administration along with gentamicin did not alter the renal uptake and/or accumulation of gentamicin in kidney tissues. These findings suggest that naringin treatment attenuates renal dysfunction and structural damage through the reduction of oxidative stress, mitochondrial dysfunction, inflammation and

Disruptive technological advances in vascular access for dialysis: an overview.

PubMed

Yeo, Wee-Song; Ng, Qin Xiang

2017-11-29

End-stage kidney disease (ESKD), one of the most prevalent diseases in the world and with increasing incidence, is associated with significant morbidity and mortality. Current available modes of renal replacement therapy (RRT) include dialysis and renal transplantation. Though renal transplantation is the preferred and ideal mode of RRT, this modality may not be available to all patients with ESKD. Moreover, renal transplant recipients are constantly at risk of complications associated with immunosuppression and immunosuppressant use, and posttransplant lymphoproliferative disorder. Dialysis may be the only available modality in certain patients. However, dialysis has its limitations, which include issues associated with lack of vascular access, risks of infections and vascular thrombosis, decreased quality of life, and absence of biosynthetic functions of the kidney. In particular, the creation and maintenance of hemodialysis vascular access in children poses a unique set of challenges to the pediatric nephrologist owing to the smaller vessel diameters and vascular hyperreactivity compared with adult patients. Vascular access issues continue to be one of the major limiting factors prohibiting the delivery of adequate dialysis in ESKD patients and is the Achilles' heel of hemodialysis. This review aims to provide a critical overview of disruptive technological advances and innovations for vascular access. Novel strategies in preventing neointimal hyperplasia, novel bioengineered products, grafts and devices for vascular access will be discussed. The potential impact of these solutions on improving the morbidity encountered by dialysis patients will also be examined.

New insights into saccular development and vascular formation in lung allografts under the renal capsule

PubMed Central

Vu, Thiennu H.; Alemayehu, Yemisrach; Werb, Zena

2009-01-01

The study of distal lung morphogenesis and vascular development would be greatly facilitated by an in vitro or ex vivo experimental model. In this study we show that the growth of mouse embryonic day 12.5 lung rudiments implanted underneath the kidney capsules of syngeneic or immunodeficient hosts follows closely lung development in utero. The epithelium develops extensively with both proximal and distal differentiation to the saccular stage. The vasculature also develops extensively. Large blood vessels accompany large airways and capillaries develop within the saccular walls. Interestingly, vessels in the lung grafts develop from endothelial progenitor cells endogenous to the explants and host vessels do not vascularize the grafts independently. This suggests that embryonic lungs possess mechanisms to prevent the inappropriate ingrowth of surrounding vessels. However, vessels in the lung grafts do connect to host vessels, showing that embryonic lungs have the ability to stimulate host angiogenesis and recruit host vessel connections. These data support the hypothesis that the lung vasculature develops by both vasculogenic and angiogenic processes: a vascular network develops in situ in lung mesenchyme, which is then connected to angiogenic processes from central vessels. The lung renal capsule allograft is thus an excellent model to study the development of the pulmonary vasculature and of late fetal lung development that requires a functional blood supply. PMID:12591600

Renal Artery Stump to Inferior Vena Cava Fistula: Unusual Clinical Presentation and Transcatheter Embolization with the Amplatzer Vascular Plug

DOE Office of Scientific and Technical Information (OSTI.GOV)

Taneja, Manish; Lath, Narayan, E-mail: lath_narayan@yahoo.com; Soo, Tan Bien

Fistulous communication between the renal artery stump and inferior vena cava following nephrectomy is rare. We describe the case of a 52-year-old man with a fistula detected on investigation for hemolytic anemia in the postoperative period. The patient had had a nephrectomy performed 2 weeks prior to presentation for blunt abdominal trauma. The fistula was successfully occluded percutaneously using an Amplatzer vascular plug. The patient recovered completely and was discharged 2 weeks later.

Zhen-wu-tang ameliorates adenine-induced chronic renal failure in rats: regulation of the canonical Wnt4/beta-catenin signaling in the kidneys.

PubMed

La, Lei; Wang, Lili; Qin, Fei; Jiang, Jian; He, Songqi; Wang, Chunxia; Li, Yuhao

2018-06-12

Zhen-wu-tang (ZWT), composed of Radix Aconiti lateralis, Rhizoma Atractylodis macrocephalae, Poria, Radix Paeoniae alba and ginger, is a classic Chinese herbal formula for the treatment of chronic kidney diseases that may cause chronic renal failure (CRF). To better understand its clinical use, this study investigated the effects and underlying mechanisms of action of ZWT on CRF. CRF was induced by adenine. ZWT was given via an oral gavage method. The serum biochemical parameters were measured enzymatically or by ELISA. The kidneys were examined pathohistologically. The gene expression was analyzed by real time PCR and Western blot. Similar to the positive control losartan, ZWT extract inhibited adenine-induced increase in serum concentrations of creatinine, BUN and advanced oxidation protein products in rats. These effects were accompanied by attenuation of proteinuria and renal pathological changes and suppression of renal mRNA and protein overexpression of Collagen IV and fibronectin, two of the key components of fibrosis. Mechanistically, renal mRNA and protein expression of Wnt4, a Wnt signaling ligand, was increased in the adenine-treated group, compared to the vehicle-treated control. Consistently, Wnt4 downstream genes beta-catenin and Axin were also overexpressed. Treatment with ZWT extract and losartan suppressed adenine-stimulated overexpression of these mRNAs and proteins. The present results demonstrate that ZWT extract ameliorates adenine-induced CRF in rats by regulation of the canonical Wnt4/beta-catenin signaling in the kidneys. Our findings provide new insight into the underlying renoprotective mechanisms of the ancient formula. Copyright © 2017. Published by Elsevier B.V.

Amelioration of pancreatic and renal derangements in streptozotocin-induced diabetic rats by polyphenol extracts of Ginger (Zingiber officinale) rhizome.

PubMed

Kazeem, Mutiu Idowu; Akanji, Musbau Adewunmi; Yakubu, Musa Toyin

2015-12-01

Free and bound polyphenol extracts of Zingiber officinale rhizome were investigated for their antidiabetic potential in the pancreatic and renal tissues of diabetic rats at a dose of 500mg/kg body weight. Forty Wistar rats were completely randomized into five groups: A-E consisting of eight animals each. Group A (control) comprises normal healthy animals and were orally administered 1.0mL distilled water on a daily basis for 42 days while group B-E were made up of 50mg/kg streptozotocin (STZ)-induced diabetic rats. Group C and D received 1.0mL 500mg/kg body weight free and bound polyphenol extracts respectively while group E received 1.0mL 0.6mg/kg of glibenclamide. Administration of the extracts to the diabetic rats significantly reduced (p<0.05) serum glucose and urea concentrations, increased (p<0.05) serum insulin and Homeostatic Model Assessment for β-cell dysfunction (HOMA-β) while the level of creatinine and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) were not affected. Histological examination of the pancreas and kidney revealed restoration of the structural derangements caused by streptozotocin in the polyphenol extracts treated diabetic rats compared to the control groups. Therefore, polyphenols from Zingiber officinale could ameliorate diabetes-induced pancreatic and renal derangements in rats. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Osteopontin deficiency ameliorates Alport pathology by preventing tubular metabolic deficits.

PubMed

Ding, Wen; Yousefi, Keyvan; Goncalves, Stefania; Goldstein, Bradley J; Sabater, Alfonso L; Kloosterboer, Amy; Ritter, Portia; Lambert, Guerline; Mendez, Armando J; Shehadeh, Lina A

2018-03-22

Alport syndrome is a rare hereditary renal disorder with no etiologic therapy. We found that osteopontin (OPN) is highly expressed in the renal tubules of the Alport mouse and plays a causative pathological role. OPN genetic deletion ameliorated albuminuria, hypertension, tubulointerstitial proliferation, renal apoptosis, and hearing and visual deficits in the Alport mouse. In Alport renal tubules we found extensive cholesterol accumulation and increased protein expression of dynamin-3 (DNM3) and LDL receptor (LDLR) in addition to dysmorphic mitochondria with defective bioenergetics. Increased pathological cholesterol influx was confirmed by a remarkably increased uptake of injected DiI-LDL cholesterol by Alport renal tubules, and by the improved lifespan of the Alport mice when crossed with the Ldlr-/- mice with defective cholesterol influx. Moreover, OPN-deficient Alport mice demonstrated significant reduction of DNM3 and LDLR expression. In human renal epithelial cells, overexpressing DNM3 resulted in elevated LDLR protein expression and defective mitochondrial respiration. Our results suggest a potentially new pathway in Alport pathology where tubular OPN causes DNM3- and LDLR-mediated enhanced cholesterol influx and impaired mitochondrial respiration.

Mild Electrical Stimulation and Heat Shock Ameliorates Progressive Proteinuria and Renal Inflammation in Mouse Model of Alport Syndrome

PubMed Central

Fukuda, Ryosuke; Morino-Koga, Saori; Suico, Mary Ann; Koyama, Kosuke; Sato, Takashi; Shuto, Tsuyoshi; Kai, Hirofumi

2012-01-01

Alport syndrome is a hereditary glomerulopathy with proteinuria and nephritis caused by defects in genes encoding type IV collagen in the glomerular basement membrane. All male and most female patients develop end-stage renal disease. Effective treatment to stop or decelerate the progression of proteinuria and nephritis is still under investigation. Here we showed that combination treatment of mild electrical stress (MES) and heat stress (HS) ameliorated progressive proteinuria and renal injury in mouse model of Alport syndrome. The expressions of kidney injury marker neutrophil gelatinase-associated lipocalin and pro-inflammatory cytokines interleukin-6, tumor necrosis factor-α and interleukin-1β were suppressed by MES+HS treatment. The anti-proteinuric effect of MES+HS treatment is mediated by podocytic activation of phosphatidylinositol 3-OH kinase (PI3K)-Akt and heat shock protein 72 (Hsp72)-dependent pathways in vitro and in vivo. The anti-inflammatory effect of MES+HS was mediated by glomerular activation of c-jun NH2-terminal kinase 1/2 (JNK1/2) and p38-dependent pathways ex vivo. Collectively, our studies show that combination treatment of MES and HS confers anti-proteinuric and anti-inflammatory effects on Alport mice likely through the activation of multiple signaling pathways including PI3K-Akt, Hsp72, JNK1/2, and p38 pathways, providing a novel candidate therapeutic strategy to decelerate the progression of patho-phenotypes in Alport syndrome. PMID:22937108

Renal denervation attenuates aldosterone expression and associated cardiovascular pathophysiology in angiotensin II-induced hypertension.

PubMed

Hong, Mo-Na; Li, Xiao-Dong; Chen, Dong-Rui; Ruan, Cheng-Chao; Xu, Jian-Zhong; Chen, Jing; Wu, Yong-Jie; Ma, Yu; Zhu, Ding-Liang; Gao, Ping-Jin

2016-10-18

The sympathetic nervous system interacts with the renin-angiotensin-aldosterone system (RAAS) contributing to cardiovascular diseases. In this study, we sought to determine if renal denervation (RDN) inhibits aldosterone expression and associated cardiovascular pathophysiological changes in angiotensin II (Ang II)-induced hypertension. Bilateral RDN or SHAM operation was performed before chronic 14-day Ang II subcutaneous infusion (200ng/kg/min) in male Sprague-Dawley rats. Bilateral RDN blunted Ang II-induced hypertension and ameliorated the mesenteric vascular dysfunction. Cardiovascular hypertrophy in response to Ang II was significantly attenuated by RDN as shown by histopathology and transthoracic echocardiography. Moreover, Ang II-induced vascular and myocardial inflammation and fibrosis were suppressed by RDN with concurrent decrease in fibronectin and collagen deposition, macrophage infiltration, and MCP-1 expression. Interestingly, RDN also inhibited Ang II-induced aldosterone expression in the plasma, kidney and heart. This was associated with the reduction of calcitonin gene-related peptide (CGRP) in the adrenal gland. Ang II promoted aldosterone secretion which was partly attenuated by CGRP in the adrenocortical cell line, suggesting a protective role of CGRP in this model. Activation of transforming growth factor-β (TGF-β)/Smad and mitogen-activated protein kinases (MAPKs) signaling pathway was both inhibited by RDN especially in the heart. These results suggest that the regulation of the renal sympathetic nerve in Ang II-induced hypertension and associated cardiovascular pathophysiological changes is likely mediated by aldosterone, with CGRP involvement.

Renal denervation attenuates aldosterone expression and associated cardiovascular pathophysiology in angiotensin II-induced hypertension

PubMed Central

Chen, Dong-Rui; Ruan, Cheng-Chao; Xu, Jian-Zhong; Chen, Jing; Wu, Yong-Jie; Ma, Yu; Zhu, Ding-Liang; Gao, Ping-Jin

2016-01-01

The sympathetic nervous system interacts with the renin-angiotensin-aldosterone system (RAAS) contributing to cardiovascular diseases. In this study, we sought to determine if renal denervation (RDN) inhibits aldosterone expression and associated cardiovascular pathophysiological changes in angiotensin II (Ang II)-induced hypertension. Bilateral RDN or SHAM operation was performed before chronic 14-day Ang II subcutaneous infusion (200ng/kg/min) in male Sprague-Dawley rats. Bilateral RDN blunted Ang II-induced hypertension and ameliorated the mesenteric vascular dysfunction. Cardiovascular hypertrophy in response to Ang II was significantly attenuated by RDN as shown by histopathology and transthoracic echocardiography. Moreover, Ang II-induced vascular and myocardial inflammation and fibrosis were suppressed by RDN with concurrent decrease in fibronectin and collagen deposition, macrophage infiltration, and MCP-1 expression. Interestingly, RDN also inhibited Ang II-induced aldosterone expression in the plasma, kidney and heart. This was associated with the reduction of calcitonin gene-related peptide (CGRP) in the adrenal gland. Ang II promoted aldosterone secretion which was partly attenuated by CGRP in the adrenocortical cell line, suggesting a protective role of CGRP in this model. Activation of transforming growth factor-β (TGF-β)/Smad and mitogen-activated protein kinases (MAPKs) signaling pathway was both inhibited by RDN especially in the heart. These results suggest that the regulation of the renal sympathetic nerve in Ang II-induced hypertension and associated cardiovascular pathophysiological changes is likely mediated by aldosterone, with CGRP involvement. PMID:27661131

Mechanism of postarrhythmic renal vasoconstriction in the anesthetized dog.

PubMed

Katholi, R E; Oparil, S; Urthaler, F; James, T N

1979-07-01

The mechanism of postarrhythmic renal vasoconstriction was studied in 28 dogs anesthetized with pentobarbital sodium (30 mg/kg i.v.). Rapid atrial or ventricular pacing or induction of atrial fibrilation were used to produce at least 20% prompt decrease in cardiac output and mean arterial blood pressure. Return to control cardiac output and blood pressure occurred within 3 minutes after cessation of the arrhythmia, but renal blood flow remained significantly decreased (26%) with gradual recovery by 17.7 +/- 6.6 min. Infusion of phentolamine (0.25 mg/min) into the renal artery, intravenous hexamethonium (l mg/kg), adrenal demedullation, or cooling the cervical vagi prevented postarrhythmic renal vasoconstriction. In contrast, renal denervation, intravenous bretylium (10 mg/kg), intravenous atropine (0.5 mg/kg) or intrarenal SQ 20881 (0.20 mg/min) has no effect on postarrhythmic renal vasoconstriction. Intravenous propranolol (0.5 mg/kg) intensified postarrhythmic renal vasoconstriction. These data suggested that the postarrhythmic renal vasoconstrictive response required intact vagi and was due to alpha adrenergic stimulation by adrenal catecholamines. However, femoral arterial catecholamine levels were not elevated above control during postarrhythmic renal vasoconstriction. We therefore sought local vascular pathways by which catecholamines might reach the kidneys. An adrenorenal vascular network was found in each dog. Collection of catecholamines from these vessels during postarrhythmic renal vasoconstriction in six dogs revealed catecholamine concentrations threefold higher than simultaneously collected femoral arterial catecholamines levels. Because ligation of these vessels abolished postarrhythmic renal vasoconstriction in each dog, we conclude that postarrhythmic renal vasconstriction is due to adrenal catecholamines reaching the kidneys through an adreno-renal vascular network and that the response requires intact vagi.

Progenitor-like cells derived from mouse kidney protect against renal fibrosis in a remnant kidney model via decreased endothelial mesenchymal transition.

PubMed

Chen, C L; Chou, K J; Fang, H C; Hsu, C Y; Huang, W C; Huang, C W; Huang, C K; Chen, H Y; Lee, P T

2015-12-02

Pathophysiological changes associated with chronic kidney disease impair angiogenic processes and increase renal fibrosis. Progenitor-like cells derived from adult kidney have been previously used to promote regeneration in acute kidney injury, even though it remained unclear whether the cells could be beneficial in chronic kidney disease (CKD). In this study, we established a CKD model by five-sixths nephrectomy and mouse kidney progenitor-like cells (MKPCs) were intravenously administered weekly for 5 weeks after establishing CKD. We examined the impact of MKPCs on the progression of renal fibrosis and the potential of MKPCs to preserve the angiogenic process and prevent endothelial mesenchymal transition in vivo and in vitro. Our results demonstrate that the MKPCs delayed interstitial fibrosis and the progression of glomerular sclerosis and ameliorated the decline of kidney function. At 17 weeks, the treated mice exhibited lower blood pressures, higher hematocrit levels, and larger kidney sizes than the control mice. In addition, the MKPC treatment prolonged the survival of the mice with chronic kidney injuries. We observed a decreased recruitment of macrophages and myofibroblasts in the interstitium and the increased tubular proliferation. Notably, MKPC both decreased the level of vascular rarefaction and prevented endothelial mesenchymal transition (EndoMT) in the remnant kidneys. Moreover, the conditioned medium from the MKPCs ameliorated endothelial cell death under hypoxic culture conditions and prevented TGF-β-induced EndoMT through downregulation of phosphorylated Smad 3 in vitro. MKPCs may be a beneficial treatment for kidney diseases characterized by progressive renal fibrosis. The enhanced preservation of angiogenic processes following MKPC injections may be associated with decreased fibrosis in the remnant kidney. These findings provide further understanding of the mechanisms involved in these processes and will help develop new cell

P2X7 receptor antagonism ameliorates renal dysfunction in a rat model of sepsis.

PubMed

Arulkumaran, Nishkantha; Sixma, Marije L; Pollen, Sean; Ceravola, Elias; Jentho, Elisa; Prendecki, Maria; Bass, Paul S; Tam, Frederick W K; Unwin, Robert J; Singer, Mervyn

2018-03-01

Sepsis is a major clinical problem associated with significant organ dysfunction and high mortality. The ATP-sensitive P2X 7 receptor activates the NLRP3 inflammasome and is a key component of the innate immune system. We used a fluid-resuscitated rat model of fecal peritonitis and acute kidney injury (AKI) to investigate the contribution of this purinergic receptor to renal dysfunction in sepsis. Six and 24 h time-points were chosen to represent early and established sepsis, respectively. A selective P2X 7 receptor antagonist (A-438079) dissolved in dimethyl sulfoxide (DMSO) was infused 2 h following induction of sepsis. Compared with sham-operated animals, septic animals had significant increases in heart rate (-1(-4 to 8)% vs. 21(12-26)%; P = 0.003), fever (37.4(37.2-37.6)°C vs. 38.6(38.2-39.0)°C; P = 0.0009), and falls in serum albumin (29(27-30)g/L vs. 26(24-28); P = 0.0242). Serum IL-1β (0(0-10)(pg/mL) vs. 1671(1445-33778)(pg/mL); P < 0.001) and renal IL-1β (86(50-102)pg/mg protein vs. 200 (147-248)pg/mg protein; P = 0.0031) were significantly elevated in septic compared with sham-operated animals at 6 h. Serum creatinine was elevated in septic animals compared with sham-operated animals at 24 h (23(22-25) μmol/L vs. 28 (25-30)μmol/L; P = 0.0321). Renal IL-1β levels were significantly lower in A-438079-treated animals compared with untreated animals at 6 h (70(55-128)pg/mg protein vs. 200(147-248)pg/mg protein; P = 0.021). At 24 h, compared with untreated animals, A-438079-treated animals had more rapid resolution of tachycardia (22(13-36)% vs. -1(-6 to 7)%; P = 0.019) and fever (39.0(38.6-39.1)°C vs. 38.2(37.6-38.7)°C; P < 0.024), higher serum albumin (23(21-25)g/L vs. (27(25-28)g/L); P = 0.006), lower arterial lactate (3.2(2.5-4.3)mmol/L vs. 1.4(0.9-1.8)mmol/L; P = 0.037), and lower serum creatinine concentrations (28(25-30)μmol/L vs. 22(17-27)μmol/L; P = 0.019). P2X 7 A treatment ameliorates the systemic

An unusual case of Y-shaped right renal vein.

PubMed

Lavy, M; Martin, L; Eouzan, D; Turco, C; Heyd, B; Mantion, G; Parratte, B; Tatu, L

2015-01-01

Vascular renal anomalies are frequent, multiple and well described and result from errors in vessel embryogenesis between the 6th and 10th week of gestation. Historically, variations are described in anatomic dissection and currently mostly in image interpretation. We report an anatomic variation concerning the right renal vein which, to our knowledge, has never been described in the literature either by dissection or by radiological examination. This variation was discovered during the routine dissection of an embalmed male body. It consists of a Y-shaped right renal vein and is associated with multiple retroperitoneal variations: a bilateral accessory renal artery, a trident ending of the right renal artery and a left testicular vein variation. Venous and arterial renal anatomy and its variations are fundamentally important in renal surgery, especially concerning living donor renal grafts. These variations may be diagnosed thanks to injected tomodensitometry which has a good sensitivity and specificity for anomalies. Preoperative diagnosis of an anatomic vascular renal variation may reduce morbidity during surgery, which is why precise examination of injected tomography should be mandatory.

Prostaglandin control of renal circulation in the unanesthetized dog and baboon

NASA Technical Reports Server (NTRS)

Swain, J. A.; Vatner, S. F.; Heyndrickx, G. R.; Boettcher, D. H.

1975-01-01

Effects of indomethacin and meclofenamate, inhibitors of prostaglandin synthesis, were evaluated in the regulation of renal blood flow in conscious and anesthetized dogs and in tranquilized baboons, instrumented with arterial pressure catheters and renal blood flow probes. Indomethacin, 10 mg/kg, did not alter renal blood flow or resistance significantly in the conscious dog. In the anesthetized dog, however, indomethacin caused a reduction in renal blood flow and an elevation of renal vascular resistance. Meclofenamate, 4 mg/kg, reduced renal flow and increased renal vascular resistance in conscious dogs. In conscious dogs and tranquilized primates, indomethacin and meclofenamate reduced the reactive hyperemia in the renal bed. Methoxamine and angiotensin II infused in graded doses induced significantly greater renal vasoconstriction in conscious dogs in the presence of indomethacin. Thus, in the conscious animal, prostaglandins appear to play only a minor part in the control of renal circulation at rest, but they are of greater importance in mediating the renal responses to reactive hyperemia and to vasoconstriction.

Renal Sympathetic Denervation in Rats Ameliorates Cardiac Dysfunction and Fibrosis Post-Myocardial Infarction Involving MicroRNAs

PubMed Central

Zheng, Xiaoxin; Li, Xiaoyan; Lyu, Yongnan; He, Yiyu; Wan, Weiguo; Jiang, Xuejun

2016-01-01

Background The role of renal sympathetic denervation (RSD) in ameliorating post-myocardial infarction (MI) left ventricular (LV) fibrosis via microRNA-dependent regulation of connective tissue growth factor (CTGF) remains unknown. Material/Methods MI and RSD were induced in Sprague–Dawley rats by ligating the left coronary artery and denervating the bilateral renal nerves, respectively. Norepinephrine, renin, angiotensin II and aldosterone in plasma, collagen, microRNA21, microRNA 101a, microRNA 133a and CTGF in heart tissue, as well as cardiac function were evaluated six weeks post-MI. Results In the RSD group, parameters of cardiac function were significantly improved as evidenced by increased LV ejection fraction (p<0.01), LV end-systolic diameter (p<0.01), end-diastolic diameter (p<0.05), LV systolic pressure (p<0.05), maximal rate of pressure rise and decline (dP/dtmax and dP/dtmin, p<0.05), and decreased LV end-diastolic pressure (p<0.05) when compared with MI rats. Further, reduced collagen deposition in peri-infarct myocardium was observed in RSD-treated rats along with higher microRNA101a and microRNA133a (p<0.05) and lower microRNA21 expression (p<0.01) than in MI rats. CTGF mRNA and protein levels were decreased in LV following RSD (p<0.01), accompanied by decreased expression of norepinephrine, renin, angiotensin II and aldosterone in plasma (p<0.05) compared with untreated MI rats. Conclusions The potential therapeutic effects of RSD on post-MI LV fibrosis may be partly mediated by inhibition of CTGF expression via upregulation of microRNA 101a and microRNA 133a and downregulation of microRNA21. PMID:27490896

Complications of transplantation. Part 1: renal transplants.

PubMed

Khaja, Minhaj S; Matsumoto, Alan H; Saad, Wael E

2014-10-01

Vascular complications after solid-organ transplantation are not uncommon and may lead to graft dysfunction and ultimately graft loss. A thorough understanding of the surgical anatomy, etiologies, and types of vascular complications, their presentation, and the options for management are important for managing these complex patients. This article reviews the basic surgical anatomy, vascular complications, and endovascular management options of vascular complications in patients with renal transplants.

1,[Formula: see text]2,[Formula: see text]3,[Formula: see text]4,[Formula: see text]6-Penta-O-Galloyl-β-D-Glucose from Galla rhois Ameliorates Renal Tubular Injury and Microvascular Inflammation in Acute Kidney Injury Rats.

PubMed

Park, Ji Hun; Kho, Min Chol; Oh, Hyun Cheol; Kim, Youn Chul; Yoon, Jung Joo; Lee, Yun Jung; Kang, Dae Gill; Lee, Ho Sub

2018-05-13

Renal ischemia-reperfusion injury (IRI), an important cause of acute kidney injury (AKI), causes increased renal tubular injury and microvascular inflammation. 1,[Formula: see text]2,[Formula: see text]3,[Formula: see text]4,[Formula: see text]6-penta-O-galloyl-[Formula: see text]-D-glucose (PGG) from Galla rhois has anticancer, anti-oxidation and angiogenesis effects. We examined protective effects of PGG on IRI-induced acute AKI. Clamping both renal arteries for 45[Formula: see text]min induced isechemia and then reperfusion. Treatment with PGG (10[Formula: see text]mg/kg/day and 50[Formula: see text]mg/kg/day for four days) significantly ameliorated urine volume, urine osmolality, creatinine clearance (Ccr) and blood urea nitrogen (BUN). In addition, PGG increased aquaporine 1/2/3, Na[Formula: see text]-K[Formula: see text]-ATPase and urea transporter (UT-B) and decreased ICAM-1, MCP-1, and HMGB-1 expression. In this histopathologic study, PGG improved glomerular and tubular damage. Immunohistochemistry results showed that PGG increased aquaporine 1/2, and Na[Formula: see text]-K[Formula: see text] ATPase and decreased ICAM-1 expression. These findings suggest that PGG ameliorates tubular injury including tubular dysfunction and microvascular inflammation in IRI-induced AKI rats.

The ethanol extract of Zingiber zerumbet rhizomes mitigates vascular lesions in the diabetic retina.

PubMed

Hong, Tang-Yao; Tzeng, Thing-Fong; Liou, Shorong-Shii; Liu, I-Min

2016-01-01

Diabetic retinopathy (DR) is a common diabetic eye disease which is well-known as the result of microvascular retinal changes. Although the ethanol extract from Zingiber zerumbet (L.) Smith rhizome (EEZZR) has been indicated to ameliorate hyperglycemia in diabetes, its protective effect on DR remains unclear. The aim of this study was to determine the effects of EEZZR on DR in streptozotocin (STZ) diabetic rats. Diabetic rats were treated orally with EEZZR (200, 300 mg/kg per day) or calcium dobesilate (CD; 500 mg/kg per day) for 12 weeks. EEZZR displayed similar characteristics to CD in reducing blood-retinal barrier permeability in diabetic rats. Retinal histopathological observation showed that retinal vessels were decreased in EEZZR-treated diabetic rats. EEZZR decreased the increased retinal expression of vascular endothelial growth factor (VEGF) and upregulate the expressions of renal pigment epithelium-derived factor (PEDF) in diabetic rats. Retinal mRNA expression of tumor necrosis factor-α, interleukin (IL)-1, IL-6, monocyte chemotactic proteins-1, intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 were all decreased in EEZZR-treated diabetic rats. Moreover, EEZZR could attenuate phosphorylation of nuclear factor Kappa B (NF-κB) p65 and extracellular signal-regulated kinase (ERK)1/2 as well as inhibit the nuclear translocation of pNF-κB p65 induced by diabetes. In conclusion, restoring the balance between stimulators and inhibitors of angiogenesis may be associated with the protective effect of EEZZR on DR. In addition, EEZZR can ameliorate retinal inflammation via transrepression of NF-κB and inhibition of ERK1/2 signaling pathway. Copyright © 2015 Elsevier Inc. All rights reserved.

Beneficial Effects of Different Flavonoids on Vascular and Renal Function in L-NAME Hypertensive Rats.

PubMed

Paredes, M Dolores; Romecín, Paola; Atucha, Noemí M; O'Valle, Francisco; Castillo, Julián; Ortiz, M Clara; García-Estañ, Joaquín

2018-04-13

we have evaluated the antihypertensive effect of several flavonoid extracts in a rat model of arterial hypertension caused by chronic administration (6 weeks) of the nitric oxide synthesis inhibitor, L-NAME. Sprague Dawley rats received L-NAME alone or L-NAME plus flavonoid-rich vegetal extracts (Lemon, Grapefruit + Bitter Orange, and Cocoa) or purified flavonoids (Apigenin and Diosmin) for 6 weeks. L-NAME treatment resulted in a marked elevation of blood pressure, and treatment with Apigenin, Lemon Extract, and Grapefruit + Bitter Orange extracts significantly reduced the elevated blood pressure of these animals. Apigenin and some of these flavonoids also ameliorated nitric oxide-dependent and -independent aortic vasodilation and elevated nitrite urinary excretion. End-organ abnormalities such as cardiac infarcts, hyaline arteriopathy and fibrinoid necrosis in coronary arteries and aorta were improved by these treatments, reducing the end-organ vascular damage. the flavonoids included in this study, specially apigenin, may be used as functional food ingredients with potential therapeutic benefit in arterial hypertension.

Vascular endothelial growth factor-A gene polymorphism is associated with congenital renal lesions in children with urinary tract infections.

PubMed

Bimpaki, Eirini; Bitsori, Maria; Choulaki, Christiana; Galanakis, Emmanouil

2017-08-01

This study investigated the relationship between vascular endothelial growth factor-A (VEGF-A)-460C/T functional gene polymorphism and renal parenchymal lesions, vesicoureteral reflux and other urinary tract abnormalities in children with a urinary tract infection (UTI). VEGF-A-460C/T gene polymorphism was investigated with restriction length polymorphism analysis in 76 children with their first UTI and in 63 controls without infections. Genotype and allele frequencies were compared between children with UTIs and controls and between different groups with UTIs. The VEGF-A-460C/T genotype frequencies differed significantly between those with and without renal parenchymal lesions in the UTI cohort. Allele C homozygosity was significantly more common in those with renal parenchymal lesions (36.6% versus 8.7%, p = 0.007). A separate analysis showed that allele C was associated with lesions compatible with hypodysplasia, rather than with focal ones associated with infections, with an odds ratio of 11.55 and 95% confidence interval of 3.03-43.9 (p = 0.0001). No significant differences in genotypes or allele frequencies were found between children with and without reflux or other urinary tract anomalies. In children with UTIs, C allele polymorphism of the VEGF-A gene was associated with hypodysplastic renal parenchymal lesions, which were possibly congenital and existed before the infection. ©2017 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

Amelioration of renal ischaemia–reperfusion injury by liposomal delivery of curcumin to renal tubular epithelial and antigen-presenting cells

PubMed Central

Rogers, NM; Stephenson, MD; Kitching, AR; Horowitz, JD; Coates, PTH

2012-01-01

BACKGROUND AND PURPOSE Renal ischaemia–reperfusion (IR) injury is an inevitable consequence of renal transplantation, causing significant graft injury, increasing the risk of rejection and contributing to poor long-term graft outcome. Renal injury is mediated by cytokine and chemokine synthesis, inflammation and oxidative stress resulting from activation of the NF-κB pathway. EXPERIMENTAL APPROACH We utilized liposomal incorporation of a potent inhibitor of the NF-κB pathway, curcumin, to target delivery to renal tubular epithelial and antigen-presenting cells. Liposomes containing curcumin were administered before bilateral renal ischaemia in C57/B6 mice, with subsequent reperfusion. Renal function was assessed from plasma levels of urea and creatinine, 4 and 24 h after reperfusion. Renal tissue was examined for NF-κB activity and oxidative stress (histology, immunostaining) and for apoptosis (TUNEL). Cytokines and chemokines were measured by RT-PCR and Western blotting. KEY RESULTS Liposomal curcumin significantly improved serum creatinine, reduced histological injury and cellular apoptosis and lowered Toll-like receptor-4, heat shock protein-70 and TNF-α mRNA expression. Liposomal curcumin also reduced neutrophil infiltration and diminished inflammatory chemokine expression. Curcumin liposomes reduced intracellular superoxide generation and increased superoxide dismutase levels, decreased inducible NOS mRNA expression and 3-nitrotyrosine staining consistent with limitations in nitrosative stress and inhibited renal tubular mRNA and protein expression of thioredoxin-interacting protein. These actions of curcumin were mediated by inhibition of NF-κB, MAPK and phospho-S6 ribosomal protein. CONCLUSIONS AND IMPLICATIONS Liposomal delivery of curcumin promoted effective, targeted delivery of this non-toxic compound that provided cytoprotection via anti-inflammatory and multiple antioxidant mechanisms following renal IR injury. PMID:21745189

Exogenous BMP7 in aortae of rats with chronic uremia ameliorates expression of profibrotic genes, but does not reverse established vascular calcification

PubMed Central

Gravesen, Eva; Lerche Mace, Maria; Nordholm, Anders; Hofman-Bang, Jacob; Hruska, Keith; Haagen Nielsen, Carsten; Kjær, Andreas; Olgaard, Klaus

2018-01-01

Hyperphosphatemia and vascular calcification are frequent complications of chronic renal failure and bone morphogenetic protein 7 (BMP7) has been shown to protect against development of vascular calcification in uremia. The present investigation examined the potential reversibility of established uremic vascular calcification by treatment of uremic rats with BMP7. A control model of isogenic transplantation of a calcified aorta from uremic rats into healthy littermates examined whether normalization of the uremic environment reversed vascular calcification. Uremia and vascular calcification were induced in rats by 5/6 nephrectomy, high phosphate diet and alfacalcidol treatment. After 14 weeks severe vascular calcification was present and rats were allocated to BMP7, vehicle or aorta transplantation. BMP7 treatment caused a significant decrease of plasma phosphate to 1.56 ± 0.17 mmol/L vs 2.06 ± 0.34 mmol/L in the vehicle group even in the setting of uremia and high phosphate diet. Uremia and alfacalcidol resulted in an increase in aortic expression of genes related to fibrosis, osteogenic transformation and extracellular matrix calcification, and the BMP7 treatment resulted in a decrease in the expression of profibrotic genes. The total Ca-content of the aorta was however unchanged both in the abdominal aorta: 1.9 ± 0.6 μg/mg tissue in the vehicle group vs 2.2 ± 0.6 μg/mg tissue in the BMP7 group and in the thoracic aorta: 71 ± 27 μg/mg tissue in the vehicle group vs 54 ± 18 μg/mg tissue in the BMP7 group. Likewise, normalization of the uremic environment by aorta transplantation had no effect on the Ca-content of the calcified aorta: 16.3 ± 0.6 μg/mg tissue pre-transplantation vs 15.9 ± 2.3 μg/mg tissue post-transplantation. Aortic expression of genes directly linked to extracellular matrix calcification was not affected by BMP7 treatment, which hypothetically might explain persistent high Ca-content in established vascular calcification. The present

How can a vascular surgeon help in kidney transplantation.

PubMed

Lejay, Anne; Thaveau, Fabien; Caillard, Sophie; Georg, Yannick; Moulin, Bruno; Wolf, Philippe; Geny, Bernard; Chakfe, Nabil

2017-04-01

Kidney transplantation is a surgical procedure involving both vascular and ureteric anastomoses. As a matter of fact, it can be performed either by urologists or vascular surgeons. However, vascular surgeon's expertise can be helpful at different times. In the present paper we describe how can vascular surgeons help at the different stages of kidney transplantation process in modern care: 1) before kidney transplantation for recipient preparation in order to allow subsequent graft implantation, either by performing percutaneous embolization of renal arteries in the setting of polycystic kidney disease or treatment of aneurysmal or occlusive lesions that would contra-indicate graft implantation; 2) at the time of surgery graft back table preparation and repair; and 3) after surgery for long-term follow-up, including transplant renal artery stenosis treatment or transplant nephrectomy.

Renal osteodystrophy, phosphate homeostasis, and vascular calcification.

PubMed

Hruska, Keith A; Saab, Georges; Mathew, Suresh; Lund, Richard

2007-01-01

New advances in the pathogenesis of renal osteodystrophy (ROD) change the perspective from which many of its features and treatment are viewed. Calcium, phosphate, parathyroid hormone (PTH), and vitamin D have been shown to be important determinants of survival associated with kidney diseases. Now ROD dependent and independent of these factors is linked to survival more than just skeletal frailty. This review focuses on recent discoveries that renal injury impairs skeletal anabolism decreasing the osteoblast compartment of the skeleton and consequent bone formation. This discovery and the discovery that PTH regulates the hematopoietic stem cell niche alters our view of secondary hyperparathyroidism in chronic kidney disease (CKD) from that of a disease to that of a necessary adaptation to renal injury that goes awry. Furthermore, ROD is shown to be an underappreciated factor in the level of the serum phosphorus in CKD. The discovery and the elucidation of the mechanism of hyperphosphatemia as a cardiovascular risk in CKD change the view of ROD. It is now recognized as more than a skeletal disorder, it is an important component of the mortality of CKD that can be treated.

Bioengineering in renal transplantation: technological advances and novel options.

PubMed

Yeo, Wee-Song; Zhang, Yao-Chun

2017-06-06

End-stage kidney disease (ESKD) is one of the most prevalent diseases in the world with significant morbidity and mortality. Current modes of renal replacement therapy include dialysis and renal transplantation. Although dialysis is an acceptable mode of renal replacement therapy, it does have its shortcomings, which include poorer life expectancy compared with renal transplantation, risk of infections and vascular thrombosis, lack of vascular access and absence of biosynthetic functions of the kidney. Renal transplantation, in contrast, is the preferred option of renal replacement therapy, with improved morbidity and mortality rates and quality of life, compared with dialysis. Renal transplantation, however, may not be available to all patients with ESKD. Some of the key factors limiting the availability and efficiency of renal transplantation include shortage of donor organs and the constant risk of rejection with complications associated with over-immunosuppression respectively. This review focuses chiefly on the potential roles of bioengineering in overcoming limitations in renal transplantation via the development of cell-based bioartificial dialysis devices as bridging options before renal transplantation, and the development of new sources of organs utilizing cell and organ engineering.

Osteopontin deficiency ameliorates Alport pathology by preventing tubular metabolic deficits

PubMed Central

Ding, Wen; Goncalves, Stefania; Goldstein, Bradley J.; Sabater, Alfonso L.; Kloosterboer, Amy; Ritter, Portia; Lambert, Guerline; Mendez, Armando J.

2018-01-01

Alport syndrome is a rare hereditary renal disorder with no etiologic therapy. We found that osteopontin (OPN) is highly expressed in the renal tubules of the Alport mouse and plays a causative pathological role. OPN genetic deletion ameliorated albuminuria, hypertension, tubulointerstitial proliferation, renal apoptosis, and hearing and visual deficits in the Alport mouse. In Alport renal tubules we found extensive cholesterol accumulation and increased protein expression of dynamin-3 (DNM3) and LDL receptor (LDLR) in addition to dysmorphic mitochondria with defective bioenergetics. Increased pathological cholesterol influx was confirmed by a remarkably increased uptake of injected DiI-LDL cholesterol by Alport renal tubules, and by the improved lifespan of the Alport mice when crossed with the Ldlr–/– mice with defective cholesterol influx. Moreover, OPN-deficient Alport mice demonstrated significant reduction of DNM3 and LDLR expression. In human renal epithelial cells, overexpressing DNM3 resulted in elevated LDLR protein expression and defective mitochondrial respiration. Our results suggest a potentially new pathway in Alport pathology where tubular OPN causes DNM3- and LDLR-mediated enhanced cholesterol influx and impaired mitochondrial respiration. PMID:29563333

Rhynchophylline Ameliorates Endothelial Dysfunction via Src-PI3K/Akt-eNOS Cascade in the Cultured Intrarenal Arteries of Spontaneous Hypertensive Rats

PubMed Central

Hao, Hui-Feng; Liu, Li-Mei; Pan, Chun-Shui; Wang, Chuan-She; Gao, Yuan-Sheng; Fan, Jing-Yu; Han, Jing-Yan

2017-01-01

Objectives: To examine the protective effect of Rhynchophylline (Rhy) on vascular endothelial function in spontaneous hypertensive rats (SHRs) and the underlying mechanism. Methods: Intrarenal arteries of SHRs and Wistar rats were suspended in myograph for force measurement. Expression and phosphorylation of endothelial nitric oxide (NO) synthase (eNOS), Akt, and Src kinase (Src) were examined by Western blotting. NO production was assayed by ELISA. Results: Rhy time- and concentration-dependently improved endothelium-dependent relaxation in the renal arteries from SHRs, but had no effect on endothelium-independent relaxation in SHR renal arteries. Wortmannin (an inhibitor of phosphatidylinositol 3-kinase) or PP2 (an inhibitor of Src) inhibited the improvement of relaxation in response to acetylcholine by 12 h-incubation with 300 μM Rhy. Western blot analysis revealed that Rhy elevated phosphorylations of eNOS, Akt, and Src in SHR renal arteries. Moreover, wortmannin reversed the increased phosphorylations of Akt and eNOS induced by Rhy, but did not affect the phosphorylation of Src. Furthermore, the enhanced phosphorylations of eNOS, Akt, and Src were blunted by PP2. Importantly, Rhy increased NO production and this effect was blocked by inhibition of Src or PI3K/Akt. Conclusion: The present study provides evidences for the first time that Rhy ameliorates endothelial dysfunction in SHRs through the activation of Src-PI3K/Akt-eNOS signaling pathway. PMID:29187825

Effect of complete hilar versus only renal artery clamping on renal histomorphology following ischemia/reperfusion injury in an experimental model.

PubMed

Umul, M; Cal, A C; Turna, B; Oktem, G; Aydın, H H

2016-01-01

To evaluate the effect of temporary complete hilar versus only renal artery clamping with different duration of warm ischemia on renal functions, and possibly identify a "safe" clamping type and duration of renal ischemia. Fifty male rabbits have been incorporated to study. Rabbits were subjected to ischemia/reperfusion injury by temporary vascular clamping. Reagents were randomized to 3 experimental groups (only renal artery clamping, complete hilar clamping, sham surgery) and sub-groups were determined according to different clamping times (30 and 60 minutes). Median laparotomy and left renal hilus dissection were performed to sham group. Only artery or complete hilar clamping was performed for 30 or 60 minutes by microvascular bulldog clamps to other reagents. Rabbits were sacrificed 10 days after primary surgery and left nephrectomy performed. Nephrectomy materials were evaluated for the level of nitric-oxide synthase (NOS) immunoreactivity, malondialdehyde (MDA) level and superoxide dismutase (SOD) activity and an electron microscopic examination was performed. NOS immunoreactivity was correlated with the temporary clamping time. We also observed that complete hilar vascular clamping entails an increase on NOS immunoreactivity. MDA levels were similar for all experimental surgery groups (p = 0.42). The SOD activity was decreased among all subgroups compared with sham surgery. But the significant decrease occurred in 30 minutes only artery and 30 minutes complete hilar clamping groups in proportion to sham surgery (p = 0.026 and p = 0.019, respectively). This current study suggested that only renal artery clamping under 30 minutes is more appropriate during renal surgical procedures requiring temporary vascular clamping.

Atorvastatin and sildenafil decrease vascular TGF-β levels and MMP-2 activity and ameliorate arterial remodeling in a model of renovascular hypertension

PubMed Central

Guimarães, Danielle A.; Rizzi, Elen; Ceron, Carla S.; Martins-Oliveira, Alisson; Gerlach, Raquel F.; Shiva, Sruti; Tanus-Santos, Jose E.

2015-01-01

Imbalanced matrix metalloproteinase (MMP)-2 activity and transforming growth factor expression (TGF-β) are involved in vascular remodeling of hypertension. Atorvastatin and sildenafil exert antioxidant and pleiotropic effects that may result in cardiovascular protection. We hypothesized that atorvastatin and sildenafil alone or in association exert antiproliferative effects by down-regulating MMP-2 and TGF-β, thus reducing the vascular hypertrophy induced by two kidney, one clip (2K1C) hypertension. Sham and 2K1C rats were treated with oral atorvastatin 50 mg/kg, sildenafil 45 mg/kg, or both, daily for 8 weeks. Blood pressure was monitored weekly. Morphologic changes in the aortas were studied. TGF-β levels were determined by immunofluorescence. MMP-2 activity and expression were determined by in situ zymography, gel zymography, Western blotting, and immunofluorescence. The effects of both drugs on proliferative responses of aortic smooth muscle cells to PDGF and on on MMP-2 activity in vitro were determined. Atorvastatin, sildenafil, or both drugs exerted antiproliferative effects in vitro. All treatments attenuated 2K1C-induced hypertension and prevented the increases in the aortic cross-sectional area and media/lumen ratio in 2K1C rats. Aortas from 2K1C rats showed higher collagen deposition, TGF-β levels and MMP-2 activity and expression when compared with Sham-operated animals. Treatment with atorvastatin and/or sildenafil was associated with attenuation of 2K1C hypertension-induced increases in these pro-fibrotic factors. However, these drugs had no in vitro effects on hr-MMP-2 activity. Atorvastatin and sildenafil was associated with decreased vascular TGF-β levels and MMP-2 activity in renovascular hypertensive rats, thus ameliorating the vascular remodeling. These novel pleiotropic effects of both drugs may translate into protective effects in patients. PMID:26343345

Amelioration of renal ischaemia-reperfusion injury by liposomal delivery of curcumin to renal tubular epithelial and antigen-presenting cells.

PubMed

Rogers, N M; Stephenson, M D; Kitching, A R; Horowitz, J D; Coates, P T H

2012-05-01

Renal ischaemia-reperfusion (IR) injury is an inevitable consequence of renal transplantation, causing significant graft injury, increasing the risk of rejection and contributing to poor long-term graft outcome. Renal injury is mediated by cytokine and chemokine synthesis, inflammation and oxidative stress resulting from activation of the NF-κB pathway. We utilized liposomal incorporation of a potent inhibitor of the NF-κB pathway, curcumin, to target delivery to renal tubular epithelial and antigen-presenting cells. Liposomes containing curcumin were administered before bilateral renal ischaemia in C57/B6 mice, with subsequent reperfusion. Renal function was assessed from plasma levels of urea and creatinine, 4 and 24 h after reperfusion. Renal tissue was examined for NF-κB activity and oxidative stress (histology, immunostaining) and for apoptosis (TUNEL). Cytokines and chemokines were measured by RT-PCR and Western blotting. Liposomal curcumin significantly improved serum creatinine, reduced histological injury and cellular apoptosis and lowered Toll-like receptor-4, heat shock protein-70 and TNF-α mRNA expression. Liposomal curcumin also reduced neutrophil infiltration and diminished inflammatory chemokine expression. Curcumin liposomes reduced intracellular superoxide generation and increased superoxide dismutase levels, decreased inducible NOS mRNA expression and 3-nitrotyrosine staining consistent with limitations in nitrosative stress and inhibited renal tubular mRNA and protein expression of thioredoxin-interacting protein. These actions of curcumin were mediated by inhibition of NF-κB, MAPK and phospho-S6 ribosomal protein. Liposomal delivery of curcumin promoted effective, targeted delivery of this non-toxic compound that provided cytoprotection via anti-inflammatory and multiple antioxidant mechanisms following renal IR injury. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

Pulse pressure and nocturnal fall in blood pressure are predictors of vascular, cardiac and renal target organ damage in hypertensive patients (LOD-RISK study).

PubMed

García-Ortiz, Luis; Gómez-Marcos, Manuel A; Martín-Moreiras, Javier; González-Elena, Luis J; Recio-Rodriguez, Jose I; Castaño-Sánchez, Yolanda; Grandes, Gonzalo; Martínez-Salgado, Carlos

2009-08-01

To analyse the relationship between various parameters derived from ambulatory blood pressure monitoring (ABPM) and vascular, cardiac and renal target organ damage. A cross-sectional, descriptive study. It included 353 patients with short-term or recently diagnosed hypertension. ABPM, carotid intima-media thickness (IMT), Cornell voltage-duration product (Cornell VDP), glomerular filtration rate and albumin/creatinine ratio to assess vascular, cardiac and renal damage. Two hundred and twenty-three patients (63.2%) were males, aged 56.12+/-11.21 years. The nocturnal fall in blood pressure was 11.33+/-8.41, with a dipper pattern in 49.0% (173), nondipper in 30.3% (107), extreme dipper in 12.7% (45) and riser in 7.9% (28). The IMT was lower in the extreme dipper (0.716+/-0.096 mm) and better in the riser pattern (0.794+/-0.122 mm) (P<0.05). The Cornell VDP and albumin/creatinine ratio were higher in the riser pattern (1818.94+/-1798.63 mm/ms and 140.78+/-366.38 mg/g, respectively) than in the other patterns. In the multivariate analysis after adjusting for age, sex and antihypertensive treatment, with IMT as dependent variable the 24-h pulse pressure (beta = 0.003), with Cornell VDP the rest pulse pressure (beta = 12.04), and with the albumin/creatinine ratio the percentage of nocturnal fall in systolic blood pressure (beta = -3.59), the rest heart rate (beta = 1.83) and the standard deviation of 24-h systolic blood pressure (beta = 5.30) remain within the equation. The estimated pulse pressure with ABPM is a predictor of vascular and cardiac organ damage. The nocturnal fall and the standard deviation in 24-h systolic blood pressure measured with the ABPM is a predictor of renal damage.

The relationship of systemic markers of renal function and vascular function with retinal blood vessel responses.

PubMed

Heitmar, R; Varma, C; De, P; Lau, Y C; Blann, A D

2016-11-01

To test the hypothesis of a significant relationship between systemic markers of renal and vascular function (processes linked to cardiovascular disease and its development) and retinal microvascular function in diabetes and/or cardiovascular disease. Ocular microcirculatory function was measured in 116 patients with diabetes and/or cardiovascular disease using static and continuous retinal vessel responses to three cycles of flickering light. Endothelial function was evaluated by von Willebrand factor (vWf), endothelial microparticles and soluble E selectin, renal function by serum creatinine, creatinine clearance and estimated glomerular filtration rate (eGFR). HbA1c was used as a control index. Central retinal vein equivalence and venous maximum dilation to flicker were linked to HbA1c (both p < 0.05). Arterial reaction time was linked to serum creatinine (p = 0.036) and eGFR (p = 0.039); venous reaction time was linked to creatinine clearance (p = 0.018). Creatinine clearance and eGFR were linked to arterial maximum dilatation (p < 0.001 and p = 0.003, respectively) and the dilatation amplitude (p = 0.038 and p = 0.048, respectively) responses in the third flicker cycle. Of venous responses to the first flicker cycle, HbA1c was linked to the maximum dilation response (p = 0.004) and dilatation amplitude (p = 0.017), vWf was linked to the maximum constriction response (p = 0.016), and creatinine clearance to the baseline diameter fluctuation (p = 0.029). In the second flicker cycle, dilatation amplitude was linked to serum creatinine (p = 0.022). Several retinal blood vessel responses to flickering light are linked to glycaemia and renal function, but only one index is linked to endothelial function. Renal function must be considered when interpreting retinal vessel responses.

Preoperative evaluation of renal anatomy and renal masses with helical CT, 3D-CT and 3D-CT angiography.

PubMed

Toprak, Uğur; Erdoğan, Aysun; Gülbay, Mutlu; Karademir, Mehmet Alp; Paşaoğlu, Eşref; Akar, Okkeş Emrah

2005-03-01

The aim of this prospective study was to determine the efficacy of three-dimensional computed tomography (3D-CT) and three-dimensional computed tomographic angiography (3D-CTA) that were reconstructed by using the axial images of the multiphasic helical CT in the preoperative evaluation of renal masses and demonstration of renal anatomy. Twenty patients that were suspected of having renal masses upon initial physical examination and ultrasonographic evaluation were examined through multiphasic helical CT. Two authors executed CT evaluations. Axial images were first examined and then used to reconstruct 3D-CT and 3D- CTA images. Number, location and size of the renal masses and other findings were noted. Renal vascularization and relationships of the renal masses with the neighboring renal structures were further investigated with 3D-CT and 3D-CTA images. Out of 20 patients, 13 had histopathologically proven renal cell carcinoma. The diagnoses of the remaining seven patients were xanthogranulomatous pyelonephritis, abscess, simple cyst, infected cyst, angiomyolipoma, oncocytoma and arteriovenous fistula. In the renal cell carcinoma group, 3 patients had stage I, 7 patients had stage II, and 3 patients had stage III disease. Sizes of renal cell carcinoma masses were between 23 mm to 60 mm (mean, 36 mm). Vascular invasion was shown in 2 renal cell carcinoma patients. Collecting system invasion was identified in 11 of 13 renal cell patients. These radiologic findings were confirmed with surgical specimens. Three-dimensional CT and 3D-CTA are non-invasive, effective imaging techniques for the preoperative evaluation of renal masses.

Endothelial bioreactor system ameliorates multiple organ dysfunction in septic rats.

PubMed

Ma, Shuai; Lin, Yuli; Deng, Bo; Zheng, Yin; Hao, Chuanming; He, Rui; Ding, Feng

2016-12-01

The endothelium is a potentially valuable target for sepsis therapy. We have previously studied an extracorporeal endothelial cell therapy system, called the endothelial bioreactor (EBR), which prolonged the survival time of endotoxemia sepsis in swine. To further study of the therapeutic effects and possible mechanisms, we established a miniature EBR system for septic rats induced by cecal ligation and puncture (CLP). In the miniature EBR system, the extracorporeal circulation first passed through a mini-hemofilter, and the ultrafiltrate (UF) was separated, then the UF passed through an EBR (a 1-mL cartridge containing approximately 2 × 10(6) endothelial cells grown on microcarriers) and interact with endothelial cells. Eighteen hours after CLP, the rats were treated for 4 h with this extracorporeal system containing either endothelial cells (EBR group) or no cells (sham EBR group). Physiologic and biochemical parameters, cytokines, endothelial functions, and 7-day survival time were monitored. In vitro, the pulmonary endothelial cells of the septic rats were treated with the EBR system and the resulting changes in their functions were monitored. The EBR system ameliorated CLP-induced sepsis compared with the sham EBR system. After CLP, the 7-day survival rate of sham-treated rats was only 25.0 %, while in the EBR-treated group, it increased to 57.1 % (p = 0.04). The EBR system protected the liver and renal function and ameliorated the kidney and lung injury. Meanwhile, this therapy reduced pulmonary vascular leakage and alleviated the infiltration of inflammatory cells in the lungs, especially neutrophils. Furthermore, after the EBR treatment both in vivo and in vitro, the expression of intercellular adhesion molecule-1 and the secretion of CXCL1 and CXCL2 of pulmonary endothelium decreased, which helped to alleviate the adhesion and chemotaxis of neutrophils. In addition, the EBR system decreased CD11b expression and intracellular free calcium level

[Vascular calcifications in subjects with and without chronic renal failure: types, sites and risk factors].

PubMed

Marinelli, Annibale; Di Napoli, Anteo

2017-04-01

Vascular calcifications worse outcomes in the general population and in patients on dialysis. We investigated 146 patients on chronic hemodialysis and 63 healthy controls with normal renal function under 65 years of age. All subjects underwent B-mode ultrasonography of common and internal carotid artery, abdominal aorta, common and superficial femoral artery and posterior tibial artery to assess the presence of intimal and medial calcifications. Intimal and media calcifications were present at the level of the carotid vessel, the abdominal aorta, the common femoral artery, the superficial femoral artery and the posterior tibial artery, respectively in 45%, 50%, 45%, 50%, 42% of patients on dialysis and in 5%, 15%, 24%, 5%, 2% of controls (p <0,01). On multivariate logistic analysis of regression, after adjustment for potential confounders, carotid intimal calcification, abdominal aortic calcification, medial calcification of the superficial femoral artery and posterior tibial artery calcification were associated with dialysis and with cardiovascular disease. Only intimal arterial calcification were associated with older age and smoking. Vascular calcifications are extremely common in middle-aged patients on chronic hemodialysis. Ultrasonography currently available in Nephrology, is a sensitive, reproducible, inexpensive imaging technique to identify arterial intimal and medial calcification in high-risk cardiovascular subjects. Copyright by Società Italiana di Nefrologia SIN, Rome, Italy.

The FXR agonist PX20606 ameliorates portal hypertension by targeting vascular remodelling and sinusoidal dysfunction.

PubMed

Schwabl, Philipp; Hambruch, Eva; Seeland, Berit A; Hayden, Hubert; Wagner, Michael; Garnys, Lukas; Strobel, Bastian; Schubert, Tim-Lukas; Riedl, Florian; Mitteregger, Dieter; Burnet, Michael; Starlinger, Patrick; Oberhuber, Georg; Deuschle, Ulrich; Rohr-Udilova, Nataliya; Podesser, Bruno K; Peck-Radosavljevic, Markus; Reiberger, Thomas; Kremoser, Claus; Trauner, Michael

2017-04-01

portal pressure to a greater extent (-22%; p=0.001). In human liver sinusoidal endothelial cells, PX increased eNOS and DDAH expression. The non-steroidal FXR agonist PX20606 ameliorates portal hypertension by reducing liver fibrosis, vascular remodelling and sinusoidal dysfunction. The novel drug PX20606 activates the bile acid receptor FXR and shows beneficial effects in experimental liver cirrhosis: In the liver, it reduces scarring and inflammation, and also widens blood vessels. Thus, PX20606 leads to an improved blood flow through the liver and decreases hypertension of the portal vein. Additionally, PX20606 improves the altered intestinal barrier and decreases bacterial migration from the gut. Copyright © 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Probucol ameliorates renal and metabolic sequelae of primary CoQ deficiency in Pdss2 mutant mice.

PubMed

Falk, Marni J; Polyak, Erzsebet; Zhang, Zhe; Peng, Min; King, Rhonda; Maltzman, Jonathan S; Okwuego, Ezinne; Horyn, Oksana; Nakamaru-Ogiso, Eiko; Ostrovsky, Julian; Xie, Letian X; Chen, Jia Yan; Marbois, Beth; Nissim, Itzhak; Clarke, Catherine F; Gasser, David L

2011-07-01

Therapy of mitochondrial respiratory chain diseases is complicated by limited understanding of cellular mechanisms that cause the widely variable clinical findings. Here, we show that focal segmental glomerulopathy-like kidney disease in Pdss2 mutant animals with primary coenzyme Q (CoQ) deficiency is significantly ameliorated by oral treatment with probucol (1% w/w). Preventative effects in missense mutant mice are similar whether fed probucol from weaning or for 3 weeks prior to typical nephritis onset. Furthermore, treating symptomatic animals for 2 weeks with probucol significantly reduces albuminuria. Probucol has a more pronounced health benefit than high-dose CoQ(10) supplementation and uniquely restores CoQ(9) content in mutant kidney. Probucol substantially mitigates transcriptional alterations across many intermediary metabolic domains, including peroxisome proliferator-activated receptor (PPAR) pathway signaling. Probucol's beneficial effects on the renal and metabolic manifestations of Pdss2 disease occur despite modest induction of oxidant stress and appear independent of its hypolipidemic effects. Rather, decreased CoQ(9) content and altered PPAR pathway signaling appear, respectively, to orchestrate the glomerular and global metabolic consequences of primary CoQ deficiency, which are both preventable and treatable with oral probucol therapy. Copyright © 2011 EMBO Molecular Medicine.

Renal effects of continuous negative pressure breathing

NASA Technical Reports Server (NTRS)

Kinney, M. J.

1975-01-01

Continuous negative pressure breathing (CNPB) was utilized to simulate the thoracic vascular distension of zero G in 11 anesthetized rats. The animals underwent renal clearance and micropuncture renal nephron studies before, during, and after CNPB. Four rats were pretreated with a high salt diet and I-M desoxycorticosterone (DOCA) in excess. None of these rats diuresed with CNPB. In contrast, five of the seven remaining rats increased the fraction of the filtered sodium excreted and their urinary flow rate. Potassium excretion increased. End proximal tubular fluid specimen's TF/P inulin ratios were unchanged. Whole kidney and single nephron glomerular filtration rates fell 10%. CNPB, a mechanism for atrial distension, appears to cause in the rat a decrease in distal tubular sodium and water reabsorption. Exogenous mineral-corticoid prevents the diuresis, saluresis, and kaluresis. The adequacy of other nonatrial volume control mechanisms in regulating renal salt and water conservation in opposition to the studied atrial-renal (Henry-Gauer) reflex of thoracic vascular distension is confirmed.

Continuous renal replacement therapies: a brief primer for the neurointensivist.

PubMed

Patel, Pritesh; Nandwani, Veena; McCarthy, Paul J; Conrad, Steven A; Keith Scott, L

2010-10-01

Continuous renal replacement therapy (CRRT) is a renal replacement modality that is often used in the ICU setting, including the neuro-ICU. This form of renal replacement therapy has been used classically for acute renal failure in patients with hemodynamic compromise, but is gaining acceptance as a method to control vascular and extra-vascular volume and mediate cytokines in non-renal diseases. Although these uses are briefly discussed, this review concentrates on the different forms of continuous renal replacement, mainly focusing on the technology of convective versus diffusive modalities and briefly on filter technology. There is also discussion on the various anticoagulation regimes used in CRRT including data on performing CRRT without anticoagulation. This review is not meant to be a discussion on the pros and cons of CRRT versus intermittent dialysis, but rather a primer on the technology of CRRT and how this therapy may affect general care of the ICU patient.

Are gadolinium-based contrast media nephrotoxic? A renal biopsy study.

PubMed

Akgun, Hulya; Gonlusen, Gulfiliz; Cartwright, Joiner; Suki, Wadi N; Truong, Luan D

2006-09-01

Gadolinium-based contrast media were originally introduced as alternatives to iodinated media for magnetic resonance imaging. Although originally thought to be nonnephrotoxic, gadolinium-based contrast media have recently been reported to be associated with acute renal failure; the mechanism and the underlying renal injury are not completely understood. We report what is, to our knowledge, the first renal biopsy in this context. A 56-year-old patient underwent 2 consecutive vascular imaging procedures in conjunction with gadolinium-based contrast medium administration. A few days later, the patient developed acute renal failure. A renal biopsy showed acute tubular cell injury including patchy tubular cell necrosis, tubular cell degeneration, and marked proliferation of tubular cells, together with mild interstitial edema and interstitial inflammation, but without significant glomerular or vascular changes. During supportive therapy, renal function was partially regained. This case emphasizes the potential nephrotoxicity of gadolinium-based contrast media and suggests that the nephrotoxicity is related to potentially reversible acute tubular cell injury.

Beneficial Effects of Different Flavonoids on Vascular and Renal Function in L-NAME Hypertensive Rats

PubMed Central

Paredes, M. Dolores; Romecín, Paola; Castillo, Julián; Ortiz, M. Clara

2018-01-01

Background: we have evaluated the antihypertensive effect of several flavonoid extracts in a rat model of arterial hypertension caused by chronic administration (6 weeks) of the nitric oxide synthesis inhibitor, L-NAME. Methods: Sprague Dawley rats received L-NAME alone or L-NAME plus flavonoid-rich vegetal extracts (Lemon, Grapefruit + Bitter Orange, and Cocoa) or purified flavonoids (Apigenin and Diosmin) for 6 weeks. Results: L-NAME treatment resulted in a marked elevation of blood pressure, and treatment with Apigenin, Lemon Extract, and Grapefruit + Bitter Orange extracts significantly reduced the elevated blood pressure of these animals. Apigenin and some of these flavonoids also ameliorated nitric oxide-dependent and -independent aortic vasodilation and elevated nitrite urinary excretion. End-organ abnormalities such as cardiac infarcts, hyaline arteriopathy and fibrinoid necrosis in coronary arteries and aorta were improved by these treatments, reducing the end-organ vascular damage. Conclusions: the flavonoids included in this study, specially apigenin, may be used as functional food ingredients with potential therapeutic benefit in arterial hypertension. PMID:29652818

Effect of renal nerve stimulation on responsiveness of the rat renal vasculature.

PubMed

DiBona, Gerald F; Sawin, Linda L

2002-11-01

When the renal nerves are stimulated with sinusoidal stimuli over the frequency range 0.04-0.8 Hz, low (< or =0.4 Hz)- but not high (> or =0.4 Hz)-frequency oscillations appear in renal blood flow (RBF) and are proposed to increase responsiveness of the renal vasculature to stimuli. This hypothesis was tested in anesthetized rats in which RBF responses to intrarenal injection of norepinephrine and angiotensin and to reductions in renal arterial pressure (RAP) were determined during conventional rectangular pulse and sinusoidal renal nerve stimulation. Conventional rectangular pulse renal nerve stimulation decreased RBF at 2 Hz but not at 0.2 or 1.0 Hz. Sinusoidal renal nerve stimulation elicited low-frequency oscillations (< or =0.4 Hz) in RBF only when the basal carrier signal frequency produced renal vasoconstriction, i.e., at 5 Hz but not at 1 Hz. Regardless of whether renal vasoconstriction occurred, neither conventional rectangular pulse nor sinusoidal renal nerve stimulation altered renal vasoconstrictor responses to norepinephrine and angiotensin. The RBF response to reduction in RAP was altered by both conventional rectangular pulse and sinusoidal renal nerve stimulation only when renal vasoconstriction occurred: the decrease in RBF during reduced RAP was greater. Sinusoidal renal nerve stimulation with a renal vasoconstrictor carrier frequency results in a decrease in RBF with superimposed low-frequency oscillations. However, these low-frequency RBF oscillations do not alter renal vascular responsiveness to vasoconstrictor stimuli.

Renal capillary haemangioma associated with renal cell carcinoma and polycythaemia in acquired cystic disease.

PubMed

Beamer, Matthew; Love, Matthew; Ghasemian, Seyed

2017-06-16

Capillary haemangiomas are relatively common tumours, typically occurring in the subcutaneous tissue during childhood. However, visceral occurrence is very rare. These tumours make up a subset of vascular lesions that have previously, although rarely, been described in case reports in association with the kidney. Here we review the literature and describe a capillary haemangioma occurring in the renal hilum found to be coexistent with end-stage renal disease, renal cell carcinoma and polycythaemia. To our knowledge, this is the first case report to describe the occurrence of this tumour in the renal hilum in association with this constitution of renal pathologies. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Silencing Of Circular RNA-ZNF609 Ameliorates Vascular Endothelial Dysfunction.

PubMed

Liu, Chang; Yao, Mu-Di; Li, Chao-Peng; Shan, Kun; Yang, Hong; Wang, Jia-Jian; Liu, Ban; Li, Xiu-Miao; Yao, Jin; Jiang, Qin; Yan, Biao

2017-01-01

Vascular dysfunction is a hallmark of ischemic, cancer, and inflammatory diseases, contributing to disease progression. Circular RNAs (circRNAs) are endogenous non-coding RNAs, which have been reported to be abnormally expressed in many human diseases. In this study, we used retinal vasculature to determine the role of circular RNA in vascular dysfunction. We revealed that cZNF609 was significantly up-regulated upon high glucose and hypoxia stress in vivo and in vitro . cZNF609 silencing decreased retinal vessel loss and suppressed pathological angiogenesis in vivo . cZNF609 silencing increased endothelial cell migration and tube formation, and protected endothelial cell against oxidative stress and hypoxia stress in vitro . By contrast, transgenic overexpression of cZNF609 showed an opposite effects. cZNF609 acted as an endogenous miR-615-5p sponge to sequester and inhibit miR-615-5p activity, which led to increased MEF2A expression. MEF2A overexpression could rescue cZNF609 silencing-mediated effects on endothelial cell migration, tube formation, and apoptosis. Moreover, dysregulated cZNF609 expression was detected in the clinical samples of the patients with diabetes, hypertension, and coronary artery disease. Intervention of cZNF609 expression is promising therapy for vascular dysfunction.

Effect of antisense oligodeoxynucleotides for ICAM-1 on renal ischaemia–reperfusion injury in the anaesthetised rat

PubMed Central

Kiew, Lik Voon; Munavvar, Abdul Sattar; Law, Chung Hiong; Azizan, Abdullah Nor; Nazarina, Abdul Rahman; Sidik, Khalifah; Johns, Edward J

2004-01-01

An antisense oligodeoxynucleotide (As-ODN) to the 3′ untranslated region of the mRNA sequence expressing the intracellular adhesion molecule-1 (ICAM-1) was employed to determine ICAM-1's role in renal ischaemia–reperfusion injury in the rat. Wistar-Kyoto rats receiving i.v. either lipofectin–As-ODN (As-ODN group), lipofectin–reverse ODN (Rv-ODN group) or lipofectin (ischaemia control group) 8 h prior to study were anaesthetized and subjected to 30 min of renal artery occlusion. Renal haemodynamic and excretory parameters were monitored before and after renal ischaemia. On termination of the study renal tissue was subjected to histological and Western blot analysis. Renal blood flow decreased in the 3 h post-ischaemia period in the ischaemia control and Rv-ODN groups, but was maintained in the As-ODN group. Glomerular filtration rate was depressed initially but gradually increased to 10% above basal levels in the ischaemia control and Rv-ODN groups, but was below basal levels (20%) in the As-ODN group. There was a three- to fourfold increase in sodium and water excretion following ischaemia in the ischaemia control and reverse-ODN groups but not in the As-ODN treated group. The As-ODN ameliorated the histological evidence of ischaemic damage and reduced ICAM-1 protein levels to a greater extent in the medulla than cortex. These observations suggested that in the post-ischaemic period afferent and efferent arteriolar tone was increased with a loss of reabsorptive capacity which was in part due to ICAM-1. The possibility arises that the action of ICAM-1 at vascular and tubular sites in the deeper regions of the kidney contributes to the ischaemia–reperfusion injury. PMID:15047774

Intrarenal hemodynamic changes following acute partial renal arterial occlusion.

DOT National Transportation Integrated Search

1965-10-01

Both an increase and a decrease in total renal vascular resistance, following a period of total renal artery occlusion, have been reported from this laboratory. The duration of the occlusive period and height of the perfusion pressure were found to p...

Vascular heterogeneity in the kidney.

PubMed

Molema, Grietje; Aird, William C

2012-03-01

Blood vessels and their endothelial lining are uniquely adapted to the needs of the underlying tissue. The structure and function of the vasculature varies both between and within different organs. In the kidney, the vascular architecture is designed to function both in oxygen/nutrient delivery and filtration of blood according to the homeostatic needs of the body. Here, we review spatial and temporal differences in renal vascular phenotypes in both health and disease. Copyright © 2012 Elsevier Inc. All rights reserved.

Renal denervation in a patient with Alport syndrome and rejected renal allograft.

PubMed

Raju, Narayana; Lloyd, Vincent; Yalagudri, Sachin; Das, Bharati; Ravikishore, A G

2015-12-01

Renal denervation is a new intervention to treat resistant hypertension. By applying radiofrequency (RF) to renal arteries, sympathetic nerves in adventitia layer of vascular wall can be denervated. Sympathetic hyperactivity is an important contributory factor in hypertension of hemodialysis patients. Hyperactive sympathetic nervous system aggravates hypertension and it can cause complications like left ventricular hypertrophy, heart failure, arrhythmias and atherogenesis. Our report illustrates the use of renal denervation using conventional RF catheter for uncontrolled hypertension in a patient with Alport syndrome and rejected renal allograft. Progressive and sustained reduction of blood pressure was obtained post-procedure and at 24 months follow-up with antihypertensives decreased from 6 to 2 per day, thereby demonstrating the safety, feasibility, and efficacy of the procedure. There are some reports available on the usefulness of this technique in hemodialysis patients; however, there are no studies of renal denervation in patients with Alport syndrome and failed allograft situation. Copyright © 2015 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.

Effect of Cuscuta chinensis on renal function in ischemia/reperfusion-induced acute renal failure rats.

PubMed

Shin, Sun; Lee, Yun Jung; Kim, Eun Ju; Lee, An Sook; Kang, Dae Gill; Lee, Ho Sub

2011-01-01

The kidneys play a central role in regulating water, ion composition and excretion of metabolic waste products in the urine. Cuscuta chinensis has been known as an important traditional Oriental medicine for the treatment of liver and kidney disorders. Thus, we studied whether an aqueous extract of Cuscuta chinensis (ACC) seeds has an effect on renal function parameters in ischemia/reperfusion-induced acute renal failure (ARF) rats. Administration of 250 mg/kg/day ACC showed that renal functional parameters including urinary excretion rate, osmolality, Na(+), K(+), Cl(-), creatinine clearance, solute-free water reabsorption were significantly recovered in ischemia/reperfusion-induced ARF. Periodic acid Schiff staining showed that administration of ACC improved tubular damage in ischemia/reperfusion-induced ARF. In immunoblot and immunohistological examinations, ischemia/reperfusion-induced ARF decreased the expressions of water channel AQP 2, 3 and sodium potassium pump Na,K-ATPase in the renal medulla. However, administration of ACC markedly incremented AQP 2, 3 and Na,K-ATPase expressions. Therefore, these data indicate that administration of ACC ameliorates regulation of the urine concentration and renal functions in rats with ischemia/reperfusion-induced ARF.

Rosiglitazone reduces renal and plasma markers of oxidative injury and reverses urinary metabolite abnormalities in the amelioration of diabetic nephropathy.

PubMed

Zhang, Hongyu; Saha, Jharna; Byun, Jaeman; Schin, MaryLee; Lorenz, Matthew; Kennedy, Robert T; Kretzler, Matthias; Feldman, Eva L; Pennathur, Subramaniam; Brosius, Frank C

2008-10-01

Recent studies suggest that thiazolidinediones ameliorate diabetic nephropathy (DN) independently of their effect on hyperglycemia. In the current study, we confirm and extend these findings by showing that rosiglitazone treatment prevented the development of DN and reversed multiple markers of oxidative injury in DBA/2J mice made diabetic by low-dose streptozotocin. These diabetic mice developed a 14.2-fold increase in albuminuria and a 53% expansion of renal glomerular extracellular matrix after 12 wk of diabetes. These changes were largely abrogated by administration of rosiglitazone beginning 2 wk after the completion of streptozotocin injections. Rosiglitazone had no effect on glycemic control. Rosiglitazone had similar effects on insulin-treated diabetic mice after 24 wk of diabetes. Podocyte loss and glomerular fibronectin accumulation, other markers of early DN, were prevented by rosiglitazone in both 12- and 24-wk diabetic models. Surprisingly, glomerular GLUT1 levels did not increase and nephrin levels did not decrease in the diabetic animals; neither changed with rosiglitazone. Plasma and kidney markers of protein oxidation and lipid peroxidation were significantly elevated in the 24-wk diabetic animals despite insulin treatment and were reduced to near-normal levels by rosiglitazone. Finally, urinary metabolites were markedly altered by diabetes. Of 1,988 metabolite features identified by electrospray ionization time of flight mass spectrometry, levels of 56 were altered more than twofold in the urine of diabetic mice. Of these, 21 were returned to normal by rosiglitazone. Thus rosiglitazone has direct effects on the renal glomerulus to reduce reactive oxygen species accumulation to prevent type 1 diabetic mice from development of DN.

The current role of vascular stents.

PubMed

Busquet, J

1993-09-01

The limitations of percutaneous balloon angioplasty have favoured the development and the use of vascular endoprostheses or stents. These thin-walled metal devices maintain after expansion, an optimal and constant diameter for the vascular lumen. Restenosis, dissection, abrupt closure, residual stenosis or re-opened total occlusion represent appropriate indications for stenting. A large experience with non-coronary application of stents is currently available in iliac, femoro-popliteal and renal arteries, aorta, large veins.

[Vascular anatomy of donor and recipient in living kidney transplantation].

PubMed

Zhang, Jiqing; Zhang, Xiaodong

2009-09-01

To review the vascular anatomy of the donor and the recipient for the living kidney transplantation. The recent literature about the vessels of donor and recipient in clinical applications was extensively reviewed. The pertinent vascular anatomy of the donor and recipient was essential for the screening of the proper candidates, surgical planning and long-term outcome. Early branching and accessory renal artery of the donor were particularly important to deciding the side of nephrectomy, surgical technique and anastomosing pattern, and their injuries were the most frequent factor of the conversion from laparoscopic to open surgery. With increase of laparoscopic nephrectomy in donors, accurate venous anatomy was paid more and more attention to because venous bleeding could also lead to conversion to open nephrectomy. Multidetector CT (MDCT) could supplant the conventional excretory urography and renal catheter angiography and could accurately depict the donors' vessels, vascular variations. In addition, MDCT can excellently evaluate the status of donor kidney, collecting system and other pertinent anatomy details. Accurate master of related vascular anatomy can facilitate operation plan and success of operation and can contribute to the rapid development of living donor kidney transplantation. MDCT has become the choice of preoperative one-stop image assessment for living renal donors.

Losartan does not decrease renal oxygenation and norepinephrine effects in rats after resuscitated haemorrhage.

PubMed

Jönsson, Sofia; Melville, Jacqueline M; Becirovic-Agic, Mediha; Hultström, Michael

2018-04-18

Renin-angiotensin-system blockers are thought to increase the risk of acute kidney injury after surgery and haemorrhage. We found that Losartan does not cause renal cortical hypoxia after haemorrhage in rats because of decreased renal vascular resistance, but did not evaluate resuscitation. Study Losartan´s effect on renal cortical and medullary oxygenation, and norepinephrine´s vasopressor effect in a model of resuscitated haemorrhage. After seven days Losartan (60 mg/kg/day) or control treatment, male Wistar rats were haemorrhaged 20 % of the blood volume and resuscitated with Ringer's Acetate. Mean arterial pressure, renal blood flow, and kidney tissue oxygenation was measured at baseline and after resuscitation. Finally, the effect of norepinephrine on mean arterial pressure and renal blood flow was investigated. As expected, Losartan lowered mean arterial pressure but not renal blood flow. Losartan did not affect renal oxygen consumption and oxygen tension. Mean arterial pressure and renal blood flow were lower after resuscitated haemorrhage. Smaller increase of renal vascular resistance in Losartan group translated to smaller decrease in cortical oxygen tension, but no significant difference seen in medullary oxygen tension either between groups or after haemorrhage. The effect of norepinephrine on mean arterial pressure and renal blood flow was similar in controls and Losartan treated rats. Losartan does not decrease renal oxygenation after resuscitated haemorrhage because of a smaller increase in renal vascular resistance. Further, Losartan does not decrease the efficiency of norepinephrine as a vasopressor indicating that blood pressure may be managed effectively during Losartan treatment.

[Recurrent vascular access trombosis associated with the prothrombin mutation G20210A in a adult patient in haemodialysis].

PubMed

Quintana, L F; Coll, E; Monteagudo, I; Collado, S; López-Pedret, J; Cases, A

2005-01-01

Vascular access-related complications are a frequent cause of morbidity in haemodialysis patients and generate high costs. We present the case of an adult patient with end-stage renal disease and recurrent vascular access thrombosis associated with the prothrombin mutation G20210A and renal graft intolerance. The clinical expression of this heterozygous gene mutation may have been favoured by inflammatory state, frequent in dialysis patients. In this patient, the inflammatory response associated with the renal graft intolerance would have favored the development of recurrent vascular access thrombosis in a adult heterozygous for prothrombin mutation G20210A. In the case of early dysfunction of haemodialysis vascular access and after ruling out technical problems, it is convenient to carry out a screening for thrombophilia.

Hypothyroidism presenting as reversible renal impairment: an interesting case report.

PubMed

Vikrant, Sanjay; Chander, Subhash; Kumar, Satish; Gupta, Dalip

2013-10-01

We describe an interesting case of reversible renal impairment secondary to hypothyroidism. A 57-years-old man was referred from peripheral institution for evaluation of elevated serum creatinine. He had vague complaints of weakness, lethargy and muscle ache but no urinary symptoms. He was found to have hypothyroidism, and thyroid hormone replacement therapy (THRT) was started which resulted in reversal of the renal dysfunction. There was marked improvement in estimated glomerular filtration rate. 99mTc DTPA renal scans done before and after THRT suggested hypothyroidism responsible for this reversible renal impairment. Several studies have described the pathophysiology of diminished renal function in hypothyroidism. Few studies or case reports have shown total amelioration of renal impairment as seen in our patient. The etiology is presumed to be multifactorial, in which hemodynamic effects and a direct effect of thyroid hormone on the kidney play an important role. We suggest that patients with renal impairment of unknown cause have thyroid function tests undertaken as part of routine investigation.

Tangshen Formula Attenuates Diabetic Nephropathy by Promoting ABCA1-Mediated Renal Cholesterol Efflux in db/db Mice.

PubMed

Liu, Peng; Peng, Liang; Zhang, Haojun; Tang, Patrick Ming-Kuen; Zhao, Tingting; Yan, Meihua; Zhao, Hailing; Huang, Xiaoru; Lan, Huiyao; Li, Ping

2018-01-01

The commonly prescribed Tangshen Formula (TSF) is a traditional Chinese formulation that has been shown to reduce plasma lipid metabolism and proteinuria and improve the estimated glomerular filtration rate (eGFR) in patients with diabetic kidney disease. This study investigated the underlying mechanism whereby TSF regulates renal lipid accumulation and ameliorates diabetic renal injuries in spontaneous diabetic db/db mice and in vitro in sodium palmitate (PA)-stimulated and Abca1-SiRNA-transfected mouse tubular epithelial cells (mTECs). The results revealed that TSF treatment significantly ameliorated the renal injuries by lowering urinary albumin excretion and improving renal tissue injuries in diabetic (db/db) mice. Interestingly, the treatment with TSF also resulted in decreased cholesterol levels in the renal tissues of db/db mice, which was associated with increased expression of the peroxisome proliferator-activated receptor γ coactivator 1-α (PGC-1α), the Liver X receptors (LXR), and ATP-binding cassette subfamily A member 1 (ABCA1), suggesting that TSF might attenuate diabetic kidney injury via a mechanism associated with improving cholesterol efflux in the diabetic kidney. This was investigated in vitro in mTECs, and the results showed that TSF reduced the PA-stimulated cholesterol accumulation in mTECs. Mechanistically, the addition of TSF was capable of reversing PA-induced downregulation of PGC-1α, LXR, and ABCA1 expression and cholesterol accumulation in mTECs, suggesting that TSF might act the protection via the PGC-1α-LXR-ABCA1 pathway to improve the cholesterol efflux in the renal tissues of db/db mice. This was further confirmed by silencing ABCA1 to block the promotive effect of TSF on cholesterol efflux in vitro . In conclusion, TSF might ameliorate diabetic kidney injuries by promoting ABCA1-mediated renal cholesterol efflux.

Renal outcomes and dietary potassium: the overshadowed electrolyte?

PubMed

Jablonski, Kristen L; Kendrick, Jessica B

2014-12-01

Smyth et al. examined the association between urinary sodium and potassium excretion and adverse renal outcomes in adults at high cardiovascular risk. They found no association between urinary sodium excretion and adverse renal outcomes, but a reduced odds of adverse renal outcomes with higher urinary potassium excretion. It will be important to ascertain whether this finding holds true in individuals free from vascular disease and diabetes, as well as in patients with chronic kidney disease.

Effects of early overnutrition on the renal response to Ang II and expression of RAAS components in rat renal tissue.

PubMed

Granado, M; Amor, S; Fernández, N; Carreño-Tarragona, G; Iglesias-Cruz, M C; Martín-Carro, B; Monge, L; García-Villalón, A L

2017-10-01

The aim of this study was to analyze the effects of early overnutrition (EON) on the expression of the renin angiotensin aldosterone system (RAAS) components in renal cortex, renal arteries and renal perivascular adipose tissue (PVAT), as well as the vascular response of renal arteries to Angiotensin II (Ang II). On birth day litters were adjusted to twelve (L12-control) or three (L3-overfed) pups per mother. Half of the animals were sacrificed at weaning (21 days old) and the other half at 5 months of age. Ang II-induced vasoconstriction of renal artery segments increased in young overfed rats and decreased in adult overfed rats. EON decreased the gene expression of angiotensinogen (Agt), Ang II receptors AT1 and AT2 and eNOS in renal arteries of young rats, while it increased the mRNA levels of AT-2 and ET-1 in adult rats. In renal PVAT EON up-regulated the gene expression of COX-2 and TNF-α in young rats and the mRNA levels of renin receptor both in young and in adult rats. On the contrary, Ang II receptors mRNA levels were downregulated at both ages. Renal cortex of overfed rats showed increased gene expression of Agt in adult rats and of AT1 in young rats. However the mRNA levels of AT1 were decreased in the renal cortex of overfed adult rats. EON is associated with alterations in the vascular response of renal arteries to Ang II and changes in the gene expression of RAAS components in renal tissue. Copyright © 2017 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

Endoglin regulates renal ischaemia-reperfusion injury.

PubMed

Docherty, Neil G; López-Novoa, José M; Arevalo, Miguel; Düwel, Annette; Rodriguez-Peña, Ana; Pérez-Barriocanal, Fernando; Bernabeu, Carmelo; Eleno, Nélida

2006-08-01

Renal ischaemia-reperfusion (I-R) can cause acute tubular necrosis and chronic renal deterioration. Endoglin, an accessory receptor for Transforming Growth Factor-beta1 (TGF-beta1), is expressed on activated endothelium during macrophage maturation and implicated in the control of fibrosis, angiogenesis and inflammation. Endoglin expression was monitored over 14 days after renal I-R in rats. As endoglin-null mice are not viable, the role of endoglin in I-R was studied by comparing renal I-R injury in haploinsufficient mice (Eng(+/-)) and their wild-type littermates (Eng(+/+)). Renal function, morphology and molecular markers of acute renal injury and inflammation were compared. Endoglin mRNA up-regulation in the post-ischaemic kidneys of rats occurred at 12 h after I-R; endoglin protein levels were elevated throughout the study period. Expression was initially localized to the vascular endothelium, then extended to fibrotic and inflamed areas of the interstitium. Two days after I-R, plasma creatinine elevation and acute tubular necrosis were less marked in Eng(+/-) than in Eng(+/+) mice. Significant up-regulation of endoglin protein was found only in the post-ischaemic kidneys of Eng(+/+) mice and coincided with an increased mRNA expression of the TGF-beta1 and collagen IV (alpha1) chain genes. Significant increases in vascular cell adhesion molecule-1 (VCAM-1) and inducible nitric oxide synthase (iNOS) expression, nitrosative stress, myeloperoxidase activity and CD68 staining for macrophages were evident in post-ischaemic kidneys of Eng(+/+), but not Eng(+/-) mice, suggesting that impaired endothelial activation and macrophage maturation may account for the reduced injury in post-ischaemic kidneys of Eng(+/-) mice. Endoglin is up-regulated in the post-ischaemic kidney and endoglin-haploinsufficient mice are protected from renal I-R injury. Endoglin may play a primary role in promoting inflammatory responses following renal I-R.

A biphasic parameter estimation method for quantitative analysis of dynamic renal scintigraphic data

NASA Astrophysics Data System (ADS)

Koh, T. S.; Zhang, Jeff L.; Ong, C. K.; Shuter, B.

2006-06-01

Dynamic renal scintigraphy is an established method in nuclear medicine, commonly used for the assessment of renal function. In this paper, a biphasic model fitting method is proposed for simultaneous estimation of both vascular and parenchymal parameters from renal scintigraphic data. These parameters include the renal plasma flow, vascular and parenchymal mean transit times, and the glomerular extraction rate. Monte Carlo simulation was used to evaluate the stability and confidence of the parameter estimates obtained by the proposed biphasic method, before applying the method on actual patient study cases to compare with the conventional fitting approach and other established renal indices. The various parameter estimates obtained using the proposed method were found to be consistent with the respective pathologies of the study cases. The renal plasma flow and extraction rate estimated by the proposed method were in good agreement with those previously obtained using dynamic computed tomography and magnetic resonance imaging.

Diffuse vascular damage in a transplanted kidney: an indication for nuclear magnetic resonance?

PubMed

Burdese, M; Consiglio, V; Mezza, E; Savio, D; Guarena, C; Rossetti, M; Messina, M; Soragna, G; Suriani, C; Rabbia, C; Segoloni, G P; Piccoli, G B

2005-06-01

Vascular lesions are an increasing challenge after renal transplantation due to the wider indications for recipients and acceptance criteria for donors. Diagnostic approach and prognostic interpretation are still matter of controversy. The case reported herein may summarize some of the issues in this regard. A 54-year-old woman, on renal replacement therapy since 1974, and a kidney graft recipient from 1975 to 1999, received a second graft in 2001. The donor age was 65 years (cold ischemia 22 hours; two mismatches). The early posttransplant follow-up was characterized by delayed graft function, hypertension, and diabetes. During the initial hypertension workup, renal graft ultrasound (US) Doppler demonstrated increased vascular resistances, stable over time (resistance index 0.74 to 0.77); renal scintiscan displayed homogeneously parenchymoa and angio-magnetic resonance imaging (MRI), an homogeneous parenchymal vascularization. Initial immunosuppression with tacrolimus and steroids was modulated by adding mycophenolate mofetil to taper tacrolimus (to reduce nephrotoxicity and hypertension). Despite this, kidney function slowly deteriorated; serum creatinine reached 3 to 3.5 mg/dL by the second year. After a severe hypertensive crisis with unchanged scintiscan and US doppler examinations, angio-MRI revealed the almost complete disappearance of parenchymal enhancement beyond the lobar arteries. A renal biopsy confirmed the severe vascular damage. The patient was switched to rapamycine and a low-dose of an angiotension converting enzyme (ACE) inhibitor. She did relatively well (serum creatinine 2.2 to 3 mg/dL) for 6 months, when rapid functional impairment forced her to restart hemodialysis. This case, almost paradigmatic of the problems occurring when the rigid vasculature of long-term dialysis patients is matched with "marginal kidneys," suggests that MRI may be a sensible good to define vascular damage in the grafted kidney.

Reduction of renal mass is lethal in mice lacking vimentin. Role of endothelin-nitric oxide imbalance.

PubMed Central

Terzi, F; Henrion, D; Colucci-Guyon, E; Federici, P; Babinet, C; Levy, B I; Briand, P; Friedlander, G

1997-01-01

Modulation of vascular tone by chemical and mechanical stimuli is a crucial adaptive phenomenon which involves cytoskeleton elements. Disruption, by homologous recombination, of the gene encoding vimentin, a class III intermediate filament protein mainly expressed in vascular cells, was reported to result in apparently normal phenotype under physiological conditions. In this study, we evaluated whether the lack of vimentin affects vascular adaptation to pathological situations, such as reduction of renal mass, a pathological condition which usually results in immediate and sustained vasodilation of the renal vascular bed. Ablation of 3/4 of renal mass was constantly lethal within 72 h in mice lacking vimentin (Vim-/-), whereas no lethality was observed in wild-type littermates. Death in Vim-/- mice resulted from end-stage renal failure. Kidneys from Vim-/- mice synthesized more endothelin, but less nitric oxide (NO), than kidneys from normal animals. In vitro, renal resistance arteries from Vim-/- mice were selectively more sensitive to endothelin, less responsive to NO-dependent vasodilators, and exhibited an impaired flow (shear stress)- induced vasodilation, which is NO dependent, as compared with those from normal littermates. Finally, in vivo administration of bosentan, an endothelin receptor antagonist, totally prevented lethality in Vim-/- mice. These results suggest that vimentin plays a key role in the modulation of vascular tone, possibly via the tuning of endothelin-nitric oxide balance. PMID:9294120

Renal Blood Flow, Glomerular Filtration Rate, and Renal Oxygenation in Early Clinical Septic Shock.

PubMed

Skytte Larsson, Jenny; Krumbholz, Vitus; Enskog, Anders; Bragadottir, Gudrun; Redfors, Bengt; Ricksten, Sven-Erik

2018-06-01

Data on renal hemodynamics, function, and oxygenation in early clinical septic shock are lacking. We therefore measured renal blood flow, glomerular filtration rate, renal oxygen consumption, and oxygenation in patients with early septic shock. Prospective comparative study. General and cardiothoracic ICUs. Patients with norepinephrine-dependent early septic shock (n = 8) were studied within 24 hours after arrival in the ICU and compared with postcardiac surgery patients without acute kidney injury (comparator group, n = 58). None. Data on systemic hemodynamics and renal variables were obtained during two 30-minute periods. Renal blood flow was measured by the infusion clearance of para-aminohippuric acid, corrected for renal extraction of para-aminohippuric acid. Renal filtration fraction was measured by renal extraction of chromium-51 labeled EDTA. Renal oxygenation was estimated from renal oxygen extraction. Renal oxygen delivery (-24%; p = 0.037) and the renal blood flow-to-cardiac index ratio (-21%; p = 0.018) were lower, renal vascular resistance was higher (26%; p = 0.027), whereas renal blood flow tended to be lower (-19%; p = 0.068) in the septic group. Glomerular filtration rate (-32%; p = 0.006) and renal sodium reabsorption (-29%; p = 0.014) were both lower in the septic group. Neither renal filtration fraction nor renal oxygen consumption differed significantly between groups. Renal oxygen extraction was significantly higher in the septic group (28%; p = 0.022). In the septic group, markers of tubular injury were elevated. In early clinical septic shock, renal function was lower, which was accompanied by renal vasoconstriction, a lower renal oxygen delivery, impaired renal oxygenation, and tubular sodium reabsorption at a high oxygen cost compared with controls.

Cordyceps cicadae extracts ameliorate renal malfunction in a remnant kidney model*

PubMed Central

Zhu, Rong; Chen, Yi-ping; Deng, Yue-yi; Zheng, Rong; Zhong, Yi-fei; Wang, Lin; Du, Lan-ping

2011-01-01

Background and Objectives: Chronic kidney disease (CKD) is a growing public health problem with an urgent need for new pharmacological agents. Cordyceps cicadae is widely used in traditional Chinese medicine (TCM) and has potential renoprotective benefits. The current study aimed to determine any scientific evidence to support its clinical use. Methods: We analyzed the potential of two kinds of C. cicadae extract, total extract (TE) and acetic ether extract (AE), in treating kidney disease simulated by a subtotal nephrectomy (SNx) model. Sprague-Dawley rats were divided randomly into seven groups: sham-operated group, vehicle-treated SNx, Cozaar, 2 g/(kg∙d) TE SNx, 1 g/(kg∙d) TE SNx, 92 mg/(kg∙d) AE SNx, and 46 mg/(kg∙d) AE SNx. Renal injury was monitored using urine and serum analyses, and hematoxylin and eosin (HE) and periodic acid-Schiff (PAS) stainings were used to analyze the level of fibrosis. The expression of type IV collagen (Col IV), fibronectin (FN), transforming growth factor-β1 (TGF-β1), and connective tissue growth factor (CTGF) was detected by immunohistochemistry. Results: Renal injury, reflected in urine and serum analyses, and pathological changes induced by SNx were attenuated by TE and AE intervention. The depositions of Col IV and FN were also decreased by the treatments and were accompanied by reduced expression of TGF-β1 and CTGF. In some respects, 2 g/(kg∙d) of TE produced better effects than Cozaar. Conclusions: For the first time, we have shown that C. cicadae may inhibit renal fibrosis in vivo through the TGF-β1/CTGF pathway. Therefore, we conclude that the use of C. cicadae could provide a rational strategy for combating renal fibrosis. PMID:22135152

The additive effects of atorvastatin and insulin on renal function and renal organic anion transporter 3 function in diabetic rats.

PubMed

Thongnak, Laongdao; Pongchaidecha, Anchalee; Jaikumkao, Krit; Chatsudthipong, Varanuj; Chattipakorn, Nipon; Lungkaphin, Anusorn

2017-10-19

Hyperglycemia-induced oxidative stress is usually found in diabetic condition. 3-hydroxy-3-methylglutaryl coenzyme-A (HMG-CoA) reductase inhibitors, statins, are widely used as cholesterol-lowering medication with several "pleiotropic" effects in diabetic patients. This study aims to evaluate whether the protective effects of atorvastatin and insulin on renal function and renal organic anion transporter 3 (Oat3) function involve the modulation of oxidative stress and pancreatic function in type 1 diabetic rats. Type 1 diabetes was induced by intraperitoneal injection of streptozotocin (50 mg/kg BW). Atorvastatin and insulin as single or combined treatment were given for 4 weeks after diabetic condition had been confirmed. Diabetic rats demonstrated renal function and renal Oat3 function impairment with an increased MDA level and decreased SOD protein expression concomitant with stimulation of renal Nrf2 and HO-1 protein expression. Insulin plus atorvastatin (combined) treatment effectively restored renal function as well as renal Oat3 function which correlated with the decrease in hyperglycemia and oxidative stress. Moreover, pancreatic inflammation and apoptosis in diabetic rats were ameliorated by the combined drugs treatment. Therefore, atorvastatin plus insulin seems to exert the additive effect in improving renal functionby alleviating hyperglycemiaand the modulation of oxidative stress, inflammation and apoptosis.

[Ultrasonographic study of blood flow in the renal arteries of patients with arterial hypertension].

PubMed

Makarenko, E S; Dombrovskiĭ, V I; Nelasov, N Iu

2012-01-01

Vascular duplex ultrasound duplex with simultaneous ECG registration was made to estimate the quantitative and time parameters of blood flow in the renal arteries with grade 1-2 arterial hypertension. There were increases in vascular resistance indices and acceleration phase index and a reduction in systolic phase index. There were correlations of the time parameters of blood flow in the renal arteries with age and lipidogram values.

Renal artery stenting in a 2-year-old child with resistant hypertension and neurofibromatosis.

PubMed

Varghese, Kiron; Adhyapak, Srilakshmi M; Lohitashwa, S B; Pais, Priya; Iyengar, Arpana A

2017-07-01

The occurrence of vascular lesions in neurofibromatosis is uncommon but well documented. These vascular lesions when present, occur predominantly in the kidneys, endocrine glands, heart and gastrointestinal tract, causing stenosis or obliteration of the lumen. We report a case of uncontrolled resistant hypertension in a 2-year-old child presenting with neurofibromatosis who was found to have a high-grade ostial left renal artery stenosis and obliteration of the right renal artery. As the right kidney was small and hypo-functioning, and its renal artery was totally occluded, we subjected the child to a left renal angioplasty and bailout stenting. Following stenting, the blood pressure decreased with anti-hypertensive treatment. Based on a review of the literature, and to the best of our knowledge, this is the youngest child to have undergone renal artery stenting.

Detailing the relation between renal T2* and renal tissue pO2 using an integrated approach of parametric magnetic resonance imaging and invasive physiological measurements.

PubMed

Pohlmann, Andreas; Arakelyan, Karen; Hentschel, Jan; Cantow, Kathleen; Flemming, Bert; Ladwig, Mechthild; Waiczies, Sonia; Seeliger, Erdmann; Niendorf, Thoralf

2014-08-01

This study was designed to detail the relation between renal T2* and renal tissue pO2 using an integrated approach that combines parametric magnetic resonance imaging (MRI) and quantitative physiological measurements (MR-PHYSIOL). Experiments were performed in 21 male Wistar rats. In vivo modulation of renal hemodynamics and oxygenation was achieved by brief periods of aortic occlusion, hypoxia, and hyperoxia. Renal perfusion pressure (RPP), renal blood flow (RBF), local cortical and medullary tissue pO2, and blood flux were simultaneously recorded together with T2*, T2 mapping, and magnetic resonance-based kidney size measurements (MR-PHYSIOL). Magnetic resonance imaging was carried out on a 9.4-T small-animal magnetic resonance system. Relative changes in the invasive quantitative parameters were correlated with relative changes in the parameters derived from MRI using Spearman analysis and Pearson analysis. Changes in T2* qualitatively reflected tissue pO2 changes induced by the interventions. T2* versus pO2 Spearman rank correlations were significant for all interventions, yet quantitative translation of T2*/pO2 correlations obtained for one intervention to another intervention proved not appropriate. The closest T2*/pO2 correlation was found for hypoxia and recovery. The interlayer comparison revealed closest T2*/pO2 correlations for the outer medulla and showed that extrapolation of results obtained for one renal layer to other renal layers must be made with due caution. For T2* to RBF relation, significant Spearman correlations were deduced for all renal layers and for all interventions. T2*/RBF correlations for the cortex and outer medulla were even superior to those between T2* and tissue pO2. The closest T2*/RBF correlation occurred during hypoxia and recovery. Close correlations were observed between T2* and kidney size during hypoxia and recovery and for occlusion and recovery. In both cases, kidney size correlated well with renal vascular conductance

Effect of endogenous angiotensin II on the frequency response of the renal vasculature.

PubMed

Dibona, Gerald F; Sawin, Linda L

2004-12-01

The renal vasculature functions as an efficient low-pass filter of the multiple frequencies contained within renal sympathetic nerve activity. This study examined the effect of angiotensin II on the frequency response of the renal vasculature. Physiological changes in the activity of the endogenous renin-angiotensin system were produced by alterations in dietary sodium intake. The frequency response of the renal vasculature was evaluated using pseudorandom binary sequence renal nerve stimulation, and the role of angiotensin II was evaluated by the administration of the angiotensin II AT(1)-receptor antagonist losartan. In low-sodium-diet rats with increased renin-angiotensin system activity, losartan steepened the renal vascular frequency response (i.e., greater attenuation); this was not seen in normal- or high-sodium-diet rats with normal or decreased renin-angiotensin system activity. Analysis of the transfer function from arterial pressure to renal blood flow, i.e., dynamic autoregulation, showed that the tubuloglomerular feedback but not the myogenic component was enhanced in low- and normal- but not in high-sodium-diet rats and that this was reversed by losartan administration. Thus physiological increases in endogenous renin-angiotensin activity inhibit the renal vascular frequency response to renal nerve stimulation while selectively enhancing the tubuloglomerular feedback component of dynamic autoregulation of renal blood flow.

The renin-angiotensin system in thyroid disorders and its role in cardiovascular and renal manifestations.

PubMed

Vargas, Félix; Rodríguez-Gómez, Isabel; Vargas-Tendero, Pablo; Jimenez, Eugenio; Montiel, Mercedes

2012-04-01

Thyroid disorders are among the most common endocrine diseases and affect virtually all physiological systems, with an especially marked impact on cardiovascular and renal systems. This review summarizes the effects of thyroid hormones on the renin-angiotensin system (RAS) and the participation of the RAS in the cardiovascular and renal manifestations of thyroid disorders. Thyroid hormones are important regulators of cardiac and renal mass, vascular function, renal sodium handling, and consequently blood pressure (BP). The RAS acts globally to control cardiovascular and renal functions, while RAS components act systemically and locally in individual organs. Various authors have implicated the systemic and local RAS in the mediation of functional and structural changes in cardiovascular and renal tissues due to abnormal thyroid hormone levels. This review analyzes the influence of thyroid hormones on RAS components and discusses the role of the RAS in BP, cardiac mass, vascular function, and renal abnormalities in thyroid disorders.

Renal hemodynamics: the influence of the renal artery ostium flow diverter

NASA Astrophysics Data System (ADS)

Rossmann, Jenn Stroud; Albert, Scott; Balaban, Robert

2013-11-01

The recently identified renal artery ostium flow diverter may preferentially direct blood flow to the renal arteries, and may also influence flow patterns and recirculation known to be involved in atherogenesis. Three-dimensional computational fluid dynamics (CFD) simulations of steady and pulsatile blood flow are performed to investigate the influence of diverter size and position, and vascular geometry, on the flow patterns and fluid mechanical forces in the neighborhood of the diverter. CFD results show that the flow diverter does affect the blood distribution: depending on the diverter's position, the flow to the renal arteries may be increased or reduced. The results of simulations also show the diverter's effect on the Wall Shear Stress (WSS) distribution, and suggest that the diverter contributes to an atherogenic environment in the abdominal aorta, while being atheroprotective in the renal arteries themselves. These results support previous clinical findings, and suggest directions for further clinical study. The results of this work have direct implications in understanding the physiological significance of the diverter, and its potential role in the pathophysiological development of atherosclerosis.

Sodium sensitive hypertension: renal and adrenal non-modulation in its pathogenesis

NASA Technical Reports Server (NTRS)

Hollenberg, N. K.; Williams, G. H.

1988-01-01

The thrust of this essay will be to organize a growing body of evidence which indicates that an abnormality of the kidney, and the adrenal, involving disordered regulation through the renin-angiotensin system, is responsible for the pathogenesis in about 45% of patients--a discrete subgroup that may be most common cause of hypertension. That fundamental abnormality leads to disordered renal sodium handling and sodium-sensitive hypertension, abnormalities in the renal vascular response to changes in sodium intake and to angiotensin II, blunted decrements of renin release in response to saline or angiotensin II, and an accentuated renal vasodilator response to angiotensin converting enzyme (ACE) inhibition. ACE inhibition not only increases renal blood flow substantially more in these patients than it does in normal subjects, ACE inhibition also restores to normal the renal vascular and adrenal response to angiotensin II, renin release in response to angiotensin II, renal sodium handling--and ultimately blood pressure. Finally, and perhaps most intriguing, similar abnormalities have been found in 50% of the normotensive offspring of patients with essential hypertension and evidence is accruing to indicate that the abnormality is inherited as a Mendelian dominant.

Anatomical study of renal arterial vasculature and its potential impact on partial nephrectomy.

PubMed

Macchi, Veronica; Crestani, Alessandro; Porzionato, Andrea; Sfriso, Maria Martina; Morra, Aldo; Rossanese, Marta; Novara, Giacomo; De Caro, Raffaele; Ficarra, Vincenzo

2017-07-01

To validate Graves' classification of the intrarenal arteries and to verify the absence of collateral arterial blood supply between different renal segments, in order to maximize peri-operative and functional outcomes of partial nephrectomy. The study was performed on 15 normal kidneys sampled from eight unembalmed cadavers. Kidneys with the surrounding perirenal fat tissue were removed en bloc with the abdominal segment of the aorta. The renal artery was injected with acrylic and radiopaque resins, with the specimen suspended in water. CT examination of the injected kidneys was performed to analyse the branches located deeply. After imaging acquisition, the specimens were treated with sodium hydroxide for removal of the parenchyma to obtain vascular casts. Ten casts (66.6%) showed the classic subdivision of the main artery into single posterior and anterior branches. With regard to the distribution of the segmental or second-order arteries, only two casts (13%) showed a pattern similar to that described by Graves, characterized by four segmental (second-order) branches coming from the anterior renal artery (apical, superior, middle and inferior). In the remaining 13 kidneys (87%) a different arterial vascular network was detected. In 10 casts (80%) a single renal segment was vascularized by two or more different branches coming from an artery leading to another segment (multiple vascularization). Multiple vascularization was observed in three (20%) apical segments, five (33%) superior segments, six (40%) middle segments, seven (47%) inferior segments and two (13%) posterior segments. This study shows that in the human kidneys the arterial vasculature is frequently different from that described by Graves. Moreover, in a significant percentage of cases, a single renal segment receives two or more branches that originate from an artery leading to another segment. © 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd.

Protective Role of Sodium-Glucose Co-Transporter 2 Inhibition Against Vascular Complications in Diabetes.

PubMed

Yamagishi, Sho-ichi; Matsui, Takanori

2016-04-01

Diabetic micro- and macroangiopathy are devastating vascular complications that could account for disabilities and high mortality rate in patients with diabetes. Indeed, diabetic nephropathy and retinopathy are the leading causes of end-stage renal failure and acquired blindness, respectively, and atherosclerotic cardiovascular diseases (CVD) accounts for about 60% of death in diabetic subjects. As a result, the average life span of diabetic patients is about 10-15 years shorter than that of non-diabetic subjects. Furthermore, tight blood glucose control might have no more than a marginal impact on CVD in general and on all-cause mortality in particular in diabetes. Therefore, therapeutic strategies that target vascular complications in diabetes need to be developed. Recently, selective inhibition of sodium-glucose co-transporter 2 (SGLT2) has been proposed as a potential therapeutic target for the treatment of patients with diabetes because of low risk of hypoglycemia and no weight gain. Because 90% of glucose filtered by the glomerulus is reabsorbed by a low-affinity/high-capacity SGLT2 expressed in the S1 and S2 segments of the proximal tubule, blockade of SGLT2 promotes urinary glucose excretion and as a result improves hyperglycemia in an insulin-independent manner. Moreover, we have shown that SGLT2-mediated glucose overload to tubular cells could elicit inflammatory and pro-apoptotic reactions in this cell, being directly involved in diabetic nephropathy. In addition, several clinical studies have also shown that SGLT2 inhibitors could reduce blood pressure, body weight, and serum uric acid levels and ameliorate cardiovascular risk in patients with diabetes. This review summarizes the pathophysiological role of SGLT2 in vascular complications in diabetes and its potential therapeutic interventions.

Anatomic variations of the renal vessels: focus on the precaval right renal artery.

PubMed

Bouali, Ourdia; Labarre, David; Molinier, François; Lopez, Raphaël; Benouaich, Vincent; Lauwers, Frédéric; Moscovici, Jacques

2012-07-01

The aim of this study was to determine the prevalence of precaval right renal artery and to investigate the distribution of renal arteries and veins. We discuss a theory of development of renal vascular variants. We retrospectively reviewed 120 arterial phase contrast material-enhanced spiral computerized tomography scans of the abdomen (1- to 2-mm section thickness) performed during a two-month period. Forty percent of the study group (48 patients) had one artery and one vein on each side, with typical course. There was a 9.17% prevalence of precaval right renal artery: 10 patients had a lower pole accessory artery in precaval position and one patient had the main and the accessory arteries that pass anterior to the inferior vena cava. In these cases, associated variations of renal vessels were higher than in the patients without precaval artery variant. There were multiple arteries in 28.3% of the right kidneys and in 26.7% of the left ones. Variants of the right renal vein consisted in multiple veins in 20% (24 cases). We detected no case of multiple left renal veins, but we described variations of its course (circum- or retroaortic vein) in 9.17% (11 cases). Twenty-six patients (21.7%) had associated variations of the renal pedicle. The current technical support allows for a minimally invasive study of vessels anatomy. In our study the prevalence of a precaval right renal artery appears to be higher than previously reported (9.17%). Knowledge on anatomical variations of right renal artery and associated renal vessels variations has major clinical implications.

Variant anatomy of renal arteries in a Kenyan population.

PubMed

Ogeng'o, Julius A; Masaki, Charles O; Sinkeet, Simeon R; Muthoka, Johnstone M; Murunga, Acleus K

2010-01-01

Variant anatomy of renal arteries is important in renal transplant, vascular reconstruction, and uroradiological procedures. The variations show ethnic and population differences. Data from Africans are scarce and altogether absent for Kenyans. To describe patterns of origin, trajectories and branching of renal arteries in a Kenyan population. Descriptive cross-sectional study conducted in the Department of Human Anatomy, University of Nairobi. Three hundred and fifty six kidneys from 178 cadavers and postmortem specimens were used in the study. Aorta, renal arteries and kidneys were exposed by dissection. Number, trajectories, level of branching, number of branches and point of entry into the kidney were recorded. Data was analyzed using SPSS version 16.0, and presented using macrographs, tables, and bar charts. Additional arteries occurred in 14.3% of the cases. In 82.4% of these, there was one additional artery. Fifty nine point five per cent of the double renal arteries were parallel and 7.1% crossed. Of the 305 single arteries, 76.4% showed hilar, 21.6% prehilar and 2% intraparenchymal branching. In the hilar branching, ladder type was present in 65% and fork type in 35%. Bifurcation and trifurcation were present in 59.6% and 33.1% respectively. Polar arteries were present in 16.9% cases. Over 14% of the Kenyan population may have additional renal arteries while more than 20% show early branching. Several trajectories and hilar branching patterns exist which renal transplant surgeons and radiologists should be aware of to avoid inadvertent vascular injury.

A Literature Review of Renal Surgical Anatomy and Surgical Strategies for Partial Nephrectomy

PubMed Central

Klatte, Tobias; Ficarra, Vincenzo; Gratzke, Christian; Kaouk, Jihad; Kutikov, Alexander; Macchi, Veronica; Mottrie, Alexandre; Porpiglia, Francesco; Porter, James; Rogers, Craig G.; Russo, Paul; Thompson, R. Houston; Uzzo, Robert G.; Wood, Christopher G.; Gill, Inderbir S.

2016-01-01

Context A detailed understanding of renal surgical anatomy is necessary to optimize preoperative planning and operative technique and provide a basis for improved outcomes. Objective To evaluate the literature regarding pertinent surgical anatomy of the kidney and related structures, nephrometry scoring systems, and current surgical strategies for partial nephrectomy (PN). Evidence acquisition A literature review was conducted. Evidence synthesis Surgical renal anatomy fundamentally impacts PN surgery. The renal artery divides into anterior and posterior divisions, from which approximately five segmental terminal arteries originate. The renal veins are not terminal. Variations in the vascular and lymphatic channels are common; thus, concurrent lymphadenectomy is not routinely indicated during PN for cT1 renal masses in the setting of clinically negative lymph nodes. Renal-protocol contrast-enhanced computed tomography or magnetic resonance imaging is used for standard imaging. Anatomy-based nephrometry scoring systems allow standardized academic reporting of tumor characteristics and predict PN outcomes (complications, remnant function, possibly histology). Anatomy-based novel surgical approaches may reduce ischemic time during PN; these include early unclamping, segmental clamping, tumor-specific clamping (zero ischemia), and unclamped PN. Cancer cure after PN relies on complete resection, which can be achieved by thin margins. Post-PN renal function is impacted by kidney quality, remnant quantity, and ischemia type and duration. Conclusions Surgical renal anatomy underpins imaging, nephrometry scoring systems, and vascular control techniques that reduce global renal ischemia and may impact post-PN function. A contemporary ideal PN excises the tumor with a thin negative margin, delicately secures the tumor bed to maximize vascularized remnant parenchyma, and minimizes global ischemia to the renal remnant with minimal complications. Patient summary In this report

A Literature Review of Renal Surgical Anatomy and Surgical Strategies for Partial Nephrectomy.

PubMed

Klatte, Tobias; Ficarra, Vincenzo; Gratzke, Christian; Kaouk, Jihad; Kutikov, Alexander; Macchi, Veronica; Mottrie, Alexandre; Porpiglia, Francesco; Porter, James; Rogers, Craig G; Russo, Paul; Thompson, R Houston; Uzzo, Robert G; Wood, Christopher G; Gill, Inderbir S

2015-12-01

A detailed understanding of renal surgical anatomy is necessary to optimize preoperative planning and operative technique and provide a basis for improved outcomes. To evaluate the literature regarding pertinent surgical anatomy of the kidney and related structures, nephrometry scoring systems, and current surgical strategies for partial nephrectomy (PN). A literature review was conducted. Surgical renal anatomy fundamentally impacts PN surgery. The renal artery divides into anterior and posterior divisions, from which approximately five segmental terminal arteries originate. The renal veins are not terminal. Variations in the vascular and lymphatic channels are common; thus, concurrent lymphadenectomy is not routinely indicated during PN for cT1 renal masses in the setting of clinically negative lymph nodes. Renal-protocol contrast-enhanced computed tomography or magnetic resonance imaging is used for standard imaging. Anatomy-based nephrometry scoring systems allow standardized academic reporting of tumor characteristics and predict PN outcomes (complications, remnant function, possibly histology). Anatomy-based novel surgical approaches may reduce ischemic time during PN; these include early unclamping, segmental clamping, tumor-specific clamping (zero ischemia), and unclamped PN. Cancer cure after PN relies on complete resection, which can be achieved by thin margins. Post-PN renal function is impacted by kidney quality, remnant quantity, and ischemia type and duration. Surgical renal anatomy underpins imaging, nephrometry scoring systems, and vascular control techniques that reduce global renal ischemia and may impact post-PN function. A contemporary ideal PN excises the tumor with a thin negative margin, delicately secures the tumor bed to maximize vascularized remnant parenchyma, and minimizes global ischemia to the renal remnant with minimal complications. In this report we review renal surgical anatomy. Renal mass imaging allows detailed delineation of the

Antiangiogenic treatment diminishes renal injury and dysfunction via regulation of local AKT in early experimental diabetes.

PubMed

Bai, Xiaoyan; Li, Xiao; Tian, Jianwei; Zhou, Zhanmei

2014-01-01

In view of increased vascular endothelial growth factor-A (VEGF-A) expression and renal dysfunction in early diabetes, we designed a study to test whether VEGF-A inhibition can prevent early renal injury and dysfunction. We investigated the relationship and mechanism between VEGF-A and AKT regulation. In vitro, VEGF-A small interfering RNA (siRNA) and AKT inhibitor MK-2206 were employed to podocytes and NRK-52 cells cultured in high glucose (30 mM). In vivo, the antiangiogenic drug endostatin was administered in 12 week-old streptozotocin-induced male Sprague Dawley rats. The levels of VEGF-A, AKT, phosphorylated Ser⁴⁷³-AKT, phosphorylated Thr³⁰⁸-AKT, nephrin, angiotensin II (Ang II), angiotensin type II receptor 1 (ATR1) were examined using quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR), Western blot analysis and immunohistochemistry. Interactions between phosphorylated Thr³⁰⁸-AKT and either nephrin in podocytes or Ang II in renal tubules were studied, respectively, using confocal immunofluorescence microscopy and immunoprecipitation. Silencing VEGF-A in podocytes upregulated phosphorylated Thr³⁰⁸-AKT and nephrin. Silencing VEGF-A in NRK-52E cells upregulated phosphorylated Thr³⁰⁸-AKT while downregulated Ang II and ATR1. MK-2206 enhanced VEGF-A expression in both podocytes and NRK-52E cells by inhibiting AKT activities. In diabetic rat kidneys, VEGF-A was upregulated and phosphorylated Thr³⁰⁸-AKT colocalized with either nephrin in podocytes or Ang II in renal tubules. With the endostatin treatment, the level of VEGF-A decreased while phosphorylated Thr³⁰⁸-AKT increased in both glomeruli and renal tubules. Treatment with endostatin upregulated nephrin in podocytes while downregulated Ang II and AT1R in renal tubules. Glomerular mesangial expansion was attenuated by the endostatin treatment, however, differences did not reach statistical significance. Endostatin ameliorated the interstitial fibrosis

Antiangiogenic Treatment Diminishes Renal Injury and Dysfunction via Regulation of Local AKT in Early Experimental Diabetes

PubMed Central

Zhou, Zhanmei

2014-01-01

In view of increased vascular endothelial growth factor-A (VEGF-A) expression and renal dysfunction in early diabetes, we designed a study to test whether VEGF-A inhibition can prevent early renal injury and dysfunction. We investigated the relationship and mechanism between VEGF-A and AKT regulation. In vitro, VEGF-A small interfering RNA (siRNA) and AKT inhibitor MK-2206 were employed to podocytes and NRK-52 cells cultured in high glucose (30 mM). In vivo, the antiangiogenic drug endostatin was administered in 12 week-old streptozotocin-induced male Sprague Dawley rats. The levels of VEGF-A, AKT, phosphorylated Ser473-AKT, phosphorylated Thr308-AKT, nephrin, angiotensin II (Ang II), angiotensin type II receptor 1 (ATR1) were examined using quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR), Western blot analysis and immunohistochemistry. Interactions between phosphorylated Thr308-AKT and either nephrin in podocytes or Ang II in renal tubules were studied, respectively, using confocal immunofluorescence microscopy and immunoprecipitation. Silencing VEGF-A in podocytes upregulated phosphorylated Thr308-AKT and nephrin. Silencing VEGF-A in NRK-52E cells upregulated phosphorylated Thr308-AKT while downregulated Ang II and ATR1. MK-2206 enhanced VEGF-A expression in both podocytes and NRK-52E cells by inhibiting AKT activities. In diabetic rat kidneys, VEGF-A was upregulated and phosphorylated Thr308-AKT colocalized with either nephrin in podocytes or Ang II in renal tubules. With the endostatin treatment, the level of VEGF-A decreased while phosphorylated Thr308-AKT increased in both glomeruli and renal tubules. Treatment with endostatin upregulated nephrin in podocytes while downregulated Ang II and AT1R in renal tubules. Glomerular mesangial expansion was attenuated by the endostatin treatment, however, differences did not reach statistical significance. Endostatin ameliorated the interstitial fibrosis, urine albumin excretion rate

[Algal oligosaccharides ameliorate osteoporosis via up-regulation of parathyroid hormone 1-84 and vascular endothelial growth factor].

PubMed

Wang, Li; Wang, Haiya; Fang, Ningyuan

2016-06-01

To determine whether algal oligosac- charide~ affects the levels of parathyroid hormone 1-84 (PTH1-84) and vascular endothelial growth fac- tor (VEGF). An osteoporosis rat model was estab- lished via bilateral ovariectomy. The model rats were fed algal oligosaccharides (molecular weights: 600-1, 200 Da) for 4 months. Bone mineral density (BMD) was then measured. MG-63 human osteo- blastic cells were treated with algal oligosaccha- rides. The expression of PTH1-84 and VEGF was then examined. Oligosaccharide-treated cells were transfected with PTH1-84 short hairpin RNA (shR- NA), VEGF shRNA, and PTH1-84-VEGF small interfer- ing RNA (siRNA). The growth rates were then com- pared between transfected and non-transfected Algal oligosaccharides increased the BMD of the osteoporosis rat model compared with untreated controls (P < 0.05). When MG-63 cells were treated with algal oligosaccharides, the growth rate increased by 25% compared with the control group at day 3 (P < 0.05). In addition, the ex- pression of P.TH84 and VEGF was. enhanced. Con- versey w hen tecells were tranfected with PTH84 shRNA, VEGF shRNA, or PTH1-84-VEGF siR- NA, the growth rate was decreased by 17%, 35% and 70%, respectively, compared with controls at day 3 (P < 0.05). Algal oligosaccharides ameliorate osteoporosis via up-regulation of PTH1-84 and VEGF. Algal oligosaccharides should be developed as a potential drug for osteoporosis treatment.

Quantification of vascular damage in acute kidney injury with fluorine magnetic resonance imaging and spectroscopy.

PubMed

Moore, Jeremy K; Chen, Junjie; Pan, Hua; Gaut, Joseph P; Jain, Sanjay; Wickline, Samuel A

2018-06-01

To design a fluorine MRI/MR spectroscopy approach to quantify renal vascular damage after ischemia-reperfusion injury, and the therapeutic response to antithrombin nanoparticles (NPs) to protect kidney function. A total of 53 rats underwent 45 min of bilateral renal artery occlusion and were treated at reperfusion with either plain perfluorocarbon NPs or NPs functionalized with a direct thrombin inhibitor (PPACK:phenyalanine-proline-arginine-chloromethylketone). Three hours after reperfusion, kidneys underwent ex vivo fluorine MRI/MR spectroscopy at 4.7 T to quantify the extent and volume of trapped NPs, as an index of vascular damage and ischemia-reperfusion injury. Microscopic evaluation of structural damage and NP trapping in non-reperfused renal segments was performed. Serum creatinine was quantified serially over 7 days. The damaged renal cortico-medullary junction trapped a significant volume of NPs (P = 0.04), which correlated linearly (r = 0.64) with the severity of kidney injury 3 h after reperfusion. Despite global large vessel reperfusion, non-reperfusion in medullary peritubular capillaries was confirmed by MRI and microscopy, indicative of continuing hypoxia due to vascular compromise. Treatment of animals with PPACK NPs after acute kidney injury did not accelerate kidney functional recovery. Quantification of ischemia-reperfusion injury after acute kidney injury with fluorine MRI/MR spectroscopy of perfluorocarbon NPs objectively depicts the extent and severity of vascular injury and its linear relationship to renal dysfunction. The lack of kidney function improvement after early posttreatment thrombin inhibition confirms the rapid onset of ischemia-reperfusion injury as a consequence of vascular damage and non-reperfusion. The prolongation of medullary ischemia renders cortico-medullary tubular structures susceptible to continued necrosis despite restoration of large vessel flow, which suggests limitations to acute interventions after

The radiologist's role in the management of papillary renal cell carcinoma.

PubMed

Corral de la Calle, M Á; Encinas de la Iglesia, J; Martín López, M R; Fernández Pérez, G C; Águeda Del Bas, D S

Papillary carcinoma is the second most common renal cell carcinoma. It has a better prognosis than the more frequent clear cell carcinoma, although this does not hold true for advanced cases, because no specific treatment exists. It presents as a circumscribed peripheral tumor (small and homogeneously solid or larger and cystic/hemorrhagic) or as an infiltrating lesion that invades the veins, which has a worse prognosis. Due to their low vascular density, papillary renal cell carcinomas enhance less than other renal tumors, and this facilitates their characterization. On computed tomography, they might not enhance conclusively, and in these cases they are impossible to distinguish from hyperattenuating cysts. Contrast-enhanced ultrasonography and magnetic resonance imaging are more sensitive for detecting vascularization. Other characteristics include a specific vascular pattern, hypointensity on T2-weighted images, restricted water diffusion, and increased signal intensity in opposed phase images. We discuss the genetic, histologic, clinical, and radiological aspects of these tumors in which radiologists play a fundamental role in management. Copyright © 2016 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.

Renal Outcomes and Dietary Potassium: The Overshadowed Electrolyte?

PubMed Central

Jablonski, Kristen L.; Kendrick, Jessica

2014-01-01

Smyth et al. examined the association between urinary sodium and potassium excretion and adverse renal outcomes in adults at high cardiovascular risk. They found no association between urinary sodium excretion and adverse renal outcomes, but a reduced odds of adverse renal outcomes with higher urinary potassium excretion. This finding is quite interesting and a major advancement from this study. It will be important to ascertain whether this finding holds true in individuals free from vascular disease and diabetes, as well as in patients with chronic kidney disease. PMID:25427082

Ameliorative effects of arctiin from Arctium lappa on experimental glomerulonephritis in rats.

PubMed

Wu, Jian-Guo; Wu, Jin-Zhong; Sun, Lian-Na; Han, Ting; Du, Jian; Ye, Qi; Zhang, Hong; Zhang, Yu-Guang

2009-11-01

Membranous glomerulonephritis (MGN) remains the most common cause of adult-onset nephrotic syndrome in the world and up to 40% of untreated patients will progress to end-stage renal disease. Although the treatment of MGN with immunosuppressants or steroid hormones can attenuate the deterioration of renal function, numerous treatment-related complications have also been established. In this study, the ameliorative effects of arctiin, a natural compound isolated from the fruits of Arctium lappa, on rat glomerulonephritis induced by cationic bovine serum albumin (cBSA) were determined. After oral administration of arctiin (30, 60, 120 mg/kgd) for three weeks, the levels of serum creatinine (Scr) and blood urea nitrogen (BUN) and 24-h urine protein content markedly decreased, while endogenous creatinine clearance rate (ECcr) significantly increased. The parameters of renal lesion, hypercellularity, infiltration of polymorphonuclear leukocyte (PMN), fibrinoid necrosis, focal and segmental proliferation and interstitial infiltration, were reversed. In addition, we observed that arctiin evidently reduced the levels of malondialdehyde (MDA) and pro-inflammatory cytokines including interleukin-6 (IL-6) and tumor necrosis factor (TNF-alpha), suppressed nuclear factor-kappaB p65 (NF-kappaB) DNA binding activity, and enhanced superoxide dismutase (SOD) activity. These findings suggest that the ameliorative effects of arctiin on glomerulonephritis is carried out mainly by suppression of NF-kappaB activation and nuclear translocation and the decreases in the levels of these pro-inflammatory cytokines, while SOD is involved in the inhibitory pathway of NF-kappaB activation. Arctiin has favorable potency for the development of an inhibitory agent of NF-kappaB and further application to clinical treatment of glomerulonephritis, though clinical studies are required.

Precise measurement of renal filtration and vascular parameters using a two-compartment model for dynamic contrast-enhanced MRI of the kidney gives realistic normal values.

PubMed

Tofts, Paul S; Cutajar, Marica; Mendichovszky, Iosif A; Peters, A Michael; Gordon, Isky

2012-06-01

To model the uptake phase of T(1)-weighted DCE-MRI data in normal kidneys and to demonstrate that the fitted physiological parameters correlate with published normal values. The model incorporates delay and broadening of the arterial vascular peak as it appears in the capillary bed, two distinct compartments for renal intravascular and extravascular Gd tracer, and uses a small-vessel haematocrit value of 24%. Four physiological parameters can be estimated: regional filtration K ( trans ) (ml min(-1) [ml tissue](-1)), perfusion F (ml min(-1) [100 ml tissue](-1)), blood volume v ( b ) (%) and mean residence time MRT (s). From these are found the filtration fraction (FF; %) and total GFR (ml min(-1)). Fifteen healthy volunteers were imaged twice using oblique coronal slices every 2.5 s to determine the reproducibility. Using parenchymal ROIs, group mean values for renal biomarkers all agreed with published values: K ( trans ): 0.25; F: 219; v ( b ): 34; MRT: 5.5; FF: 15; GFR: 115. Nominally cortical ROIs consistently underestimated total filtration (by ~50%). Reproducibility was 7-18%. Sensitivity analysis showed that these fitted parameters are most vulnerable to errors in the fixed parameters kidney T(1), flip angle, haematocrit and relaxivity. These renal biomarkers can potentially measure renal physiology in diagnosis and treatment. • Dynamic contrast-enhanced magnetic resonance imaging can measure renal function. • Filtration and perfusion values in healthy volunteers agree with published normal values. • Precision measured in healthy volunteers is between 7 and 15%.

Successful Embolization of a Renal Artery Pseudoaneurysm with Arteriovenous Fistula and Extravasations Using Onyx After Partial Nephrectomy for Renal Cell Carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zelenak, Kamil, E-mail: zelenak@mfn.s; Sopilko, Igor; Svihra, Jan

2009-01-15

Partial nephrectomy can be associated with vascular complications. Computed tomography (CT) with CT angiography is ideal for noninvasive imaging of this process. The treatment of choice is selective embolization. Successful transcatheter embolization of right renal subsegmental artery pseudoaneurysm with arteriovenous fistula and extravasations using Onyx was performed in a 66-year-old woman with macrohematuria 12 days after partial nephrectomy for renal cell carcinoma.

Fibromuscular Dysplasia-Related Renal Artery Stenosis Associated with Aneurysm: Successive Endovascular Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Serter, Selim; Oran, Ismail; Parildar, Mustafa

2007-04-15

Fibromuscular dysplasia (FMD) is a nonatherosclerotic, noninflammatory vascular disease. FMD of the renal arteries is one of the leading causes of curable hypertension. The simultaneous occurrence of FMD and renal artery aneurysm has been described previously. In this case, we present a fibrodysplastic lesion and an aneurysm in a renal artery treated with a percutanous transluminal angioplasty and coil embolization.

Ameliorative Effect of Caffeic Acid on Capecitabine-Induced Hepatic and Renal Dysfunction: Involvement of the Antioxidant Defence System

PubMed Central

Olayinka, Ebenezer Tunde; Ore, Ayokanmi; Adeyemo, Oluwatobi Adewumi

2017-01-01

Background: It has been postulated that during liver and kidney damage there is a decreased in the antioxidant status associated with a simultaneous increase in the reactive oxygen species and lipid peroxidation. In consonant with this, Capecitabine, an oral chemotherapy and inactive non-cytotoxic fluoropyrimidine considered for the treatment of advance colorectal cancer, has also been shown to induce oxidative stress in liver tissues. Caffeic acid, a typical hydroxycinnamic, has been claimed to be effective against oxidative stress. Therefore, this present work studied the protective effect of caffeic acid on oxidative stress-induced liver and kidney damage by the administration of capecitabine. Methods: Twenty-four male Wistar strain rats were randomly divided into four treatment groups: A. control, B. capecitabine (CPTB)-treated group (30 mg/kg b.w. CPTB), C. caffeic acid (CFA)-treated group (100 mg/kg b.w. CFA) and D. co-treated group with CFA (100 mg/kg b.w.) and CPTB (30 mg/kg b.w.). Results: Caffeic acid administration significantly ameliorated the elevated plasma biomarkers of hepatic and renal tissue damage induced by the capecitabine and improved enzymatic and non-enzymatic antioxidant levels in liver organ. Conclusions: The protective effect of caffeic acid could be attributed to its ability to boost the antioxidant defence system and reduce lipid peroxidation. PMID:29068374

Effects of levosimendan on glomerular filtration rate, renal blood flow, and renal oxygenation after cardiac surgery with cardiopulmonary bypass: a randomized placebo-controlled study.

PubMed

Bragadottir, Gudrun; Redfors, Bengt; Ricksten, Sven-Erik

2013-10-01

Acute kidney injury develops in a large proportion of patients after cardiac surgery because of the low cardiac output syndrome. The inodilator levosimendan increases cardiac output after cardiac surgery with cardiopulmonary bypass, but a detailed analysis of its effects on renal perfusion, glomerular filtration, and renal oxygenation in this group of patients is lacking. We therefore evaluated the effects of levosimendan on renal blood flow, glomerular filtration rate, renal oxygen consumption, and renal oxygen demand/supply relationship, i.e., renal oxygen extraction, early after cardiac surgery with cardiopulmonary bypass. Prospective, placebo-controlled, and randomized trial. Cardiothoracic ICU of a tertiary center. Postcardiac surgery patients (n=30). The patients were randomized to receive levosimendan, 0.1 µg/kg/min after a loading dose of 12 µg/kg (n=15), or placebo (n=15). The experimental procedure started 4-6 hours after surgery in the ICU during propofol sedation and mechanical ventilation. Systemic hemodynamic were evaluated by a pulmonary artery thermodilution catheter. Renal blood flow and glomerular filtration rate were measured by the renal vein retrograde thermodilution technique and by renal extraction of Cr-EDTA, respectively. Central venous pressure was kept constant by colloid/crystalloid infusion. Compared to placebo, levosimendan increased cardiac index (22%), stroke volume index (15%), and heart rate (7%) and decreased systemic vascular resistance index (21%), whereas mean arterial pressure was not affected. Levosimendan induced significant increases in renal blood flow (12%, p<0.05) and glomerular filtration rate (21%, p<0.05), decreased renal vascular resistance (18%, p<0.05) but caused no significant changes in filtration fraction, renal oxygen consumption, or renal oxygen extraction, compared to placebo. After cardiac surgery with cardiopulmonary bypass, levosimendan induces a vasodilation, preferentially of preglomerular resistance

Outcome of renal replacement treatment in patients with diabetes mellitus.

PubMed Central

McMillan, M A; Briggs, J D; Junor, B J

1990-01-01

OBJECTIVE--To compare the outcome of renal replacement treatment in patients with diabetes mellitus and in non-diabetic patients with end stage renal failure. DESIGN--Retrospective comparison of cases and matched controls. SETTING--Renal unit, Western Infirmary, Glasgow, providing both dialysis and renal transplantation. PATIENTS--82 Diabetic patients starting renal replacement treatment between 1979 and 1988, compared with 82 matched non-diabetic controls with renal failure and 39 different matched controls undergoing renal transplantation. MAIN OUTCOME MEASURES--Patient characteristics, history of smoking, prevalence of left ventricular hypertrophy and myocardial ischaemia at start of renal replacement treatment; survival of patients with renal replacement treatment and of patients and allografts with renal transplantation. RESULTS--The overall survival of the diabetic patients during the treatment was 83%, 59%, and 50% at one, three, and five years. Survival was significantly poorer in the diabetic patients than the controls (p less than 0.001). Particularly adverse features for outcome at the start of treatment were increasing age (p less than 0.01) and current cigarette smoking (relative risk (95% confidence interval) 2.28 (0.93 to 4.84), p less than 0.05). Deaths were mainly from cardiac and vascular causes. The incidence of peritonitis in patients on continuous ambulatory peritoneal dialysis was the same in diabetic patients and controls (49% in each group remained free of peritonitis after one year), and the survival of renal allografts was not significantly worse in diabetic patients (p less than 0.5). CONCLUSIONS--Renal replacement treatment may give good results in diabetic patients, although the outlook remains less favourable than for non-diabetic patients because of coexistent, progressive vascular disease, which is more severe in older patients. PMID:2207427

Angiography in the Isolated Perfused Kidney: Radiological Evaluation of Vascular Protection in Tissue Ablation by Nonthermal Irreversible Electroporation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wendler, Johann Jakob, E-mail: johann.wendler@med.ovgu.de; Pech, Maciej; Blaschke, Simon

2012-04-15

Purpose: The nonthermal irreversible electroporation (NTIRE) is a novel nonthermal tissue ablation technique by local application of high-voltage current within microseconds leading to a delayed apoptosis. The purpose of this experimental study was the first angiographic evaluation of the acute damage of renal vascular structure in NTIRE. Methods: Results of conventional dynamic digital substraction angiography (DSA) and visualization of the terminal vascular bed of renal parenchyma by high-resolution X-ray in mammography technique were evaluated before, during, and after NTIRE of three isolated perfused porcine ex vivo kidneys. Results: In the dedicated investigation, no acute vascular destruction of the renal parenchymamore » and no dysfunction of the kidney perfusion model were observed during or after NTIRE. Conspicuous were concentric wave-like fluctuations of the DSA contrast agent simultaneous to the NTIRE pulses resulting from NTIRE pulse shock wave. Conclusion: The NTIRE offers an ablation method with no acute collateral vascular damage in angiographic evaluation.« less

Renal accumulation of pentosidine in non-diabetic proteinuria-induced renal damage in rats.

PubMed

Waanders, Femke; Greven, Wendela L; Baynes, John W; Thorpe, Suzanne R; Kramer, Andrea B; Nagai, Ryoji; Sakata, Noriyuki; van Goor, Harry; Navis, Gerjan

2005-10-01

Advanced glycation end-products (AGEs) contribute to the pathogenesis of diabetic glomerulopathy. The role of AGEs in non-diabetic renal damage is not well characterized. First, we studied whether renal AGE accumulation occurs in non-diabetic proteinuria-induced renal damage and whether this is ameliorated by renoprotective treatment. Secondly, we investigated whether renal AGE accumulation was due to intrarenal effects of local protein trafficking. Pentosidine was measured (by high-performance liquid chromatography) in rats with chronic bilateral adriamycin nephropathy (AN), untreated and treated with lisinopril. Age-matched healthy rats served as negative controls. Secondly, we compared renal pentosidine in mild proteinuric and non-proteinuric kidneys of unilateral AN and in age-matched controls at 12 and 30 weeks. Intrarenal localization of pentosidine was studied by immunohistochemistry. Renal pentosidine was elevated in untreated AN (0.14+/-0.04 micromol/mol valine) vs healthy controls (0.04+/-0.01 micromol/mol valine, P<0.01). In lisinopril-treated AN, pentosidine was lower (0.09+/-0.02 micromol/mol valine) than in untreated AN (P<0.05). In unilateral proteinuria, pentosidine was similar in non-proteinuric and proteinuric kidneys. After 30 weeks of unilateral proteinuria, pentosidine was increased in both kidneys (0.26+/-0.10 micromol/mol valine) compared with controls (0.18+/-0.06 micromol/mol valine, P<0.05). Pentosidine (AN, week 30) was also increased compared with AN at week 12 (0.16+/-0.06 micromol/mol valine, P<0.01). In control and diseased kidneys, pentosidine was present in the collecting ducts. In proteinuric kidneys, in addition, pentosidine was present in the brush border and cytoplasm of dilated tubular structures, i.e. at sites of proteinuria-induced tubular damage. Pentosidine accumulates in non-diabetic proteinuric kidneys in damaged tubules, and renoprotective treatment by angiotensin-converting enzyme (ACE) inhibitors inhibits AGE

The Renal Renin-Angiotensin System

ERIC Educational Resources Information Center

Harrison-Bernard, Lisa M.

2009-01-01

The renin-angiotensin system (RAS) is a critical regulator of sodium balance, extracellular fluid volume, vascular resistance, and, ultimately, arterial blood pressure. In the kidney, angiotensin II exerts its effects to conserve salt and water through a combination of the hemodynamic control of renal blood flow and glomerular filtration rate and…

[Census 2004 of the Italian Renal and Dialysis Units. Emilia-Romagna, Toscana].

PubMed

Lusenti, T; Santoro, A; Cappelli, G; Cagnoli, L; Moriconi, L; Rindi, P; Lippi, A; Alloatti, S

2006-01-01

The 2004 SIN census of the Italian nephrology and dialysis centres showed many interesting data about the epidemiology and the organization in the Regions of Emilia-Romagna (ER) and Tuscany (T). A) Epidemiology: incidence of dialysis patients 169 pmp (patients per million population) in ER, 147 ppm in T; prevalence of dialysis patients 639 pmp and 665 pmp, respectively; prevalence of transplanted patients 325 ppm in ER and 233 pmp in T; gross mortality of dialysis patients 16.3% and 13.4%, respectively; B) Type of vascular access in prevalently dialysis patients: arteriovenous fistula 83% and 78%; central venous catheter 13% and 12%; vascular graft 5% and 9%. C) Structural resources: nephrology beds 44 mp (per million population) and 50 mp; dialysis places 157 and 146 mp. D) Personnel resources : renal physicians 29 and 41 mp; renal nurses 171 and 202 mp ; each renal physician cares for 22 and 16 dialysis patients, and each renal nurse takes care of 3.7 and 3.3 dialysis patients. E) Activity: hospital admissions 1572, 1769 pmp; renal biopsies 115 and 166 pmp.

[Mineral and bone disorders in renal transplantation].

PubMed

Bacchetta, Justine; Lafage-Proust, Marie-Hélène; Chapurlat, Roland

2013-12-01

The deregulation of bone and mineral metabolism during chronic kidney disease (CKD) is a daily challenge for physicians, its management aiming at decreasing the risk of both fractures and vascular calcifications. Renal transplantation in the context of CKD, with pre-existing renal osteodystrophy as well as nutritional impairment, chronic inflammation, hypogonadism and corticosteroids exposure, represents a major risk factor for bone impairment in the post-transplant period. The aim of this review is therefore to provide an update on the pathophysiology of mineral and bone disorders after renal transplantation. Copyright © 2013 Association Société de néphrologie. Published by Elsevier SAS. All rights reserved.

Application of Onyx for Renal Arteriovenous Malformation With First Case Report of a Renal Hyperdense Striation Sign

PubMed Central

Juan, Yu-Hsiang; Lin, Yu-Ching; Sheng, Ting-Wen; Cheung, Yun-Chung; Ng, Shu-Hang; Yu, Chin-Wei; Wong, Ho-Fai

2015-01-01

Abstract Onyx is an emerging treatment modality for visceral vascular malformations, especially in cases in which delicate nidal penetration of the arteriovenous malformation (AVM) is desired. A computed tomography (CT) image presentation of hyperdense striations along the renal medulla secondary to the tantalum powder has not been previously reported. A 65-year-old woman presented to our institution with intermittent gross hematuria and left flank pain for 10 days. Both CT and conventional angiographies confirmed cirsoid-type renal AVM, which was successfully treated with Onyx. Follow-up CT after treatment revealed presence of hyperdense striations along the renal medulla, which resolved during later image follow-up. Despite its frequent usage in neural intervention, the application of Onyx in visceral AVM is gradually gaining interest, especially in cases in which delicate nidal penetration of the AVM is desired. Renal hyperdense striation sign should be recognized to avoid confusion with embolizer migration, and further studies in patients with renal function impairment may be helpful in understanding its influence of renal function. PMID:26426661

Less contribution of mast cells to the progression of renal fibrosis in Rat kidneys with chronic renal failure.

PubMed

Baba, Asuka; Tachi, Masahiro; Ejima, Yutaka; Endo, Yasuhiro; Toyama, Hiroaki; Saito, Kazutomo; Abe, Nozomu; Yamauchi, Masanori; Miura, Chieko; Kazama, Itsuro

2017-02-01

Chronic renal failure (CRF) is histopathologically characterized by tubulointerstitial fibrosis in addition to glomerulosclerosis. Although mast cells are known to infiltrate into the kidneys with chronic inflammation, we know little about their contribution to the pathogenesis of renal fibrosis associated with CRF. The aim of this study was to reveal the involvement of mast cells in the progression of renal fibrosis in CRF. Using a rat model with CRF resulting from 5/6 nephrectomy, we examined the histopathological features of the kidneys and the infiltration of mast cells into the renal interstitium. By treating the rats with a potent mast cell stabilizer, tranilast, we also examined the involvement of mast cells in the progression of renal fibrosis associated with CRF. The CRF rat kidneys were characterized by the wide staining of collagen III and increased number of myofibroblasts, indicating the progression of renal fibrosis. Compared to T-lymphocytes or macrophages, the number of tryptase-positive mast cells was much smaller within the fibrotic kidneys and they did not proliferate in situ. The mRNA expression of mast cell-derived fibroblast-activating factors was not increased in the renal cortex isolated from CRF rat kidneys. Treatment with tranilast did not suppress the progression of renal fibrosis, nor did it ameliorate the progression of glomerulosclerosis and the interstitial proliferation of inflammatory leukocytes. This study demonstrated for the first time that mast cells are neither increased nor activated in the fibrotic kidneys of CRF rats. Compared to T-lymphocytes or macrophages that proliferate in situ within the fibrotic kidneys, mast cells were less likely to contribute to the progression of renal fibrosis associated with CRF. © 2016 Asian Pacific Society of Nephrology.

Exercise training and cardiometabolic diseases: focus on the vascular system.

PubMed

Roque, Fernanda R; Hernanz, Raquel; Salaices, Mercedes; Briones, Ana M

2013-06-01

The regular practice of physical activity is a well-recommended strategy for the prevention and treatment of several cardiovascular and metabolic diseases. Physical exercise prevents the progression of vascular diseases and reduces cardiovascular morbidity and mortality. Exercise training also ameliorates vascular changes including endothelial dysfunction and arterial remodeling and stiffness, usually present in type 2 diabetes, obesity, hypertension and metabolic syndrome. Common to these diseases is excessive oxidative stress, which plays an important role in the processes underlying vascular changes. At the vascular level, exercise training improves the redox state and consequently NO availability. Moreover, growing evidence indicates that other mediators such as prostanoids might be involved in the beneficial effects of exercise. The purpose of this review is to update recent findings describing the adaptation response induced by exercise in cardiovascular and metabolic diseases, focusing more specifically on the beneficial effects of exercise in the vasculature and the underlying mechanisms.

Protection of ischemic preconditioning on renal neural function in rats with acute renal failure.

PubMed

Wu, Ming-Shiou; Chien, Chiang-Ting; Ma, Ming-Chieh; Chen, Chau-Fong

2009-11-30

We tested whether tolerance induced by ischemic preconditioning (IPC) in kidneys was related to renal nerves. Experimental acute renal failure (ARF) in a rat model was induced for 45 min of left renal arterial occlusion (RAO), followed by 6 or 24 h of reperfusion (ischemic reperfusion (I/R) group). The episode of IPC was four cycles of 4 min of RAO at 11 min intervals and then the I/R injury was treated as above (IPC-I/R group). After 6 h of reperfusion, polyuria was found in the I/R group associated with an enhancement of afferent renal nerve activity (ARNA) and a reflexive decrease in efferent renal nerve activity (ERNA). Changes in nerve responses were related with a reduction in neutral endopeptidase (NEP) activity and an increased release of substance P (SP). After 24 h of reperfusion, the I/R group showed oliguria which was associated with a lower ARNA, hyperactivity of ERNA and a nine-fold increase in SP release due to a further 52% loss in NEP activity. Prior IPC treatment did not affect the changed ischemia-induced excretory and nervous activity patterns during the first 6 h of reperfusion, but normalized both responses in the kidneys 24 h after ischemia. The IPC-mediated protection in oliguric ARF was related to the preservation of NEP activity to only 25% loss that caused an increase of SP amounts of only three-fold and a minor change in neurokinin 1 receptor (NK-1R) activities. Finally, both excretory and sensory responses in oliguric ARF after saline loading were significantly ameliorated by IPC. We conclude that IPC results in preservation of the renal sensory response in postischemic kidneys and has a beneficial effect on controlling efferent renal sympathetic nerve activity and excretion of solutes and water.

Inhibition of p38 MAPK attenuates renal atrophy and fibrosis in a murine renal artery stenosis model.

PubMed

Wang, Diping; Warner, Gina M; Yin, Ping; Knudsen, Bruce E; Cheng, Jingfei; Butters, Kim A; Lien, Karen R; Gray, Catherine E; Garovic, Vesna D; Lerman, Lilach O; Textor, Stephen C; Nath, Karl A; Simari, Robert D; Grande, Joseph P

2013-04-01

Renal artery stenosis (RAS) is an important cause of chronic renal dysfunction. Recent studies have underscored a critical role for CCL2 (MCP-1)-mediated inflammation in the progression of chronic renal damage in RAS and other chronic renal diseases. In vitro studies have implicated p38 MAPK as a critical intermediate for the production of CCL2. However, a potential role of p38 signaling in the development and progression of chronic renal disease in RAS has not been previously defined. We sought to test the hypothesis that inhibition of p38 MAPK ameliorates chronic renal injury in mice with RAS. We established a murine RAS model by placing a cuff on the right renal artery and treated mice with the p38 inhibitor SB203580 or vehicle for 2 wk. In mice treated with vehicle, the cuffed kidney developed interstitial fibrosis, tubular atrophy, and interstitial inflammation. In mice treated with SB203580, the RAS-induced renal atrophy was reduced (70% vs. 39%, P < 0.05). SB203580 also reduced interstitial inflammation and extracellular matrix deposition but had no effect on the development of hypertension. SB203580 partially blocked the induction of CCL2, CCL7 (MCP-3), CC chemokine receptor 2 (CCR2), and collagen 4 mRNA expression in the cuffed kidneys. In vitro, blockade of p38 hindered both TNF-α and TGF-β-induced CCL2 upregulation. Based on these observations, we conclude that p38 MAPK plays a critical role in the induction of CCL2/CCL7/CCR2 system and the development of interstitial inflammation in RAS.

Evaluating Renal Transplant Status Using Viscoelastic Response (VisR) Ultrasound.

PubMed

Hossain, Md Murad; Selzo, Mallory R; Hinson, Robert M; Baggesen, Leslie M; Detwiler, Randal K; Chong, Wui K; Burke, Lauren M; Caughey, Melissa C; Fisher, Melrose W; Whitehead, Sonya B; Gallippi, Caterina M

2018-05-10

Chronic kidney disease is most desirably and cost-effectively treated by renal transplantation, but graft survival is a major challenge. Although irreversible graft damage can be averted by timely treatment, intervention is delayed when early graft dysfunction goes undetected by standard clinical metrics. A more sensitive and specific parameter for delineating graft health could be the viscoelastic properties of the renal parenchyma, which are interrogated non-invasively by Viscoelastic Response (VisR) ultrasound, a new acoustic radiation force (ARF)-based imaging method. Assessing the performance of VisR imaging in delineating histologically confirmed renal transplant pathologies in vivo is the purpose of the study described here. VisR imaging was performed in patients with (n = 19) and without (n = 25) clinical indication for renal allograft biopsy. The median values of VisR outcome metrics (τ, relative elasticity [RE] and relative viscosity [RV]) were calculated in five regions of interest that were manually delineated in the parenchyma (outer, center and inner) and in the pelvis (outer and inner). The ratios of a given VisR metric for all possible region-of-interest combinations were calculated, and the corresponding ratios were statistically compared between biopsied patients subdivided by diagnostic categories versus non-biopsied, control allografts using the two-sample Wilcoxon test (p <0.05). Although τ ratios non-specifically differentiated allografts with vascular disease, tubular/interstitial scarring, chronic allograft nephropathy and glomerulonephritis from non-biopsied control allografts, RE distinguished only allografts with vascular disease and tubular/interstitial scarring, and RV distinguished only vascular disease. These results suggest that allografts with scarring and vascular disease can be identified using non-invasive VisR RE and RV metrics. Copyright © 2018 World Federation for Ultrasound in Medicine and Biology. Published by

Effects of N-acetyl-L-cysteine on redox status and markers of renal function in mice inoculated with Bothrops jararaca and Crotalus durissus terrificus venoms.

PubMed

Barone, Juliana Marton; Frezzatti, Rodrigo; Silveira, Paulo Flavio

2014-03-01

Renal dysfunction is an important aggravating factor in accidents caused by Crotalus durissus terrificus (Cdt) and Bothrops jararaca (Bj) bites. N-acetyl-l-cysteine (NAC) is well known as a nephroprotective antioxidant with low toxicity. The present study investigated the effects of NAC on redox status and markers of renal function in mice that received vehicle (controls) or venoms (v) of Cdt and Bj. In controls NAC promoted hypercreatinemia, hypouremia, hyperosmolality with decreased urea in urine, hyperproteinuria, decreased protein and increased dipeptidyl peptidase IV (DPPIV) in membrane-bound fraction (MF) from renal cortex (RC) and medulla (RM). NAC ameliorated or normalized altered creatinuria, proteinemia and aminopeptidase (AP) acid in MF, AP basic (APB) in soluble fraction (SF), and neutral AP in SF and MF from RC and RM in vBj envenomation. NAC ameliorated or normalized altered neutral AP in SF from RC and RM, and DPPIV and protein in MF from RC in vCdt envenomation. NAC ameliorated or restored renal redox status respectively in vCdt and vBj, and normalized uricemia in both envenomations. These data are promising perspectives that recommend the clinical evaluation of NAC as potential coadjuvant in the anti venom serotherapy for accidents with these snake's genera. Copyright © 2014 Elsevier Ltd. All rights reserved.

Estrogen administered after cardiac arrest and cardiopulmonary resuscitation ameliorates acute kidney injury in a sex- and age-specific manner.

PubMed

Ikeda, Mizuko; Swide, Thomas; Vayl, Alexandra; Lahm, Tim; Anderson, Sharon; Hutchens, Michael P

2015-09-18

There is a sex difference in the risk of ischemic acute kidney injury (AKI), and estrogen mediates the protective effect of female sex. We previously demonstrated that preprocedural chronic restoration of physiologic estrogen to ovariectomized female mice ameliorated AKI after cardiac arrest and cardiopulmonary resuscitation (CA/CPR). In the present study, we hypothesized that male mice and aged female mice would benefit from estrogen administration after CA/CPR. We tested the effect of estrogen in a clinically relevant manner by administrating it after CA/CPR. CA/CPR was performed in young (10-15 weeks), middle-aged (43-48 weeks), and aged (78-87 weeks) C57BL/6 male and female mice. Mice received intravenous 17β-estradiol or vehicle 15 min after resuscitation. Serum chemistries and unbiased stereological assessment of renal injury were completed 24 h after CA. Regional renal cortical blood flow was measured by a laser Doppler, and renal levels of estrogen receptor alpha (ERα) and G protein-coupled estrogen receptor (GPER) were evaluated with immunoblotting. Post-arrest estrogen administration reduced injury in young males without significant changes in renal blood flow (percentage reduction compared with vehicle: serum urea nitrogen, 30 %; serum creatinine (sCr), 41 %; volume of necrotic tubules (VNT), 31 %; P < 0.05). In contrast, estrogen did not affect any outcomes in young females. In aged mice, estrogen significantly reduced sCr (80 %) and VNT (73 %) in males and VNT (51 %) in females. Serum estrogen levels in aged female mice after CA/CPR were the same as levels in male mice. With age, renal ERα was upregulated in females. Estrogen administration after resuscitation from CA ameliorates renal injury in young males and aged mice in both sexes. Because injury was small, young females were not affected. The protective effect of exogenous estrogen may be detectable with loss of endogenous estrogen in aged females and could be mediated by differences in renal

Simultaneous characterization of metabolic, cardiac, vascular and renal phenotypes of lean and obese SHHF rats.

PubMed

Youcef, Gina; Olivier, Arnaud; L'Huillier, Clément P J; Labat, Carlos; Fay, Renaud; Tabcheh, Lina; Toupance, Simon; Rodriguez-Guéant, Rosa-Maria; Bergerot, Damien; Jaisser, Frédéric; Lacolley, Patrick; Zannad, Faiez; Laurent Vallar; Pizard, Anne

2014-01-01

Individuals with metabolic syndrome (MetS) are prone to develop heart failure (HF). However, the deleterious effects of MetS on the continuum of events leading to cardiac remodeling and subsequently to HF are not fully understood. This study characterized simultaneously MetS and cardiac, vascular and renal phenotypes in aging Spontaneously Hypertensive Heart Failure lean (SHHF(+/?) regrouping (+/+) and (+/cp) rats) and obese (SHHF(cp/cp), "cp" defective mutant allele of the leptin receptor gene) rats. We aimed to refine the milestones and their onset during the progression from MetS to HF in this experimental model. We found that SHHF(cp/cp )but not SHHF(+/?) rats developed dyslipidemia, as early as 1.5 months of age. This early alteration in the lipidic profile was detectable concomitantly to impaired renal function (polyuria, proteinuria but no glycosuria) and reduced carotid distensibility as compared to SHHF(+/?) rats. By 3 months of age SHHFcp/cp animals developed severe obesity associated with dislipidemia and hypertension defining the onset of MetS. From 6 months of age, SHHF(+/?) rats developed concentric left ventricular hypertrophy (LVH) while SHHF(cp/cp) rats developed eccentric LVH apparent from progressive dilation of the LV dimensions. By 14 months of age only SHHF(cp/cp) rats showed significantly higher central systolic blood pressure and a reduced ejection fraction resulting in systolic dysfunction as compared to SHHF(+/?). In summary, the metabolic and hemodynamic mechanisms participating in the faster decline of cardiac functions in SHHF(cp/cp) rats are established long before their physiological consequences are detectable. Our results suggest that the molecular mechanisms triggered within the first three months after birth of SHHF(cp/cp) rats should be targeted preferentially by therapeutic interventions in order to mitigate the later HF development.

Simultaneous Characterization of Metabolic, Cardiac, Vascular and Renal Phenotypes of Lean and Obese SHHF Rats

PubMed Central

Youcef, Gina; Olivier, Arnaud; L'Huillier, Clément P. J.; Labat, Carlos; Fay, Renaud; Tabcheh, Lina; Toupance, Simon; Rodriguez-Guéant, Rosa-Maria; Bergerot, Damien; Jaisser, Frédéric; Lacolley, Patrick; Zannad, Faiez; Laurent Vallar; Pizard, Anne

2014-01-01

Individuals with metabolic syndrome (MetS) are prone to develop heart failure (HF). However, the deleterious effects of MetS on the continuum of events leading to cardiac remodeling and subsequently to HF are not fully understood. This study characterized simultaneously MetS and cardiac, vascular and renal phenotypes in aging Spontaneously Hypertensive Heart Failure lean (SHHF+/? regrouping +/+ and +/cp rats) and obese (SHHFcp/cp, “cp” defective mutant allele of the leptin receptor gene) rats. We aimed to refine the milestones and their onset during the progression from MetS to HF in this experimental model. We found that SHHFcp/cp but not SHHF+/? rats developed dyslipidemia, as early as 1.5 months of age. This early alteration in the lipidic profile was detectable concomitantly to impaired renal function (polyuria, proteinuria but no glycosuria) and reduced carotid distensibility as compared to SHHF+/? rats. By 3 months of age SHHFcp/cp animals developed severe obesity associated with dislipidemia and hypertension defining the onset of MetS. From 6 months of age, SHHF+/? rats developed concentric left ventricular hypertrophy (LVH) while SHHFcp/cp rats developed eccentric LVH apparent from progressive dilation of the LV dimensions. By 14 months of age only SHHFcp/cp rats showed significantly higher central systolic blood pressure and a reduced ejection fraction resulting in systolic dysfunction as compared to SHHF+/?. In summary, the metabolic and hemodynamic mechanisms participating in the faster decline of cardiac functions in SHHFcp/cp rats are established long before their physiological consequences are detectable. Our results suggest that the molecular mechanisms triggered within the first three months after birth of SHHFcp/cp rats should be targeted preferentially by therapeutic interventions in order to mitigate the later HF development. PMID:24831821

Alteration of the Intestinal Environment by Lubiprostone Is Associated with Amelioration of Adenine-Induced CKD

PubMed Central

Mishima, Eikan; Fukuda, Shinji; Shima, Hisato; Hirayama, Akiyoshi; Akiyama, Yasutoshi; Takeuchi, Yoichi; Fukuda, Noriko N.; Suzuki, Takehiro; Suzuki, Chitose; Yuri, Akinori; Kikuchi, Koichi; Tomioka, Yoshihisa; Ito, Sadayoshi; Soga, Tomoyoshi

2015-01-01

The accumulation of uremic toxins is involved in the progression of CKD. Various uremic toxins are derived from gut microbiota, and an imbalance of gut microbiota or dysbiosis is related to renal failure. However, the pathophysiologic mechanisms underlying the relationship between the gut microbiota and renal failure are still obscure. Using an adenine-induced renal failure mouse model, we evaluated the effects of the ClC-2 chloride channel activator lubiprostone (commonly used for the treatment of constipation) on CKD. Oral administration of lubiprostone (500 µg/kg per day) changed the fecal and intestinal properties in mice with renal failure. Additionally, lubiprostone treatment reduced the elevated BUN and protected against tubulointerstitial damage, renal fibrosis, and inflammation. Gut microbiome analysis of 16S rRNA genes in the renal failure mice showed that lubiprostone treatment altered their microbial composition, especially the recovery of the levels of the Lactobacillaceae family and Prevotella genus, which were significantly reduced in the renal failure mice. Furthermore, capillary electrophoresis–mass spectrometry-based metabolome analysis showed that lubiprostone treatment decreased the plasma level of uremic toxins, such as indoxyl sulfate and hippurate, which are derived from gut microbiota, and a more recently discovered uremic toxin, trans-aconitate. These results suggest that lubiprostone ameliorates the progression of CKD and the accumulation of uremic toxins by improving the gut microbiota and intestinal environment. PMID:25525179

Multiple variations of the coeliac axis, hepatic and renal vasculature as incidental findings illustrated by MDCTA.

PubMed

Rafailidis, Vasileios; Papadopoulos, Georgios; Kouskouras, Konstantinos; Chryssogonidis, Ioannis; Velnidou, Anastasia; Kalogera-Fountzila, Anna

2016-08-01

Vascular anatomical variations are not uncommon and may affect any organ's arterial or venous vasculature. The coexistence of variations in different organic systems is less commonly found, but of great clinical significance in a series of clinical conditions like organ transplantation and surgical preoperative planning. Multidetector computed tomography angiography (MDCTA) has emerged as a valuable alternative to the conventional angiography for accurate evaluation of vascular anatomy and pathology. Radiologists should be familiar with each organ's vascular variations and always report them to the clinician, even if they represent an incidental finding. This case report presents a 52-year-old female patient undergoing abdominal MDCTA for characterization of a renal lesion. This examination revealed the presence of three hilar arteries on the left kidney, a main renal vein in combination with an additional renal vein in both sides along with a replaced right hepatic artery originating from the superior mesenteric artery. Moreover, both inferior phrenic arteries were found originating from the coeliac axis. 3D volume rendering technique images were used in the evaluation of vascular anatomy as illustrated in this case report.

Protection from renal fibrosis, putative role of TRIB3 gene silencing.

PubMed

Ding, Wen-yuan; Li, Wen-bo; Ti, Yun; Bi, Xiu-ping; Sun, Hui; Wang, Zhi-hao; Zhang, Yun; Zhang, Wei; Zhong, Ming

2014-02-01

Renal fibrosis is thought to be the common pathway in most cases of chronic kidney disease. Recently, TRIB3 was found to play an important role in progression of cardiac fibrosis in an insulin-resistant state. We investigated whether TRIB3 might participate in the pathogenesis of renal fibrosis in insulin-resistant rats. We randomly separated 40 male Sprague-Dawley into 4 groups for treatment (n = 10 each): control and high-fat diet (HFD) with TRIB3 siRNA adenovirus transfection, vehicle transfection or HFD alone. Insulin resistance markers were measured. Renal tissues were stained with hematoxylin and eosin, Masson's trichrome and periodic acid-Schiff. Rats with HFD showed insulin resistance and TRIB3 overexpression. Upregulated TRIB3 expression could induce renal fibrosis accompanied by increased phosphorylation of extracellular signal-regulated kinase (ERK). Also, TRIB3 siRNA knockdown could ameliorate renal fibrosis, which was accompanied by decreased phosphorylation of ERK. TRIB3 gene silencing can attenuate renal fibrosis for beneficial effect on the development of renal fibrosis in chronic kidney disease in rat. Crown Copyright © 2014. Published by Elsevier Inc. All rights reserved.

Aortic intimal sarcoma masquerading as bilateral renal artery stenosis.

PubMed

Sethi, Supreet; Pothineni, Naga Krishna; Syal, Gaurav; Ali, Syed Mujtaba; Krause, Michelle W

2013-01-01

Aortic intimal sarcoma is a rare tumor with poor prognosis. The most common manifestations are thromboembolic phenomena and vascular obstruction. We present a case of aortic intimal sarcoma causing bilateral renal artery stenosis which manifested as resistant hypertension and acute kidney inury. Multiple attempts to stent the renal arteries were unsuccessful. Eventually the patient developed acute limb ischemia and oliguric kidney failure as complications of the primary tumor.

ADVANCE: Study to Evaluate Cinacalcet Plus Low Dose Vitamin D on Vascular Calcification in Subjects With Chronic Kidney Disease Receiving Hemodialysis

ClinicalTrials.gov

2014-07-14

Chronic Kidney Disease; End Stage Renal Disease; Coronary Artery Calcification; Vascular Calcification; Calcification; Cardiovascular Disease; Chronic Renal Failure; Hyperparathyroidism; Kidney Disease; Nephrology; Secondary Hyperparathyroidism

Supplementation with chromium picolinate recovers renal Cr concentration and improves carbohydrate metabolism and renal function in type 2 diabetic mice.

PubMed

Mita, Yukiko; Ishihara, Kengo; Fukuchi, Yoshiko; Fukuya, Yoko; Yasumoto, Kyoden

2005-01-01

To study the preventive effect of supplemented chromium picolinate (CrPic) on the development of diabetic nephropathy in mice, we analyzed the effects of CrPic supplementation on renal function and concentrations of serum glucose and tissue chromium (Cr). In experiment 1, male KK-Ay obese diabetic mice were fed either a control diet (control) or a diet supplemented with 2 mg/kg diet (Cr2) or 10 mg/kg diet (Cr10) of Cr for 12 wk. Cr10 significantly ameliorated hyperglycemia after a glucose load, creatinine clearance rates, and urinary microalbumin levels (p<0.05). In experiment 2, the Cr10 diet was fed to male KK-Ay obese diabetic mice and C57BL nondiabetic mice for 4 wk. The CrPic diet reduced urinary albumin excretion in the diabetic mice (p<0.05). Inductively coupled plasma-mass spectrometry analysis revealed that the renal Cr content and the recovery of renal Cr concentration after Cr supplementation were significantly lower in the diabetic mice than in the nondiabetic mice (p<0.01). These observations suggest that Cr supplementation of type 2 diabetic mice reduces the symptoms of hyperglycemia and improves the renal function by recovering renal Cr concentration.

Intra-renal arterial injection of autologous bone marrow mesenchymal stromal cells ameliorates cisplatin-induced acute kidney injury in a rhesus Macaque mulatta monkey model.

PubMed

Moghadasali, Reza; Azarnia, Mahnaz; Hajinasrollah, Mostafa; Arghani, Hassan; Nassiri, Seyed Mahdi; Molazem, Mohammad; Vosough, Ahmad; Mohitmafi, Soroush; Najarasl, Mostafa; Ajdari, Zahra; Yazdi, Reza Salman; Bagheri, Mohsen; Ghanaati, Hossein; Rafiei, Behrooz; Gheisari, Yousof; Baharvand, Hossein; Aghdami, Nasser

2014-06-01

Clinically, acute kidney injury (AKI) is a potentially devastating condition for which no specific therapy improves efficacy of the repair process. Bone marrow mesenchymal stromal cells (BM-MSCs) are proven to be beneficial for the renal repair process after AKI in different experimental rodent models, but their efficacy in large animals and humans remains unknown. This study aims to assess the effect of autologous rhesus Macaque mulatta monkey BM-MSC transplantation in cisplatin-induced AKI. We chose a model of AKI induced by intravenous administration of 5 mg/kg cisplatin. BM-MSCs were transplanted through intra-arterial injection. The animals were followed for survival, biochemistry analysis and pathology. Transplantation of 5 × 10(6) cells/kg ameliorated renal function during the first week, as shown by significantly lower serum creatinine and urea values and higher urine creatinine and urea clearance without hyponatremia, hyperkalemia, proteinuria and polyuria up to 84 d compared with the vehicle and control groups. The superparamagnetic iron oxide nanoparticle-labeled cells were found in both the glomeruli and tubules. BM-MSCs markedly accelerated Foxp3+ T-regulatory cells in response to cisplatin-induced damage, as revealed by higher numbers of Foxp3+ cells within the tubuli of these monkeys compared with cisplatin-treated monkeys in the control and vehicle groups. These data demonstrate that BM-MSCs in this unique large-animal model of cisplatin-induced AKI exhibited recovery and protective properties. Copyright © 2014 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Sickle cell disease: renal manifestations and mechanisms

PubMed Central

Nath, Karl A.; Hebbel, Robert P.

2015-01-01

Sickle cell disease (SCD) substantially alters renal structure and function, and causes various renal syndromes and diseases. Such diverse renal outcomes reflect the uniquely complex vascular pathobiology of SCD and the propensity of red blood cells to sickle in the renal medulla because of its hypoxic, acidotic, and hyperosmolar conditions. Renal complications and involvement in sickle cell nephropathy (SCN) include altered haemodynamics, hypertrophy, assorted glomerulopathies, chronic kidney disease, acute kidney injury, impaired urinary concentrating ability, distal nephron dysfunction, haematuria, and increased risks of urinary tract infections and renal medullary carcinoma. SCN largely reflects an underlying vasculopathy characterized by cortical hyperperfusion, medullary hypoperfusion, and an increased, stress-induced vasoconstrictive response. Renal involvement is usually more severe in homozygous disease (sickle cell anaemia, HbSS) than in compound heterozygous types of SCD (for example HbSC and HbSβ+-thalassaemia), and is typically mild, albeit prevalent, in the heterozygous state (sickle cell trait, HbAS). Renal involvement contributes substantially to the diminished life expectancy of patients with SCD, accounting for 16–18% of mortality. As improved clinical care promotes survival into adulthood, SCN imposes a growing burden on both individual health and health system costs. This Review addresses the renal manifestations of SCD and focuses on their underlying mechanisms. PMID:25668001

Cardio-renal syndrome: an entity cardiologists and nephrologists should be dealing with collegially.

PubMed

Palazzuoli, Alberto; Ronco, Claudio

2011-11-01

Heart failure may lead to acute kidney injury and vice versa. Chronic kidney disease may affect the clinical outcome in terms of cardiovascular morbidity and mortality while chronic heart failure may cause CKD. All these disorders contribute to the composite definition of cardio-renal syndromes. Renal impairment in HF patients has been increasingly recognized as an independent risk factor for morbidity and mortality; however, the most important clinical trials in HF tend to exclude patients with significant renal dysfunction. The mechanisms whereby renal insufficiency worsens the outcome in HF are not known, and several pathways could contribute to the "vicious heart/kidney circle." Traditionally, renal impairment has been attributed to the renal hypoperfusion due to reduced cardiac output and decreased systemic pressure. The hypovolemia leads to sympathetic activity, increased renin-angiotensin-aldosterone pathways and arginine-vasopressin release. All these mechanisms cause fluid and sodium retention, peripheral vasoconstriction and an increased congestion as well as cardiac workload. Therapy addressed to improve renal dysfunction, reduce neurohormonal activation and ameliorate renal blood flow could lead to a reduction in mortality and hospitalization in patients with cardio-renal syndrome.

Effect of a stable prostacyclin analogue on canine renal allograft rejection.

PubMed Central

Tobimatsu, M; Ueda, Y; Toyoda, K; Saito, S; Konomi, K

1987-01-01

The effect of OP-41483 (Ono Pharmaceutical Co., Osaka, Japan), a stable prostacyclin analogue, on canine renal allograft rejection was investigated. Administration for 4 days after transplantation significantly increased renal cortical blood flow and urine output when compared with untreated dogs with renal allografts. Serum creatinine levels remained relatively low during postoperative days 1-4. Mean animal survival time was prolonged. Vascular lesions and mononuclear cell infiltration were greatly diminished in biopsy specimens removed on day 4. This stable prostacyclin analogue provided a degree of protection against canine renal allograft rejection. Images Figs. 1A and B. PMID:3545109

Revascularization to preserve renal function in patients with atherosclerotic renovascular disease.

PubMed

Novick, A C; Textor, S C; Bodie, B; Khauli, R B

1984-08-01

There are a significant number of patients with advanced atherosclerotic renovascular disease whose blood pressure is well controlled with medical therapy but in whom such vascular disease poses a grave risk to overall renal function. This article reviews current concepts regarding screening, evaluation, and selection of patients with this disease for revascularization to preserve renal function. The underlying rationale for this approach is an increasing awareness that, in selected patients, atherosclerotic renovascular disease represents a surgically correctable cause of progressive renal failure.

Electroacupuncture Ameliorates Acute Renal Injury in Lipopolysaccharide-Stimulated Rabbits via Induction of HO-1 through the PI3K/Akt/Nrf2 Pathways

PubMed Central

Gong, Li-rong; Dong, Shu-an; Cao, Xin-shun; Wu, Li-li; Wu, Li-na

2015-01-01

Electroacupuncture at select acupoints have been verified to protect against organ dysfunctions during endotoxic shock. And, heme oxygenase (HO)-1 as a phase II enzyme and antioxidant contributed to the protection of kidney in septic shock rats. The phosphatidylinositol 3-kinase (PI3K)-Akt pathway mediated the activation of NF-E2 related factor-2 (Nrf2), which was involved in HO-1 induction. To understand the efficacy of electroacupuncture stimulation in ameliorating acute kidney injury (AKI) through the PI3K/Akt/Nrf2 pathway and subsequent HO-1 upregulation, a dose of LPS 5mg/kg was administered intravenously to replicate the rabbit model of AKI induced by endotoxic shock. Electroacupuncture pretreatment was handled bilaterally at Zusanli and Neiguan acupoints for five consecutive days while sham electroacupuncture at non-acupoints as control. Results displayed that electroacupuncture stimulation significantly alleviated the morphologic renal damage, attenuated renal tubular apoptosis, suppressed the elevated biochemical indicators of AKI caused by LPS, enhanced the expressions of phospho-Akt, HO-1protein, Nrf2 total and nucleoprotein, and highlighted the proportions of Nrf2 nucleoprotein as a parallel. Furthermore, partial protective effects of elecroacupuncture were counteracted by preconditioning with wortmannin (the selective PI3K inhibitor), indicating a direct involvement of PI3K/Akt pathway. Inconsistently, wortmannin pretreatment made little difference to the expressions of HO-1, Nrf2 nucleoprotein and total protein, which indicated that PI3K/Akt may be not the only pathway responsible for electroacupuncture-afforded protection against LPS-induced AKI. These findings provide new insights into the potential future clinical applications of electroacupuncture for AKI induced by endotoxic shock instead of traditional remedies. PMID:26524181

Electroacupuncture Ameliorates Acute Renal Injury in Lipopolysaccharide-Stimulated Rabbits via Induction of HO-1 through the PI3K/Akt/Nrf2 Pathways.

PubMed

Yu, Jian-Bo; Shi, Jia; Zhang, Yuan; Gong, Li-Rong; Dong, Shu-An; Cao, Xin-Shun; Wu, Li-Li; Wu, Li-Na

2015-01-01

Electroacupuncture at select acupoints have been verified to protect against organ dysfunctions during endotoxic shock. And, heme oxygenase (HO)-1 as a phase II enzyme and antioxidant contributed to the protection of kidney in septic shock rats. The phosphatidylinositol 3-kinase (PI3K)-Akt pathway mediated the activation of NF-E2 related factor-2 (Nrf2), which was involved in HO-1 induction. To understand the efficacy of electroacupuncture stimulation in ameliorating acute kidney injury (AKI) through the PI3K/Akt/Nrf2 pathway and subsequent HO-1 upregulation, a dose of LPS 5mg/kg was administered intravenously to replicate the rabbit model of AKI induced by endotoxic shock. Electroacupuncture pretreatment was handled bilaterally at Zusanli and Neiguan acupoints for five consecutive days while sham electroacupuncture at non-acupoints as control. Results displayed that electroacupuncture stimulation significantly alleviated the morphologic renal damage, attenuated renal tubular apoptosis, suppressed the elevated biochemical indicators of AKI caused by LPS, enhanced the expressions of phospho-Akt, HO-1protein, Nrf2 total and nucleoprotein, and highlighted the proportions of Nrf2 nucleoprotein as a parallel. Furthermore, partial protective effects of elecroacupuncture were counteracted by preconditioning with wortmannin (the selective PI3K inhibitor), indicating a direct involvement of PI3K/Akt pathway. Inconsistently, wortmannin pretreatment made little difference to the expressions of HO-1, Nrf2 nucleoprotein and total protein, which indicated that PI3K/Akt may be not the only pathway responsible for electroacupuncture-afforded protection against LPS-induced AKI. These findings provide new insights into the potential future clinical applications of electroacupuncture for AKI induced by endotoxic shock instead of traditional remedies.

Retro-aortic left renal vein--an anatomic variation description and review of literature.

PubMed

Suma, H Yekappa; Roopa, Kulkarni

2011-01-01

This study reports the presence of a retro-aortic renal vein on the left side draining into the inferior vena cava. This variation was observed during routine dissection in a female cadaver aged about 55 years. This variation is of importance because of its implications in renal transplantation, renal surgery, vascular surgery, uroradiology and gonadal surgeries. The knowledge of such variations can help the clinicians for its recognition and protection.

β-Arrestin-1 deficiency ameliorates renal interstitial fibrosis by blocking Wnt1/β-catenin signaling in mice.

PubMed

Xu, Huiyan; Li, Quanxin; Liu, Jiang; Zhu, Jiaqing; Li, Liang; Wang, Ziying; Zhang, Yan; Sun, Yu; Sun, Jinpeng; Wang, Rong; Yi, Fan

2018-01-01

Despite substantial progress being made in understanding the mechanisms contributing to the pathogenesis of renal fibrosis, there are only a few therapies available to treat or prevent renal fibrosis in clinical use today. Therefore, identifying the key cellular and molecular mediators involved in the pathogenesis of renal fibrosis will provide new therapeutic strategy for treating patients with chronic kidney disease (CKD). β-Arrestin-1, a member of β-arrestin family, not only is a negative adaptor of G protein-coupled receptors (GPCRs), but also acts as a scaffold protein and regulates a diverse array of cellular functions independent of GPCR activation. In this study, we identified for the first time that β-arrestin-1 was upregulated in the kidney from mice with unilateral ureteral obstruction nephropathy as well as in the paraffin-embedded sections of human kidneys from the patients with diabetic nephropathy, polycystic kidney, or uronephrosis, which normally causes renal fibrosis. Deficiency of β-arrestin-1 in mice significantly alleviated renal fibrosis by the regulation of inflammatory responses, kidney fibroblast activation, and epithelial-mesenchymal transition (EMT) in both in vivo and in vitro studies. Furthermore, we found that among the major isoforms of Wnts, Wnt1 was regulated by β-arrestin-1 and gene silencing of Wnt1 inhibited the activation of β-catenin and suppressed β-arrestin-1-mediated renal fibrosis. Collectively, our results indicate that β-arrestin-1 is one of the critical components of signal transduction pathways in the development of renal fibrosis. Modulation of these pathways may be an innovative therapeutic strategy for treating patients with renal fibrosis. β-Arrestin-1 was upregulated in the kidney from mice with UUO nephropathy. β-Arrestin-1 regulated kidney fibroblast activation and epithelial-mesenchymal transition. β-Arrestin-1 exacerbated renal fibrosis via mediating Wnt1/β-catenin signaling.

[Beneficial effects of renal denervation on pulmonary vascular remodeling in experimental pulmonary artery hypertension].

PubMed

Zhang, Shujuan; Zhao, Qingyan; Jiang, Xuejun; Yang, Bo; Dai, Zixuan; Wang, Xiaozhan; Wang, Xule; Guo, Zongwen; Yu, Shengbo; Tang, Yanhong; Hu, Wei; Huang, Congxin

2015-04-14

To explore the effects of renal sympathetic denervation (RSD) on pulmonary vascular remodeling in a model of pulmonary arterial hypertension (PAH). According to the random number table, 24 beagles were randomized into control, PAH and PAH+RSD groups (n=8 each). The levels of neurohormone, echocardiogram and dynamics parameters were measured. Then 0.1 ml/kg dimethylformamide (control group) or 2 mg/kg dehydromonocrotaline (PAH and PAH+RSD groups) were injected. The PAH+RSD group underwent RSD after injection. At week 8 post-injection, the neurohormone levels, echocardiogram, dynamics parameters and pulmonary tissue morphology were observed. The values of right ventricular systolic pressure (RVSP) and pulmonary arterial systolic pressure (PASP) in PAH and PAH+RSD groups were both significantly higher than those in control group ((42.8±8.7), (30.8±6.8) vs (23.2±5.7) mmHg (1 mmHg=0.133 kPa) and (45.1±11.2), (32.6±7.9) vs (24.7±7.1) mmHg). Meanwhile, the values of RVSP and PASP in PAH group were higher than those in PAH+RSD group (all P<0.01). The levels of serum angiotensin II (Ang II) and endothelin-1 significantly increased after 8 weeks in PAH dogs ((228±41) vs (113±34) pg/ml and (135±15) vs (77±7) pg/ml, all P<0.01). And Ang II and endothelin-1 were higher in lung tissues of PAH group ((65±10) and (96±10) pg/ml) than in those of control group ((38±7) and (54±6) pg/ml) and PAH+RSD group ((46±8) and (67±9) pg/ml) (all P<0.01). Pulmonary tissues had marked collagen hyperplasia and lamellar corpuscles of type 2 alveolar cells were damaged more severely in PAH dogs than in PAH+RSD dogs. RSD suppresses pulmonary vascular remodeling and decreases pulmonary arterial pressure in experimental PAH. And the effect of RSD on PAH may contribute to decreased neurohormone levels.

Challenges in Pathologic Staging of Renal Cell Carcinoma: A Study of Interobserver Variability Among Urologic Pathologists.

PubMed

Williamson, Sean R; Rao, Priya; Hes, Ondrej; Epstein, Jonathan I; Smith, Steven C; Picken, Maria M; Zhou, Ming; Tretiakova, Maria S; Tickoo, Satish K; Chen, Ying-Bei; Reuter, Victor E; Fleming, Stewart; Maclean, Fiona M; Gupta, Nilesh S; Kuroda, Naoto; Delahunt, Brett; Mehra, Rohit; Przybycin, Christopher G; Cheng, Liang; Eble, John N; Grignon, David J; Moch, Holger; Lopez, Jose I; Kunju, Lakshmi P; Tamboli, Pheroze; Srigley, John R; Amin, Mahul B; Martignoni, Guido; Hirsch, Michelle S; Bonsib, Stephen M; Trpkov, Kiril

2018-06-06

Staging criteria for renal cell carcinoma differ from many other cancers, in that renal tumors are often spherical with subtle, finger-like extensions into veins, renal sinus, or perinephric tissue. We sought to study interobserver agreement in pathologic stage categories for challenging cases. An online survey was circulated to urologic pathologists interested in kidney tumors, yielding 89% response (31/35). Most questions included 1 to 4 images, focusing on: vascular and renal sinus invasion (n=24), perinephric invasion (n=9), and gross pathology/specimen handling (n=17). Responses were collapsed for analysis into positive and negative/equivocal for upstaging. Consensus was regarded as an agreement of 67% (2/3) of participants, which was reached in 20/33 (61%) evaluable scenarios regarding renal sinus, perinephric, or vein invasion, of which 13/33 (39%) had ≥80% consensus. Lack of agreement was especially encountered regarding small tumor protrusions into a possible vascular lumen, close to the tumor leading edge. For gross photographs, most were interpreted as suspicious but requiring histologic confirmation. Most participants (61%) rarely used special stains to evaluate vascular invasion, usually endothelial markers (81%). Most agreed that a spherical mass bulging well beyond the kidney parenchyma into the renal sinus (71%) or perinephric fat (90%) did not necessarily indicate invasion. Interobserver agreement in pathologic staging of renal cancer is relatively good among urologic pathologists interested in kidney tumors, even when selecting cases that test the earliest and borderline thresholds for extrarenal extension. Disagreements remain, however, particularly for tumors with small, finger-like protrusions, closely juxtaposed to the main mass.

Gold nanoparticles ameliorate acetaminophen induced hepato-renal injury in rats.

PubMed

Reshi, Mohd Salim; Shrivastava, Sadhana; Jaswal, Amita; Sinha, Neelu; Uthra, Chhavi; Shukla, Sangeeta

2017-04-04

Valuable effects of gold particles have been reported and used in complementary medicine for decades. The aim of this study was to evaluate the therapeutic efficacy of gold nanoparticles (AuNPs) against acetaminophen (APAP) induced toxicity. Albino rats were administered APAP at a dose of 2g/kg p.o. once only. After 24h of APAP intoxication, animals were treated with three different doses of AuNPs (50μg/kg, 100μg/kg, 150μg/kg) orally or silymarin at a dose of 50mg/kg p.o., once only. Animals of all the groups were sacrificed after 24h of last treatment. APAP administered group showed a significant rise in the AST, ALT, SALP, LDH, cholesterol, bilirubin, albumin, urea and creatinine in serum which indicated the hepato-renal damage. A significantly enhanced LPO and a depleted level of GSH were observed in APAP intoxicated rats. Declined activities of SOD and Catalase, after acetaminophen exposure indicated oxidative stress in liver and kidney. The activities of ATPase and glucose-6-Phosphatase were significantly inhibited after APAP administration. AuNPs treatment reversed all variables significantly towards normal level and was found nontoxic. Thus it is concluded that gold nanoparticles played a beneficial role in reducing acetaminophen induced toxicity and can be used in the development of drug against hepatic as well as renal diseases, after further preclinical and clinical studies. Copyright © 2017 Elsevier GmbH. All rights reserved.

Does the type of renal artery anatomic variant determine the diameter of the main vessel supplying a kidney? A study based on CT data with a particular focus on the presence of multiple renal arteries.

PubMed

Majos, Marcin; Stefańczyk, Ludomir; Szemraj-Rogucka, Zofia; Elgalal, Marcin; De Caro, Raffaele; Macchi, Veronica; Polguj, Michał

2018-04-01

An in-depth knowledge of renal vascular anatomy is essential when planning many surgical procedures; however, a few data exists regarding renal artery diameter. The aim of this study was to assess this morphological feature and to investigate whether a correlation exists between renal artery diameter and the type of arterial supply, with a particular emphasis on variant anatomy and the presence of multiple renal arteries. Computed tomography angiography (CTA) studies of 248 patients, i.e., a total of 496 kidneys, were evaluated. The mean age of the patients was 66.4 ± 15.01 years. Renal artery diameter was measured based on the type of arterial blood supply. The frequency of occurrence of three anatomic variants of renal arterial supply was established: single renal artery (RA) 43.35%, single artery with prehilar branching (pRA) 37.30%, and multiple renal artery (mRA) 19.35%. The diameter of single renal arteries, with either prehilar or hilar branching, was significantly larger than when multiple arteries were present. A detailed analysis of just the mRA variant demonstrated that the diameter of the renal arteries in men was larger (p = 0.012) than those in women and that there was no difference in diameter with regard to the side of the body (p = 0.219). The classification described in our study containing a detailed description of renal artery diameter. It may be helpful in clinical practice, especially for transplantologists, surgeons, and vascular surgeons.

Renal Autoregulation in Health and Disease

PubMed Central

Carlström, Mattias; Wilcox, Christopher S.; Arendshorst, William J.

2015-01-01

Intrarenal autoregulatory mechanisms maintain renal blood flow (RBF) and glomerular filtration rate (GFR) independent of renal perfusion pressure (RPP) over a defined range (80–180 mmHg). Such autoregulation is mediated largely by the myogenic and the macula densa-tubuloglomerular feedback (MD-TGF) responses that regulate preglomerular vasomotor tone primarily of the afferent arteriole. Differences in response times allow separation of these mechanisms in the time and frequency domains. Mechanotransduction initiating the myogenic response requires a sensing mechanism activated by stretch of vascular smooth muscle cells (VSMCs) and coupled to intracellular signaling pathways eliciting plasma membrane depolarization and a rise in cytosolic free calcium concentration ([Ca2+]i). Proposed mechanosensors include epithelial sodium channels (ENaC), integrins, and/or transient receptor potential (TRP) channels. Increased [Ca2+]i occurs predominantly by Ca2+ influx through L-type voltage-operated Ca2+ channels (VOCC). Increased [Ca2+]i activates inositol trisphosphate receptors (IP3R) and ryanodine receptors (RyR) to mobilize Ca2+ from sarcoplasmic reticular stores. Myogenic vasoconstriction is sustained by increased Ca2+ sensitivity, mediated by protein kinase C and Rho/Rho-kinase that favors a positive balance between myosin light-chain kinase and phosphatase. Increased RPP activates MD-TGF by transducing a signal of epithelial MD salt reabsorption to adjust afferent arteriolar vasoconstriction. A combination of vascular and tubular mechanisms, novel to the kidney, provides for high autoregulatory efficiency that maintains RBF and GFR, stabilizes sodium excretion, and buffers transmission of RPP to sensitive glomerular capillaries, thereby protecting against hypertensive barotrauma. A unique aspect of the myogenic response in the renal vasculature is modulation of its strength and speed by the MD-TGF and by a connecting tubule glomerular feedback (CT-GF) mechanism

Renal artery anatomy assessed by quantitative analysis of selective renal angiography in 1,000 patients with hypertension.

PubMed

Lauder, Lucas; Ewen, Sebastian; Tzafriri, Abraham Rami; Edelman, Elazer Reuven; Lüscher, Thomas Felix; Blankenstijn, Peter J; Dörr, Oliver; Schlaich, Markus; Sharif, Faisal; Voskuil, Michiel; Zeller, Thomas; Ukena, Christian; Scheller, Bruno; Böhm, Michael; Mahfoud, Felix

2018-05-20

With increasing attention to renovascular causes and targets for hypertension there arises a critical need for more detailed knowledge of renal arterial anatomy. However, a standardised nomenclature is lacking. The present study sought to develop a standardised nomenclature for renal anatomy considering the complexity and variation of the renal arterial tree and to assess the applicability of the nomenclature. One thousand hypertensive patients underwent invasive selective renal artery angiography in nine centres. Further, renovasography was performed in 249 healthy swine as a surrogate for normotensive anatomy. Anatomical parameters were assessed by quantitative vascular analysis. Patients' mean blood pressure was 168/90±26/17 mmHg. The right main renal artery was longer than the left (41±15 mm vs. 35±13 mm, p<0.001), but the left had a greater diameter (5.4±1.2 vs. 5.2±1.2 mm, p<0.001). Accessory renal arteries and renal artery disease were documented in 22% and 9% of the patients, respectively. Other than exhibiting a longer left main renal artery in uncontrolled hypertensives (+2.7 mm, p=0.034) there was no anatomical difference between patients with controlled and uncontrolled hypertension. Main renal artery mean diameter was smaller in patients with impaired kidney function (GFR <90 ml/min, left -0.5 mm, right -0.4 mm, both p<0.001). Renal arterial anatomy differs between sides but shows no difference between patients with and without blood pressure control. Impaired GFR was associated with small main renal artery diameter.

Vascular Multiplicity Should Not Be a Contra-Indication for Live Kidney Donation and Transplantation

PubMed Central

van Bruggen, Mark; Kimenai, Hendrikus J. A. N.; Tran, Thi C. K.; Terkivatan, Türkan; Betjes, Michiel G. H.; IJzermans, Jan N. M.; Dor, Frank J. M. F.

2016-01-01

Background Whether vascular multiplicity should be considered as contraindication and therefore ‘extended donor criterion’ is still under debate. Methods Data from all live kidney donors from 2006–2013 (n = 951) was retrospectively reviewed. Vascular anatomy as imaged by MRA, CTA or other modalities was compared with intraoperative findings. Furthermore, the influence of vascular multiplicity on outcome of donors and recipients was studied. Results In 237 out of 951 donors (25%), vascular multiplicity was present. CTA had the highest accuracy levels regarding vascular anatomy assessment. Regarding outcome of donors with vascular multiplicity, warm ischemia time (WIT) and skin-to-skin time were significantly longer if arterial multiplicity (AM) was present (5.1 vs. 4.0 mins and 202 vs. 178 mins). Skin-to-skin time was significantly longer, and complication rates were higher in donors with venous multiplicity (203 vs. 180 mins and 17.2% vs. 8.4%). Outcome of renal transplant recipients showed a significantly increased WIT (30 vs. 26.7 minutes), higher rate of DGF (13.9% vs. 6.9%) and lower rate of BPAR (6.9% vs. 13.9%) in patients receiving a kidney with AM compared to kidneys with singular anatomy. Conclusions We conclude that vascular multiplicity should not be a contra-indication, since it has little impact on clinical outcome in the donor as well as in renal transplant recipients. PMID:27077904

Vascular Multiplicity Should Not Be a Contra-Indication for Live Kidney Donation and Transplantation.

PubMed

Lafranca, Jeffrey A; van Bruggen, Mark; Kimenai, Hendrikus J A N; Tran, Thi C K; Terkivatan, Türkan; Betjes, Michiel G H; IJzermans, Jan N M; Dor, Frank J M F

2016-01-01

Whether vascular multiplicity should be considered as contraindication and therefore 'extended donor criterion' is still under debate. Data from all live kidney donors from 2006-2013 (n = 951) was retrospectively reviewed. Vascular anatomy as imaged by MRA, CTA or other modalities was compared with intraoperative findings. Furthermore, the influence of vascular multiplicity on outcome of donors and recipients was studied. In 237 out of 951 donors (25%), vascular multiplicity was present. CTA had the highest accuracy levels regarding vascular anatomy assessment. Regarding outcome of donors with vascular multiplicity, warm ischemia time (WIT) and skin-to-skin time were significantly longer if arterial multiplicity (AM) was present (5.1 vs. 4.0 mins and 202 vs. 178 mins). Skin-to-skin time was significantly longer, and complication rates were higher in donors with venous multiplicity (203 vs. 180 mins and 17.2% vs. 8.4%). Outcome of renal transplant recipients showed a significantly increased WIT (30 vs. 26.7 minutes), higher rate of DGF (13.9% vs. 6.9%) and lower rate of BPAR (6.9% vs. 13.9%) in patients receiving a kidney with AM compared to kidneys with singular anatomy. We conclude that vascular multiplicity should not be a contra-indication, since it has little impact on clinical outcome in the donor as well as in renal transplant recipients.

Cardiac and renal antioxidant enzymes and effects of tempol in hyperthyroid rats.

PubMed

Moreno, Juan Manuel; Rodríguez Gómez, Isabel; Wangensteen, Rosemary; Osuna, Antonio; Bueno, Pablo; Vargas, Félix

2005-11-01

This study evaluated the activity of cardiac and renal antioxidant enzymes [superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), and glutathione reductase (GR)] and whether chronic treatment with tempol, a cell membrane-permeable SOD mimetic, ameliorates the hypertension of hyperthyroidism. Two experiments were performed. In experiment I, the following four groups of male Wistar rats were used: control group and three groups that received thyroxine (T4) at 10, 50, or 75 microg x rat(-1) x day(-1). In experiment II, tempol was orally administered (18 mg x kg(-1) x day(-1)) to control and T4-treated (75 microg x rat(-1) x day(-1)) rats. All treatments were maintained for 6 wk. Body weight, tail systolic blood pressure (BP), and heart rate were measured one time a week, and direct BP and morphological, metabolic, plasma, and renal variables were measured at the end of the experiment. Enzymatic activities were measured in renal cortex and medulla and right and left ventricles. In renal cortex, SOD activity was decreased in the T4-75 group, and there was a dose-related increase in CAT activity and decrease in GPX and GR activities in T4-treated groups. Activity of all antioxidant enzymes was reduced in left ventricle in T4-50 and T4-75 groups and in right ventricle in the T4-75 group. Tempol reduced BP, plasma malondialdehyde, and total urinary excretion of F2 isoprostanes in hypertensive hyperthyroid rats but not in controls. Tempol did not improve cardiac hypertrophy, proteinuria, or creatinine clearance in hyperthyroid rats. In conclusion, the results obtained indicate that the activity of SOD, GPX, and GR in renal and cardiac tissues is decreased in hyperthyroidism and that antioxidant treatment with tempol ameliorates T4-induced hypertension.

Serum cystatin C is an independent biomarker associated with the renal resistive index in patients with chronic kidney disease.

PubMed

Ogawa-Akiyama, Ayu; Sugiyama, Hitoshi; Kitagawa, Masashi; Tanaka, Keiko; Onishi, Akifumi; Yamanari, Toshio; Morinaga, Hiroshi; Uchida, Haruhito Adam; Nakamura, Kazufumi; Ito, Hiroshi; Wada, Jun

2018-01-01

Cystatin C is a cysteine protease inhibitor that is produced by nearly all human cells. The serum level of cystatin C is a stronger predictor of the renal outcome and the risk of cardiovascular events than the creatinine level. The resistive index (RI) on renal Doppler ultrasonography is a good indicator of vascular resistance as well as the renal outcomes in patients with chronic kidney disease (CKD). However, it is unclear whether serum cystatin C is associated with signs of vascular dysfunction, such as the renal RI. We measured the serum cystatin C levels in 101 CKD patients and investigated the relationships between cystatin C and markers of vascular dysfunction, including the renal RI, ankle-brachial pulse wave velocity (baPWV), intima-media thickness (IMT), and cardiac function. The renal RI was significantly correlated with the serum cystatin C level (p < 0.0001, r = 0.6920). The serum cystatin C level was found to be a significant determinant of the renal RI (p < 0.0001), but not the baPWV, in a multivariate regression analysis. The multivariate odds ratio of the serum cystatin C level for a renal RI of more than 0.66 was statistically significant (2.92, p = 0.0106). The area under the receiver-operating characteristic curve comparing the sensitivity and specificity of cystatin C for predicting an RI of more than 0.66 was 0.882 (cutoff value: 2.04 mg/L). In conclusion, the serum cystatin C level is an independent biomarker associated with the renal RI in patients with CKD.

In vivo three-dimensional photoacoustic imaging of the renal vasculature in preclinical rodent models.

PubMed

Ogunlade, Olumide; Connell, John J; Huang, Jennifer L; Zhang, Edward; Lythgoe, Mark F; Long, David A; Beard, Paul

2018-06-01

Noninvasive imaging of the kidney vasculature in preclinical murine models is important for the assessment of renal development, studying diseases and evaluating new therapies but is challenging to achieve using existing imaging modalities. Photoacoustic imaging is a promising new technique that is particularly well suited to visualizing the vasculature and could provide an alternative to existing preclinical imaging methods for studying renal vascular anatomy and function. To investigate this, an all-optical Fabry-Perot-based photoacoustic scanner was used to image the abdominal region of mice. High-resolution three-dimensional, noninvasive, label-free photoacoustic images of the mouse kidney and renal vasculature were acquired in vivo. The scanner was also used to visualize and quantify differences in the vascular architecture of the kidney in vivo due to polycystic kidney disease. This study suggests that photoacoustic imaging could be utilized as a novel preclinical imaging tool for studying the biology of renal disease.

Physical Exercise and Patients with Chronic Renal Failure: A Meta-Analysis.

PubMed

Qiu, Zhenzhen; Zheng, Kai; Zhang, Haoxiang; Feng, Ji; Wang, Lizhi; Zhou, Hao

2017-01-01

Chronic renal failure is a severe clinical problem which has some significant socioeconomic impact worldwide and hemodialysis is an important way to maintain patients' health state, but it seems difficult to get better in short time. Considering these, the aim in our research is to update and evaluate the effects of exercise on the health of patients with chronic renal failure. The databases were used to search for the relevant studies in English or Chinese. And the association between physical exercise and health state of patients with chronic renal failure has been investigated. Random-effect model was used to compare the physical function and capacity in exercise and control groups. Exercise is helpful in ameliorating the situation of blood pressure in patients with renal failure and significantly reduces VO 2 in patients with renal failure. The results of subgroup analyses show that, in the age >50, physical activity can significantly reduce blood pressure in patients with renal failure. The activity program containing warm-up, strength, and aerobic exercises has benefits in blood pressure among sick people and improves their maximal oxygen consumption level. These can help patients in physical function and aerobic capacity and may give them further benefits.

Alteration of the Intestinal Environment by Lubiprostone Is Associated with Amelioration of Adenine-Induced CKD.

PubMed

Mishima, Eikan; Fukuda, Shinji; Shima, Hisato; Hirayama, Akiyoshi; Akiyama, Yasutoshi; Takeuchi, Yoichi; Fukuda, Noriko N; Suzuki, Takehiro; Suzuki, Chitose; Yuri, Akinori; Kikuchi, Koichi; Tomioka, Yoshihisa; Ito, Sadayoshi; Soga, Tomoyoshi; Abe, Takaaki

2015-08-01

The accumulation of uremic toxins is involved in the progression of CKD. Various uremic toxins are derived from gut microbiota, and an imbalance of gut microbiota or dysbiosis is related to renal failure. However, the pathophysiologic mechanisms underlying the relationship between the gut microbiota and renal failure are still obscure. Using an adenine-induced renal failure mouse model, we evaluated the effects of the ClC-2 chloride channel activator lubiprostone (commonly used for the treatment of constipation) on CKD. Oral administration of lubiprostone (500 µg/kg per day) changed the fecal and intestinal properties in mice with renal failure. Additionally, lubiprostone treatment reduced the elevated BUN and protected against tubulointerstitial damage, renal fibrosis, and inflammation. Gut microbiome analysis of 16S rRNA genes in the renal failure mice showed that lubiprostone treatment altered their microbial composition, especially the recovery of the levels of the Lactobacillaceae family and Prevotella genus, which were significantly reduced in the renal failure mice. Furthermore, capillary electrophoresis-mass spectrometry-based metabolome analysis showed that lubiprostone treatment decreased the plasma level of uremic toxins, such as indoxyl sulfate and hippurate, which are derived from gut microbiota, and a more recently discovered uremic toxin, trans-aconitate. These results suggest that lubiprostone ameliorates the progression of CKD and the accumulation of uremic toxins by improving the gut microbiota and intestinal environment. Copyright © 2015 by the American Society of Nephrology.

Comparative analysis of COX-2, vascular endothelial growth factor and microvessel density in human renal cell carcinomas.

PubMed

Hemmerlein, B; Galuschka, L; Putzer, N; Zischkau, S; Heuser, M

2004-12-01

Cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF) are frequently up-regulated in malignant tumours and play a role in proliferation, apoptosis, angiogenesis and tumour invasion. In the present study, the expression of COX-2 and VEGF in renal cell carcinoma (RCC) was analysed and correlated with the microvessel density (MVD). COX-2 and VEGF were analysed by realtime reverse transcriptase-polymerase chain reaction and immunohistochemistry. The MVD was assessed by CD31 immunohistochemistry. The expression of COX-2 and VEGF was determined in the RCC cell lines A498 and Caki-1 under short-term hypoxia and in multicellular tumour cell aggregates. COX-2 was expressed in RCC by tumour epithelia, endothelia and macrophages in areas of cystic tumour regression and tumour necrosis. COX-2 protein in RCC was not altered in comparison with normal renal tissue. VEGF mRNA was up-regulated in RCC and positively correlated with MVD. RCC with high up-regulation of VEGF mRNA showed weak intracytoplasmic expression of VEGF in tumour cells. Intracytoplasmic VEGF protein expression was negatively correlated with MVD. In RCC with necrosis the MVD was reduced in comparison with RCC without necrosis. A498 RCC cells down-regulated COX-2 and up-regulated VEGF under conditions of hypoxia. In Caki-1 cells COX-2 expression remained stable, whereas VEGF was significantly up-regulated. In multicellular A498 cell aggregates COX-2 and VEGF were up-regulated centrally, whereas no gradient was found in Caki-1 cells. COX-2 and VEGF are potential therapeutic targets because COX-2 and VEGF are expressed in RCC and associated cell populations such as endothelia and monocytes/macrophages.

Cytochrome P450 and Lipoxygenase Metabolites on Renal Function

PubMed Central

Imig, John D.; Hye Khan, Md. Abdul

2018-01-01

Arachidonic acid metabolites have a myriad of biological actions including effects on the kidney to alter renal hemodynamics and tubular transport processes. Cyclooxygenase metabolites are products of an arachidonic acid enzymatic pathway that has been extensively studied in regards to renal function. Two lesser-known enzymatic pathways of arachidonic acid metabolism are the lipoxygenase (LO) and cytochrome P450 (CYP) pathways. The importance of LO and CYP metabolites to renal hemodynamics and tubular transport processes is now being recognized. LO and CYP metabolites have actions to alter renal blood flow and glomerular filtration rate. Proximal and distal tubular sodium transport and fluid and electrolyte homeostasis are also significantly influenced by renal CYP and LO levels. Metabolites of the LO and CYP pathways also have renal actions that influence renal inflammation, proliferation, and apoptotic processes at vascular and epithelial cells. These renal LO and CYP pathway actions occur through generation of specific metabolites and cell-signaling mechanisms. Even though the renal physiological importance and actions for LO and CYP metabolites are readily apparent, major gaps remain in our understanding of these lipid mediators to renal function. Future studies will be needed to fill these major gaps regarding LO and CYP metabolites on renal function. PMID:26756638

Kidney transplantation in the context of renal replacement therapy.

PubMed

Pesavento, Todd E

2009-12-01

Kidney transplantation has dramatically evolved from a life-saving yet unproven therapy for patients with renal failure to a mature field that is the preferred treatment for those suffering from ESRD. Patients who receive a transplant experience a 68% lower risk of death compared with those waiting on dialysis for a transplant. This benefit is afforded to all patient subgroups including the elderly (> or =70 yr), and diabetics, who can gain 11 yr of extra life with transplantation. Prolonged transplant wait times result in a higher risk of death but this can be ameliorated with preemptive transplantation. Future challenges will focus on appropriate organ allocation and addressing long-term renal function and comorbid conditions so patients can enjoy the full benefits of transplantation.

Elevated bilirubin levels are associated with a better renal prognosis and ameliorate kidney fibrosis.

PubMed

Park, Sehoon; Kim, Do Hyoung; Hwang, Jin Ho; Kim, Yong-Chul; Kim, Jin Hyuk; Lim, Chun Soo; Kim, Yon Su; Yang, Seung Hee; Lee, Jung Pyo

2017-01-01

Bilirubin has been reported to protect against kidney injury. However, further studies highlighting the beneficial effects of bilirubin on renal fibrosis and chronic renal function decline are necessary. We assessed a prospective cohort with a reference range of total bilirubin levels. The primary outcome was a 30% reduction in the estimated glomerular filtration rate (eGFR) from baseline, and the secondary outcome was a doubling of the serum creatinine levels, halving of the eGFR and the initiation of dialysis. In addition, experiments with tubular epithelial cells and C57BL/6 mice were performed to investigate the protective effects of bilirubin on kidney fibrosis. As a result, 1,080 patients were included in the study cohort. The study group with relative hyperbilirubinemia (total bilirubin 0.8-1.2 mg/dL) showed a better prognosis in terms of the primary outcome (adjusted hazard ratio (HR) 0.33, 95% confidence interval (CI) 0.19-0.59, P < 0.001) and the secondary outcome (adjusted HR 0.20, 95% CI 0.05 to 0.71, P = 0.01) than that of the control group. Moreover, the bilirubin-treated mice showed less fibrosis in the unilateral ureteral obstruction (UUO) model (P < 0.05). In addition, bilirubin treatment decreased fibronectin expression in tubular epithelial cells in a dose-dependent manner (P < 0.05). Mildly elevated serum bilirubin levels were associated with better renal prognosis, and bilirubin treatment induced a beneficial effect on renal fibrosis. Therefore, bilirubin could be a potential therapeutic target to delay fibrosis-related kidney disease progression.

Mesenchymal stem cell-derived microparticles ameliorate peritubular capillary rarefaction via inhibition of endothelial-mesenchymal transition and decrease tubulointerstitial fibrosis in unilateral ureteral obstruction.

PubMed

Choi, Hoon Young; Lee, Hyun Gyu; Kim, Beom Seok; Ahn, Sun Hee; Jung, Ara; Lee, Mirae; Lee, Jung Eun; Kim, Hyung Jong; Ha, Sung Kyu; Park, Hyeong Cheon

2015-03-11

Microparticles (MPs) derived from kidney-derived mesenchymal stem cells (KMSCs) have recently been reported to ameliorate rarefaction of peritubular capillaries (PTC) in ischemic kidneys via delivery of proangiogenic effectors. This study aimed to investigate whether KMSC-derived MPs show anti-fibrotic effects by ameliorating endothelial-to-mesenchymal transition (EndoMT) in human umbilical vein endothelial cells (HUVEC) in vitro and by preserving PTC in kidneys with unilateral ureteral obstruction (UUO) in vivo. MPs isolated from the supernatants of KMSC were co-cultured with HUVEC to assess their in vitro biologic effects on endothelial cells. Mice were treated with MPs via the tail vein after UUO injury to assess their anti-fibrotic and PTC sparing effects. Renal tubulointerstitial damage and inflammatory cell infiltration were examined with Masson's trichrome, F4/80 and α-smooth muscle actin (α-SMA) staining and PTC rarefaction index was determined by CD31 staining. KMSC-derived MPs significantly ameliorated EndoMT and improved in vitro proliferation of TGF-β1 treated HUVEC. In vivo administration of KMSC-derived MPs significantly inhibited EndoMT of PTC endothelial cells and improved PTC rarefaction in UUO kidneys. Furthermore, administration of KMSC-derived MPs inhibited inflammatory cell infiltration as well as tubulointerstitial fibrosis in UUO mice as demonstrated by decreased F4/80 and α-SMA-positive cells and Masson's trichrome staining, respectively. Our results suggest that KMSC-derived MPs ameliorate PTC rarefaction via inhibition of EndoMT and protect against progression of renal damage by inhibiting tubulointerstitial fibrosis.

Successful Endovascular Control of Renal Artery in a Transplant Kidney During Nephron Sparing Surgery (NSS) for Large Centrally Located Tumor.

PubMed

Shprits, Sagi; Moskovits, Boaz; Sachner, Robert; Nativ, Ofer

2016-05-01

Renal cell carcinoma in a transplant kidney is a rare condition. Nephron Sparing Surgery (NSS) is the treatment of choice. One of the main technical challenges is obtaining adequate vascular control. We present a rare case of large centrally located hillar tumor in a kidney 18 years after transplantation treated with NSS. Vascular control was achieved by using a novel approach. Post-operative course was uneventful with minimal decrease in renal function. We believe that this unique choice of treatment can be used in cases of NSS where the access to the renal pedicle is limited.

Hematopoietic stem cells derived from human umbilical cord ameliorate cisplatin-induced acute renal failure in rats

PubMed Central

Shalaby, Rokaya H; Rashed, Laila A; Ismaail, Alaa E; Madkour, Naglaa K; Elwakeel, Sherien H

2014-01-01

Injury to a target organ can be sensed by bone marrow stem cells that migrate to the site of damage, undergo differentiation, and promote structural and functional repair. This remarkable stem cell capacity prompted an investigation of the potential of mesenchymal and hematopoietic stem cells to cure acute renal failure. On the basis of the recent demonstration that hematopoietic stem cells (HSCs) can differentiate into renal cells, the current study tested the hypothesis that HSCs can contribute to the regeneration of renal tubular epithelial cells after renal injury. HSCs from human umbilical cord blood which isolated and purified by magnetic activated cell sorting were transplanted intraperitoneal into acute renal failure (ARF) rats which was established by a single dose of cisplatin 5 mg/kg for five days. The Study was carried on 48 male white albino rats, of average weight 120-150 gm. The animals were divided into 4 groups, Group one Served as control and received normal saline throughout the experiments. Group two (model control) received a single dose of cisplatin. Group three and four male-albino rats with induced ARF received interapritoneally (HSCs) at two week and four week respectively. Injection of a single dose of cisplatin resulted in a significant increase in serum creatinine and urea levels, histo-pathological examination of kidney tissue from cisplatin showed severe nephrotoxicity in which 50-75% of glomeruli and renal tubules exhibited massive degenerative change. Four weeks after HSC transplantation, Serum creatinine and urea nitrogen decreased 3.5 times and 2.1 times as well as HGF, IGF-1, VEGF and P53 using quantitative real-time PCR increased 4.3 times, 3.2, 2.4 and 4.2 times compared to ARF groups, respectively. The proliferation of cell nuclear antigen (PCNA)-positive cells (500.083±35.167) was higher than that in the cisplatin groups (58.612±15.743). In addition, the transplanted umbilical cord hematopoietic stem cells UC-HSCs could

Post-transplantation nephroptosis causing recurrent episodes of acute renal failure and hypertension secondary to intermittent vascular torsion of intraperitoneal renal allograft

PubMed Central

Dosch, Austin R.; Pahl, Madeleine; Reddy, Uttam; Foster, Clarence E.

2017-01-01

Abstract Nephroptosis is a rare complication in renal transplantation, but one with significant associated risk. Due to non-specific clinical features, there may be a substantial delay in diagnosis and loss of the transplanted kidney due to renal pedicle thrombosis. We present a case of post-transplantation nephroptosis after simultaneous pancreas and kidney transplant, which resulted in accelerated hypertension and reversible acute kidney injury >1 year after transplantation. Prompt detection of this rare entity leading to expeditious surgical intervention is necessary to preserve viability of the renal allograft. PMID:28560019

Qi-Dan Fang ameliorates adriamycin-induced nephrotic syndrome rat model by enhancing renal function and inhibiting podocyte injury.

PubMed

Wu, Jun-Biao; Ye, Shu-Fang; Liang, Chun-Ling; Li, Yu-Cui; Yu, Ying-Jia; Lai, Jie-Mei; Lin, Hui; Zheng, Jie; Zhou, Jiu-Yao

2014-02-12

Nephrotic syndrome (NS) is a clinical syndrome with a variety of causes, mainly characterized by heavy proteinuria. Podocyte injury plays a key role in proteinuria, one of the principal means for the control of NS is to prevent podocyte injury. Qi-Dan Fang consists of two of the most extensively applied herbal remedies among Traditional Chinese Medicine (TCM) (Radix Astragali Mongolici and Radix Salviae Miltiorrhizae, with a weight ratio of 5:1) which are specifically used for the treatment of various kidney diseases. In previous studies, we found that Qi-Dan Fang provides improvement to patients with adriamycin-induced nephrotic syndrome by alleviating proteinuria and serum lipid. The aim of this study is to study the efficiency of Qi-Dan Fang on NS model rat with renal dysfunction and podocyte injury, something which has not been carried out yet. The rats were divided into Normal, Model, Jin Gui Shen Qi Pill (4.12 g/kg), Qi-Dan Fang (3.09, 6.17 and 12.34 g/kg/d) groups, they were each given a single tail intravenous injection of Adriamycin (6.0 mg/kg) except for the Normal group and were orally administered dosages of Qi-Dian Fang and Jin Gui Shen Qi pills once daily for 7 weeks. Following the treatment, the content of cystation C (CysC), blood urea nitrogen (BUN), serum creatinine (Scr) were measured with an autobiochemical analyser. The pathomorphological changes to the glomeruli, the mRNA expressions of nephrin, podocin, CD2AP genes and p53, bax, bcl-2 proteins expressions were also carried out to probe the effects of Qi-Dan Fang. (1) Qi-Dan Fang treatment raised the level of CysC in blood serum while lowering the content of BUN and Scr in the adriamycin-induced nephrotic syndrome rat model; (2) Long-term administration of Qi-Dan Fang was able to ameliorate pathomorphological change of glomeruli and repair the organization structure of Glomerulus; (3) Qi-Dan Fang could increase the mRNA expression of nephrin, podocin and CD2AP genes, down-regulate the

Different reactivity to angiotensin II of peripheral and renal arteries in spontaneously hypertensive rats: effect of acute and chronic angiotensin converting enzyme inhibition

NASA Technical Reports Server (NTRS)

Guidi, E.; Hollenberg, N. K.

1986-01-01

We assessed renal blood flow and pressor responses to graded angiotensin II doses in spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats ingesting a diet containing 1.6% sodium basally and after acute and chronic angiotensin converting enzyme (ACE) inhibition with captopril. In the basal state the pressor response to angiotensin II was enhanced (P<0.0005) and the renal vascular response was blunted (P<0.005) in SHR compared with WKY rats. After acute captopril administration the pressor response was enhanced in both strains, and the difference between them was maintained, while the renal vascular response was enhanced in both, but more in SHR, so that the renal vascular response in the SHR became larger than in WKY (P<0.0001). Chronic captopril treatment blunted both pressor and renal responses in WKY rats, but only the pressor response in SHR. The renal vessels of SHR seem to be different from those of WKY rats in reaction to exogenous angiotensin II, and in response to both acute administration of captopril (probably acting through blockade of angiotensin II production) and chronic administration of captopril (probably acting mainly through accumulation of kinin or production of prostaglandins).

Predictive value of vascular endothelial growth factor polymorphisms on the risk of renal cell carcinomas.

PubMed

Xian, W; Zheng, H; Wu, W J

2015-07-13

We conducted a case-control study in a Chinese population to assess whether 5 common single-nucleotide polymorphisms in the vascular endothelial growth factor gene (VEGF) affect the risk of renal cell carcinoma (RCC). The study population included 266 RCC patients who were newly diagnosed and histologically confirmed to have RCC as well as 532 cancer-free controls. Genotyping of VEGF -2578C/A, -1156G/A, +1612G/A, +936C/T, and -634G/C was conducted by polymerase chain reaction-restriction fragment length polymorphism. RCC patients were more likely to have higher body mass index, and have a habit of tobacco smoking as well as suffer from diabetes. Conditional logistic regression analyses showed that individuals with the AA genotype and A allele of -2578C/A significantly increased the risk of RCC when compared with the CC genotype. Individuals carrying the CT and TT geno-types of +936C/T were correlated with an increased risk of RCC compared to the CC genotype. The T allele of +936C/T was associated with an increased risk of RCC. The -2578C/A and +936C/T polymorphisms in the VEGF gene may play a role in the etiology of RCC.

Natriuretic Peptide Receptor Guanylyl Cyclase-A in Podocytes is Renoprotective but Dispensable for Physiologic Renal Function.

PubMed

Staffel, Janina; Valletta, Daniela; Federlein, Anna; Ehm, Katharina; Volkmann, Regine; Füchsl, Andrea M; Witzgall, Ralph; Kuhn, Michaela; Schweda, Frank

2017-01-01

The cardiac natriuretic peptides (NPs), atrial NP and B-type NP, regulate fluid homeostasis and arterial BP through renal actions involving increased GFR and vascular and tubular effects. Guanylyl cyclase-A (GC-A), the transmembrane cGMP-producing receptor shared by these peptides, is expressed in different renal cell types, including podocytes, where its function is unclear. To study the effects of NPs on podocytes, we generated mice with a podocyte-specific knockout of GC-A (Podo-GC-A KO). Despite the marked reduction of GC-A mRNA in GC-A KO podocytes to 1% of the control level, Podo-GC-A KO mice and control littermates did not differ in BP, GFR, or natriuresis under baseline conditions. Moreover, infusion of synthetic NPs similarly increased the GFR and renal perfusion in both genotypes. Administration of the mineralocorticoid deoxycorticosterone-acetate (DOCA) in combination with high salt intake induced arterial hypertension of similar magnitude in Podo-GC-A KO mice and controls. However, only Podo-GC-A KO mice developed massive albuminuria (controls: 35-fold; KO: 5400-fold versus baseline), hypoalbuminemia, reduced GFR, and marked glomerular damage. Furthermore, DOCA treatment led to decreased expression of the slit diaphragm-associated proteins podocin, nephrin, and synaptopodin and to enhanced transient receptor potential canonical 6 (TRPC6) channel expression and ATP-induced calcium influx in podocytes of Podo-GC-A KO mice. Concomitant treatment of Podo-GC-A KO mice with the TRPC channel blocker SKF96365 markedly ameliorated albuminuria and glomerular damage in response to DOCA. In conclusion, the physiologic effects of NPs on GFR and natriuresis do not involve podocytes. However, NP/GC-A/cGMP signaling protects podocyte integrity under pathologic conditions, most likely by suppression of TRPC channels. Copyright © 2016 by the American Society of Nephrology.

Natriuretic Peptide Receptor Guanylyl Cyclase-A in Podocytes is Renoprotective but Dispensable for Physiologic Renal Function

PubMed Central

Staffel, Janina; Valletta, Daniela; Federlein, Anna; Ehm, Katharina; Volkmann, Regine; Füchsl, Andrea M.; Witzgall, Ralph; Kuhn, Michaela

2017-01-01

The cardiac natriuretic peptides (NPs), atrial NP and B-type NP, regulate fluid homeostasis and arterial BP through renal actions involving increased GFR and vascular and tubular effects. Guanylyl cyclase-A (GC-A), the transmembrane cGMP-producing receptor shared by these peptides, is expressed in different renal cell types, including podocytes, where its function is unclear. To study the effects of NPs on podocytes, we generated mice with a podocyte-specific knockout of GC-A (Podo-GC-A KO). Despite the marked reduction of GC-A mRNA in GC-A KO podocytes to 1% of the control level, Podo-GC-A KO mice and control littermates did not differ in BP, GFR, or natriuresis under baseline conditions. Moreover, infusion of synthetic NPs similarly increased the GFR and renal perfusion in both genotypes. Administration of the mineralocorticoid deoxycorticosterone-acetate (DOCA) in combination with high salt intake induced arterial hypertension of similar magnitude in Podo-GC-A KO mice and controls. However, only Podo-GC-A KO mice developed massive albuminuria (controls: 35-fold; KO: 5400-fold versus baseline), hypoalbuminemia, reduced GFR, and marked glomerular damage. Furthermore, DOCA treatment led to decreased expression of the slit diaphragm-associated proteins podocin, nephrin, and synaptopodin and to enhanced transient receptor potential canonical 6 (TRPC6) channel expression and ATP-induced calcium influx in podocytes of Podo-GC-A KO mice. Concomitant treatment of Podo-GC-A KO mice with the TRPC channel blocker SKF96365 markedly ameliorated albuminuria and glomerular damage in response to DOCA. In conclusion, the physiologic effects of NPs on GFR and natriuresis do not involve podocytes. However, NP/GC-A/cGMP signaling protects podocyte integrity under pathologic conditions, most likely by suppression of TRPC channels. PMID:27153922

Renal Sympathetic Denervation for Treatment of Hypertension.

PubMed

Pimenta, Eduardo; Oparil, Suzanne

2012-02-01

OPINION STATEMENT: Sympathetic nervous system activation of the heart, kidney and peripheral vasculature increases cardiac output, fluid retention and vascular resistance and plays an important role in acute and chronic BP elevation. Renal sympathetic denervation via a percutaneous radiofrequency catheter based approach is a safe and effective procedure that lowers BP in patients with resistant hypertension. Exploratory studies in patients with resistant hypertension and a variety of comorbidities, including insulin resistance/metabolic syndrome, obstructive sleep apnea and the polycystic ovary syndrome, have shown benefit of renal denervation in attenuating the severity of the comorbid conditions, as well as reducing BP. However, more studies are needed to further address the long term effects of renal denervation and its safety and effectiveness in other disease states such as congestive heart failure.

Arctium lappa ameliorates endothelial dysfunction in rats fed with high fat/cholesterol diets.

PubMed

Lee, Yun Jung; Choi, Deok Ho; Cho, Guk Hyun; Kim, Jin Sook; Kang, Dae Gill; Lee, Ho Sub

2012-08-06

Arctium lappa L. (Asteraceae), burdock, is a medicinal plant that is popularly used for treating hypertension, gout, hepatitis, and other inflammatory disorders. This study was performed to test the effect of ethanol extract of Arctium lappa L. (EAL) seeds on vascular reactivity and inflammatory factors in rats fed a high fat/cholesterol diet (HFCD). EAL-I (100 mg·kg-1/day), EAL-II (200 mg·kg-1/day), and fluvastatin (3 mg·kg-1/day) groups initially received HFCD alone for 8 weeks, with EAL supplementation provided during the final 6 weeks. Treatment with low or high doses of EAL markedly attenuated plasma levels of triglycerides and augmented plasma levels of high-density lipoprotein (HDL) in HFCD-fed rats. Chronic treatment with EAL markedly reduced impairments of acetylcholine (ACh)-induced relaxation of aortic rings. Furthermore, chronic treatment with EAL significantly lowered systolic blood pressure (SBP) and maintained smooth and flexible intimal endothelial layers in HFCD-fed rats. Chronic treatment with EAL suppressed upregulation of intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1, and E-selectin in the aorta. Chronic treatment with EAL also suppressed increases in matrix metalloproteinase (MMP)-2 expression. These results suggested that EAL can inhibit HFCD-induced vascular inflammation in the rat model. The present study provides evidence that EAL ameliorates HFCD-induced vascular dysfunction through protection of vascular relaxation and suppression of vascular inflammation.

Arctium lappa ameliorates endothelial dysfunction in rats fed with high fat/cholesterol diets

PubMed Central

2012-01-01

Background Arctium lappa L. (Asteraceae), burdock, is a medicinal plant that is popularly used for treating hypertension, gout, hepatitis, and other inflammatory disorders. This study was performed to test the effect of ethanol extract of Arctium lappa L. (EAL) seeds on vascular reactivity and inflammatory factors in rats fed a high fat/cholesterol diet (HFCD). Method EAL-I (100 mg·kg−1/day), EAL-II (200 mg·kg−1/day), and fluvastatin (3 mg·kg−1/day) groups initially received HFCD alone for 8 weeks, with EAL supplementation provided during the final 6 weeks. Results Treatment with low or high doses of EAL markedly attenuated plasma levels of triglycerides and augmented plasma levels of high-density lipoprotein (HDL) in HFCD-fed rats. Chronic treatment with EAL markedly reduced impairments of acetylcholine (ACh)-induced relaxation of aortic rings. Furthermore, chronic treatment with EAL significantly lowered systolic blood pressure (SBP) and maintained smooth and flexible intimal endothelial layers in HFCD-fed rats. Chronic treatment with EAL suppressed upregulation of intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1, and E-selectin in the aorta. Chronic treatment with EAL also suppressed increases in matrix metalloproteinase (MMP)-2 expression. These results suggested that EAL can inhibit HFCD-induced vascular inflammation in the rat model. Conclusion The present study provides evidence that EAL ameliorates HFCD-induced vascular dysfunction through protection of vascular relaxation and suppression of vascular inflammation. PMID:22866890

Partial renal coverage in endovascular aneurysm repair causes unfavorable renal flow patterns in an infrarenal aneurysm model.

PubMed

van de Velde, Lennart; Donselaar, Esmé J; Groot Jebbink, Erik; Boersen, Johannes T; Lajoinie, Guillaume P R; de Vries, Jean-Paul P M; Zeebregts, Clark J; Versluis, Michel; Reijnen, Michel M P J

2018-05-01

To achieve an optimal sealing zone during endovascular aneurysm repair, the intended positioning of the proximal end of the endograft fabric should be as close as possible to the most caudal edge of the renal arteries. Some endografts exhibit a small offset between the radiopaque markers and the proximal fabric edge. Unintended partial renal artery coverage may thus occur. This study investigated the consequences of partial coverage on renal flow patterns and wall shear stress (WSS). In vitro models of an abdominal aortic aneurysm were used to visualize pulsatile flow using two-dimensional particle image velocimetry under physiologic resting conditions. One model served as control and two models were stented with an Endurant endograft (Medtronic Inc, Minneapolis, Minn), one without and one with partial renal artery coverage with 1.3 mm of stent fabric extending beyond the marker (16% area coverage). The magnitude and oscillation of WSS, relative residence time, and backflow in the renal artery were analyzed. In both stented models, a region along the caudal renal artery wall presented with low and oscillating WSS, not present in the control model. A region with very low WSS (<0.1 Pa) was present in the model with partial coverage over a length of 7 mm compared with a length of 2 mm in the model without renal coverage. Average renal backflow area percentage in the renal artery incrementally increased from control (0.9%) to the stented model without (6.4%) and with renal coverage (18.8%). In this flow model, partial renal coverage after endovascular aneurysm repair causes low and marked oscillations in WSS, potentially promoting atherosclerosis and subsequent renal artery stenosis. Awareness of the device-dependent offset between the fabric edge and the radiopaque markers is therefore important in endovascular practice. Copyright © 2017 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Perivascular radiofrequency renal denervation lowers blood pressure and ameliorates cardiorenal fibrosis in spontaneously hypertensive rats

PubMed Central

Zhang, Yan; Su, Linan; Zhang, Yunrong; Wang, Qiang; Yang, Dachun; Li, De; Yang, Yongjian; Ma, Shuangtao

2017-01-01

Background Catheter-based renal denervation (RDN) is a promising approach to treat hypertension, but innervation patterns limit the response to endovascular RDN and the post-procedural renal artery narrowing or stenosis questions the endovascular ablation strategy. This study was performed to investigate the anti-hypertensive and target organ protective effects of perivascular RDN in spontaneously hypertensive rats (SHR). Methods SHR and normotensive Wistar-Kyoto (WKY) rats were divided into sham group (n = 10), radiofrequency ablation group (n = 20) in which rats received bilateral perivascular ablation with radiofrequency energy (2 watts), and chemical (10% phenol in 95% ethanol) ablation group (n = 12). The tail-cuff blood pressure was measured before the ablation and on day 14 and day 28 after the procedure. The plasma levels of creatinine, urea nitrogen, and catecholamines, urinary excretion of electrolytes and protein, and myocardial and glomerular fibrosis were analyzed and compared among the groups on day 28 after the procedure. Results We identified that 2-watt is the optimal radiofrequency power for perivascular RDN in rats. Perivascular radiofrequency and chemical ablation achieved roughly comparable blood pressure reduction in SHR but not in WKY on day 14 and day 28 following the procedure. Radiofrequency-mediated ablation substantially destroyed the renal nerves surrounding the renal arteries of both SHR and WKY without damaging the renal arteries and diminished the expression of tyrosine hydroxylase, the enzyme marker for postganglionic sympathetic nerves. Additionally, perivascular radiofrequency ablation also decreased the plasma catecholamines of SHR. Interestingly, both radiofrequency and chemical ablation decreased the myocardial and glomerular fibrosis of SHR, while neither increased the plasma creatinine and blood urea nitrogen nor affected the urinary excretion of electrolytes and protein when compared to sham group. Conclusions Radiofrequency

Perivascular radiofrequency renal denervation lowers blood pressure and ameliorates cardiorenal fibrosis in spontaneously hypertensive rats.

PubMed

Wei, Shujie; Li, Dan; Zhang, Yan; Su, Linan; Zhang, Yunrong; Wang, Qiang; Yang, Dachun; Li, De; Yang, Yongjian; Ma, Shuangtao

2017-01-01

Catheter-based renal denervation (RDN) is a promising approach to treat hypertension, but innervation patterns limit the response to endovascular RDN and the post-procedural renal artery narrowing or stenosis questions the endovascular ablation strategy. This study was performed to investigate the anti-hypertensive and target organ protective effects of perivascular RDN in spontaneously hypertensive rats (SHR). SHR and normotensive Wistar-Kyoto (WKY) rats were divided into sham group (n = 10), radiofrequency ablation group (n = 20) in which rats received bilateral perivascular ablation with radiofrequency energy (2 watts), and chemical (10% phenol in 95% ethanol) ablation group (n = 12). The tail-cuff blood pressure was measured before the ablation and on day 14 and day 28 after the procedure. The plasma levels of creatinine, urea nitrogen, and catecholamines, urinary excretion of electrolytes and protein, and myocardial and glomerular fibrosis were analyzed and compared among the groups on day 28 after the procedure. We identified that 2-watt is the optimal radiofrequency power for perivascular RDN in rats. Perivascular radiofrequency and chemical ablation achieved roughly comparable blood pressure reduction in SHR but not in WKY on day 14 and day 28 following the procedure. Radiofrequency-mediated ablation substantially destroyed the renal nerves surrounding the renal arteries of both SHR and WKY without damaging the renal arteries and diminished the expression of tyrosine hydroxylase, the enzyme marker for postganglionic sympathetic nerves. Additionally, perivascular radiofrequency ablation also decreased the plasma catecholamines of SHR. Interestingly, both radiofrequency and chemical ablation decreased the myocardial and glomerular fibrosis of SHR, while neither increased the plasma creatinine and blood urea nitrogen nor affected the urinary excretion of electrolytes and protein when compared to sham group. Radiofrequency-mediated perivascular RDN may become a

Elevated bilirubin levels are associated with a better renal prognosis and ameliorate kidney fibrosis

PubMed Central

Hwang, Jin Ho; Kim, Yong-Chul; Kim, Jin Hyuk; Lim, Chun Soo; Kim, Yon Su; Yang, Seung Hee; Lee, Jung Pyo

2017-01-01

Background Bilirubin has been reported to protect against kidney injury. However, further studies highlighting the beneficial effects of bilirubin on renal fibrosis and chronic renal function decline are necessary. Methods We assessed a prospective cohort with a reference range of total bilirubin levels. The primary outcome was a 30% reduction in the estimated glomerular filtration rate (eGFR) from baseline, and the secondary outcome was a doubling of the serum creatinine levels, halving of the eGFR and the initiation of dialysis. In addition, experiments with tubular epithelial cells and C57BL/6 mice were performed to investigate the protective effects of bilirubin on kidney fibrosis. Results As a result, 1,080 patients were included in the study cohort. The study group with relative hyperbilirubinemia (total bilirubin 0.8–1.2 mg/dL) showed a better prognosis in terms of the primary outcome (adjusted hazard ratio (HR) 0.33, 95% confidence interval (CI) 0.19–0.59, P < 0.001) and the secondary outcome (adjusted HR 0.20, 95% CI 0.05 to 0.71, P = 0.01) than that of the control group. Moreover, the bilirubin-treated mice showed less fibrosis in the unilateral ureteral obstruction (UUO) model (P < 0.05). In addition, bilirubin treatment decreased fibronectin expression in tubular epithelial cells in a dose-dependent manner (P < 0.05). Conclusions Mildly elevated serum bilirubin levels were associated with better renal prognosis, and bilirubin treatment induced a beneficial effect on renal fibrosis. Therefore, bilirubin could be a potential therapeutic target to delay fibrosis-related kidney disease progression. PMID:28225832

Deletion of protein kinase C-ε attenuates mitochondrial dysfunction and ameliorates ischemic renal injury.

PubMed

Nowak, Grazyna; Takacsova-Bakajsova, Diana; Megyesi, Judit

2017-01-01

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 PKC-ε decreases dysfunction of renal cortical mitochondria and improves kidney function after renal ischemia. PKC-ε levels in mitochondria of ischemic kidneys increased 24 h 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. Respiratory control ratio coupled to glutamate/malate oxidation decreased 50% in WT but not in KO mice. Activities of complexes I, III, and IV were decreased 59, 89, and 61%, respectively, in WT but not in KO ischemic kidneys. Proteomics revealed increases in levels of ATP synthase (α-subunit), complexes I and III, cytochrome oxidase, α-ketoglutarate dehydrogenase, and thioredoxin-dependent peroxide reductase after ischemia in KO but not in WT animals. PKC-ε deletion prevented ischemia-induced increases in oxidant production. Plasma creatinine levels increased 12-fold in WT and 3-fold in KO ischemic mice. PKC-ε deletion reduced tubular necrosis, brush border loss, and distal segment damage in ischemic kidneys. PKC-ε activation in hypoxic RPTC in primary culture exacerbated, whereas PKC-ε inhibition reduced, decreases in: 1) complex I- and complex II-coupled state 3 respirations and 2) activities of complexes I, III, and IV. We conclude that PKC-ε activation mediates 1) dysfunction of complexes I and III of the respiratory chain, 2) oxidant production, 3) morphological damage to the kidney, and 4) decreases in renal functions after ischemia. Copyright © 2017 the American Physiological Society.

Deletion of protein kinase C-ε attenuates mitochondrial dysfunction and ameliorates ischemic renal injury

PubMed Central

Takacsova-Bakajsova, Diana; Megyesi, Judit

2016-01-01

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 PKC-ε decreases dysfunction of renal cortical mitochondria and improves kidney function after renal ischemia. PKC-ε levels in mitochondria of ischemic kidneys increased 24 h 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. Respiratory control ratio coupled to glutamate/malate oxidation decreased 50% in WT but not in KO mice. Activities of complexes I, III, and IV were decreased 59, 89, and 61%, respectively, in WT but not in KO ischemic kidneys. Proteomics revealed increases in levels of ATP synthase (α-subunit), complexes I and III, cytochrome oxidase, α-ketoglutarate dehydrogenase, and thioredoxin-dependent peroxide reductase after ischemia in KO but not in WT animals. PKC-ε deletion prevented ischemia-induced increases in oxidant production. Plasma creatinine levels increased 12-fold in WT and 3-fold in KO ischemic mice. PKC-ε deletion reduced tubular necrosis, brush border loss, and distal segment damage in ischemic kidneys. PKC-ε activation in hypoxic RPTC in primary culture exacerbated, whereas PKC-ε inhibition reduced, decreases in: 1) complex I- and complex II-coupled state 3 respirations and 2) activities of complexes I, III, and IV. We conclude that PKC-ε activation mediates 1) dysfunction of complexes I and III of the respiratory chain, 2) oxidant production, 3) morphological damage to the kidney, and 4) decreases in renal functions after ischemia. PMID:27760765

The Putative Role of the Antiageing Protein Klotho in Cardiovascular and Renal Disease

PubMed Central

Maltese, Giuseppe; Karalliedde, Janaka

2012-01-01

Ageing is a multifactorial process often characterized by a progressive decline in physiological function(s). Ageing can and is often associated with an increased incidence of cardiovascular and renal disease. Klotho is a novel antiageing gene that encodes a protein with multiple pleiotropic functions including an emerging role in cardiorenal disease. Mice deficient for this gene display a phenotype of premature human ageing characterized by diffuse vascular calcification, altered calcium/phosphate metabolism, and shortened lifespan. Klotho is mainly expressed in the renal tubules but it also exists as circulating soluble form detectable in the blood, with systemic effects. Reduction in soluble Klotho has been associated with renal disease, hyperphosphataemia, increased oxidative stress, endothelial dysfunction, and diffuse vascular calcification. Conversely, overexpression of Klotho promotes cardiovascular-renal protection. The majority of the research on Klotho has been conducted in vitro and in animal studies but there is emerging data from human studies which suggest that Klotho may be a modifiable factor involved in the pathogenesis of cardiovascular and renal disease in at-risk populations. Further data is required to confirm if this novel protein can emerge as therapeutic tool that may be used to prevent or slow progression of cardiorenal disease. PMID:22121479

Physical Exercise and Patients with Chronic Renal Failure: A Meta-Analysis

PubMed Central

Qiu, Zhenzhen; Zheng, Kai; Zhang, Haoxiang; Feng, Ji; Wang, Lizhi

2017-01-01

Chronic renal failure is a severe clinical problem which has some significant socioeconomic impact worldwide and hemodialysis is an important way to maintain patients' health state, but it seems difficult to get better in short time. Considering these, the aim in our research is to update and evaluate the effects of exercise on the health of patients with chronic renal failure. The databases were used to search for the relevant studies in English or Chinese. And the association between physical exercise and health state of patients with chronic renal failure has been investigated. Random-effect model was used to compare the physical function and capacity in exercise and control groups. Exercise is helpful in ameliorating the situation of blood pressure in patients with renal failure and significantly reduces VO2 in patients with renal failure. The results of subgroup analyses show that, in the age >50, physical activity can significantly reduce blood pressure in patients with renal failure. The activity program containing warm-up, strength, and aerobic exercises has benefits in blood pressure among sick people and improves their maximal oxygen consumption level. These can help patients in physical function and aerobic capacity and may give them further benefits. PMID:28316986

Reduction of vascular leakage by imatinib is associated with preserved microcirculatory perfusion and reduced renal injury markers in a rat model of cardiopulmonary bypass.

PubMed

Koning, N J; de Lange, F; van Meurs, M; Jongman, R M; Ahmed, Y; Schwarte, L A; van Nieuw Amerongen, G P; Vonk, A B A; Niessen, H W; Baufreton, C; Boer, C

2018-06-01

Cardiopulmonary bypass during cardiac surgery leads to impaired microcirculatory perfusion. We hypothesized that vascular leakage is an important contributor to microcirculatory dysfunction. Imatinib, a tyrosine kinase inhibitor, has been shown to reduce vascular leakage in septic mice. We investigated whether prevention of vascular leakage using imatinib preserves microcirculatory perfusion and reduces organ injury markers in a rat model of cardiopulmonary bypass. Male Wistar rats underwent cardiopulmonary bypass after treatment with imatinib or vehicle (n=8 per group). Cremaster muscle microcirculatory perfusion and quadriceps microvascular oxygen saturation were measured using intravital microscopy and reflectance spectroscopy. Evans Blue extravasation was determined in separate experiments. Organ injury markers were determined in plasma, intestine, kidney, and lungs. The onset of cardiopulmonary bypass decreased the number of perfused microvessels by 40% in the control group [9.4 (8.6-10.6) to 5.7 (4.8-6.2) per microscope field; P<0.001 vs baseline], whereas this reduction was not seen in the imatinib group. In the control group, the number of perfused capillaries remained low throughout the experiment, whilst perfusion remained normal after imatinib administration. Microvascular oxygen saturation was less impaired after imatinib treatment compared with controls. Imatinib reduced vascular leakage and decreased fluid resuscitation compared with control [3 (3-6) vs 12 ml (7-16); P=0.024]. Plasma neutrophil-gelatinase-associated-lipocalin concentrations were reduced by imatinib. Prevention of endothelial barrier dysfunction using imatinib preserved microcirculatory perfusion and oxygenation during and after cardiopulmonary bypass. Moreover, imatinib-induced protection of endothelial barrier integrity reduced fluid-resuscitation requirements and attenuated renal and pulmonary injury markers. Copyright © 2017 British Journal of Anaesthesia. Published by Elsevier

Can We Clinically Recognize a Vascular Depression?

PubMed Central

Turk, Bela R.; Gschwandtner, Michael E.; Mauerhofer, Michaela; Löffler-Stastka, Henriette

2015-01-01

Abstract The vascular depression (VD) hypothesis postulates that cerebrovascular disease may “predispose, precipitate, or perpetuate” a depressive syndrome in elderly patients. Clinical presentation of VD has been shown to differ to major depression in quantitative disability; however, as little research has been made toward qualitative phenomenological differences in the personality aspects of the symptom profile, clinical diagnosis remains a challenge. We attempted to identify differences in clinical presentation between depression patients (n = 50) with (n = 25) and without (n = 25) vascular disease using questionnaires to assess depression, affect regulation, object relations, aggressiveness, alexithymia, personality functioning, personality traits, and counter transference. We were able to show that patients with vascular dysfunction and depression exhibit significantly higher aggressive and auto-aggressive tendencies due to a lower tolerance threshold. These data indicate that VD is a separate clinical entity and secondly that the role of personality itself may be a component of the disease process. We propose an expanded threshold disease model incorporating personality functioning and mood changes. Such findings might also aid the development of a screening program, by serving as differential criteria, ameliorating the diagnostic procedure. PMID:25950684

Nervous kidney. Interaction between renal sympathetic nerves and the renin-angiotensin system in the control of renal function.

PubMed

DiBona, G F

2000-12-01

Increases in renal sympathetic nerve activity regulate the functions of the nephron, the vasculature, and the renin-containing juxtaglomerular granular cells. Because increased activity of the renin-angiotensin system can also influence nephron and vascular function, it is important to understand the interactions between the renal sympathetic nerves and the renin-angiotensin system in the control of renal function. These interactions can be intrarenal, for example, the direct (by specific innervation) and indirect (by angiotensin II) contributions of increased renal sympathetic nerve activity to the regulation of renal function. The effects of increased renal sympathetic nerve activity on renal function are attenuated when the activity of the renin-angiotensin system is suppressed or antagonized with ACE inhibitors or angiotensin II-type AT(1)-receptor antagonists. The effects of intrarenal administration of angiotensin II are attenuated after renal denervation. These interactions can also be extrarenal, for example, in the central nervous system, wherein renal sympathetic nerve activity and its arterial baroreflex control are modulated by changes in activity of the renin-angiotensin system. In addition to the circumventricular organs, whose permeable blood-brain barrier permits interactions with circulating angiotensin II, there are interactions at sites behind the blood-brain barrier that depend on the influence of local angiotensin II. The responses to central administration of angiotensin II-type AT(1)-receptor antagonists into the ventricular system or microinjected into the rostral ventrolateral medulla are modulated by changes in activity of the renin-angiotensin system produced by physiological changes in dietary sodium intake. Similar modulation is observed in pathophysiological models wherein activity of both the renin-angiotensin and sympathetic nervous systems is increased (eg, congestive heart failure). Thus, both renal and extrarenal sites of

Nebivolol ameliorated kidney damage in Zucker diabetic fatty rats by regulation of oxidative stress/NO pathway: comparison with captopril.

PubMed

Wang, Yan; An, Wenjing; Zhang, Fei; Niu, Mengzhen; Liu, Yu; Shi, Ruizan

2018-06-23

The aim was to evaluate the effects and mechanisms of nebivolol on renal damage in Zucker diabetic fatty (ZDF) rats, in comparison with those of atenolol and captopril. Animals were divided into: control lean Zucker rats, ZDF rats, ZDF rats orally treated with nebivolol (10 mg/kg), atenolol (100 mg/kg) or captopril (40 mg/kg) for 6 months. Systolic blood pressure (SBP), blood glucose, kidney structure and function, plasma and kidney levels of nitric oxide (NO) and asymmetric dimethylarginine (ADMA), and oxidant status were evaluated. Kidney expressions of AMP-activated protein kinase (AMPK), NADPH oxidase (NOX) isoforms 2 and 4 and subunit p22 phox , nitric oxide synthase (NOS) isoforms, eNOS uncoupling, protein arginine N-methyltransferase (PRMT) 1, and dimethylarginine dimethylaminohydrolase (DDAH) 1 and 2 were tested. All drugs induced a similar control of SBP. Nebivolol did not affect the increased plasma glucose. Unlike atenolol, nebivolol prevented the decrease in plasma insulin, and, like captopril, it reduced plasma lipid contents. Nebivolol ameliorated, to a greater extent than captopril, damages to renal structure and function, which were associated with an improvement in interlobular artery dysfunction. Nebivolol elevated kidney phosphorylation of AMPK, attenuated NOX4 and p22 phox expression and oxidative stress marker levels. Nebivolol increased plasma and renal NO, enhanced expressions of eNOS, p-eNOS and nNOS, and suppressed eNOS uncoupling and iNOS expression. High ADMA in plasma and kidney were decreased by nebivolol through increasing DDAH2 and decreasing PRMT1. Long-term treatment of nebivolol ameliorated diabetic nephropathy, at least in part, via regulation of renal oxidative stress/NO pathway. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

6-gingerol ameliorates gentamicin induced renal cortex oxidative stress and apoptosis in adult male albino rats.

PubMed

Hegazy, Ahmed M S; Mosaed, Mohammed M; Elshafey, Saad H; Bayomy, Naglaa A

2016-06-01

Ginger or Zingiber officinale which is used in traditional medicine has been found to possess antioxidant effect that can control the generation of free radicals. Free radicals are the causes of renal cell degeneration that leads to renal failure in case of gentamicin induced toxicity. This study was done to evaluate the possible protective effects of 6-gingerol as natural antioxidant on gentamicin-induced renal cortical oxidative stress and apoptosis in adult male albino rats. Forty adult male albino rats were used in this study and were randomly divided into four groups, control group; 6-gingerol treated group; gentamicin treated group and protected group (given simultaneous 6-gingerol and gentamicin). At the end of the study, blood samples were drawn for biochemical study. Kidney sections were processed for histological, and immunohistochemical examination for caspase-3 to detect apoptosis and anti heat shock protein 47 (HSP47) to detect oxidative damage. Gentamicin treated rats revealed a highly significant increase in renal function tests, tubular dilatation with marked vacuolar degeneration and desquamation of cells, interstitial hemorrhage and cellular infiltration. Immunohistochemically, gentamicin treated rats showed a strong positive immunoreaction for caspase-3 and anti heat shock protein 47 (HSP47). Protected rats showed more or less normal biochemical, histological, and immunohistochemical pictures. In conclusion, co-administration of 6-gingerol during gentamicin 'therapy' has a significant reno-protective effect in a rat model of gentamicin-induced renal damage. It is recommended that administration of ginger with gentamicin might be beneficial in men who receive gentamicin to treat infections. Copyright © 2016 Elsevier Ltd. All rights reserved.

Phytochemical screening, and assessment of ameliorating effect of aqueous and ethanolic extracts of Gmelina arborea on drug induced hepatic and renal insufficiency in rats.

PubMed

Anthony, Ogbonnaya Enyinnaya; Mbuh, Awah Francis; Emmanuel, Mounmbegna Philippe

2012-04-01

Phytochemical screening of stem bark and leaves of Gmelina arborea; and effect of aqueous and ethanolic extracts of Gmelina arborea stembark on hepatic and renal insufficiency in rats was assessed in this study. Phytochemical screening was carried out on the air-dried leaf, oven-dried leaf, air-dried stembark and oven-dried stembark samples. Sixty five (65) wister albino rats, (50.7-117.5 g) were divided into thirteen groups of five animals each. Three groups serve as Controls and were administered Cisplatin (5mg/kg b.w; i.p), Paracetamol (200mg/kg b.w; i.p) and Normal saline (0.002 ml/kg b.w; oral). Other groups were administered, either, cisplatin and extracts (1g/kg b.w; oral); Paracetamol and extracts (1g/kg b.w; oral); extracts alone; or drugs and combination of extracts. Animals were starved, 24 hours prior to sacrifice and sacrificed on the 9th day after commencement of treatment. Phytochemical screening results show the presence of alkaloid, flavonoid, tannin, saponin, cyanogenic glycoside, phytate, and carbohydrate. Saponin and carbohydrate were shown to be much higher in concentration than other phytochemicals. The percentage composition of cyanogenic glycoside and phytate were highest in air-dried stembark and oven-dried leaf samples, respectively. All the Gmelina arborea extracts and extract mixture administered to both paracetamol and cisplatin treated animals, significantly, lowers both the activities of the SGOT and SGPT, and the levels of serum creatinine and urea. When administered alone, the aqueous and ethanolic extracts show little or no sign of toxicity. Thus Gmelina arborea extracts may have ameliorating effect on hepatic and renal insufficiency caused by paracetamol and cisplatin respectively, and any inherent toxicity may be reduced or eliminated through adequate heat treatment.

[Pulmonary-renal crosstalk in the critically ill patient].

PubMed

Donoso F, Alejandro; Arriagada S, Daniela; Cruces R, Pablo

2015-01-01

Despite advances in the development of renal replacement therapy, mortality of acute renal failure remains high, especially when occurring simultaneously with distant organic failure as it is in the case of the acute respiratory distress syndrome. In this update, birideccional deleterious relationship between lung and kidney on the setting of organ dysfunction is reviewed, which presents important clinical aspects of knowing. Specifically, the renal effects of acute respiratory distress syndrome and the use of positive-pressure mechanical ventilation are discussed, being ventilator induced lung injury one of the most common models for studying the lung-kidney crosstalk. The role of renal failure induced by mechanical ventilation (ventilator-induced kidney injury) in the pathogenesis of acute renal failure is emphasized. We also analyze the impact of the acute renal failure in the lung, recognizing an increase in pulmonary vascular permeability, inflammation, and alteration of sodium and water channels in the alveolar epithelial. This conceptual model can be the basis for the development of new therapeutic strategies to use in patients with multiple organ dysfunction syndrome. Copyright © 2015 Sociedad Chilena de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

Sunitinib-Induced Acute Interstitial Nephritis in a Thrombocytopenic Renal Cell Cancer Patient.

PubMed

Azar, Ibrahim; Esfandiarifard, Saghi; Sinai, Pedram; Wazir, Ali; Foulke, Llewellyn; Mehdi, Syed

2017-01-01

Sunitinib, a multitargeted tyrosine kinase inhibitor (TKI), is currently the standard of care for patients with metastatic renal cell carcinoma. Renal adverse events associated with sunitinib include proteinuria, renal insufficiency secondary to focal segmental glomerulosclerosis (FSGS), and thrombotic microangiopathy. We describe the second reported instance of biopsy-proven sunitinib-induced acute interstitial nephritis (AIN), in a challenging case complicated by thrombocytopenia. The case illustrates the importance of early diagnosis and intervention in ensuring long-term recovery from renal complications. Four other cases of AIN reported along with inhibition of the vascular endothelial growth factor (VEGF) by either TKI (sunitinib and sorafenib) or antibodies (bevacizumab) suggest a possible class effect. Given our experience, we recommend monitoring renal function with VEGF inhibition, and in the case of renal failure in the setting of an unclear diagnosis, we recommend prompt biopsy.

Vascular structure and oxidative stress in salt-loaded spontaneously hypertensive rats: effects of losartan and atenolol.

PubMed

de Cavanagh, Elena M V; Ferder, León F; Ferder, Marcelo D; Stella, Inés Y; Toblli, Jorge E; Inserra, Felipe

2010-12-01

Renin-angiotensin system (RAS) modulation by high dietary sodium may contribute to salt-induced hypertension, oxidative stress, and target organ damage. We investigated whether angiotensin II (Ang-II) type 1 (AT1)-receptor blockade (losartan) could protect the aorta and renal arteries from combined hypertension- and high dietary salt-related oxidative stress. Spontaneously hypertensive rats (3-month-old, n = 10/group) received tap water (SHR), water containing 1.5% NaCl (SHR+S), 1.5% NaCl and 30 mg losartan/kg/day (SHR+S+L), or 50 mg atenolol/kg/day (SHR+S+A). Atenolol was used for comparison. Ten Wistar-Kyoto rats (WKY) were controls. Systolic blood pressure (SBP) was determined by tail plethysmography. After 5 months of treatment, vascular remodeling and oxidative stress (superoxide production and NAD(P)H-oxidase activity (chemiluminescence), malondialdehyde (MDA) content (high-performance liquid chromatography), endothelial nitric oxide synthase (eNOS) activity [(14)C-arginine to (14)C citrulline], CuZn-SOD activity (spectrophotometry)) were studied. In SHR, salt-loading significantly aggravated hypertension, urinary protein excretion, intraparenchymal renal artery (IPRArt) perivascular fibrosis, aortic and renal artery oxidative stress, and induced endothelial cell loss in IPRArts. In salt-loaded SHR, 5-month losartan and atenolol treatments similarly reduced SBP, but only losartan significantly prevented (i) urinary protein excretion increase, (ii) or attenuated hypertension-related vascular remodeling, (iii) aortic MDA accumulation, (iv) renal artery eNOS activity lowering, and (v) aortic and renal artery superoxide dismutase (SOD) activity reduction. In SHR+S, the contributions to aortic superoxide production were as follows: uncoupled eNOS > xanthine oxidase (XO) > NAD(P)H oxidase. In this salt-sensitive genetic hypertension model, losartan protects from hypertension- and high dietary salt-related vascular oxidative stress, exceeding the benefits of BP

Mechanism of grape seeds extract protection against paracetamol renal cortical damage in male Albino rats.

PubMed

Abdel-Hafez, S M N; Rifaai, R A; Abd Elzaher, W Y

2017-01-01

The aim of the study was to assess the possible protective role of grape seeds extract (GSE) in ameliorating the toxic effects of paracetamol overdose on the rat renal cortical tissue. Paracetamol is one of the widely used non-steroidal anti-inflammatory drugs (NSAIDs). Unfortunately, it was reported as the most common cause of toxic ingestion in the world. Grape seeds extract (GSE) is known to have a strong antioxidant and anti-inflammatory properties. The rats were divided into 4 groups; control group, GSE group, paracetamol group and GSE with paracetamol group. Kidney specimens were processed for biochemical, histological and immunohisto-chemical studies. The study showed marked biological changes in the form of significant increase in serum urea and creatinine levels with significant decrease in renal superoxide dismutase with paracetamol group. Furthermore, Proximal (PCT) and distal convoluted tubules showed marked degeneration, dense nuclear staining, cytoplasmic vacuolization, and partial loss of the brush borders. Most tubules were dilated, irregular and were filled with hyaline casts. PCT and DCT showed less PAS reaction and more COX-2 and caspase expression if compared with the control and the GSE groups. Concomitant administration of grape seeds extract with paracetamol revealed a noticeable amelioration of these biochemical and histological changes. Proximal and distal convoluted tubules showed less PAS reaction and more COX2 and caspase expression if compared with the control and the GSE. Concomitant administration of GSE with paracetamol revealed a noticeable amelioration of these biochemical and histological changes. Grape seeds extract provided biochemical and histo-pathological improvement in paracetamol induced renal cortical toxicity. These findings revealed that this improvement was associated with a decrease in oxidative damage and apoptosis (Tab. 1, Fig. 7, Ref. 55).

Anatomic variations of the renal vessels pertinent to transperitoneal vascular control in the management of trauma.

PubMed

Kaneko, Naoyuki; Kobayashi, Yasushi; Okada, Yoshiaki

2008-05-01

Operative exposure and control of the renal vessels through a transabdominal retroperitoneal (TARP) approach has been advocated for emergency management of renal trauma. The pertinent anatomic variations of the renal vasculature have not been well described. In 190 cadavers, the renal vessels were examined. The first 20 cadavers were examined via TARP approach, and 170 cadavers were investigated after evisceration. The findings were interpreted as they might relate to the TARP approach to the renal pedicle. The renal artery (RA) originated dorsally or inferiorly to the left renal vein (RV) in 70% of the cadavers on each side. Additional RAs emerging below the inferior mesenteric artery were present in 2.4% of cadavers on the right side and 1.8% on the left. Approach to the inferior vena cava (IVC) adequate for the management of trauma through the TARP approach was impossible, although it has been recommended in some research. The clinically significant incidence of variations was as follows: 47% multiple RAs, 13% multiple RVs, and 50% of at least 1 RA that coursed superior to the right RV on the right margin of the IVC. Knowledge of the varied anatomy of the renal vessels facilitates a safe approach to the kidneys in trauma management. The varied and unpredictable anatomy of the renal vasculature requires prompt change when the TARP approach fails to provide access to the vessels. In such cases, the colon should be mobilized promptly. On the right side of the IVC, the vessels are located so as to require clamping together almost always.

Canonical WNT signaling components in vascular development and barrier formation.

PubMed

Zhou, Yulian; Wang, Yanshu; Tischfield, Max; Williams, John; Smallwood, Philip M; Rattner, Amir; Taketo, Makoto M; Nathans, Jeremy

2014-09-01

Canonical WNT signaling is required for proper vascularization of the CNS during embryonic development. Here, we used mice with targeted mutations in genes encoding canonical WNT pathway members to evaluate the exact contribution of these components in CNS vascular development and in specification of the blood-brain barrier (BBB) and blood-retina barrier (BRB). We determined that vasculature in various CNS regions is differentially sensitive to perturbations in canonical WNT signaling. The closely related WNT signaling coreceptors LDL receptor-related protein 5 (LRP5) and LRP6 had redundant functions in brain vascular development and barrier maintenance; however, loss of LRP5 alone dramatically altered development of the retinal vasculature. The BBB in the cerebellum and pons/interpeduncular nuclei was highly sensitive to decrements in canonical WNT signaling, and WNT signaling was required to maintain plasticity of barrier properties in mature CNS vasculature. Brain and retinal vascular defects resulting from ablation of Norrin/Frizzled4 signaling were ameliorated by stabilizing β-catenin, while inhibition of β-catenin-dependent transcription recapitulated the vascular development and barrier defects associated with loss of receptor, coreceptor, or ligand, indicating that Norrin/Frizzled4 signaling acts predominantly through β-catenin-dependent transcriptional regulation. Together, these data strongly support a model in which identical or nearly identical canonical WNT signaling mechanisms mediate neural tube and retinal vascularization and maintain the BBB and BRB.

High Prevalence of Multiple Arterial Bed Lesions in Patients With Fibromuscular Dysplasia: The ARCADIA Registry (Assessment of Renal and Cervical Artery Dysplasia).

PubMed

Plouin, Pierre-François; Baguet, Jean-Philippe; Thony, Frédéric; Ormezzano, Olivier; Azarine, Arshid; Silhol, François; Oppenheim, Catherine; Bouhanick, Béatrice; Boyer, Louis; Persu, Alexandre; Hammer, Frank; Gosse, Philippe; Mounier-Vehier, Claire; Le Hello, Claire; Jeunemaitre, Xavier; Azizi, Michel; Amar, Laurence; Chatellier, Gilles; Mousseaux, Elie; Touzé, Emmanuel

2017-09-01

Fibromuscular dysplasia (FMD) commonly affects the renal and cervical arteries but has been described to affect other vascular beds as well. The prevalence of and clinical characteristics associated with multisite FMD (string-of-beds or focal stenoses affecting at least 2 vascular beds) are not known. In the prospective ARCADIA registry (Assessment of Renal and Cervical Artery Dysplasia), symptomatic patients with renal artery (RA) FMD underwent tomographic- or magnetic resonance-angiography from the aortic arch to the intracranial arteries and those with cervical FMD from the diaphragm to the pelvis. Of 469 patients (84.0% women), 225 (48.0%) had multisite FMD. In addition, 86 of 244 patients with single-site disease had dissections or aneurisms affecting other vascular beds, totaling 311 patients (66.3%) with lesions in >1 vascular bed. Among patients with a cerebrovascular presentation, the prevalence of RA lesions was higher in patients with than in those without hypertension (odds ratio, 3.4; 95% confidence interval, 1.99-6.15). Among patients with a renal presentation, the prevalence of cervical lesions was higher in patients with bilateral than in those with unilateral RA lesions (odds ratio, 1.9; 95% confidence interval, 0.99-3.57). In conclusion, FMD is a systemic arterial disease. At least 2 vascular beds were affected by dysplastic stenoses in 48.0% of cases and by dysplastic stenoses, aneurysms, and dissections in 66.1% of cases. RA imaging should be proposed to hypertensive patients with a cerebrovascular presentation. Cervical artery imaging should be considered in patients with a renal presentation and bilateral RA lesions. URL: www.Clinicaltrials.gov. Unique identifier: NCT02884141. © 2017 American Heart Association, Inc.

The Association Between PD-L1 Expression and the Clinical Outcomes to Vascular Endothelial Growth Factor-Targeted Therapy in Patients With Metastatic Clear Cell Renal Cell Carcinoma

PubMed Central

Shin, Su-Jin; Jeon, Yoon Kyung; Cho, Yong Mee; Lee, Jae-Lyun; Chung, Doo Hyun; Park, Ji Young

2015-01-01

Background. Vascular endothelial growth factor pathway (VEGF)-tyrosine kinase inhibitors (TKIs) are used as the first-line treatment for patients with metastatic clear cell renal cell carcinoma (mCCRCC). Recently, programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1) blockade emerged as promising therapy for renal cell carcinoma. However, the expression pattern and prognostic implication of programmed death-ligands (PD-Ls) in mCCRCC patients receiving VEGF-TKI remain unclear. Patients and Methods. PD-L1 and PD-L2 expression in tumor cells and the quantities of PD-1+ tumor-infiltrating lymphocytes were immunohistochemically evaluated in 91 mCCRCC patients treated with VEGF-TKI, and their associations with VEGF-TKI responsiveness and clinical outcome were analyzed. Results. PD-L1 immunopositivity was observed in 17.6% and significantly associated with a high International Society of Urological Pathology grade (p = .031) and sarcomatoid features (p = .014). PD-L2 immunopositivity was observed in 39.6% and was not associated with any of the assessed clinicopathological variables. PD-L1-positive cases showed poor VEGF-TKI responsiveness (p = .012) compared with PD-L1-negative cases. In univariate survival analysis, PD-L1 immunopositivity was significantly associated with shorter overall survival (OS) (p = .037) and progression-free survival (PFS) (p = .043). Multivariate survival analysis revealed that PD-L1 expression was independently associated with poor OS (p = .038) and PFS (p = .013) in addition to tumor necrosis (p = .006; p = .029, respectively) and Memorial Sloan Kettering Cancer Center score (p = .018; p = .032, respectively). PD-L2 expression was neither associated with VEGF-TKI responsiveness nor patients’ outcome. Conclusion. PD-L1 expression was significantly related to lack of VEGF-TKI responsiveness and independently associated with shorter survival in mCCRCC patients after VEGF-TKI treatment. PD-L1 may have a predictive and prognostic value

The Renin-Angiotensin-Aldosterone System in Vascular Inflammation and Remodeling

PubMed Central

Pacurari, Maricica; Kafoury, Ramzi; Tchounwou, Paul B.; Ndebele, Kenneth

2014-01-01

The RAAS through its physiological effectors plays a key role in promoting and maintaining inflammation. Inflammation is an important mechanism in the development and progression of CVD such as hypertension and atherosclerosis. In addition to its main role in regulating blood pressure and its role in hypertension, RAAS has proinflammatory and profibrotic effects at cellular and molecular levels. Blocking RAAS provides beneficial effects for the treatment of cardiovascular and renal diseases. Evidence shows that inhibition of RAAS positively influences vascular remodeling thus improving CVD outcomes. The beneficial vascular effects of RAAS inhibition are likely due to decreasing vascular inflammation, oxidative stress, endothelial dysfunction, and positive effects on regeneration of endothelial progenitor cells. Inflammatory factors such as ICAM-1, VCAM-1, TNFα, IL-6, and CRP have key roles in mediating vascular inflammation and blocking RAAS negatively modulates the levels of these inflammatory molecules. Some of these inflammatory markers are clinically associated with CVD events. More studies are required to establish long-term effects of RAAS inhibition on vascular inflammation, vascular cells regeneration, and CVD clinical outcomes. This review presents important information on RAAS's role on vascular inflammation, vascular cells responses to RAAS, and inhibition of RAAS signaling in the context of vascular inflammation, vascular remodeling, and vascular inflammation-associated CVD. Nevertheless, the review also equates the need to rethink and rediscover new RAAS inhibitors. PMID:24804145

Endovascular management of arterial injuries after blunt or iatrogenic renal trauma

PubMed Central

Chevallier, Olivier; Gehin, Sophie; Midulla, Marco; Berthod, Pierre-Emmanuel; Galland, Christophe; Briche, Pascale; Duperron, Céline; Majbri, Nabil; Mousson, Christiane; Falvo, Nicolas

2017-01-01

The kidney is the third most common abdominal organ to be injured in trauma, following the spleen and liver, respectively. The most commonly used classification scheme is the American Association for the Surgery of Trauma (AAST) classification of blunt renal injuries, which grades renal injury according to the size of laceration and its proximity to the renal hilum. Arteriovenous fistula and pseudoaneurysm are the most common iatrogenic biopsy-related or surgery-related vascular injuries in native kidneys. The approach to renal artery injuries has changed over time from more aggressive intervention to more conservative observational or endovascular management, including selective transcatheter arterial embolization (TAE) and the placement of stents/stent grafts. In this article, we describe the role and technical aspects of endovascular interventions in the management of arterial injuries after blunt or iatrogenic renal trauma. PMID:28932700

Functional significance of the pattern of renal sympathetic nerve activation.

PubMed

Dibona, G F; Sawin, L L

1999-08-01

To assess the renal functional significance of the pattern of renal sympathetic nerve activation, computer-generated stimulus patterns (delivered at constant integrated voltage) were applied to the decentralized renal sympathetic nerve bundle and renal hemodynamic and excretory responses determined in anesthetized rats. When delivered at the same integrated voltage, stimulus patterns resembling those observed in in vivo multifiber recordings of renal sympathetic nerve activity (diamond-wave patterns) produced greater renal vasoconstrictor responses than conventional square-wave patterns. Within diamond-wave patterns, increasing integrated voltage by increasing amplitude produced twofold greater renal vasoconstrictor responses than by increasing duration. With similar integrated voltages that were subthreshold for renal vasoconstriction, neither diamond- nor square-wave pattern altered glomerular filtration rate, whereas diamond- but not square-wave pattern reversibly decreased urinary sodium excretion by 25 +/- 3%. At the same number of pulses per second, intermittent stimulation produced faster and greater renal vasoconstriction than continuous stimulation. At the same number of pulses per second, increases in rest period during intermittent stimulation proportionally augmented the renal vasoconstrictor response compared with that observed with continuous stimulation; the maximum augmentation of 55% occurred at a rest period of 500 ms. These results indicate that the pattern of renal sympathetic nerve stimulation (activity) significantly influences the rapidity, magnitude, and selectivity of the renal vascular and tubular responses.

Ameliorating activity of ginger (Zingiber officinale) extract against lead induced renal toxicity in male rats.

PubMed

Reddy, Y Amarnath; Chalamaiah, M; Ramesh, B; Balaji, G; Indira, P

2014-05-01

Lead poisoning has been known to be associated with structural and functional abnormalities of multiple organ systems of human body. The aim of this investigation was to study the renal protective effects of ginger (Zingiber officinale) extract in lead induced toxicity rats. In this study renal glutathione (GSH) level, glutathione peroxidase (GPX), glutathione-s-transferase (GST), and catalase enzymes were measured in lead nitrate (300 mg/kg BW), and lead nitrate plus ginger extract (150 mg/kg BW) treated rat groups for 1 week and 3 weeks respectively. The glutathione level and GSH dependent antioxidant enzymes such as glutathione peroxidase, glutathione-s-transferase, and catalase significantly (P < 0.05) increased in ginger extract treated rat groups. In addition, histological studies showed lesser renal changes in lead plus ginger extract treated rat groups than that of lead alone treated rat groups. These results indicate that ginger extract alleviated lead toxic effects by enhancing the levels of glutathione, glutathione peroxidase, glutathione-s-transferase and catalase.

Heme oxygenase: the key to renal function regulation

PubMed Central

Cao, Jian; Sacerdoti, David; Li, Xiaoying; Drummond, George

2009-01-01

Heme oxygenase (HO) plays a critical role in attenuating the production of reactive oxygen species through its ability to degrade heme in an enzymatic process that leads to the production of equimolar amounts of carbon monoxide and biliverdin/bilirubin and the release of free iron. The present review examines the beneficial role of HO-1 (inducible form of HO) that is achieved by increased expression of this enzyme in renal tissue. The influence of the HO system on renal physiology, obesity, vascular dysfunction, and blood pressure regulation is reviewed, and the clinical potential of increased levels of HO-1 protein, HO activity, and HO-derived end products of heme degradation is discussed relative to renal disease. The use of pharmacological and genetic approaches to investigate the role of the HO system in the kidney is key to the development of therapeutic approaches to prevent the adverse effects that accrue due to an impairment in renal function. PMID:19570878

Angiogenesis and expression of vascular endothelial growth factor, tumour necrosis factor-α and hypoxia inducible factor-1α in canine renal cell carcinoma.

PubMed

Yhee, J Y; Yu, C H; Kim, J H; Im, K S; Kim, N H; Brodersen, B W; Doster, A R; Sur, J-H

2012-01-01

The aim of the present study was to determine the distribution and characteristics of microvessels in various histological types of canine renal cell carcinoma (RCC). The study compared microvessel density (MVD) and distribution of blood vessels according to histological type and evaluated the presence of angiogenesis-related proteins. Nine archival samples of canine RCC were studied. MVD was calculated as the mean number of blood vessels per mm(2). The diameter of blood vessels was calculated by determining either the length of the long axis of blood vessels (diameter(max)) or the mean distance from the centre of each blood vessel to the tunica adventia (diameter(mean)). A significant difference in MVD was evident between RCCs and normal kidneys (46.6 ± 28.0 versus 8.4 ± 2.2 microvessels/mm(2)). Diameter(max) in canine RCCs (34.1 ± 14.7 μm) was also significantly different from normal canine kidney (23.2 ± 3.4 μm). Vascular endothelial growth factor (VEGF) was expressed by tumour cells and vascular endothelial cells and tumour necrosis factor (TNF)-α expression was observed in vascular endothelial cells in both neoplastic and normal kidney. Although VEGF is involved in angiogenesis and correlates with tumour stage of development, no correlation was found between VEGF expression and MVD. Tumour-associated macrophages expressing TNF-α and hypoxia inducible factor 1α were identified in peritumoural tissue and may play an important role in angiogenesis. Copyright © 2011 Elsevier Ltd. All rights reserved.

The renal response to electrical stimulation of renal efferent sympathetic nerves in the anaesthetized greyhound.

PubMed Central

Poucher, S M; Karim, F

1991-01-01

1. The effect of direct electrical stimulation of the renal efferent nerves upon renal haemodynamics and function was studied in greyhounds anaesthetized with chloralose and artificially ventilated. The left kidney was neurally and vascularly isolated, and perfused with blood from one of the femoral arteries at a constant pressure of 99 +/- 1 mmHg. Renal blood flow was measured with a cannulating electromagnetic flow probe placed in the perfusion circuit, glomerular filtration rate by creatinine clearance, urinary sodium excretion by flame photometry and solute excretion by osmometry. Beta-Adrenergic receptor activation was blocked by the infusion of dl-propranolol (17 micrograms kg-1 min-1). The peripheral ends of the ligated renal nerves were stimulated at 0.5, 1.0, 1.5 and 2.0 Hz. 2. At 0.5 Hz frequency only osmolar excretion was significantly reduced (10.3 +/- 3.2%, P less than 0.05, n = 6). Reductions in sodium excretion (53.6 +/- 8.5%, P less than 0.01, n = 6) and water excretion (26.9 +/- 8.0%, P less than 0.05, n = 6) and further reductions of osmolar excretion (20.7 +/- 3.7%, P less than 0.01, n = 6) were observed at 1.0 Hz; however, these were observed in the absence of significant changes in renal blood flow and glomerular filtration rate. Significant reductions were observed in glomerular filtration rate at 1.5 Hz (16.3 +/- 4.1%, P less than 0.02, n = 5) and in renal blood flow at 2.0 Hz (13.1 +/- 4.0%, P less than 0.05, n = 5). Further reductions in urine flow and sodium excretion were also observed at these higher frequencies. 3. These results clearly show that significant changes in renal tubular function can occur in the absence of changes in renal blood flow and glomerular filtration rate when the renal nerves are stimulated electrically from a zero baseline activity up to a frequency of 1.5 Hz. Higher frequencies caused significant changes in both renal haemodynamics and function. PMID:2023113

Wegener's granulomatosis presenting as multiple bilateral renal masses: case report and literature review.

PubMed

Frigui, Makram; Ben Hmida, Mohamed; Kechaou, Manel; Jlidi, Rachid; Bahloul, Zouhir

2009-04-01

Wegener's granulomatosis (WG) is a disease of unknown etiology characterized by necrotizing granulomatous vascularitis. The upper and lower respiratory tract and kidney involvements are very common; however, its presentation as bilateral renal masses is unusual. We report a case of a 59-year-old female patient who presented with multiple bilateral renal masses. The patient presented with sinusal and ocular symptoms suggestive of WG, and positive antineutrophil cytoplasmic antibodies (c-ANCA) with an anti-PR3 pattern. Histopathologic examination of the renal biopsy specimen revealed granulomatous inflammation with vasculitis and fibrinoid necrosis. The patient management, including prednisone and cyclophosphamid, induced a marked improvement of the renal masses. This case illustrates that WG should be considered in the differential diagnosis of renal masses.

The Role of Cell Swelling in Ischemic Renal Damage and the Protective Effect of Hypertonic Solute

PubMed Central

Flores, Jorge; DiBona, Donald R.; Beck, Clyde H.; Leaf, Alexander

1972-01-01

The failure of blood flow to return to the kidney following a transient period of ischemia has long been recognized. The cause of this “no-reflow” has been investigated in the rat after a transient period of total obstruction of the renal arteries. The vascular pattern of the kidneys as visualized with silicone rubber injection shows a diffuse patchy ischemia throughout the kidney, which persists after release of the obstructed renal artery. Electron microscopic studies of ischemic kidneys showed that all cellular elements were swollen and limiting the available vascular space. Functional studies revealed an increase in plasma urea nitrogen and creatinine after 1 hr or longer ischemic periods. The ischemia, cell swelling, “no-reflow,” and subsequent renal dysfunction occurring after obstruction to the renal arteries were corrected by the administration of hypertonic mannitol, but were unaffected by an equivalent expansion of the extracellular fluid volume either with isotonic saline or isotonic mannitol, showing that the osmotic effect was primary. The hypothesis is presented that ischemic swelling of cells may occlude small blood vessels so that recirculation does not resume even after the initial cause of the ischemia is no longer present; solutes which do not penetrate cell membranes are able to shrink swollen cells, increase the available vascular space and thus permit reflow of blood to the ischemic organ. Images PMID:5007042

Abscisic acid ameliorates experimental IBD by downregulating cellular adhesion molecule expression and suppressing immune cell infiltration.

PubMed

Guri, Amir J; Hontecillas, Raquel; Bassaganya-Riera, Josep

2010-12-01

Abscisic acid (ABA) has shown effectiveness in ameliorating inflammation in obesity, diabetes and cardiovascular disease models. The objective of this study was to determine whether ABA prevents or ameliorates experimental inflammatory bowel disease (IBD). C57BL/6J mice were fed diets with or without ABA (100mg/kg) for 35 days prior to challenge with 2.5% dextran sodium sulfate (DSS). The severity of clinical disease was assessed daily. Colonic mucosal lesions were evaluated by histopathology, and cellular adhesion molecular and inflammatory markers were assayed by real-time quantitative PCR. Flow cytometry was used to quantify leukocyte populations in the blood, spleen, and mesenteric lymph nodes (MLN). The effect of ABA on cytotoxic T-lymphocyte antigen 4 (CTLA-4) expression in splenocytes was also investigated. ABA significantly ameliorated disease activity, colitis and reduced colonic leukocyte infiltration and inflammation. These improvements were associated with downregulation in vascular cell adhesion marker-1 (VCAM-1), E-selectin, and mucosal addressin adhesion marker-1 (MAdCAM-1) expression. ABA also increased CD4(+) and CD8(+) T-lymphocytes in blood and MLN and regulatory T cells in blood. In vitro, ABA increased CTLA-4 expression through a PPAR γ-dependent mechanism. We conclude that ABA ameliorates gut inflammation by modulating T cell distribution and adhesion molecule expression. Copyright © 2010 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Abscisic acid ameliorates experimental IBD by downregulating cellular adhesion molecule expression and suppressing immune cell infiltration

PubMed Central

Guri, Amir J; Hontecillas, Raquel; Bassaganya-Riera, Josep

2010-01-01

Background & Aims Abscisic acid (ABA) has shown effectiveness in ameliorating inflammation in obesity, diabetes and cardiovascular disease models. The objective of this study was to determine whether ABA prevents or ameliorates experimental inflammatory bowel disease (IBD). Methods C57BL/6J mice were fed diets with or without ABA (100 mg/kg) for 35 days prior to challenge with 2.5% dextran sodium sulfate (DSS). The severity of clinical disease was assessed daily. Colonic mucosal lesions were evaluated by histopathology, and cellular adhesion molecular and inflammatory markers were assayed by real-time quantitative PCR. Flow cytometry was used to quantify leukocyte populations in the blood, spleen, and mesenteric lymph nodes (MLN). The effect of ABA on cytotoxic T-lymphocyte antigen 4 (CTLA-4) expression in splenocytes was also investigated. Results ABA significantly ameliorated disease activity, colitis and reduced colonic leukocyte infiltration and inflammation. These improvements were associated with down-regulation in vascular cell adhesion marker-1 (VCAM-1), E-selectin, and mucosal addressin adhesion marker-1 (MAdCAM-1) expression. ABA also increased CD4+ and CD8+ T-lymphocytes in blood and MLN and regulatory T-cells in blood. In vitro, ABA increased CTLA-4 expression through a PPAR γ-dependent mechanism. Conclusions We conclude that ABA ameliorates gut inflammation by modulating T cell distribution and adhesion molecule expression. PMID:20236740

Hand-assisted laparoscopic radical nephrectomy in the treatment of a renal cell carcinoma with a level II vena cava thrombus.

PubMed

Kovac, Jason R; Luke, Patrick P

2010-01-01

Excision of renal cell carcinoma (RCC) with corresponding vena cava thrombus is a technical challenge requiring open resection and vascular clamping. A 58 year old male with a right kidney tumor presented with a thrombus extending 1 cm into the vena cava. Using a hand-assisted transperitoneal approach through a 7 cm gel-port, the right kidney was dissected and the multiple vascular collaterals supplying the tumor were identified and isolated. The inferior vena cava was mobilized 4 cm cephalad and 4 cm caudal to the right renal vein. Lateral manual traction was applied to the right kidney allowing the tumor thrombus to be retracted into the renal vein, clear of the vena cava. After laparoscopic ultrasonographic confirmation of the location of the tip of the tumor thrombus, an articulating laparoscopic vascular stapler was used to staple the vena cava at the ostium of the right renal vein. This allowed removal of the tumor thrombus without the need for a Satinsky clamp. The surgery was completed in 243 minutes with no intra-operative complications. The entire kidney and tumor thrombus was removed with negative surgical margins. Estimated blood loss was 300 cc. We present a laparoscopic resection of a renal mass with associated level II thrombus using a hand-assisted approach. In patients with minimal caval involvement, our surgical approach presents an option to the traditional open resection of a renal mass.

Renal Tumor Necrosis Factor α Contributes to Hypertension in Dahl Salt-Sensitive Rats

PubMed Central

Huang, Baorui; Cheng, Yuan; Usa, Kristie; Liu, Yong; Baker, Maria Angeles; Mattson, David L.; He, Yongcheng; Wang, Niansong; Liang, Mingyu

2016-01-01

Tumor necrosis factor α (TNFα) is a major proinflammatory cytokine and its level is elevated in hypertensive states. Inflammation occurs in the kidneys during the development of hypertension. We hypothesized that TNFα specifically in the kidney contributes to the development of hypertension and renal injury in Dahl salt-sensitive (SS) rats, a widely used model of human salt-sensitive hypertension and renal injury. SS rats were chronically instrumented for renal interstitial infusion and blood pressure measurement in conscious, freely moving state. Gene expression was measured using real-time PCR and renal injury assessed with histological analysis. The abundance of TNFα in the renal medulla of SS rats, but not the salt-insensitive congenic SS.13BN26 rats, was significantly increased when rats had been fed a high-salt diet for 7 days (n = 6 or 9, p < 0.01). The abundance of TNFα receptors in the renal medulla was significantly higher in SS rats than SS.13BN26 rats. Renal interstitial administration of Etanercept, an inhibitor of TNFα, significantly attenuated the development of hypertension in SS rats on a high-salt diet (n = 7–8, p < 0.05). Glomerulosclerosis and interstitial fibrosis were also significantly ameliorated. These findings indicate intrarenal TNFα contributes to the development of hypertension and renal injury in SS rats. PMID:26916681

The lymphotoxin β receptor is a potential therapeutic target in renal inflammation.

PubMed

Seleznik, Gitta; Seeger, Harald; Bauer, Judith; Fu, Kai; Czerkowicz, Julie; Papandile, Adrian; Poreci, Uriana; Rabah, Dania; Ranger, Ann; Cohen, Clemens D; Lindenmeyer, Maja; Chen, Jin; Edenhofer, Ilka; Anders, Hans J; Lech, Maciej; Wüthrich, Rudolf P; Ruddle, Nancy H; Moeller, Marcus J; Kozakowski, Nicolas; Regele, Heinz; Browning, Jeffrey L; Heikenwalder, Mathias; Segerer, Stephan

2016-01-01

Accumulation of inflammatory cells in different renal compartments is a hallmark of progressive kidney diseases including glomerulonephritis (GN). Lymphotoxin β receptor (LTβR) signaling is crucial for the formation of lymphoid tissue, and inhibition of LTβR signaling has ameliorated several non-renal inflammatory models. Therefore, we tested whether LTβR signaling could also have a role in renal injury. Renal biopsies from patients with GN were found to express both LTα and LTβ ligands, as well as LTβR. The LTβR protein and mRNA were localized to tubular epithelial cells, parietal epithelial cells, crescents, and cells of the glomerular tuft, whereas LTβ was found on lymphocytes and tubular epithelial cells. Human tubular epithelial cells, mesangial cells, and mouse parietal epithelial cells expressed both LTα and LTβ mRNA upon stimulation with TNF in vitro. Several chemokine mRNAs and proteins were expressed in response to LTβR signaling. Importantly, in a murine lupus model, LTβR blockade improved renal function without the reduction of serum autoantibody titers or glomerular immune complex deposition. Thus, a preclinical mouse model and human studies strongly suggest that LTβR signaling is involved in renal injury and may be a suitable therapeutic target in renal diseases. Copyright © 2015 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Gender Difference in Renal Blood Flow Response to Angiotensin II Administration after Ischemia/Reperfusion in Rats: The Role of AT2 Receptor.

PubMed

Maleki, Maryam; Nematbakhsh, Mehdi

2016-01-01

Background. Renal ischemia/reperfusion (I/R) is one of the major causes of kidney failure, and it may interact with renin angiotensin system while angiotensin II (Ang II) type 2 receptor (AT2R) expression is gender dependent. We examined the role of AT2R blockade on vascular response to Ang II after I/R in rats. Methods. Male and female rats were subjected to 30 min renal ischemia followed by reperfusion. Two groups of rats received either vehicle or AT2R antagonist, PD123319. Mean arterial pressure (MAP), and renal blood flow (RBF) responses were assessed during graded Ang II (100, 300, and 1000 ng/kg/min, i.v.) infusion at controlled renal perfusion pressure (RPP). Results. Vehicle or antagonist did not alter MAP, RPP, and RBF levels significantly; however, 30 min after reperfusion, RBF decreased insignificantly in female treated with PD123319 (P = 0.07). Ang II reduced RBF and increased renal vascular resistance (RVR) in a dose-related fashion (P dose < 0.0001), and PD123319 intensified the reduction of RBF response in female (P group < 0.005), but not in male rats. Conclusion. The impact of the AT2R on vascular responses to Ang II in renal I/R injury appears to be sexually dimorphic. PD123319 infusion promotes these hemodynamic responses in female more than in male rats.

Testosterone Deficiency Accelerates Neuronal and Vascular Aging of SAMP8 Mice: Protective Role of eNOS and SIRT1

PubMed Central

Ota, Hidetaka; Akishita, Masahiro; Akiyoshi, Takuyu; Kahyo, Tomoaki; Setou, Mitsutoshi; Ogawa, Sumito; Iijima, Katsuya; Eto, Masato; Ouchi, Yasuyoshi

2012-01-01

Oxidative stress and atherosclerosis-related vascular disorders are risk factors for cognitive decline with aging. In a small clinical study in men, testosterone improved cognitive function; however, it is unknown how testosterone ameliorates the pathogenesis of cognitive decline with aging. Here, we investigated whether the cognitive decline in senescence-accelerated mouse prone 8 (SAMP8), which exhibits cognitive impairment and hypogonadism, could be reversed by testosterone, and the mechanism by which testosterone inhibits cognitive decline. We found that treatment with testosterone ameliorated cognitive function and inhibited senescence of hippocampal vascular endothelial cells of SAMP8. Notably, SAMP8 showed enhancement of oxidative stress in the hippocampus. We observed that an NAD+-dependent deacetylase, SIRT1, played an important role in the protective effect of testosterone against oxidative stress-induced endothelial senescence. Testosterone increased eNOS activity and subsequently induced SIRT1 expression. SIRT1 inhibited endothelial senescence via up-regulation of eNOS. Finally, we showed, using co-culture system, that senescent endothelial cells promoted neuronal senescence through humoral factors. Our results suggest a critical role of testosterone and SIRT1 in the prevention of vascular and neuronal aging. PMID:22238626

[Cooling shell in renal transplantation. Thermometric evaluation of a prototype].

PubMed

Desgrandchamps, F; Eugene, M; Tuchschmid, Y; Muller, F; Teillac, P; Idatte, J M; Le Duc, A

1996-02-01

We have developed a cooling system for renal transplants designed to eliminate the second period of warm ischaemia corresponding to the vascular anastomosis phase of renal transplantation. This is an autonomous and independent system which forms a shell around the transplant. Following application of the system, cooling is achieved by refrigeration of a Multitherm sponge contained in the wall of the shell. The thermometric characteristics of a prototype were evaluated in vitro and in vivo in pigs. This system allows the kidney to be preserved at a temperature of less than 10 degrees C for 1 hour without inducing any risk of lesions of the renal surface. Human applications should be developed in the near future.

Effects of taurine and housing density on renal function in laying hens*

PubMed Central

Ma, Zi-li; Gao, Yang; Ma, Hai-tian; Zheng, Liu-hai; Dai, Bin; Miao, Jin-feng; Zhang, Yuan-shu

2016-01-01

This study investigated the putative protective effects of supplemental 2-aminoethane sulfonic acid (taurine) and reduced housing density on renal function in laying hens. We randomly assigned fifteen thousand green-shell laying hens into three groups: a free range group, a low-density caged group, and a high-density caged group. Each group was further divided equally into a control group (C) and a taurine treatment group (T). After 15 d, we analyzed histological changes in kidney cells, inflammatory mediator levels, oxidation and anti-oxidation levels. Experimental data revealed taurine supplementation, and rearing free range or in low-density housing can lessen morphological renal damage, inflammatory mediator levels, and oxidation levels and increase anti-oxidation levels. Our data demonstrate that taurine supplementation and a reduction in housing density can ameliorate renal impairment, increase productivity, enhance health, and promote welfare in laying hens. PMID:27921400

Hydrogen sulfide ameliorates aging-associated changes in the kidney.

PubMed

Lee, Hak Joo; Feliers, Denis; Barnes, Jeffrey L; Oh, Sae; Choudhury, Goutam Ghosh; Diaz, Vivian; Galvan, Veronica; Strong, Randy; Nelson, James; Salmon, Adam; Kevil, Christopher G; Kasinath, Balakuntalam S

2018-04-01

Aging is associated with replacement of normal kidney parenchyma by fibrosis. Because hydrogen sulfide (H 2 S) ameliorates kidney fibrosis in disease models, we examined its status in the aging kidney. In the first study, we examined kidney cortical H 2 S metabolism and signaling pathways related to synthesis of proteins including matrix proteins in young and old male C57BL/6 mice. In old mice, increase in renal cortical content of matrix protein involved in fibrosis was associated with decreased H 2 S generation and AMPK activity, and activation of insulin receptor (IR)/IRS-2-Akt-mTORC1-mRNA translation signaling axis that can lead to increase in protein synthesis. In the second study, we randomized 18-19 month-old male C57BL/6 mice to receive 30 μmol/L sodium hydrosulfide (NaHS) in drinking water vs. water alone (control) for 5 months. Administration of NaHS increased plasma free sulfide levels. NaHS inhibited the increase in kidney cortical content of matrix proteins involved in fibrosis and ameliorated glomerulosclerosis. NaHS restored AMPK activity and inhibited activation of IR/IRS-2-Akt-mTORC1-mRNA translation axis. NaHS inhibited age-related increase in kidney cortical content of p21, IL-1β, and IL-6, components of the senescence-associated secretory phenotype. NaHS abolished increase in urinary albumin excretion seen in control mice and reduced serum cystatin C levels suggesting improved glomerular clearance function. We conclude that aging-induced changes in the kidney are associated with H 2 S deficiency. Administration of H 2 S ameliorates aging-induced kidney changes probably by inhibiting signaling pathways leading to matrix protein synthesis.

Molecular mechanisms and cell signaling of 20-hydroxyeicosatetraenoic acid in vascular pathophysiology

PubMed Central

Fan, Fan; Ge, Ying; Lv, Wenshan; Elliott, Matthew R.; Muroya, Yoshikazu; Hirata, Takashi; Booz, George W.; Roman, Richard J.

2016-01-01

Cytochrome P450s enzymes catalyze the metabolism of arachidonic acid to epoxyeicosatrienoic acids (EETs), dihydroxyeicosatetraenoic acid and hydroxyeicosatetraeonic acid (HETEs). 20-HETE is a vasoconstrictor that depolarizes vascular smooth muscle cells by blocking K+ channels. EETs serve as endothelial derived hyperpolarizing factors. Inhibition of the formation of 20-HETE impairs the myogenic response and autoregulation of renal and cerebral blood flow. Changes in the formation of EETs and 20-HETE have been reported in hypertension and drugs that target these pathways alter blood pressure in animal models. Sequence variants in CYP4A11 and CYP4F2 that produce 20-HETE, UDP-glucuronosyl transferase involved in the biotransformation of 20-HETE and soluble epoxide hydrolase that inactivates EETs are associated with hypertension in human studies. 20-HETE contributes to the regulation of vascular hypertrophy, restenosis, angiogenesis and inflammation. It also promotes endothelial dysfunction and contributes to cerebral vasospasm and ischemia-reperfusion injury in the brain, kidney and heart. This review will focus on the role of 20-HETE in vascular dysfunction, inflammation, ischemic and hemorrhagic stroke and cardiac and renal ischemia reperfusion injury. PMID:27100515

SU-E-QI-11: Measurement of Renal Pyruvate-To-Lactate Exchange with Hyperpolarized 13C MRI

DOE Office of Scientific and Technical Information (OSTI.GOV)

Adamson, E; Johnson, K; Fain, S

Purpose: Previous work [1] modeling the metabolic flux between hyperpolarized [1-13C]pyruvate and [1-13C]lactate in magnetic resonance spectroscopic imaging (MRSI) experiments failed to account for vascular signal artifacts. Here, we investigate a method to minimize the vascular signal and its impact on the fidelity of metabolic modeling. Methods: MRSI was simulated for renal metabolism in MATLAB both with and without bipolar gradients. The resulting data were fit to a two-site exchange model [1], and the effects of vascular partial volume artifacts on kinetic modeling were assessed. Bipolar gradients were then incorporated into a gradient echo sequence to validate the simulations experimentally.more » The degree of diffusion weighting (b = 32 s/mm{sup 2}) was determined empirically from 1H imaging of murine renal vascular signal. The method was then tested in vivo using MRSI with bipolar gradients following injection of hyperpolarized [1-{sup 13}C]pyruvate (∼80 mM at 20% polarization). Results: In simulations, vascular signal contaminated the renal metabolic signal at resolutions as high as 2 × 2 mm{sup 2} due to partial volume effects. The apparent exchange rate from pyruvate to lactate (k{sub p}) was underestimated in the presence of these artifacts due to contaminating pyruvate signal. Incorporation of bipolar gradients suppressed vascular signal and improved the accuracy of kp estimation. Experimentally, the in vivo results supported the ability of bipolar gradients to suppress vascular signal. The in vivo exchange rate increased, as predicted in simulations, from k{sub p} = 0.012 s-{sup 1} to k{sub p} = 0.020-{sup 1} after vascular signal suppression. Conclusion: We have demonstrated the limited accuracy of the two-site exchange model in the presence of vascular partial volume artifacts. The addition of bipolar gradients suppressed vascular signal and improved model accuracy in simulations. Bipolar gradients largely affected kp estimation in vivo

Impact of Iodinated Contrast on Renal Function and Hemodynamics in Rats with Chronic Hyperglycemia and Chronic Kidney Disease

PubMed Central

Fernandes, Sheila Marques; Martins, Daniel Malisani; da Fonseca, Cassiane Dezoti; Watanabe, Mirian; Vattimo, Maria de Fátima Fernandes

2016-01-01

Iodinated contrast (IC) is clinically used in diagnostic and interventional procedures, but its use can result in contrast-induced acute kidney injury (CI-AKI). Chronic kidney disease (CKD) and chronic hyperglycemia (CH) are important predisposing factors to CI-AKI. The aim of this study was to investigate the impact of iodinated contrast on the renal function and hemodynamics in rats with chronic hyperglycemia and chronic kidney disease. A total of 30 rats were divided into six groups; Sham: control of chronic renal disease; Citrate: control of chronic hyperglycemia (CH); Nx5/6: rats with 5/6 nephrectomy; Chronic Hyperglycemia: rats receiving Streptozotocin 65 mg/kg; Nx5/6 + IC: rats Nx5/6 received 6 mL/kg of IC; CH + IC: Chronic hyperglycemia rats receiving 6 mL/kg of IC. Renal function (inulin clearance; urinary neutrophil gelatinase-associated lipocalin, NGAL) and hemodynamics (arterial blood pressure; renal blood flow; renal vascular resistance) were evaluated. Iodinated contrast significantly increased urinary NGAL and reduced inulin clearance, while the hemodynamics parameters showed changes in arterial blood pressure, renal blood flow, and renal vascular resistance in both CKD and CH groups. The results suggest that the iodinated contrast in risk factors models has important impact on renal function and hemodynamics. NGAL was confirmed to play a role of highlight in diagnosis of CI-AKI. PMID:27034930

Metastatic renal cell carcinoma in the nasopharynx.

PubMed

Atar, Yavuz; Topaloglu, Ilhan; Ozcan, Deniz

2013-01-01

Metastatic renal cell carcinoma of the nasopharynx, nasal cavity, and paranasal sinuses can be misdiagnosed as primary malignant or benign diseases. A 33-year-old male attended our outpatient clinic complaining of difficulty breathing through the nose, bloody nasal discharge, postnasal drop, snoring, and discharge of phlegm. Endoscopic nasopharyngeal examination showed a vascularized nasopharyngeal mass. Under general anesthesia, multiple punch biopsies were taken from the nasopharynx. Pathologically, the tumor cells had clear cytoplasm and were arranged in a trabecular pattern lined by a layer of endothelial cells. After the initial pathological examination, the pathologist requested more information about the patient's clinical status. A careful history revealed that the patient had undergone left a nephrectomy for a kidney mass diagnosed as renal cell carcinoma 3 years earlier. Subsequently, nasopharyngeal metastatic renal cell carcinoma was diagnosed by immunohistochemical staining with CD10 and vimentin. Radiotherapy was recommended for treatment.

Mechanistic insights into the vascular effects of blueberries: Evidence from recent studies.

PubMed

Cutler, Brett Ronald; Petersen, Chrissa; Anandh Babu, Pon Velayutham

2017-06-01

Cardiovascular disease is the leading cause of death in the United States. Dietary habits influence a variety of cardiovascular complications such as peripheral artery disease, heart failure, and kidney disease. We along with others have previously reported the cardiovascular beneficial effects of dietary flavonoids. Anthocyanins, one class of flavonoids widely available in berries, have recently drawn wide scientific attention because of their diverse health benefits. Epidemiological, clinical, and animal studies indicate that blueberry anthocyanins exert protection against cardiovascular complications by acting on multiple targets in the vascular system. These include activating endothelial nitric oxide synthase signaling, reducing oxidative stress, improving inflammatory pathways, and ameliorating dyslipidemia. Anthocyanins are extensively metabolized in humans suggesting that their vascular benefits are likely mediated by their circulating metabolites. However, the bioactivities of blueberry metabolites are unknown. Evaluating the bioactivities of metabolites, analyzing their structure-activity relationship, and well-designed human trials are needed to understand the potential vascular effects of blueberries and their metabolites. Understanding the vascular effects will provide a solid scientific foundation to recommend blueberries to improve vascular health. This review highlights the recent developments in the understanding of the vascular effects of blueberries with special emphasis on the molecular mechanisms involved. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Renal vascular lesions as a marker of poor prognosis in patients with lupus nephritis. Gruppo Italiano per lo Studio della Nefrite Lupica (GISNEL).

PubMed

Banfi, G; Bertani, T; Boeri, V; Faraggiana, T; Mazzucco, G; Monga, G; Sacchi, G

1991-08-01

The frequency of renal vascular lesions (RVL) and their relevance in the progression of renal damage were evaluated by the Pathology Group of the "Gruppo Italiano per lo Studio della Nefrite Lupica" (GISNEL). Of 285 patients with lupus nephritis collected from 20 nephrology centers in Italy and classified according to World Health Organization (WHO) criteria, 79 cases (27.7%) with RVL were identified and classified as follows: (1) lupus vasculopathy (n = 27); (2) hemolytic-uremic syndrome/thrombotic thrombocytopenic purpura (HUS/TTP) malignant hypertension-like lesions (n = 24); (3) vasculitis (n = 8); (4) arterio-arteriosclerosis (n = 20). At the time of renal biopsy, patients with RVL had mean serum creatinine levels significantly higher than patients without RVL (201.8 +/- 195.9 mumol/L [2.2 +/- 2.2 mg/dL] v 108.1 +/- 108.0 mumol/L [1.2 +/- 1.2 mg/dL]; P less than 0.01). Hypertension was more frequent in patients with RVL than in those without (68.4% v 30.5%; P less than 0.01). The probability of kidney survival assessed according to the Kaplan-Meier method at 5 and 10 years was, respectively, 74.3% +/- 5.9% and 58.0% +/- 8.9% in patients with RVL, compared with 89.6% +/- 2.7% and 85.9% +/- 3.7% in patients without RVL. However, the two groups did not differ significantly as regards overall survival, the probability of survival at 5 and 10 years being 86.5% +/- 4.5% and 78.8% +/- 6.6% in patients with RVL and 92.2% +/- 2.2% and 83.3% +/- 4.4% in patients without RVL.(ABSTRACT TRUNCATED AT 250 WORDS)

Albumin stimulates renal tubular inflammation through an HSP70-TLR4 axis in mice with early diabetic nephropathy

PubMed Central

Jheng, Huei-Fen; Tsai, Pei-Jane; Chuang, Yi-Lun; Shen, Yi-Ting; Tai, Ting-An; Chen, Wen-Chung; Chou, Chuan-Kai; Ho, Li-Chun; Tang, Ming-Jer; Lai, Kuei-Tai A.; Sung, Junne-Ming; Tsai, Yau-Sheng

2015-01-01

ABSTRACT Increased urinary albumin excretion is not simply an aftermath of glomerular injury, but is also involved in the progression of diabetic nephropathy (DN). Whereas Toll-like receptors (TLRs) are incriminated in the renal inflammation of DN, whether and how albumin is involved in the TLR-related renal inflammatory response remains to be clarified. Here, we showed that both TLR2 and TLR4, one of their putative endogenous ligands [heat shock protein 70 (HSP70)] and nuclear factor-κB promoter activity were markedly elevated in the kidneys of diabetic mice. A deficiency of TLR4 but not of TLR2 alleviated albuminuria, tubulointerstitial fibrosis and inflammation induced by diabetes. The protection against renal injury in diabetic Tlr4−/− mice was associated with reduced tubular injuries and preserved cubilin levels, rather than amelioration of glomerular lesions. In vitro studies revealed that albumin, a stronger inducer than high glucose (HG), induced the release of HSP70 from proximal tubular cells. HSP70 blockade ameliorated albumin-induced inflammatory mediators. HSP70 triggered the production of inflammatory mediators in a TLR4-dependent manner. Moreover, HSP70 inhibition in vivo ameliorated diabetes-induced albuminuria, inflammatory response and tubular injury. Finally, we found that individuals with DN had higher levels of TLR4 and HSP70 in the dilated tubules than non-diabetic controls. Thus, activation of the HSP70-TLR4 axis, stimulated at least in part by albumin, in the tubular cell is a newly identified mechanism associated with induction of tubulointerstitial inflammation and aggravation of pre-existing microalbuminuria in the progression of DN. PMID:26398934

Renovascular disease, microcirculation, and the progression of renal injury: role of angiogenesis

PubMed Central

2011-01-01

Emerging evidence supports the pivotal role of renal microvascular disease as a determinant of tubulo-interstitial and glomerular fibrosis in chronic kidney disease. An intact microcirculation is vital to restore blood flow to the injured tissues, which is a crucial step to achieve a successful repair response. The purpose of this review is to discuss the impact and mechanisms of the functional and structural changes of the renal microvascular network, as well as the role of these changes in the progression and irreversibility of renal injury. Damage of the renal microcirculation and deterioration of the angiogenic response may constitute early steps in the complex pathways involved in progressive renal injury. There is limited but provocative evidence that stimulation of vascular proliferation and repair may stabilize renal function and slow the progression of renal disease. The feasibility of novel potential therapeutic interventions for stabilizing the renal microvasculature is also discussed. Targeted interventions to enhance endogenous renoprotective mechanisms focused on the microcirculation, such as cell-based therapy or the use of angiogenic cytokines have shown promising results in some experimental and clinical settings. PMID:21307362

Emodin ameliorates high glucose induced-podocyte epithelial-mesenchymal transition in-vitro and in-vivo.

PubMed

Chen, Tingfang; Zheng, Li Yang; Xiao, Wenzhen; Gui, Dingkun; Wang, Xiaoxia; Wang, Niansong

2015-01-01

Epithelial-to-mesenchymal transition (EMT) is a potential pathway leading to podocyte depletion and proteinuria in diabetic kidney disease (DKD). Here, we investigated the protective effects of Emodin (EMO) on high glucose (HG) induced-podocyte EMT in-vitro and in-vivo. Conditionally immortalized mouse podocytes were exposed to HG with 30 μg /ml of EMO and 1 μmol/ml of integrin-linked kinase (ILK) inhibitor QLT0267 for 24 h. Streptozotocin (STZ)-induced diabetic rats were treated with EMO at 20 mg· kg(-1)· d(-1) and QLT0267 at 10 mg· kg(-1)· w(-1) p.o., for 12 weeks. Albuminuria and blood glucose level were measured. Immunohistochemistry, immunofluorescence, western blotting and real-time PCR were used to detect expression of ILK, the epithelial marker of nephrin and the mesenchymal marker of desmin in-vitro and in-vivo. HG increased podocyte ILK and desmin expression while decreased nephrin expression. However, EMO significantly inhibited ILK and desmin expression and partially restored nephrin expression in HG-stimulated podocytes. These in-vitro observations were further confirmed in-vivo. Treatment with EMO for 12 weeks attenuated albuminuria, renal histopathology and podocyte foot process effacement in diabetic rats. EMO also repressed renal ILK and desmin expression, preserved nephrin expression, as well as ameliorated albuminuria in STZ-induced diabetic rats. EMO ameliorated glucose-induced EMT and subsequent podocyte dysfunction partly through ILK and desmin inhibition as well as nephrin upregulatiotion, which might provide a potential novel therapeutic option for DKD. © 2015 S. Karger AG, Basel.

Adjuvant Vascular Endothelial Growth Factor-targeted Therapy in Renal Cell Carcinoma: A Systematic Review and Pooled Analysis.

PubMed

Sun, Maxine; Marconi, Lorenzo; Eisen, Tim; Escudier, Bernard; Giles, Rachel H; Haas, Naomi B; Harshman, Lauren C; Quinn, David I; Larkin, James; Pal, Sumanta K; Powles, Thomas; Ryan, Christopher W; Sternberg, Cora N; Uzzo, Robert; Choueiri, Toni K; Bex, Axel

2018-05-18

Contradictory data exist with regard to adjuvant vascular endothelial growth factor receptor (VEGFR)-targeted therapy in surgically managed patients for localized renal cell carcinoma (RCC). To systematically evaluate the current evidence regarding the therapeutic benefit (disease-free survival [DFS] and overall survival [OS]) and grade 3-4 adverse events (AEs) for adjuvant VEGFR-targeted therapy for resected localized RCC. A critical review of PubMed/Medline, Embase, and the Cochrane Library in January 2018 according to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement was performed. We identified reports and reviewed them according to the Consolidated Standards of Reporting Trials and Standards for the Reporting of Diagnostic Accuracy Studies criteria. Of eight full-text articles that were eligible for inclusion, five studies (two of five were updated analyses) were retained in the final synthesis. Study characteristics were abstracted and the number needed to treat (NNT) per trial was estimated. The three randomized controlled phase III trials included the following comparisons: sunitinib versus placebo or sorafenib versus placebo (Adjuvant Sorafenib or Sunitinib for Unfavorable Renal Carcinoma [ASSURE] study, n=1943), sunitinib versus placebo (S-TRAC, n=615), and pazopanib versus placebo (Pazopanib As Adjuvant Therapy in Localized/Locally Advanced RCC After Nephrectomy study, n=1135). The NNT ranged from 10 (S-TRAC) to 137 (ASSURE study). The pooled analysis showed that VEGFR-targeted therapy was not statistically significantly associated with improved DFS (hazard ratio [HR random ]: 0.92, 95% confidence interval [CI]: 0.82-1.03, p=0.16) or OS (HR random : 0.98, 95% CI: 0.84-1.15, p=0.84) compared with the control group. The adjuvant therapy group experienced significantly higher odds of grade 3-4 AEs (OR random : 5.89, 95% CI: 4.85-7.15, p<0.001). In exploratory analyses focusing on patients who started on the full

Anatomical variations of hepatic arterial system, coeliac trunk and renal arteries: an analysis with multidetector CT angiography.

PubMed

Ugurel, M S; Battal, B; Bozlar, U; Nural, M S; Tasar, M; Ors, F; Saglam, M; Karademir, I

2010-08-01

The purpose of our investigation was to determine the anatomical variations in the coeliac trunk-hepatic arterial system and the renal arteries in patients who underwent multidetector CT (MDCT) angiography of the abdominal aorta for various reasons. A total of 100 patients were analysed retrospectively. The coeliac trunk, hepatic arterial system and renal arteries were analysed individually and anatomical variations were recorded. Statistical analysis of the relationship between hepatocoeliac variations and renal artery variations was performed using a chi(2) test. There was a coeliac trunk trifurcation in 89% and bifurcation in 8% of the cases. Coeliac trunk was absent in 1%, a hepatosplenomesenteric trunk was seen in 1% and a splenomesenteric trunk was present in 1%. Hepatic artery variation was present in 48% of patients. Coeliac trunk and/or hepatic arterial variation was present in 23 (39.7%) of the 58 patients with normal renal arteries, and in 27 (64.3%) of the 42 patients with accessory renal arteries. There was a statistically significant correlation between renal artery variations and coeliac trunk-hepatic arterial system variations (p = 0.015). MDCT angiography permits a correct and detailed evaluation of hepatic and renal vascular anatomy. The prevalence of variations in the coeliac trunk and/or hepatic arteries is increased in people with accessory renal arteries. For that reason, when undertaking angiographic examinations directed towards any single organ, the possibility of variations in the vascular structure of other organs should be kept in mind.

Vascular effects of aldosterone: sorting out the receptors and the ligands.

PubMed

Feldman, Ross D; Gros, Robert

2013-12-01

Aldosterone has actions far beyond its role as a renal regulator of sodium reabsorption, and broader mechanisms of action than simply a transcriptional regulator. Aldosterone has a number of vascular effects, including regulation of vascular reactivity and vascular growth and/or development. Aldosterone-mediated effects on vascular reactivity reflect a balance between its endothelial-dependent vasodilator effects and its direct smooth muscle vasoconstrictor effects. The endothelial vasodilator effects of aldosterone are mediated by phosphatidylinositol 3-kinase-dependent activation of nitric oxide synthase. G-Protein oestrogen receptor (GPER) is a recently recognized G-protein coupled receptor (GPCR) that is activated by steroid hormones. It was first recognized as the GPCR mediating the rapid effects of oestrogens. Activation of GPER also mediates at least some of the vascular effects of aldosterone in smooth muscle and endothelial cells. In vascular endothelial cells, aldosterone activation of GPER mediates vasodilation. In contrast, activation of endothelial mineralocorticoid receptors has been linked to enhanced vasoconstrictor and/or impaired vasodilator responses. © 2013 Wiley Publishing Asia Pty Ltd.

Inhibitor of G protein-coupled receptor kinase 2 normalizes vascular endothelial function in type 2 diabetic mice by improving β-arrestin 2 translocation and ameliorating Akt/eNOS signal dysfunction.

PubMed

Taguchi, Kumiko; Matsumoto, Takayuki; Kamata, Katsuo; Kobayashi, Tsuneo

2012-07-01

In type 2 diabetes, although Akt/endothelial NO synthase (eNOS) activation is known to be negatively regulated by G protein-coupled receptor kinase 2 (GRK2), it is unclear whether the GRK2 inhibitor would have therapeutic effects. Here we examined the hypotensive effect of the GRK2 inhibitor and its efficacy agonist both vascular (aortic) endothelial dysfunction (focusing especially on the Akt/eNOS pathway) and glucose intolerance in two type 2 diabetic models (ob/ob mice and nicotinamide+streptozotocin-induced diabetic mice). Mice were treated with a single injection of the GRK2 inhibitor or vehicle, and the therapeutic effects were compared by examining vascular function and by Western blotting. The GRK2 inhibitor lowered blood pressure in both diabetic models but not in their age-matched controls. The GRK2 inhibitor significantly improved clonidine-induced relaxation only in diabetic (ob/ob and DM) mice, with accompanying attenuations of GRK2 activity and translocation to the plasma membrane. These protective effects of the GRK2 inhibitor may be attributable to the augmented Akt/eNOS pathway activation (as evidenced by increases in Akt phosphorylation at Ser(473) and at Thr(308), and eNOS phosphorylation at Ser(1177)) and to the prevention of the GRK2 translocation and promotion of β-arrestin 2 translocation to the membrane under clonidine stimulation. Moreover, the GRK2 inhibitor significantly improved the glucose intolerance seen in the ob/ob mice. Our work provides the first evidence that in diabetes, the GRK2 inhibitor ameliorates vascular endothelial dysfunction via the Akt/eNOS pathway by inhibiting GRK2 activity and enhancing β-arrestin 2 translocation under clonidine stimulation, thereby contributing to a blood pressure-lowering effect. We propose that the GRK2 inhibitor may be a promising therapeutic agent for cardiovascular complications in type 2 diabetes.

Allopurinol attenuates rhabdomyolysis-associated acute kidney injury: Renal and muscular protection.

PubMed

Gois, Pedro H F; Canale, Daniele; Volpini, Rildo A; Ferreira, Daniela; Veras, Mariana M; Andrade-Oliveira, Vinicius; Câmara, Niels O S; Shimizu, Maria H M; Seguro, Antonio C

2016-12-01

Acute kidney injury (AKI) is the most severe complication of rhabdomyolysis. Allopurinol (Allo), a xanthine oxidase inhibitor, has been in the spotlight in the last decade due to new therapeutic applications related to its potent antioxidant effect. The aim of this study was to evaluate the efficacy of Allo in the prevention and treatment of rhabdomyolysis-associated AKI. Male Wistar rats were divided into five groups: saline control group; prophylactic Allo (300mg/L of drinking water, 7 days); glycerol (50%, 5ml/kg, IM); prophylactic Allo + glycerol; and therapeutic Allo (50mg/Kg, IV, 30min after glycerol injection) + glycerol. Glycerol-injected rats showed markedly reduced glomerular filtration rate associated with renal vasoconstriction, renal tubular damage, increased oxidative stress, apoptosis and inflammation. Allo ameliorated all these alterations. We found 8-isoprostane-PGF 2a (F2-IsoP) as a main factor involved in the oxidative stress-mediated renal vasoconstriction following rhabdomyolysis. Allo reduced F2-IsoP renal expression and restored renal blood flow. Allo also reduced oxidative stress in the damaged muscle, attenuated muscle lesion/inflammation and accelerated muscular recovery. Moreover, we showed new insights into the pathogenesis of rhabdomyolysis-associated AKI, whereas Allo treatment reduced renal inflammation by decreasing renal tissue uric acid levels and consequently inhibiting the inflammasome cascade. Allo treatment attenuates renal dysfunction in a model of rhabdomyolysis-associated AKI by reducing oxidative stress (systemic, renal and muscular), apoptosis and inflammation. This may represent a new therapeutic approach for rhabdomyolysis-associated AKI - a new use for an old and widely available medication. Copyright © 2016 Elsevier Inc. All rights reserved.

Sinomenine Hydrochloride Attenuates Renal Fibrosis by Inhibiting Excessive Autophagy Induced by Adriamycin: An Experimental Study

PubMed Central

Zhao, Ming-ming

2017-01-01

The objective of this study is to investigate if sinomenine hydrochloride (SIN-HCl) could be effective against adriamycin-induced renal fibrosis by regulating autophagy in a rat model. Forty male Sprague-Dawley (SD) rats were randomly divided into control group, model group, telmisartan group, and SIN-HCl group; rat model was induced by adriamycin; all rats were given intragastric administration for 6 weeks. Urine was collected from rats in metabolic cages to determine 24 h protein level. This was done after intragastric administration for the first two weeks and then once for every two weeks. Renal pathological changes were examined by the staining of HE, Masson, and PASM. Expressions and distributions of fibronectin (FN), laminin (LN), light chain 3 (LC3), and Beclin-1 were observed by immunohistochemistry. SIN-HCl ameliorates proteinuria, meanwhile attenuating the renal pathological changes in adriamycin-induced rats and also attenuating renal fibrosis and excessive autophagy by reducing the expression of FN, LN, LC3, and Beclin-1. SIN-HCl attenuates renal fibrosis by inhibiting excessive autophagy induced by adriamycin and upregulates the basal autophagy. PMID:28798804

[Renal angiomyolipoma rupture as a cause of lumbar pain: report of one case].

PubMed

Cifuentes, Melissa; Calleja, Félix; Hola, José; Daviú, Antonio; Jara, Danilo; Vallejos, Humberto

2008-08-01

Renal angiomyolipoma is a benign tumor formed by smooth muscle, adipose tissue and blood vessels. It is commonly found incidentally and its clinical manifestations are pain and abdominal mass or spontaneous tumor rupture with retroperitoneal bleeding. The clinical presentation of a hemorrhagic shock secondary to a retroperitoneal hematoma is uncommon. We report a 40 year-old male who presented to the emergency room with lumbar pain and deterioration of hemodynamic parameters. The CT scan showed a left renal injury associated to an expansive retroperitoneal process. The abdominal exploration, vascular control of the renal pedicle and nephrectomy allowed a successful outcome.

A Role for Cytosolic Fumarate Hydratase in Urea Cycle Metabolism and Renal Neoplasia

PubMed Central

Adam, Julie; Yang, Ming; Bauerschmidt, Christina; Kitagawa, Mitsuhiro; O’Flaherty, Linda; Maheswaran, Pratheesh; Özkan, Gizem; Sahgal, Natasha; Baban, Dilair; Kato, Keiko; Saito, Kaori; Iino, Keiko; Igarashi, Kaori; Stratford, Michael; Pugh, Christopher; Tennant, Daniel A.; Ludwig, Christian; Davies, Benjamin; Ratcliffe, Peter J.; El-Bahrawy, Mona; Ashrafian, Houman; Soga, Tomoyoshi; Pollard, Patrick J.

2013-01-01

Summary The identification of mutated metabolic enzymes in hereditary cancer syndromes has established a direct link between metabolic dysregulation and cancer. Mutations in the Krebs cycle enzyme, fumarate hydratase (FH), predispose affected individuals to leiomyomas, renal cysts, and cancers, though the respective pathogenic roles of mitochondrial and cytosolic FH isoforms remain undefined. On the basis of comprehensive metabolomic analyses, we demonstrate that FH1-deficient cells and tissues exhibit defects in the urea cycle/arginine metabolism. Remarkably, transgenic re-expression of cytosolic FH ameliorated both renal cyst development and urea cycle defects associated with renal-specific FH1 deletion in mice. Furthermore, acute arginine depletion significantly reduced the viability of FH1-deficient cells in comparison to controls. Our findings highlight the importance of extramitochondrial metabolic pathways in FH-associated oncogenesis and the urea cycle/arginine metabolism as a potential therapeutic target. PMID:23643539

Spanish Clinical Guidelines on Vascular Access for Haemodialysis.

PubMed

Ibeas, José; Roca-Tey, Ramon; Vallespín, Joaquín; Moreno, Teresa; Moñux, Guillermo; Martí-Monrós, Anna; Del Pozo, José Luis; Gruss, Enrique; Ramírez de Arellano, Manel; Fontseré, Néstor; Arenas, María Dolores; Merino, José Luis; García-Revillo, José; Caro, Pilar; López-Espada, Cristina; Giménez-Gaibar, Antonio; Fernández-Lucas, Milagros; Valdés, Pablo; Fernández-Quesada, Fidel; de la Fuente, Natalia; Hernán, David; Arribas, Patricia; Sánchez de la Nieta, María Dolores; Martínez, María Teresa; Barba, Ángel

2017-11-01

Vascular access for haemodialysis is key in renal patients both due to its associated morbidity and mortality and due to its impact on quality of life. The process, from the creation and maintenance of vascular access to the treatment of its complications, represents a challenge when it comes to decision-making, due to the complexity of the existing disease and the diversity of the specialities involved. With a view to finding a common approach, the Spanish Multidisciplinary Group on Vascular Access (GEMAV), which includes experts from the five scientific societies involved (nephrology [S.E.N.], vascular surgery [SEACV], vascular and interventional radiology [SERAM-SERVEI], infectious diseases [SEIMC] and nephrology nursing [SEDEN]), along with the methodological support of the Cochrane Center, has updated the Guidelines on Vascular Access for Haemodialysis, published in 2005. These guidelines maintain a similar structure, in that they review the evidence without compromising the educational aspects. However, on one hand, they provide an update to methodology development following the guidelines of the GRADE system in order to translate this systematic review of evidence into recommendations that facilitate decision-making in routine clinical practice, and, on the other hand, the guidelines establish quality indicators which make it possible to monitor the quality of healthcare. Copyright © 2017 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

Renin-angiotensin system (RAS) blockade attenuates growth and metastatic potential of renal cell carcinoma in mice.

PubMed

Araújo, Wedson F; Naves, Marcelo A; Ravanini, Juliana N; Schor, Nestor; Teixeira, Vicente P C

2015-09-01

Renal cell carcinoma (RCC) is the most frequent type of cancer among renal neoplasms in adults and responds poorly to radiotherapy and chemotherapy. There is evidence that blockade of the renin-angiotensin system (RAS) might have antineoplastic effects. The aim of this study was to investigate the effects of RAS blockade on RCC in a murine model. Murine renal cancer cells (Renca) were injected (1 × 10(5)) into the subcapsular space of the left kidney of BALB/c mice (8 wk of age). The animals were divided into 4 groups: a control group (no treatment), angiotensin-receptor blockers group (losartan 100mg/kg/d), angiotensin-converting enzyme inhibitor group (captopril 10mg/kg/d), and angiotensin-receptor blockers +angiotensin-converting enzyme inhibitor group (losartan 100mg/kg/d +captopril 10mg/kg/d). The animals received the drugs by gavage for 21 days after inoculation, beginning 2 days before tumor induction, and were then euthanized. After killing the animals, the kidneys and lungs were removed, weighed, and processed for histopathological and immunohistochemical analyses. Angiogenesis and vascular microvessels were assessed with the antibodies anti-vascular endothelial growth factor and anti-CD34. Angiotensin II-inoculated animals developed renal tumors. Treated animals presented smaller tumors, regardless of the therapeutic regimen, and far fewer lung metastases in both quantity and dimension compared with the controls. The expression of vascular endothelial growth factor and CD34 were significantly decreased in renal tumors of treated animals compared with the controls. Our findings suggest that blockade of RAS decreases tumor proliferation and metastatic capacity of RCC in this experimental model. Copyright © 2015 Elsevier Inc. All rights reserved.

Energy-Specific Optimization of Attenuation Thresholds for Low-Energy Virtual Monoenergetic Images in Renal Lesion Evaluation.

PubMed

Patel, Bhavik N; Farjat, Alfredo; Schabel, Christoph; Duvnjak, Petar; Mileto, Achille; Ramirez-Giraldo, Juan Carlos; Marin, Daniele

2018-05-01

The purpose of this study was to determine in vitro and in vivo the optimal threshold for renal lesion vascularity at low-energy (40-60 keV) virtual monoenergetic imaging. A rod simulating unenhanced renal parenchymal attenuation (35 HU) was fitted with a syringe containing water. Three iodinated solutions (0.38, 0.57, and 0.76 mg I/mL) were inserted into another rod that simulated enhanced renal parenchyma (180 HU). Rods were inserted into cylindric phantoms of three different body sizes and scanned with single- and dual-energy MDCT. In addition, 102 patients (32 men, 70 women; mean age, 66.8 ± 12.9 [SD] years) with 112 renal lesions (67 nonvascular, 45 vascular) measuring 1.1-8.9 cm underwent single-energy unenhanced and contrast-enhanced dual-energy CT. Optimal threshold attenuation values that differentiated vascular from nonvascular lesions at 40-60 keV were determined. Mean optimal threshold values were 30.2 ± 3.6 (standard error), 20.9 ± 1.3, and 16.1 ± 1.0 HU in the phantom, and 35.9 ± 3.6, 25.4 ± 1.8, and 17.8 ± 1.8 HU in the patients at 40, 50, and 60 keV. Sensitivity and specificity for the thresholds did not change significantly between low-energy and 70-keV virtual monoenergetic imaging (sensitivity, 87-98%; specificity, 90-91%). The AUC from 40 to 70 keV was 0.96 (95% CI, 0.93-0.99) to 0.98 (95% CI, 0.95-1.00). Low-energy virtual monoenergetic imaging at energy-specific optimized attenuation thresholds can be used for reliable characterization of renal lesions.

[Volume Homeostasis and Renal Function in Rats Exposed to Simulated and Actual Microgravity

NASA Technical Reports Server (NTRS)

Tucker, Bryan J.

1993-01-01

This project has investigated mechanisms that influence alterations in compartmental fluid and electrolyte balance in microgravity and evaluates countermeasures to control renal fluid and electrolyte losses. Determining the alterations due to space flight in fluid compartments and renal function is an important component in understanding long term adaptation to spaceflight and the contribution to post-flight orthostatic intolerance. Four definition phase studies and two studies examining neuro-humoral and vascular mechanisms have been completed.

Angiotensin II activates collagen type I gene in the renal vasculature of transgenic mice during inhibition of nitric oxide synthesis: evidence for an endothelin-mediated mechanism.

PubMed

Boffa, J J; Tharaux, P L; Placier, S; Ardaillou, R; Dussaule, J C; Chatziantoniou, C

1999-11-02

Hypertension is frequently associated with renal vascular fibrosis. The purpose of this study was to investigate whether angiotensin II (Ang II) is involved in this fibrogenic process. Experiments were performed on transgenic mice harboring the luciferase gene under the control of the collagen I-alpha(2) chain promoter [procolalpha(2)(I)]. Hypertension was induced by chronic inhibition of NO synthesis (N(G)-nitro-L-arginine methyl ester, L-NAME). Procolalpha(2)(I) activity started to increase in the renal vasculature after 4 weeks of L-NAME treatment (P<0.01) and at 14 weeks reached 3- and 8-fold increases over control in afferent arterioles and glomeruli, respectively (P<0.001). Losartan, an AT(1) receptor antagonist, given simultaneously with L-NAME prevented the increase of procolalpha(2)(I) levels and attenuated the development of renal vascular fibrosis without normalizing systolic pressure increase. Because we found previously that endothelin mediated renal vascular fibrosis in the L-NAME model, the interaction between Ang II, endothelin, and procolalpha(2)(I) was investigated in ex vivo and short-term in vivo experiments. In both conditions, the Ang II-induced activation of procolalpha(2)(I) in renal cortex was blocked by an endothelin receptor antagonist. During chronic inhibition of NO, the collagen I gene becomes activated, leading to the development of renal vascular fibrosis. Ang II is a major player in this fibrogenic process, and its effect on collagen I gene is independent of systemic hemodynamics and is at least partly mediated by the profibrogenic action of endothelin.

Prostaglandins and nonsteroidal anti-inflammatory drugs. Effects on renal hemodynamics.

PubMed

DiBona, G F

1986-01-17

Renal prostaglandins are important modulators of renal hemodynamic function. Their synthesis from arachidonic acid precursor is regulated by neurohumoral vasoactive substances as well as by intrarenal factors. Endogenous renal prostaglandins exert little influence on renal blood flow and glomerular filtration rate in the basal state. In contrast, inhibition of cyclooxygenase-dependent arachidonic acid metabolism with nonsteroidal anti-inflammatory drugs in states of decreased renal perfusion causes marked alterations in these variables. Thus, clinical states characterized by decreased intravascular volume (decreased effective blood volume) with decreased renal perfusion augment the activity of various neurohumoral vasoactive systems and result in an increased dependence of renal hemodynamics on endogenous renal prostaglandin synthesis, which is stimulated, in a compensatory manner, by these same systems. The development of newer drugs that undergo biotransformation in the kidney between active and inactive forms may permit a lesser degree of renal cyclooxygenase inhibition, with the possibility of a reduction in the adverse effects on renal blood flow and glomerular filtration rate. Appropriate clinical use of nonsteroidal anti-inflammatory drugs requires careful consideration of the potential deleterious consequences of prostaglandin synthesis inhibition. Prostaglandins are considered to be autacoids and, as such, they exert their physiologic actions close to or at the site of synthesis. Therefore, production of prostaglandins, thromboxanes, and, possibly, leukotrienes in the renal cortex by the constituent cells of the glomeruli and the arterioles would be anticipated to influence their hemodynamic functions, that is, glomerular filtration rate, renal blood flow, renal vascular resistance, and juxtaglomerular granular cell renin release.

Ultrasound evaluation of valsartan therapy for renal cortical perfusion.

PubMed

Kishimoto, Noriko; Mori, Yasukiyo; Nishiue, Takashi; Nose, Atsuko; Kijima, Yasuaki; Tokoro, Toshiko; Yamahara, Hideki; Okigaki, Mitsuhiko; Kosaki, Atsushi; Iwasaka, Toshiji

2004-05-01

An increase in renal blood flow with a concomitant decrease in filtration fraction at the onset of angiotensin II receptor blocker treatment has been shown to predict a long-term renoprotective effect. However, no studies are available regarding angiotensin receptor blocker-induced changes in renal cortical perfusion observed in the clinical setting. We have recently developed a convenient method of evaluating human renal cortical blood flow with contrast-enhanced harmonic ultrasonography. The goal of this study was to use this method to examine the effect of valsartan, an angiotensin II receptor blocker, on renal cortical perfusion. We performed intermittent second harmonic imaging with venous infusion of a microbubble contrast agent in 7 healthy volunteers. Contrast-enhanced harmonic ultrasonography performed after oral administration of valsartan (80mg) showed a significant increase in microbubble velocity, which correlated well with the increase in total renal blood flow determined by p-aminohippurate clearance (r=0.950, p < 0.001). Although fractional vascular volume was not significantly increased, alterations in renal cortical blood flow calculated by the product of microbubble velocity and fractional volume were also correlated with the change in total renal blood flow (r=0.756, p < 0.05). These results indicate that valsartan increases the renal cortical blood flow in normal kidneys, mainly by increasing blood flow velocity. Contrast-enhanced harmonic ultrasonography is a promising technique for evaluating the precise effect on renal cortical perfusion and optimal dose of valsartan in diseased kidneys.

Diesel Exhaust Particles Induce Impairment of Vascular and Cardiac Homeostasis in Mice: Ameliorative Effect of Emodin.

PubMed

Nemmar, Abderrahim; Al Dhaheri, Rauda; Alamiri, Jawaher; Al Hefeiti, Suhaila; Al Saedi, Hajar; Beegam, Sumaya; Yuvaraju, Priya; Yasin, Javed; Ali, Badreldin H

2015-01-01

There is strong epidemiological and clinical evidence that components of the cardiovascular system are adversely affected by particulate air pollutants through the generation of inflammation and oxidative stress. Emodin (1,3,8-trihydroxy-6- methylanthraquinone), which is commonly found in the roots of rhubarb plant, has strong antioxidant and anti-inflammatory effects. However, its possible protective effect on the cardiovascular effect of particulate air pollutants has never been reported before. We tested, in Tuck-Ordinary mice, the possible ameliorative effect of emodin on the acute (24h) cardiovascular effects of diesel exhaust particles (DEP, 1 mg/kg) or saline (control). Emodin (4 mg/kg) was administered intraperitoneally 1h before and 7h after pulmonary exposure to DEP. Twenty four h following DEP exposure, several cardiovascular endpoints were assessed. Emodin significantly prevented the increase of leukocyte (n=8, P<0.001) and erythrocyte (n=8, P<0.01) numbers caused by DEP. Likewise, emodin abrogated DEP-induced increase of heart tissue levels of interleukin 1β (n=8, P<0.01) and tumour necrosis factor α (n=8, P<0.05), and significantly mitigated the change of the activities of antioxidant enzymes superoxide dismutase (n=8, P<0.001) and glutathione reductase (n=8, P<0.05). Emodin abolished the in vivo prothrombotic effect of DEP in pial arterioles (n=6, P<0.01) and venules (n=6, P<0.001). Similarly, emodin prevented platelet aggregation in vitro in whole blood (n=4-5, P<0.01), and the shortening of activated partial thromboplastin time (n=4, P<0.001) and prothrombin time (n=4, P<0.01) caused by DEP. We conclude that emodin treatment has consistently protected against DEP-induced impairment of vascular and cardiac homeostasis in mice. Our study provides experimental evidence that the use of functional food such as emodin, pending further studies, can be considered a useful agent and may have the potential to protect or mitigate the cardiovascular

Renal effects of felodipine: a review of experimental evidence and clinical data.

PubMed

DiBona, G F

1990-01-01

The dihydropyridine calcium channel antagonist felodipine has a wide spectrum of effects on the kidney. From a variety of studies in normotensive and hypertensive animals and human subjects, felodipine produces a decrease in renal vascular resistance that, although predominantly dependent on the decrease in mean arterial pressure (MAP), may be associated with an increase in renal blood flow (RBF). The glomerular filtration rate (GFR) is unchanged. In response to acute felodipine administration, the significant diuresis and natriuresis observed is caused by a direct inhibitory effect on net renal tubular sodium and water reabsorption. While the acute natriuretic response to felodipine administration is modulated by compensatory adaptations over the remainder of the 24-h period and during chronic treatment, the negative sodium balance established is sustained over the duration of the treatment. Renal sodium and water retention are not observed and there is little effect on renal potassium handling. As a vasodilator antihypertensive agent, felodipine produces renal vasodilatation (normal or increased but not decreased RBF) without adverse effects on the GFR or renal sodium and water retention.

Bilateral Renal Anastomosing Hemangiomas: A Tale of Two Kidneys

PubMed Central

Abboudi, Hamid; Tschobotko, Benjamin; Carr, Christopher

2017-01-01

Abstract Background: Renal anastomosing hemangioma (RAH) is an extremely rare benign vascular tumor first described in 2009. Making this diagnosis is fraught with challenges. Radiologically they share features consistent with renal cell carcinomas (RCCs). Their vascular nature poses risks if considering preoperative biopsy and histologically they share characteristics akin to angiosarcomas. The few reports published in the literature suggest presentation with hematuria, flank pain, and polycythemia although the majority are diagnosed at postnephrectomy histologic examination. This case represents the first metachronous RAH in the literature, and is the first RAH presenting with severe hemorrhage. Case Presentation: A 62-year-old woman of Albanian heritage presented to urology with visible hematuria and positive urine cytology. Three years before this presentation, she had undergone an elective radical right-sided nephrectomy for a suspected RCC detected on magnetic resonance imaging, which proved to be an RAH after postoperative histologic examination of the specimen. The patient was investigated with cystoscopy and ureteroscopy for this new hematuria presentation, both of which were unremarkable. Fourteen hours post ureteroscopy, the patient became severely hypotensive and developed acute kidney injury. A CT scan indicated a large left-sided renal subcapsular and retroperitoneal hematoma that was actively bleeding. The patient was hemodynamically unstable and, therefore, required an emergency open left-sided nephrectomy, rendering her anephric and dialysis dependent. Postoperative histologic examination proved that the left kidney also contained an RAH. Conclusion: The anastomosing hemangioma is an important subtype to differentiate from angiosarcoma before and after a nephrectomy. Urologists should carefully consider invasive tests in patients with previously diagnosed vascular lesions as there may be an increased risk of bleeding. Patients with a previously

Bilateral Renal Anastomosing Hemangiomas: A Tale of Two Kidneys.

PubMed

Abboudi, Hamid; Tschobotko, Benjamin; Carr, Christopher; DasGupta, Ranan

2017-01-01

Background: Renal anastomosing hemangioma (RAH) is an extremely rare benign vascular tumor first described in 2009. Making this diagnosis is fraught with challenges. Radiologically they share features consistent with renal cell carcinomas (RCCs). Their vascular nature poses risks if considering preoperative biopsy and histologically they share characteristics akin to angiosarcomas. The few reports published in the literature suggest presentation with hematuria, flank pain, and polycythemia although the majority are diagnosed at postnephrectomy histologic examination. This case represents the first metachronous RAH in the literature, and is the first RAH presenting with severe hemorrhage. Case Presentation: A 62-year-old woman of Albanian heritage presented to urology with visible hematuria and positive urine cytology. Three years before this presentation, she had undergone an elective radical right-sided nephrectomy for a suspected RCC detected on magnetic resonance imaging, which proved to be an RAH after postoperative histologic examination of the specimen. The patient was investigated with cystoscopy and ureteroscopy for this new hematuria presentation, both of which were unremarkable. Fourteen hours post ureteroscopy, the patient became severely hypotensive and developed acute kidney injury. A CT scan indicated a large left-sided renal subcapsular and retroperitoneal hematoma that was actively bleeding. The patient was hemodynamically unstable and, therefore, required an emergency open left-sided nephrectomy, rendering her anephric and dialysis dependent. Postoperative histologic examination proved that the left kidney also contained an RAH. Conclusion: The anastomosing hemangioma is an important subtype to differentiate from angiosarcoma before and after a nephrectomy. Urologists should carefully consider invasive tests in patients with previously diagnosed vascular lesions as there may be an increased risk of bleeding. Patients with a previously diagnosed

Agmatine improves renal function in gentamicin-induced nephrotoxicity in rats.

PubMed

El-Kashef, Dalia H; El-Kenawi, Asmaa E; Abdel Rahim, Mona; Suddek, Ghada M; Salem, Hatem A

2016-03-01

The present study was designed to explore the possible protective effects of agmatine, a known nitric oxide (NO) synthase inhibitor, against gentamicin-induced nephrotoxicity in rats. For this purpose, we quantitatively evaluated gentamicin-induced renal structural and functional alterations using histopathological and biochemical approaches. Furthermore, the effect of agmatine on gentamicin-induced hypersensitivity of urinary bladder rings to acetylcholine (ACh) was evaluated. Twenty-four male Wistar albino rats were randomly divided into 3 groups, namely control, gentamicin (100 mg/kg, i.p.), and gentamicin plus agmatine (40 mg/kg, orally). At the end of the study, all rats were sacrificed and then blood and urine samples and kidneys were taken. Administration of agmatine significantly decreased kidney/body mass ratio, serum creatinine, lactate dehydrogenase (LDH), renal malondialdehyde (MDA), myeloperoxidase (MPO), NO, and tumor necrosis factor-alpha (TNF-α) while it significantly increased creatinine clearance and renal superoxide dismutase (SOD) activity when compared with the gentamicin-treated group. Additionally, agmatine ameliorated tissue morphology as evidenced by histological evaluation and reduced the responses of isolated bladder rings to ACh. Our study indicates that agmatine administration with gentamicin attenuates oxidative-stress associated renal injury by reducing oxygen free radicals and lipid peroxidation, restoring NO level and inhibiting inflammatory mediators such as TNF-α.

Retrograde renal hilar dissection and segmental arterial clamping: a simple modification to achieve super-selective robotic partial nephrectomy.

PubMed

Greene, Richard N; Sutherland, Douglas E; Tausch, Timothy J; Perez, Deo S

2014-03-01

Super-selective vascular control prior to robotic partial nephrectomy (also known as 'zero-ischemia') is a novel surgical technique that promises to reduce warm ischemia time. The technique has been shown to be feasible but adds substantial technical complexity and cost to the procedure. We present a simplified retrograde dissection of the renal hilum to achieve selective vascular control during robotic partial nephrectomy. Consecutive patients with stage 1 solid and complex cystic renal masses underwent robotic partial nephrectomies with selective vascular control using a modification to previously described super-selective robotic partial nephrectomy. In each case, the renal arterial branch supplying the mass and surrounding parenchyma was dissected in a retrograde fashion from the tumor. Intra-renal dissection of the interlobular artery was not performed. Intra-operative immunofluorescence was not utilized as assessment of parenchymal ischemia was documented before partial nephrectomy. Data was prospectively collected in an IRB-approved partial nephrectomy database. Operative variables between patients undergoing super-selective versus standard robotic partial nephrectomy were compared. Super-selective partial nephrectomy with retrograde hilar dissection was successfully completed in five consecutive patients. There were no complications or conversions to traditional partial nephrectomy. All were diagnosed with renal cell carcinoma and surgical margins were all negative. Estimated blood loss, warm ischemia time, operative time and length of stay were all comparable between patients undergoing super-selective and standard robotic partial nephrectomy. Retrograde hilar dissection appears to be a feasible and safe approach to super-selective partial nephrectomy without adding complex renovascular surgical techniques or cost to the procedure.

Thalidomide Ameliorates Inflammation and Vascular Injury but Aggravates Tubular Damage in the Irradiated Mouse Kidney

DOE Office of Scientific and Technical Information (OSTI.GOV)

Scharpfenecker, Marion, E-mail: m.scharpfenecker@nki.nl; Floot, Ben; Russell, Nicola S.

Purpose: The late side effects of kidney irradiation include vascular damage and fibrosis, which are promoted by an irradiation-induced inflammatory response. We therefore treated kidney-irradiated mice with the anti-inflammatory and angiogenesis-modulating drug thalidomide in an attempt to prevent the development of late normal tissue damage and radiation nephropathy in the mouse kidney. Methods and Materials: Kidneys of C57Bl/6 mice were irradiated with a single dose of 14 Gy. Starting from week 16 after irradiation, the mice were fed with thalidomide-containing chow (100 mg/kg body weight/day). Gene expression and kidney histology were analyzed at 40 weeks and blood samples at 10, 20, 30, andmore » 40 weeks after irradiation. Results: Thalidomide improved the vascular structure and vessel perfusion after irradiation, associated with a normalization of pericyte coverage. The drug also reduced infiltration of inflammatory cells but could not suppress the development of fibrosis. Irradiation-induced changes in hematocrit and blood urea nitrogen levels were not rescued by thalidomide. Moreover, thalidomide worsened tubular damage after irradiation and also negatively affected basal tubular function. Conclusions: Thalidomide improved the inflammatory and vascular side effects of kidney irradiation but could not reverse tubular toxicity, which probably prevented preservation of kidney function.« less

Birt-Hogg-Dubé syndrome and intracranial vascular pathologies.

PubMed

Kapoor, Rahul; Evins, Alexander I; Steitieh, Diala; Bernardo, Antonio; Stieg, Philip E

2015-12-01

Birt-Hogg-Dubé syndrome, first described in 1977, is a rare autosomal dominant condition that commonly presents with skin lesions, including fibrofolliculomas and trichodiscomas; pulmonary cysts; spontaneous pneumothoraces; and renal cancer. We present the only known cases of intracranial vascular pathologies in patients with Birt-Hogg-Dubé syndrome. We present three cases (three female; age range 18-50) of intracranial vascular lesions in Birt-Hogg-Dubé patients, including two aneurysms and one arteriovenous malformation, and review one previously reported case of carotid aplasia. Due to the rarity of Birt-Hogg-Dubé syndrome and significant variations in its clinical presentation, it is difficult to assess whether or not Birt-Hogg-Dubé patients are predisposed to intracranial vascular pathologies. We hypothesize that increased transcription of hypoxia-inducible factor 1-alpha, resulting from a mutated form of the protein folliculin transcribed by the Birt-Hogg-Dubé gene, may be associated with vascular pathogenesis in Birt-Hogg-Dubé patients and thus provide a possible molecular basis for a link between these two conditions.

Decreased contraction induced by endothelium-derived contracting factor in prolonged treatment of rat renal artery with endoplasmic reticulum stress inducer.

PubMed

Ando, Makoto; Matsumoto, Takayuki; Taguchi, Kumiko; Kobayashi, Tsuneo

2018-05-04

Recent evidence suggests that endoplasmic reticulum (ER) stress is involved in the regulation of various physiological functions, including those of the vascular system. However, the relationship between ER stress and vascular function is poorly understood. The endothelial cells control the vascular tone by releasing endothelium-derived relaxing factors and contracting factors (EDCFs). We hypothesized that tunicamycin, an inducer of ER stress, modifies endothelium-dependent contraction and prostaglandins (PGs), a major class of EDCFs, induced contractions in the rat renal artery in rats. An organ-culture technique was used to purely investigate the effects of ER stress on the vascular tissue. We observed that tunicamycin treatment (20 μg/mL for 23 ± 1 h) did not affect acetylcholine (ACh)-induced relaxation and decreased EDCF-mediated contractions under nitric oxide synthase (NOS) inhibition induced by ACh, ATP, or A23187 (a calcium ionophore) in the renal arteries. Under NOS inhibition, U46619 (a thromboxane A 2 mimetic)- and beraprost (a prostacyclin analog)-induced contractions were also decreased in the renal arteries of the tunicamycin-treated group (vs. vehicle), while PGE 2 - and PGF 2α -induced contractions were similar between the groups. Tunicamycin treatment slightly enhanced the contractions induced by phenylephrine, an α 1 adrenoceptor ligand. Isotonic high-K + -induced contractions were similar between the vehicle- and tunicamycin-treated groups. Another ER stress inducer, thapsigargin (4 μmol/L for 23 ± 1 h), also caused substantial reduction of ACh-induced EDCF-mediated contraction (vs. vehicle-treated group). In the cultured renal arteries, tunicamycin and thapsigargin increased the expression of binding immunoglobulin protein (BiP), an ER stress marker. In conclusion, ER stress induction directly affects renal arterial function, especially in reducing EDCF-mediated contractions.

Vascular rarefaction mediates whitening of brown fat in obesity

PubMed Central

Shimizu, Ippei; Aprahamian, Tamar; Kikuchi, Ryosuke; Shimizu, Ayako; Papanicolaou, Kyriakos N.; MacLauchlan, Susan; Maruyama, Sonomi; Walsh, Kenneth

2014-01-01

Brown adipose tissue (BAT) is a highly vascularized organ with abundant mitochondria that produce heat through uncoupled respiration. Obesity is associated with a reduction of BAT function; however, it is unknown how obesity promotes dysfunctional BAT. Here, using a murine model of diet-induced obesity, we determined that obesity causes capillary rarefaction and functional hypoxia in BAT, leading to a BAT “whitening” phenotype that is characterized by mitochondrial dysfunction, lipid droplet accumulation, and decreased expression of Vegfa. Targeted deletion of Vegfa in adipose tissue of nonobese mice resulted in BAT whitening, supporting a role for decreased vascularity in obesity-associated BAT. Conversely, introduction of VEGF-A specifically into BAT of obese mice restored vascularity, ameliorated brown adipocyte dysfunction, and improved insulin sensitivity. The capillary rarefaction in BAT that was brought about by obesity or Vegfa ablation diminished β-adrenergic signaling, increased mitochondrial ROS production, and promoted mitophagy. These data indicate that overnutrition leads to the development of a hypoxic state in BAT, causing it to whiten through mitochondrial dysfunction and loss. Furthermore, these results link obesity-associated BAT whitening to impaired systemic glucose metabolism. PMID:24713652

Notoginsenoside R1 attenuates renal ischemia-reperfusion injury in rats.

PubMed

Liu, Wen-Jun; Tang, Hong-Tai; Jia, Yi-Tao; Ma, Bing; Fu, Jin-Feng; Wang, Yu; Lv, Kai-Yang; Xia, Zhao-Fan

2010-09-01

Ischemia-reperfusion (I/R) injury of the kidney is a complex pathophysiological process and a major cause of acute renal failure. It has been shown that I/R injury is related to inflammatory responses and activation of apoptotic pathways. Inhibition of certain elements of inflammatory responses and apoptotic pathway seemed to ameliorate renal I/R injury. As an effective element of Panax notoginseng, NR1 has antioxidant, anti-inflammatory, antiapoptotic, and immune-stimulatory activities. Therefore, we speculate that NR1 can attenuate renal I/R injury. Ischemia-reperfusion injury was induced by renal pedicle ligation followed by reperfusion along with a contralateral nephrectomy. Male Sprague-Dawley rats were randomized to four groups: sham group, I/R control group, NR1-1 group (rats treated with NR1, 20 mg.kg.d) and NR1-2 group (rats treated with NR1, 40 mg.kg.d). All animals were killed 72 h after I/R induction. Blood and renal tissues were collected. Renal dysfunction was observed by the level of serum creatinine and histological evaluation. Apoptosis and inflammatory response in the tissue of kidney were detected mainly with molecular biological methods. NR1 attenuated I/R-induced renal dysfunction as indicated by the level of serum creatinine and histological evaluation. It prevented the I/R-induced increases in the levels of proinflammatory cytokine TNF-alpha, myeloperoxidase activity, phosphorylation of p38, and activation of nuclear factor kappaB with cell apoptosis in the kidney and enhanced expression of antiapoptosis cytokine bcl-2. Treatment with NR1 improves renal function after I/R associated with a significant reduction in cell apoptosis and inflammatory responses, which may be related to p38 and nuclear factor kappaB inhibition.

Adverse effects of meglumine diatrizoate on renal function in the early post-transplant period.

PubMed

Light, J A; Perloff, L J; Etheredge, E E; Hill, G; Spees, E K

1975-11-01

Thirty-four renal transplant recipients received drip infusion urograms from 2-24 days post-transplantation. Twenty-two patients exhibited changes in renal function within 1-4 days of the urogram that were indistinguishable from allograft rejection: a tender, swollen kidney, elevation of serum creatinine, oliguria, decreased urine sodium concentration, weight gain, and hypertension. Two patients developed acute tubular necrosis and required hemodialysis, but renal function in the remaining 20 patients improved after therapy for "graft rejection" with i.v. methyprednisolone sodium succinnate. Kidneys from older-age donors that were functioning suboptimally and kidneys which exhibited subsequent clinical allograft rejection were more at risk for contrast media toxicity. This suggests that occult vascular lesions may have been present in the allograft which were exacerbated when exposed to the irritant vascular effects of contrast media, producing a mild, reversible toxic nephritis. However, several kidneys with normal function and several kidneys which never exhibited rejection activity were also adversely affected by exposure to contrast media. It appears these agents should be used cautiously, if at all, in the early post-transplant period.

A local renal renin-angiotensin system activation via renal uptake of prorenin and angiotensinogen in diabetic rats.

PubMed

Tojo, Akihiro; Kinugasa, Satoshi; Fujita, Toshiro; Wilcox, Christopher S

2016-01-01

The mechanism of activation of local renal renin-angiotensin system (RAS) has not been clarified in diabetes mellitus (DM). We hypothesized that the local renal RAS will be activated via increased glomerular filtration and tubular uptake of prorenin and angiotensinogen in diabetic kidney with microalbuminuria. Streptozotocin (STZ)-induced DM and control rats were injected with human prorenin and subsequently with human angiotensinogen. Human prorenin uptake was increased in podocytes, proximal tubules, macula densa, and cortical collecting ducts of DM rats where prorenin receptor (PRR) was expressed. Co-immunoprecipitation of kidney homogenates in DM rats revealed binding of human prorenin to the PRR and to megalin. The renal uptake of human angiotensinogen was increased in DM rats at the same nephron sites as prorenin. Angiotensin-converting enzyme was increased in podocytes, but decreased in the proximal tubules in DM rats, which may have contributed to unchanged renal levels of angiotensin despite increased angiotensinogen. The systolic blood pressure increased more after the injection of 20 μg of angiotensinogen in DM rats than in controls, accompanied by an increased uptake of human angiotensinogen in the vascular endothelium. In conclusion, endocytic uptake of prorenin and angiotensinogen in the kidney and vasculature in DM rats was contributed to increased tissue RAS and their pressor response to angiotensinogen.

Predicting vascular complications in percutaneous coronary interventions.

PubMed

Piper, Winthrop D; Malenka, David J; Ryan, Thomas J; Shubrooks, Samuel J; O'Connor, Gerald T; Robb, John F; Farrell, Karen L; Corliss, Mary S; Hearne, Michael J; Kellett, Mirle A; Watkins, Matthew W; Bradley, William A; Hettleman, Bruce D; Silver, Theodore M; McGrath, Paul D; O'Mears, John R; Wennberg, David E

2003-06-01

Using a large, current, regional registry of percutaneous coronary interventions (PCI), we identified risk factors for postprocedure vascular complications and developed a scoring system to estimate individual patient risk. A vascular complication (access-site injury requiring treatment or bleeding requiring transfusion) is a potentially avoidable outcome of PCI. Data were collected on 18,137 consecutive patients undergoing PCI in northern New England from January 1997 to December 1999. Multivariate regression was used to identify characteristics associated with vascular complications and to develop a scoring system to predict risk. The rate of vascular complication was 2.98% (541 cases). Variables associated with increased risk in the multivariate analysis included age >or=70, odds ratio (OR) 2.7, female sex (OR 2.4), body surface area <1.6 m(2) (OR 1.9), history of congestive heart failure (OR 1.4), chronic obstructive pulmonary disease (OR 1.5), renal failure (OR 1.9), lower extremity vascular disease (OR 1.4), bleeding disorder (OR 1.68), emergent priority (OR 2.3), myocardial infarction (OR 1.7), shock (1.86), >or=1 type B2 (OR 1.32) or type C (OR 1.7) lesions, 3-vessel PCI (OR 1.5), use of thienopyridines (OR 1.4) or use of glycoprotein IIb/IIIa receptor inhibitors (OR 1.9). The model performed well in tests for significance, discrimination, and calibration. The scoring system captured 75% of actual vascular complications in its highest quintiles of predicted risk. Predicting the risk of post-PCI vascular complications is feasible. This information may be useful for clinical decision-making and institutional efforts at quality improvement.

[Relevance of contrast ultrasound with microbubbles in vascular medecine].

PubMed

Erdmann, Andreas; Ney, Barbara; Alatri, Adriano; Calanca, Luca; Mazzolai, Lucia

2016-12-07

Application of ultrasound contrast media has become a standard in diagnostic imaging in cardiology and in the characterization of focal lesions in multiple organs, especially of the liver. In the past years there was a growing body of evidence for their usefulness in vascular medicine. The development of contrast media, microbubbles with a stabilizing envelope and filled with gaz, small enough to pass through pulmonary capillaries made real-time imaging of organ perfusion possible. Ultrasound contrast media are rapidly eliminated by exhalation and can safely be administered to patients with renal failure. The objective of this review is to describe the basic principles of ultrasound contrast imaging and to inform about vascular applications of contrast ultrasound.

Matcha, a powdered green tea, ameliorates the progression of renal and hepatic damage in type 2 diabetic OLETF rats.

PubMed

Yamabe, Noriko; Kang, Ki Sung; Hur, Jong Moon; Yokozawa, Takako

2009-08-01

Matcha, a powdered green tea produced by grinding with a stone mill, has been popularly used in the traditional tea ceremony and foods in Japan. Matcha is well known to be richer in some nutritional elements and epigallocatechin 3-O-gallate than other green teas. In our previous study, epigallocatechin 3-O-gallate exhibited protective effects against renal damage in a rat model of diabetic nephropathy. In the present study, we investigated the preventive effects of Matcha (50, 100, or 200 mg/kg/day) on the progression of hepatic and renal damage in type 2 diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats. OLETF rats were orally administered Matcha for 16 weeks, and we assessed biochemical parameters in the serum, liver, and kidney and expression levels of major products of advanced glycation end products (AGEs), N(6)-(carboxylmethyl)lysine (CML) and N(6)-(carboxylethyl)lysine (CEL), receptor for AGE (RAGE), and sterol regulatory element binding proteins (SREBPs)-1 and -2. Serum total protein levels were significantly increased by Matcha administration, whereas the serum albumin and glycosylated protein levels as well as the renal glucose and triglyceride levels were only slightly or not at all affected. However, Matcha treatment significantly lowered the glucose, triglyceride, and total cholesterol levels in the serum and liver, renal AGE levels, and the serum thiobarbituric acid-reactive substances levels. In addition, Matcha supplementation resulted in decreases in the renal CML, CEL, and RAGE expressions as well as an increase in hepatic SREBP-2 expression, but not that of SREBP-1. These results suggest that Matcha protects against hepatic and renal damage through the suppression of renal AGE accumulation, by decreases in hepatic glucose, triglyceride, and total cholesterol levels, and by its antioxidant activities.

Probiotic Amelioration of Azotemia in 5/6th Nephrectomized Sprague-Dawley Rats

PubMed Central

Ranganathan, Natarajan; Patel, Beena; Ranganathan, Pari; Marczely, Joseph; Dheer, Rahul; Chordia, Tushar; Dunn, Stephen R.; Friedman, Eli A.

2005-01-01

The present study was to test the hypothesis that selected bacteria instilled into the gastrointestinal tract could help in converting nitrogenous wastes accumulated due to renal insufficiency into nontoxic compounds; thereby, ameliorating the biochemical imbalance. Herein we describe a prospective, blinded, placebo-controlled pilot study, using 5/6th nephrectomized Sprague Dawley rat as a chronic renal failure model. The study group consisted of 36 nephrectomized and 7 non-nephrectomized (control) rats. After two-week nephrectomy stabilization, cohorts of six nephrectomized rats were fed casein-based diet plus one of the following regimens: (A) Control, (B) Placebo (casein-based diet without probiotics), (C) Bacillus pasteurii, (D) Sporolac®, (E) Kibow cocktail, (F) CHR Hansen Cocktail, and (G) ECONORMTM. Subsequently, blood (retro-orbital) and urine (collected for measurements of blood urea-nitrogen and creatinine respectively), body weight and bacterial counts (feces) were obtained at regular intervals. The study end-points were to determine if any of the probiotic dietary supplements facilitated, (1) decreased blood concentrations of uremic toxins, (2) altered renal function, and (3) prolonged survival. After 16 weeks of treatment, regimens C and D significantly prolonged the life span of uremic rats, in addition to showing a reduction in blood urea-nitrogen levels, concluding that supplementation of probiotic formulation to uremic rats slows the progression of azotemia, which may correlate with prolonged life span of uremic rats. Derivative trials of probiotic treatment of larger animals and humans will further assess the potential role of probiotic formulations in delaying the onset and clinical severity of clinical illness at different stages of renal failure. PMID:16127597

DNA damage response in renal ischemia-reperfusion and ATP-depletion injury of renal tubular cells.

PubMed

Ma, Zhengwei; Wei, Qingqing; Dong, Guie; Huo, Yuqing; Dong, Zheng

2014-07-01

Renal ischemia-reperfusion leads to acute kidney injury (AKI) that is characterized pathologically by tubular damage and cell death, followed by tubular repair, atrophy and interstitial fibrosis. Recent work suggested the possible presence of DNA damage response (DDR) in AKI. However, the evidence is sketchy and the role and regulation of DDR in ischemic AKI remain elusive. In this study, we demonstrated the induction of phosphorylation of ATM, H2AX, Chk2 and p53 during renal ischemia-reperfusion in mice, suggesting DDR in kidney tissues. DDR was also induced in vitro during the recovery or "reperfusion" of renal proximal tubular cells (RPTCs) after ATP depletion. DDR in RPTCs was abrogated by supplying glucose to maintain ATP via glycolysis, indicating that the DDR depends on ATP depletion. The DDR was also suppressed by the general caspase inhibitor z-VAD and the overexpression of Bcl-2, supporting a role of apoptosis-associated DNA damage in the DDR. N-acetylcysteine (NAC), an antioxidant, suppressed the phosphorylation of ATM and p53 and, to a less extent, Chk2, but NAC increased the phosphorylation and nuclear foci formation of H2AX. Interestingly, NAC increased apoptosis, which may account for the observed H2AX activation. Ku55933, an ATM inhibitor, blocked ATM phosphorylation and ameliorated the phosphorylation of Chk2 and p53, but it increased H2AX phosphorylation and nuclear foci formation. Ku55933 also increased apoptosis in RPTCs following ATP depletion. The results suggest that DDR occurs during renal ischemia-reperfusion in vivo and ATP-depletion injury in vitro. The DDR is partially induced by apoptosis and oxidative stress-related DNA damage. ATM, as a sensor in the DDR, may play a cytoprotective role against tubular cell injury and death. Copyright © 2014 Elsevier B.V. All rights reserved.

DNA damage response in renal ischemia-reperfusion and ATP-depletion injury of renal tubular cells

PubMed Central

Ma, Zhengwei; Wei, Qingqing; Dong, Guie; Huo, Yuqing; Dong, Zheng

2014-01-01

Renal ischemia-reperfusion leads to acute kidney injury (AKI) that is characterized pathologically by tubular damage and cell death, followed by tubular repair, atrophy and interstitial fibrosis. Recent work suggested the possible presence of DNA damage response (DDR) in AKI. However, the evidence is sketchy and the role and regulation of DDR in ischemic AKI remain elusive. In this study, we demonstrated the induction of phosphorylation of ATM, H2AX, Chk2 and p53 during renal ischemia-reperfusion in mice, suggesting DDR in kidney tissues. DDR was also induced in vitro during the recovery or “reperfusion” of renal proximal tubular cells (RPTCs) after ATP-depletion. DDR in RPTCs was abrogated by supplying glucose to maintain ATP via glycolysis, indicating that the DDR depends on ATP depletion. The DDR was also suppressed by the general caspase inhibitor z-VAD and the overexpression of Bcl-2, supporting a role of apoptosis-associated DNA damage in the DDR. N-acetylcysteine (NAC), an antioxidant, suppressed the phosphorylation of ATM and p53 and, to a less extent, Chk2, but NAC increased the phosphorylation and nuclear foci formation of H2AX. Interestingly, NAC increased apoptosis, which may account for the observed H2AX activation. Ku55933, an ATM inhibitor, blocked ATM phosphorylation and ameliorated the phosphorylation of Chk2 and p53, but it increased H2AX phosphorylation and nuclear foci formation. Ku55933 also increased apoptosis in RPTCs following ATP-depletion. The results suggest that DDR occurs during renal ischemia-reperfusion in vivo and ATP-depletion injury in vitro. The DDR is partially induced by apoptosis and oxidative stress-related DNA damage. ATM, as a sensor in the DDR, may play a cytoprotective role against tubular cell injury and death. PMID:24726884

A role for cytosolic fumarate hydratase in urea cycle metabolism and renal neoplasia.

PubMed

Adam, Julie; Yang, Ming; Bauerschmidt, Christina; Kitagawa, Mitsuhiro; O'Flaherty, Linda; Maheswaran, Pratheesh; Özkan, Gizem; Sahgal, Natasha; Baban, Dilair; Kato, Keiko; Saito, Kaori; Iino, Keiko; Igarashi, Kaori; Stratford, Michael; Pugh, Christopher; Tennant, Daniel A; Ludwig, Christian; Davies, Benjamin; Ratcliffe, Peter J; El-Bahrawy, Mona; Ashrafian, Houman; Soga, Tomoyoshi; Pollard, Patrick J

2013-05-30

The identification of mutated metabolic enzymes in hereditary cancer syndromes has established a direct link between metabolic dysregulation and cancer. Mutations in the Krebs cycle enzyme, fumarate hydratase (FH), predispose affected individuals to leiomyomas, renal cysts, and cancers, though the respective pathogenic roles of mitochondrial and cytosolic FH isoforms remain undefined. On the basis of comprehensive metabolomic analyses, we demonstrate that FH1-deficient cells and tissues exhibit defects in the urea cycle/arginine metabolism. Remarkably, transgenic re-expression of cytosolic FH ameliorated both renal cyst development and urea cycle defects associated with renal-specific FH1 deletion in mice. Furthermore, acute arginine depletion significantly reduced the viability of FH1-deficient cells in comparison to controls. Our findings highlight the importance of extramitochondrial metabolic pathways in FH-associated oncogenesis and the urea cycle/arginine metabolism as a potential therapeutic target. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

Study of the renal segmental arterial anatomy with contrast-enhanced multi-detector computed tomography.

PubMed

Rocco, Francesco; Cozzi, Luigi Alberto; Cozzi, Gabriele

2015-07-01

To use triphasic multi-detector computed tomography (MDCT) to study the renal segmental arterial anatomy and its relationship with the urinary tract to plan nephron-sparing surgery (NSS). One hundred and fifty nine patients underwent abdominal contrast-enhanced MDCT. We evaluated renal arteries and parenchymal vasculature. In 61 patients, the arteries and the urinary tract were represented simultaneously. 86.60% presented a single renal artery; 13.4%, multiple arteries. All single renal arteries divided into anterior and posterior branch before the hilum. The anterior artery branched into a superior, middle, and inferior branch. In 43.14%, the inferior artery arose before the others; in 45.75%, the superior artery arose before the others; in 9.80%, the branches shared a common trunk. In 26.80%, the posterior artery supplies the entire posterior surface; in 73.20%, it ends along the inferior calyx. In 96.73%, the upper pole was vascularized by the anterior superior branch and the posterior artery: the "tuning fork". MDCT showed four vascular segments in 96.73% and five in 3.27%. MDCT showed two avascular areas: the first along the projection of the inferior calyx on the posterior aspect, the second between the branches of the "tuning fork". The arterial phase provides the arterial tree representation; the delayed phase shows arteries and urinary tract simultaneously. MDCT provides a useful representation of the renal anatomy prior to intervascular-intrarenal NSS.

Pelvi-ureteric junction obstruction related to crossing vessels: vascular anatomic variations and implication for surgical approaches.

PubMed

Panthier, Frédéric; Lareyre, Fabien; Audouin, Marie; Raffort, Juliette

2018-03-01

Pelvi-ureteric junction obstruction corresponds to an impairment of urinary transport that can lead to renal dysfunction if not treated. Several mechanisms can cause the obstruction of the ureter including intrinsic factors or extrinsic factors such as the presence of crossing vessels. The treatment of the disease relies on surgical approaches, pyeloplasty being the standard reference. The technique consists in removing the pathologic ureteric segment and renal pelvis and transposing associated crossing vessels if present. The vascular anatomy of the pelvi-ureteric junction is complex and varies among individuals, and this can impact on the disease development and its surgical treatment. In this review, we summarize current knowledge on vascular anatomic variations in the pelvi-ureteric junction. Based on anatomic characteristics, we discuss implications for surgical approaches during pyeloplasty and vessel transposition.

Human pluripotent stem cell-derived erythropoietin-producing cells ameliorate renal anemia in mice.

PubMed

Hitomi, Hirofumi; Kasahara, Tomoko; Katagiri, Naoko; Hoshina, Azusa; Mae, Shin-Ichi; Kotaka, Maki; Toyohara, Takafumi; Rahman, Asadur; Nakano, Daisuke; Niwa, Akira; Saito, Megumu K; Nakahata, Tatsutoshi; Nishiyama, Akira; Osafune, Kenji

2017-09-27

The production of erythropoietin (EPO) by the kidneys, a principal hormone for the hematopoietic system, is reduced in patients with chronic kidney disease (CKD), eventually resulting in severe anemia. Although recombinant human EPO treatment improves anemia in patients with CKD, returning to full red blood cell production without fluctuations does not always occur. We established a method to generate EPO-producing cells from human induced pluripotent stem cells (hiPSCs) by modifying previously reported hepatic differentiation protocols. These cells showed increased EPO expression and secretion in response to low oxygen conditions, prolyl hydroxylase domain-containing enzyme inhibitors, and insulin-like growth factor 1. The EPO protein secreted from hiPSC-derived EPO-producing (hiPSC-EPO) cells induced the erythropoietic differentiation of human umbilical cord blood progenitor cells in vitro. Furthermore, transplantation of hiPSC-EPO cells into mice with CKD induced by adenine treatment improved renal anemia. Thus, hiPSC-EPO cells may be a useful tool for clarifying the mechanisms of EPO production and may be useful as a therapeutic strategy for treating renal anemia. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Expression of receptor-type protein tyrosine phosphatase in developing and adult renal vasculature

PubMed Central

Takahashi, Keiko; Kim, Rachel; Lauhan, Colette; Park, Yuna; Nguyen, Nghiep G.; Vestweber, Dietmar; Dominguez, Melissa G.; Valenzuela, David M.; Murphy, Andrew J.; Yancopoulos, George D.; Gale, Nicholas W.; Takahashi, Takamune

2017-01-01

Renal vascular development is a coordinated process that requires ordered endothelial cell proliferation, migration, intercellular adhesion, and morphogenesis. In recent decades, studies have defined the pivotal role of endothelial receptor tyrosine kinases (RPTKs) in the development and maintenance of renal vasculature. However, the expression and the role of receptor tyrosine phosphatases (RPTPs) in renal endothelium are poorly understood, though coupled and counterbalancing roles of RPTKs and RPTPs are well defined in other systems. In this study, we evaluated the promoter activity and immunolocalization of two endothelial RPTPs, VE-PTP and PTPμ, in developing and adult renal vasculature using the heterozygous LacZ knock-in mice and specific antibodies. In adult kidneys, both VE-PTP and PTPμ were expressed in the endothelium of arterial, glomerular, and medullary vessels, while their expression was highly limited in peritubular capillaries and venous endothelium. VE-PTP and PTPμ promoter activity was also observed in medullary tubular segments in adult kidneys. In embryonic (E12.5, E13.5, E15.5, E17.5) and postnatal (P0, P3, P7) kidneys, these RPTPs were expressed in ingrowing renal arteries, developing glomerular microvasculature (as early as the S-shaped stage), and medullary vessels. Their expression became more evident as the vasculatures matured. Peritubular capillary expression of VE-PTP was also noted in embryonic and postnatal kidneys. Compared to VE-PTP, PTPμ immunoreactivity was relatively limited in embryonic and neonatal renal vasculature and evident immunoreactivity was observed from the P3 stage. These findings indicate 1) VE-PTP and PTPμ are expressed in endothelium of arterial, glomerular, and medullary renal vasculature, 2) their expression increases as renal vascular development proceeds, suggesting that these RPTPs play a role in maturation and maintenance of these vasculatures, and 3) peritubular capillary VE-PTP expression is down

Renal blood flow measurement with contrast-enhanced harmonic ultrasonography: evaluation of dopamine-induced changes in renal cortical perfusion in humans.

PubMed

Kishimoto, N; Mori, Y; Nishiue, T; Shibasaki, Y; Iba, O; Nose, A; Uchiyama-Tanaka, Y; Masaki, H; Matsubara, H; Iwasaka, T

2003-06-01

An accessible non-invasive method for evaluating renal regional blood flow in real time is highly desirable in the clinical setting. Recent progress in ultrasonography with microbubble contrast has allowed quantification of regional blood flow in animal models. Goal ofthis study was to establish a convenient contrast--enhanced harmonic ultrasonography (CEHU) method for evaluating renal cortical blood flow in humans. We carried out intermittent second harmonic imaging in 9 healthy volunteers. Pulse interval was progressively decreased from 4 s - 0.2 s during continuous venous infusion of the microbubble contrast agent. Pulse interval versus CEHU-derived acoustic intensity plots provided microbubble velocity (MV) and fractional vascular volume (FVV) during renal cortical perfusion in humans. Low-dose dopamine infusion (2 microg/min/kg) resulted in a significant increase in MV which correlated well with the increase in total renal blood flow (RBF) determined by a conventional study of p-aminohippurate clearance (C(PAH)) (r = 0.956, p < 0.0001). Although FVV was not significantly increased, alterations in CEHU-derived renal cortical blood flow calculated by the products of MV and FVV were also correlated with alterations in total RBF (r = 0.969, p < 0.0001). Thus, low-dose dopamine infusion increases renal cortical blood flow observed in CEHU, mainly by increasing MV. The present study shows that renal cortical blood flow in humans can be measured non-invasively by CEHU and that CEHU can be used for quantitatively evaluating changes induced by a therapeutic agent such as dopamine in flow velocity and in FVV.

Renal and femoral venous blood flows are regulated by different mechanisms dependent on α-adrenergic receptor subtypes and nitric oxide in anesthetized rats.

PubMed

Fioretti, Alexandre C; Ogihara, Cristiana A; Cafarchio, Eduardo M; Venancio, Daniel P; de Almeida, Roberto Lopes; Antonio, Bruno B; Sato, Monica A

2017-12-01

Venous and arterial walls are responsive to sympathetic system and circulating substances, nevertheless, very few is known about the venous blood flow regulation simultaneously to arterial vascular beds. In this study, we compared the venous and arterial blood flow regulation in visceral and muscular beds upon injection of different doses of vasoactive drugs which act in arterial vascular beds. Anesthetized adult male Wistar rats underwent to right femoral artery and vein cannulation for hemodynamic recordings and infusion of drugs. Doppler flow probes were placed around the left renal artery and vein, and left femoral artery and vein to evaluate the changes in flood flow. Phenylephrine (PHE) injection (α 1 -adrenergic receptor agonist) elicited vasoconstriction in all arteries and veins. Intravenous prazosin (PZS) (1mg/kg, α 1 -adrenergic receptor blocker) caused renal artery vasodilation, but not in the other beds. Vasoconstrictor effect of PHE was abolished by PZS in all vascular beds, except in femoral vein. Phentolamine (PTL) injection (1mg/kg, α 1 /α 2 -adrenergic receptor blocker) produced renal artery vasodilation with no change in other beds. After PTL, the vasoconstriction evoked by PHE was abolished in all vascular beds. Sodium Nitroprusside (SNP), a nitric oxide donor, elicited vasodilation in all beds, and after PTL but not post PZS injection, SNP enhanced the vasodilatory effect in femoral vein. Our findings suggest that the vasoconstriction in renal and femoral veins is mediated by different subtypes of α-adrenoceptors. The nitric oxide-dependent vasodilation in femoral vein enhances when α 2 -adrenoceptors are not under stimulation, but not in the other vascular beds investigated. Copyright © 2017 Elsevier Inc. All rights reserved.

Renal Sympathetic Denervation by CT-scan-Guided Periarterial Ethanol Injection in Sheep

DOE Office of Scientific and Technical Information (OSTI.GOV)

Firouznia, Kavous, E-mail: k-firouznia@yahoo.com; Hosseininasab, Sayed jaber, E-mail: dr.hosseininasab@gmail.com; Amanpour, Saeid, E-mail: saeidamanpour@yahoo.com

BackgroundRenal nerves are a recent target in the treatment of hypertension. Renal sympathetic denervation (RSD) is currently performed using catheter-based radiofrequency ablation (RFA) and because this method has limitations, percutaneous magnetic resonance (MR)-guided periarterial ethanol injection is a suggested alternative. However, few studies have been conducted on the effectiveness of percutaneous ethanol injection for RSD.AimTo evaluate the feasibility, efficacy, and complications of computed tomography (CT)-guided periarterial ethanol injection.MethodsEthanol (10 ml, 99.6 %) was injected around the right renal artery in six sheep under CT guidance with the left kidney serving as a control. Before and after the intervention, the sheep underwent MRmore » imaging studies and the serum creatinine level was measured. One month after the intervention, the sheep were euthanized and norepinephrine (NE) concentration in the renal parenchyma was measured to evaluate the efficacy of the procedure. The treated tissues were also examined histopathologically to evaluate vascular, parenchymal, and neural injury.ResultsThe right kidney parenchymal NE concentration decreased significantly compared with the left kidney after intervention (average reduction: 40 %, P = 0.0016). Histologic examination revealed apparent denervation with no other vascular or parenchymal injuries observed in the histological and imaging studies.ConclusionEffective and feasible RSD was achieved using CT-guided periarterial ethanol injection. This technique may be a potential alternative to catheter-based RFA in the treatment of hypertension.« less

The giraffe kidney tolerates high arterial blood pressure by high renal interstitial pressure and low glomerular filtration rate.

PubMed

Damkjaer, M; Wang, T; Brøndum, E; Østergaard, K H; Baandrup, U; Hørlyck, A; Hasenkam, J M; Smerup, M; Funder, J; Marcussen, N; Danielsen, C C; Bertelsen, M F; Grøndahl, C; Pedersen, M; Agger, P; Candy, G; Aalkjaer, C; Bie, P

2015-08-01

The tallest animal on earth, the giraffe (Giraffa camelopardalis) is endowed with a mean arterial blood pressure (MAP) twice that of other mammals. The kidneys reside at heart level and show no sign of hypertension-related damage. We hypothesized that a species-specific evolutionary adaption in the giraffe kidney allows normal for size renal haemodynamics and glomerular filtration rate (GFR) despite a MAP double that of other mammals. Fourteen anaesthetized giraffes were instrumented with vascular and bladder catheters to measure glomerular filtration rate (GFR) and effective renal plasma flow (ERPF). Renal interstitial hydrostatic pressure (RIHP) was assessed by inserting a needle into the medullary parenchyma. Doppler ultrasound measurements provided renal artery resistive index (RI). Hormone concentrations as well as biomechanical, structural and histological characteristics of vascular and renal tissues were determined. GFR averaged 342 ± 99 mL min(-1) and ERPF 1252 ± 305 mL min(-1) . RIHP varied between 45 and 140 mmHg. Renal pelvic pressure was 39 ± 2 mmHg and renal venous pressure 32 ± 4 mmHg. A valve-like structure at the junction of the renal and vena cava generated a pressure drop of 12 ± 2 mmHg. RI was 0.27. The renal capsule was durable with a calculated burst pressure of 600 mmHg. Plasma renin and AngII were 2.6 ± 0.5 mIU L(-1) and 9.1 ± 1.5 pg mL(-1) respectively. In giraffes, GFR, ERPF and RI appear much lower than expected based on body mass. A strong renal capsule supports a RIHP, which is >10-fold that of other mammals effectively reducing the net filtration pressure and protecting against the high MAP. © 2015 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

Role of L-arginine in the pathogenesis and treatment of renal disease.

PubMed

Cherla, Gautam; Jaimes, Edgar A

2004-10-01

L-arginine is a semi essential amino acid and also a substrate for the synthesis of nitric oxide (NO), polyamines, and agmatine. These L-arginine metabolites may participate in the pathogenesis of renal disease and constitute the rationale for manipulating L-arginine metabolism as a strategy to ameliorate kidney disease. Modification of dietary L-arginine intake in experimental models of kidney diseases has been shown to have both beneficial as well as deleterious effects depending on the specific model studied. L-arginine supplementation in animal models of glomerulonephritis has been shown to be detrimental, probably by increasing the production of NO from increased local expression of inducible NO synthase (iNOS). L-arginine supplementation does not modify the course of renal disease in humans with chronic glomerular diseases. However, beneficial effects of L-arginine supplementation have been reported in several models of chronic kidney disease including renal ablation, ureteral obstruction, nephropathy secondary to diabetes, and salt-sensitive hypertension. L-arginine is reduced in preeclampsia and recent experimental studies indicate that L-arginine supplementation may be beneficial in attenuating the symptoms of preeclampsia. Administration of exogenous L-arginine has been shown to be protective in ischemic acute renal failure. In summary, the role of L-arginine in the pathogenesis and treatment of renal disease is not completely understood and remains to be established.

Role of 2',3'-cyclic nucleotide 3'-phosphodiesterase in the renal 2',3'-cAMP-adenosine pathway.

PubMed

Jackson, Edwin K; Gillespie, Delbert G; Mi, Zaichuan; Cheng, Dongmei; Bansal, Rashmi; Janesko-Feldman, Keri; Kochanek, Patrick M

2014-07-01

Energy depletion increases the renal production of 2',3'-cAMP (a positional isomer of 3',5'-cAMP that opens mitochondrial permeability transition pores) and 2',3'-cAMP is converted to 2'-AMP and 3'-AMP, which in turn are metabolized to adenosine. Because the enzymes involved in this "2',3'-cAMP-adenosine pathway" are unknown, we examined whether 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) participates in the renal metabolism of 2',3'-cAMP. Western blotting and real-time PCR demonstrated expression of CNPase in rat glomerular mesangial, preglomerular vascular smooth muscle and endothelial, proximal tubular, thick ascending limb and collecting duct cells. Real-time PCR established the expression of CNPase in human glomerular mesangial, proximal tubular and vascular smooth muscle cells; and the level of expression of CNPase was greater than that for phosphodiesterase 4 (major enzyme for the metabolism of 3',5'-cAMP). Overexpression of CNPase in rat preglomerular vascular smooth muscle cells increased the metabolism of exogenous 2',3'-cAMP to 2'-AMP. Infusions of 2',3'-cAMP into isolated CNPase wild-type (+/+) kidneys increased renal venous 2'-AMP, and this response was diminished by 63% in CNPase knockout (-/-) kidneys, whereas the conversion of 3',5'-cAMP to 5'-AMP was similar in CNPase +/+ vs. -/- kidneys. In CNPase +/+ kidneys, energy depletion (metabolic poisons) increased kidney tissue levels of adenosine and its metabolites (inosine, hypoxanthine, xanthine, and uric acid) without accumulation of 2',3'-cAMP. In contrast, in CNPase -/- kidneys, energy depletion increased kidney tissue levels of 2',3'-cAMP and abolished the increase in adenosine and its metabolites. In conclusion, kidneys express CNPase, and renal CNPase mediates in part the renal 2',3'-cAMP-adenosine pathway. Copyright © 2014 the American Physiological Society.

RAPAMYCIN INCREASES LENGTH AND MECHANOSENSORY FUNCTION OF PRIMARY CILIA IN RENAL EPITHELIAL AND VASCULAR ENDOTHELIAL CELLS.

PubMed

Sherpa, Rinzhin T; Atkinson, Kimberly F; Ferreira, Viviana P; Nauli, Surya M

2016-12-01

Primary cilia arebiophysically-sensitive organelles responsible for sensing fluid-flow and transducing this stimulus into intracellular responses. Previous studies have shown that the primary cilia mediate flow-induced calcium influx, and sensitivity of cilia function to flow is correlated to cilia length. Cells with abnormal cilia length or function can lead to a host of diseases that are collectively termed as ciliopathies. Rapamycin, a potent inhibitor of mTOR (mammalian target of rapamycin), has been demonstrated to be a potential pharmacological agent against the aberrant mTOR signaling seen in ciliopathies such as polycystic kidney disease (PKD) and tuberous sclerosis complex (TSC). Here we look at the effects of rapamycin on ciliary length and function for the first time. Compared to controls, primary cilia in rapamycin-treated porcine renal epithelial and mouse vascular endothelial cells showed a significant increase in length. Graded increases in fluid-shear stress further indicates that rapamycin enhances cilia sensitivity to fluid flow. Treatment with rapamycin led to G0 arrest in porcine epithelial cells while no significant change in cell cycle were observed in rapamycin-treated mouse epithelial or endothelial cells, indicating a species-specific effect of rapamycin. Given the previousin vitro and in vivo studies establishing rapamycin as a potential therapeutic agent for ciliopathies, such as PKD and TSC, our studies show that rapamycin enhances ciliary function and sensitivity to fluid flow. The results of our studies suggest a potential ciliotherapeutic effect of rapamycin.

Ameliorative Effect of Gallic Acid on Cyclophosphamide-Induced Oxidative Injury and Hepatic Dysfunction in Rats

PubMed Central

Olayinka, Ebenezer Tunde; Ore, Ayokanmi; Ola, Olaniyi Solomon; Adeyemo, Oluwatobi Adewumi

2015-01-01

Cyclophosphamide (CP), a bifunctional alkylating agent used in chemotherapy has been reported to induce organ toxicity mediated by generation of reactive oxygen species and oxidative stress. Gallic acid (GA), a phenolic substance, is a natural antioxidant with proven free radical scavenging activity and offers protection against oxidative damage. This research study was designed to investigate the ameliorative effect of GA against CP-induced toxicity in rats. Twenty-five male Wistar rats (180–200 g) were randomized into five treatment groups: (A) control, (B) CP, 2 mg/kg body weight (b.w.), (C) pre-treatment with GA (20 mg/kg b.w.) for seven days followed by CP (2 mg/kg b.w.) for seven days, (D) co-treatment with GA (20 mg/kg b.w) and CP (2 mg/kg b.w.) for seven days, and (E) GA (20 mg/kg b.w.) for seven days. CP induced marked renal and hepatic damages as plasma levels of urea, creatinine, bilirubin and activities of AST, ALT, ALP and GGT were significantly elevated (p < 0.05) in the CP-treated group relative to control. In addition, hepatic levels of GSH, vitamin C and activities of SOD, catalase and GST significantly reduced in the CP-treated group when compared with control. This was accompanied with a significant increase in hepatic lipid peroxidation. The restoration of the markers of renal and hepatic damages as well as antioxidant indices and lipid peroxidation by pre- and co-treatment with GA clearly shows that GA offers ameliorative effect by scavenging the reactive oxygen species generated by CP. This protective effect may be attributed to the antioxidant property of gllic acid. PMID:29083393

Food-advanced glycation end products aggravate the diabetic vascular complications via modulating the AGEs/RAGE pathway.

PubMed

Lv, Xing; Lv, Gao-Hong; Dai, Guo-Ying; Sun, Hong-Mei; Xu, Hui-Qin

2016-11-01

The aim of this study was to investigate the effects of high-advanced glycation end products (AGEs) diet on diabetic vascular complications. The Streptozocin (STZ)-induced diabetic mice were fed with high-AGEs diet. Diabetic characteristics, indicators of renal and cardiovascular functions, and pathohistology of pancreas, heart and renal were evaluated. AGEs/RAGE/ROS pathway parameters were determined. During the experiments, the diabetic mice exhibited typical characteristics including weight loss, polydipsia, polyphagia, polyuria, high-blood glucose, and low-serum insulin levels. However, high-AGEs diet effectively aggravated these diabetic characteristics. It also increased the 24-h urine protein levels, serum levels of urea nitrogen, creatinine, c-reactive protein (CRP), low density lipoprotein (LDL), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in the diabetic mice. High-AGEs diet deteriorated the histology of pancreas, heart, and kidneys, and caused structural alterations of endothelial cells, mesangial cells and podocytes in renal cortex. Eventually, high-AGEs diet contributed to the high-AGE levels in serum and kidneys, high-levels of reactive oxygen species (ROS) and low-levels of superoxide dismutase (SOD) in serum, heart, and kidneys. It also upregulated RAGE mRNA and protein expression in heart and kidneys. Our results showed that high-AGEs diet deteriorated vascular complications in the diabetic mice. The activation of AGEs/RAGE/ROS pathway may be involved in the pathogenesis of vascular complications in diabetes. Copyright © 2016 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

[Pregnancy in patients with renal transplantation: maternal and fetal morbidity].

PubMed

Romero Arauz, Juan Fernando; Ayala Méndez, José Antonio; Jiménez Solís, Guillermo

2008-11-01

Preeclampsia is a multisystemic syndrome with unknown etiology and characterized by abnormal vascular placentation response. Patients with renal transplantation restore them fertility 10 months after the intervention. To evaluate incidence of preeclampsia and maternal-perinatal outcome in patients with renal transplantation. Comparative, observational and retrospective study performed in pregnant patients with renal transplantation, from December 1999 to April 2008 at Perinatology of Hypertensive Diseases Department of the Unidad Medica de Alta Especialidad de Ginecoobstetricia Luis Castelazo Ayala, IMSS. Davison' guide, descriptive statistic, and Fischer exact test were used. Thirty patients were analyzed, 27 cases satisfy Davison's recommended guidelines, and the rest did not achieve these criteria (p = 0.001). Preeclampsia occurred in 15 cases (50%), preterm delivery in 15 (50%), and fetal growth restriction in 6 (20%). Among the 11 patients with previous chronic hypertension, 8 developed superimposed preeclampsia (72%), and 9 had delivery before 37 weeks of gestation (82%). Malfunction of renal transplantation, before pregnancy, was associated with maternal and perinatal poor outcome (p = 0.006). There were no maternal deaths, but one perinatal (3%) Successful pregnancy is possible in patients with renal transplantation, however there is a high risk of preeclampsia, infection, and fetal growth restriction. Patients with renal transplantation must fulfill Davison's pre-pregnancy guidelines.

Sodium thiosulfate protects brain in rat model of adenine induced vascular calcification.

PubMed

Subhash, N; Sriram, R; Kurian, Gino A

2015-11-01

Vascular bed calcification is a common feature of ends stage renal disease that may lead to a complication in cardiovascular and cerebrovascular beds, which is a promoting cause of myocardial infarction, stroke, dementia and aneurysms. Sodium thiosulfate (STS) due to its multiple properties such as antioxidant and calcium chelation has been reported to prevent vascular calcification in uremic rats, without mentioning its impact on cerebral function. Moreover, the previous studies have not explored the effect of STS on the mitochondrial dysfunction, one of the main pathophysiological features associated with the disease and the main site for STS metabolism. The present study addresses this limitation by using a rat model where 0.75% adenine was administered to induce vascular calcification and 400 mg/kg b wt. of STS was given as preventive and curative agent. The blood and urine chemistries along with histopathology of aorta confirms the renal protective effect of STS in two modes of administration. The brain oxidative stress assessment was made through TBARS level, catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities, found to be in the near normal level. STS administration not only reduced the mitochondrial oxidative stress (measured by TBARS, SOD, GPx and CAT) but also preserved the mitochondrial respiratory enzyme activities (NADH dehydrogenase, Succinate dehydrogenase and Malate dehydrogenase) and its physiology (measured by P/O ratio and RCR). In fact, the protective effect of STS was prominent, when it was administered as a curative agent, where low H2S and high thiosulfate level was observed along with low cystathionine β synthase activity, confirms thiosulfate mediated renal protection. In conclusion, STS when given after induction of calcification is protective to the brain by preserving its mitochondria, compared to the treatment given concomitantly. Copyright © 2015 Elsevier Ltd. All rights reserved.

Cyanidin-3-O-glucoside ameliorates diabetic nephropathy through regulation of glutathione pool.

PubMed

Qin, Yan; Zhai, Qianqian; Li, Yan; Cao, Meng; Xu, Yun; Zhao, Kelei; Wang, Tao

2018-07-01

Diabetic nephropathy (DN) is a common complication of diabetes and the major cause of chronic kidney disease. Cyanidin 3-glucoside (C3G) is the most widespread anthocyanin in nature. In the present study, we aimed to investigate the possible effects of C3G on DN in db/db mice. We found that body weights and high levels of fasting blood glucose, serum insulin, C-peptide, glycosylated hemoglobin A1c, and systolic blood pressure in diabetic mice were significantly reduced by C3G. C3G also reduced the ratio of kidney to body weight and the levels of blood urea nitrogen (BUN), serum creatinine, urinary albumin content and albumin/creatinine ratio (ACR), ameliorated the pathological changes of kidneys, reduced the surface area of Bowman's capsule, glomerular tuft, Bowman's space, and decreased renal expression of collagen IV, fibronectin, transforming growth factor β 1 (TGFβ1), matrix metalloprotein 9 (MMP9) and α-smooth muscle actin (α-SMA) in db/db mice. The Lee's index, perirenal white adipose tissue weight, and high levels of blood and renal triglyceride and cholesterol were decreased by C3G. Moreover, C3G reduced systemic levels and renal expression of tumor necrosis factor ɑ (TNFɑ), IL-1ɑ, and monocyte chemotactic protein-1 (MCP-1), indicating the inhibition of inflammation. Furthermore, C3G increased glutathione (GSH) level and decreased GSSG level in kidneys of diabetic mice. The renal mRNA expression of glutamate-cysteine ligase catalytic subunit (GCLC) and glutamate-cysteine ligase modifier subunit (GCLM) was increased by C3G in diabetic mice. Buthionine sulphoximine (BSO), an inhibitor of GSH synthesis, inhibited the effects of C3G on glucose metabolic dysfunction and DN. The data demonstrates that enhancement of GSH pool is involved in the renal-protective effects of C3G. Overall, C3G could be a promising therapeutic option for attenuation of diabetes and DN. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Berberine ameliorates diabetic nephropathy by inhibiting TLR4/NF-κB pathway.

PubMed

Zhu, Liping; Han, Jiakai; Yuan, Rongrong; Xue, Lei; Pang, Wuyan

2018-03-31

Diabetic nephropathy (DN) is the leading cause of end-stage renal failure, contributing to severe morbidity and mortality in diabetic patients. Berberine (BBR) has been well characterized to exert renoprotective effects in DN progression. However, the action mechanism of BBR in DN remains to be fully understood. The DN rat model was generated by intraperitoneal injection of streptozotocin (STZ, 65 mg/kg body weight) while 30 mM high glucose (HG)-treated podocytes were used as an in vitro DN model. The fasting blood glucose level and ratio of kidney weight to body weight were measured after BBR treatment (50, 100, or 200 mg/kg) in STZ-induced DN rats. The renal injury parameters including 24-h urinary protein, blood urea nitrogen and serum creatinine were assessed. qRT-PCR was performed to detect the transcript amounts of inflammatory factors. The concentrations of inflammatory factors were evaluated by ELISA kits. Western blot analysis was conducted to measure the amounts of TLR4/NF-κB-related proteins. The apoptotic rate of podocytes was analyzed by flow cytometry using Annexin V/propidium iodide. Berberine reduced renal injury in STZ-induced DN rat model, as evidenced by the decrease in fasting blood glucose, ratio of kidney weight to body weight, 24-h urinary protein, serum creatinine, and blood urine nitrogen. BBR attenuated the systemic and renal cortex inflammatory response and inhibited TLR4/NF-κB pathway in STZ-induced DN rats and HG-induced podocytes. Also, HG-induced apoptosis of podocytes was lowered by BBR administration. Furthermore, blockade of TLR4/NF-κB pathway by resatorvid (TAK-242) or pyrrolidine dithiocarbamate aggravated the inhibitory effect of BBR on HG-induced inflammatory response and apoptosis in podocytes. Berberine ameliorated DN through relieving STZ-induced renal injury, inflammatory response, and podocyte HG-induced apoptosis via inactivating TLR4/NF-κB pathway.

Incidental Anatomic Finding of Celiacomesenteric Trunk Associated with 'Nutcracker Phenomenon,' or Compression of the Left Renal Vein.

PubMed

Peterson, Joshua; Hage, Anthony N; Diljak, Stephan; Long, Benjamin D; Marcusa, Daniel P; Stribley, John M; Brzezinski, David W; Eliason, Jonathan

2017-12-15

BACKGROUND Celiacomesenteric trunk (CMT) is a very rare anatomic finding in which the celiac artery and the superior mesenteric artery (SMA) originate from the abdominal aorta through a common trunk. Clinical associations with CMT include arterial aneurysm, thrombosis, and celiac artery compression. However, an association between CMT and abdominal venous congestion caused by left renal vein compression, or 'nutcracker phenomenon,' has not been previously reported. CASE REPORT A 91-year-old woman, who died from a cerebrovascular accident (CVA), underwent a cadaveric examination at our medical school. On examination of the abdomen, there was an incidental finding of CMT. The arterial and venous diameters were measured, and vascular histopathology was undertaken. The vascular anatomy was consistent with CMT type 1-b. Nutcracker phenomenon (NCP) (left renal vein compression) was seen anatomically as dilatation and engorgement of the left renal vein, relative to the right renal vein (10.77±0.13 mm vs. 4.49±0.56 mm, respectively), and dilatation and engorgement of the left ovarian vein, relative to the right ovarian vein (4.37±0.15 mm vs. 1.06±0.09 mm, respectively) with left ovarian varicocele. The aortoceliac angle (ACA) and the aortomesenteric angle (AMA) approached zero degrees. CONCLUSIONS We have described a rare anatomic finding of CMT that created an acute AMA and NCP. Awareness of this rare association between CMT and NCP by clinicians, vascular surgeons, and radiologists may be of value in the future evaluation and surgical management of patients who present clinically with 'nutcracker syndrome.'

Endovascular management of recurrent stenosis following left renal vein transposition for the treatment of Nutcracker syndrome.

PubMed

Baril, Donald T; Polanco, Patricio; Makaroun, Michel S; Chaer, Rabih A

2011-04-01

Nutcracker syndrome is an entity resulting from left renal vein compression by the superior mesenteric artery and the aorta, leading to symptoms of left flank pain and hematuria. Conventional treatment has been surgical, commonly through transposition of the left renal vein to a more caudal location on the inferior vena cava. Additionally, endovascular approaches, primarily via renal vein stenting, have been described for treatment of this syndrome. We report the case of a patient with Nutcracker syndrome who underwent successful left renal vein transposition but then developed recurrent symptoms 10 months postoperatively and was successfully treated with angioplasty and stenting. Copyright © 2011 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.

Vitamin D in Vascular Calcification: A Double-Edged Sword?

PubMed

Wang, Jeffrey; Zhou, Jimmy J; Robertson, Graham R; Lee, Vincent W

2018-05-22

Vascular calcification (VC) as a manifestation of perturbed mineral balance, is associated with aging, diabetes and kidney dysfunction, as well as poorer patient outcomes. Due to the current limited understanding of the pathophysiology of vascular calcification, the development of effective preventative and therapeutic strategies remains a significant clinical challenge. Recent evidence suggests that traditional risk factors for cardiovascular disease, such as left ventricular hypertrophy and dyslipidaemia, fail to account for clinical observations of vascular calcification. Therefore, more complex underlying processes involving physiochemical changes to mineral balance, vascular remodelling and perturbed hormonal responses such as parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF-23) are likely to contribute to VC. In particular, VC resulting from modifications to calcium, phosphate and vitamin D homeostasis has been recently elucidated. Notably, deregulation of vitamin D metabolism, dietary calcium intake and renal mineral handling are associated with imbalances in systemic calcium and phosphate levels and endothelial cell dysfunction, which can modulate both bone and soft tissue calcification. This review addresses the current understanding of VC pathophysiology, with a focus on the pathogenic role of vitamin D that has provided new insights into the mechanisms of VC.

Maternal separation diminishes α-adrenergic receptor density and function in renal vasculature from male Wistar-Kyoto rats.

PubMed

Loria, Analia S; Osborn, Jeffrey L

2017-07-01

Adult rats exposed to maternal separation (MatSep) are normotensive but display lower glomerular filtration rate and increased renal neuroadrenergic drive. The aim of this study was to determine the renal α-adrenergic receptor density and the renal vascular responsiveness to adrenergic stimulation in male rats exposed to MatSep. In addition, baroreflex sensitivity was assessed to determine a component of neural control of the vasculature. Using tissue collected from 4-mo-old MatSep and control rats, α 1 -adrenergic receptors (α 1 -ARs) were measured in renal cortex and isolated renal vasculature using receptor binding assay, and the α-AR subtype gene expression was determined by RT-PCR. Renal cortical α 1 -AR density was similar between MatSep and control tissues (B max = 44 ± 1 vs. 42 ± 2 fmol/mg protein, respectively); however, MatSep reduced α 1 -AR density in renal vasculature (B max = 47 ± 4 vs. 62 ± 4 fmol/mg protein, P < 0.05, respectively). In a separate group of rats, the pressor, bradycardic, and renal vascular constrictor responses to acute norepinephrine injection (NE, 0.03-0.25 μg/μl) were determined under anesthesia. Attenuated NE-induced renal vasoconstriction was observed in rats exposed to MatSep compared with control ( P < 0.05). A third group of rats was infused at steady state with the α 1 agonist phenylephrine (10 μg/min iv) and vasodilator sodium nitroprusside (5 μg/min iv). The difference between the change in heart rate/mean arterial pressure slopes was indicative of reduced baroreflex sensitivity in MatSep vs. control rats (-0.45 ± 0.04 vs. -0.95 ± 0.07 beats·min -1 ·mmHg -1 , P < 0.05). These data support the notion that reduced α-adrenergic receptor expression and function in the renal vasculature could develop secondary to MatSep-induced overactivation of the renal neuroadrenergic tone. Copyright © 2017 the American Physiological Society.

Orbital Atherectomy in the Renal Artery: A New Frontier for an Emerging Technology?

PubMed

Valle, Javier A; Armstrong, Ehrin J; Waldo, Stephen W

2017-01-01

Orbital atherectomy has been developed as a method to modify calcified plaque in the peripheral vasculature, with extensive experience and data supporting its use in infrainguinal peripheral arterial disease. However, calcific atherosclerotic disease occurs in other vascular beds and may benefit from the application of this technology. In this case report, we describe the first reported use of orbital atherectomy in a renal artery. A 55-year-old male with severe drug-refractory hypertension was found to have renal artery stenosis, with severe calcification of the right renal artery. Orbital atherectomy was utilized for initial plaque modification, and he underwent stenting of the renal artery lesion with an excellent angiographic and clinical result at follow-up. In conclusion, orbital atherectomy is a safe and effective means of plaque modification for severely calcified lesions. The safe and effective use of orbital atherectomy in the renal vasculature suggests an opportunity for ongoing evaluation into expanded roles for this technology beyond the coronary and lower-extremity arterial beds.

Renoprotective effects of berberine and its potential effect on the expression of β-arrestins and intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 in streptozocin-diabetic nephropathy rats.

PubMed

Tang, Li-Qin; Ni, Wei-Jian; Cai, Ming; Ding, Hai-Hua; Liu, Sheng; Zhang, Shan-Tang

2016-09-01

Berberine has been shown to exert protective effects against diabetic nephropathy (DN), but the mechanisms involved have not been fully characterized. The aim of the present study was to explore the effects of berberine on the expression of β-arrestins, intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in DN rat kidneys and investigate the underlying molecular mechanisms. To create the DN model, rats fed a high-fat and high-glucose diet were injected with a single dose of streptozotocin (35 mg/kg, i.p.). Then, DN rats were either treated or not with berberine (50, 100, 200 mg/kg per day, i.g., 8 weeks). Periodic acid-Schiff staining was used to evaluate renal histopathological changes. Renal tissue levels of β-arrestin 1 and β-arrestin 2 were determined by Western blot analysis, whereas immunohistochemistry was used to determine renal ICAM-1 and VCAM-1 levels. Berberine (100, 200 mg/kg) ameliorated the histopathological changes in the diabetic kidney. Western blot analysis revealed significant increases in ICAM-1 and VCAM-1 levels in the kidneys of DN rats, which were reversed by treatment with 100 and 200 mg/kg berberine. In addition, berberine treatment (50, 100, 200 mg/kg) increased diabetic-induced decreases in β-arrestin 1 and β-arrestin 2. Berberine exhibited renoprotective effects in DN rats. The underlying molecular mechanisms may be associated with changes in the levels and regulation of β-arrestin expression, as well as ICAM-1 and VCAM-1 levels in the rat kidney. © 2015 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

Renalase Protects against Renal Fibrosis by Inhibiting the Activation of the ERK Signaling Pathways

PubMed Central

Wu, Yiru; Wang, Liyan; Deng, Dai; Zhang, Qidong; Liu, Wenhu

2017-01-01

Renal interstitial fibrosis is a common pathway for the progression of chronic kidney disease (CKD) to end-stage renal disease. Renalase, acting as a signaling molecule, has been reported to have cardiovascular and renal protective effects. However, its role in renal fibrosis remains unknown. In this study, we evaluated the therapeutic efficacy of renalase in rats with complete unilateral ureteral obstruction (UUO) and examined the inhibitory effects of renalase on transforming growth factor-β1 (TGF-β1)-induced epithelial–mesenchymal transition (EMT) in human proximal renal tubular epithelial (HK-2) cells. We found that in the UUO model, the expression of renalase was markedly downregulated and adenoviral-mediated expression of renalase significantly attenuated renal interstitial fibrosis, as evidenced by the maintenance of E-cadherin expression and suppressed expression of α-smooth muscle actin (α-SMA), fibronectin and collagen-I. In vitro, renalase inhibited TGF-β1-mediated upregulation of α-SMA and downregulation of E-cadherin. Increased levels of Phospho-extracellular regulated protein kinases (p-ERK1/2) in TGF-β1-stimulated cells were reversed by renalase cotreatment. When ERK1 was overexpressed, the inhibition of TGF-β1-induced EMT and fibrosis mediated by renalase was attenuated. Our study provides the first evidence that renalase can ameliorate renal interstitial fibrosis by suppression of tubular EMT through inhibition of the ERK pathway. These results suggest that renalase has potential renoprotective effects in renal interstitial fibrosis and may be an effective agent for slowing CKD progression. PMID:28448446

The effect of losartan and carvedilol on renal haemodynamics and altered metabolism in fructose-fed Sprague-Dawley rats.

PubMed

Abdulla, Mohammed H; Sattar, Munavvar A; Abdullah, Nor A; Johns, Edward J

2012-09-01

The aim of this study is to assess the effects of losartan and carvedilol on metabolic parameters and renal haemodynamic responses to angiotensin II (Ang II) and adrenergic agonists in the model of fructose-fed rat. Thirty-six Sprague-Dawley rats were fed for 8 weeks either 20% fructose solution (F) or tap water (C) ad libitum. F or C group received either losartan or carvedilol (10 mg/kg p.o.) daily for the last 3 weeks of the study (FL and L) and (FCV and CV), respectively, then in acute studies the renal vasoconstrictor actions of Ang II, noradrenaline (NA), phenylephrine (PE) and methoxamine (ME) were determined. Data, mean±SEM were analysed using ANOVA with significance at P <0.05. Losartan and carvedilol decreased the area under the glucose tolerance curve of the fructose-fed group. The responses (%) to NA, PE, ME and Ang II in F were lower (P <0.05) than C (F vs. C, 17±2 vs. 38±3; 24±2 vs. 48±2; 12±2 vs. 34±2; 17±2 vs. 26±2), respectively. L had higher (P <0.05) responses to NA and PE while CV had blunted (P <0.05) responses to NA, PE and Ang II compared to C (L, CV vs. C, 47±3, 9±2 vs. 38±3; 61±3, 29±3 vs. 48±2; 16±3, 4±3 vs. 26±2), respectively. FL but not FCV group had enhanced (P <0.05) responses to NA, PE and ME compared to F (FL vs. F, 33±3 vs. 17±2; 45±3 vs. 24±2; 26±3 vs. 12±2), respectively. Losartan and carvedilol had an important ameliorating effect on fructose-induced insulin resistance. Losartan treatment could be an effective tool to restore normal vascular reactivity in the renal circulation of the fructose-fed rat.

Stretch-activation of angiotensin II type 1a receptors contributes to the myogenic response of mouse mesenteric and renal arteries.

PubMed

Schleifenbaum, Johanna; Kassmann, Mario; Szijártó, István András; Hercule, Hantz C; Tano, Jean-Yves; Weinert, Stefanie; Heidenreich, Matthias; Pathan, Asif R; Anistan, Yoland-Marie; Alenina, Natalia; Rusch, Nancy J; Bader, Michael; Jentsch, Thomas J; Gollasch, Maik

2014-07-07

Vascular wall stretch is the major stimulus for the myogenic response of small arteries to pressure. The molecular mechanisms are elusive, but recent findings suggest that G protein-coupled receptors can elicit a stretch response. To determine whether angiotensin II type 1 receptors (AT1R) in vascular smooth muscle cells exert mechanosensitivity and identify the downstream ion channel mediators of myogenic vasoconstriction. We used mice deficient in AT1R signaling molecules and putative ion channel targets, namely AT1R, angiotensinogen, transient receptor potential channel 6 (TRPC6) channels, or several subtypes of the voltage-gated K+ (Kv7) gene family (KCNQ3, 4, or 5). We identified a mechanosensing mechanism in isolated mesenteric arteries and in the renal circulation that relies on coupling of the AT1R subtype a to a Gq/11 protein as a critical event to accomplish the myogenic response. Arterial mechanoactivation occurs after pharmacological block of AT1R and in the absence of angiotensinogen or TRPC6 channels. Activation of AT1R subtype a by osmotically induced membrane stretch suppresses an XE991-sensitive Kv channel current in patch-clamped vascular smooth muscle cells, and similar concentrations of XE991 enhance mesenteric and renal myogenic tone. Although XE991-sensitive KCNQ3, 4, and 5 channels are expressed in vascular smooth muscle cells, XE991-sensitive K+ current and myogenic contractions persist in arteries deficient in these channels. Our results provide definitive evidence that myogenic responses of mouse mesenteric and renal arteries rely on ligand-independent, mechanoactivation of AT1R subtype a. The AT1R subtype a signal relies on an ion channel distinct from TRPC6 or KCNQ3, 4, or 5 to enact vascular smooth muscle cell activation and elevated vascular resistance. © 2014 American Heart Association, Inc.

Bmi-1 plays a critical role in protection from renal tubulointerstitial injury by maintaining redox balance

PubMed Central

Jin, Jianliang; Lv, Xianhui; Chen, Lulu; Zhang, Wei; Li, Jinbo; Wang, Qian; Wang, Rong; Lu, Xiang; Miao, Dengshun

2014-01-01

To determine whether Bmi-1 deficiency could lead to renal tubulointerstitial injury by mitochondrial dysfunction and increased oxidative stress in the kidney, 3-week-old Bmi-1-/- mice were treated with the antioxidant N-acetylcysteine (NAC, 1 mg mL−1) in their drinking water, or pyrro-quinoline quinone (PQQ, 4 mg kg−1 diet) in their diet for 2 weeks, and their renal phenotypes were compared with vehicle-treated Bmi1-/- and wild-type mice. Bmi-1 was knocked down in human renal proximal tubular epithelial (HK2) cells which were treated with 1 mm NAC for 72 or 96 h, and their phenotypes were compared with control cells. Five-week-old vehicle-treated Bmi-1-/- mice displayed renal interstitial fibrosis, tubular atrophy, and severe renal function impairment with decreased renal cell proliferation, increased renal cell apoptosis and senescence, and inflammatory cell infiltration. Impaired mitochondrial structure, decreased mitochondrial numbers, and increased oxidative stress occurred in Bmi-1-/- mice; subsequently, this caused DNA damage, the activation of TGF-β1/Smad signaling, and the imbalance between extracellular matrix synthesis and degradation. Oxidative stress-induced epithelial-to-mesenchymal transition of renal tubular epithelial cells was enhanced in Bmi-1 knocked down HK2 cells. All phenotypic alterations caused by Bmi-1 deficiency were ameliorated by antioxidant treatment. These findings indicate that Bmi-1 plays a critical role in protection from renal tubulointerstitial injury by maintaining redox balance and will be a novel therapeutic target for preventing renal tubulointerstitial injury. PMID:24915841

[Atheroembolism renal disease: diagnosis and etiologic factors].

PubMed

Granata, A; Insalaco, M; Di Pietro, F; Di Rosa, S; Romano, G; Scuderi, R

2012-07-01

Atheromatous renal disease is the major cause of renal insufficiency in the elderly, and cholesterol embolism is a manifestation of this disease. Cholesterol embolism occurs in patients suffering from diffuse erosive atherosclerosis, usually after triggering causes, such as aortic surgery, arterial invasive procedures (angiography, left heart catheterization and coronary angioplasty) and anticoagulant or thrombolytic therapy. It is characterized by occlusion of small arteries with cholesterol emboli deriving from eroded atheromatous plaques of the aorta or large feeder arteries. The proximity of the kidneys to the abdominal aorta and the large renal blood supply make the kidney a frequent target organ for cholesterol atheroembolism. The exact incidence of atheroembolic renal disease (AERD) is not known. The reported incidence AERD varied in the literature because of the differences in study design and the different criteria used for making the diagnosis. Retrospective data derived from autopsy or biopsy studies may exaggerate the frequency by including many subclinical cases. Clinical observations that are based on a short duration of follow-up after an invasive vascular procedure and the infrequency of the confirmatory renal biopsies can lead to an underestimation of the true incidence of AERD. The initial signs and symptoms in patients diagnosed with cholesterol embolism were blue toes syndrome, livedo reticularis, gangrene, leg, toe or foot pain, abdominal pain and flank or back pain, gross haematuria, accelerated hypertension and renal failure. Cholesterol embolism may also be associated with fever, increased erythrocyte sedimentation rate and eosinophilia. Thus, in the cases of spontaneous cholesterol embolism, differential diagnosis includes, polyarteritis nodosa, allergic vasculitis and subacute bacterial endocarditis. Skin and renal biopsy specimens are the best sample for histologic diagnosis. There is, at present, no pharmacological treatments shown to be

Losartan corrects abnormal frequency response of renal vasculature in congestive heart failure.

PubMed

DiBona, Gerald F; Sawin, Linda L

2003-11-01

In congestive heart failure, renal blood flow is decreased and renal vascular resistance is increased in a setting of increased activity of both the sympathetic nervous and renin-angiotensin systems. The renal vasoconstrictor response to renal nerve stimulation is enhanced. This is associated with an abnormality in the low-pass filter function of the renal vasculature wherein higher frequencies (> or =0.01 Hz) within renal sympathetic nerve activity are not normally attenuated and are passed into the renal blood flow signal. This study tested the hypothesis that excess angiotensin II action mediates the abnormal frequency response characteristics of the renal vasculature in congestive heart failure. In anesthetized rats, the renal vasoconstrictor response to graded frequency renal nerve stimulation was significantly greater in congestive heart failure than in control rats. Losartan attenuated the renal vasoconstrictor response to a significantly greater degree in congestive heart failure than in control rats. In control rats, the frequency response of the renal vasculature was that of a first order (-20 dB/frequency decade) low-pass filter with a corner frequency (-3 dB, 30% attenuation) of 0.002 Hz and 97% attenuation (-30 dB) at > or =0.1 Hz. In congestive heart failure rats, attenuation did not exceed 45% (-5 dB) over the frequency range of 0.001-0.6 Hz. The frequency response of the renal vasculature was not affected by losartan treatment in control rats but was completely restored to normal by losartan treatment in congestive heart failure rats. The enhanced renal vasoconstrictor response to renal nerve stimulation and the associated abnormality in the frequency response characteristics of the renal vasculature seen in congestive heart failure are mediated by the action of angiotensin II on renal angiotensin II AT1 receptors.

Naringin ameliorates gentamicin-induced nephrotoxicity and associated mitochondrial dysfunction, apoptosis and inflammation in rats: possible mechanism of nephroprotection.

PubMed

Sahu, Bidya Dhar; Tatireddy, Srujana; Koneru, Meghana; Borkar, Roshan M; Kumar, Jerald Mahesh; Kuncha, Madhusudana; Srinivas, R; Shyam Sunder, R; Sistla, Ramakrishna

2014-05-15

Gentamicin-induced nephrotoxicity has been well documented, although its underlying mechanisms and preventive strategies remain to be investigated. The present study was designed to investigate the protective effect of naringin, a bioflavonoid, on gentamicin-induced nephrotoxicity and to elucidate the potential mechanism. Serum specific renal function parameters (blood urea nitrogen and creatinine) and histopathology of kidney tissues were evaluated to assess the gentamicin-induced nephrotoxicity. Renal oxidative stress (lipid peroxidation, protein carbonylation, enzymatic and non-enzymatic antioxidants), inflammatory (NF-kB [p65], TNF-α, IL-6 and MPO) and apoptotic (caspase 3, caspase 9, Bax, Bcl-2, p53 and DNA fragmentation) markers were also evaluated. Significant decrease in mitochondrial NADH dehydrogenase, succinate dehydrogenase, cytochrome c oxidase and mitochondrial redox activity indicated the gentamicin-induced mitochondrial dysfunction. Naringin (100mg/kg) treatment along with gentamicin restored the mitochondrial function and increased the renal endogenous antioxidant status. Gentamicin induced increased renal inflammatory cytokines (TNF-α and IL-6), nuclear protein expression of NF-κB (p65) and NF-κB-DNA binding activity and myeloperoxidase (MPO) activity were significantly decreased upon naringin treatment. In addition, naringin treatment significantly decreased the amount of cleaved caspase 3, Bax, and p53 protein expression and increased the Bcl-2 protein expression. Naringin treatment also ameliorated the extent of histologic injury and reduced inflammatory infiltration in renal tubules. U-HPLS-MS data revealed that naringin co-administration along with gentamicin did not alter the renal uptake and/or accumulation of gentamicin in kidney tissues. These findings suggest that naringin treatment attenuates renal dysfunction and structural damage through the reduction of oxidative stress, mitochondrial dysfunction, inflammation and apoptosis in

Peripheral and central interactions between the renin-angiotensin system and the renal sympathetic nerves in control of renal function.

PubMed

DiBona, G F

2001-06-01

Increases in renal sympathetic nerve activity (RSNA) regulate the functions of the nephron, the vasculature, and the renin-containing juxtaglomerular granular cells. As increased activity of the renin-angiotensin system can also influence nephron and vascular function, it is important to understand the interactions between RSNA and the renin-angiotensin system in the control of renal function. These interactions can be intrarenal, that is, the direct (via specific innervation) and indirect (via angiotensin II) contributions of increased RSNA to the regulation of renal function. The effects of increased RSNA on renal function are attenuated when the activity of the renin-angiotensin system is suppressed or antagonized with angiotensin-converting enzyme inhibitors or angiotensin II-type AT1 receptor antagonists. The effects of intrarenal administration of angiotensin II are attenuated following renal denervation. These interactions can also be extrarenal, that is, in the central nervous system, wherein RSNA and its arterial baroreflex control are modulated by changes in activity of the renin-angiotensin system. In addition to the circumventricular organs, the permeable blood-brain barrier of which permits interactions with circulating angiotensin II, there are interactions at sites behind the blood-brain barrier that depend on the influence of local angiotensin II. The responses to central administration of angiotensin II type AT1 receptor antagonists, into the ventricular system or microinjected into the rostral ventrolateral medulla, are modulated by changes in activity of the renin-angiotensin system produced by physiological changes in dietary sodium intake. Similar modulation is observed in pathophysiological models wherein activity of both the renin-angiotensin and sympathetic nervous systems is increased (e.g., congestive heart failure). Thus, both renal and extrarenal sites of interaction between the renin-angiotensin system and RSNA are involved in

REDUCTION OF ALDOSTERONE PRODUCTION IMPROVES RENAL OXIDATIVE STRESS AND FIBROSIS IN DIABETIC RATS

PubMed Central

Matavelli, Luis C.; Siragy, Helmy M.

2012-01-01

SUMMARY Aldosterone is increased in diabetes and contributes to the development of diabetic nephropathy. We hypothesized that reduction in aldosterone production in diabetes by amlodipine or aliskiren improves diabetic kidney disease by attenuating renal oxidative stress and fibrosis. Normoglycemic and streptozotocin-induced diabetes Sprague-Dawley rats were given vehicle, amlodipine or aliskiren individually and combined for six weeks. At the end of study, we evaluated BP, 24h urinary sodium (UNaV) and aldosterone excretion rates, renal interstitial fluid (RIF) levels of nitric oxide (NO), cGMP and 8-isoprostane, and renal morphology. BP was not significantly different between any of experimental groups. UNaV increased in diabetic animals and was not affected by different treatments. Urinary aldosterone excretion increased in diabetic rats receiving vehicle and decreased with amlodipine and aliskiren individually or combined. RIF NO and cGMP levels were reduced in vehicle treated diabetic rats and increased with amlodipine or aliskiren given individually and combined. RIF 8-isoprostane levels and renal immunostaining for PAS and fibronectin were increased in vehicle treated diabetic rats and decreased with aliskiren individually or combined with amlodipine. We conclude that inhibition of aldosterone by amlodipine or aliskiren ameliorates diabetes induced renal injury via improvement of NO-cGMP pathway, and reduction in oxidative stress and fibrosis, independent of BP changes. PMID:23011470

Ameliorating effects of goby fish protein hydrolysates on high-fat-high-fructose diet-induced hyperglycemia, oxidative stress and deterioration of kidney function in rats.

PubMed

Nasri, Rim; Abdelhedi, Ola; Jemil, Ines; Daoued, Ines; Hamden, Khaled; Kallel, Choumous; Elfeki, Abdelfattah; Lamri-Senhadji, Myriem; Boualga, Ahmed; Nasri, Moncef; Karra-Châabouni, Maha

2015-12-05

This study investigated the therapeutic potential of undigested goby fish (Zosterisessor ophiocephalus) muscle proteins (UGP) and their hydrolysates on high-fat-high-fructose diet (HFFD)-fed rats. HFFD induced hyperglycemia, manifested by a significant increase in the levels of glucose and glycogen as well as α-amylase activity when compared to normal rats. The administration of GPHs to HFFD-fed rats significantly decreased α-amylase activity and the contents of blood glucose and hepatic glycogen. By contrast, the UGP increased the glucose metabolic disorders in HFFD-fed rats. Furthermore, HFFD-fed rats showed oxidative stress, as evidenced by decreased antioxidant enzyme activities and glutathione (GSH) levels and increased concentration of the lipid peroxidation product malondialdehyde in liver and kidney. Interestingly, the daily gavage of UGP and GPHs improved the redox status in liver and kidney of HFFD-rats by ameliorating or reversing the above-mentioned changes. Moreover, GPHs exhibited a renal protective role by reversing the HFFD-induced decease of uric acid and increase of creatinine levels in serum and preventing some HFFD-induced changes in kidney architecture. The results demonstrate that GPHs contain bioactive peptides that possess significant hypoglycemic and antioxidant properties, and ameliorate renal damage in rats fed hypercaloric diet. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Clinical efficacy and safety of transcatheter embolization for vascular complications after percutaneous nephrolithotomy.

PubMed