Reducing renal uptake of 111In-DOTATOC: a comparison among various basic amino acids.

PubMed

Lin, Yung-Chang; Hung, Guang-Uei; Luo, Tsai-Yueh; Tsai, Shih-Chuan; Sun, Shung-Shung; Hsia, Chien-Chung; Chen, Shu-Ling; Lin, Wan-Yu

2007-01-01

Several studies have reported significant renal toxicity after the use of a high dose of 90Y-DOTATOC. Thus, renal protection is necessary in treatments with 90Y-DOTA Tyr3-octreotide (DOTATOC). The infusion of certain positively charged amino acids has been shown to effectively reduce renal uptake of DOTATOC. In this study, we compared the effectiveness of three kinds of amino acids, D-lysine (lysine), L-arginine (arginine) and histidine, on renal protection in healthy rats and tried to determine which one was the most effective. Twenty SD healthy male rats were divided into 4 groups: lysine, histidine, arginine, and control. The rats were injected with a dose of 400 mg/kg of amino acid or 2 ml of phosphate-buffered saline (PBS) (as control) intraperitoneally. All rats were sacrificed at 4 hrs after the injection of 1 MBq 111In-DOTATOC. Samples of the kidney were taken and weighed carefully. The counts of radioactivity were measured by a gamma counter and renal concentrations were calculated and expressed as percent injected dose per gram (% ID/g). The renal uptake of 111In-DOTATOC was significantly lower for all three kinds of amino acids when compared to the control group. The renal uptake of 111In-DOTATOC in the lysine group was significantly lower than those in the histidine and arginine groups. The renal uptake of 111In-DOTATOC in the histidine group was lower than that in the arginine group, but no statistical difference was noted. Among these three amino acids, lysine had the best reduction rate of renal uptake of DOTATOC. Histidine was more effective than arginine but no statistical difference was noted.

Comparison of renal ultrasonography and dimercaptosuccinic acid renal scintigraphy in febrile urinary tract infection.

PubMed

Ayazi, Parviz; Mahyar, Abolfazl; Noroozian, Elham; Esmailzadehha, Neda; Barikani, Ameneh

2015-12-01

Accurate and early diagnosis and appropriate treatment of patient with urinary tract infection (UTI) are essential for the prevention or restriction of permanent damage to the kidneys in children. The aim of this study was to compare renal ultrasonography (US) and dimercaptosuccinic acid (DMSA) renal scan in the diagnosis of patients with febrile urinary tract infection. This study involved the medical records of children with febrile urinary tract infection who were admitted to the children's hospital in Qazvin, Iran. Pyelonephritis was diagnosed on the basis of clinical symptoms, laboratory tests and abnormal DMSA renal scans. The criteria for abnormality of renal US were an increase or a decrease in diffuse or focal parenchymal echogenicity, loss of corticomedullary differentiation, kidney position irregularities, parenchymal reduction and increased kidney size. Of the 100 study patients, 23% had an abnormal US and 46% had an abnormal DMSA renal scan. Of the latter patients, 15 had concurrent abnormal US (P value ≤ 0.03, concordance rate: 18%). Renal US had a sensitivity of 32%, specificity of 85%, positive predictive value of 65% and negative predictive value of 60%. Of the 77 patients with normal US, 31 (40.2%) had an abnormal DMSA renal scan. Despite the benefits and accessibility of renal US, its value in the diagnosis of pyelonephritis is limited.

Sclerotherapy of renal cysts using acetic acid: a comparison with ethanol sclerotherapy.

PubMed

Cho, D S; Ahn, H S; Kim, S I; Kim, Y S; Kim, S J; Jeon, G S; Won, J H

2008-12-01

This study compared percutaneous sclerotherapy using 50% acetic acid with that using 99% ethanol for patients with simple renal cysts. The study included 72 simple renal cysts in 64 patients (male/female ratio = 31/33; age range, 31-75 years). Under fluoroscopic guidance, the cyst fluid was aspirated completely. Sclerotherapy was then performed using 50% acetic acid for 32 cysts and 99% ethanol for 40 cysts. The volumes of each renal cyst before and after sclerotherapy were compared using ultrasonography or CT. Medical records were reviewed to analyse any complications. The mean follow-up period was 21.5 months (range, 3-75 months). The mean remnant volume of the cyst after sclerotherapy was 2.6% of the initial volume in the acetic acid group and 14.0% in the ethanol group. The rates of complete remission, partial remission and treatment failure were 90.6%, 9.4% and 0%, respectively, in the acetic acid group, and 60.0%, 30.0% and 10.0%, respectively, in the ethanol group. There were no complications related to sclerotherapy in either group. In conclusion, acetic acid is a safe and effective sclerosing agent, with clinical results superior to those of ethanol, and is an alternative to ethanol for sclerotherapy of renal cysts.

Renoprotective Effect of Humic Acid on Renal Ischemia-Reperfusion Injury: An Experimental Study in Rats.

PubMed

Akbas, Alpaslan; Silan, Coskun; Gulpinar, Murat Tolga; Sancak, Eyup Burak; Ozkanli, Sidika Seyma; Cakir, Dilek Ulker

2015-12-01

Humic acid is an antioxidant molecule used in agriculture and livestock breeding, as well as in medicine. Our aim was to investigate the potential renoprotective effects of humic acid in a renal ischemia reperfusion model. Twenty-one rats were randomly divided into three equal groups. Intraperitoneal serum or humic acid was injected at 1, 12, and 24 h. Non-ischemic group I was evaluated as sham. The left renal artery was clamped in serum (group II) and intraperitoneal humic acid (group III) to subject to left renal ischemic reperfusion procedure. Ischemia and reperfusion time was 60 min for each. Total antioxidant status, total oxidative status, oxidative stress index, and ischemia-modified albumin levels were analyzed biochemically from the serum samples. Kidneys were evaluated histopatologically and immunohistochemically. Biochemical results showed that total oxidative status, ischemia-modified albumin, and oxidative stress index levels were significantly decreased, but total antioxidant status was increased in the humic acid group (III) compared with the ischemia group (II) On histopathological examination, renal tubular dilatation, tubular cell damage and necrosis, dilatation of Bowman's capsule, hyaline casts, and tubular cell spillage were decreased in the humic acid group (III) compared with the ischemia group (II). Immunohistochemical results showed that apoptosis was deteriorated in group III. Renal ischemia reperfusion injury was attenuated by humic acid administration. These observations indicate that humic acid may have a potential therapeutic effect on renal ischemia reperfusion injury by preventing oxidative stress.

Relocation of net-acid-generating waste to improve post-mining water chemistry.

PubMed

Morin, K A; Hutt, N M

2001-01-01

Acidic drainage and metal leaching are long-term environmental liabilities that can persist for many decades to millennia. One technique to improve the water chemistry and ecology of post-mining landscapes is to relocate and submerge net-acid-generating mine materials in a lake or water-retaining impoundment. One example of a carefully executed relocation of waste rock took place at the Eskay Creek Mine in Canada. Pre-relocation studies included an empirical relationship that related (1) the amount of acidity retained by the waste rock during past oxidation to (2) the amount of lime needed in each truckload for neutralization of the acidity and for suppression of metal release. During relocation, thousands of rinse pH measurements indicated net acidity varied significantly over short distances within the waste rock and that acidic rock could not be reliably segregated from near-netural rock. After relocation, water from the watershed continued to be acidic for a few years, then returned to near-neutral pH and near-background concentrations of metals. The chemistry of the lake where the waste rock was submerged remains near background conditions. Therefore, with careful planning and implementation, the relocation and submergence of net-acid-generating materials can greatly improve post-mining water chemistry.

Prevalence of renal uric acid stones in the adult.

PubMed

Trinchieri, Alberto; Montanari, Emanuele

2017-12-01

The aim of this study was to estimate uric acid renal stone prevalence rates of adults in different countries of the world. PubMed was searched for papers dealing with "urinary calculi and prevalence or composition" for the period from January 1996 to June 2016. Alternative searches were made to collect further information on specific topics. The prevalence rate of uric acid stones was computed by the general renal stone prevalence rate and the frequency of uric acid stones in each country. After the initial search, 2180 papers were extracted. Out of them, 79 papers were selected after the reading of the titles and of the abstracts. For ten countries, papers relating to both the renal stone prevalence in the general population and the frequency of uric stones were available. Additional search produced 13 papers that completed information on 11 more countries in 5 continents. Estimated prevalence rate of uric acid stones was >0.75% in Thailand, Pakistan, Saudi Arabia, Iran, South Africa (white population), United States and Australia; ranged 0.50-0.75% in Turkey, Israel, Italy, India (Southern), Spain, Taiwan, Germany, Brazil; and <0.50% in Tunisia, China, Korea, Japan, Caribe, South Africa (blacks), India (Northern). Climate and diet are major determinants of uric acid stone formation. A hot and dry climate increases fluid losses reducing urinary volume and urinary pH. A diet rich in meat protein causes low urinary pH and increased uric acid excretion. On the other hand, uric acid stone formation is frequently associated with obesity, metabolic syndrome and diabetes type 2 that are linked to dietary energy excess mainly from carbohydrate and saturated fat and also present with low urine pH values. An epidemic of uric acid stone formation could be if current nutritional trends will be maintained both in developed countries and in developing countries and the areas of greater climatic risk for the formation of uric acid stones will enlarge as result of the "global

Effect of potential renal acid load of foods on urinary citrate excretion in calcium renal stone formers.

PubMed

Trinchieri, Alberto; Lizzano, Renata; Marchesotti, Federica; Zanetti, Giampaolo

2006-02-01

The aim of this study was to investigate the influence of the potential renal acid load (PRAL) of the diet on the urinary risk factors for renal stone formation. The present series comprises 187 consecutive renal calcium stone patients (114 males, 73 females) who were studied in our stone clinic. Each patient was subjected to an investigation including a 24-h dietary record and 24-h urine sample taken over the same period. Nutrients and calories were calculated by means of food composition tables using a computerized procedure. Daily PRAL was calculated considering the mineral and protein composition of foods, the mean intestinal absorption rate for each nutrient and the metabolism of sulfur-containing amino acids. Sodium, potassium, calcium, magnesium, phosphate, oxalate, urate, citrate, and creatinine levels were measured in the urine. The mean daily PRAL was higher in male than in female patients (24.1+/-24.0 vs 16.1+/-20.1 mEq/day, P=0.000). A significantly (P=0.01) negative correlation (R=-0.18) was found between daily PRAL and daily urinary citrate, but no correlation between PRAL and urinary calcium, oxalate, and urate was shown. Daily urinary calcium (R=0.186, P=0.011) and uric acid (R=0.157, P=0.033) were significantly related to the dietary intake of protein. Daily urinary citrate was significantly related to the intakes of copper (R=0.178, P=0.015), riboflavin (R=0.20, P=0.006), piridoxine (R=0.169, P=0.021) and biotin (R=0.196, P=0.007). The regression analysis by stepwise selection confirmed the significant negative correlation between PRAL and urinary citrate (P=0.002) and the significant positive correlation between riboflavin and urinary citrate (P=0.000). Urinary citrate excretion of renal stone formers (RSFs) is highly dependent from dietary acid load. The computation of the renal acid load is advisable to investigate the role of diet in the pathogenesis of calcium stone disease and it is also a useful tool to evaluate the lithogenic potential of

Serum uric acid levels contribute to new renal damage in systemic lupus erythematosus patients.

PubMed

Reátegui-Sokolova, C; Ugarte-Gil, Manuel F; Gamboa-Cárdenas, Rocío V; Zevallos, Francisco; Cucho-Venegas, Jorge M; Alfaro-Lozano, José L; Medina, Mariela; Rodriguez-Bellido, Zoila; Pastor-Asurza, Cesar A; Alarcón, Graciela S; Perich-Campos, Risto A

2017-04-01

This study aims to determine whether uric acid levels contribute to new renal damage in systemic lupus erythematosus (SLE) patients. This prospective study was conducted in consecutive patients seen since 2012. Patients had a baseline visit and follow-up visits every 6 months. Patients with ≥2 visits were included; those with end-stage renal disease (regardless of dialysis or transplantation) were excluded. Renal damage was ascertained using the SLICC/ACR damage index (SDI). Univariable and multivariable Cox-regression models were performed to determine the risk of new renal damage. Uric acid was included as a continuous and dichotomous (per receiving operating characteristic curve) variable. Multivariable models were adjusted for age at diagnosis, disease duration, socioeconomic status, SLEDAI, SDI, serum creatinine, baseline use of prednisone, antimalarials, and immunosuppressive drugs. One hundred and eighty-six patients were evaluated; their mean (SD) age at diagnosis was 36.8 (13.7) years; nearly all patients were mestizo. Disease duration was 7.7 (6.8) years. Follow-up time was 2.3 (1.1) years. The SLEDAI was 5.2 (4.3) and the SDI 0.8 (1.1). Uric acid levels were 4.5 (1.3) mg/dl. During follow-up, 16 (8.6%) patients developed at least one new point in the renal domain of the SDI. In multivariable analyses, uric acid levels (continuous and dichotomous) at baseline predicted the development of new renal damage (HR 3.21 (1.39-7.42), p 0.006; HR 18.28 (2.80-119.48), p 0.002; respectively). Higher uric acid levels contribute to the development of new renal damage in SLE patients independent of other well-known risk factors for such occurrence.

Epoxyeicosatrienoic Acid Analog Decreases Renal Fibrosis by Reducing Epithelial-to-Mesenchymal Transition

PubMed Central

Skibba, Melissa; Hye Khan, Md. Abdul; Kolb, Lauren L.; Yeboah, Michael M.; Falck, John R.; Amaradhi, Radhika; Imig, John D.

2017-01-01

Renal fibrosis, which is a critical pathophysiological event in chronic kidney diseases, is associated with renal epithelial-to-mesenchymal transition (EMT). Epoxyeicosatrienoic acids (EETs) are Cyp epoxygenase arachidonic acid metabolites that demonstrate biological actions that result in kidney protection. Herein, we investigated the ability of 14,15-EET and its synthetic analog, EET-A, to reduce kidney fibrosis induced by unilateral ureter obstruction (UUO). C57/BL6 male mice underwent sham or UUO surgical procedures and were treated with 14,15-EET or EET-A in osmotic pump (i.p.) for 10 days following UUO surgery. UUO mice demonstrated renal fibrosis with an 80% higher kidney-collagen positive area and 70% higher α-smooth muscle actin (SMA) positive renal areas compared to the sham group. As a measure of collagen content, kidney hydroxyproline content was also higher in UUO (6.4 ± 0.5 μg/10 mg) compared to sham group (2.5 ± 0.1 μg/10 mg). Along with marked renal fibrosis, UUO mice had reduced renal expression of EET producing Cyp epoxygenase enzymes. Endogenous 14,15-EET or EET-A demonstrated anti-fibrotic action in UUO by reducing kidney-collagen positive area (50–60%), hydroxyproline content (50%), and renal α-SMA positive area (85%). In UUO mice, renal expression of EMT inducers, Snail1 and ZEB1 were higher compared to sham group. Accordingly, renal epithelial marker E-cadherin expression was reduced and mesenchymal marker expression was elevated in the UUO compared to sham mice. Interestingly, EET-A reduced EMT in UUO mice by deceasing renal Snail1 and ZEB1 expression. EET-A treatment also opposed the decrease in renal E-cadherin expression and markedly reduced several prominent renal mesenchymal/myofibroblast markers in UUO mice. Overall, our results demonstrate that EET-A is a novel anti-fibrotic agent that reduces renal fibrosis by decreasing renal EMT. PMID:28713267

The role of keto acids in the supportive treatment of children with chronic renal failure.

PubMed

Mir, Sevgi; Ozkayin, Nese; Akgun, Aysegul

2005-07-01

According to the hyperfiltration theory of renal diseases characterized by a decrease in the number of functional nephrons, increased arterial blood pressure, excessive protein intake in the diet, high levels of calcium (Ca) and phosphorus (P), secondary hyperparathyroidism, hypertriglyceridemia and/or hypercholesterolemia, proteinuria and metabolic acidosis are some factors that impair the prognosis of the disease. The amount of protein in the diet is the most important of these factors. A protein-restricted diet administered to patients with chronic renal failure results in the risk of inadequate amino acid intake. To overcome this problem, the use of dysaminated alpha-keto analogues has been considered to reduce the risk of nitrogenemia resulting from the continuous intake of essential amino acids. Currently, the necessity of essential amino acids even in adult patients with chronic renal failure is controversial; besides, trials on the use of these amino acids in pediatric patients are scarce. The aim of this study is to investigate the efficacy and applicability of conservative therapy with a protein-restricted diet supplemented with keto acids in the management of chronic renal insufficiency or failure.

Therapeutic efficacy of DL-alpha-lipoic acid on cyclosporine A induced renal alterations.

PubMed

Amudha, Ganapathy; Josephine, Anthony; Mythili, Yenjerla; Sundarapandiyan, Rajaguru; Varalakshmi, Palaninathan

2007-10-01

The present study was designed to evaluate the possible beneficial effect of lipoic acid in preventing the renal damage induced by cyclosporine A in rats. Male albino rats of Wistar strain were divided into four groups and treated as follows. Two groups received cyclosporine A by oral gavage (25 mg/kg/body weight) for 21 days to induce nephrotoxicity, one of which simultaneously received lipoic acid treatment (20 mg/kg body weight) for 21 days. A vehicle (olive oil) and a lipoic acid drug control were also included. Cyclosporine A induced renal damage was evident from the decreased activities of tissue marker enzymes (alkaline phosphatase, acid phosphatase, lactate dehydrogenase, aspartate transaminase and alanine transaminase) and decreased activities of ATPases (Na+, K+-ATPase, Ca2+-ATPase and Mg2+ ATPase). An apparent increase in the levels of serum constituents (urea, uric acid and creatinine) and urinary marker enzymes (N-acetyl-beta-D-glucosaminidase, beta-glucosidase, beta-galactosidase, cathepsin-D and gamma-glutamyl transpeptidase) along with significant decline in creatinine clearance were seen in the cyclosporine treated rats, which was reversed upon treatment with lipoic acid. Ultrastructural observations were also in agreement with the above abnormal changes. Lipoic acid effectively reverted these abnormal biochemical changes and minimized the morphological lesions in renal tissue. Hence, this study clearly exemplifies that lipoic acid might be an ideal choice against cyclosporine A induced cellular abnormalities.

Diet-dependent net endogenous acid load of vegan diets in relation to food groups and bone health-related nutrients: results from the German Vegan Study.

PubMed

Ströhle, Alexander; Waldmann, Annika; Koschizke, Jochen; Leitzmann, Claus; Hahn, Andreas

2011-01-01

Dietary composition has been shown to affect acid-base homeostasis and bone health in humans. We investigated the potential renal acid load (PRAL) and the estimated diet-dependent net acid load (net endogenous acid production, NEAP) in adult vegans and evaluated the relationships between NEAP, food groups and intake of bone health-related nutrients. The German Vegan Study (GVS) is a cross-sectional study. Data from healthy men (n = 67) and women (n = 87), aged 21-75 years, who fulfilled the study criteria (vegan diet for ≥1 year prior to study start; age ≥18 years, and no pregnancy/childbirth during the last 12 months) were included in the analysis. NEAP values were calculated from diet composition using two models: one based on the protein/potassium quotient and another taking into account an anthropometry-based loss of urinary organic anions. Mean daily intakes of phosphorus, potassium, sodium, magnesium and vitamin C were above, and vitamin D and calcium below Dietary Reference Intake (DRI). Regardless of the model used, the diet in the GVS was characterized by a nearly neutral NEAP. A strong correlation was observed between the NEAP values of the two models (r(s) = 0.873, p < 0.001). Only the consumption of fruits decreased constantly across the increasing quartiles of NEAP. It can be hypothesized that vegan diets do not affect acid-base homeostasis. With respect to bone health, the significance of this finding needs further investigation. Copyright © 2011 S. Karger AG, Basel.

Net acidity indicates the whole effluent toxicity of pH and dissolved metals in metalliferous saline waters.

PubMed

Degens, Bradley P; Krassoi, Rick; Galvin, Lynette; Reynolds, Brad; Micevska, Tina

2018-05-01

Measurements of potential acidity in water are used to manage aquatic toxicity risks of discharge from acid sulfate soils or acid mine drainage. Net acidity calculated from pH, dissolved metals and alkalinity is a common measurement of potential acidity but the relevance of current risk thresholds to aquatic organisms are unclear. Aquatic toxicity testing was carried out using four halophytic organisms with water from four saline sources in southern Western Australia (3 acidic drains and one alkaline river; 39-40 g TDS/L) where acidity was varied by adjusting pH to 4.5-6.5. The test species were brine shrimps (Artemia salina), locally sourced ostracods (Platycypris baueri), microalgae (Dunaliella salina) and amphipods (Allorchestes compressa). Testing found the EC 10 and IC 10 of net acidity ranged from -7.8 to 10.5 mg CaCO 3 /L with no survival or growth of any species at >47 mg CaCO 3 /L. Reduced net acidity indicated reduced whole effluent toxicity more reliably than increased pH alone with organisms tolerating pH up to 1.1 units lower in the absence of dissolved metals. Variation in toxicity indicated by net acidity was mostly attributed to reduced concentrations of dissolved Al and Fe combined with higher pH and alkalinity and some changes in speciation of Al and Fe with pH. These results indicate that rapid in-field assessments of net acidity in acidic, Al dominated waters may be an indicator of potential acute and sub-chronic impacts on aquatic organisms. Crown Copyright © 2018. Published by Elsevier Ltd. All rights reserved.

Amino Acid Metabolism in Acute Renal Failure: Influence of Intravenous Essential L-Amino Acid Hyperalimentation Therapy

PubMed Central

Abel, Ronald M.; Shih, Vivian E.; Abbott, William M.; Beck, Clyde H.; Fischer, Josef E.

1974-01-01

A solution of 8 essential I-amino acids and hypertonic dextrose was administered to 5 patients in acute postoperative renal failure in a program of hyperalimentation designed to decrease the patient's catabolic state and to accrue certain metabolic benefits. A sixth patient receiving intravenous glucose alone served as a control. The pretreatment plasma concentrations of amino acids in all 6 patients did not differ significantly from normal; following intravenous essential amino acids at a dose of approximately 12.6 gm/24 hours, no significant elevations out of the normal range of these substances occurred. Since urinary excretion rates did not dramatically increase, urinary loss was excluded as a possible cause for the failure of increase of plasma concentrations. The results suggest that the administration of an intravenous solution of 1-amino acids and hypertonic dextrose is associated with rapid clearance from the blood of these substances and, with a failure of increased urinary excretion, indirect evidence of amino acid utilization for protein synthesis has been obtained. Histidine supplementation in patients with acute renal failure is probably unnecessary based on the lack of significant decreases in histidine concentrations in these patients. PMID:4850497

Extra-Renal Elimination of Uric Acid via Intestinal Efflux Transporter BCRP/ABCG2

PubMed Central

Hosomi, Atsushi; Nakanishi, Takeo; Fujita, Takuya; Tamai, Ikumi

2012-01-01

Urinary excretion accounts for two-thirds of total elimination of uric acid and the remainder is excreted in feces. However, the mechanism of extra-renal elimination is poorly understood. In the present study, we aimed to clarify the mechanism and the extent of elimination of uric acid through liver and intestine using oxonate-treated rats and Caco-2 cells as a model of human intestinal epithelium. In oxonate-treated rats, significant amounts of externally administered and endogenous uric acid were recovered in the intestinal lumen, while biliary excretion was minimal. Accordingly, direct intestinal secretion was thought to be a substantial contributor to extra-renal elimination of uric acid. Since human efflux transporter BCRP/ABCG2 accepts uric acid as a substrate and genetic polymorphism causing a decrease of BCRP activity is known to be associated with hyperuricemia and gout, the contribution of rBcrp to intestinal secretion was examined. rBcrp was confirmed to transport uric acid in a membrane vesicle study, and intestinal regional differences of expression of rBcrp mRNA were well correlated with uric acid secretory activity into the intestinal lumen. Bcrp1 knockout mice exhibited significantly decreased intestinal secretion and an increased plasma concentration of uric acid. Furthermore, a Bcrp inhibitor, elacridar, caused a decrease of intestinal secretion of uric acid. In Caco-2 cells, uric acid showed a polarized flux from the basolateral to apical side, and this flux was almost abolished in the presence of elacridar. These results demonstrate that BCRP contributes at least in part to the intestinal excretion of uric acid as extra-renal elimination pathway in humans and rats. PMID:22348008

Arteriovenous fistula and prolonged hematuria after renal biopsy: treatment with epsilon aminocaproic acid

PubMed Central

Silverberg, D. S.; Dossetor, J. B.; Eid, T. C.; Mant, M. J.; Miller, J. D. R.

1974-01-01

A patient with membranoproliferative glomerulonephritis and mild hypertension is described who, after a renal biopsy, developed an arteriovenous fistula and then severe continuous hematuria from the seventh to the 38th postbiopsy day. Treatment with epsilon aminocaproic acid was associated with rapid and permanent cessation of bleeding, gradual improvement in renal function, and disappearance of the renal artery bruit. No complications were encountered. ImagesFIG. 2FIG. 3FIG. 4FIG. 5FIG. 6 PMID:4817213

Uric acid upregulates the adiponectin-adiponectin receptor 1 pathway in renal proximal tubule epithelial cells

PubMed Central

Yang, Qingmei; Fu, Chensheng; Xiao, Jing; Ye, Zhibin

2018-01-01

Adiponectin (APN) is a protein hormone that is primarily derived from adipocytes. It can also be secreted by renal cells. Hypoadiponectinemia has been documented in patients with hyperuricemia, however, whether soluble uric acid (SUA) regulates the expression of APN and APN receptor 1 (AdipoR1) in renal proximal tubule epithelial cells (PTECs) remains to be elucidated. The present study investigated the expression of APN and AdipoR1 in cultured PTECs that were exposed to SUA through immunofluorescence and western blot analysis. In addition, Sprague-Dawley rats with oxonic acid-induced hyperuricemia (HUA) with or without febuxostat treatment were employed as an animal model to measure 24 h urine protein, serum creatinine, urea nitrogen, uric acid and homeostasis model assessment of insulin resistance. Renal pathology was evaluated using hematoxylin and eosin and immunohistochemical staining. APN and AdipoR1 expression in the renal cortex were evaluated by western blotting. The results demonstrated that, in PTECs, the expression of APN and AdipoR1 was constant and increased upon SUA exposure. Similar observations were made within the proximal renal tubules of rats, and the oxonic acid-induced increases in APN and AdipoR1 were offset by febuxostat treatment. Furthermore, SUA-treated PTECs exhibited an increase in the expression of NLR family pyrin domain-containing (NLRP) 3, which was dose-dependent. NLRP3 expression was also significantly increased in the renal cortex of HUA rats compared with control and febuxostat-treated rats. In conclusion, SUA enhanced the expression of APN and AdipoR1 in PTECs, which was associated with an increase in NLRP3 expression. The APN-AdipoR1 pathway was demonstrated to have an important role in in vitro and in vivo models of renal proximal tubule inflammatory injury. Therefore, this pathway may be a potential therapy target in urate nephropathy. PMID:29359786

Effect of monofluoroacetate on renal H+ excretion in the rat.

PubMed

Simonnet, H; Gauthier, C; Pellet, M V

1979-05-01

In order to investigate the effect of monofluoroacetate (MFA) on renal H+ excretion, anesthetized rats under mannitol diuresis were given intraperitoneally MFA and some of the acido-basic status parameters were determined. Urinary pH and pCO2 did not change after MFA administration, while urinary flow rate increased. MFA induced a decrease in H+ net excretion and in ammonia excretion. Titratable acidity did not change significantly within the experiment.

Serum uric acid and renal function in patients with type 1 diabetes: a nationwide study in Brazil.

PubMed

Pizarro, Marcela Haas; Santos, Deborah Conte; Barros, Bianca Senger Vasconcelos; de Melo, Laura Gomes Nunes; Gomes, Marilia Brito

2018-01-01

Diabetes nephropathy is a microvascular complication associated with high morbidity and mortality in patients with type 1 diabetes, and its pathogenesis is not fully understood. Our aim was to evaluate the association between levels of serum uric acid and renal function assessed by glomerular filtration rate (GFR) and albuminuria in patients with type 1 diabetes. This is a multicenter, cross-sectional, observational study with 1686 patients, conducted between August 2011 and August 2014 in 14 public clinics from ten Brazilian cities. Renal function was estimated by CKD-EPI (adults) and by Schwartz (adolescents). We analyzed 1686 patients, aged 30.1 ± 12.0, with 15.4 ± 9.3 years of duration of diabetes; 55.8% were female and 54.0% were Caucasians. Serum uric acid was related to renal function, with a mean of 4.8 ± 1.4 (in the normal renal function group) vs 5.2 ± 2.0 (GFR ≥ 60 ml/min and albuminuria) vs 6.5 ± 2.6 mg/dl (GFR < 60 ml/min). In the pooled group, multivariate analysis showed an inverse correlation between serum uric acid and GFR (r = - 0.316, p < 0.001) with a decrease of 4.11 ml/min in the GFR for every increase of 1 mg/dl in serum uric acid. Considering only patients with normal renal function (n = 1170), a decrease of 2.04 ml/min in the GFR for every increase of 1 mg/dl in Serum uric acid was noted using multivariate analysis. Patients with higher levels of serum uric acid have worse renal function, independently of HbA1c or duration of diabetes, which persisted even in patients with normal renal function. Further prospective studies are necessary to establish if patients with higher serum uric acid may have an elevated risk for developing chronic kidney disease.

Effect of dietary protein restriction on renal ammonia metabolism

PubMed Central

Lee, Hyun-Wook; Osis, Gunars; Handlogten, Mary E.; Guo, Hui; Verlander, Jill W.

2015-01-01

Dietary protein restriction has multiple benefits in kidney disease. Because protein intake is a major determinant of endogenous acid production, it is important that net acid excretion change in parallel during protein restriction. Ammonia is the primary component of net acid excretion, and inappropriate ammonia excretion can lead to negative nitrogen balance. Accordingly, we examined ammonia excretion in response to protein restriction and then we determined the molecular mechanism of the changes observed. Wild-type C57Bl/6 mice fed a 20% protein diet and then changed to 6% protein developed an 85% reduction in ammonia excretion within 2 days, which persisted during a 10-day study. The expression of multiple proteins involved in renal ammonia metabolism was altered, including the ammonia-generating enzymes phosphate-dependent glutaminase (PDG) and phosphoenolpyruvate carboxykinase (PEPCK) and the ammonia-metabolizing enzyme glutamine synthetase. Rhbg, an ammonia transporter, increased in expression in the inner stripe of outer medullary collecting duct intercalated cell (OMCDis-IC). However, collecting duct-specific Rhbg deletion did not alter the response to protein restriction. Rhcg deletion did not alter ammonia excretion in response to dietary protein restriction. These results indicate 1) dietary protein restriction decreases renal ammonia excretion through coordinated regulation of multiple components of ammonia metabolism; 2) increased Rhbg expression in the OMCDis-IC may indicate a biological role in addition to ammonia transport; and 3) Rhcg expression is not necessary to decrease ammonia excretion during dietary protein restriction. PMID:25925252

Genetic variation underlying renal uric acid excretion in Hispanic children: the Viva La Familia Study.

PubMed

Chittoor, Geetha; Haack, Karin; Mehta, Nitesh R; Laston, Sandra; Cole, Shelley A; Comuzzie, Anthony G; Butte, Nancy F; Voruganti, V Saroja

2017-01-17

Reduced renal excretion of uric acid plays a significant role in the development of hyperuricemia and gout in adults. Hyperuricemia has been associated with chronic kidney disease and cardiovascular disease in children and adults. There are limited genome-wide association studies associating genetic polymorphisms with renal urate excretion measures. Therefore, we investigated the genetic factors that influence the excretion of uric acid and related indices in 768 Hispanic children of the Viva La Familia Study. We performed a genome-wide association analysis for 24-h urinary excretion measures such as urinary uric acid/urinary creatinine ratio, uric acid clearance, fractional excretion of uric acid, and glomerular load of uric acid in SOLAR, while accounting for non-independence among family members. All renal urate excretion measures were significantly heritable (p <2 × 10 -6 ) and ranged from 0.41 to 0.74. Empirical threshold for genome-wide significance was set at p <1 × 10 -7 . We observed a strong association (p < 8 × 10 -8 ) of uric acid clearance with a single nucleotide polymorphism (SNP) in zinc finger protein 446 (ZNF446) (rs2033711 (A/G), MAF: 0.30). The minor allele (G) was associated with increased uric acid clearance. Also, we found suggestive associations of uric acid clearance with SNPs in ZNF324, ZNF584, and ZNF132 (in a 72 kb region of 19q13; p <1 × 10 -6 , MAFs: 0.28-0.31). For the first time, we showed the importance of 19q13 region in the regulation of renal urate excretion in Hispanic children. Our findings indicate differences in inherent genetic architecture and shared environmental risk factors between our cohort and other pediatric and adult populations.

Interaction of ethacrynic acid with control sites of renal glucose metabolism.

PubMed

Fúlgraff, G; Dingler-Núnemann, H

1975-01-01

Ethacrynic acid stimulates in vitro concentration dependent renal gluconeogenesis from substrates which enter the gluconeogenic pathway at the level of the triosephosphates like glycerol or fructose or from substrates which have to pass the oxaloacetate shuttle like pyruvate or from intermediary products of fatty acid oxydation or citrate cycle. Our results suggest that a site of action of ethacrynic acid in this metabolic aspect is the enzyme system fructose diphosphatase/frutose-6-phosphate kinase and eventually additionally pyruvate carboxylase.

Renal Liver-Type Fatty Acid Binding Protein (L-FABP) Attenuates Acute Kidney Injury in Aristolochic Acid Nephrotoxicity

PubMed Central

Matsui, Katsuomi; Kamijo-Ikemorif, Atsuko; Sugaya, Takeshi; Yasuda, Takashi; Kimura, Kenjiro

2011-01-01

Injection of aristolochic acid (AA) in mice causes AA-induced nephrotoxicity, in which oxidative stress contributes to development of tubulointerstitial damage (TID). Liver-type fatty acid binding protein (L-FABP) is expressed in human proximal tubules and has an endogenous antioxidative function. The renoprotection of renal L-FABP was examined in a model of AA-induced nephrotoxicity. Established human L-FABP (hL-FABP) transgenic (Tg) mice and wild-type (WT) mice were treated with AA for up to 5 days. Mice were sacrificed on days 1, 3, and 5 after the start of AA injection. Although mouse L-FABP was not expressed in proximal tubules of WT mice, hL-FABP was expressed in proximal tubules of Tg mice. The expression of renal hL-FABP was significantly increased in Tg mice administered AA (Tg-AA), compared with the control (saline-treated Tg mice). In WT-AA mice, there was high urinary excretion of Nε-(hexanoyl)-lysine, the production of heme oxygenase-1 and receptor for advanced glycation end products increased, and TID was provoked. In contrast, renal hL-FABP in Tg-AA mice suppressed production of Nε-(hexanoyl)lysine, heme oxygenase-1, and receptor for advanced glycation end products. Renal dysfunction was significantly milder in Tg-AA mice than in WT-AA mice. The degree of TID was significantly attenuated in Tg-AA mice, compared with WT-AA. In conclusion, renal hL-FABP reduced the oxidative stress in AA-induced nephrotoxicity and attenuated TID. PMID:21356355

Atlantic salmon (Salmo salar L.) as a net producer of long-chain marine ω-3 fatty acids.

PubMed

Sanden, Monica; Stubhaug, Ingunn; Berntssen, Marc H G; Lie, Øyvind; Torstensen, Bente E

2011-12-14

The objective of the present study was to investigate the effects of replacing high levels of marine ingredients with vegetable raw materials and with emphasis on lipid metabolism and net production of long-chain polyunsaturated ω-3 fatty acids (EPA + DHA). Atlantic salmon were fed three different replacement vegetable diets and one control marine diet before sensory attributes, β-oxidation capacity, and fatty acid productive value (FAPV) of ingested fatty acids (FAs) were evaluated. Fish fed the high replacement diet had a net production of 0.8 g of DHA and a FAPV of 142%. Fish fed the marine diet had a net loss of DHA. The present work shows that Atlantic salmon can be a net producer of marine DHA when dietary fish oil is replaced by vegetable oil with minor effects on sensory attributes and lipid metabolism.

Acid-Base Homeostasis

PubMed Central

Nakhoul, Nazih; Hering-Smith, Kathleen S.

2015-01-01

Acid-base homeostasis and pH regulation are critical for both normal physiology and cell metabolism and function. The importance of this regulation is evidenced by a variety of physiologic derangements that occur when plasma pH is either high or low. The kidneys have the predominant role in regulating the systemic bicarbonate concentration and hence, the metabolic component of acid-base balance. This function of the kidneys has two components: reabsorption of virtually all of the filtered HCO3− and production of new bicarbonate to replace that consumed by normal or pathologic acids. This production or generation of new HCO3− is done by net acid excretion. Under normal conditions, approximately one-third to one-half of net acid excretion by the kidneys is in the form of titratable acid. The other one-half to two-thirds is the excretion of ammonium. The capacity to excrete ammonium under conditions of acid loads is quantitatively much greater than the capacity to increase titratable acid. Multiple, often redundant pathways and processes exist to regulate these renal functions. Derangements in acid-base homeostasis, however, are common in clinical medicine and can often be related to the systems involved in acid-base transport in the kidneys. PMID:26597304

Dietary supplementation of branched-chain amino acids increases muscle net amino acid fluxes through elevating their substrate availability and intramuscular catabolism in young pigs.

PubMed

Zheng, Liufeng; Zuo, Fangrui; Zhao, Shengjun; He, Pingli; Wei, Hongkui; Xiang, Quanhang; Pang, Jiaman; Peng, Jian

2017-04-01

Branched-chain amino acids (BCAA) have been clearly demonstrated to have anabolic effects on muscle protein synthesis. However, little is known about their roles in the regulation of net AA fluxes across skeletal muscle in vivo. This study was aimed to investigate the effect and related mechanisms of dietary supplementation of BCAA on muscle net amino acid (AA) fluxes using the hindlimb flux model. In all fourteen 4-week-old barrows were fed reduced-protein diets with or without supplemental BCAA for 28 d. Pigs were implanted with carotid arterial, femoral arterial and venous catheters, and fed once hourly with intraarterial infusion of p-amino hippurate. Arterial and venous plasma and muscle samples were obtained for the measurement of AA, branched-chain α-keto acids (BCKA) and 3-methylhistidine (3-MH). Metabolomes of venous plasma were determined by HPLC-quadrupole time-of-flight-MS. BCAA-supplemented group showed elevated muscle net fluxes of total essential AA, non-essential AA and AA. As for individual AA, muscle net fluxes of each BCAA and their metabolites (alanine, glutamate and glutamine), along with those of histidine, methionine and several functional non-essential AA (glycine, proline and serine), were increased by BCAA supplementation. The elevated muscle net AA fluxes were associated with the increase in arterial and intramuscular concentrations of BCAA and venous metabolites including BCKA and free fatty acids, and were also related to the decrease in the intramuscular concentration of 3-MH. Correlation analysis indicated that muscle net AA fluxes are highly and positively correlated with arterial BCAA concentrations and muscle net BCKA production. In conclusion, supplementing BCAA to reduced-protein diet increases the arterial concentrations and intramuscular catabolism of BCAA, both of which would contribute to an increase of muscle net AA fluxes in young pigs.

Renal responses of trout to chronic respiratory and metabolic acidoses and metabolic alkalosis.

PubMed

Wood, C M; Milligan, C L; Walsh, P J

1999-08-01

Exposure to hyperoxia (500-600 torr) or low pH (4.5) for 72 h or NaHCO(3) infusion for 48 h were used to create chronic respiratory (RA) or metabolic acidosis (MA) or metabolic alkalosis in freshwater rainbow trout. During alkalosis, urine pH increased, and [titratable acidity (TA) - HCO(-)(3)] and net H(+) excretion became negative (net base excretion) with unchanged NH(+)(4) efflux. During RA, urine pH did not change, but net H(+) excretion increased as a result of a modest rise in NH(+)(4) and substantial elevation in [TA - HCO(-)(3)] efflux accompanied by a large increase in inorganic phosphate excretion. However, during MA, urine pH fell, and net H(+) excretion was 3.3-fold greater than during RA, reflecting a similar increase in [TA - HCO(-)(3)] and a smaller elevation in phosphate but a sevenfold greater increase in NH(+)(4) efflux. In urine samples of the same pH, [TA - HCO(-)(3)] was greater during RA (reflecting phosphate secretion), and [NH(+)(4)] was greater during MA (reflecting renal ammoniagenesis). Renal activities of potential ammoniagenic enzymes (phosphate-dependent glutaminase, glutamate dehydrogenase, alpha-ketoglutarate dehydrogenase, alanine aminotransferase, phosphoenolpyruvate carboxykinase) and plasma levels of cortisol, phosphate, ammonia, and most amino acids (including glutamine and alanine) increased during MA but not during RA, when only alanine aminotransferase increased. The differential responses to RA vs. MA parallel those in mammals; in fish they may be keyed to activation of phosphate secretion by RA and cortisol mobilization by MA.

Acute supplementation of amino acids increases net protein accretion in IUGR fetal sheep

PubMed Central

Rozance, Paul J.; Thorn, Stephanie R.; Friedman, Jacob E.; Hay, William W.

2012-01-01

Placental insufficiency decreases fetal amino acid uptake from the placenta, plasma insulin concentrations, and protein accretion, thus compromising normal fetal growth trajectory. We tested whether acute supplementation of amino acids or insulin into the fetus with intrauterine growth restriction (IUGR) would increase net fetal protein accretion rates. Late-gestation IUGR and control (CON) fetal sheep received acute, 3-h infusions of amino acids (with euinsulinemia), insulin (with euglycemia and euaminoacidemia), or saline. Fetal leucine metabolism was measured under steady-state conditions followed by a fetal muscle biopsy to quantify insulin signaling. In CON, increasing amino acid delivery rates to the fetus by 100% increased leucine oxidation rates by 100%. In IUGR, amino acid infusion completely suppressed fetal protein breakdown rates but increased leucine oxidation rate by only 25%, resulting in increased protein accretion rates by 150%. Acute insulin infusion, however, had very little effect on amino acid delivery rates, fetal leucine disposal rates, or fetal protein accretion rates in CON or IUGR fetuses despite robust signaling of the fetal skeletal muscle insulin-signaling cascade. These results indicate that, when amino acids are given directly into the fetal circulation independently of changes in insulin concentrations, IUGR fetal sheep have suppressed protein breakdown rates, thus increasing net fetal protein accretion. PMID:22649066

Protective effect of 20-hydroxyeicosatetraenoic acid (20-HETE) on adriamycin-induced toxicity of human renal tubular epithelial cell (HK-2).

PubMed

Tian, Ting; Li, Jin; Wang, Meng-Ying; Xie, Xian-Fei; Li, Qi-Xiong

2012-05-15

20-Hydroxyeicosatetraenoic acid is a cytochrome P4504A11 metabolite of arachidonic acid that plays an important role in the regulation of human renal functions. In the present study, we investigated the role of 20-hydroxyeicosatetraenoic acid on adriamycin induced toxicity in human renal tubular epithelial cells. Results showed that cell viability was decreased significantly and lactate dehydrogenase activity was increased significantly in a concentration-dependent manner when human renal tubular epithelial cells were incubated with adriamycin (10⁻⁷-10⁻³ mol/l) for 24h. In contrast, 20-hydroxyeicosatetraenoic acid (0.1, 1, 10, 50 μmol/l) increased cell survival and decreased lactate dehydrogenase activity concentration dependently in human renal tubular epithelial cells. When 20-hydroxyeicosatetraenoic acid (10, 50 μmol/l) was co-administered with adriamycin (10⁻³ mol/l), it significantly increased cell viability and decreased lactate dehydrogenase activity. On the other hand, N-hydroxy-N'-(4-butyl-2-methylphenyl)formamidine (HET-0016) (1 μM), a selective inhibitor of 20-hydroxyeicosatetraenoic acid synthesizing enzyme exaggerated cell viability reduction and lactate dehydrogenase activity augmentation induced by adriamycin. Adriamycin suppressed the expression of cytochrome P4504A11 gene and its protein production in human renal tubular epithelial cells. Furthermore, adriamycin was more effective than N-hydroxy-N'-(4-butyl-2-methylphenyl)formamidine at lowering the expression of cytochrome P4504A11 gene and its protein. These results suggest that 20-hydroxyeicosatetraenoic acid may protect adriamycin-induced toxicity of human renal tubular epithelial cells, meanwhile, adriamycin-induced toxicity of human renal tubular epithelial cells possibly involves inhibiting cytochrome P4504A11 expression. Crown Copyright © 2012. Published by Elsevier B.V. All rights reserved.

Validity of /sup 99m/Tc dimercaptosuccinic acid renal uptake for an assessment for individual kidney function

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

Kawamura, J.; Hosakawa, S.; Yoshida, O.

/sup 99m/Tc dimercaptosuccinic acid is a new renal scanning agent that provides a good quality of renal image as a result of preferential cortical accumulation and also makes feasible a quantitative assessment of separate kidney function, correlating well with renal plasma flow obtained from a /sup 131/I hippuran renogram of each kidney. By measuring the dimercaptosuccinic acid uptake, the cortical functioning nephrons can be determined independent of the activity from the urinary outflow tract. Such evaluations may replace the conventional split renal function study in which traumatic procedures, such as cystoscopy and ureteral catheterizations, are required. /sup 99m/Tc dimercaptosuccinic acidmore » scintigraphy causes less discomfort to the patient and can be performed repeatedly and routinely even in children and debilitated geriatric patients.« less

Comparison of acetic acid and ethanol sclerotherapy for simple renal cysts: clinical experience with 86 patients.

PubMed

Cho, Young Jun; Shin, Ji Hoon

2016-01-01

To compare the efficacy and treatment session numbers of acetic acid to that of ethanol sclerotherapy for the treatment of simple renal cysts. Between February 2004 and June 2013, 86 patients with simple renal cysts underwent percutaneous aspiration and injection of 50 %-acetic-acid (42 cysts) and 95 %-ethanol (44 cysts). The patient demographics, volume reduction rate, number of treatment sessions, and complications were then analyzed. The volume reduction rate was 94.1 ± 7.6 % in the 50 %-acetic acid group and 94.7 ± 11.7 % in the 95 %-ethanol group, and without a statistical difference. The rates of complete remission, partial remission, and no response were 57.1, 42.9 and 0 %, respectively, for the acetic acid group, and 70.5, 25.0, and 4.5 %, respectively, for the ethanol group. No statistical difference was observed between the two groups. Compared to the acetic acid group, the ethanol group had a higher number of treatment sessions, i.e. 1.10 ± 0.30 in the acetic acid group and 1.80 ± 0.79 in the ethanol group. Mild flank pain was a minor complication that occurred in both groups. Acetic acid seems to have equivalent sclerosing effects on simple renal cysts compared with those of ethanol despites of fewer treatment sessions.

Roles of organic anion transporters in the renal excretion of perfluorooctanoic acid.

PubMed

Nakagawa, Hatsuki; Hirata, Taku; Terada, Tomohiro; Jutabha, Promsuk; Miura, Daisaku; Harada, Kouji H; Inoue, Kayoko; Anzai, Naohiko; Endou, Hitoshi; Inui, Ken-Ichi; Kanai, Yoshikatsu; Koizumi, Akio

2008-07-01

Perfluorooctanoic acid, an environmental contaminant, is found in both wild animals and human beings. There are large species and sex differences in the renal excretion of perfluorooctanoic acid. In the present study, we aimed to characterize organic anion transporters 1-3 (OAT1-3) in human beings and rats to investigate whether the species differences in the elimination kinetics of perfluorooctanoic acid from the kidneys can be attributed to differences in the affinities of these transporters for perfluorooctanoic acid. We used human (h) and rat (r) OAT transient expression cell systems and measured the [(14)C] perfluorooctanoic acid transport activities. Both human and rat OAT1 and OAT3 mediated perfluorooctanoic acid transport to similar degrees. Specifically, the kinetic parameters, K(m), were 48.0 +/- 6.4 microM for h OAT1; 51.0 +/- 12.0 microM for rOAT1; 49.1 +/- 21.4 microM for hOAT3 and 80.2 +/- 17.8 microM for rOAT3, respectively. These data indicate that both human and rat OAT1 and OAT3 have high affinities for perfluorooctanoic acid and that the species differences in its renal elimination are not attributable to affinity differences in these OATs between human beings and rats. In contrast, neither hOAT2 nor rOAT2 transported perfluorooctanoic acid. In conclusion, OAT1 and OAT3 mediated perfluorooctanoic acid transport in vitro, suggesting that these transporters also transport perfluorooctanoic acid through the basolateral membrane of proximal tubular cells in vivo in both human beings and rats. Neither human nor rat OAT2 mediated perfluorooctanoic acid transport. Collectively, the difference between the perfluorooctanoic acid half-lives in human beings and rats is not likely to be attributable to differences in the affinities of these transporters for perfluorooctanoic acid.

Perioperative renal outcome in cardiac surgical patients with preoperative renal dysfunction: aprotinin versus epsilon aminocaproic acid.

PubMed

Maslow, Andrew D; Chaudrey, Alyas; Bert, Arthur; Schwartz, Carl; Singh, Arun

2008-02-01

The administration of aprotinin to patients with pre-existing renal dysfunction who are undergoing cardiac surgery is controversial. Therefore, the authors present their experience with the use of aprotinin for patients with preoperative renal dysfunction who underwent elective cardiac surgery requiring cardiopulmonary bypass (CPB). Retrospective analysis. University hospital. Consecutive cardiac surgical patients with preoperative serum creatinine (SCr) > or =1.8 mg/dL undergoing nonemergent cardiac surgery requiring CPB. None. One hundred twenty-three patients either received epsilon aminocaproic acid (EACA, n = 82) or aprotinin (n = 41) as decided by the attending anesthesiologist and surgeon. Data were collected from the Society of Thoracic Surgeons database and from automated intraoperative anesthesia records. Renal function was assessed from measured serum creatinine (SCr) and calculated creatinine clearances (CrCls). Acute perioperative renal dysfunction was defined as a worsening of perioperative renal function by > or =25% and/or the need for hemodialysis (HD). Data were recorded as mean and standard deviation or percentage of population depending on whether the data were continuous or not. Data were compared by using an analysis of variance, chi-square analysis, Student paired and unpaired t tests, Fisher exact test, Wilcoxon rank sum test, and Mann-Whitney U test. A p value <0.05 was considered significant. Overall, 32% and 41% of patients had acute perioperative renal dysfunction measured by CrCl and SCr, respectively. Seven patients required HD (5.7%). Six of these 7 had complicated postoperative courses. Of all the variables measured, only the duration of the aortic crossclamp (AoXCl) and CPB were significantly associated with acute perioperative renal dysfunction. Acute perioperative renal dysfunction was associated with increased intensive care unit and hospital stays, postoperative blood transfusion, dialysis, and major infection. Aprotinin

Complicated pregnancies in inherited distal renal tubular acidosis: importance of acid-base balance.

PubMed

Seeger, Harald; Salfeld, Peter; Eisel, Rüdiger; Wagner, Carsten A; Mohebbi, Nilufar

2017-06-01

Inherited distal renal tubular acidosis (dRTA) is caused by impaired urinary acid excretion resulting in hyperchloremic metabolic acidosis. Although the glomerular filtration rate (GFR) is usually preserved, and hypertension and overt proteinuria are absent, it has to be considered that patients with dRTA also suffer from chronic kidney disease (CKD) with an increased risk for adverse pregnancy-related outcomes. Typical complications of dRTA include severe hypokalemia leading to cardiac arrhythmias and paralysis, nephrolithiasis and nephrocalcinosis. Several physiologic changes occur in normal pregnancy including alterations in acid-base and electrolyte homeostasis as well as in GFR. However, data on pregnancy in women with inherited dRTA are scarce. We report the course of pregnancy in three women with hereditary dRTA. Complications observed were severe metabolic acidosis, profound hypokalemia aggravated by hyperemesis gravidarum, recurrent urinary tract infection (UTI) and ureteric obstruction leading to renal failure. However, the outcome of all five pregnancies (1 pregnancy each for mothers n. 1 and 2; 3 pregnancies for mother n. 3) was excellent due to timely interventions. Our findings highlight the importance of close nephrologic monitoring of women with inherited dRTA during pregnancy. In addition to routine assessment of creatinine and proteinuria, caregivers should especially focus on acid-base status, plasma potassium and urinary tract infections. Patients should be screened for renal obstruction in the case of typical symptoms, UTI or renal failure. Furthermore, genetic identification of the underlying mutation may (a) support early nephrologic referral during pregnancy and a better management of the affected woman, and (b) help to avoid delayed diagnosis and reduce complications in affected newborns.

A micropuncture study of the effect of parathyroid hormone on renal bicarbonate reabsorption.

PubMed Central

Bank, N; Aynediian, H S

1976-01-01

Renal micropuncture and clearance experiments were carried out in rats to study the effect of parathyroid hormone (PTH) on renal tubular HCO-/3 reabsorption. The rats were studied during an initial period of parathyroid deficiency (acute thyroidparathyroidectomy, TPTX) and during infusion of large amounts of bovine PTH. Under normal acid-base conditions, PTH administration to TPTX rats caused a significant rise in proximal tubular fluid HCO-/3 concentration (TFHCO-/3), a decrease in fluid reabsorption, and a fall in proximal HCO-/3 reabsorption from 94.0 to 88.2% (P less than 0.01). In control experiments with mannitol infusion, a comparable reduction in proximal fluid reabsorption occurred without any significant effect on intraluminal HCO-/3 concentration. During acute intravenous HCO-/3 loading, PTH inhibited proximal HCO-/3 reabsorption. However, no change in whole kidney HCO-/3 reabsorption was observed in these experiments or in the animals studied under normal acid-base conditions. The findings are consistent with the view that PTH inhibits proximal tubular HCO-/3 reabsorption with normal or high filtered loads of HCO-/3, but distal segments of the nephron are able to reabsorb the excess delivered from the proximal tubule. Measurements of urinary ammonium and titratable acid indicate that net acid excretion (NH+/4 + TA -- HCO-/3) increases significantly after PTH administration. These results do not provide support for the view that PTH excess causes metabolic acidosis by reducing renal acid excretion. PMID:956369

Familial Non-VHL Clear Cell Renal Cell Carcinoma

MedlinePlus

... Cell Carcinoma Request Permissions Familial Non-VHL Clear Cell Renal Cell Carcinoma Approved by the Cancer.Net Editorial Board , 12/2017 What is familial non-VHL clear cell renal cell carcinoma? Familial non-VHL clear cell ...

Fanconi's syndrome, interstitial fibrosis and renal failure by aristolochic acid in Chinese herbs.

PubMed

Hong, Yin-Tai; Fu, Lin-Shien; Chung, Lin-Huei; Hung, Shien-Chung; Huang, Yi-Ting; Chi, Chin-Shiang

2006-04-01

Aristolochic acid-associated nephropathy (AAN) has been identified as a separate entity of progressive tubulo-interstitial nephropathy. Its characteristic pathological findings, including hypocellular interstitial fibrosis, intimal thickening of interlobular and afferent arterioles with glomeruli sparing or mild sclerosis, have been identified. Many cases of AAN in adults have been reported in Taiwan as well as throughout the world, but it has seldom been described in children. We report on a 10-year-old boy who presented with severe anemia, Fanconi's syndrome, and progressive renal failure. Renal biopsy revealed typical findings of AAN. Aristolochic acids I and II were identified from a Chinese herb mixture ingested by the boy. AAN was diagnosed after other etiologies had been excluded. The case demonstrates the hazards of Chinese herbs with regard to children's health in Taiwan and suggests that more attention should be paid to this issue.

Enhanced renal prostaglandin production in the dog. I. Effects on renal function.

PubMed

Tannenbaum, J; Splawinski, J A; Oates, J A; Nies, A S

1975-01-01

The changes in renal function produced by endogenous synthesis of prostaglandins by the kidney were evaluated by infusing sodium arachidonate, the prescursor of the prostaglandins, into one renal artery of the dog. These changes were compared with those produced by similar infusions on performed prostaglandin (PG) E2 and F2alpha.PGE2given at 0.01-0.3 mug/kg min--1 produced dose-related increases in urine flow, sodium and potassium excretion, free water clearance, and renal blood flow. The glomerular filtration rage increased only at the lowest dose and the calculated filtration fraction fell. Arachidonic acid at 1.0-30.0 mug/kg min--1 similarly produced dose-related increases in electrolyte excretion, but the increase in renal blood flow was much less than that produced by PGE2 and there were no changes in glomerular filtration rate, filtration fraction, or free water clearances. PGF2alpha had essentially no effects at infusion rates of 0.03-1.0 mug/kg min--1. All renal effects of arachidonic acid were inhibited by simultaneous infusions of an inhibitor of prostaglandin synthetase, 5, 8, 11,14-eicosatetraynoic acid (20:4). None of the effects produced by PGE2 were inhibited by 20:4. These results indicate that enhanced endogenous renal prostaglandin synthesis, which can be produced by arachidonate infusion, results in significant alterations of renal function. This finding strengthens the hypothesis that renal prostaglandins formed in vivo have physiological importance as regulators of renal function.

Regulation of renal amino acid transporters during metabolic acidosis.

PubMed

Moret, Caroline; Dave, Mital H; Schulz, Nicole; Jiang, Jean X; Verrey, Francois; Wagner, Carsten A

2007-02-01

The kidney plays a major role in acid-base homeostasis by adapting the excretion of acid equivalents to dietary intake and metabolism. Urinary acid excretion is mediated by the secretion of protons and titratable acids, particularly ammonia. NH(3) is synthesized in proximal tubule cells from glutamine taken up via specific amino acid transporters. We tested whether kidney amino acid transporters are regulated in mice in which metabolic acidosis was induced with NH(4)Cl. Blood gas and urine analysis confirmed metabolic acidosis. Real-time RT-PCR was performed to quantify the mRNAs of 16 amino acid transporters. The mRNA of phosphoenolpyruvate carboxykinase (PEPCK) was quantified as positive control for the regulation and that of GAPDH, as internal standard. In acidosis, the mRNA of kidney system N amino acid transporter SNAT3 (SLC38A3/SN1) showed a strong induction similar to that of PEPCK, whereas all other tested mRNAs encoding glutamine or glutamate transporters were unchanged or reduced in abundance. At the protein level, Western blotting and immunohistochemistry demonstrated an increased abundance of SNAT3 and reduced expression of the basolateral cationic amino acid/neutral amino acid exchanger subunit y(+)-LAT1 (SLC7A7). SNAT3 was localized to the basolateral membrane of the late proximal tubule S3 segment in control animals, whereas its expression was extended to the earlier S2 segment of the proximal tubule during acidosis. Our results suggest that the selective regulation of SNAT3 and y(+)LAT1 expression may serve a major role in the renal adaptation to acid secretion and thus for systemic acid-base balance.

The effect of pregnancy on renal clearance of boron in rats given boric acid orally.

PubMed

Vaziri, N D; Oveisi, F; Culver, B D; Pahl, M V; Andersen, M E; Strong, P L; Murray, F J

2001-04-01

Boric acid (H(3)BO(3)) has been shown to cause developmental abnormalities in the offspring of pregnant rats. Comparative data on the renal clearance of boron (B) in rats and humans, both pregnant and nonpregnant, exposed to boric acid (BA) would reduce uncertainty in interspecies extrapolation from rats to humans. The purpose of this study was to evaluate the effect of pregnancy on the plasma half-life and renal clearance of boron in Sprague-Dawley rats given a single oral dose of boric acid. For the half-life study, nonpregnant and pregnant (gestation day 16) rats were given a single dose of 30 mg/kg of boric acid by gavage, and plasma samples were collected at 2-3 h intervals. The plasma half-life of boron was determined to be 2.9 +/- 0.2 and 3.2 +/- 0.3 h in nonpregnant and pregnant rats, respectively. In the clearance study, nonpregnant and pregnant (GD 16) rats were given a single gavage dose of 0.3, 3, or 30 mg/kg of boric acid. Boron clearance was slightly higher in pregnant rats (3.3 +/- 0.6, 3.2 +/- 0.5, and 3.4 +/- 0.5 ml/min/kg, respectively) compared to nonpregnant rats (3.1 +/- 0.8, 3.0 +/- 0.6, and 3.2 +/- 0.5 ml/min/kg, respectively), but the difference was not statistically significant and not dose-related. Boron clearance was less than creatinine clearance, suggesting tubular reabsorption in both groups. In conclusion, pregnancy did not appear to significantly alter the renal clearance or the plasma half-life of boron in Sprague-Dawley rats under the conditions of this study.

Mechanisms of epoxyeicosatrienoic acids to improve cardiac remodeling in chronic renal failure disease.

PubMed

Zhang, Kun; Wang, Ju; Zhang, Huanji; Chen, Jie; Zuo, Zhiyi; Wang, Jingfeng; Huang, Hui

2013-02-15

Both clinical and basic science studies have demonstrated that cardiac remodeling in patients with chronic renal failure (CRF) is very common. It is a key feature during the course of heart failure and an important risk factor for subsequent cardiac mortality. Traditional drugs or therapies rarely have effects on cardiac regression of CRF and cardiovascular events are still the first cause of death. Epoxyeicosatrienoic acids (EETs) are the products of arachidonic acids metabolized by cytochrome P450 epoxygenases. It has been found that EETs have important biological effects including anti-hypertension and anti-inflammation. Recent data suggest that EETs are involved in regulating cardiomyocyte injury, renal dysfunction, chronic kidney disease (CKD)-related risk factors and signaling pathways, all of which play key roles in cardiac remodeling induced by CRF. This review analyzes the literature to identify the possible mechanisms for EETs to improve cardiac remodeling induced by CRF and indicates the therapeutic potential of EETs in it. Copyright © 2012 Elsevier B.V. All rights reserved.

Cost-Savings Analysis of Renal Scintigraphy, Stratified by Renal Function Thresholds: Mercaptoacetyltriglycine Versus Diethylene Triamine Penta-Acetic Acid.

PubMed

Parikh, Kushal R; Davenport, Matthew S; Viglianti, Benjamin L; Hubers, David; Brown, Richard K J

2016-07-01

To determine the financial implications of switching technetium (Tc)-99m mercaptoacetyltriglycine (MAG-3) to Tc-99m diethylene triamine penta-acetic acid (DTPA) at certain renal function thresholds before renal scintigraphy. Institutional review board approval was obtained, and informed consent was waived for this HIPAA-compliant, retrospective, cohort study. Consecutive adult subjects (27 inpatients; 124 outpatients) who underwent MAG-3 renal scintigraphy, in the period from July 1, 2012 to June 30, 2013, were stratified retrospectively by hypothetical serum creatinine and estimated glomerular filtration rate (eGFR) thresholds, based on pre-procedure renal function. Thresholds were used to estimate the financial effects of using MAG-3 when renal function was at or worse than a given cutoff value, and DTPA otherwise. Cost analysis was performed with consideration of raw material and preparation costs, with radiotracer costs estimated by both vendor list pricing and proprietary institutional pricing. The primary outcome was a comparison of each hypothetical threshold to the clinical reality in which all subjects received MAG-3, and the results were supported by univariate sensitivity analysis. Annual cost savings by serum creatinine threshold were as follows (threshold given in mg/dL): $17,319 if ≥1.0; $33,015 if ≥1.5; and $35,180 if ≥2.0. Annual cost savings by eGFR threshold were as follows (threshold given in mL/min/1.73 m(2)): $21,649 if ≤60; $28,414 if ≤45; and $32,744 if ≤30. Cost-savings inflection points were approximately 1.25 mg/dL (serum creatinine) and 60 mL/min/1.73m(2) (eGFR). Secondary analysis by proprietary institutional pricing revealed similar trends, and cost savings of similar magnitude. Sensitivity analysis confirmed cost savings at all tested thresholds. Reserving MAG-3 utilization for patients who have impaired renal function can impart substantial annual cost savings to a radiology department. Copyright © 2016 American College

Non-Traditional Aspects of Renal Diets: Focus on Fiber, Alkali and Vitamin K1 Intake.

PubMed

Cupisti, Adamasco; D'Alessandro, Claudia; Gesualdo, Loreto; Cosola, Carmela; Gallieni, Maurizio; Egidi, Maria Francesca; Fusaro, Maria

2017-04-29

Renal diets for advanced chronic kidney disease (CKD) are structured to achieve a lower protein, phosphate and sodium intake, while supplying adequate energy. The aim of this nutritional intervention is to prevent or correct signs, symptoms and complications of renal insufficiency, delaying the start of dialysis and preserving nutritional status. This paper focuses on three additional aspects of renal diets that can play an important role in the management of CKD patients: the vitamin K1 and fiber content, and the alkalizing potential. We examined the energy and nutrients composition of four types of renal diets according to their protein content: normal diet (ND, 0.8 g protein/kg body weight (bw)), low protein diet (LPD, 0.6 g protein/kg bw), vegan diet (VD, 0.7 g protein/kg bw), very low protein diet (VLPD, 0.3 g protein/kg bw). Fiber content is much higher in the VD and in the VLPD than in the ND or LPD. Vitamin K1 content seems to follow the same trend, but vitamin K2 content, which could not be investigated, might have a different pattern. The net endogenous acid production (NEAP) value decreases from the ND and LPD to the vegetarian diets, namely VD and VLPD; the same finding occurred for the potential renal acid load (PRAL). In conclusion, renal diets may provide additional benefits, and this is the case of vegetarian diets. Namely, VD and VLPD also provide high amounts of fibers and Vitamin K1, with a very low acid load. These features may have favorable effects on Vitamin K1 status, intestinal microbiota and acid-base balance. Hence, we can speculate as to the potential beneficial effects on vascular calcification and bone disease, on protein metabolism, on colonic environment and circulating levels of microbial-derived uremic toxins. In the case of vegetarian diets, attention must be paid to serum potassium levels.

Non-Traditional Aspects of Renal Diets: Focus on Fiber, Alkali and Vitamin K1 Intake

PubMed Central

Cupisti, Adamasco; D’Alessandro, Claudia; Gesualdo, Loreto; Cosola, Carmela; Gallieni, Maurizio; Egidi, Maria Francesca; Fusaro, Maria

2017-01-01

Renal diets for advanced chronic kidney disease (CKD) are structured to achieve a lower protein, phosphate and sodium intake, while supplying adequate energy. The aim of this nutritional intervention is to prevent or correct signs, symptoms and complications of renal insufficiency, delaying the start of dialysis and preserving nutritional status. This paper focuses on three additional aspects of renal diets that can play an important role in the management of CKD patients: the vitamin K1 and fiber content, and the alkalizing potential. We examined the energy and nutrients composition of four types of renal diets according to their protein content: normal diet (ND, 0.8 g protein/kg body weight (bw)), low protein diet (LPD, 0.6 g protein/kg bw), vegan diet (VD, 0.7 g protein/kg bw), very low protein diet (VLPD, 0.3 g protein/kg bw). Fiber content is much higher in the VD and in the VLPD than in the ND or LPD. Vitamin K1 content seems to follow the same trend, but vitamin K2 content, which could not be investigated, might have a different pattern. The net endogenous acid production (NEAP) value decreases from the ND and LPD to the vegetarian diets, namely VD and VLPD; the same finding occurred for the potential renal acid load (PRAL). In conclusion, renal diets may provide additional benefits, and this is the case of vegetarian diets. Namely, VD and VLPD also provide high amounts of fibers and Vitamin K1, with a very low acid load. These features may have favorable effects on Vitamin K1 status, intestinal microbiota and acid-base balance. Hence, we can speculate as to the potential beneficial effects on vascular calcification and bone disease, on protein metabolism, on colonic environment and circulating levels of microbial-derived uremic toxins. In the case of vegetarian diets, attention must be paid to serum potassium levels. PMID:28468236

Embolic protection for renal artery stenting.

PubMed

Henry, M; Henry, I; Polydorou, A; Hugel, M

2008-10-01

A renal artery stenosis (RAS) is frequent and usually caused by atherosclerosis. Percutaneous renal artery angioplasty (PTRA) and stenting gives good immediate and long-term Concern has arisen in the postprocedural deterioration of the renal function (RF), which may occur in 20-40% of the patients therefore limiting the immediate benefits of the technique. Atheroembolism seems to play an important role in postprocedural deterioration. The authors postulated that the use of renal embolic protection devices could reduce the risk of renal embolism and avoid deterioration of the RF. One hundred forty-eight PTRA and stenting procedures were performed under protection in 121 hypertensive patients (M: 85), mean age: 64.5+/-11.8 years (22-87) with atherosclerotic renal artery stenosis. Eleven patients had solitary kidneys and 48 had renal insufficiency. Both occlusion balloons (N=46) and filters (N=95) were used. Of the 95 filters, the new FiberNet EP system (Lumen Biomedical) was included. This filter has the ability to capture particles as small as 30-40 microns without compromising flow. Generated debris was then removed and analysed, and blood pressure and serum creatinine levels were followed. Immediate technical success: was achieved in 100% os the cases. 112/141 lesions were stented directly. Visible debris with Percusurge (Medtronic) was aspirated and removed under aspiration from all patients and in 80% of the cases with filters. Debris was aspirated in 100% of the cases completed with the FiberNet). The mean particulate retrieved with the Percusurge system was 98.1+/-60.0 mu with a mean diameter ranging from 201+/-76 m (38-6 206). Mean occlusion time was 6.55+/-2.46 min and mean time in situ (filters) 4.2+/-1.1 min. Five times more particulate was removed with the FiberNet than with current available filters. One acute RF deterioration was observed. The mean follow-up was 29.6+/-14 months and the mean creatinine level remained constant during follow-up. At 6

Chemical renal denervation in the rat.

PubMed

Consigny, Paul M; Davalian, Dariush; Donn, Rosy; Hu, Jie; Rieser, Matthew; Stolarik, Deanne

2014-02-01

The recent success of renal denervation in lowering blood pressure in drug-resistant hypertensive patients has stimulated interest in developing novel approaches to renal denervation including local drug/chemical delivery. The purpose of this study was to develop a rat model in which depletion of renal norepinephrine (NE) could be used to determine the efficacy of renal denervation after the delivery of a chemical to the periadventitial space of the renal artery. Renal denervation was performed on a single renal artery of 90 rats (n = 6 rats/group). The first study determined the time course of renal denervation after surgical stripping of a renal artery plus the topical application of phenol in alcohol. The second study determined the efficacy of periadventitial delivery of hypertonic saline, guanethidine, and salicylic acid. The final study determined the dose-response relationship for paclitaxel. In all studies, renal NE content was determined by liquid chromatography-mass spectrometry. Renal NE was depleted 3 and 7 days after surgical denervation. Renal NE was also depleted by periadventitial delivery of all agents tested (hypertonic saline, salicylic acid, guanethidine, and paclitaxel). A dose response was observed after the application of 150 μL of 10(-5) M through 10(-2) M paclitaxel. We developed a rat model in which depletion of renal NE was used to determine the efficacy of renal denervation after perivascular renal artery drug/chemical delivery. We validated this model by demonstrating the efficacy of the neurotoxic agents hypertonic saline, salicylic acid, and guanethidine and increasing doses of paclitaxel.

Uric acid is a strong independent predictor of renal dysfunction in patients with rheumatoid arthritis.

PubMed

Daoussis, Dimitrios; Panoulas, Vasileios; Toms, Tracey; John, Holly; Antonopoulos, Ioannis; Nightingale, Peter; Douglas, Karen M J; Klocke, Rainer; Kitas, George D

2009-01-01

Recent evidence suggests that uric acid (UA), regardless of crystal deposition, may play a direct pathogenic role in renal disease. We have shown that UA is an independent predictor of hypertension and cardiovascular disease (CVD), and that CVD risk factors associate with renal dysfunction, in patients with rheumatoid arthritis (RA). In this study we investigated whether UA associates with renal dysfunction in patients with RA and whether such an association is independent or mediated through other comorbidities or risk factors for renal impairment. Renal function was assessed in 350 consecutive RA patients by estimated glomerular filtration rate (GFR) using the six-variable Modification of Diet in Renal Disease equation. Risk factors for renal dysfunction were recorded or measured in all participants. Linear regression was used to test the independence of the association between GFR and UA. Univariable analysis revealed significant associations between GFR and age, systolic blood pressure, total cholesterol, triglycerides, RA duration and UA. UA had the most powerful association with renal dysfunction (r = -0.45, P < 0.001). A basic model was created, incorporating all of the above parameters along with body mass index and gender. UA ranked as the first correlate of GFR (P < 0.001) followed by age. Adjustments for the use of medications (diuretics, low-dose aspirin, cyclooxygenase II inhibitors and nonsteroidal anti-inflammatory drugs) and further adjustment for markers of inflammation and insulin resistance did not change the results. UA is a strong correlate of renal dysfunction in RA patients. Further studies are needed to address the exact causes and clinical implications of this new finding. RA patients with elevated UA may require screening for renal dysfunction and appropriate management.

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.

Renal-protective and ameliorating impacts of omega-3 fatty acids against aspartame damaged MDCK cells.

PubMed

Pandurangan, Muthuraman; Enkhtaivan, Gansukh; Veerappan, Muthuviveganandavel; Mistry, Bhupendra; Patel, Rahul; Moon, So Hyun; Nagajyothi, Patnamsetty Chidanandha; Kim, Doo Hwan

2017-11-01

Aspartame is widely used artificial sweeteners as food additives. Several researchers have pointed that the controversial report on the use of aspartame over more than decades. Omega-3 fatty acids are essential and unsaturated fatty acids, and it plays a remarkable role in vision, intelligence, neural development, and metabolism of neurotransmitters. Therefore, the present study was aimed to investigate the effect of omega-3 fatty acids on aspartame treated renal cells. Experimental groups were divided into three such as sham control, aspartame treated, and aspartame with omega-3 fatty acids. Cell viability was determined by sulforhodamine-b assay and flow cytometric analysis. The experimental results showed that the aspartame induced altered cell viability were reduced following treatment of aspartame with omega-3 fatty acids. Altered cell morphology was recovered by omega-3 fatty acids. DNA damage appeared in the highest concentration of aspartame used in this study. DNA damage characteristics such as comet tail and tiny head sections did not appear in the omega-3 fatty acids treated cells. Several microvilli and vesicular structures were found in aspartame treated cells. Altered morphology such as rounding, microvilli, and formation of dome-like structures did not appear in the omega-3 fatty acids with aspartame treated cells. Caspase-3 mRNA and protein expression were increased in aspartame treated cells, and these levels were reduced following omega-3 fatty acids treatment. Taking all these data together, it is suggested that the omega-3 fatty acids may be a therapeutic agent to reduce the aspartame induced biochemical and morphological alterations in normal renal cells. © 2017 BioFactors, 43(6):847-857, 2017. © 2017 International Union of Biochemistry and Molecular Biology.

Association of lead exposure, serum uric acid and parameters of renal function in Nigerian lead-exposed workers.

PubMed

Alasia, D D; Emem-Chioma, P C; Wokoma, F S

2010-10-01

The presence of hyperuricemia and renal function impairment, especially in the absence of urate stone formation is strongly suggestive of lead nephropathy. The evaluation of this association is essential in areas where lead exposure is still prevalent and uncontrolled. To determine the relationship between serum uric acid and renal function indices in lead-exposed workers. A cross-sectional study of 190 adults with occupational lead exposure and 80 adults (comparison group), matched for age and sex was performed in Port Harcourt, South-south Nigeria. Blood lead was used as the biomarker of lead exposure while serum urea, serum creatinine, urine albumin (using urine albumin:creatinine ratio), estimated glomerular filtration rate (GFR) and serum uric acid were the renal function indices measured. Occupationally lead-exposed subjects had a significantly (p = 0.008) higher mean±SD blood lead levels (50.37±24.58 μg/dL) than the comparison group (41.40±26.85). The mean±SD serum urea (8.6±2.3 mg/dL), creatinine (1.0±0.2 mg/dL) and serum uric acid (4.6±1.2 mg/dL) were significantly (p < 0.01) higher in the study subjects than the comparison group (7.6±2.4, 0.9±0.2, and 3.9±1.1 mg/dL, respectively). The mean±SD creatinine clearance was significantly (p = 0.002) lower in the study subjects than the comparison group (98.9±21.3 vs. 108.2±25.2 mL/min/1.72 m2). Serum uric acid level correlated positively with serum creatinine (r = 0.134) and negatively with GFR (r = -0.151). People with occupational lead exposure are at risk of developing hyperuricemia and renal impairment.

Metastatic Neuroendocrine Tumour in a Renal Transplant Recipient: Dual-Tracer PET-CT with (18)F-FDG and (68)Ga-DOTANOC in This Rare Setting.

PubMed

Karunanithi, Sellam; Roy, Shambo Guha; Sharma, Punit; Yadav, Rajni; Bal, Chandrasekhar; Kumar, Rakesh

2015-03-01

Recipients of renal transplant are at increased risk of developing various malignancies, especially post-transplant lymphoproliferative disorder (PTLD) and skin cancers. Neuroendocrine tumours (NET) of the gastrointestinal tract have not been reported in this setting. Here we describe the case of a 75-year-old male who had undergone renal transplant 8 years back and now presented with significant weight loss and backache, clinically suspected as PTLD. (18)F-Fluordeoxyglucose ((18)F-FDG) positron emission tomography-computed tomography (PET-CT) showed hypermetabolic lesions in the liver and rectum, raising the suspicion of PTLD. However, biopsy from the liver lesion showed poorly differentiated NET. (68)Ga-labelled [1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid]-1-NaI(3)-octreotide ((68)Ga-DOTANOC) PET-CT was then done, which confirmed the primary lesion in the rectum with liver metastases.

[Quantitative determination of the main metabolites of acetylsalicylic acid/2nd communication: the concentrations of salicylic acid and its metabolites in patients with renal insufficiency (author's transl)].

PubMed

Daneels, R; Loew, D; Pütter, J

1975-07-01

Quantitative Determination of the Main Metabolites of Acetylsalicylic Acid / 2nd Communication: The concentrations of salicylic acid and its metabolies in patients with renal insufficiency 9 patients suffering from renal insufficiencies of varing degrees and treated regularly by hemodialysis were given 1.5 g Colfarit (microcapsulated acetyl salicylic acid) as a single dose. The concentrations of salicylic acid (SA), salicyluric acid (SU), further salicylic acid conjugates (SAC) and salicyluric acid conjugates (SUC) were determined in the blood plasma. Likewise urea and creatinine were determined. SA concentration decreased continually and, at the end of the trial (72 h after application), had vanished almost completely from the plasma of most patients. SU increased at first and decreased afterwards. With the exception of the dailysis time SAC and SUC increased during the trial. After 3 days the SUC level was more than 50% of total salicylate (SSS) in most patients. SSS (the sum of SA + SU + SAC + SUC) did not change very much before dialysis, but showed a rather high decrease during the first hours of dialysis. tafter dialysis the SSS levels rose again, apparently as a consequence of a redistribution and of the synthesis of conjugates with decreased tissue affinity. It could be shown that SSS in the blood plasma does not parallel SSS in the whole body. The interindividual variation of SA metabolism as well as the variation of the biological blank values was rather high. The results are discussed with regard to salicylate pharmacokinetics in renal insufficiency and to normal salicylate metabolism.

Urinary and proximal tubule acidification during reduction of renal blood flow in the rat.

PubMed Central

Jaramillo-Juárez, F; Aires, M M; Malnic, G

1990-01-01

1. The effects of reduction in renal blood flow (RBF) on urinary acidification and proximal tubule H+ ion secretion were studied after partial aortic clamping in rats. 2. Acute reduction of the renal perfusion pressure (from 109 +/- 3.88 to 77.4 +/- 1.05 mmHg) decreased both inulin and PAH (p-aminohippurate) clearances to about one-third of their control values. Absolute levels of urinary sodium excretion also decreased markedly, but fractional sodium excretion did not change significantly. 3. Urine pH and bicarbonate levels were not affected, but titratable acidity increased significantly from 0.12 +/- 0.011 to 0.25 +/- 0.042 muequiv min-1 ml-1 glomerular filtration rate (GFR). During aortic clamping, cortical PCO2 as determined by means of Severinghaus microelectrodes was reduced by a mean value of 7.0 +/- 1.5 mmHg. 4. Proximal tubule acidification kinetics were studied by stationary microperfusion techniques in which the time course of pH changes was monitored by pH microelectrodes. Steady-state pH fell from a mean control value of 6.77 +/- 0.03 to 6.65 +/- 0.02, and stationary bicarbonate concentrations from 4.70 +/- 0.27 to 2.84 +/- 0.18 mM. Acidification half-time decreased from 5.07 +/- 0.30 to 4.39 +/- 0.19 s, and net bicarbonate reabsorption increased from 1.63 +/- 0.14 to 1.99 +/- 0.12 nmol cm-2 s-1, these changes being statistically significant. 5. The experiments demonstrate that both overall acid excretion and proximal acid secretion are not compromised by a large decrease of RBF to about one-third of the control value; titratable acid excretion and proximal net bicarbonate reabsorption were even moderately increased under these conditions. PMID:2348400

The association between elevated serum uric acid level and an increased risk of renal function decline in a health checkup cohort in China.

PubMed

Cao, Xia; Wu, Liuxin; Chen, Zhiheng

2018-03-01

To investigate whether an elevated serum uric acid (SUA) level is an independent risk factor for rapid decline in renal function or new-onset chronic kidney disease (CKD) in a Chinese health checkup population. A cohort study of 6495 Chinese individuals who underwent health checkups with normal estimated glomerular filtration rate (eGFR) at baseline was carried out from May 2011 to April 2016. Examinations included a questionnaire, physical measurements, and blood sampling. The gender-specific quartiles of blood uric acid were used to present baseline descriptive data. Rapid decline of renal function was defined as eGFR loss of > 3 mL/min/1.73 m 2 /year. New-onset CKD was defined as follow-up eGFR < 60 mL/min/1.73 m 2 or positive proteinuria. Multivariable logistic regression was used to assess the relationship between serum uric acid and the following outcomes: rapid decline of renal function, incident CKD, and combined renal outcomes. During mean follow-up of 52.8 months, 1608 (24.8%) individuals reached combined renal events. Rapid decline in renal function developed in 1506 (23.2%) individuals, and incident CKD was documented in 372 (5.7%) individuals. In a multivariate model adjusted for age, BMI, diabetes, hypertension, alcohol drinking, SBP, total cholesterol, and eGFR, the odds ratio for rapid decline of renal function increased across quartiles of serum uric acid level, reaching a 1.32 (95% CI 1.02-2.97) for the top quartile compared to the lowest quartile (P for trend < 0.001). Meanwhile, higher SUA was also associated with incident CKD in all models. Furthermore, an increased risk of reaching renal outcomes across increasing quartiles of SUA levels appeared to be similar among subgroups stratified according to age, eGFR, and SBP (P < 0.05 in all). These findings suggest that higher SUA may predict progressive renal damage and dysfunction in a health checkup population in China.

Bonding the foe – NETting neutrophils immobilize the pro-inflammatory monosodium urate crystals

PubMed Central

Schorn, Christine; Janko, Christina; Krenn, Veit; Zhao, Yi; Munoz, Luis E.; Schett, Georg; Herrmann, Martin

2012-01-01

In the presence of sodium, uric acid from purine metabolism precipitates as monosodium urate (MSU) needles and forms renal calculi or causes gouty arthritis in kidneys and joints, respectively. The latter is characterized by red, hot, and swollen arthritic joints. Here we report the in vitro effect of MSU crystals on blood granulocytes and analyze their contribution to granuloma formation and neutrophil extracellular traps (NETs) formation (NETosis) in synovial fluid of patients with gouty arthritis in vivo. We observed that MSU crystals induce NETosis in vitro in a reactive oxygen species (ROS)-dependent manner. Indeed, blocking ROS (e.g., the oxidative burst) by various anti-oxidants partially inhibited NETosis induced by MSU crystals. Analyses of synovial fluids and of tissue sections of patients suffering from gout revealed that NETs are also formed in vivo, especially during acute gouty flares and/or granuloma formation. Since prolonged exposure to NETs carries the risk for the development of chronic inflammation we also studied the opsonization of NETs, as a prerequisite for their clearance. The established dead cells’ opsonins C3b, galectin-9, and CRP decorated the residual dead cells’ corpses and opsonized these for disposal. Surprisingly, all three soluble pattern recognizing molecules spared the spread NET structures. We conclude that (i) MSU crystals are strong inducers of ROS-dependent NETosis and (ii) that the prolonged presence of NET-pathogen or NET-crystal aggregates observed in patients with systemic autoimmunity, especially in those with low serum DNase-1 activity, cannot be compensated by CRP, complement, and galectin-mediated phagocytic clearance. PMID:23233855

Amino acid repletion does not decrease muscle protein catabolism during hemodialysis.

PubMed

Raj, Dominic S C; Adeniyi, Oladipo; Dominic, Elizabeth A; Boivin, Michel A; McClelland, Sandra; Tzamaloukas, Antonios H; Morgan, Nancy; Gonzales, Lawrence; Wolfe, Robert; Ferrando, Arny

2007-06-01

Intradialytic protein catabolism is attributed to loss of amino acids in the dialysate. We investigated the effect of amino acid infusion during hemodialysis (HD) on muscle protein turnover and amino acid transport kinetics by using stable isotopes of phenylalanine, leucine, and lysine in eight patients with end-stage renal disease (ESRD). Subjects were studied at baseline (pre-HD), 2 h of HD without amino acid infusion (HD-O), and 2 h of HD with amino acid infusion (HD+AA). Amino acid depletion during HD-O augmented the outward transport of amino acids from muscle into the vein. Increased delivery of amino acids to the leg during HD+AA facilitated the transport of amino acids from the artery into the intracellular compartment. Increase in muscle protein breakdown was more than the increase in synthesis during HD-O (46.7 vs. 22.3%, P < 0.001). Net balance (nmol.min(-1).100 ml (-1)) was more negative during HD-O compared with pre-HD (-33.7 +/- 1.5 vs. -6.0 +/- 2.3, P < 0.001). Despite an abundant supply of amino acids, the net balance (-16.9 +/- 1.8) did not switch from net release to net uptake. HD+AA induced a proportional increase in muscle protein synthesis and catabolism. Branched chain amino acid catabolism increased significantly from baseline during HD-O and did not decrease during HD+AA. Protein synthesis efficiency, the fraction of amino acid in the intracellular pool that is utilized for muscle protein synthesis decreased from 42.1% pre-HD to 33.7 and 32.6% during HD-O and HD+AA, respectively (P < 0.01). Thus amino acid repletion during HD increased muscle protein synthesis but did not decrease muscle protein breakdown.

Creatinine, urea, uric acid, water and electrolytes renal handling in the healthy oldest old

PubMed Central

Musso, Carlos Guido; Álvarez Gregori, Joaquín; Jauregui, José Ricardo; Macías Núñez, Juan Florencio

2012-01-01

Renal physiology in the healthy oldest old has the following characteristics, in comparison with the renal physiology in the young: a reduced creatinine clearance, tubular pattern of creatinine back-filtration, preserved proximal tubule sodium reabsorption and uric acid secretion, reduced sodium reabsorption in the thick ascending loop of Henle, reduced free water clearance, increased urea excretion, presence of medulla hypotonicity, reduced urinary dilution and concentration capabilities, and finally a reduced collecting tubules response to furosemide which expresses a reduced potassium excretion in this segment due to a sort of aldosterone resistance. All physiological changes of the aged kidney are the same in both genders. PMID:24175249

Genetic variation underlying renal uric acid excretion in Hispanic children: The Viva La Familia Study

USDA-ARS?s Scientific Manuscript database

Reduced renal excretion of uric acid plays a significant role in the development of hyperuricemia and gout in adults. Hyperuricemia has been associated with chronic kidney disease and cardiovascular disease in children and adults. There are limited genome-wide association studies associating genetic...

Attenuation of Folic Acid-Induced Renal Inflammatory Injury in Platelet-Activating Factor Receptor-Deficient Mice

PubMed Central

Doi, Kent; Okamoto, Koji; Negishi, Kousuke; Suzuki, Yoshifumi; Nakao, Akihide; Fujita, Toshiro; Toda, Akiko; Yokomizo, Takehiko; Kita, Yoshihiro; Kihara, Yasuyuki; Ishii, Satoshi; Shimizu, Takao; Noiri, Eisei

2006-01-01

Platelet-activating factor (PAF), a potent lipid mediator with various biological activities, plays an important role in inflammation by recruiting leukocytes. In this study we used platelet-activating factor receptor (PAFR)-deficient mice to elucidate the role of PAF in inflammatory renal injury induced by folic acid administration. PAFR-deficient mice showed significant amelioration of renal dysfunction and pathological findings such as acute tubular damage with neutrophil infiltration, lipid peroxidation observed with antibody to 4-hydroxy-2-hexenal (day 2), and interstitial fibrosis with macrophage infiltration associated with expression of monocyte chemoattractant protein-1 and tumor necrosis factor-α in the kidney (day 14). Acute tubular damage was attenuated by neutrophil depletion using a monoclonal antibody (RB6-8C5), demonstrating the contribution of neutrophils to acute phase injury. Macrophage infiltration was also decreased when treatment with a PAF antagonist (WEB2086) was started after acute phase. In vitro chemotaxis assay using a Boyden chamber demonstrated that PAF exhibits a strong chemotactic activity for macrophages. These results indicate that PAF is involved in pathogenesis of folic acid-induced renal injury by activating neutrophils in acute phase and macrophages in chronic interstitial fibrosis. Inhibiting the PAF pathway might be therapeutic to kidney injury from inflammatory cells. PMID:16651609

High dietary acid load is associated with increased prevalence of hypertension: the Furukawa Nutrition and Health Study.

PubMed

Akter, Shamima; Eguchi, Masafumi; Kurotani, Kayo; Kochi, Takeshi; Pham, Ngoc Minh; Ito, Rie; Kuwahara, Keisuke; Tsuruoka, Hiroko; Mizoue, Tetsuya; Kabe, Isamu; Nanri, Akiko

2015-02-01

Acid-base status has been suggested to influence blood pressure, but there is a paucity of epidemiologic evidence linking dietary acid load to hypertension. We examined cross-sectionally the association between dietary acid load and hypertension in a Japanese working population. Data were derived from health surveys from 2028 employees, ages 18 to 70 y, in two workplaces in Japan. A validated brief diet history questionnaire was used to assess diet. Two measures were used to characterize dietary acid load: potential renal acid load and estimated net endogenous acid production, which were derived from nutrient intakes. Multilevel logistic regression was used to examine the association between dietary acid load and hypertension with adjustment of potential confounding variables. High dietary acid load was suggestively associated with increased prevalence of hypertension. The multivariable adjusted odds ratios (95% confidence interval) of hypertension for the lowest through highest tertiles of net endogenous acid production were 1.00 (reference), 1.07 (0.80-1.42), and 1.33 (0.998-1.78), respectively (P for trend = 0.053). This positive association was statistically significant among normal-weight (body mass index <23 kg/m(2); P for trend = 0.03) and non-shift workers (P for trend = 0.04). Similar positive associations were observed between potential renal acid load and hypertension. The present findings suggest that high dietary acid load may be associated with increased prevalence of hypertension among those who were normal weight and non-shift workers. Copyright © 2015 Elsevier Inc. All rights reserved.

Circulating nucleic acids as possible damage-associated molecular patterns in different stages of renal failure.

PubMed

Kocić, Gordana; Radenkovic, Sonja; Cvetkovic, Tatjana; Cencic, Avrelija; Carluccio, Francesco; Musovic, Dijana; Nikolić, Goran; Jevtović-Stoimenov, Tatjana; Sokolović, Dusan; Milojkovic, Boban; Basic, Jelena; Veljkovic, Andrej; Stojanović, Svetlana

2010-05-01

Chronic renal failure (CRF) is a condition associated with the risk of cardiovascular complications. Systemic inflammatory response, initiated by the pathogen-associated molecular-pattern (PAMP) molecules, exerts many similarities with the damage-associated molecular-pattern (DAMP) molecule-induced systemic response. Up to now, a number of DAMP molecules were identified. We hypothesized that the available circulating nucleic acids, acting as DAMPs, may modulate immunoinflammatory reaction in CRF. Patients with the different stages of chronic kidney disease, kidney transplantation, and patients on dialysis were included in the study. Obtained results about higher concentration of circulating ribonucleic acid (RNA), according to the stages of kidney diseases, may contribute to the hypothesis that damaged kidney tissue releases nucleic acids. Circulating RNAs expressed maximal absorbance peak at 270 nm in spectrophotometric scan analysis, which corresponded to polyC, compared to different standard samples. During in vitro conditions, by using the culture of human residential macrophages, circulating RNA isolated from patients with IV-V-stage renal diseases, patients on hemodialysis, and patients who underwent renal transplantation were able to significantly change signal transduction proteins related to inflammation and antiviral response. They significantly increased the intracellular concentration of active nuclear transcription factor nuclear factor kappa B (NF-kappaB), interferon regulatory factors (IRF)-3, and IRF-7 and significantly decreased melanoma differentiation-associated protein-5 (MDA-5) and p38. In this way, it seems that circulating RNA, acting as DAMP, may contribute to the mechanisms of additional inflammatory reaction, possible immune destruction, and decreased antiviral response, related to complications in kidney diseases.

Alteration of Fatty Acid Oxidation in Tubular Epithelial Cells: From Acute Kidney Injury to Renal Fibrogenesis

PubMed Central

Simon, Noémie; Hertig, Alexandre

2015-01-01

Renal proximal tubular cells are the most energy-demanding cells in the body. The ATP that they use is mostly produced in their mitochondrial and peroxisomal compartments, by the oxidation of fatty acids. When those cells are placed under a biological stress, such as a transient hypoxia, fatty acid oxidation (FAO) is shut down for a period of time that outlasts injury, and carbohydrate oxidation does not take over. Facing those metabolic constraints, surviving tubular epithelial cells exhibit a phenotypic switch that includes cytoskeletal rearrangement and production of extracellular matrix proteins, most probably contributing to acute kidney injury-induced renal fibrogenesis, thence to the development of chronic kidney disease. Here, we review experimental evidence that dysregulation of FAO profoundly affects the fate of tubular epithelial cells, by promoting epithelial-to-mesenchymal transition, inflammation, and eventually interstitial fibrosis. Restoring physiological production of energy is undoubtedly a possible therapeutic approach to unlock the mesenchymal reprograming of tubular epithelial cells in the kidney. In this respect, the benefit of the use of fibrates is uncertain, but new drugs that could specifically target this metabolic pathway, and, hopefully, attenuate renal fibrosis merit future research. PMID:26301223

End-Stage Renal Disease Outcomes among the Kaiser Permanente Southern California Creatinine Safety Program (Creatinine SureNet): Opportunities to Reflect and Improve

PubMed Central

Sim, John J; Batech, Michael; Danforth, Kim N; Rutkowski, Mark P; Jacobsen, Steven J; Kanter, Michael H

2017-01-01

Objectives: The Kaiser Permanente Southern California (KPSC) creatinine safety program (Creatinine SureNet) identifies and outreaches to thousands of people annually who may have had a missed diagnosis for chronic kidney disease (CKD). We sought to determine the value of this outpatient program and evaluate opportunities for improvement. Methods: Longitudinal cohort study (February 2010 through December 2015) of KPSC members captured into the creatinine safety program who were characterized using demographics, laboratory results, and different estimations of glomerular filtration rate. Age- and sex-adjusted rates of end-stage renal disease (ESRD) were compared with those in the overall KPSC population. Results: Among 12,394 individuals, 83 (0.7%) reached ESRD. The age- and sex-adjusted relative risk of ESRD was 2.7 times higher compared with the KPSC general population during the same period (94.7 vs 35.4 per 100,000 person-years; p < 0.001). Screening with the Chronic Kidney Disease Epidemiology Collaboration (vs Modification Diet in Renal Diseases) equation would capture 44% fewer individuals and have a higher predictive value for CKD. Of those who had repeated creatinine measurements, only 13% had a urine study performed (32% among patients with confirmed CKD). Conclusion: Our study found a higher incidence of ESRD among individuals captured into the KPSC creatinine safety program. If the Chronic Kidney Disease Epidemiology Collaboration equation were used, fewer people would have been captured while improving the accuracy for diagnosing CKD. Urine testing was low even among patients with confirmed CKD. Our findings demonstrate the importance of a creatinine safety net program in an integrated health system but also suggest opportunities to improve CKD care and screening. PMID:28241912

End-Stage Renal Disease Outcomes among the Kaiser Permanente Southern California Creatinine Safety Program (Creatinine SureNet): Opportunities to Reflect and Improve.

PubMed

Sim, John J; Batech, Michael; Danforth, Kim N; Rutkowski, Mark P; Jacobsen, Steven J; Kanter, Michael H

2017-01-01

The Kaiser Permanente Southern California (KPSC) creatinine safety program (Creatinine SureNet) identifies and outreaches to thousands of people annually who may have had a missed diagnosis for chronic kidney disease (CKD). We sought to determine the value of this outpatient program and evaluate opportunities for improvement. Longitudinal cohort study (February 2010 through December 2015) of KPSC members captured into the creatinine safety program who were characterized using demographics, laboratory results, and different estimations of glomerular filtration rate. Age- and sex-adjusted rates of end-stage renal disease (ESRD) were compared with those in the overall KPSC population. Among 12,394 individuals, 83 (0.7%) reached ESRD. The age- and sex-adjusted relative risk of ESRD was 2.7 times higher compared with the KPSC general population during the same period (94.7 vs 35.4 per 100,000 person-years; p < 0.001). Screening with the Chronic Kidney Disease Epidemiology Collaboration (vs Modification Diet in Renal Diseases) equation would capture 44% fewer individuals and have a higher predictive value for CKD. Of those who had repeated creatinine measurements, only 13% had a urine study performed (32% among patients with confirmed CKD). Our study found a higher incidence of ESRD among individuals captured into the KPSC creatinine safety program. If the Chronic Kidney Disease Epidemiology Collaboration equation were used, fewer people would have been captured while improving the accuracy for diagnosing CKD. Urine testing was low even among patients with confirmed CKD. Our findings demonstrate the importance of a creatinine safety net program in an integrated health system but also suggest opportunities to improve CKD care and screening.

Basolateral choline transport in isolated rabbit renal proximal tubules.

PubMed

Dantzler, W H; Evans, K K; Wright, S H

1998-11-01

Choline can undergo both net secretion and net reabsorption by renal proximal tubules, but at physiological plasma levels net reabsorption occurs. During this process, choline enters the cells at the luminal side down an electrochemical gradient via a specific transporter with a high affinity for choline. It appeared likely that choline was then transported out of the cells against an electrochemical gradient at the basolateral membrane by countertransport for another organic cation. This possibility was examined by studying net transepithelial reabsorption and basolateral uptake and efflux of [14C]choline in isolated S2 segments of rabbit renal proximal tubules. Basolateral uptake, which was inhibited by other organic cations such as tetraethylammonium (TEA), appeared to occur by the standard organic cation transport pathway. However, the addition of TEA to the bathing medium not only failed to trans-stimulate net transepithelial reabsorption and basolateral efflux of [14C]choline but it actually inhibited transepithelial reabsorption by @60%. The results do not support the presence of a countertransport step for choline against an electrochemical gradient at the basolateral membrane. Instead, they suggest that choline crosses this membrane by some form of carrier-mediated diffusion even during the reabsorptive process.

[Nutrition, acid-base metabolism, cation-anion difference and total base balance in humans].

PubMed

Mioni, R; Sala, P; Mioni, G

2008-01-01

The relationship between dietary intake and acid-base metabolism has been investigated in the past by means of the inorganic cation-anion difference (C(+)(nm)-A(-)(nm)) method based on dietary ash-acidity titration after the oxidative combustion of food samples. Besides the inorganic components of TA (A(-)(nm)-C(+)(nm)), which are under renal control, there are also metabolizable components (A(-)(nm)-C(+)(nm)) of TA, which are under the control of the intermediate metabolism. The whole body base balance, NBb(W), is obtained only by the application of C(+)(nm)-A(-)(nm) to food, feces and urine, while the metabolizable component (A(-)(nm)-C(+)(nm)) is disregarded. A novel method has been subsequently suggested to calculate the net balance of fixed acid, made up by the difference between the input of net endogenous acid production: NEAP = SO(4)(2-)+A(-)(m)-(C(+)(nm)-A(-)(nm)), and the output of net acid excretion: NAE = TA + NH(4)(+) - HCO(3)(-). This approach has been criticized because 1) it includes metabolizable acids, whose production cannot be measured independently; 2) the specific control of metabolizable acid and base has been incorrectly attributed to the kidney; 3) the inclusion of A-m in the balance input generates an acid overload; 4) the object of measurement in making up a balance has to be the same, a condition not fulfilled as NEAP is different from NAE. Lastly, by rearranging the net balance of the acid equation, the balance of nonmetabolizable acid equation is obtained. Therefore, any discrepancy between these two equations is due to the inaccuracy in the urine measurement of metabolizable cations and/or anions.

Epoxyeicosatrienoic Acids Prevent Cisplatin-Induced Renal Apoptosis through a p38 Mitogen-Activated Protein Kinase–Regulated Mitochondrial Pathway

PubMed Central

Liu, Yingmei; Lu, Xiaodan; Nguyen, Sinh; Olson, Jean L.; Webb, Heather K.

2013-01-01

Soluble epoxide hydrolase (sEH) catalyzes the conversion of epoxyeicosatrienoic acids into less active eicosanoids, and inhibitors of sEH have anti-inflammatory and antiapoptotic properties. Based on previous observations that sEH inhibition attenuates cisplatin-induced nephrotoxicity by modulating nuclear factor-κB signaling, we hypothesized that this strategy would also attenuate cisplatin-induced renal apoptosis. Inhibition of sEH with AR9273 [1-adamantan-1-yl-3-(1-methylsulfonyl-piperidin-4-yl-urea)] reduced cisplatin-induced apoptosis through mechanisms involving mitochondrial apoptotic pathways and by reducing reactive oxygen species. Renal mitochondrial Bax induction following cisplatin treatment was significantly decreased by treatment of mice with AR9273 and these antiapoptotic effects involved p38 mitogen-activated protein kinase signaling. Similar mechanisms contributed to reduced apoptosis in Ephx2−/− mice treated with cisplatin. Moreover, in pig kidney proximal tubule cells, cisplatin-induced mitochondrial trafficking of Bax and cytochrome c, caspase-3 activation, and oxidative stress are significantly attenuated in the presence of epoxyeicosatrienoic acids (EETs). Collectively, these in vivo and in vitro studies demonstrate a role for EETs in limiting cisplatin-induced renal apoptosis. Inhibition of sEH represents a novel therapeutic strategy for protection against cisplatin-induced renal damage. PMID:24092818

Does the serum uric acid level have any relation to arterial stiffness or blood pressure in adults with congenital renal agenesis and/or hypoplasia?

PubMed

Yazici, Raziye; Guney, İbrahim; Altintepe, Lutfullah; Yazici, Mehmet

2017-01-01

The relationship between serum uric acid and arterial stiffness or blood pressure is not clear. The serum uric acid level and its association with cardiovascular risk is not well known in patients with reduced renal mass. We aimed to investigate the relation between serum uric acid levels and arterial stiffness and also blood pressure in patients with congenital renal agenesis and/or hypoplasia. In this single center, cross-sectional study, a total of 55 patients (39 (% 70.9) with unilateral small kidney and 16 (%29.1) with renal agenesis) were included. The median age was 35 (21-50) years. The study population was divided into tertiles of serum uric acid (according to 2.40-3.96, 3.97-5.10, and 5.11-9.80 mg/dl cut-off values of serum uric acid levels). Official and 24-h ambulatory non-invasive blood pressures of all patients were measured. The arterial stiffness was assessed by pulse wave velocity (PWV). PWV values were increased from first to third tertile (5.5 ± 0.6, 5.7 ± 0.8, 6.1 ± 0.7, respectively), but this gradual increase between tertiles did not reach significance. Linear regression analyses showed a positive correlation between serum uric acid levels and PWV (β = 0.40, p = 0.010), but no correlation was found between uric acid and daytime systolic blood pressure (β = 0.24, p = 0.345). In congenital renal agenesis/hypoplasia, the serum uric acid level was positively correlated with arterial stiffness, but there was no correlation with blood pressure.

Magnetic properties, acid neutralization capacity, and net acid production of rocks in the Animas River Watershed Silverton, Colorado

USGS Publications Warehouse

McCafferty, Anne E.; Yager, Douglas B.; Horton, Radley M.; Diehl, Sharon F.

2006-01-01

Federal land managers along with local stakeholders in the Upper Animas River watershed near Silverton, Colorado are actively designing and implementing mine waste remediation projects to mitigate the effects of acid mine drainage from several abandoned hard rock metal mines and mills. Local source rocks with high acid neutralization capacity (ANC) within the watershed are of interest to land managers for use in these remediation projects. A suite of representative samples was collected from propylitic to weakly sericitic-altered volcanic and plutonic rocks exposed in outcrops throughout the watershed. Acid-base accounting laboratory methods coupled with mineralogic and geochemical characterization provide insight into lithologies that have a range of ANC and net acid production (NAP). Petrophysical lab determinations of magnetic susceptibility converted to estimates for percent magnetite show correlation with the environmental properties of ANC and NAP for many of the lithologies. A goal of our study is to interpret watershed-scale airborne magnetic data for regional mapping of rocks that have varying degrees of ANC and NAP. Results of our preliminary work are presented here.

Tauroursodeoxycholic Acid Attenuates Renal Tubular Injury in a Mouse Model of Type 2 Diabetes

PubMed Central

Zhang, Jing; Fan, Ying; Zeng, Chuchu; He, Li; Wang, Niansong

2016-01-01

Renal tubular injury is a critical factor in the pathogenesis of diabetic nephropathy (DN). Endoplasmic reticulum (ER) stress is involved in diabetic nephropathy. Tauroursodeoxycholic acid (TUDCA) is an effective inhibitor of ER stress. Here, we investigated the role of TUDCA in the progression of tubular injury in DN. For eight weeks, being treated with TUDCA at 250 mg/kg intraperitoneal injection (i.p.) twice a day, diabetic db/db mice had significantly reduced blood glucose, albuminuria and attenuated renal histopathology. These changes were associated with a significant decreased expression of ER stress markers. At the same time, diabetic db/db mice had more TUNEL-positive nuclei in the renal tubule, which were attenuated by TUDCA treatment, along with decreases in ER stress–associated apoptotic markers in the kidneys. In summary, the effect of TUDCA on tubular injury, in part, is associated with inhibition of ER stress in the kidneys of diabetic db/db mice. TUDCA shows potential as a therapeutic target for the prevention and treatment of DN. PMID:27669287

Estimation of the net acid load of the diet of ancestral preagricultural Homo sapiens and their hominid ancestors.

PubMed

Sebastian, Anthony; Frassetto, Lynda A; Sellmeyer, Deborah E; Merriam, Renée L; Morris, R Curtis

2002-12-01

Natural selection has had < 1% of hominid evolutionary time to eliminate the inevitable maladaptations consequent to the profound transformation of the human diet resulting from the inventions of agriculture and animal husbandry. The objective was to estimate the net systemic load of acid (net endogenous acid production; NEAP) from retrojected ancestral preagricultural diets and to compare it with that of contemporary diets, which are characterized by an imbalance of nutrient precursors of hydrogen and bicarbonate ions that induces a lifelong, low-grade, pathogenically significant systemic metabolic acidosis. Using established computational methods, we computed NEAP for a large number of retrojected ancestral preagricultural diets and compared them with computed and measured values for typical American diets. The mean (+/- SD) NEAP for 159 retrojected preagricultural diets was -88 +/- 82 mEq/d; 87% were net base-producing. The computational model predicted NEAP for the average American diet (as recorded in the third National Health and Nutrition Examination Survey) as 48 mEq/d, within a few percentage points of published measured values for free-living Americans; the model, therefore, was not biased toward generating negative NEAP values. The historical shift from negative to positive NEAP was accounted for by the displacement of high-bicarbonate-yielding plant foods in the ancestral diet by cereal grains and energy-dense, nutrient-poor foods in the contemporary diet-neither of which are net base-producing. The findings suggest that diet-induced metabolic acidosis and its sequelae in humans eating contemporary diets reflect a mismatch between the nutrient composition of the diet and genetically determined nutritional requirements for optimal systemic acid-base status.

Effects of long-term high-saturated and unsaturated fatty acid diets on relaxation and contraction of renal arteries in insulin resistant rats.

PubMed

Gao, Yu; Song, Guang-Yao; Ma, Hui-Juan; Zhang, Wen-Jie; Zhou, Yu

2007-06-25

The present study was designed to investigate the effects of high-saturated and high-unsaturated fatty acid diets on relaxation and contraction of the renal arteries in insulin resistance (IR) rats. Wistar rats were fed normal chow diet (control), high-saturated fatty acid diet or high-unsaturated fatty acid diet for 6 months (n=14 in each group). IR was evaluated by glucose infusion rate (GIR) of hyperinsulinemic euglycemic clamp. Blood pressure was measured via the tail-cuff method. Body weight (BW), plasma total triglyceride (TG), free fatty acid (FFA), insulin, fasting blood glucose (FBG) and nitric oxide metabolite (NO2(-)/NO3(-)) were compared among the three groups. The rats were sacrificed and the renal arterial rings were placed in the physiological tissue baths for measurement of vascular response to various agents. After the arterial rings were constricted with 3 mmol/L noradrenaline (NA), endothelium-dependent vasorelaxation to acetylcholine (ACh) and endothelium-independent vasorelaxation to sodium nitroprusside (NTP) were measured. Endothelium-dependent vasorelaxation to ACh was also observed in renal arterial rings incubated with L-arginine (L-Arg), N(omega)-nitro-L-arginine (L-NNA) and methylene blue (MB), respectively. Arterial contractility was evaluated from concentration-response curves to 10 nmol/L-100 micromol/L NA. Saturated or unsaturated fatty acids led to moderate rises in blood pressure (P<0.05). It was associated with higher levels of plasma lipids and lower whole body insulin sensitivity (P<0.01). There were no significant differences in BW, FBG, TG, insulin and FFA between saturated and unsaturated fatty acid-fed rats. A decrease in endothelium-dependent vasorelaxation of the renal arteries in saturated and unsaturated fatty acid-fed rats was observed (P<0.01), but there was no marked difference between the two high-fatty acid diet groups. Endothelium-dependent vasorelaxation was increased when the arteries were incubated with L

Higher Estimated Net Endogenous Acid Production May Be Associated with Increased Prevalence of Nonalcoholic Fatty Liver Disease in Chinese Adults in Hong Kong

PubMed Central

Chan, Ruth; Wong, Vincent Wai-Sun; Chu, Winnie Chiu-Wing; Wong, Grace Lai-Hung; Li, Liz Sin; Leung, Jason; Chim, Angel Mei-Ling; Yeung, David Ka-Wai; Sea, Mandy Man-Mei; Woo, Jean; Chan, Francis Ka-Leung; Chan, Henry Lik-Yuen

2015-01-01

Nonalcoholic fatty liver disease (NAFLD) has been associated with reduced growth hormone levels and signaling. Such hormonal changes also occur in metabolic acidosis. Since mild metabolic acidosis can be diet induced, diet-induced acid load may constitute a nutritional factor with possible influence on NAFLD development. This study explored whether a higher diet-induced acid load is associated with an increased likelihood of NAFLD. Apparently healthy Chinese adults (330 male, 463 female) aged 19-72 years were recruited through population screening between 2008 and 2010 in a cross-sectional population-based study in Hong Kong. Estimated net endogenous acid production (NEAP) was calculated using Frassetto’s method and potential renal acid load (PRAL) was calculated using Remer’s method based on dietary data from a food frequency questionnaire. NAFLD was defined as intrahepatic triglyceride content at >5% by proton-magnetic resonance spectroscopy. Possible advanced fibrosis was defined as liver stiffness at >7.9 kPa by transient elastography. Multivariate logistic regression models were used to examine the association between each measure of dietary acid load and prevalent NAFLD or possible advanced fibrosis with adjustment for potential anthropometric and lifestyle factors. 220 subjects (27.7%) were diagnosed with NAFLD. Estimated NEAP was positively associated with the likelihood of having NAFLD after adjustment for age, sex, body mass index, current drinker status and the presence of metabolic syndrome [OR (95% CI) = 1.25 (1.02-1.52), p = 0.022]. The association was slightly attenuated but remained significant when the model was further adjusted for other dietary variables. No association between PRAL and NAFLD prevalence was observed. Both estimated NEAP and PRAL were not associated with the presence of possible advance fibrosis. Our findings suggest that there may be a modest association between diet-induced acid load and NAFLD. More studies are needed to

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

Dietary acid load and renal function have varying effects on blood acid-base status and exercise performance across age and sex.

PubMed

Hietavala, Enni-Maria; Stout, Jeffrey R; Frassetto, Lynda A; Puurtinen, Risto; Pitkänen, Hannu; Selänne, Harri; Suominen, Harri; Mero, Antti A

2017-12-01

Diet composition influences acid-base status of the body. This may become more relevant as renal functional capacity declines with aging. We examined the effects of low (LD) versus high dietary acid load (HD) on blood acid-base status and exercise performance. Participants included 22 adolescents, 33 young adults (YA), and 33 elderly (EL), who followed a 7-day LD and HD in a randomized order. At the end of both diet periods the subjects performed a cycle ergometer test (3 × 10 min at 35%, 55%, 75%, and (except EL) until exhaustion at 100% of maximal oxygen uptake). At the beginning of and after the diet periods, blood samples were collected at rest and after all workloads. Oxygen uptake, respiratory exchange ratio (RER), and heart rate (HR) were monitored during cycling. In YA and EL, bicarbonate (HCO 3 - ) and base excess (BE) decreased over the HD period, and HCO 3 - , BE, and pH were lower at rest after HD compared with LD. In YA and EL women, HCO 3 - and BE were lower at submaximal workloads after HD compared with LD. In YA women, the maximal workload was 19% shorter and maximal oxygen uptake, RER, and HR were lower after HD compared with LD. Our data uniquely suggests that better renal function is associated with higher availability of bases, which may diminish exercise-induced acidosis and improve maximal aerobic performance. Differences in glomerular filtration rate between the subject groups likely explains the larger effects of dietary acid load in the elderly compared with younger subjects and in women compared with men.

Digestion and nutrient net fluxes across the rumen, and the mesenteric- and portal-drained viscera in sheep fed with fresh forage twice daily: net balance and dynamic aspects.

PubMed

Rémond, Didier; Bernard, Laurence; Chauveau, Béatrice; Nozière, Pierre; Poncet, Claude

2003-05-01

Digestion and portal net flux of nutrients were studied in sheep fed twice daily with fresh orchard-grass. Digestive flows were measured in six fistulated sheep using the double-marker technique. Three sheep were fitted with catheters and blood-flow probes, allowing nutrient net flux measurements across the portal-drained viscera (PDV), the mesenteric-drained viscera (MDV) and the rumen. Total tract apparent digestion of N was similar to portal net appearance of N, calculated as the sum of free amino acids (FAA), peptide amino acids (PAA), NH3, and urea net fluxes. PAA accounted for 25 % of non-protein amino acid net release across the PDV. With the exception of glycine and glutamate, the small intestine was the main contributor to this PAA net release. The essential amino acid (EAA) apparent disappearance between the duodenum and the ileum was lower than the net appearance of EAA (FAA + PAA) across the MDV. The value of PDV:MDV flux of free EAA was, on average, 78 %. The rumen accounted for 30 % of the net uptake of EAA by the PDV tissues not drained by the mesenteric vein. Rumen net release of acetate, propionate, butyrate, 3-hydroxybutyrate, and lactate accounted for 70, 55, 46, 77 and 52 %, respectively, of their portal net releases. Conversely, the small intestine was a net consumer of arterial acetate and 3-hydroxybutyrate. Dynamic study of nutrient net fluxes across the PDV showed that throughout a feeding cycle, the liver faced a constant flux of amino acids (AA), whereas volatile fatty acid and NH3 net fluxes varied in response to the meal. The present study specified, in forage-fed sheep, the partitioning of nutrient net fluxes across the PDV and the role of peptides in portal net release of AA.

Uric Acid Induces Renal Inflammation via Activating Tubular NF-κB Signaling Pathway

PubMed Central

Zhou, Yang; Fang, Li; Jiang, Lei; Wen, Ping; Cao, Hongdi; He, Weichun; Dai, Chunsun; Yang, Junwei

2012-01-01

Inflammation is a pathologic feature of hyperuricemia in clinical settings. However, the underlying mechanism remains unknown. Here, infiltration of T cells and macrophages were significantly increased in hyperuricemia mice kidneys. This infiltration of inflammatory cells was accompanied by an up-regulation of TNF-α, MCP-1 and RANTES expression. Further, infiltration was largely located in tubular interstitial spaces, suggesting a role for tubular cells in hyperuricemia-induced inflammation. In cultured tubular epithelial cells (NRK-52E), uric acid, probably transported via urate transporter, induced TNF-α, MCP-1 and RANTES mRNA as well as RANTES protein expression. Culture media of NRK-52E cells incubated with uric acid showed a chemo-attractive ability to recruit macrophage. Moreover uric acid activated NF-κB signaling. The uric acid-induced up-regulation of RANTES was blocked by SN 50, a specific NF-κB inhibitor. Activation of NF-κB signaling was also observed in tubule of hyperuricemia mice. These results suggest that uric acid induces renal inflammation via activation of NF-κB signaling. PMID:22761883

[Clinical characteristics and renal uric acid excretion in early-onset gout patients].

PubMed

Li, Q H; Liang, J J; Chen, L X; Mo, Y Q; Wei, X N; Zheng, D H; Dai, L

2018-03-01

Objective: To investigate clinical characteristics and renal uric acid excretion in early-onset gout patients. Methods: Consecutive inpatients with primary gout were recruited between 2013 and 2017. The patients with gout onset younger than 30 were defined as early-onset group while the others were enrolled as control group. Clinical characteristics and uric acid (UA) indicators were compared between two groups. Results: Among 202 recruited patients, the early-onset group included 36 patients (17.8%). Compared with control group, the early-onset group presented more patients with obesity [13 patients (36.1%) vs. 22 patients (13.3%), P< 0.05], significantly higher serum UA level [(634±124)μmol/L vs.(527±169)μmol/L] and glomerular load of UA[(7.2±2.8)mg·min(-1)·1.73m(-2) vs. (4.4±2.2)mg·min(-1)·1.73m(-2)] and estimated glomerular filtration rate (GFR) [(83±21)ml·min(-1)·1.73m(-2) vs. (67±21)ml·min(-1)·1.73m(-2)] (all P< 0.05), lower fractional excretion of UA [4.4% (3.4%,6.1%) vs. 7.2% (5.2%,9.6%), P< 0.05], whereas 24h urinary UA excretion was comparable [(2 788±882)μmol/1.73m(2) vs. (2 645±1 140)μmol/1.73m(2), P= 0.274]. Subgroup analysis of patients without chronic kidney disease showed significantly lower fractional excretion of UA in the early-onset group [4.5%(3.3%,6.1%) vs. 6.7% (5.1%,8.7%), P< 0.05]. Logistic regression analysis showed that obesity ( OR= 3.25) and fractional excretion of UA less than 7% ( OR= 9.01, all P< 0.05) were risk factors of gout early onset. Conclusion: The gout patients with early-onset younger than 30 present high serum and glomerular load of uric acid which might be due to obesity and relative under-excretion of renal uric acid.

Relationship between serum uric acid and mortality among hemodialysis patients: Retrospective analysis of Korean end-stage renal disease registry data

PubMed Central

Kim, Chang Seong; Jin, Dong-Chan; Yun, Young Cheol; Bae, Eun Hui; Ma, Seong Kwon; Kim, Soo Wan

2017-01-01

Background It is thought that hyperuricemia might lower the risk of mortality among hemodialysis patients, unlike in the general population, but the evidence is controversial. The aim of the current study was to evaluate the impact of serum uric acid level on the long-term clinical outcomes of hemodialysis patients in Korea. Methods Retrospective analysis was performed on data from the End-Stage Renal Disease Registry of the Korean Society of Nephrology. This included data for 7,333 patients (mean age, 61 ± 14 years; 61% male) who received hemodialysis from January 2001 through April 2015. Initial laboratory data were used in the analysis. Results The mean serum uric acid level in this study was 7.1 ± 1.7 mg/dL. Body mass index, normalized protein catabolic rate, albumin, and cholesterol were positively correlated with serum uric acid level after controlling for age and sex. After controlling for demographic data, comorbidities, and residual renal function, a higher uric acid level was independently associated with a significantly lower all-cause mortality (hazard ratio [HR], 0.90 per 1 mg/dL increase in uric acid level; 95% confidence interval [CI], 0.83–0.97; P = 0.008), but not cardiovascular mortality (HR, 0.90; 95% CI, 0.80–1.01; P = 0.078). Comparing uric acid levels in the highest and lowest quintiles, the HR for all-cause mortality was 0.65 (95% CI, 0.42–0.99; P = 0.046). Conclusion Hyperuricemia was strongly associated with a lower risk of all-cause mortality, but there seems to be no significant association between serum uric acid level and cardiovascular mortality among Korean hemodialysis patients with end-stage renal disease. PMID:29285429

Homozygous SLC2A9 Mutations Cause Severe Renal Hypouricemia

PubMed Central

Gray, Nicola K.; Campbell, Susan; Shu, Xinhua; Sawyer, Lindsay; Richardson, William; Rechavi, Gideon; Amariglio, Ninette; Ganon, Liat; Sela, Ben-Ami; Bahat, Hilla; Goldman, Michael; Weissgarten, Joshua; Millar, Michael R.; Wright, Alan F.; Holtzman, Eliezer J.

2010-01-01

Hereditary hypouricemia may result from mutations in the renal tubular uric acid transporter URAT1. Whether mutation of other uric acid transporters produces a similar phenotype is unknown. We studied two families who had severe hereditary hypouricemia and did not have a URAT1 defect. We performed a genome-wide homozygosity screen and linkage analysis and identified the candidate gene SLC2A9, which encodes the glucose transporter 9 (GLUT9). Both families had homozygous SLC2A9 mutations: A missense mutation (L75R) in six affected members of one family and a 36-kb deletion, resulting in a truncated protein, in the other. In vitro, the L75R mutation dramatically impaired transport of uric acid. The mean concentration of serum uric acid of seven homozygous individuals was 0.17 ± 0.2 mg/dl, and all had a fractional excretion of uric acid >150%. Three individuals had nephrolithiasis, and three had a history of exercise-induced acute renal failure. In conclusion, homozygous loss-of-function mutations of GLUT9 cause a total defect of uric acid absorption, leading to severe renal hypouricemia complicated by nephrolithiasis and exercise-induced acute renal failure. In addition to clarifying renal handling of uric acid, our findings may provide a better understanding of the pathophysiology of acute renal failure, nephrolithiasis, hyperuricemia, and gout. PMID:19926891

Renal Gene Expression Database (RGED): a relational database of gene expression profiles in kidney disease

PubMed Central

Zhang, Qingzhou; Yang, Bo; Chen, Xujiao; Xu, Jing; Mei, Changlin; Mao, Zhiguo

2014-01-01

We present a bioinformatics database named Renal Gene Expression Database (RGED), which contains comprehensive gene expression data sets from renal disease research. The web-based interface of RGED allows users to query the gene expression profiles in various kidney-related samples, including renal cell lines, human kidney tissues and murine model kidneys. Researchers can explore certain gene profiles, the relationships between genes of interests and identify biomarkers or even drug targets in kidney diseases. The aim of this work is to provide a user-friendly utility for the renal disease research community to query expression profiles of genes of their own interest without the requirement of advanced computational skills. Availability and implementation: Website is implemented in PHP, R, MySQL and Nginx and freely available from http://rged.wall-eva.net. Database URL: http://rged.wall-eva.net PMID:25252782

Renal Gene Expression Database (RGED): a relational database of gene expression profiles in kidney disease.

PubMed

Zhang, Qingzhou; Yang, Bo; Chen, Xujiao; Xu, Jing; Mei, Changlin; Mao, Zhiguo

2014-01-01

We present a bioinformatics database named Renal Gene Expression Database (RGED), which contains comprehensive gene expression data sets from renal disease research. The web-based interface of RGED allows users to query the gene expression profiles in various kidney-related samples, including renal cell lines, human kidney tissues and murine model kidneys. Researchers can explore certain gene profiles, the relationships between genes of interests and identify biomarkers or even drug targets in kidney diseases. The aim of this work is to provide a user-friendly utility for the renal disease research community to query expression profiles of genes of their own interest without the requirement of advanced computational skills. Website is implemented in PHP, R, MySQL and Nginx and freely available from http://rged.wall-eva.net. http://rged.wall-eva.net. © The Author(s) 2014. Published by Oxford University Press.

Corosolic Acid Induces Non-Apoptotic Cell Death through Generation of Lipid Reactive Oxygen Species Production in Human Renal Carcinoma Caki Cells.

PubMed

Woo, Seon Min; Seo, Seung Un; Min, Kyoung-Jin; Im, Seung-Soon; Nam, Ju-Ock; Chang, Jong-Soo; Kim, Shin; Park, Jong-Wook; Kwon, Taeg Kyu

2018-04-27

Corosolic acid is one of the pentacyclic triterpenoids isolated from Lagerstroemia speciose and has been reported to exhibit anti-cancer and anti-proliferative activities in various cancer cells. In the present study, we investigated the molecular mechanisms of corosolic acid in cancer cell death. Corosolic acid induces a decrease of cell viability and an increase of cell cytotoxicity in human renal carcinoma Caki cells. Corosolic acid-induced cell death is not inhibited by apoptosis inhibitor (z-VAD-fmk, a pan-caspase inhibitor), necroptosis inhibitor (necrostatin-1), or ferroptosis inhibitors (ferrostatin-1 and deferoxamine (DFO)). Furthermore, corosolic acid significantly induces reactive oxygen species (ROS) levels, but antioxidants ( N -acetyl-l-cysteine (NAC) and trolox) do not inhibit corosolic acid-induced cell death. Interestingly, corosolic acid induces lipid oxidation, and α-tocopherol markedly prevents corosolic acid-induced lipid peroxidation and cell death. Anti-chemotherapeutic effects of α-tocopherol are dependent on inhibition of lipid oxidation rather than inhibition of ROS production. In addition, corosolic acid induces non-apoptotic cell death in other renal cancer (ACHN and A498), breast cancer (MDA-MB231), and hepatocellular carcinoma (SK-Hep1 and Huh7) cells, and α-tocopherol markedly inhibits corosolic acid-induced cell death. Therefore, our results suggest that corosolic acid induces non-apoptotic cell death in cancer cells through the increase of lipid peroxidation.

[Correlation between serum uric acid level and acute renal injury after coronary artery bypass grafting].

PubMed

Xu, D Q; Du, J; Zheng, Z; Tang, Y; Zou, L; Zhang, Y H; Zhang, H T

2017-07-11

Objective: To evaluate whether early postoperative serum uric acid level can predict postoperative acute renal injury (AKI) among patients undergoing coronary artery bypass grafting (CABG). Methods: The study retrospectively enrolled 1 306 patients undergoing CABG in Fuwai Hospital between September 2012 and December 2013. The patients were divided into 5 groups by the concentrations of serum uric acid measured on the morning of the first postoperative day, and uric acid categories were as follow: less than 195 μmol/L (Q1 group, 262 cases), 195-236 μmol/L (Q2 group, 263 cases), 237-280 μmol/L (Q3 group, 260 cases), 281-336 μmol/L (Q4 group, 261 cases), more than 336 μmol/L (Q5 group, 260 cases). The primary end points were AKI (RIFLE criteria), severe AKI (AKI≥stage Ⅰ), postoperative continuous renal replacement therapy (CRRT) requirement, in-hospital death, length of stay in hospital and intensive care unit(ICU). The area under the receiver-operating characteristic (ROC) curve (AUC) was used to determine the ability of the early postoperative serum uric acid level as a risk factor for postoperative AKI prediction. Results: Among the 1 306 patients enrolled in the study, AKI was found in 335 patients (25.65%). After adjusting for variables that were different between the 5 groups, the Q5 group had significantly higher risk of AKI, AKI≥ stage Ⅰ and the requirement of CRRT ( P <0.01). The ROC for the outcome of postoperative AKI had an AUC of 0.648 (95% CI: 0.612-0.683) when serum creatinine levels alone were used and 0.722 (95% CI: 0.688-0.755) when serum uric acid levels alone were used (both P <0.001). Early postoperative serum uric acid was a better predictor than serum creatinine( P <0.001). Conclusion: The serum uric acid concentration within 12 hours after operation is an independent predictor of postoperative AKI in patients undergoing CABG, which could be used to identify patients at high risk for AKI.

Renal ammonium production--une vue canadienne.

PubMed

Brosnan, J T; Lowry, M; Vinay, P; Gougoux, A; Halperin, M L

1987-04-01

The purpose of this review is to examine the factors regulating ammonium production in the kidney and to place these factors in the perspective of acid-base balance. Renal ammonium production and excretion are required to maintain acid-base balance. However, only a portion of renal ammonium production is specifically stimulated by metabolic acidosis. One should examine urinary ammonium excretion at three levels: distribution of ammonium between blood and urine, augmented glutamine metabolism, and an energy constraint due to ATP balance considerations. With respect to the biochemical regulation of acid-base renal ammonium production, an acute stimulation of alpha-ketoglutarate dehydrogenase by a fall in pH seems to be important but this may not be the entire story. In chronic metabolic acidosis augmented glutamine entry into mitochondria (dog) or increased phosphate-dependent glutaminase activity (rat) become critical to support a high flux rate. Metabolic alterations, which diminish the rate of oxidation of alternate fuels, might also be important. The above principles are discussed in the ketoacidosis of fasting, the clinically important situation of high rates of renal ammonium production.

The Bohr Effect Is Not a Likely Promoter of Renal Preglomerular Oxygen Shunting

PubMed Central

Olgac, Ufuk; Kurtcuoglu, Vartan

2016-01-01

The aim of this study was to evaluate whether possible preglomerular arterial-to-venous oxygen shunting is affected by the interaction between renal preglomerular carbon dioxide and oxygen transport. We hypothesized that a reverse (venous-to-arterial) shunting of carbon dioxide will increase partial pressure of carbon dioxide and decrease pH in the arteries and thereby lead to increased oxygen offloading and consequent oxygen shunting. To test this hypothesis, we employed a segment-wise three-dimensional computational model of coupled renal oxygen and carbon dioxide transport, wherein coupling is achieved by shifting the oxygen-hemoglobin dissociation curve in dependence of local changes in partial pressure of carbon dioxide and pH. The model suggests that primarily due to the high buffering capacity of blood, there is only marginally increased acidity in the preglomerular vasculature compared to systemic arterial blood caused by carbon dioxide shunting. Furthermore, effects of carbon dioxide transport do not promote but rather impair preglomerular oxygen shunting, as the increase in acidity is higher in the veins compared to that in the arteries. We conclude that while substantial arterial-to-venous oxygen shunting might take place in the postglomerular vasculature, the net amount of oxygen shunted at the preglomerular vasculature appears to be marginal. PMID:27833564

Transient renal tubulopathy in a racing Greyhound.

PubMed

Abraham, L A; Tyrrell, D; Charles, J A

2006-11-01

A 2-year-old female Greyhound was presented for inappetence and lethargy. On referral, results of diagnostic tests indicated renal glucosuria, increased excretion of selected amino acids and abnormal fractional excretion of electrolytes consistent with renal tubular dysfunction. Systemic blood pressure was elevated. Renal biopsy revealed mild proximal renal tubular damage consistent with a subacute toxic or hypoxic insult. Systemic hypertension, renal glucosuria and altered fractional excretion of electrolytes resolved during the 7 day period of hospital treatment. The Greyhound resumed training without recurrence of renal dysfunction.

Deletion of the pH sensor GPR4 decreases renal acid excretion.

PubMed

Sun, Xuming; Yang, Li V; Tiegs, Brian C; Arend, Lois J; McGraw, Dennis W; Penn, Raymond B; Petrovic, Snezana

2010-10-01

Proton receptors are G protein-coupled receptors that accept protons as ligands and function as pH sensors. One of the proton receptors, GPR4, is relatively abundant in the kidney, but its potential role in acid-base homeostasis is unknown. In this study, we examined the distribution of GPR4 in the kidney, its function in kidney epithelial cells, and the effects of its deletion on acid-base homeostasis. We observed GPR4 expression in the kidney cortex, in the outer and inner medulla, in isolated kidney collecting ducts, and in cultured outer and inner medullary collecting duct cells (mOMCD1 and mIMCD3). Cultured mOMCD1 cells exhibited pH-dependent accumulation of intracellular cAMP, characteristic of GPR4 activation; GPR4 knockdown attenuated this accumulation. In vivo, deletion of GPR4 decreased net acid secretion by the kidney and resulted in a nongap metabolic acidosis, indicating that GPR4 is required to maintain acid-base homeostasis. Collectively, these findings suggest that GPR4 is a pH sensor with an important role in regulating acid secretion in the kidney collecting duct.

Mendelian randomization analysis associates increased serum urate, due to genetic variation in uric acid transporters, with improved renal function.

PubMed

Hughes, Kim; Flynn, Tanya; de Zoysa, Janak; Dalbeth, Nicola; Merriman, Tony R

2014-02-01

Increased serum urate predicts chronic kidney disease independent of other risk factors. The use of xanthine oxidase inhibitors coincides with improved renal function. Whether this is due to reduced serum urate or reduced production of oxidants by xanthine oxidase or another physiological mechanism remains unresolved. Here we applied Mendelian randomization, a statistical genetics approach allowing disentangling of cause and effect in the presence of potential confounding, to determine whether lowering of serum urate by genetic modulation of renal excretion benefits renal function using data from 7979 patients of the Atherosclerosis Risk in Communities and Framingham Heart studies. Mendelian randomization by the two-stage least squares method was done with serum urate as the exposure, a uric acid transporter genetic risk score as instrumental variable, and estimated glomerular filtration rate and serum creatinine as the outcomes. Increased genetic risk score was associated with significantly improved renal function in men but not in women. Analysis of individual genetic variants showed the effect size associated with serum urate did not correlate with that associated with renal function in the Mendelian randomization model. This is consistent with the possibility that the physiological action of these genetic variants in raising serum urate correlates directly with improved renal function. Further studies are required to understand the mechanism of the potential renal function protection mediated by xanthine oxidase inhibitors.

Effects of chronic lithium administration on renal acid excretion in humans and rats

PubMed Central

Weiner, I. David; Leader, John P.; Bedford, Jennifer J.; Verlander, Jill W.; Ellis, Gaye; Kalita, Priyakshi; Vos, Frederiek; de Jong, Sylvia; Walker, Robert J.

2014-01-01

Abstract Lithium therapy's most common side effects affecting the kidney are nephrogenic diabetes insipidus (NDI) and chronic kidney disease. Lithium may also induce a distal renal tubular acidosis. This study investigated the effect of chronic lithium exposure on renal acid–base homeostasis, with emphasis on ammonia and citrate excretion. We compared 11 individuals on long‐term lithium therapy with six healthy individuals. Under basal conditions, lithium‐treated individuals excreted significantly more urinary ammonia than did control subjects. Following an acute acid load, urinary ammonia excretion increased approximately twofold above basal rates in both lithium‐treated and control humans. There were no significant differences between lithium‐treated and control subjects in urinary pH or urinary citrate excretion. To elucidate possible mechanisms, rats were randomized to diets containing lithium or regular diet for 6 months. Similar to humans, basal ammonia excretion was significantly higher in lithium‐treated rats; in addition, urinary citrate excretion was also significantly greater. There were no differences in urinary pH. Expression of the critical ammonia transporter, Rhesus C Glycoprotein (Rhcg), was substantially greater in lithium‐treated rats than in control rats. We conclude that chronic lithium exposure increases renal ammonia excretion through mechanisms independent of urinary pH and likely to involve increased collecting duct ammonia secretion via the ammonia transporter, Rhcg. PMID:25501430

Expression of Renal Aquaporins in Aristolochic Acid I and Aristolactam I-Induced Nephrotoxicity.

PubMed

Li, Ji; Zhang, Liang; Jiang, ZhenZhou; He, XiuQin; Zhang, LuYong; Xu, Ming

2016-01-01

Exposure to aristolochic acid (AA) can cause AA nephropathy, which is characterized by extensive proximal tubular damage and polyuria. To test the hypothesis that polyuria might be induced by altered regulation of aquaporins (AQPs) in the kidney, different doses of AA-I or aristolactam I (AL-I) were administered intraperitoneally to Sprague-Dawley rats, and urine, blood, and kidney samples were analyzed. In addition, AQP1, AQP2, AQP4 and AQP6 expression in the kidney were determined. The results showed dose-dependent proximal tubular damage and polyuria in the AA-I- and AL-I-treated groups, and the nephrotoxicity of AL-I was higher than that of AA-I. The expression of renal AQP1, AQP2 and AQP4, but not AQP6 were significantly inhibited by AA-I and AL-I. Comparison of the inhibition potencies of AA-I and AL-I showed that AL-I was a stronger inhibitor of AQP1 expression than AA-I, while there was no difference in their effects on AQP2 and AQP4. These results suggested that AA induced renal damage and polyuria were associated with a specific decrease in the expression of renal AQP1 AQP2 and AQP4, and AL-I showed higher nephrotoxicity than AA-I, which might be attributable to the differences in their inhibition of AQP1. © 2016 S. Karger AG, Basel.

Short-term menhaden oil rich diet changes renal lipid profile in acute kidney injury.

PubMed

Ossani, Georgina P; Denninghoff, Valeria C; Uceda, Ana M; Díaz, Maria L; Uicich, Raúl; Monserrat, Alberto J

2015-01-01

Weanling male Wistar rats fed a choline-deficient diet develop acute kidney injury. Menhaden oil, which is a very important source of omega-3 fatty acids, has a notorious protective effect. The mechanism of this protection is unknown; one possibility could be that menhaden oil changes renal lipid profile, with an impact on the functions of biological membranes. The aim of this work was to study the renal lipid profile in rats fed a choline-deficient diet with menhaden oil or vegetable oil as lipids. Rats were divided into 4 groups and fed four different diets for 7 days: choline-deficient or choline-supplemented diets with corn and hydrogenated oils or menhaden oil. Serum homocysteine, vitamin B12, and folic acid were analyzed. Renal lipid profile, as well as the fatty acid composition of the three oils, was measured. Choline-deficient rats fed vegetable oils showed renal cortical necrosis. Renal omega-6 fatty acids were higher in rats fed a cholinedeficient diet and a choline-supplemented diet with vegetable oils, while renal omega-3 fatty acids were higher in rats fed a choline-deficient diet and a choline-supplemented diet with menhaden oil. Rats fed menhaden oil diets had higher levels of renal eicosapentaenoic and docosahexaenoic acids. Renal myristic acid was increased in rats fed menhaden oil. The lipid renal profile varied quickly according to the type of oil present in the diet.

Facilitated transporters mediate net efflux of amino acids to the fetus across the basal membrane of the placental syncytiotrophoblast

PubMed Central

Cleal, J K; Glazier, J D; Ntani, G; Crozier, S R; Day, P E; Harvey, N C; Robinson, S M; Cooper, C; Godfrey, K M; Hanson, M A; Lewis, R M

2011-01-01

Fetal growth depends on placental transfer of amino acids from maternal to fetal blood. The mechanisms of net amino acid efflux across the basal membrane (BM) of the placental syncytiotrophoblast to the fetus, although vital for amino acid transport, are poorly understood. We examined the hypothesis that facilitated diffusion by the amino acid transporters TAT1, LAT3 and LAT4 plays an important role in this process, with possible effects on fetal growth. Amino acid transfer was measured in isolated perfused human placental cotyledons (n= 5 per experiment) using techniques which distinguish between different transport processes. Placental TAT1, LAT3 and LAT4 proteins were measured, and mRNA expression levels (measured using real-time quantitative-PCR) were related to fetal and neonatal anthropometry and dual-energy X-ray absorptiometry measurements of neonatal lean mass in 102 Southampton Women's Survey (SWS) infants. Under conditions preventing transport by amino acid exchangers, all amino acids appearing in the fetal circulation were substrates of TAT1, LAT3 or LAT4. Western blots demonstrated the presence of TAT1, LAT3 and LAT4 in placental BM preparations. Placental TAT1 and LAT3 mRNA expression were positively associated with measures of fetal growth in SWS infants (P < 0.05). We provide evidence that the efflux transporters TAT1, LAT3 and LAT4 are present in the human placental BM, and may play an important role in the net efflux of amino acids to the fetus. Unlike other transporters they can increase fetal amino acid concentrations. Consistent with a role in placental amino acid transfer capacity and fetal growth TAT1 and LAT3 mRNA expression showed positive associations with infant size at birth. PMID:21224231

Very Low-Protein Diet (VLPD) Reduces Metabolic Acidosis in Subjects with Chronic Kidney Disease: The "Nutritional Light Signal" of the Renal Acid Load.

PubMed

Di Iorio, Biagio Raffaele; Di Micco, Lucia; Marzocco, Stefania; De Simone, Emanuele; De Blasio, Antonietta; Sirico, Maria Luisa; Nardone, Luca

2017-01-17

Metabolic acidosis is a common complication of chronic kidney disease; current guidelines recommend treatment with alkali if bicarbonate levels are lower than 22 mMol/L. In fact, recent studies have shown that an early administration of alkali reduces progression of CKD. The aim of the study is to evaluate the effect of fruit and vegetables to reduce the acid load in CKD. We conducted a case-control study in 146 patients who received sodium bicarbonate. Of these, 54 patients assumed very low-protein diet (VLPD) and 92 were controls (ratio 1:2). We calculated every three months the potential renal acid load (PRAL) and the net endogenous acid production (NEAP), inversely correlated with serum bicarbonate levels and representing the non-volatile acid load derived from nutrition. Un-paired T -test and Chi-square test were used to assess differences between study groups at baseline and study completion. Two-tailed probability values ≤0.05 were considered statistically significant. At baseline, there were no statistical differences between the two groups regarding systolic blood pressure (SBP), diastolic blood pressure (DBP), protein and phosphate intake, urinary sodium, potassium, phosphate and urea nitrogen, NEAP, and PRAL. VLPD patients showed at 6 and 12 months a significant reduction of SBP ( p < 0.0001), DBP ( p < 0.001), plasma urea ( p < 0.0001) protein intake ( p < 0.0001), calcemia ( p < 0.0001), phosphatemia ( p < 0.0001), phosphate intake ( p < 0.0001), urinary sodium ( p < 0.0001), urinary potassium ( p < 0.002), and urinary phosphate ( p < 0.0001). NEAP and PRAL were significantly reduced in VLPD during follow-up. VLPD reduces intake of acids; nutritional therapy of CKD, that has always taken into consideration a lower protein, salt, and phosphate intake, should be adopted to correct metabolic acidosis, an important target in the treatment of CKD patients. We provide useful indications regarding acid load of food and drinks-the "acid load dietary traffic

Functional Renal Imaging with 2-Deoxy-2-18F-Fluorosorbitol PET in Rat Models of Renal Disorders.

PubMed

Werner, Rudolf A; Wakabayashi, Hiroshi; Chen, Xinyu; Hirano, Mitsuru; Shinaji, Tetsuya; Lapa, Constantin; Rowe, Steven P; Javadi, Mehrbod S; Higuchi, Takahiro

2018-05-01

Precise regional quantitative assessment of renal function is limited with conventional 99m Tc-labeled renal radiotracers. A recent study reported that the PET radiotracer 2-deoxy-2- 18 F-fluorosorbitol ( 18 F-FDS) has ideal pharmacokinetics for functional renal imaging. Furthermore, 18 F-FDS is available via simple reduction from routinely used 18 F-FDG. We aimed to further investigate the potential of 18 F-FDS PET as a functional renal imaging agent using rat models of kidney disease. Methods: Two different rat models of renal impairment were investigated: induction of acute renal failure by intramuscular administration of glycerol in the hind legs, and induction of unilateral ureteral obstruction by ligation of the left ureter. At 24 h after these procedures, dynamic 30-min 18 F-FDS PET data were acquired using a dedicated small-animal PET system. Urine 18 F-FDS radioactivity 30 min after radiotracer injection was measured together with coinjected 99m Tc-diethylenetriaminepentaacetic acid urine activity. Results: Dynamic PET imaging demonstrated rapid 18 F-FDS accumulation in the renal cortex and rapid radiotracer excretion via the kidneys in healthy control rats. On the other hand, significantly delayed renal radiotracer uptake (continuous slow uptake) was observed in acute renal failure rats and unilateral ureteral obstruction kidneys. Measured urine radiotracer concentrations of 18 F-FDS and 99m Tc-diethylenetriaminepentaacetic acid correlated well with each other ( R = 0.84, P < 0.05). Conclusion: 18 F-FDS PET demonstrated favorable kinetics for functional renal imaging in rat models of kidney diseases. 18 F-FDS PET imaging, with its advantages of high spatiotemporal resolution and simple tracer production, could potentially complement or replace conventional renal scintigraphy in select cases and significantly improve the diagnostic performance of renal functional imaging. © 2018 by the Society of Nuclear Medicine and Molecular Imaging.

Augmented renal clearance implies a need for increased amoxicillin-clavulanic acid dosing in critically ill children.

PubMed

De Cock, Pieter A J G; Standing, Joseph F; Barker, Charlotte I S; de Jaeger, Annick; Dhont, Evelyn; Carlier, Mieke; Verstraete, Alain G; Delanghe, Joris R; Robays, Hugo; De Paepe, Peter

2015-11-01

There is little data available to guide amoxicillin-clavulanic acid dosing in critically ill children. The primary objective of this study was to investigate the pharmacokinetics of both compounds in this pediatric subpopulation. Patients admitted to the pediatric intensive care unit (ICU) in whom intravenous amoxicillin-clavulanic acid was indicated (25 to 35 mg/kg of body weight every 6 h) were enrolled. Population pharmacokinetic analysis was conducted, and the clinical outcome was documented. A total of 325 and 151 blood samples were collected from 50 patients (median age, 2.58 years; age range, 1 month to 15 years) treated with amoxicillin and clavulanic acid, respectively. A three-compartment model for amoxicillin and a two-compartment model for clavulanic acid best described the data, in which allometric weight scaling and maturation functions were added a priori to scale for size and age. In addition, plasma cystatin C and concomitant treatment with vasopressors were identified to have a significant influence on amoxicillin clearance. The typical population values of clearance for amoxicillin and clavulanic acid were 17.97 liters/h/70 kg and 12.20 liters/h/70 kg, respectively. In 32% of the treated patients, amoxicillin-clavulanic acid therapy was stopped prematurely due to clinical failure, and the patient was switched to broader-spectrum antibiotic treatment. Monte Carlo simulations demonstrated that four-hourly dosing of 25 mg/kg was required to achieve the therapeutic target for both amoxicillin and clavulanic acid. For patients with augmented renal function, a 1-h infusion was preferable to bolus dosing. Current published dosing regimens result in subtherapeutic concentrations in the early period of sepsis due to augmented renal clearance, which risks clinical failure in critically ill children, and therefore need to be updated. (This study has been registered at Clinicaltrials.gov as an observational study [NCT02456974].). Copyright © 2015, American

Renal targeting potential of a polymeric drug carrier, poly-l-glutamic acid, in normal and diabetic rats.

PubMed

Chai, Hann-Juang; Kiew, Lik-Voon; Chin, Yunni; Norazit, Anwar; Mohd Noor, Suzita; Lo, Yoke-Lin; Looi, Chung-Yeng; Lau, Yeh-Siang; Lim, Tuck-Meng; Wong, Won-Fen; Abdullah, Nor Azizan; Abdul Sattar, Munavvar Zubaid; Johns, Edward J; Chik, Zamri; Chung, Lip-Yong

2017-01-01

Poly-l-glutamic acid (PG) has been used widely as a carrier to deliver anticancer chemotherapeutics. This study evaluates PG as a selective renal drug carrier. 3 H-deoxycytidine-labeled PGs (17 or 41 kDa) and 3 H-deoxycytidine were administered intravenously to normal rats and streptozotocin-induced diabetic rats. The biodistribution of these compounds was determined over 24 h. Accumulation of PG in normal kidneys was also tracked using 5-(aminoacetamido) fluorescein (fluoresceinyl glycine amide)-labeled PG (PG-AF). To evaluate the potential of PGs in ferrying renal protective anti-oxidative stress compounds, the model drug 4-(2-aminoethyl)benzenesulfonyl fluoride hydrochloride (AEBSF) was conjugated to 41 kDa PG to form PG-AEBSF. PG-AEBSF was then characterized and evaluated for intracellular anti-oxidative stress efficacy (relative to free AEBSF). In the normal rat kidneys, 17 kDa radiolabeled PG (PG-Tr) presents a 7-fold higher, while 41 kDa PG-Tr shows a 15-fold higher renal accumulation than the free radiolabel after 24 h post injection. The accumulation of PG-AF was primarily found in the renal tubular tissues at 2 and 6 h after an intravenous administration. In the diabetic (oxidative stress-induced) kidneys, 41 kDa PG-Tr showed the greatest renal accumulation of 8-fold higher than the free compound 24 h post dose. Meanwhile, the synthesized PG-AEBSF was found to inhibit intracellular nicotinamide adenine dinucleotide phosphate oxidase (a reactive oxygen species generator) at an efficiency that is comparable to that of free AEBSF. This indicates the preservation of the anti-oxidative stress properties of AEBSF in the conjugated state. The favorable accumulation property of 41 kDa PG in normal and oxidative stress-induced kidneys, along with its capabilities in conserving the pharmacological properties of the conjugated renal protective drugs, supports its role as a potential renal targeting drug carrier.

High Endogenous Accumulation of ω-3 Polyunsaturated Fatty Acids Protect against Ischemia-Reperfusion Renal Injury through AMPK-Mediated Autophagy in Fat-1 Mice.

PubMed

Gwon, Do Hyeong; Hwang, Tae Woong; Ro, Ju-Ye; Kang, Yoon-Joong; Jeong, Jin Young; Kim, Do-Kyung; Lim, Kyu; Kim, Dong Woon; Choi, Dae Eun; Kim, Jwa-Jin

2017-09-30

Regulated autophagy is involved in the repair of renal ischemia-reperfusion injury (IRI). Fat-1 transgenic mice produce ω3-Polyunsaturated fatty acids (ω3-PUFAs) from ω6-Polyunsaturated fatty acids (ω6-PUFAs) without a dietary ω3-PUFAs supplement, leading to a high accumulation of omega-3 in various tissues. ω3-PUFAs show protective effects against various renal injuries and it has recently been reported that ω3-PUFAs regulate autophagy. We assessed whether ω3-PUFAs attenuated IR-induced acute kidney injury (AKI) and evaluated its associated mechanisms. C57Bl/6 background fat-1 mice and wild-type mice (wt) were divided into four groups: wt sham ( n = 10), fat-1 sham ( n = 10), wt IRI (reperfusion 35 min after clamping both the renal artery and vein; n = 15), and fat-1 IRI ( n = 15). Kidneys and blood were harvested 24 h after IRI and renal histological and molecular data were collected. The kidneys of fat-1 mice showed better renal cell survival, renal function, and pathological damage than those of wt mice after IRI. In addition, fat-1 mice showed less oxidative stress and autophagy impairment; greater amounts of microtubule-associated protein 1A/1B-light chain 3 (LC3)-II, Beclin-1, and Atg7; lower amounts of p62; and, higher levels of renal cathepsin D and ATP6E than wt kidneys. They also showed more adenosine monophosphate-activated protein kinase (AMPK) activation, which resulted in the inhibition of phosphorylation of the mammalian target of rapamycin (mTOR). Collectively, ω3-PUFAs in fat-1 mice contributed to AMPK mediated autophagy activation, leading to a renoprotective response.

Contribution of the net charge to the regulatory effects of amino acids and epsilon-poly(L-lysine) on the gelatinization behavior of potato starch granules.

PubMed

Ito, Azusa; Hattori, Makoto; Yoshida, Tadashi; Takahashi, Koji

2006-01-01

The effects of lysine (Lys), monosodium glutamate (GluNa), glycine, alanine and epsilon-poly(L-lysine) (PL) with different degrees of polymerization on the gelatinization behavior of potato starch granules were investigated by DSC, viscosity and swelling measurements, microscopic observation, and measurement of the retained amino acid amount to clarify the contribution of the net charge to their regulatory effects on the gelatinization behavior. The amino acids and PL each contributed to an increase in the gelatinization temperature, and a decrease in the peak viscosity and swelling. These effects strongly depended on the absolute value of their net charge. The disappearance of a negative or positive net charge by adjusting the pH value weakened the contribution. The swelling index and size of the potato starch granules changed according to replacement of the swelling medium. The amino acids and PL were easily retained by the swollen potato starch granules according to replacement of the outer solution of the starch granules.

Dietary Protein and Potassium, Diet-Dependent Net Acid Load, and Risk of Incident Kidney Stones.

PubMed

Ferraro, Pietro Manuel; Mandel, Ernest I; Curhan, Gary C; Gambaro, Giovanni; Taylor, Eric N

2016-10-07

Protein and potassium intake and the resulting diet-dependent net acid load may affect kidney stone formation. It is not known whether protein type or net acid load is associated with risk of kidney stones. We prospectively examined intakes of protein (dairy, nondairy animal, and vegetable), potassium, and animal protein-to-potassium ratio (an estimate of net acid load) and risk of incident kidney stones in the Health Professionals Follow-Up Study ( n =42,919), the Nurses' Health Study I ( n =60,128), and the Nurses' Health Study II ( n =90,629). Multivariable models were adjusted for age, body mass index, diet, and other factors. We also analyzed cross-sectional associations with 24-hour urine ( n =6129). During 3,108,264 person-years of follow-up, there were 6308 incident kidney stones. Dairy protein was associated with lower risk in the Nurses' Health Study II (hazard ratio for highest versus lowest quintile, 0.84; 95% confidence interval, 0.73 to 0.96; P value for trend <0.01). The hazard ratios for nondairy animal protein were 1.15 (95% confidence interval, 0.97 to 1.36; P value for trend =0.04) in the Health Professionals Follow-Up Study and 1.20 (95% confidence interval, 0.99 to 1.46; P value for trend =0.06) in the Nurses' Health Study I. Potassium intake was associated with lower risk in all three cohorts (hazard ratios from 0.44 [95% confidence interval, 0.36 to 0.53] to 0.67 [95% confidence interval, 0.57 to 0.78]; P values for trend <0.001). Animal protein-to-potassium ratio was associated with higher risk ( P value for trend =0.004), even after adjustment for animal protein and potassium. Higher dietary potassium was associated with higher urine citrate, pH, and volume ( P values for trend <0.002). Kidney stone risk may vary by protein type. Diets high in potassium or with a relative abundance of potassium compared with animal protein could represent a means of stone prevention. Copyright © 2016 by the American Society of Nephrology.

Dietary Protein and Potassium, Diet–Dependent Net Acid Load, and Risk of Incident Kidney Stones

PubMed Central

Mandel, Ernest I.; Curhan, Gary C.; Gambaro, Giovanni; Taylor, Eric N.

2016-01-01

Background and objectives Protein and potassium intake and the resulting diet–dependent net acid load may affect kidney stone formation. It is not known whether protein type or net acid load is associated with risk of kidney stones. Design, setting, participants, & measurements We prospectively examined intakes of protein (dairy, nondairy animal, and vegetable), potassium, and animal protein-to-potassium ratio (an estimate of net acid load) and risk of incident kidney stones in the Health Professionals Follow-Up Study (n=42,919), the Nurses’ Health Study I (n=60,128), and the Nurses’ Health Study II (n=90,629). Multivariable models were adjusted for age, body mass index, diet, and other factors. We also analyzed cross-sectional associations with 24-hour urine (n=6129). Results During 3,108,264 person-years of follow-up, there were 6308 incident kidney stones. Dairy protein was associated with lower risk in the Nurses’ Health Study II (hazard ratio for highest versus lowest quintile, 0.84; 95% confidence interval, 0.73 to 0.96; P value for trend <0.01). The hazard ratios for nondairy animal protein were 1.15 (95% confidence interval, 0.97 to 1.36; P value for trend =0.04) in the Health Professionals Follow-Up Study and 1.20 (95% confidence interval, 0.99 to 1.46; P value for trend =0.06) in the Nurses’ Health Study I. Potassium intake was associated with lower risk in all three cohorts (hazard ratios from 0.44 [95% confidence interval, 0.36 to 0.53] to 0.67 [95% confidence interval, 0.57 to 0.78]; P values for trend <0.001). Animal protein-to-potassium ratio was associated with higher risk (P value for trend =0.004), even after adjustment for animal protein and potassium. Higher dietary potassium was associated with higher urine citrate, pH, and volume (P values for trend <0.002). Conclusions Kidney stone risk may vary by protein type. Diets high in potassium or with a relative abundance of potassium compared with animal protein could represent a means of

Oxidative stress, histopathological and electron microscopic alterations induced by dimethylnitrosamine in renal male mice and the protective effect of α-lipoic acid.

PubMed

Hamza, Reham Z; Ismail, Hayat A A; El-Shenawy, Nahla S

2017-03-01

Dimethylnitrosamine (DMN) is a waste product of several industrial processes. α-Lipoic acid (ALA) is a vitamin-like chemical also called as an antioxidant. Therefore, the study was designed to investigate the potential benefits of ALA in reducing the nephropathy of DMN in male mice. Animals were divided into 6 groups (n=8) and received their treatment for 4 weeks as follows: groups 1-4 served as control, ALA-treatment (16.12 mg/kg), DMN low dose treatment and DMN high dose treatment, respectively. Groups 5 and 6 received ALA before DMN low dose and DMN high dose, respectively. Superoxide dismutase, catalase, glutathione peroxidase and xanthine oxidase, total antioxidant capacity, nitric oxide, lipid peroxidation as well as the levels of uric acid and creatinine were determined. The histological and ultrastructure changes of renal tissue were also evaluated. Treatment of the DMN mice with ALA showed a reduction in the levels of kidney nitric oxide, lipid peroxidation, as well as creatinine and uric acid levels as compared with the DMN group. The results show that ALA plays an important role in quenching the free radicals resulting from the metabolism of DMN, thereby inhibiting lipid peroxidation and protecting membrane lipids from oxidative damage and, in turn, preventing oxidative stress and apoptosis. Histopathological and ultrastructure analysis of renal tissue confirmed the oxidative stress results occurred in DMN renal mice. Concomitant administration of ALA with DMN significantly decreased all the histopathological changes induced by DMN. The present study elucidated the therapeutic effects of ALA administered in combination with DMN to minimize its renal toxicity.

Established dietary estimates of net acid production do not predict measured net acid excretion in patients with Type 2 diabetes on Paleolithic-Hunter-Gatherer-type diets

PubMed Central

Frassetto, Lynda A; Shi, Lijie; Schloetter, Monique; Sebastian, Anthony; Remer, Thomas

2014-01-01

Background Formulas developed to estimate diet-dependent net acid excretion (NAE) generally agree with measured values for typical Western diets. Whether they can also appropriately predict NAE for "Paleolithic-type" (Paleo) diets – which contain very high amounts of fruits and vegetables (F&V) and concurrent high amounts of protein is unknown. Here we compare measured NAEs with established NAE-estimates in subjects with Type 2 diabetes (T2D). Methods Thirteen subjects with well controlled T2D were randomized to either a Paleo or American Diabetes Association (ADA) diet for 14 days. 24-hour urine collections were performed at baseline and end of the diet period, and analyzed for titratable acid, bicarbonate, and ammonium to calculate measured NAE. Three formulas for estimating NAE from dietary intake were used; two (NAE_diet R or L) that include dietary mineral intake and sulfate- and organic acid (OA) production, and one that is empirically-derived (NAE_diet F) only considering potassium and protein intake. Results Measured NAE on the Paleo diet was significantly lower than on the ADA diet (+31±22 vs. 112±52 mEq/day, p=0.002). Although all formula estimates showed similar and reasonable correlations (r=0.52–0.76) with measured NAE, each one underestimated measured values. The formula with the best correlation did not contain an estimate of dietary organic acid production. Conclusions Paleo diets are lower in NAE than typical Western diets. However, commonly used formulas clearly underestimate NAE, especially for diets with very high F&V (as the Paleo diet), and in subjects with T2D. This may be due to an inappropriate estimation of proton loads stemming from OAs, underlining the necessity for improved measures of OA-related proton sources. PMID:23859996

Renal Control of Calcium, Phosphate, and Magnesium Homeostasis

PubMed Central

Chonchol, Michel; Levi, Moshe

2015-01-01

Calcium, phosphate, and magnesium are multivalent cations that are important for many biologic and cellular functions. The kidneys play a central role in the homeostasis of these ions. Gastrointestinal absorption is balanced by renal excretion. When body stores of these ions decline significantly, gastrointestinal absorption, bone resorption, and renal tubular reabsorption increase to normalize their levels. Renal regulation of these ions occurs through glomerular filtration and tubular reabsorption and/or secretion and is therefore an important determinant of plasma ion concentration. Under physiologic conditions, the whole body balance of calcium, phosphate, and magnesium is maintained by fine adjustments of urinary excretion to equal the net intake. This review discusses how calcium, phosphate, and magnesium are handled by the kidneys. PMID:25287933

Soluble epoxide hydrolase contamination of specific catalase preparations inhibits epoxyeicosatrienoic acid vasodilation of rat renal arterioles

PubMed Central

Olson, Lauren; Harder, Adam; Isbell, Marilyn; Imig, John D.; Gutterman, David D.; Falck, J. R.; Campbell, William B.

2011-01-01

Cytochrome P-450 metabolites of arachidonic acid, the epoxyeicosatrienoic acids (EETs) and hydrogen peroxide (H2O2), are important signaling molecules in the kidney. In renal arteries, EETs cause vasodilation whereas H2O2 causes vasoconstriction. To determine the physiological contribution of H2O2, catalase is used to inactivate H2O2. However, the consequence of catalase action on EET vascular activity has not been determined. In rat renal afferent arterioles, 14,15-EET caused concentration-related dilations that were inhibited by Sigma bovine liver (SBL) catalase (1,000 U/ml) but not Calbiochem bovine liver (CBL) catalase (1,000 U/ml). SBL catalase inhibition was reversed by the soluble epoxide hydrolase (sEH) inhibitor tAUCB (1 μM). In 14,15-EET incubations, SBL catalase caused a concentration-related increase in a polar metabolite. Using mass spectrometry, the metabolite was identified as 14,15-dihydroxyeicosatrienoic acid (14,15-DHET), the inactive sEH metabolite. 14,15-EET hydrolysis was not altered by the catalase inhibitor 3-amino-1,2,4-triazole (3-ATZ; 10–50 mM), but was abolished by the sEH inhibitor BIRD-0826 (1–10 μM). SBL catalase EET hydrolysis showed a regioisomer preference with greatest hydrolysis of 14,15-EET followed by 11,12-, 8,9- and 5,6-EET (Vmax = 0.54 ± 0.07, 0.23 ± 0.06, 0.18 ± 0.01 and 0.08 ± 0.02 ng DHET·U catalase−1·min−1, respectively). Of five different catalase preparations assayed, EET hydrolysis was observed with two Sigma liver catalases. These preparations had low specific catalase activity and positive sEH expression. Mass spectrometric analysis of the SBL catalase identified peptide fragments matching bovine sEH. Collectively, these data indicate that catalase does not affect EET-mediated dilation of renal arterioles. However, some commercial catalase preparations are contaminated with sEH, and these contaminated preparations diminish the biological activity of H2O2 and EETs. PMID:21753077

Very Low-Protein Diet (VLPD) Reduces Metabolic Acidosis in Subjects with Chronic Kidney Disease: The “Nutritional Light Signal” of the Renal Acid Load

PubMed Central

Di Iorio, Biagio Raffaele; Di Micco, Lucia; Marzocco, Stefania; De Simone, Emanuele; De Blasio, Antonietta; Sirico, Maria Luisa; Nardone, Luca

2017-01-01

Background: Metabolic acidosis is a common complication of chronic kidney disease; current guidelines recommend treatment with alkali if bicarbonate levels are lower than 22 mMol/L. In fact, recent studies have shown that an early administration of alkali reduces progression of CKD. The aim of the study is to evaluate the effect of fruit and vegetables to reduce the acid load in CKD. Methods: We conducted a case-control study in 146 patients who received sodium bicarbonate. Of these, 54 patients assumed very low-protein diet (VLPD) and 92 were controls (ratio 1:2). We calculated every three months the potential renal acid load (PRAL) and the net endogenous acid production (NEAP), inversely correlated with serum bicarbonate levels and representing the non-volatile acid load derived from nutrition. Un-paired T-test and Chi-square test were used to assess differences between study groups at baseline and study completion. Two-tailed probability values ≤0.05 were considered statistically significant. Results: At baseline, there were no statistical differences between the two groups regarding systolic blood pressure (SBP), diastolic blood pressure (DBP), protein and phosphate intake, urinary sodium, potassium, phosphate and urea nitrogen, NEAP, and PRAL. VLPD patients showed at 6 and 12 months a significant reduction of SBP (p < 0.0001), DBP (p < 0.001), plasma urea (p < 0.0001) protein intake (p < 0.0001), calcemia (p < 0.0001), phosphatemia (p < 0.0001), phosphate intake (p < 0.0001), urinary sodium (p < 0.0001), urinary potassium (p < 0.002), and urinary phosphate (p < 0.0001). NEAP and PRAL were significantly reduced in VLPD during follow-up. Conclusion: VLPD reduces intake of acids; nutritional therapy of CKD, that has always taken into consideration a lower protein, salt, and phosphate intake, should be adopted to correct metabolic acidosis, an important target in the treatment of CKD patients. We provide useful indications regarding acid load of food and drinks�

Evaluation of renal function in patients with a main renal stone larger than 1 cm and perioperative renal functional change in minimally invasive renal stone surgery: a prospective, observational study.

PubMed

Piao, Songzhe; Park, Juhyun; Son, Hwancheol; Jeong, Hyeon; Cho, Sung Yong

2016-05-01

To compare the perioperative relative renal function and determine predictors of deterioration and recovery of separate renal function in patients with renal stones >10 mm and who underwent mini-percutaneous nephrolithotomy or retrograde intra-renal surgery. A main stone >10 mm or stones growing, high-risk stone formers and extracorporeal shock-wave lithotripsy-resistant stones were prospectively included in 148 patients. Patients with bilateral renal stones and anatomical deformities were excluded. Renal function was evaluated by estimated glomerular filtration rate, 99m-technetium dimercaptosuccinic acid and 99m-technetium diethylenetriamine pentaacetate prior to intervention and at postoperative 3 months. Logistic regression analyses were performed to find predictors of functional deterioration and recovery. The overall stone-free rate was 85.1 %. A third of patients (53/148, 35.8 %) with renal stones >10 mm showed deterioration of separate renal function. Mean renal function of operative sites showed 58.2 % (36.8 %/63.2 %) of that of contralateral sites in these patients. Abnormal separate renal function showed postoperative recovery in 31 patients (58.5 %). Three cases (5.7 %) showed deterioration of separate renal function despite no presence of remnant stones. Improvement rates of the abnormal separate renal function did not differ according to the type of surgery. The presence of hydronephrosis and three or more stones were significant predictors for renal function deterioration. Female gender and three or more stones were significantly correlated with postoperative recovery. Mini-percutaneous nephrolithotomy or retrograde intra-renal surgery was effective and safe for renal function preservation. Patients with multiple large stones should be considered for candidates of active surgical removal.

Ameliorative effect of ursolic acid on renal fibrosis in adenine-induced chronic kidney disease in rats.

PubMed

Thakur, Richa; Sharma, Anshuk; Lingaraju, Madhu C; Begum, Jubeda; Kumar, Dhirendra; Mathesh, Karikalan; Kumar, Pawan; Singh, Thakur Uttam; Kumar, Dinesh

2018-05-01

Ursolic acid (UA), an ursane-type pentacyclic triterpenoid commonly found in apple peels and holy basil has been shown to possess many beneficial effects. Renal fibrosis is a complication of kidney injury and associated with increased risk of morbidity and mortality. In our previous investigation, a lupane-type pentacyclic triterpenoid, betulinic acid (BA) was found to have protective effect on chronic kidney disease (CKD) and renal fibrosis. This prompted us to explore the therapeutic value of UA, a chemically related compound to BA in CKD. CKD was induced by feeding adenine with the feed at a concentration of 0.75% for 28 days. UA at the dose rate of 30 mg/kg in 0.5% carboxy methyl cellulose (CMC) was administered by oral route, simultaneously with adenine feeding for 28 days. Adenine feeding increased the kidney weight to body weight index, decreased the kidney function due to injury as indicated by increased markers like serum urea, uric acid, creatinine, cystatin C and neutrophil gelatinase-associated lipocalin (NGAL) and initiated the fibrotic response in kidney by increasing the profibrotic proteins viz. transforming growth factor-beta (TGF-β), connective tissue growth factor (CTGF), fibronectin and collagen. However, treatment with UA reversed the damage induced by adenine as shown by reduced kidney injury and fibrosis markers which was further clearly evident in histological picture indicating the suitability of UA for use in CKD. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Patients with gout differ from healthy subjects in renal response to changes in serum uric acid.

PubMed

Liu, Sha; Perez-Ruiz, Fernando; Miner, Jeffrey N

2017-03-01

Our objectives were to determine whether a change in serum uric acid (sUA) resulted in a corresponding change in the fractional excretion of uric acid (FEUA) and whether the renal response was different in patients with gout versus healthy subjects. FEUA was calculated from previously published studies and four new phase I studies in healthy subjects and/or patients with gout before and after treatment to lower or raise sUA. Treatments included xanthine oxidase inhibitors to lower sUA as well as infusion of uric acid and provision of a high-purine diet to raise sUA. Plots were created of FEUA versus sUA before and after treatment. For the phase I studies, percent change in FEUA per mg/dL change in sUA was calculated separately for healthy subjects and patients with gout, and compared using Student's t test. Analysis of previously published data and the new phase I clinical data indicates that changing sUA by a non-renal mechanism leads to a change in FEUA. The magnitude of change is greater in subjects with higher baseline FEUA versus patients with gout. Healthy subjects excrete more urate than do patients with gout at physiological urate-filtered load; this difference disappears when the urate-filtered load is decreased to ∼5000mg/24hours. These observations are consistent with a less saturated urate reabsorption system in patients with gout versus healthy subjects, resulting in elevated retention of uric acid. Further investigation could lead to the discovery of mechanisms responsible for the etiology of hyperuricemia/gout. Copyright © 2016 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

Renal calculi in primary hyperaldosteronism.

PubMed Central

Kabadi, U. M.

1995-01-01

Increased urinary calcium (Ca++) excretion and the presence of negative Ca++ balance is well documented in primary hyperaldosteronism. However, renal calculi as a major manifestation of this disorder has not previously been described. This report describes a patient who presented with renal calculi in association with primary hyperaldosteronism. We believe that primary hyperaldosteronism was a major pathogenetic factor in the formation of renal calculi since the increased urinary excretion of Ca++ and uric acid noted at onset declined following a short-term spironolactone administration and remission from renal calculi has persisted following initial nephrolithotomy and continued spironolactone therapy, which also corrected hypertension and hypokalemia, a hallmark of this disorder. Images Figure PMID:7479473

Activated renal tubular Wnt/β-catenin signaling triggers renal inflammation during overload proteinuria.

PubMed

Wong, Dickson W L; Yiu, Wai Han; Chan, Kam Wa; Li, Ye; Li, Bin; Lok, Sarah W Y; Taketo, Makoto M; Igarashi, Peter; Chan, Loretta Y Y; Leung, Joseph C K; Lai, Kar Neng; Tang, Sydney C W

2018-06-01

Imbalance of Wnt/β-catenin signaling in renal cells is associated with renal dysfunction, yet the precise mechanism is poorly understood. Previously we observed activated Wnt/β-catenin signaling in renal tubules during proteinuric nephropathy with an unknown net effect. Therefore, to identify the definitive role of tubular Wnt/β-catenin, we generated a novel transgenic "Tubcat" mouse conditionally expressing stabilized β-catenin specifically in renal tubules following tamoxifen administration. Four weeks after tamoxifen injection, uninephrectomized Tubcat mice displayed proteinuria and elevated blood urea nitrogen levels compared to non-transgenic mice, implying a detrimental effect of the activated signaling. This was associated with infiltration of the tubulointerstitium predominantly by M1 macrophages and overexpression of the inflammatory chemocytokines CCL-2 and RANTES. Induction of overload proteinuria by intraperitoneal injection of low-endotoxin bovine serum albumin following uninephrectomy for four weeks aggravated proteinuria and increased blood urea nitrogen levels to a significantly greater extent in Tubcat mice. Renal dysfunction correlated with the degree of M1 macrophage infiltration in the tubulointerstitium and renal cortical up-regulation of CCL-2, IL-17A, IL-1β, CXCL1, and ICAM-1. There was overexpression of cortical TLR-4 and NLRP-3 in Tubcat mice, independent of bovine serum albumin injection. Finally, there was no fibrosis, activation of epithelial-mesenchymal transition or non-canonical Wnt pathways observed in the kidneys of Tubcat mice. Thus, conditional activation of renal tubular Wnt/β-catenin signaling in a novel transgenic mouse model demonstrates that this pathway enhances intrarenal inflammation via the TLR-4/NLRP-3 inflammasome axis in overload proteinuria. Copyright © 2018 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Renal control of calcium, phosphate, and magnesium homeostasis.

PubMed

Blaine, Judith; Chonchol, Michel; Levi, Moshe

2015-07-07

Calcium, phosphate, and magnesium are multivalent cations that are important for many biologic and cellular functions. The kidneys play a central role in the homeostasis of these ions. Gastrointestinal absorption is balanced by renal excretion. When body stores of these ions decline significantly, gastrointestinal absorption, bone resorption, and renal tubular reabsorption increase to normalize their levels. Renal regulation of these ions occurs through glomerular filtration and tubular reabsorption and/or secretion and is therefore an important determinant of plasma ion concentration. Under physiologic conditions, the whole body balance of calcium, phosphate, and magnesium is maintained by fine adjustments of urinary excretion to equal the net intake. This review discusses how calcium, phosphate, and magnesium are handled by the kidneys. Copyright © 2015 by the American Society of Nephrology.

Renal targeting potential of a polymeric drug carrier, poly-l-glutamic acid, in normal and diabetic rats

PubMed Central

Chai, Hann-Juang; Kiew, Lik-Voon; Chin, Yunni; Norazit, Anwar; Mohd Noor, Suzita; Lo, Yoke-Lin; Looi, Chung-Yeng; Lau, Yeh-Siang; Lim, Tuck-Meng; Wong, Won-Fen; Abdullah, Nor Azizan; Abdul Sattar, Munavvar Zubaid; Johns, Edward J; Chik, Zamri; Chung, Lip-Yong

2017-01-01

Background and purpose Poly-l-glutamic acid (PG) has been used widely as a carrier to deliver anticancer chemotherapeutics. This study evaluates PG as a selective renal drug carrier. Experimental approach 3H-deoxycytidine-labeled PGs (17 or 41 kDa) and 3H-deoxycytidine were administered intravenously to normal rats and streptozotocin-induced diabetic rats. The biodistribution of these compounds was determined over 24 h. Accumulation of PG in normal kidneys was also tracked using 5-(aminoacetamido) fluorescein (fluoresceinyl glycine amide)-labeled PG (PG-AF). To evaluate the potential of PGs in ferrying renal protective anti-oxidative stress compounds, the model drug 4-(2-aminoethyl)benzenesulfonyl fluoride hydrochloride (AEBSF) was conjugated to 41 kDa PG to form PG-AEBSF. PG-AEBSF was then characterized and evaluated for intracellular anti-oxidative stress efficacy (relative to free AEBSF). Results In the normal rat kidneys, 17 kDa radiolabeled PG (PG-Tr) presents a 7-fold higher, while 41 kDa PG-Tr shows a 15-fold higher renal accumulation than the free radiolabel after 24 h post injection. The accumulation of PG-AF was primarily found in the renal tubular tissues at 2 and 6 h after an intravenous administration. In the diabetic (oxidative stress-induced) kidneys, 41 kDa PG-Tr showed the greatest renal accumulation of 8-fold higher than the free compound 24 h post dose. Meanwhile, the synthesized PG-AEBSF was found to inhibit intracellular nicotinamide adenine dinucleotide phosphate oxidase (a reactive oxygen species generator) at an efficiency that is comparable to that of free AEBSF. This indicates the preservation of the anti-oxidative stress properties of AEBSF in the conjugated state. Conclusion/Implications The favorable accumulation property of 41 kDa PG in normal and oxidative stress-induced kidneys, along with its capabilities in conserving the pharmacological properties of the conjugated renal protective drugs, supports its role as a potential renal

Nonesterified fatty acids and development of graft failure in renal transplant recipients.

PubMed

Klooster, Astrid; Hofker, H Sijbrand; Navis, Gerjan; Homan van der Heide, Jaap J; Gans, Reinold O B; van Goor, Harry; Leuvenink, Henri G D; Bakker, Stephan J L

2013-06-15

Chronic transplant dysfunction is the most common cause of graft failure on the long term. Proteinuria is one of the cardinal clinical signs of chronic transplant dysfunction. Albumin-bound fatty acids (FA) have been hypothesized to be instrumental in the etiology of renal damage induced by proteinuria. We therefore questioned whether high circulating FA could be associated with an increased risk for future development of graft failure in renal transplant recipients (RTR). To this end, we prospectively investigated the association of fasting concentrations of circulating nonesterified FA (NEFA) with the development of graft failure in RTR. Baseline measurements were performed between 2001 and 2003 in outpatient RTR with a functioning graft of more than 1 year. Follow-up was recorded until May 19, 2009. Graft failure was defined as return to dialysis or retransplantation. We included 461 RTR at a median (interquartile range [IQR]) of 6.1 (3.3-11.3) years after transplantation. Median (IQR) fasting concentrations of NEFA were 373 (270-521) μM/L. Median (IQR) follow-up for graft failure beyond baseline was 7.1 (6.1-7.5) years. Graft failure occurred in 23 (15%), 14 (9%), and 9 (6%) of RTR across increasing gender-specific tertiles of NEFA (P=0.04). In a gender-adjusted Cox-regression analysis, log-transformed NEFA level was inversely associated with the development of graft failure (hazard ratio, 0.61; 95% confidence interval, 0.47-0.81; P<0.001). In this prospective cohort study in RTR, we found an inverse association between fasting NEFA concentrations and risk for development of graft failure. This association suggests a renoprotective rather than a tubulotoxic effect of NEFA. Further studies on the role of different types of NEFA in the progression of renal disease are warranted.

Renoprotective effects of gamma-aminobutyric acid on cisplatin-induced acute renal injury in rats.

PubMed

Ali, Badreldin H; Al-Salam, Suhail; Al Za'abi, Mohammed; Al Balushi, Khalid A; AlMahruqi, Ahmed S; Beegam, Somyia; Al-Lawatia, Intisar; Waly, Mostafa I; Nemmar, Abderrahim

2015-01-01

To investigate the effect of gamma-aminobutyric acid (GABA) on acute renal injury (ARI), we used here a rat model of acute tubular necrosis induced by the anticancer drug cisplatin (CP). GABA was given orally (100 or 500 mg/kg/day for ten consecutive days), and on the 6th day, some of the treated rats were also injected intraperitoneally with either saline or CP (6 mg/kg). Four days after CP treatment, urine was collected from all rats, which were then anaesthetized for blood pressure and renal blood flow monitoring. This was followed by intravenous injection of norepinephrine for the assessment of renal vasoconstrictor responses. Thereafter, blood and kidneys were collected for measurement of several functional, biochemical and structural parameters. GABA treatment (at 500 but not 100 mg/kg) significantly mitigated all the measured physiological and biochemical indices. Sections from saline- and GABA-treated rats showed apparently normal proximal tubules. However, kidneys of CP-treated rats had a moderate degree of necrosis. This was markedly lessened when CP was given simultaneously with GABA (500 mg/kg). The concentration of platinum in the cortical tissues was not significantly altered by GABA treatment. The results suggested that GABA can ameliorate CP nephrotoxicity in rats. Pending further pharmacological and toxicological studies, GABA may be considered a potentially useful nephroprotective agent in CP-induced ARI. © 2014 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

A rapid food screener ranks potential renal acid load of renal stone formers similarly to a diet history questionnaire.

PubMed

Trinchieri, Alberto

2013-02-01

Dietary acid load was reported to be inversely related to urinary citrate excretion. The calcium renal stone formers (RSFs) should be recommended to lower their dietary potential renal acid load (PRAL) to reduce stone recurrence. Reduction of dietary PRAL also showed a promising role for the prevention of other metabolic diseases. However, clinicians often fail to provide nutritional screening and counseling due to lack of simple tools to obtain a reliable dietary history. A one-page food screener (LAKE score) was recently designed to obtain a reliable measure of dietary PRAL in short time. We report the testing of such an instrument in the evaluation of PRAL: in a population of 135 healthy subjects (60 males, 75 females; age range 18-73), living in the area of Milan, Italy. Each participant received both the one-page LAKE food screener and an extensive 24-h dietary questionnaire. We examined agreement between the LAKE food screener scores, and estimates of PRAL and other nutrients produced by the computerized processing of thorough 24-h dietary histories. Spearman rank order correlation coefficient (r > 0.50) showed that LAKE score ranked subjects quite well with respect to dietary PRAL. LAKE positive subscore ranked patients with respect to dietary intake of total protein (r = 0.642) and phosphate (r = 0.648). We also obtained an excellent correlation of LAKE negative subscore with potassium intake (r = -0.531) and vitamin C (r = -0.554) as estimated by 24 h recalls. The LAKE score ranked patients similar to the estimates of 24-h dietary recalls, used as the "gold standard" for the evaluation of dietary PRAL. This rapid, simple and inexpensive food screener for the evaluation of dietary PRAL could provide a "snapshot" of the diet of the RSFs to allow an immediate feedback to the patient during office consultation.

Essentials of equine renal and urinary tract physiology.

PubMed

Toribio, Ramiro E

2007-12-01

Knowledge of urinary tract anatomy and the numerous functions of the kidney in regulating fluids, electrolytes, acid-base balance, and waste products improves the ability of the clinician to diagnose, treat, and make appropriate recommendations for the management of the horse with renal disease. Several conditions can directly or indirectly affect renal function on a temporary or permanent basis. Endogenous and exogenous compounds (eg, drugs, toxins, hemoglobin) alone or in combination with inappropriate renal blood flow can promote or exacerbate renal disease.

Food composition and acid-base balance: alimentary alkali depletion and acid load in herbivores.

PubMed

Kiwull-Schöne, Heidrun; Kiwull, Peter; Manz, Friedrich; Kalhoff, Hermann

2008-02-01

Alkali-enriched diets are recommended for humans to diminish the net acid load of their usual diet. In contrast, herbivores have to deal with a high dietary alkali impact on acid-base balance. Here we explore the role of nutritional alkali in experimentally induced chronic metabolic acidosis. Data were collected from healthy male adult rabbits kept in metabolism cages to obtain 24-h urine and arterial blood samples. Randomized groups consumed rabbit diets ad libitum, providing sufficient energy but variable alkali load. One subgroup (n = 10) received high-alkali food and approximately 15 mEq/kg ammonium chloride (NH4Cl) with its drinking water for 5 d. Another group (n = 14) was fed low-alkali food for 5 d and given approximately 4 mEq/kg NH4Cl daily for the last 2 d. The wide range of alimentary acid-base load was significantly reflected by renal base excretion, but normal acid-base conditions were maintained in the arterial blood. In rabbits fed a high-alkali diet, the excreted alkaline urine (pH(u) > 8.0) typically contained a large amount of precipitated carbonate, whereas in rabbits fed a low-alkali diet, both pH(u) and precipitate decreased considerably. During high-alkali feeding, application of NH4Cl likewise decreased pH(u), but arterial pH was still maintained with no indication of metabolic acidosis. During low-alkali feeding, a comparably small amount of added NH4Cl further lowered pH(u) and was accompanied by a significant systemic metabolic acidosis. We conclude that exhausted renal base-saving function by dietary alkali depletion is a prerequisite for growing susceptibility to NH4Cl-induced chronic metabolic acidosis in the herbivore rabbit.

Determination of Domoic Acid in Plankton Net Samples from Golden Horn Estuary, Turkey, Using HPLC with Fluorescence Detection.

PubMed

Dursun, Fuat; Ünlü, Selma; Yurdun, Türkan

2018-03-01

This study focused on the fluctuations of domoic acid (DA) levels in plankton net samples collected from the Golden Horn Estuary (GHE), Turkey, between August 2011 and July 2012. DA concentrations were determined by high-performance liquid chromatography (HPLC), using a fluorenylmethoxycarbonyl (FMOC) derivatization technique. Monthly and biweekly data were evaluated with environmental variables, and their influence on DA production is discussed. DA levels in plankton net samples varied between 0.36 and 94.34 µg L - 1 . DA levels showed remarkable seasonal variation and they were generally higher in May, 2012, but no DA was detected between February and April, 2012. DA production was mostly controlled by temperature, with nitrate and silicate limitations being secondary factors that influenced DA concentrations.

Whey versus soy protein diets and renal status in rats.

PubMed

Aparicio, Virginia A; Nebot, Elena; Tassi, Mohamed; Camiletti-Moirón, Daniel; Sanchez-Gonzalez, Cristina; Porres, Jesús M; Aranda, Pilar

2014-09-01

Different dietary protein sources can promote different renal statuses. We examined the effects of whey protein (WP) and soy protein (SP) intake on plasma, urinary, and morphological renal parameters in rats. One hundred and twenty Wistar rats were randomly distributed into 2 experimental groups fed with either WP or SP diets over 12 weeks. These diets were based on commercial WP or SP isolates. The urinary calcium content was higher in the WP diet compared to the SP diet group (P<.001) whereas the urinary citrate level was lower (P<.001). The urinary pH was more acidic in the WP diet group compared to the SP diet group (P<.001); however, no differences were observed between the groups for any of the renal morphological parameters analyzed (all, P>.05) or other plasma renal markers such as albumin or urea concentrations. The increase of acid and urinary calcium and the lower urinary citrate level observed in the WP diet group could increase the incidence of nephrolithiasis compared to the SP diet group. Despite the WP showed poorer acid-base profile, no significant morphological renal changes were observed. These results suggest that the use of SP instead of WP appears to promote a more alkaline plasma and urinary profile, with their consequent renal advantages.

Pregnancy Increases the Renal Secretion of N1-methylnicotinamide, an Endogenous Probe for Renal Cation Transporters, in Patients Prescribed Metformin.

PubMed

Bergagnini-Kolev, Mackenzie C; Hebert, Mary F; Easterling, Thomas R; Lin, Yvonne S

2017-03-01

N 1 -methylnicotinamide (1-NMN) has been investigated as an endogenous probe for the renal transporter activity of organic cation transporter 2 (OCT2) and multidrug and toxin extrusion proteins 1 and 2-K (MATE1 and MATE2-K). As pregnancy increased the renal secretion of metformin, a substrate for OCT2, MATE1, and MATE2-K, we hypothesized that the renal secretion of 1-NMN would be similarly affected. Blood and urine samples collected from women prescribed metformin for type 2 diabetes, gestational diabetes, and polycystic ovarian syndrome during early, mid, and late pregnancy ( n = 34 visits) and postpartum ( n = 14 visits) were analyzed for 1-NMN using liquid chromatography-mass spectrometry. The renal clearance and secretion clearance, using creatinine clearance to correct for glomerular filtration, were estimated for 1-NMN and correlated with metformin renal clearance. 1-NMN renal clearance was higher in both mid (504 ± 293 ml/min, P < 0.01) and late pregnancy (557 ± 305 ml/min, P < 0.01) compared with postpartum (240 ± 106 ml/min). The renal secretion of 1-NMN was 3.5-fold higher in mid pregnancy (269± 267, P < 0.05) and 4.5-fold higher in late pregnancy compared with postpartum (342 ± 283 versus 76 ± 92 ml/min, P < 0.01). Because creatinine is also a substrate of OCT2, MATE1, and MATE2-K, creatinine clearance likely overestimates filtration clearance, whereas the calculated 1-NMN secretion clearance is likely underestimated. Metformin renal clearance and 1-NMN renal clearance were positively correlated (r s = 0.68, P < 0.0001). 1-NMN renal clearance increases during pregnancy due to increased glomerular filtration and net secretion by renal transporters. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

Pregnancy-associated polyuria in familial renal glycosuria.

PubMed

Toka, Hakan R; Yang, Jun; Zera, Chloe A; Duffield, Jeremy S; Pollak, Martin R; Mount, David B

2013-12-01

A pregnant woman presented at gestational week 28 with loss of consciousness and profound polyuria. Further characterization revealed osmotic diuresis due to massive glycosuria without hyperglycemia. Glycosuria reduced substantially postpartum, from approximately 100 to approximately 30 g/1.73 m2 per day. DNA sequencing analysis of the SLC5A2 gene encoding the renal glucose transporter SGLT2 showed a homozygous frame-shift mutation (occurring after the glutamine at amino acid 168 and leading to premature termination of the protein at amino acid 186) diagnostic of familial renal glycosuria. Pregnant women with familial renal glycosuria can be at risk of profound polyuria during pregnancy due to the associated increase in glycosuria. These findings also have implications for the use of SGLT2 inhibitors in clinical practice. Published by Elsevier Inc.

Combined use of late phase dimercapto-succinic acid renal scintigraphy and ultrasound as first line screening after urinary tract infection in children.

PubMed

Quirino, Isabel G; Silva, Jose Maria P; Diniz, Jose S; Lima, Eleonora M; Rocha, Ana Cristina S; Simões e Silva, Ana Cristina; Oliveira, Eduardo A

2011-01-01

The aim of this study was to evaluate the diagnostic accuracy of dimercapto-succinic acid renal scintigraphy and renal ultrasound in identifying high grade vesicoureteral reflux in children after a first episode of urinary tract infection. A total of 533 children following a first urinary tract infection were included in the analysis. Patients were assessed by 3 diagnostic imaging studies, renal ultrasound, dimercapto-succinic acid scan and voiding cystourethrography. The main event of interest was the presence of high grade (III to V) vesicoureteral reflux. The combined and separate diagnostic accuracy of screening methods was assessed by calculation of diagnostic OR, sensitivity, specificity, positive predictive value, negative predictive value and likelihood ratio. A total of 246 patients had reflux, of whom 144 (27%) had high grade (III to V) disease. Sensitivity, negative predictive value and diagnostic OR of ultrasound for high grade reflux were 83.3%, 90.8% and 7.9, respectively. Dimercapto-succinic acid scan had the same sensitivity as ultrasound but a higher negative predictive value (91.7%) and diagnostic OR (10.9). If both tests were analyzed in parallel by using the OR rule, ie a negative diagnosis was established only when both test results were normal, sensitivity increased to 97%, negative predictive value to 97% and diagnostic OR to 25.3. Only 9 children (6.3%) with dilating reflux had an absence of alterations in both tests. Our findings support the idea that ultrasound and dimercapto-succinic acid scan used in combination are reliable predictors of dilating vesicoureteral reflux. Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Serum uric acid levels are associated with lupus nephritis in patients with normal renal function.

PubMed

Calich, Ana Luisa; Borba, Eduardo Ferreira; Ugolini-Lopes, Michelle Remião; da Rocha, Luiza Fuoco; Bonfá, Eloisa; Fuller, Ricardo

2018-05-01

Uric acid has been recognised as a potential marker of endothelial dysfunction and kidney disease but there are scarce data about its importance in systemic lupus erythematosus (SLE) nephritis. This study aimed to evaluate serum uric acid (UA) levels in lupus nephritis (LN), by comparing SLE patients with normal renal function, with and without nephritis. Forty-six female SLE patients were consecutively selected and divided in two groups according to renal activity at the evaluation: presence of a recently diagnosed lupus nephritis (LN+, n = 18) and absence of lupus nephritis (LN-, n = 28). Age-matched healthy women were selected (CONTROL, n = 28). Patients with gout, creatinine clearance lower than 80 ml/min and use of drugs that interfere in UA were excluded. Laboratory and clinical data were analysed by appropriate tests. A multivariate analysis was performed, and a receiver operating characteristic (ROC) curve was plotted, and the area under the curve was calculated to assess the diagnostic strength of UA in LN. The mean age was similar among LN+, LN- and CONTROL groups (32.44 ± 6.09 vs. 30.68 ± 5.36 vs. 30.86 ± 5.00 years, p = 0.52). UA was significantly higher in LN+ compared to LN- (5.54 ± 1.67 vs. 3.65 ± 1.090 mg/dL, p < 0.001) and CONTROL (5.54 ± 1.67 vs. 3.92 ± 0.95 mg/dL p < 0.001). Multivariate analysis confirmed that high UA was an independent variable related to LN (p < 0.001). The cut-off value for UA using the ROC curve was 4.47 mg/dL (AUC 0.86, p = 0.00004, CI 95% 0.75-0.96). Lupus nephritis was associated with higher UA. Hyperuricemia as a predictor of renal damage in SLE needs to be evaluated in further studies.

Chronic Arachidonic Acid Administration Decreases Docosahexaenoic Acid- and Eicosapentaenoic Acid-Derived Metabolites in Kidneys of Aged Rats.

PubMed

Katakura, Masanori; Hashimoto, Michio; Inoue, Takayuki; Mamun, Abdullah Al; Tanabe, Yoko; Arita, Makoto; Shido, Osamu

2015-01-01

Arachidonic acid (ARA) metabolites produced by cyclo-oxygenase and lipoxygenase are important mediators maintaining physiological renal function. However, the effects of exogenous ARA on kidney function in vivo remain unknown. This study examined the effects of long-term oral ARA administration on normal renal function as well as inflammation and oxidative stress in aged rats. In addition, we measured levels of renal eicosanoids and docosanoids using liquid chromatography-tandem mass spectrometry. Control or ARA oil (240 mg/kg body weight/day) was orally administered to 21-month-old Wistar rats for 13 weeks. Levels of plasma creatinine, blood urea nitrogen, inflammatory and anti-inflammatory cytokines, reactive oxygen species, and lipid peroxidation were not significantly different between the two groups. The ARA concentration in the plasma, kidney, and liver increased in the ARA-administered group. In addition, levels of free-form ARA, prostaglandin E2, and 12- and 15-hydroxyeicosatetraenoic acid increased in the ARA-administered group, whereas renal concentration of docosahexaenoic acid and eicosapentaenoic acid decreased in the ARA-administered group. Levels of docosahexaenoic acid-derived protectin D1, eicosapentaenoic acid-derived 5-, and 18-hydroxyeicosapentaenoic acids, and resolvin E2 and E3 decreased in the ARA-administered group. Our results indicate that long-term ARA administration led to no serious adverse reactions under normal conditions and to a decrease in anti-inflammatory docosahexaenoic acid- and eicosapentaenoic acid-derived metabolites in the kidneys of aged rats. These results indicate that there is a possibility of ARA administration having a reducing anti-inflammatory effect on the kidney.

Chronic Arachidonic Acid Administration Decreases Docosahexaenoic Acid- and Eicosapentaenoic Acid-Derived Metabolites in Kidneys of Aged Rats

PubMed Central

Katakura, Masanori; Hashimoto, Michio; Inoue, Takayuki; Mamun, Abdullah Al; Tanabe, Yoko; Arita, Makoto; Shido, Osamu

2015-01-01

Arachidonic acid (ARA) metabolites produced by cyclo-oxygenase and lipoxygenase are important mediators maintaining physiological renal function. However, the effects of exogenous ARA on kidney function in vivo remain unknown. This study examined the effects of long-term oral ARA administration on normal renal function as well as inflammation and oxidative stress in aged rats. In addition, we measured levels of renal eicosanoids and docosanoids using liquid chromatography–tandem mass spectrometry. Control or ARA oil (240 mg/kg body weight/day) was orally administered to 21-month-old Wistar rats for 13 weeks. Levels of plasma creatinine, blood urea nitrogen, inflammatory and anti-inflammatory cytokines, reactive oxygen species, and lipid peroxidation were not significantly different between the two groups. The ARA concentration in the plasma, kidney, and liver increased in the ARA-administered group. In addition, levels of free-form ARA, prostaglandin E2, and 12- and 15-hydroxyeicosatetraenoic acid increased in the ARA-administered group, whereas renal concentration of docosahexaenoic acid and eicosapentaenoic acid decreased in the ARA-administered group. Levels of docosahexaenoic acid-derived protectin D1, eicosapentaenoic acid-derived 5-, and 18-hydroxyeicosapentaenoic acids, and resolvin E2 and E3 decreased in the ARA-administered group. Our results indicate that long-term ARA administration led to no serious adverse reactions under normal conditions and to a decrease in anti-inflammatory docosahexaenoic acid- and eicosapentaenoic acid-derived metabolites in the kidneys of aged rats. These results indicate that there is a possibility of ARA administration having a reducing anti-inflammatory effect on the kidney. PMID:26485038

Established dietary estimates of net acid production do not predict measured net acid excretion in patients with Type 2 diabetes on Paleolithic-Hunter-Gatherer-type diets.

PubMed

Frassetto, L A; Shi, L; Schloetter, M; Sebastian, A; Remer, T

2013-09-01

Formulas developed to estimate diet-dependent net acid excretion (NAE) generally agree with measured values for typical Western diets. Whether they can also appropriately predict NAE for 'Paleolithic-type' (Paleo) diets-which contain very high amounts of fruits and vegetables (F&V) and concurrent high amounts of protein is unknown. Here, we compare measured NAEs with established NAE estimates in subjects with Type 2 diabetes (T2D). Thirteen subjects with well-controlled T2D were randomized to either a Paleo or American Diabetes Association (ADA) diet for 14 days. Twenty-four hour urine collections were performed at baseline and end of the diet period, and analyzed for titratable acid, bicarbonate and ammonium to calculate measured NAE. Three formulas for estimating NAE from dietary intake were used; two (NAE_diet R or L) that include dietary mineral intake and sulfate- and organic acid (OA) production, and one that is empirically derived (NAE_diet F) only considering potassium and protein intake. Measured NAE on the Paleo diet was significantly lower than on the ADA-diet (+31±22 vs 112±52 mEq/day, P=0.002). Although all formula estimates showed similar and reasonable correlations (r=0.52-0.76) with measured NAE, each one underestimated measured values. The formula with the best correlation did not contain an estimate of dietary OA production. Paleo-diets are lower in NAE than typical Western diets. However, commonly used formulas clearly underestimate NAE, especially for diets with very high F&V (as the Paleo diet), and in subjects with T2D. This may be due to an inappropriate estimation of proton loads stemming from OAs, underlining the necessity for improved measures of OA-related proton sources.

Activation of PPARα by Oral Clofibrate Increases Renal Fatty Acid Oxidation in Developing Pigs.

PubMed

He, Yonghui; Khan, Imad; Bai, Xiumei; Odle, Jack; Xi, Lin

2017-12-08

The objective of this study was to evaluate the effects of peroxisome proliferator-activated receptor α (PPARα) activation by clofibrate on both mitochondrial and peroxisomal fatty acid oxidation in the developing kidney. Ten newborn pigs from 5 litters were randomly assigned to two groups and fed either 5 mL of a control vehicle (2% Tween 80) or a vehicle containing clofibrate (75 mg/kg body weight, treatment). The pigs received oral gavage daily for three days. In vitro fatty acid oxidation was then measured in kidneys with and without mitochondria inhibitors (antimycin A and rotenone) using [1- 14 C]-labeled oleic acid (C18:1) and erucic acid (C22:1) as substrates. Clofibrate significantly stimulated C18:1 and C22:1 oxidation in mitochondria ( p < 0.001) but not in peroxisomes. In addition, the oxidation rate of C18:1 was greater in mitochondria than peroxisomes, while the oxidation of C22:1 was higher in peroxisomes than mitochondria ( p < 0.001). Consistent with the increase in fatty acid oxidation, the mRNA abundance and enzyme activity of carnitine palmitoyltransferase I (CPT I) in mitochondria were increased. Although mRNA of mitochondrial 3-hydroxy-3-methylglutaryl-coenzyme A synthase (mHMGCS) was increased, the β-hydroxybutyrate concentration measured in kidneys did not increase in pigs treated with clofibrate. These findings indicate that PPARα activation stimulates renal fatty acid oxidation but not ketogenesis.

Dietary docosahexaenoic acid ameliorates, but rapeseed oil and safflower oil accelerate renal injury in stroke-prone spontaneously hypertensive rats as compared with soybean oil, which is associated with expression for renal transforming growth factor-beta, fibronectin and renin.

PubMed

Miyazaki, M; Takemura, N; Watanabe, S; Hata, N; Misawa, Y; Okuyama, H

2000-01-03

We have noted that n-3 fatty acid-rich oils, such as fish oil, perilla oil and flaxseed oil as well as ethyl docosahexaenoate (DHA) prolonged the survival time of stroke-prone spontaneously hypertensive rats (SHRSP) rats by approximately 10% as compared with linoleate (n-6)-rich safflower oil. Rapeseed oil with a relatively low n-6/n-3 ratio unusually shortened the survival time by approximately 40%, suggesting the presence of minor components unfavorable to SHRSP rats. This study examined the effects of dietary oils and DHA on renal injury and gene expression related to renal injury in SHRSP rats. Rats fed rapeseed oil- and safflower oil-supplemented diets developed more severe proteinuria than those fed soybean oil-supplemented diet used as a control, but there were no significant differences in blood pressure. In contrast, the DHA-supplemented diet inhibited the development of proteinuria and suppressed hypertension. The mRNA levels for renal TGF-beta, fibronectin and renin were higher in the rapeseed oil and safflower oil groups after 9 weeks of feeding of the experimental diet than in the soybean oil and DHA groups. The fatty acid composition of kidney phospholipids was markedly affected by these diets. These results indicate that the renal injury observed in the groups fed safflower oil with a high n-6/n-3 ratio and rapeseed oil with presumed minor components is accompanied by increased expression of the TGF-beta, renin and fibronectin genes, and that dietary DHA suppresses renal injury and gene expression as compared with soybean oil.

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.

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.

Higher estimates of daily dietary net endogenous acid production (NEAP) in the elderly as compared to the young in a healthy, free-living elderly population of Pakistan

PubMed Central

Alam, Iftikhar; Alam, Ibrar; Paracha, Parvez I; Pawelec, Graham

2012-01-01

Dietary intake has been shown to influence the acid–base balance in human subjects; however, this phenomenon is poorly understood and rarely reported for the least well-studied segment of older people in a developing country. The aims of the present study were to: (1) quantify estimates of daily net endogenous acid production (NEAP) (mEq/d) in a sample of otherwise healthy elderly aged 50 years and above; and (2) compare NEAP between the elderly and young to determine the effects of aging, which could contribute to changes in the acid–base balance. Analyses were carried out among 526 elderly and 131 young participants (aged 50–80 and 23–28 years, respectively), all of whom were free of discernible disease, nonsmokers, and not on any chronic medication. Selected anthropometric factors were measured and 24-hour dietary recall was recorded. We used two measures to characterize dietary acid load: (1) NEAP estimated as the dietary potential renal acid load plus organic acid excretion, the latter as a multiple of estimated body surface area; and (2) estimated NEAP based on protein and K. For the young and elderly, the ranges of NEAP were 12.1–67.8 mEq/d and 2.0–78.3 mEq/d, respectively. Regardless of the method used, the mean dietary acid–base balance (NEAP) was significantly higher for the elderly than the young (P = 0.0035 for NEAP [elderly, 44.1 mEq/d versus young 40.1 mEq/d]; and P = 0.0035 for the protein:potassium ratio [elderly, 1.4 mEq/d versus young 1.1 mEq/d]). A positive and significant correlation was found between NEAP and energy, protein, and phosphorus (P < 0.05 for all trends). The findings from this study provide evidence of the relatively higher production of NEAP in older people, possibly as an effect of higher consumption of certain acid-producing foods by the elderly. PMID:23271903

Renal pathophysiologic role of cortical tubular inclusion bodies.

PubMed

Radi, Zaher A; Stewart, Zachary S; Grzemski, Felicity A; Bobrowski, Walter F

2013-01-01

Renal tubular inclusion bodies are rarely associated with drug administration. The authors describe the finding of renal cortical tubular intranuclear and intracytoplasmic inclusion bodies associated with the oral administration of a norepinephrine/serotonin reuptake inhibitor (NSRI) test article in Sprague-Dawley (SD) rats. Rats were given an NSRI daily for 4 weeks, and kidney histopathologic, ultrastructural pathology, and immunohistochemical examinations were performed. Round eosinophilic intranuclear inclusion bodies were observed histologically in the tubular epithelial cells of the renal cortex in male and female SD rats given the NSRI compound. No evidence of degeneration or necrosis was noted in the inclusion-containing renal cells. By ultrastructural pathology, inclusion bodies consisted of finely granular, amorphous, and uniformly stained nonmembrane-bound material. By immunohistochemistry, inclusion bodies stained positive for d-amino acid oxidase (DAO) protein. In addition, similar inclusion bodies were noted in the cytoplasmic tubular epithelial compartment by ultrastructural and immunohistochemical examination.  This is the first description of these renal inclusion bodies after an NSRI test article administration in SD rats. Such drug-induced renal inclusion bodies are rat-specific, do not represent an expression of nephrotoxicity, represent altered metabolism of d-amino acids, and are not relevant to human safety risk assessment.

The role of the kidney in compensating the alkaline tide, electrolyte load, and fluid balance disturbance associated with feeding in the freshwater rainbow trout, Oncorhynchus mykiss.

PubMed

Bucking, Carol; Landman, Michael J; Wood, Chris M

2010-05-01

The effect in freshwater rainbow trout of digesting a commercial pellet meal on the renal handling of water, ions and acid-base equivalents was investigated through urine collection over a 48 h period following meal ingestion. The glomerular filtration rate (GFR) and urine flow rate (UFR) were reduced in fed fish between 12 and 24h following the meal, likely reflecting a loss of endogenous water across the gastric epithelium as a result of ingesting dry, ion-rich food pellets. The kidney was also responsible for the excretion of some excess dietary Ca(2+), and, to a much lesser extent, Na(+) and Cl(-), while the urinary excretion of K(+) was unaffected. The most dramatic effect of feeding was the elevation of renal Mg(2+) excretion, with the kidney transitioning from net Mg(2+) reabsorption to net Mg(2+) secretion during digestion. The renal handling of dietary ions accounted for 3-27% of the total ions absorbed from the diet, indicating that a majority of the ions are excreted extra-renally or incorporated into growth. However this does highlight the underestimation of renal ion handling when using unfed fish models. The metabolic alkalosis created by digestion (the alkaline tide) resulted in an increase in urine pH as well as a transition from net acidic equivalent excretion in the urine to net basic equivalent excretion. This was due to a decrease in the titratable acidity minus bicarbonate component of urine as well as a decrease in ammonia secretion. Additionally, the experimental separation of the urinary component of acid-base excretion from that of the gills highlighted the substantially larger contribution of the latter. During the alkaline tide, renal excretion accounted for approximately 5% of the total basic equivalent excretion to the external water. Copyright 2009 Elsevier Inc. All rights reserved.

Gastrin stimulates renal dopamine production by increasing the renal tubular uptake of l-DOPA.

PubMed

Jiang, Xiaoliang; Zhang, Yanrong; Yang, Yu; Yang, Jian; Asico, Laureano D; Chen, Wei; Felder, Robin A; Armando, Ines; Jose, Pedro A; Yang, Zhiwei

2017-01-01

Gastrin is a peptide hormone that is involved in the regulation of sodium balance and blood pressure. Dopamine, which is also involved in the regulation of sodium balance and blood pressure, directly or indirectly interacts with other blood pressure-regulating hormones, including gastrin. This study aimed to determine the mechanisms of the interaction between gastrin and dopamine and tested the hypothesis that gastrin produced in the kidney increases renal dopamine production to keep blood pressure within the normal range. We show that in human and mouse renal proximal tubule cells (hRPTCs and mRPTCs, respectively), gastrin stimulates renal dopamine production by increasing the cellular uptake of l-DOPA via the l-type amino acid transporter (LAT) at the plasma membrane. The uptake of l-DOPA in RPTCs from C57Bl/6J mice is lower than in RPTCs from normotensive humans. l-DOPA uptake in renal cortical slices is also lower in salt-sensitive C57Bl/6J than in salt-resistant BALB/c mice. The deficient renal cortical uptake of l-DOPA in C57Bl/6J mice may be due to decreased LAT-1 activity that is related to its decreased expression at the plasma membrane, relative to BALB/c mice. We also show that renal-selective silencing of Gast by the renal subcapsular injection of Gast siRNA in BALB/c mice decreases renal dopamine production and increases blood pressure. These results highlight the importance of renal gastrin in stimulating renal dopamine production, which may give a new perspective in the prevention and treatment of hypertension. Copyright © 2017 the American Physiological Society.

[Safety and effectiveness of nicotinic acid in the management of patients with chronic renal disease and hyperlipidemia associated to hyperphosphatemia].

PubMed

Restrepo Valencia, C A; Cruz, J

2008-01-01

To establish if the nicotinic acid in patients with chronic renal disease reduce significantly and with security the levels of lipids and serum phosphate in refractory patients to the classical management. Observational study Place: Renal Unity RTS Ltda Caldas Santa Sofìa Hospital. All the patients with chronic renal disease in dialysis therapy to whom the classical treatment for their hyperlipidaemia and hyperphosphatemia didn't manage a satisfactory reduce of their serum levels. It was identified that those patients who in the 3 previous months to the intervention hadn't presented changes in the lipids profile even though they received low fats diet and a lipid lowering therapies (statin o fibric acid derivates). It was determined in them whether they presented levels of serum phosphorus greater than 5.5 mg/dl even though having received nutritional recommendations and treatment with oral phosphate binding agents (Aluminum hydroxide, Calcium salts or Sevelamer). In them it was proceeded to administrate nicotinic acid via oral at night until a doses of 1,000 milligrams was reached (preceded of 100 mgs of acetylsalicylic acid 1 hour before) during a period of 8 months, observing its therapeutical effectivity and security profile to improve the lipids profile and reduce the serum phosphorus. 9 patients complied with the requirements, average time in dialysis 34 months, 3 in hemodialysis and 6 in peritoneal dialysis. All patients started with 500 mgs and 3 months later correctly tolerated the dose of 1,000 mgs. Between the evaluated variables, the most important changes were: the phosphorus reduced reaching a significant value at eight months: initial 6.46+/-0.53, four months 4.37+/-0.63 (p>0.05) and eight months 3.94+/-0.76 (p<0.01); the product Ca x P obtained important reductions at four and eight months; the total Cholesterol and Triglyceride was significant reduced at all periods, not being so for the LDL, although the HDL elevated to significant values at

Effects of Hyperbaric Oxygen Treatment on Renal System.

PubMed

Tezcan, Orhan; Caliskan, Ahmet; Demirtas, Sinan; Yavuz, Celal; Kuyumcu, Mahir; Nergiz, Yusuf; Guzel, Abdulmenap; Karahan, Oguz; Ari, Seyhmus; Soker, Sevda; Yalinkilic, Ibrahim; Turkdogan, Kenan Ahmet

2017-01-01

Hyperbaric oxygen (HBO) treatment is steadily increasing as a therapeutic modality for various types of diseases. Although good clinical outcomes were reported with HBO treatment for various diseases, the multisystemic effects of this modality are still unclear. This study aimed to investigate the renal effects of HBO experimentally. Fourteen New Zealand White rabbits were divided into 2 groups randomly as the control group and the study group. The study group received HBO treatment for 28 days (100% oxygen at 2.5 atmospheres for 90 minutes daily) and the control group was used to obtain normal renal tissue of the animal genus. After the intervention period, venous blood samples were obtained, and renal tissue samples were harvested for comparisons. Normal histological morphology was determined with Masson trichrome staining and periodic acid-Schiff staining in the control group. Atrophic glomerular structures, vacuolated tubule cells, and degeneration were detected in the renal samples of the study group with Masson trichrome staining. Additionally, flattening was observed on the brush borders of the proximal tubules, and tubular dilatation was visualized with periodic acid-Schiff staining. The histopathologic disruption of renal morphology was verified with detection of significantly elevated kidney function laboratory biomarkers in the study group. Our findings suggests that HBO has adverse effects on renal glomerulus and proximal tubules. However, the functional effects of this alteration should be investigated with further studies.

Renal and prostate stones composition in alkaptonuria: a case report.

PubMed

Wolff, Fleur; Biaou, Ibrahim; Koopmansch, Caroline; Vanden Bossche, Marc; Pozdzik, Agnieszka; Roumeguère, Thierry; Cotton, Frédéric

2015-12-01

Alkaptonuria is a genetic disorder characterized by an accumulation of homogentisic acid due to an enzymatic defect of homogentisate 1,2 dioxygenase. The homogentisic acid is excreted exclusively by both glomerular filtration and tubular secretion leading to the renal parenchyma being exposed to high concentrations of homogentisic acid. The alkaptonuric patients are at higher risk of renal stones (and of prostate stones for males), usually in the later stages of the disease. We describe the case of a 51-year-old man whose renal and prostate stones were analyzed by X-ray diffraction and infrared spectroscopy, respectively. We review the cases of alkaptonuria (AKU) patients reported in the literature for whom the composition of kidney or prostate stones was assessed with physical or chemical techniques. In this paper, we also discuss the advantages and drawbacks of the different methodologies.

Rodent renal structure differs among species.

PubMed

Ichii, Osamu; Yabuki, Akira; Ojima, Toshimichi; Matsumoto, Mitsuharu; Suzuki, Shusaku

2006-05-01

In the present study, we histologically and morphometrically investigated species differences in renal structure using laboratory rodents (mice, gerbils, hamsters, rats, and guinea pigs). Morphometric parameters were as follows, 1) diameter of the cortical renal corpuscles, 2) diameter of the juxtamedullary renal corpuscles, 3) percentage of the renal corpuscles with a cuboidal parietal layer, 4) number of nuclei in proximal convoluted tubules (PCTs) per unit area of cortex, 5) semi-quantitative score of the periodic acid-Schiff (PAS) -positive granules in PCTs, and 6) semi-quantitative score of the PAS-positive granules in proximal straight tubules (PSTs). Significant species differences were detected for each parameter, and particularly severe differences were observed in the PAS-positive granules of PCTs and PSTs. Granular scores varied among species and sexes. Vacuolar structures that did not stain with PAS or hematoxylin-eosin were observed in the renal proximal tubules. The appearance and localization of these vacuolar structures differed remarkably between species and sexes.

Effects of renal function on pharmacokinetics and pharmacodynamics of lesinurad in adult volunteers.

PubMed

Gillen, Michael; Valdez, Shakti; Zhou, Dongmei; Kerr, Bradley; Lee, Caroline A; Shen, Zancong

2016-01-01

Lesinurad is a selective uric acid reabsorption inhibitor approved for the treatment of gout in combination with a xanthine oxidase inhibitor (XOI) in patients who have not achieved target serum uric acid (sUA) levels with an XOI alone. Most people with gout have chronic kidney disease. The pharmacokinetics, pharmacodynamics, and safety of lesinurad were assessed in subjects with impaired renal function. Two Phase I, multicenter, open-label, single-dose studies enrolled subjects with normal renal function (estimated creatinine clearance [eCrCl] >90 mL/min; N=12) or mild (eCrCl 60-89 mL/min; N=8), moderate (eCrCl 30-59 mL/min; N=16), or severe (eCrCl <30 mL/min; N=6) renal impairment. Subjects were given a single oral lesinurad dose of 200 mg (N=24) or 400 mg (N=18). Blood and urine samples were analyzed for plasma lesinurad concentrations and serum and urine uric acid concentrations. Safety was assessed by adverse events and laboratory data. Mild, moderate, and severe renal impairment increased lesinurad plasma area under the plasma concentration-time curve by 34%, 54%-65%, and 102%, respectively. Lesinurad plasma C max was unaffected by renal function status. Lower renal clearance and urinary excretion of lesinurad were associated with the degree of renal impairment. The sUA-lowering effect of a single dose of lesinurad was similar between mild renal impairment and normal function, reduced in moderate impairment, and greatly diminished in severe impairment. Lesinurad increased urinary urate excretion in normal function and mild renal impairment; the increase was less with moderate or severe renal impairment. Lesinurad was well tolerated by all subjects. Lesinurad exposure increased with decreasing renal function; however, the effects of lesinurad on sUA were attenuated in moderate to severe renal impairment.

Serum uric acid is a GFR-independent long-term predictor of acute and chronic renal insufficiency: the Jerusalem Lipid Research Clinic cohort study

PubMed Central

Kark, Jeremy D.

2011-01-01

Background. Kidney disease is commonly accompanied by hyperuricemia. However, the contribution of serum uric acid (SUA) to kidney injury is debated. Our objective was to assess the long-term prediction of renal failure by SUA. Methods. Visit 2 participants in the Jerusalem Lipid Research Clinic cohort with normal baseline kidney function were followed for 24–28 years. SUA levels were assessed for associations with acute renal failure (ARF) and chronic renal failure (CRF) as defined by hospital discharge records, and mortality, ascertained through linkage with the national population registry. Results. Among 2449 eligible participants (1470 men, 979 women aged 35–78 years in 1976–79), SUA was positively linked with male sex, serum creatinine and components of the metabolic syndrome but was lower in smokers and in diabetic subjects. The 22- to 25-year incidence of hospital-diagnosed kidney failure (145 first events, 67% CRF) and the 24- to 28-year mortality (587 events) were higher in subject with hyperuricemia (>6.5 mg/dL in men and >5.3 mg/dL in women, reflecting the upper quintiles), independent of baseline kidney function and covariates. Hyperuricemia conferred adjusted hazard ratios of 1.36 (P = 0.003), 2.14 (P < 0.001) and 2.87 (P = 0.003) for mortality, CRF and ARF, respectively. Conclusions. SUA predicts renal failure incidence and all-cause mortality independently of demographic and clinical covariates. These results lend support to the undertaking of clinical trials to examine the effect of uric acid-lowering strategies on kidney outcomes. PMID:21220750

Urinary Liver Type Fatty Acid Binding Protein Is Negatively Associated With Estimated Glomerular Filtration Rate in Renal Transplant Recipients With Graft Loss.

PubMed

Huang, Y-C; Chang, Y-S; Chen, C-C; Tsai, S-F; Yu, T-M; Wu, M-J; Chen, C-H

2018-05-01

Liver type fatty acid binding protein (L-FABP) is abundant not only in the liver but also in the kidney and is excreted in urine. Its primary function is to facilitate intracellular long chain fatty acid transport and it might also act as an endogenous antioxidant molecular. The purpose of this study was to investigate whether plasma or urinary L-FABP levels were associated with graft function in renal transplant recipients. Sixty-seven renal transplant recipients with a mean age of 48.8 years were recruited. The mean duration of renal transplantation was 4131 days. Recipients were divided into 2 groups based on their estimated glomerular filtration rate (eGFR) values: moderate graft function (eGFR ≥60 mL/min/1.73 m 2 ) and low graft function (eGFR <60 mL/min/1.73 m 2 ). Fasting plasma and urinary L-FABP levels were measured. There was no significant difference in plasma L-FABP level between the 2 groups, although recipients in the low graft function group had significantly lower urinary L-FABP level when compared with recipients in the moderate graft function group. Plasma and urinary L-FABP levels were not associated with eGFR in the 67 recipients; however, urinary L-FABP level (β = -1.24, P = .037) and level adjusted by urinary creatinine (β = -0.75, P = .046) were significantly negatively associated with eGFR in recipients with low graft function after adjusting for potential confounders. Increased urinary L-FABP level seems to be a significant indicator of decreased graft function in renal transplant recipients with loss of graft function. Copyright © 2018 Elsevier Inc. All rights reserved.

Metabolic effects of keto acid--amino acid supplementation in patients with chronic renal insufficiency receiving a low-protein diet and recombinant human erythropoietin--a randomized controlled trial.

PubMed

Teplan, V; Schück, O; Votruba, M; Poledne, R; Kazdová, L; Skibová, J; Malý, J

2001-09-17

Supplement with keto acids/amino acids (KA) and erythropoietin can independently improve the metabolic sequels of chronic renal insufficiency. Our study was designed to establish whether a supplementation with keto acids/amino acids (KA) exerts additional beneficial metabolic effects in patients with chronic renal insufficiency (CRF) treated with a low-protein diet (LPD) and recombinant human erythropoietin (EPO). In a prospective randomized controlled trial over a period of 12 months, we evaluated a total of 38 patients (20 M/18 F) aged 32-68 years with a creatinine clearance (CCr) of 20-36 ml/min. All patients were receiving EPO (40 U/kg twice a week s.c.) and a low-protein diet (0.6 g protein/kg/day and 145 kJ/kg/day). The diet of 20 patients (Group I) was supplemented with KA at a dosage of 100 mg/kg/day while 18 patients (Group II) received no supplementation. During the study period, the glomerular filtration rate slightly decreased (CCr from 28.2 +/- 3.4 to 26.4 +/- 4.1 ml/min and 29.6 +/- 4.8 to 23.4 +/- 4.4 ml/min in groups I and II, respectively and Cin); this however was more marked in Group II (Group I vs. Group II, p < 0.01). The serum levels of urea also declined (p < 0.01), more pronouncedly in Group I (p < 0.025). In Group I, there was a significant rise in the levels of leucine (p < 0.01), isoleucine (p < 0.01), valine (p < 0.02) and albumin (p < 0.01) and a decrease in protein-uria (p < 0.01). Analysis of the lipid spectrum revealed a mild yet significant decrease in total cholesterol and LDL-cholesterol (p < 0.02), more pronounced in Group I. In Group I, there was a decrease in plasma triglycerides (from 4.2 +/- 0.8 down to values a low as 2.2 +/- 0.6 mmol/L; p < 0.01) whereas HDL-cholesterol levels increased (from 0.9 +/- 0.1 to 1.2 +/- 0.1 mmol/L, p < 0.01). A further remarkable finding was a reduction in the serum concentration of free radicals (p < 0.01). We conclude that a KA supplementation in patients with CRF receiving LPD and EPO

Modeled dosage-response relationship on the net photosynthetic rate for the sensitivity to acid rain of 21 plant species.

PubMed

Deng, Shihuai; Gou, Shuzhen; Sun, Baiye; Lv, Wenlin; Li, Yuanwei; Peng, Hong; Xiao, Hong; Yang, Gang; Wang, Yingjun

2012-08-01

This study investigated the sensitivity of plant species to acid rain based on the modeled dosage-response relationship on the net photosynthetic rate (P (N)) of 21 types of plant species, subjected to the exposure of simulated acid rain (SAR) for 5 times during a period of 50 days. Variable responses of P (N) to SAR occurred depending on the type of plant. A majority (13 species) of the dosage-response relationship could be described by an S-shaped curve and be fitted with the Boltzmann model. Model fitting allowed quantitative evaluation of the dosage-response relationship and an accurate estimation of the EC(10), termed as the pH of the acid rain resulting in a P (N) 10 % lower than the reference value. The top 9 species (Camellia sasanqua, Cinnamomum camphora, etc. EC(10) ≤ 3.0) are highly endurable to very acid rain. The rare, relict plant Metasequoia glyptostroboides was the most sensitive species (EC(10) = 5.1) recommended for protection.

Environment or development? Lifetime net CO2 exchange and control of the expression of Crassulacean acid metabolism in Mesembryanthemum crystallinum.

PubMed

Winter, Klaus; Holtum, Joseph A M

2007-01-01

The relative influence of plant age and environmental stress signals in triggering a shift from C(3) photosynthesis to Crassulacean acid metabolism (CAM) in the annual halophytic C(3)-CAM species Mesembryanthemum crystallinum was explored by continuously monitoring net CO(2) exchange of whole shoots from the seedling stage until seed set. Plants exposed to high salinity (400 mm NaCl) in hydroponic culture solution or grown in saline-droughted soil acquired between 11% and 24% of their carbon via net dark CO(2) uptake involving CAM. In contrast, plants grown under nonsaline, well-watered conditions were capable of completing their life cycle by operating in the C(3) mode without ever exhibiting net CO(2) uptake at night. These observations are not consistent with the widely expressed view that the induction of CAM by high salinity in M. crystallinum represents an acceleration of preprogrammed developmental processes. Rather, our study demonstrates that the induction of the CAM pathway for carbon acquisition in M. crystallinum is under environmental control.

Renal, hepatic, pulmonary and adrenal tumors induced by prenatal inorganic arsenic followed by dimethylarsinic acid in adulthood in CD1 mice

PubMed Central

Tokar, Erik J.; Diwan, Bhalchandra A.; Waalkes, Michael P.

2012-01-01

Inorganic arsenic, an early life carcinogen in humans and mice, can initiate lesions promotable by other agents in later life. The biomethylation product of arsenic, dimethylarsinic acid (DMA), is a multi-site tumor promoter. Thus, pregnant CD1 mice were given drinking water (0 or 85 ppm arsenic) from gestation day 8 to 18 and after weaning male offspring received DMA (0 or 200 ppm; drinking water) for up to 2 years. No renal tumors occurred in controls or DMA alone treated mice while gestational arsenic exposure plus later DMA induced a significant renal tumor incidence of 17% (primarily renal cell carcinoma). Arsenic plus DMA or arsenic alone also increased renal hyperplasia over control but DMA alone did not. Arsenic alone, DMA alone and arsenic plus DMA all induced urinary bladder hyperplasia (33–35%) versus control (2%). Compared to control (6%), arsenic alone tripled hepatocellular carcinoma (20%), and arsenic plus DMA doubled this rate again (43%), but DMA alone had no effect. DMA alone, arsenic alone, and arsenic plus DMA increased lung adenocarcinomas and adrenal adenomas versus control. Overall, DMA in adulthood promoted tumors/lesions initiated by prenatal arsenic in the kidney and liver, but acted independently in the urinary bladder, lung and adrenal. PMID:22230260

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.

Effects of ellagic acid pretreatment on renal functions disturbances induced by global cerebral ischemic-reperfusion in rat.

PubMed

Nejad, Khojasteh Hoseiny; Gharib-Naseri, Mohammad Kazem; Sarkaki, Alireza; Dianat, Mahin; Badavi, Mohammad; Farbood, Yaghoub

2017-01-01

Global cerebral ischemia-reperfusion (GCIR) causes disturbances in brain functions as well as other organs such as kidney. Our aim was to evaluate the protective effects of ellagic acid (EA) on certain renal disfunction after GCIR. Adult male Wistar rats (n=32, 250-300 g) were used. GCIR was induced by bilateral vertebral and common carotid arteries occlusion (4-VO). Animal groups were: 1) received DMSO/saline (10%) as solvent of EA, 2) solvent + GCIR, 3) EA + GCIR, and 4) EA. Under anesthesia with ketamine/xylazine, GCIR was induced (20 and 30 min respectively) in related groups. EA (100 mg/kg, dissolved in DMSO/saline (10%) or solvent was administered (1.5 ml/kg) orally for 10 consecutive days to the related groups. EEG was recorded from NTS in GCIR treated groups. Our data showed that: a) EEG in GCIR treated groups was flattened. b) GCIR reduced GFR ( P <0.01) and pretreatment with EA attenuated this reduction. c) BUN was increased by GCIR ( P <0.001) and pretreatment with EA improved the BUN to normal level. d) Serum creatinine concentration was elevated by GCIR but not significantly, however, in EA+GCIR group serum creatinine was reduced ( P <0.05). e) GCIR induced proteinuria ( P <0.05) but, EA was unable to reduced proteinuria. Results indicate that GCIR impairs certain renal functions and EA as an antioxidant can improve these functions. Our results suggest the possible usefulness of ellagic acid in patients with brain stroke.

[Acute renal failure in the transretinoic syndrome].

PubMed

Sastre, A; Gago, E; Baños, M; Gómez, E

2007-01-01

The all-trans retinoic acid (ATRA) is the treatment of first line of acute promyelocytic leukemia (APL). ATRA is usually well tolerated, but a few major side effects can be observed, ATRA syndrome (RAS) being the most important of them, potentially fatal. The manifestations of this Syndrome are fever, weight gain, pulmonary infiltrates, pleural or pericardial effusions, hypotension, liver dysfunction and renal failure. We studied to the 29 patients diagnosed in (January of 2002 - December of 2004) of acute promyelocytic leukemia (APL), which were treated with ATRA, all received the 45 dose of mg/m(2)/d . The diagnosis of the leukemia was made by citomorphologist analysis. The criterion of renal insufficiency, it was an increase of the creatinina superior to 20% of the basal level. The definition of the transretinoico acid Syndrome was based on the clinical criteria of Frankel. Fourteen patients presented the Transretinoico Syndrome (48.3%), 11 of which (37.9%) died. The fundamental differences between the patients with or without ATRA were: fever (14 vs. 9, p=0,017), gain of weight (14 vs 0, p=0,000), pleural effusion (14 vs 2, p=0.000), pulmonary infiltrates (13 vs 1, p=0,000), cardiac failure (12 versus 2, p=0,000), respiratory distress (12 versus 4, p=0,003), presence of renal failure (10 vs 4, p=0,02), necessity of substitute renal treatment (6 vs 0, p=0,006) and arterial hypotension (12 vs. 3, p=0,001). The acute renal failure appeared in 10 of the 14 patients with SAR (71.4%), to 12+/-5 (1-25) days of the beginning of the treatment and their duration it was of 14+/-5 (1-46) days. Six (60%) needed substitute renal treatment and 5 (50%) died. Of the patients who survived, only a patient continues in dialysis. In both patient in that renal biopsy was made, the study showed signs of cortical necrosis. The appearance of acute renal failure in the course of the SAR is frequent, being observed deterioration of the renal function that needs substitute renal treatment

Shuttle Net, Tuna Net

NASA Technical Reports Server (NTRS)

1983-01-01

Rockwell International, NASA's prime contractor for the Space Shuttle, asked West Coast Netting (WCN) to develop a safety net for personnel working on the Shuttle Orbiter. This could not be an ordinary net, it had to be relatively small, yet have extraordinary tensile strength. It also had to be fire resistant and resistant to ultraviolet (UV) light. After six months, WCN found the requisite fiber, a polyester-like material called NOMEX. The company was forced to invent a more sophisticated twisting process since conventional methods did not approach specified breaking strength. The resulting product, the Hyperester net, sinks faster and fishes deeper, making it attractive to fishing fleets. A patented treatment for UV protection and greater abrasion resistance make Hyperester nets last longer, and the no-shrink feature is an economic bonus.

Nod2 deficiency protects mice from cholestatic liver disease by increasing renal excretion of bile acids

PubMed Central

Wang, Lirui; Hartmann, Phillipp; Haimerl, Michael; Bathena, Sai P.; Sjöwall, Christopher; Almer, Sven; Alnouti, Yazen; Hofmann, Alan F.; Schnabl, Bernd

2014-01-01

Background & aims Chronic liver disease is characterized by fibrosis that may progress to cirrhosis. Nucleotide oligomerization domain 2 (Nod2), a member of the Nod-like receptor (NLR) family of intracellular immune receptors, plays an important role in the defense against bacterial infection through binding to the ligand muramyl dipeptide (MDP). Here, we investigated the role of Nod2 in the development of liver fibrosis. Methods We studied experimental cholestatic liver disease induced by bile duct ligation or toxic liver disease induced by carbon tetrachloride in wild type and Nod2−/− mice. Results Nod2 deficiency protected mice from cholestatic but not toxin-induced liver injury and fibrosis. Most notably, the hepatic bile acid concentration was lower in Nod2−/− mice than wild type mice following bile duct ligation for 3 weeks. In contrast to wild type mice, Nod2−/− mice had increased urinary excretion of bile acids, including sulfated bile acids, and an upregulation of the bile acid efflux transporters MRP2 and MRP4 in tubular epithelial cells of the kidney. MRP2 and MRP4 were downregulated by IL-1β in a Nod2 dependent fashion. Conclusions Our findings indicate that Nod2 deficiency protects mice from cholestatic liver injury and fibrosis through enhancing renal excretion of bile acids that in turn contributes to decreased concentration of bile acids in the hepatocyte. PMID:24560660

Live Donor Renal Anatomic Asymmetry and Posttransplant Renal Function.

PubMed

Tanriover, Bekir; Fernandez, Sonalis; Campenot, Eric S; Newhouse, Jeffrey H; Oyfe, Irina; Mohan, Prince; Sandikci, Burhaneddin; Radhakrishnan, Jai; Wexler, Jennifer J; Carroll, Maureen A; Sharif, Sairah; Cohen, David J; Ratner, Lloyd E; Hardy, Mark A

2015-08-01

Relationship between live donor renal anatomic asymmetry and posttransplant recipient function has not been studied extensively. We analyzed 96 live kidney donors, who had anatomical asymmetry (>10% renal length and/or volume difference calculated from computerized tomography angiograms) and their matching recipients. Split function differences (SFD) were quantified with technetium-dimercaptosuccinic acid renography. Implantation biopsies at time 0 were semiquantitatively scored. A comprehensive model using donor renal volume adjusted to recipient weight (Vol/Wgt), SFD, and biopsy score was used to predict recipient estimated glomerular filtration rate (eGFR) at 1 year. Primary analysis consisted of a logistic regression model of outcome (odds of developing eGFR>60 mL/min/1.73 m(2) at 1 year), a linear regression model of outcome (predicting recipient eGFR at one-year, using the chronic kidney disease-epidemiology collaboration formula), and a Monte Carlo simulation based on the linear regression model (N=10,000 iterations). In the study cohort, the mean Vol/Wgt and eGFR at 1 year were 2.04 mL/kg and 60.4 mL/min/1.73 m(2), respectively. Volume and split ratios between 2 donor kidneys were strongly correlated (r = 0.79, P < 0.001). The biopsy scores among SFD categories (<5%, 5%-10%, >10%) were not different (P = 0.190). On multivariate models, only Vol/Wgt was significantly associated with higher odds of having eGFR > 60 mL/min/1.73 m (odds ratio, 8.94, 95% CI 2.47-32.25, P = 0.001) and had a strong discriminatory power in predicting the risk of eGFR less than 60 mL/min/1.73 m(2) at 1 year [receiver operating curve (ROC curve), 0.78, 95% CI, 0.68-0.89]. In the presence of donor renal anatomic asymmetry, Vol/Wgt appears to be a major determinant of recipient renal function at 1 year after transplantation. Renography can be replaced with CT volume calculation in estimating split renal function.

Helminth.net: expansions to Nematode.net and an introduction to Trematode.net

PubMed Central

Martin, John; Rosa, Bruce A.; Ozersky, Philip; Hallsworth-Pepin, Kymberlie; Zhang, Xu; Bhonagiri-Palsikar, Veena; Tyagi, Rahul; Wang, Qi; Choi, Young-Jun; Gao, Xin; McNulty, Samantha N.; Brindley, Paul J.; Mitreva, Makedonka

2015-01-01

Helminth.net (http://www.helminth.net) is the new moniker for a collection of databases: Nematode.net and Trematode.net. Within this collection we provide services and resources for parasitic roundworms (nematodes) and flatworms (trematodes), collectively known as helminths. For over a decade we have provided resources for studying nematodes via our veteran site Nematode.net (http://nematode.net). In this article, (i) we provide an update on the expansions of Nematode.net that hosts omics data from 84 species and provides advanced search tools to the broad scientific community so that data can be mined in a useful and user-friendly manner and (ii) we introduce Trematode.net, a site dedicated to the dissemination of data from flukes, flatworm parasites of the class Trematoda, phylum Platyhelminthes. Trematode.net is an independent component of Helminth.net and currently hosts data from 16 species, with information ranging from genomic, functional genomic data, enzymatic pathway utilization to microbiome changes associated with helminth infections. The databases’ interface, with a sophisticated query engine as a backbone, is intended to allow users to search for multi-factorial combinations of species’ omics properties. This report describes updates to Nematode.net since its last description in NAR, 2012, and also introduces and presents its new sibling site, Trematode.net. PMID:25392426

A role for the organic anion transporter OAT3 in renal creatinine secretion in mice

PubMed Central

Eraly, Satish A.; Rao, Satish Ramachandra; Gerasimova, Maria; Rose, Michael; Nagle, Megha; Anzai, Naohiko; Smith, Travis; Sharma, Kumar; Nigam, Sanjay K.; Rieg, Timo

2012-01-01

Tubular secretion of the organic cation, creatinine, limits its value as a marker of glomerular filtration rate (GFR) but the molecular determinants of this pathway are unclear. The organic anion transporters, OAT1 and OAT3, are expressed on the basolateral membrane of the proximal tubule and transport organic anions but also neutral compounds and cations. Here, we demonstrate specific uptake of creatinine into mouse mOat1- and mOat3-microinjected Xenopus laevis oocytes at a concentration of 10 μM (i.e., similar to physiological plasma levels), which was inhibited by both probenecid and cimetidine, prototypical competitive inhibitors of organic anion and cation transporters, respectively. Renal creatinine clearance was consistently greater than inulin clearance (as a measure of GFR) in wild-type (WT) mice but not in mice lacking OAT1 (Oat1−/−) and OAT3 (Oat3−/−). WT mice presented renal creatinine net secretion (0.23 ± 0.03 μg/min) which represented 45 ± 6% of total renal creatinine excretion. Mean values for renal creatinine net secretion and renal creatinine secretion fraction were not different from zero in Oat1−/− (−0.03 ± 0.10 μg/min; −3 ± 18%) and Oat3−/− (0.01 ± 0.06 μg/min; −6 ± 19%), with greater variability in Oat1−/−. Expression of OAT3 protein in the renal membranes of Oat1−/− mice was reduced to ∼6% of WT levels, and that of OAT1 in Oat3−/− mice to ∼60%, possibly as a consequence of the genes for Oat1 and Oat3 having adjacent chromosomal locations. Plasma creatinine concentrations of Oat3−/− were elevated in clearance studies under anesthesia but not following brief isoflurane anesthesia, indicating that the former condition enhanced the quantitative contribution of OAT3 for renal creatinine secretion. The results are consistent with a contribution of OAT3 and possibly OAT1 to renal creatinine secretion in mice. PMID:22338083

The impact of serum uric acid reduction on renal function and blood pressure in chronic kidney disease patients with hyperuricemia.

PubMed

Tsuji, Takayuki; Ohishi, Kazuhisa; Takeda, Asumi; Goto, Daiki; Sato, Taichi; Ohashi, Naro; Fujigaki, Yoshihide; Kato, Akihiko; Yasuda, Hideo

2018-04-26

Febuxostat is tolerable in chronic kidney disease (CKD) patients with hyperuricemia. However, the long-term effect of lowering uric acid with febuxostat on renal function and blood pressure has not been elucidated. This was a 2 years retrospective observational study. 86 CKD patients with hyperuricemia who continued with allopurinol (allopurinol group, n = 30), switched from allopurinol to febuxostat (switched group, n = 25), or were newly prescribed febuxostat (febuxostat group, n = 31) were included in this study. Serum uric acid, estimated glomerular filtration rate (eGFR), blood pressure, and urinary protein were analyzed. Moreover, the impact of serum uric acid reduction on renal function and blood pressure was assessed. Serum uric acid in the switched and febuxostat groups was significantly reduced at 6 months (switched group; 8.49 ± 1.32-7.19 ± 1.14 mg/dL, p < 0.0001, febuxostat group; 9.43 ± 1.63-6.31 ± 0.90 mg/dL, p < 0.0001). In the allopurinol group, serum uric acid was increased (6.86 ± 0.87-7.10 ± 0.85 mg/dL, p = 0.0213). eGFR was significantly increased (35.2 ± 12.8-37.3 ± 13.9 mL/min/1.73 m 2 , p = 0.0232), while mean arterial pressure (93.1 ± 10.8-88.2 ± 9.5 mmHg, p = 0.0039) was significantly decreased at 6 months in the febuxostat group, resulting in the retention of eGFR for 2 years. The impact of serum uric acid reduction might have beneficial effects on CKD progression and blood pressure. However, a large prospective study is needed to determine the long-term efficacy of febuxostat therapy in CKD patients with hyperuricemia.

Effects of Nigella sativa oil and ascorbic acid against oxytetracycline-induced hepato-renal toxicity in rabbits.

PubMed

Abdel-Daim, Mohamed M; Ghazy, Emad W

2015-03-01

Oxytetracycline (OTC) is a broad spectrum antibiotic widely used for treatment of a wide range of infections. However, its improper human and animal use leads to toxic effects, including hepatonephrotoxicity. Our objective was to evaluate protective effects of Nigella sativa oil (NSO) and/or ascorbic acid (AA), against OTC-induced hepatonephrotoxicity in rabbits. Forty male white New Zealand rabbits were divided into 5 groups of eight each. The 1(st) group (control) was given saline. The 2(nd) group was given OTC (200 mg/kg, orally). The 3(rd) and 4(th) groups were orally administered NSO and AA (2 ml/kg and 200 mg/kg respectively) 1 hr before OTC administration at the same dose regimen used for the 2(nd) group. Both NSO and AA were given in combination for the 5(th) group along with OTC administration. Serum biochemical parameters related to liver and kidney injury were evaluated, and lipid peroxidation as well as antioxidant markers in hepatic and renal tissues were examined. OTC-treated animals revealed significant alterations in serum biochemical hepato-renal injury markers, and showed a markedly increase in hepato-renal lipid peroxidation and inhibition in tissue antioxidant biomarkers. NSO and AA protect against OTC-induced serum and tissue biochemical alterations when each of them is used alone or in combination along with OTC treatment. Furthermore, both NSO and AA produced synergetic hepatoprotective and antioxidant properties. The present study revealed the preventive role of NSO and/or AA against the toxic effects of OTC through their free radical-scavenging and potent antioxidant activities.

PAH clearance after renal ischemia and reperfusion is a function of impaired expression of basolateral Oat1 and Oat3.

PubMed

Bischoff, Ariane; Bucher, Michael; Gekle, Michael; Sauvant, Christoph

2014-02-01

Determination of renal plasma flow (RPF) by para-aminohippurate (PAH) clearance leads to gross underestimation of this respective parameter due to impaired renal extraction of PAH after renal ischemia and reperfusion injury. However, no mechanistic explanation for this phenomenon is available. Based on our own previous studies we hypothesized that this may be due to impairment of expression of the basolateral rate limiting organic anion transporters Oat1 and Oat3. Thus, we investigated this phenomenon in a rat model of renal ischemia and reperfusion by determining PAH clearance, PAH extraction, PAH net secretion, and the expression of rOat1 and rOat3. PAH extraction was seriously impaired after ischemia and reperfusion which led to a threefold underestimation of RPF when PAH extraction ratio was not considered. PAH extraction directly correlated with the expression of basolateral Oat1 and Oat3. Tubular PAH secretion directly correlated with PAH extraction. Consequently, our data offer an explanation for impaired renal PAH extraction by reduced expression of the rate limiting basolateral organic anion transporters Oat1 and Oat3. Moreover, we show that determination of PAH net secretion is suitable to correct PAH clearance for impaired extraction after ischemia and reperfusion in order to get valid results for RPF.

Ensete superbum ameliorates renal dysfunction in experimental diabetes mellitus.

PubMed

Sreekutty, M S; Mini, S

2016-01-01

Hyperglycemia mediated oxidative stress plays a key role in the pathogenesis of diabetic complications like nephropathy. In the present study, we evaluated the effect of ethanolic extract of Ensete superbum seeds (ESSE) on renal dysfunction and oxidative stress in streptozotocin-induced diabetic rats. Glucose, HbA1c, total protein, albumin, renal function markers (urea, uric acid and creatinine), and lipid peroxidation levels were evaluated. Renal enzymatic and non-enzymatic antioxidants were examined along with renal histopathological study. ESSE (400 mg/kg BW t) administration reduced glucose and HbA1c, and improved serum total protein and albumin in diabetic rats. ESSE in diabetic rats recorded decrement in renal function markers and renal lipid peroxidation products along with significant increment in enzymatic and non-enzymatic antioxidants. Renal morphological abnormalities of diabetic rats were markedly ameliorated by E. superbum. These results suggest that the antioxidant effect of E. superbum could ameliorate oxidative stress and delay/prevent the progress of diabetic nephropathy in diabetes mellitus.

CD44-targeted hyaluronic acid-curcumin prodrug protects renal tubular epithelial cell survival from oxidative stress damage.

PubMed

Hu, Jing-Bo; Li, Shu-Juan; Kang, Xu-Qi; Qi, Jing; Wu, Jia-Hui; Wang, Xiao-Juan; Xu, Xiao-Ling; Ying, Xiao-Ying; Jiang, Sai-Ping; You, Jian; Du, Yong-Zhong

2018-08-01

Based on the abnormally increased expression of CD44 receptors on renal tubule epithelial cells during ischemia/reperfusion-induced acute kidney injury (AKI), we developed a hyaluronic acid-curcumin (HA-CUR) polymeric prodrug targeting to epithelial cells and then relieving oxidative stress damages. The water solubility of HA-CUR was significantly enhanced and approximately 27-fold higher than that of CUR. Cellular uptake test showed HA-CUR was preferably internalized by H 2 O 2 -pretreated tubular epithelial (HK-2) cells compared with free CUR benefiting from the specific binding between HA and CD44 receptors. Biodistribution results further demonstrated the increased accumulation of HA-CUR in kidneys with 13.9-fold higher than that of free CUR. Pharmacodynamic studies indicated HA-CUR effectively ameliorated AKI, and the exact mechanism was that HA-CUR protected renal tubule epithelial cells from oxidative stress damage via inhibiting PtdIns3K-AKT-mTOR signaling pathway. Taken together, this study provides a new therapeutic strategy for the treatment of AKI based on the pathogenesis of the disease. Copyright © 2018 Elsevier Ltd. All rights reserved.

Early impact of robot-assisted partial nephrectomy on renal function as assessed by renal scintigraphy.

PubMed

Luciani, Lorenzo G; Chiodini, Stefano; Donner, Davide; Cai, Tommaso; Vattovani, Valentino; Tiscione, Daniele; Giusti, Guido; Proietti, Silvia; Chierichetti, Franca; Malossini, Gianni

2016-06-01

To measure the early impact of robot-assisted partial nephrectomy (RAPN) on renal function as assessed by renal scan (Tc 99m-DTPA), addressing the issue of risk factors for ischemic damage to the kidney. All patients undergoing RAPN for cT1 renal masses between June 2013 and May 2014 were included in this prospective study. Renal function as expressed by glomerular filtration rate (GFR) was assessed by Technetium 99m-diethylenetriaminepentaacetic acid (Tc 99m-DTPA) renal scan preoperatively and postoperatively at 1 month in every patient. A multivariable analysis was used for the determination of independent factors predictive of GFR decrease of the operated kidney. Overall, 32 patients underwent RAPN in the time interval. Median tumor size, blood loss, and ischemia time were 4 cm, 200 mL, and 24 min, respectively. Two grade III complications occurred (postoperative bleeding in the renal fossa, urinoma). The GFR of the operated kidney decreased significantly from 51.7 ± 15.1 mL/min per 1.73 m(2) preoperatively to 40, 12 ± 12.4 mL/min per 1.73 m(2) 1 month postoperatively (p = 0.001) with a decrease of 22.4 %. On multivariable analysis, only tumor size (p = 0.05) was a predictor of GFR decrease of the operated kidney. Robotic-assisted partial nephrectomy had a detectable impact on early renal function in a series of relatively large tumors and prevailing intermediate nephrometric risk. A mean decrease of 22 % of GFR as assessed by renal scan in the operated kidney was found at 1 month postoperatively. In multivariable analysis, tumor size only was a significant predictor of renal function loss.

Environment or Development? Lifetime Net CO2 Exchange and Control of the Expression of Crassulacean Acid Metabolism in Mesembryanthemum crystallinum1

PubMed Central

Winter, Klaus; Holtum, Joseph A.M.

2007-01-01

The relative influence of plant age and environmental stress signals in triggering a shift from C3 photosynthesis to Crassulacean acid metabolism (CAM) in the annual halophytic C3-CAM species Mesembryanthemum crystallinum was explored by continuously monitoring net CO2 exchange of whole shoots from the seedling stage until seed set. Plants exposed to high salinity (400 mm NaCl) in hydroponic culture solution or grown in saline-droughted soil acquired between 11% and 24% of their carbon via net dark CO2 uptake involving CAM. In contrast, plants grown under nonsaline, well-watered conditions were capable of completing their life cycle by operating in the C3 mode without ever exhibiting net CO2 uptake at night. These observations are not consistent with the widely expressed view that the induction of CAM by high salinity in M. crystallinum represents an acceleration of preprogrammed developmental processes. Rather, our study demonstrates that the induction of the CAM pathway for carbon acquisition in M. crystallinum is under environmental control. PMID:17056756

Gender difference following high cholesterol diet induced renal injury and the protective role of rutin and ascorbic acid combination in Wistar albino rats

PubMed Central

2012-01-01

Background An increased interest is given to the impact of high fat diet on health worldwide. Abnormalities in lipid metabolism induced by high cholesterol diet (HCD) were reported to exacerbate renal diseases via oxidative stress pathways. Rutin and ascorbic acid showed a protective role against oxidative stress-mediated diseases. Furthermore, both lipid metabolism and tissue response to oxidative stress damage was found to vary according to animal gender. Thus, the objective of this work was to examine possible gender-related differences and the possible protective effects of rutin and ascorbic acid supplementation on high cholesterol diet induced nephrotoxicity. Methods 96 young male and female Wistar albino rats were used. HCD supplemented animals were treated with rutin alone or in combination with ascorbic acid for 6 weeks. Creatinine plasma level was estimated. Furthermore, kidney levels of nucleic acids, total protein, malondialdehyde (MDA), reduced glutathione (GSH), total cholesterol, and triglycerides were determined. Finally, kidney tissues were used for histopathological examination. Results HCD supplementation decreased kidney level of nucleic acids, which was more prominent in female animals. Both vitamin combination significantly attenuated HCD induced decrease in nucleic acids. Moreover, kidney level of MDA was significantly altered by HCD in both genders, which was inhibited by rutin and ascorbic acid alone or in combination in male groups and by both vitamins in female groups. There was a reduction in kidney level of GSH by HCD, especially in male groups, which was attenuated by rutin and ascorbic acid combination. Kidney levels of total cholesterol and triglycerides were significantly increased by HCD supplementation in both genders. Coadministration with rutin and/or ascorbic acid protected from such increase, which was more obvious in both vitamins combination. Histopathological investigation supported vitamins protective effect, which was

Gender difference following high cholesterol diet induced renal injury and the protective role of rutin and ascorbic acid combination in Wistar albino rats.

PubMed

Al-Rejaie, Salim Salih; Abuohashish, Hatem Mustafa; Alkhamees, Osama Abdelrahman; Aleisa, Abdulaziz Mohammed; Alroujayee, Abdulaziz S

2012-03-16

An increased interest is given to the impact of high fat diet on health worldwide. Abnormalities in lipid metabolism induced by high cholesterol diet (HCD) were reported to exacerbate renal diseases via oxidative stress pathways. Rutin and ascorbic acid showed a protective role against oxidative stress-mediated diseases. Furthermore, both lipid metabolism and tissue response to oxidative stress damage was found to vary according to animal gender. Thus, the objective of this work was to examine possible gender-related differences and the possible protective effects of rutin and ascorbic acid supplementation on high cholesterol diet induced nephrotoxicity. 96 young male and female Wistar albino rats were used. HCD supplemented animals were treated with rutin alone or in combination with ascorbic acid for 6 weeks. Creatinine plasma level was estimated. Furthermore, kidney levels of nucleic acids, total protein, malondialdehyde (MDA), reduced glutathione (GSH), total cholesterol, and triglycerides were determined. Finally, kidney tissues were used for histopathological examination. HCD supplementation decreased kidney level of nucleic acids, which was more prominent in female animals. Both vitamin combination significantly attenuated HCD induced decrease in nucleic acids. Moreover, kidney level of MDA was significantly altered by HCD in both genders, which was inhibited by rutin and ascorbic acid alone or in combination in male groups and by both vitamins in female groups. There was a reduction in kidney level of GSH by HCD, especially in male groups, which was attenuated by rutin and ascorbic acid combination. Kidney levels of total cholesterol and triglycerides were significantly increased by HCD supplementation in both genders. Coadministration with rutin and/or ascorbic acid protected from such increase, which was more obvious in both vitamins combination. Histopathological investigation supported vitamins protective effect, which was more prominent in male

Cyclopiazonic acid augments the hepatic and renal oxidative stress in broiler chicks.

PubMed

Malekinejad, H; Akbari, P; Allymehr, M; Hobbenaghi, R; Rezaie, A

2011-08-01

Generation of reactive oxygen species (ROS) leads to serious tissue injuries. The effect of cyclopiazonic acid (CPA) on oxidative stress markers in the liver and kidneys of broiler chicks was studied. Ten-day-old male broiler chicks (Ross 308) were assigned into the control and test groups, which received normal saline and 10, 25, and 50 μg/kg CPA, respectively, for 28 days. Body weight gain, serum level of alkaline phosphatase (ALP), γ-glutamyl transferase (GGT), uric acid, creatinine, and blood urea nitrogen (BUN) were measured after 2 and 4 weeks exposure. Moreover, the total thiol molecules (TTM) and malondialdehyde (MDA) content of the liver and kidneys were assessed. No significant differences (p > 0.05) were found in body weight gain between the control and test groups. Whereas, the hepatic weight increased significantly (p < 0.05) in animals that received 25 and 50 μg/kg CPA. Both ALP and GGT level in serum were elevated in comparison to the control group. CPA also resulted in uric acid, creatinine, and BUN enhancement in broilers. The MDA content of the liver and kidneys showed remarkable increase. By contrast, the TTM levels in the liver and kidneys were significantly (p < 0.05) attenuated. Histopathological findings confirmed the biochemical changes in either organ characterized by inflammatory cells infiltration along with severe congestion and cell swelling, suggesting an inflammatory response. These data suggest that exposure to CPA resulted in hepatic and renal disorders, which were reflected as biochemical markers alteration and pathological injuries in either organ. The biochemical alteration and pathological abnormalities may be attributed to CPA-induced oxidative stress.

In vivo effects of high-dose steroids on nucleic acid content of immunocompetent cells of renal allograft recipients

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

Walle, A.J.; Wong, G.Y.; Suthanthiran, M.

1988-03-01

High-dose steroids administered to renal allograft recipients for treatment of acute graft rejection episodes may affect cell cycle progression of peripheral blood mononuclear (PBM) cells. DNA synthesis and cellular DNA and RNA contents of PBM cells were measured in 8 patients during clinically stable periods, and in another 10 patients both during acute rejection episodes and during 7 days of administration of high-dose steroids. Improved renal function documented successful reversal of the rejection episodes in the 10 patients. Compared with the stable patients, the rejecting patients had higher numbers of cells undergoing clonal expansion--namely, higher proportions of G1-cells and ofmore » proliferating, or S, G2, and M (SG2M) cells. Steroid treatment had no acute effects on proportions of G1 or SG2M cells in vivo or on incorporation of /sup 3/H thymidine by PBM cells in vitro. However, cells in the prereplicative compartment of the cell cycle (G0/1 cells) had significantly lower RNA content within 7 days of treatment with high doses of steroids. The results suggest that steroids do not acutely influence the posttranscriptional synthesis and the contents of nucleic acids of cells undergoing clonal expansion in vivo. The prereplicative phase of allogeneically stimulated PBM cells of renal allograft recipients may therefore be the cell cycle phase most sensitive to steroids in vivo.« less

Longitudinal development of renal damage and renal function in infants with high grade vesicoureteral reflux.

PubMed

Sjöström, Sofia; Jodal, Ulf; Sixt, Rune; Bachelard, Marc; Sillén, Ulla

2009-05-01

We sought to study renal abnormality and renal function through time in infants with high grade vesicoureteral reflux. This prospective observational study included 115 infants (80 boys and 35 girls) younger than 1 year with grade III to V vesicoureteral reflux. The diagnosis was made after prenatal ultrasound in 26% of the patients and after urinary tract infection in 71%. Patients were followed by renal scintigraphy, 51chromium edetic acid clearance and video cystometry. Median followup was 62 months. Renal abnormality, which was found in 90% of the children at followup, was generalized in 71% and focal in 29%. The abnormality was bilateral in 28% of the affected patients. Total glomerular filtration rate was less than 80% of expected in 30% of the patients. Single kidney function was less than 40% of expected total glomerular filtration rate in 71% of the patients. Renal status (parenchymal abnormality and function) remained unchanged through time in 84 of 108 available cases (78%), improved in 5 (5%) and deteriorated in 19 (18%). Predictive factors for deterioration were recurrent febrile urinary tract infection, bilateral abnormality and reduced total glomerular filtration rate. Deteriorated renal status was more common in cases diagnosed prenatally than in those detected after urinary tract infection. Among these infants with high grade vesicoureteral reflux renal abnormality was frequent and was associated with subnormal filtration of one of the kidneys. Decreased total glomerular filtration rate was seen in about a third of the patients. Overall deterioration of renal status was seen in only a fifth of the patients. Infection control seems to be an important factor to minimize the risk.

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.

Niacin improves renal lipid metabolism and slows progression in chronic kidney disease.

PubMed

Cho, Kyu-hyang; Kim, Hyun-ju; Kamanna, Vaijinath S; Vaziri, Nosratola D

2010-01-01

Mounting evidence points to lipid accumulation in the diseased kidney and its contribution to progression of nephropathy. We recently found heavy lipid accumulation and marked dysregulation of lipid metabolism in the remnant kidneys of rats with chronic renal failure (CRF). Present study sought to determine efficacy of niacin supplementation on renal tissue lipid metabolism in CRF. Kidney function, lipid content, and expression of molecules involved in cholesterol and fatty acid metabolism were determined in untreated CRF (5/6 nephrectomized), niacin-treated CRF (50 mg/kg/day in drinking water for 12 weeks) and control rats. CRF resulted in hypertension, proteinuria, renal tissue lipid accumulation, up-regulation of scavenger receptor A1 (SR-A1), acyl-CoA cholesterol acyltransferase-1 (ACAT1), carbohydrate-responsive element binding protein (ChREBP), fatty acid synthase (FAS), acyl-CoA carboxylase (ACC), liver X receptor (LXR), ATP binding cassette (ABC) A-1, ABCG-1, and SR-B1 and down-regulation of sterol responsive element binding protein-1 (SREBP-1), SREBP-2, HMG-CoA reductase, PPAR-alpha, fatty acid binding protein (L-FABP), and CPT1A. Niacin therapy attenuated hypertension, proteinuria, and tubulo-interstitial injury, reduced renal tissue lipids, CD36, ChREBP, LXR, ABCA-1, ABCG-1, and SR-B1 abundance and raised PPAR-alpha and L-FABP. Niacin administration improves renal tissue lipid metabolism and renal function and structure in experimental CRF.

Effect of Huanshuai Recipe Oral Liquid ([characters: see text]) on renal dysfunction progression in patients with atherosclerotic renal artery stenosis.

PubMed

Wang, Xiu-juan; Rao, Xiang-rong; Li, Shen; Wang, Li; Liu, Chang; Zhang, Gai-hua; Han, Dong-yan; Zhao, Yu; Zhang, Nan-nan; Li, Xue-xia; Chen, Shuai

2015-11-01

To investigate the effect of Huanshuai Recipe Oral Liquid ([characters: see text], HSR) on retarding the progression of renal dysfunction in patients with atherosclerotic renal artery stenosis (ARAS). A total of 52 ARAS patients with the Chinese medicine (CM) syndrome of qi deficiency and blood stasis, phlegm and dampness retention were recruited and randomly assigned into the treatment group (36 cases) and the control group (16 cases). Both groups received a basic treatment (high-quality low-protein diet, blood pressure control, lipid-lowering, correcting the acidosis, etc.). In addition, the treatment group received 20 mL HSR and the control group received placebo, 3 times a day for 6 months. Renal function (serum creatinine, blood urea nitrogen and uric acid) and blood lipids (cholesterol, triglycerides and low density lipoprotein) were examined monthly. The estimated glomerular filtration rate (eGFR) and CM syndrome score were compared between groups. After treatment, compared with the control group, the serum creatinine level, uric acid level and CM syndrome score of the treatment group were significantly decreased (P<0.05 or P<0.01), and the eGFR in the treatment group were significantly increased (P<0.05). HSR can effectively improve the renal function and clinical symptoms of ARAS patients.

Renal function and plasma volume following ultramarathon cycling.

PubMed

Neumayr, G; Pfister, R; Hoertnagl, H; Mitterbauer, G; Prokop, W; Joannidis, M

2005-01-01

In recreational cyclists marathon cycling influences renal function only on a minimal scale. Respective information on extreme ultramarathon cycling in better trained athletes is not available. The objective was to evaluate the renal and haematological effects of ultraendurance cycling in the world's best ultramarathon cyclists. Creatinine (CR), urea, haemoglobin (Hb), haematocrit (Hct) and plasma volume (PV) were investigated in 16 male ultramarathon cyclists during the 1st Race Across the Alps in 2001 (distance: 525 km; cumulative altitude difference: 12,600 m). All renal functional parameters were normal pre-exercise. During the race serum CR, urea and uric acid rose significantly by 33, 97 % and 18 % (p <0.001 respectively) and nearly normalised again on the following day. The decline in calculated CR clearance was 25 %. There was a negative correlation (r=- 0.575, p=0.02) between the rise in serum CR and the athlete's training kilometers. The serum urea/CR ratio rose above 40 in 12 athletes (75 %). Mean fractional sodium excretion and fractional uric acid excretion fell below 0.5 % (p <0.001) and 7 %, indicating reduced renal perfusion. The deflection of the renal functional parameters was temporary and nearly gone after 24 hours of recovery. Hct declined during the race from 0.44 to 0.42, and continued falling on the next day (0.42 --> 0.40; p <0.001). The corresponding rises in calculated PV were + 8 % and + 22 %. The study affirms that in world class cyclists the enormous strains of ultramarathon cycling influence renal function only on a minimal scale. The impact on the PV, however, is pronounced leading to marked haemodilution post-exercise. This very temporary "impairment of renal function" seems to be the physiological response to ultramarathon cycling and may be attenuated to some extent by preceding high-volume training.

New insights into the dynamic regulation of water and acid-base balance by renal epithelial cells.

PubMed

Brown, Dennis; Bouley, Richard; Păunescu, Teodor G; Breton, Sylvie; Lu, Hua A J

2012-05-15

Maintaining tight control over body fluid and acid-base homeostasis is essential for human health and is a major function of the kidney. The collecting duct is a mosaic of two cell populations that are highly specialized to perform these two distinct processes. The antidiuretic hormone vasopressin (VP) and its receptor, the V2R, play a central role in regulating the urinary concentrating mechanism by stimulating accumulation of the aquaporin 2 (AQP2) water channel in the apical membrane of collecting duct principal cells. This increases epithelial water permeability and allows osmotic water reabsorption to occur. An understanding of the basic cell biology/physiology of AQP2 regulation and trafficking has informed the development of new potential treatments for diseases such as nephrogenic diabetes insipidus, in which the VP/V2R/AQP2 signaling axis is defective. Tubule acidification due to the activation of intercalated cells is also critical to organ function, and defects lead to several pathological conditions in humans. Therefore, it is important to understand how these "professional" proton-secreting cells respond to environmental and cellular cues. Using epididymal proton-secreting cells as a model system, we identified the soluble adenylate cyclase (sAC) as a sensor that detects luminal bicarbonate and activates the vacuolar proton-pumping ATPase (V-ATPase) via cAMP to regulate tubular pH. Renal intercalated cells also express sAC and respond to cAMP by increasing proton secretion, supporting the hypothesis that sAC could function as a luminal sensor in renal tubules to regulate acid-base balance. This review summarizes recent advances in our understanding of these fundamental processes.

New insights into the dynamic regulation of water and acid-base balance by renal epithelial cells

PubMed Central

Bouley, Richard; Pǎunescu, Teodor G.; Breton, Sylvie; Lu, Hua A. J.

2012-01-01

Maintaining tight control over body fluid and acid-base homeostasis is essential for human health and is a major function of the kidney. The collecting duct is a mosaic of two cell populations that are highly specialized to perform these two distinct processes. The antidiuretic hormone vasopressin (VP) and its receptor, the V2R, play a central role in regulating the urinary concentrating mechanism by stimulating accumulation of the aquaporin 2 (AQP2) water channel in the apical membrane of collecting duct principal cells. This increases epithelial water permeability and allows osmotic water reabsorption to occur. An understanding of the basic cell biology/physiology of AQP2 regulation and trafficking has informed the development of new potential treatments for diseases such as nephrogenic diabetes insipidus, in which the VP/V2R/AQP2 signaling axis is defective. Tubule acidification due to the activation of intercalated cells is also critical to organ function, and defects lead to several pathological conditions in humans. Therefore, it is important to understand how these “professional” proton-secreting cells respond to environmental and cellular cues. Using epididymal proton-secreting cells as a model system, we identified the soluble adenylate cyclase (sAC) as a sensor that detects luminal bicarbonate and activates the vacuolar proton-pumping ATPase (V-ATPase) via cAMP to regulate tubular pH. Renal intercalated cells also express sAC and respond to cAMP by increasing proton secretion, supporting the hypothesis that sAC could function as a luminal sensor in renal tubules to regulate acid-base balance. This review summarizes recent advances in our understanding of these fundamental processes. PMID:22460710

In vitro effects of Panax ginseng in aristolochic acid-mediated renal tubulotoxicity: apoptosis versus regeneration.

PubMed

Bunel, Valérian; Antoine, Marie-Hélène; Nortier, Joëlle; Duez, Pierre; Stévigny, Caroline

2015-03-01

This in vitro study aimed to determine the effects of a Panax ginseng extract on aristolochic acid-mediated toxicity in HK-2 cells. A methanolic extract of ginseng (50 µg/mL) was able to reduce cell survival after treatment with 50 µM aristolochic acid for 24, 48, and 72 h, as evidenced by a resazurin reduction assay. This result was confirmed by a flow cytometric evaluation of apoptosis using annexin V-PI staining, and indicated higher apoptosis rates in cells treated with aristolochic acid and P. ginseng extract compared with aristolochic acid alone. However, P. ginseng extract by itself (5 and 50 µg/mL) increased the Ki-67 index, indicating an enhancement in cellular proliferation. Cell cycle analysis excluded a P. ginseng extract-mediated induction of G2/M cell cycle arrest such as the one typically observed with aristolochic acid. Finally, β-catenin acquisition was found to be accelerated when cells were treated with both doses of ginseng, suggesting that the epithelial phenotype of renal proximal tubular epithelial cells was maintained. Also, ginseng treatment (5 and 50 µg/mL) reduced the oxidative stress activity induced by aristolochic acid after 24 and 48 h. These results indicate that the ginseng extract has a protective activity towards the generation of cytotoxic reactive oxygen species induced by aristolochic acid. However, the ginseng-mediated alleviation of oxidative stress did not correlate with a decrease but rather with an increase in aristolochic acid-induced apoptosis and death. This deleterious herb-herb interaction could worsen aristolochic acid tubulotoxicity and reinforce the severity and duration of the injury. Nevertheless, increased cellular proliferation and migration, along with the improvement in the epithelial phenotype maintenance, indicate that ginseng could be useful for improving tubular regeneration and the recovery following drug-induced kidney injury. Such dual activities of ginseng certainly warrant further in vivo

Citric acid urine test

MedlinePlus

Urine - citric acid test; Renal tubular acidosis - citric acid test; Kidney stones - citric acid test; Urolithiasis - citric acid test ... No special preparation is necessary for this test. But the results ... test is usually done while you are on a normal diet. Ask your ...

Use of prazosin in management of hypertension in patients with chronic renal failure and in renal transplant recipients.

PubMed Central

Curtis, J R; Bateman, F J

1975-01-01

Prazosin was used in combination with other antihypertensive drugs in the successful management of hypertension in seven patients with chronic renal failure and six renal transplant recipients, also with chronic renal failure. The addition of small doses of prazosin (mean 3 mg/day) to the antihypertensive regimen produced significant falls in systolic and diastolic blood pressures in both the lying and standing positions. The standing blood pressures were significantly lower than the lying blood pressures during prazosin treatment. Neither the mean blood urea concentrations nor the mean plasma creatinine concentrations changed significantly during prazosin administration. Chromium-51 edetic acid clearances did not change significantly during prazosin treatment in the seven patients in whom it was measured. Severe symptomatic postural hypotension occurred in one patient a week after starting prazosin 3 mg/day. This hypotensive episode was associated with a transient and reversible deterioration in renal function. Another patient developed a rash while on prazosin but it was probably related to propranolol rather than prazosin. Prazosin is thus an effective antihypertensive drug in patients with chronic renal failure, and it may be used with a variety of other drugs. It should be used cautiously, however, since patients with chronic renal failure may respond to small doses, and significant postural falls in blood pressure may result. There was no evidence that the use of prazosin resulted in progressive deterioration in the residual renal function of the patients with chronic renal failure. PMID:811312

Use of prazosin in management of hypertension in patients with chronic renal failure and in renal transplant recipients.

PubMed

Curtis, J R; Bateman, F J

1975-11-22

Prazosin was used in combination with other antihypertensive drugs in the successful management of hypertension in seven patients with chronic renal failure and six renal transplant recipients, also with chronic renal failure. The addition of small doses of prazosin (mean 3 mg/day) to the antihypertensive regimen produced significant falls in systolic and diastolic blood pressures in both the lying and standing positions. The standing blood pressures were significantly lower than the lying blood pressures during prazosin treatment. Neither the mean blood urea concentrations nor the mean plasma creatinine concentrations changed significantly during prazosin administration. Chromium-51 edetic acid clearances did not change significantly during prazosin treatment in the seven patients in whom it was measured. Severe symptomatic postural hypotension occurred in one patient a week after starting prazosin 3 mg/day. This hypotensive episode was associated with a transient and reversible deterioration in renal function. Another patient developed a rash while on prazosin but it was probably related to propranolol rather than prazosin. Prazosin is thus an effective antihypertensive drug in patients with chronic renal failure, and it may be used with a variety of other drugs. It should be used cautiously, however, since patients with chronic renal failure may respond to small doses, and significant postural falls in blood pressure may result. There was no evidence that the use of prazosin resulted in progressive deterioration in the residual renal function of the patients with chronic renal failure.

Renal Involvement in Inflammatory Bowel Diseases.

PubMed

Corica, Domenico; Romano, Claudio

2016-02-01

The prevalence of extraintestinal manifestations in inflammatory bowel diseases varies from 6% to 46%. The aetiology of extraintestinal manifestations remains unclear. There are theories based on an immunological response influenced by genetic factors. Extraintestinal manifestations can involve almost every organ system. They may originate from the same pathophysiological mechanism of intestinal disease, or as secondary complications of inflammatory bowel diseases, or autoimmune diseases susceptibility. The most frequently involved organs are the joints, skin, eyes, liver and biliary tract. Renal involvement has been considered as an extraintestinal manifestation and has been described in both Crohn's disease and ulcerative colitis. The most frequent renal involvements in patients with inflammatory bowel disease are nephrolithiasis, tubulointerstitial nephritis, glomerulonephritis and amyloidosis. The aim of this review is to evaluate and report the most important data in the literature on renal involvement in patients with inflammatory bowel disease. Bibliographical searches were performed of the MEDLINE electronic database from January 1998 to January 2015 with the following key words (all fields): (inflammatory bowel disease OR Crohn's disease OR ulcerative colitis) AND (kidney OR renal OR nephrotoxicity OR renal function OR kidney disease OR renal disease OR glomerulonephritis OR interstitial nephritis OR amyloidosis OR kidney failure OR renal failure) AND (5-aminosalicylic acid OR aminosalicylate OR mesalazine OR TNF-α inhibitors OR cyclosporine OR azathioprine OR drugs OR pediatric). Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Net Acid Production, Acid Neutralizing Capacity, and Associated Mineralogical and Geochemical Characteristics of Animas River Watershed Igneous Rocks Near Silverton, Colorado

USGS Publications Warehouse

Yager, Douglas B.; Choate, LaDonna; Stanton, Mark R.

2008-01-01

This report presents results from laboratory and field studies involving the net acid production (NAP), acid neutralizing capacity (ANC), and magnetic mineralogy of 27 samples collected in altered volcanic terrain in the upper Animas River watershed near Silverton, Colo., during the summer of 2005. Sampling focused mainly on the volumetrically important, Tertiary-age volcanic and plutonic rocks that host base- and precious-metal mineralization in the study area. These rocks were analyzed to determine their potential for neutralization of acid-rock drainage. Rocks in the study area have been subjected to a regional propylitic alteration event, which introduced calcite, chlorite (clinochlore), and epidote that have varying amounts and rates of acid neutralizing capacity (ANC). Locally, hydrothermal alteration has consumed any ANC and introduced minerals, mainly pyrite, that have a high net acid production (NAP). Laboratory studies included hydrogen pyroxide (H2O2) acid digestion and subsequent sodium hydroxide (NaOH) titration to determine NAP, and sulfuric acid (H2SO4) acid titration experiments to determine ANC. In addition to these environmental rock-property determinations, mineralogical, chemical, and petrographic characteristics of each sample were determined through semiquantitative X-ray diffractometry (Rietveld method), optical mineralogy, wavelength dispersive X-ray fluorescence, total carbon-carbonate, and inductively coupled plasma?mass spectrometric analysis. An ANC ranking was assigned to rock samples based on calculated ANC quantity in kilograms/ton (kg/t) calcium carbonate equivalent and ratios of ANC to NAP. Results show that talus near the southeast Silverton caldera margin, composed of andesite clasts of the Burns Member of the Silverton Volcanics, has the highest ANC (>100 kg/t calcium carbonate equivalent) with little to no NAP. The other units found to have moderate to high ANC include (a) andesite lavas and volcaniclastic rocks of the San Juan

Effects of microgravity on renal stone risk assessment

NASA Technical Reports Server (NTRS)

Pietrzyk, R. A.; Pak, C. Y. C.; Cintron, N. M.; Whitson, P. A.

1992-01-01

Physiologic changes induced during human exposure to the microgravity environment of space may contribute to an increased potential for renal stone formation. Renal stone risk factors obtained 10 days before flight and immediately after return to earth indicated that calcium oxalate and uric acid stone-forming potential was increased after space flights of 4-10 days. These data describe the need for examining renal stone risk during in-flight phases of space missions. Because of limited availability of space and refrigerated storage on spacecraft, effective methods must be developed for collecting urine samples in-flight and for preserving (or storing) them at temperatures and under conditions commensurate with mission constraints.

Contributions of nuclear magnetic resonance to renal biochemistry

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

Ross, B.; Freeman, D.; Chan, L.

/sup 31/P NMR as a descriptive technique is of interest to nephrologists. Particular contributions of /sup 31/P NMR to our understanding of renal function may be enumerated.: Free metabolite levels are different from those classically accepted; in particular, ADP and Pi are low with implications for the control of renal metabolism and Pi transport, and, via the phosphorylation potential, for Na+ transport. Renal pH is heterogeneous; between cortex, outer medulla, and papilla, and between cell and lumen, a large pH gradient exists. Also, quantitation between cytosol and mitochondrion of the pH gradient is now feasible. In acute renal failure ofmore » either ischemic or nonischemic origin, both ATP depletion and acidification of the renal cell result in damage, with increasing evidence for the importance of the latter. Measurements of renal metabolic rate in vivo suggest the existence of a prodromal phase of acute renal failure, which could lead to its detection at an earlier and possibly reversible stage. Human renal cancers show a unique /sup 31/P NMR spectrum and a very acidic environment. Cancer chemotherapy may alter this and detection of such changes with NMR offers a method of therapeutic monitoring with significance beyond nephrology. Renal cortex and medulla have a different T1 relaxation time, possibly due to differences in lipid composition. It seems that NMR spectroscopy has much to offer to the future understanding of the relationship between renal biochemistry and function. 56 references.« less

Well Preserved Renal Function in Children With Untreated Chronic Liver Disease.

PubMed

Berg, Ulla B; Németh, Antal

2018-04-01

On the basis of studies with hepatorenal syndrome, it is widely regarded that renal function is impacted in chronic liver disease (CLD). Therefore, we investigated renal function in children with CLD. In a retrospective study of 277 children with CLD, renal function was investigated as glomerular filtration rate (GFR) and effective renal plasma flow (ERPF), measured as clearance of inulin and para-amino hippuric acid or clearance of iohexol. The data were analyzed with regard to different subgroups of liver disease and to the grade of damage. Hyperfiltration (>+2 SD of controls) was found in the subgroups of progressive familial intrahepatic cholestasis (44%), glycogenosis (75%), and acute fulminant liver failure (60%). Patients with biliary atresia, most other patients with metabolic disease and intrahepatic cholestasis, and those with vascular anomalies and cryptogenic cirrhosis had normal renal function. Decreased renal function was found in patients with Alagille's syndrome (64% < -2 SD). Increased GFR and ERPF was found in patients with elevated transaminases, low prothrombin level, high bile acid concentration, and high aspartate-aminotransferase-to-platelet ratio. Most children with CLD had surprisingly well preserved renal function and certain groups had even hyperfiltration. The finding that children with decompensated liver disease and ongoing liver failure had stable kidney function suggests that no prognostic markers of threatening hepatorenal syndrome were at hand. Moreover, estimation of GFR based on serum creatinine fails to reveal hyperfiltration.

Renal Calculi

PubMed Central

Yendt, E. R.

1970-01-01

The pathogenesis of renal calculi is reviewed in general terms followed by the results of investigation of 439 patients with renal calculi studied by the author at Toronto General Hospital over a 13-year period. Abnormalities of probable pathogenetic significance were encountered in 76% of patients. Idiopathic hypercalciuria was encountered in 42% of patients, primary hyperparathyroidism in 11%, urinary infection in 8% and miscellaneous disorders in 8%. The incidence of uric acid stones and cystinuria was 5% and 2% respectively. In the remaining 24% of patients in whom no definite abnormalities were encountered the mean urinary magnesium excretion was less than normal. Of 180 patients with idiopathic hypercalciuria, only 24 were females. In the diagnosis of hyperparathyroidism, the importance of detecting minimal degrees of hypercalcemia is stressed; attention is also drawn to the new observation that the upper limit of normal for serum calcium is slightly lower in females than in males. The efficacy of various measures advocated for the prevention of renal calculi is also reviewed. In the author's experience the administration of thiazides has been particularly effective in the prevention of calcium stones. Thiazides cause a sustained reduction in urinary calcium excretion and increase in urinary magnesium excretion. These agents also appear to affect the skeleton by diminishing bone resorption and slowing down bone turnover. PMID:5438766

Metronidazole pharmacokinetics in patients with acute renal failure.

PubMed

Somogyi, A A; Kong, C B; Gurr, F W; Sabto, J; Spicer, W J; McLean, A J

1984-02-01

The pharmacokinetics and metabolism of intravenous metronidazole were studied in six patients with acute renal failure. In two of the patients a single dose (500 mg) of metronidazole was administered, whereas in four patients the steady-state pharmacokinetics were studied after four days therapy of 500 mg twice daily. Plasma concentrations of metronidazole and its hydroxy and acetic acid metabolites were measured by a specific and sensitive HPLC method. The volume of distribution was 0.65 +/- 0.13 l/kg (mean +/- S.D.), elimination half-life was 9.9 +/- 2.5 h and total plasma clearance was 55.5 +/- 17.7 ml/min. Renal clearance was almost non-existent (1.4 +/- 1.4 ml/min), whereas non-renal clearance was 54.0 +/- 18.2 ml/min. Steady-state plasma concentrations of metronidazole were 15.3 +/- 3.8 mg/l, the hydroxy metabolite were 17.4 +/- 2.0 mg/l and the acetic acid metabolite were 1.2 +/- 0.8 mg/l. In the patients studied, a dosing regimen of 500 mg twice daily resulted in therapeutically adequate blood levels of metronidazole.

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

Aristolochic Acid in the Etiology of Renal Cell Carcinoma

PubMed Central

Hoang, Margaret L.; Chen, Chung-Hsin; Chen, Pau-Chung; Roberts, Nicholas J.; Dickman, Kathleen G.; Yun, Byeong Hwa; Turesky, Robert J.; Pu, Yeong-Shiau; Vogelstein, Bert; Papadopoulos, Nickolas; Grollman, Arthur P.; Kinzler, Kenneth W.; Rosenquist, Thomas A.

2017-01-01

Background Aristolochia species used in the practice of traditional herbal medicine contains aristolochic acid (AA), an established human carcinogen contributing to urothelial carcinomas of the upper urinary tract. AA binds covalently to genomic DNA, forming aristolactam (AL)–DNA adducts. Here we investigated whether AA is also an etiologic factor in clear cell renal cell carcinoma (ccRCC). Methods We conducted a population-based case–control study to investigate the linkage between Aristolochia prescription history, cumulative AA consumption, and ccRCC incidence in Taiwan (5,709 cases and 22,836 matched controls). The presence and level of mutagenic dA-AL-I adducts were determined in the kidney DNA of 51 Taiwanese ccRCC patients. The whole-exome sequences of ccRCC tumors from 10 Taiwanese ccRCC patients with prior exposure to AA were determined. Results Cumulative ingestion of more than 250 mg of AA increased risk of ccRCC (OR, 1.25), and we detected dA-AL-I adducts in 76% of Taiwanese ccRCC patients. Furthermore, the distinctive AA mutational signature was evident in six of 10 sequenced ccRCC exomes from Taiwanese patients. Conclusions This study strongly suggests that AA contributes to the etiology of certain RCCs. Impact The current study offers compelling evidence implicating AA in a significant fraction of the RCC arising in Taiwan and illustrates the power of integrating epidemiologic, molecular, and genetic data in the investigation of cancer etiology. PMID:27555084

Panel-reactive antibody levels and renal transplantation rates in sensitized patients after desensitization and human leucocyte antigen amino acid residue matching.

PubMed

Shang, Wenjun; Dong, Laidong; Feng, Guiwen; Wang, Yue; Pang, Xinlu; Li, Jinfeng; Liu, Lei; Zhang, Weihong

2013-08-01

To determine whether a new desensitization protocol (mycophenolate mofetil [MMF], plasmapheresis and antithymocyte globulin [ATG], complemented with human leucocyte antigen [HLA] amino acid residue matching) could reduce panel-reactive antibody (PRA) levels in sensitized patients, to facilitate successful renal transplantation. Patients awaiting transplantation with PRA levels >10% received treatment with MMF; those with PRA levels >30% were also treated with plasmapheresis. Patients whose PRA level was <20% after desensitization were eligible for transplantation. When a donor became available, traditional HLA matching and HLA amino acid residue matching were performed. All patients received ATG induction therapy postoperatively. Thirty-two sensitized patients were enrolled. Desensitization produced a significant decrease in PRA levels; 27 patients (84.4%) became eligible for transplantation and 26 (81.2%) subsequently underwent successful transplantation. Residue matching improved the proportion with a mismatch number of 0-1 from 7.7% to 65.4%, compared with traditional HLA matching. Postoperatively, all patients showed immediate graft function. Acute rejection occurred in three patients (11.5%) and infections in seven patients (25.9%); all were treated successfully. The combination of a desensitization protocol (MMF, plasmapheresis and ATG) and residue matching appears to be an effective strategy for sensitized patients awaiting renal transplantation.

Maternal supplementation with citrulline increases renal nitric oxide in young spontaneously hypertensive rats and has long-term antihypertensive effects.

PubMed

Koeners, Maarten P; van Faassen, Ernst E; Wesseling, Sebastiaan; de Sain-van der Velden, Monique; Koomans, Hein A; Braam, Branko; Joles, Jaap A

2007-12-01

NO deficiency is associated with development of hypertension. Defects in the renal citrulline-arginine pathway or arginine reabsorption potentially reduce renal NO in prehypertensive spontaneously hypertensive rats (SHRs). Hence, we investigated genes related to the citrulline-arginine pathway or arginine reabsorption, amino acid pools, and renal NO in 2-week-old prehypertensive SHRs. In addition, because perinatally supporting NO availability reduces blood pressure in SHRs, we supplemented SHR dams during pregnancy and lactation with citrulline, the rate-limiting amino acid for arginine synthesis. In female offspring, gene expression of argininosuccinate synthase (involved in renal arginine synthesis) and renal cationic amino acid Y-transporter (involved in arginine reabsorption) were both decreased in 2-day and 2-week SHRs compared with normotensive WKY, although no abnormalities in amino acid pools were observed. In addition, 2-week-old female SHRs had much less NO in their kidneys (0.46+/-0.01 versus 0.68+/-0.05 nmol/g of kidney weight, respectively; P<0.001) but not in their heart. Furthermore, perinatal supplementation with citrulline increased renal NO to 0.59+/-0.02 nmol/g of kidney weight (P<0.001) at 2 weeks and persistently ameliorated the development of hypertension in females and until 20 weeks in male SHR offspring. Defects in both the renal citrulline-arginine pathway and in arginine reabsorption precede hypertension in SHRs. We propose that the reduced cationic amino acid transporter disables the developing SHR kidney to use arginine reabsorption to compensate for reduced arginine synthesis, resulting in organ-specific NO deficiency. This early renal deficiency and its adverse sequels can be corrected by perinatal citrulline supplementation persistently in female and transiently in male SHRs.

Lack of formic acid production in rat hepatocytes and human renal proximal tubule cells exposed to chloral hydrate or trichloroacetic acid

PubMed Central

Lock, Edward A; Reed, Celia J; McMillan, JoEllyn M; Oatis, John R; Schnellmann, Rick G

2007-01-01

The industrial solvent trichloroethylene (TCE) and its major metabolites have been shown to cause formic aciduria in male rats. We have examined whether chloral hydrate (CH) and trichloroacetic acid (TCA), known metabolites of TCE, produce an increase in formic acid in vitro in cultures of rat hepatocytes or human renal proximal tubule cells (HRPTC). The metabolism and cytotoxicity of CH was also examined to establish that the cells were metabolically active and not compromised by toxicity. Rat hepatocytes and HRPTC were cultured in serum-free medium and then treated with 0.3–3mM CH for 3 days or 0.03–3mM CH for 10 days respectively and formic acid production, metabolism to trichloroethanol (TCE-OH) and TCA and cytotoxicity determined. No increase in formic acid production in rat hepatocytes or HRPTC exposed to CH was observed over and above that due to chemical degradation, neither was formic acid production observed in rat hepatocytes exposed to TCA. HRPTC metabolised CH to TCE-OH and TCA with a 12-fold greater capacity to form TCE-OH versus TCA. Rat hepatocytes exhibited a 1.6-fold and 3-fold greater capacity than HRPTC to form TCE-OH and TCA respectively. CH and TCA were not cytotoxic to rat hepatocytes at concentrations up to 3mM/day for 3 days. With HRPTC, one sample showed no cytotoxicity to CH at concentrations up to 3mM/day for 10 days, while in another cytotoxicity was seen at 1mM/day for 3 days. In summary, increased formic acid production was not observed in rat hepatocytes or HRPTC exposed to TCE metabolites, suggesting that the in vivo response cannot be modelled in vitro. CH was toxic to HRPTC at millimolar concentrations/day over 10 days, while glutathione derived metabolites of TCE were toxic at micromolar concentrations/day over 10 days (Lock et al., 2006) supporting the view that glutathione derived metabolites are likely to be responsible for nephrotoxicity. PMID:17161896

Folic Acid and Grape Seed Extract Prevent Azathioprine-induced Fetal Malformations and Renal Toxicity in Rats.

PubMed

El-Ashmawy, Ibrahim M; Bayad, Aida E

2016-12-01

Azathioprine (AZA) is an important drug commonly used in the therapy of the autoimmune system disorders. It induces many hazard effects that restrict its use. The present study was designed to investigate the influence of AZA on the fetal development and renal function and its co-administration with either folic acid (FA) or grape seed extract (GSE). The effects of administration of GSE or FA on AZA toxicity by gavage simultaneously for 4 weeks were studied by determining the changes in kidney histology, the glutathione level (GSH), and lipid per oxidation content as malondialdehyde in the kidney tissue. Additionally, their effects on the fetal development were investigated. Azathioprine induced a renal damage as indicated from the pronounced changes in histological structure, a significant increase in serum urea and creatinine, and malondialdehyde content in the kidney tissue. Meanwhile, the GSH activity was significantly decreased. Co-treatment with GSE significantly minimized the previously mentioned hazard effects of AZA by ameliorating the antioxidant activity. At this point, FA induced a nonsignificant protective activity. The results also revealed that administration of FA or GSE at 6th to 15th day of gestation did not altered fetal development. While, AZA administration clearly disturbed fetal development as indicated from a significant decrease in fetal weights. Furthermore, co-administration of both drugs significantly minimized similarly the hazards of AZA on the fetal development. It may be concluded that GSE and FA are a useful remedies. Maternal administrations of either both are protective agents against AZA-induced fetal malformations. Grape seed extract was more active than FA in potentiating the antioxidative defenses for controlling AZA-induced oxidative renal damages. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Multidrug Resistance Proteins and the Renal Elimination of Inorganic Mercury Mediated by 2,3-Dimercaptopropane-1-Sulfonic Acid and Meso-2,3-dimercaptosuccinic Acid

PubMed Central

Bridges, Christy C.; Joshee, Lucy; Zalups, Rudolfs K.

2008-01-01

Current therapies for inorganic mercury (Hg2+) intoxication include administration of a metal chelator, either 2,3-dimercaptopropane-1-sulfonic acid (DMPS) or meso-2,3-dimercaptosuccinic acid (DMSA). After exposure to either chelator, Hg2+ is rapidly eliminated from the kidneys and excreted in the urine, presumably as an S-conjugate of DMPS or DMSA. The multidrug resistance protein 2 (Mrp2) has been implicated in this process. We hypothesize that Mrp2 mediates the secretion of DMPS- or DMSA-S-conjugates of Hg2+ from proximal tubular cells. To test this hypothesis, the disposition of Hg2+ was examined in control and Mrp2-deficient TR− rats. Rats were injected i.v. with 0.5 μmol/kg HgCl2 containing 203Hg2+. Twenty-four and 28 h later, rats were injected with saline, DMPS, or DMSA. Tissues were harvested 48 h after HgCl2 exposure. The renal and hepatic burden of Hg2+ in the saline-injected TR− rats was greater than that of controls. In contrast, the amount of Hg2+ excreted in urine and feces of TR− rats was less than that of controls. DMPS, but not DMSA, significantly reduced the renal and hepatic content of Hg2+ in both groups of rats, with the greatest reduction in controls. A significant increase in urinary and fecal excretion of Hg2+, which was greater in the controls, was also observed following DMPS treatment. Experiments utilizing inside-out membrane vesicles expressing MRP2 support these observations by demonstrating that DMPS- and DMSA-S-conjugates of Hg2+ are transportable substrates of MRP2. Collectively, these data support a role for Mrp2 in the DMPS- and DMSA-mediated elimination of Hg2+ from the kidney. PMID:17940195

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

Influence of hesperidin on renal cell surface glycoprotein content, nucleic acids, lysosomal enzymes and macromolecules against 7, 12-dimethylbenz [a] anthracene induced experimental breast carcinoma.

PubMed

Nandakumar, Natarajan; Jayaprakash, Ramachandran; Balasubramanian, Maruthaiveeran Periyasamy

2012-01-01

Therapeutic substances may reduce the risk of developing cancer by modulating the factors responsible for carcinogenesis. To evaluate these hypotheses, the present study was designed to investigate the modulatory effect of bioflavonoid "Hesperidin" against DMBA induced experimental breast cancer with reference to renal cell surface glycoproteins, nucleic acids, protein content, lipid profile and lysosomal enzymes. The female sprague-dawley rats were orally administered with single dose of 7, 12-DMBA to induce breast cancer and were treated with hesperidin [30 mg/kg/body weight] for a consecutive 45 days. The results revealed that there was a significant elevation in the levels of glycoproteins, nucleic acids, lysosomal enzymes and also significant alterations in macromolecules in renal tissues of cancer bearing animals. Interestingly, the altered levels of these parameters were remarkably reverted back to near normal in hesperidin treatment. The histopathological analysis of liver and kidney tissues were well supported the biochemical alterations and inevitably proves the protective role of hesperidin. It is proposed that, the effect of hesperidin during DMBA induced breast cancer could be due to the intervention strategies of hesperidin in the protein, nucleic acid biosynthesis, membrane stabilizing potentials on lysosomal compartment and inhibitory effect on cell surface glycoproteins and bio-fuel such as lipids.

Assessment of melamine and cyanuric acid toxicity in cats.

PubMed

Puschner, Birgit; Poppenga, Robert H; Lowenstine, Linda J; Filigenzi, Michael S; Pesavento, Patricia A

2007-11-01

The major pet food recall associated with acute renal failure in dogs and cats focused initially on melamine as the suspect toxicant. In the course of the investigation, cyanuric acid was identified in addition to melamine in the offending food. The purpose of this study was to characterize the toxicity potential of melamine, cyanuric acid, and a combination of melamine and cyanuric acid in cats. In this pilot study, melamine was added to the diet of 2 cats at 0.5% and 1%, respectively. Cyanuric acid was added to the diet of 1 cat at increasing doses of 0.2%, 0.5%, and 1% over the course of 10 days. Melamine and cyanuric acid were administered together at 0%, 0.2%, 0.5%, and 1% to 1 cat per dose group. No effect on renal function was observed in cats fed with melamine or cyanuric acid alone. Cats dosed with a combination were euthanized at 48 hours after dosing because of acute renal failure. Urine and touch impressions of kidneys from all cats dosed with the combination revealed the presence of fan-shaped, birefringent crystals. Histopathologic findings were limited to the kidneys and included crystals primarily within tubules of the distal nephron, severe renal interstitial edema, and hemorrhage at the corticomedullary junction. The kidneys contained estimated melamine concentrations of 496 to 734 mg/kg wet weight and estimated cyanuric acid concentrations of 487 to 690 mg/kg wet weight. The results demonstrate that the combination of melamine and cyanuric acid is responsible for acute renal failure in cats.

Renal Hemodynamics in AKI: In Search of New Treatment Targets.

PubMed

Matejovic, Martin; Ince, Can; Chawla, Lakhmir S; Blantz, Roland; Molitoris, Bruce A; Rosner, Mitchell H; Okusa, Mark D; Kellum, John A; Ronco, Claudio

2016-01-01

Novel therapeutic interventions are required to prevent or treat AKI. To expedite progress in this regard, a consensus conference held by the Acute Dialysis Quality Initiative was convened in April of 2014 to develop recommendations for research priorities and future directions. Here, we highlight the concepts related to renal hemodynamics in AKI that are likely to reveal new treatment targets on investigation. Overall, we must better understand the interactions between systemic, total renal, and glomerular hemodynamics, including the role of tubuloglomerular feedback. Furthermore, the net consequences of therapeutic maneuvers aimed at restoring glomerular filtration need to be examined in relation to the nature, magnitude, and duration of the insult. Additionally, microvascular blood flow heterogeneity in AKI is now recognized as a common occurrence; timely interventions to preserve the renal microcirculatory flow may interrupt the downward spiral of injury toward progressive kidney failure and should, therefore, be investigated. Finally, development of techniques that permit an integrative physiologic approach, including direct visualization of renal microvasculature and measurement of oxygen kinetics and mitochondrial function in intact tissue in all nephron segments, may provide new insights into how the kidney responds to various injurious stimuli and allow evaluation of new therapeutic strategies. Copyright © 2016 by the American Society of Nephrology.

Renal Hemodynamics in AKI: In Search of New Treatment Targets

PubMed Central

Matejovic, Martin; Ince, Can; Chawla, Lakhmir S.; Blantz, Roland; Molitoris, Bruce A.; Okusa, Mark D.; Kellum, John A.; Ronco, Claudio

2016-01-01

Novel therapeutic interventions are required to prevent or treat AKI. To expedite progress in this regard, a consensus conference held by the Acute Dialysis Quality Initiative was convened in April of 2014 to develop recommendations for research priorities and future directions. Here, we highlight the concepts related to renal hemodynamics in AKI that are likely to reveal new treatment targets on investigation. Overall, we must better understand the interactions between systemic, total renal, and glomerular hemodynamics, including the role of tubuloglomerular feedback. Furthermore, the net consequences of therapeutic maneuvers aimed at restoring glomerular filtration need to be examined in relation to the nature, magnitude, and duration of the insult. Additionally, microvascular blood flow heterogeneity in AKI is now recognized as a common occurrence; timely interventions to preserve the renal microcirculatory flow may interrupt the downward spiral of injury toward progressive kidney failure and should, therefore, be investigated. Finally, development of techniques that permit an integrative physiologic approach, including direct visualization of renal microvasculature and measurement of oxygen kinetics and mitochondrial function in intact tissue in all nephron segments, may provide new insights into how the kidney responds to various injurious stimuli and allow evaluation of new therapeutic strategies. PMID:26510884

Cellular distribution of cell cycle-related molecules in the renal tubules of rats treated with renal carcinogens for 28 days: relationship between cell cycle aberration and carcinogenesis.

PubMed

Taniai, Eriko; Hayashi, Hitomi; Yafune, Atsunori; Watanabe, Maiko; Akane, Hirotoshi; Suzuki, Kazuhiko; Mitsumori, Kunitoshi; Shibutani, Makoto

2012-09-01

Some renal carcinogens can induce karyomegaly, which reflects aberrant cell division in the renal tubules, from the early stages of exposure. To clarify the cell cycle-related changes during the early stages of renal carcinogenesis, we performed immunohistochemical analysis of tubular cells in male F344 rats treated with carcinogenic doses of representative renal carcinogens for 28 days. For this purpose, the karyomegaly-inducing carcinogens ochratoxin A (OTA), ferric nitrilotriacetic acid, and monuron, and the non-karyomegaly-inducing carcinogens tris(2-chloroethyl) phosphate and potassium bromate were examined. For comparison, a karyomegaly-inducing non-carcinogen, p-nitrobenzoic acid, and a non-carcinogenic non-karyomegaly-inducing renal toxicant, acetaminophen, were also examined. The outer stripe of the outer medulla (OSOM) and the cortex + OSOM were subjected to morphometric analysis of immunoreactive proximal tubular cells. Renal carcinogens, irrespective of their karyomegaly-inducing potential, increased proximal tubular cell proliferation accompanied by an increase in topoisomerase IIα-immunoreactive cells, suggesting a reflection of cell proliferation. Karyomegaly-inducing carcinogens increased nuclear Cdc2-, γH2AX-, and phosphorylated Chk2-immunoreactive cells in both areas, the former two acting in response to DNA damage and the latter one suggestive of sustained G₂. OTA, an OSOM-targeting carcinogen, could easily be distinguished from untreated controls and non-carcinogens by evaluation of molecules responding to DNA damage and G₂/M transition in the OSOM. Thus, all renal carcinogens examined facilitated proximal tubular proliferation by repeated short-term treatment. Among these, karyomegaly-inducing carcinogens may cause DNA damage and G₂ arrest in the target tubular cells.

Comorbid renal tubular damage and hypoalbuminemia exacerbate cardiac prognosis in patients with chronic heart failure.

PubMed

Otaki, Yoichiro; Watanabe, Tetsu; Takahashi, Hiroki; Funayama, Akira; Kinoshita, Daisuke; Yokoyama, Miyuki; Takahashi, Tetsuya; Nishiyama, Satoshi; Arimoto, Takanori; Shishido, Tetsuro; Miyamoto, Takuya; Konta, Tsuneo; Kubota, Isao

2016-02-01

Renal tubular damage (RTD) and hypoalbuminemia are risks for poor prognosis in patients with chronic heart failure (CHF). Renal tubules play a pivotal role in amino acid and albumin reabsorption, which maintain serum albumin levels. The aims of the present study were to (1) examine the association of RTD with hypoalbuminemia, and (2) assess the prognostic importance of comorbid RTD and hypoalbuminemia in patients with CHF. We measured N-acetyl-β-D-glucosamidase (NAG) levels and the urinary β2-microglobulin to creatinine ratio (UBCR) in 456 patients with CHF. RTD was defined as UBCR ≥ 300 μg/g or NAG ≥ 14.2 U/g. There were moderate correlations between RTD markers and serum albumin (NAG, r = -0.428, P < 0.0001; UBCR, r = -0.399, P < 0.0001). Multivariate logistic analysis showed that RTD was significantly related to hypoalbuminemia in patients with CHF. There were 134 cardiac events during a median period of 808 days. The comorbidity of RTD and hypoalbuminemia was increased with advancing New York Heart Association functional class. Multivariate Cox proportional hazard regression analysis showed that the presence of RTD and hypoalbuminemia was associated with cardiac events. The net reclassification index was significantly improved by adding RTD and hypoalbuminemia to the basic risk factors. Comorbid RTD and hypoalbuminemia are frequently observed and increase the risk for extremely poor outcome in patients with CHF.

Partitioning of nutrient net fluxes across the portal-drained viscera in sheep fed twice daily: effect of dietary protein degradability.

PubMed

Rémond, Didier; Bernard, Laurence; Savary-Auzeloux, Isabelle; Nozière, Pierre

2009-08-01

Extrusion is used to decrease leguminous seed protein degradability in the rumen in order to shift part of the dietary protein digestion towards the small intestine. The effect of such displacement of digestion site on the partitioning of nutrient net fluxes across the gastrointestinal tract was studied using four sheep fitted with catheters and blood-flow probes, allowing measurements across the rumen, the mesenteric-drained viscera (MDV) and the portal-drained viscera (PDV). Two diets containing 34 % of pea seeds were tested in a crossover design. They differed only according to pea treatment: raw pea (RP) or extruded pea (EP) diet. Rumen undegradable protein (RUP) accounted for 23 and 40 % of dietary crude protein for RP and EP diets, respectively. Across the rumen wall, ammonia net flux was lower with EP diet, whereas urea net flux was not different. Across the MDV, free amino acid (FAA) net flux was greater with EP diet, whereas peptide amino acid net flux was not different, accounting for 7 % of the non-protein amino acid net release. From RP to EP diet, PDV net flux of ammonia decreased by 23 %, whereas FAA net release increased by 21 %. The difference in dietary RUP did not affect the PDV net flux of SCFA, 3-hydroxybutyrate, lactate and glucose. In conclusion, the partial shift in pea protein digestion from the rumen to the small intestine did not affect the portal net balance of N, but decreased N loss from the rumen, and increased amino acid intestinal absorption and portal delivery.

The dopamine precursor L-dihydroxyphenylalanine is transported by the amino acid transporters rBAT and LAT2 in renal cortex.

PubMed

Quiñones, Henry; Collazo, Roberto; Moe, Orson W

2004-07-01

The intrarenal autocrine-paracrine dopamine (DA) system is critical for Na(+) homeostasis. l-Dihydroxyphenylalanine (l-DOPA) uptake from the glomerular filtrate and plasma provides the substrate for DA generation by the renal proximal tubule. The transporter(s) responsible for proximal tubule l-DOPA uptake has not been characterized. Renal cortical poly-A(+) RNA injected into Xenopus laevis oocytes induced l-DOPA uptake in a time- and dose-dependent fashion with biphasic K(m)s in the millimolar and micromolar range and independent of inward Na(+), K(+), or H(+) gradients, suggesting the presence of low- and high-affinity l-DOPA carriers. Complementary RNA from two amino acid transporters yielded l-DOPA uptake significantly above water-injected controls the rBAT/b(0,+)AT dimer (rBAT) and the LAT2/4F2 dimer (LAT2). In contradistinction to renal cortical poly-A(+), l-DOPA kinetics of rBAT and LAT2 showed classic Michaelis-Menton kinetics with K(m)s in the micromolar and millimolar range, respectively. Sequence-specific antisense oligonucleotides to rBAT or LAT2 (AS) caused inhibition of rBAT and LAT2 cRNA-induced l-DOPA transport and cortical poly-A(+)-induced arginine and phenylalanine transport. However, the same ASs only partially blocked poly-A(+)-induced l-DOPA transport. In cultured kidney cells, silencing inhibitory RNA (siRNA) to rBAT significantly inhibited l-DOPA uptake. We conclude that rBAT and LAT2 can mediate apical and basolateral l-DOPA uptake into the proximal tubule, respectively. Additional l-DOPA transport mechanisms exist in the renal cortex that remain to be identified.

Effect of Γ-aminobutyric acid on kidney injury induced by renal ischemia-reperfusion in male and female rats: Gender-related difference.

PubMed

Vafapour, Marzieh; Nematbakhsh, Mehdi; Monajemi, Ramesh; Mazaheri, Safoora; Talebi, Ardeshir; Talebi, Nahid; Shirdavani, Soheyla

2015-01-01

The most important cause of kidney injury is renal ischemia/reperfusion injury (IRI), which is gender-related. This study was designed to investigate the protective role of Γ-aminobutyric acid (GABA (against IRI in male and female rats. Thirty-six female and male wistar rats were assigned to six experimental groups. The IRI was induced by clamping renal vessels for 45 min then was performed reperfusion for 24 h. The group sex posed to IRI were pretreated with GABA and were compared with the control groups. Serum levels of creatinine and blood urea nitrogen, kidney weight, and kidney tissue damage score increased in the IRI alone groups, (P < 0.05), while GABA decreased these parameters in female significantly (P < 0.05), but not in male rats. Uterus weight decreased significantly in female rats treated with GABA. Testis weight did not alter in male rats. Serum level of nitrite and kidney level of malondialdehyde (MDA) had no significant change in both female and male rats. Kidney level of nitrite increased significantly in female rats experienced IRI and serum level of MDA increased significantly in males that were exposed to IRI (P < 0.05). GABA could ameliorate kidney injury induced by renal IRI in a gender dependent manner.

[Renal physiology].

PubMed

Gueutin, Victor; Deray, Gilbert; Isnard-Bagnis, Corinne

2012-03-01

The kidneys are responsible for the urinary excretion of uremic toxins and the regulation of several body systems such as intra and extracellular volume status, acid-base status, calcium and phosphate metabolism or erythropoiesis. They adapt quantitative and qualitative composition of the urine to keep these systems in balance. The flow of plasma is filtered in the range of 120 mL/min, and depends on the systemic and renal hemodynamics which is subject to self-regulation. The original urine will then be modified in successive segments of the nephron. The proximal nephron is to lead the massive reabsorption of water and essential elements such as sodium, bicarbonates, amino-acids and glucose. The distal nephron includes the distal convoluted tubule, the connector tube and the collecting duct. Its role is to adapt the quality composition of urine to the needs of the body.

The effects of environmental chemicals on renal function.

PubMed

Kataria, Anglina; Trasande, Leonardo; Trachtman, Howard

2015-10-01

The global incidence of chronic kidney disease (CKD) is increasing among individuals of all ages. Despite advances in proteomics, genomics and metabolomics, there remains a lack of safe and effective drugs to reverse or stabilize renal function in patients with glomerular or tubulointerstitial causes of CKD. Consequently, modifiable risk factors that are associated with a progressive decline in kidney function need to be identified. Numerous reports have documented the adverse effects that occur in response to graded exposure to a wide range of environmental chemicals. This Review summarizes the effects of such chemicals on four aspects of cardiorenal function: albuminuria, glomerular filtration rate, blood pressure and serum uric acid concentration. We focus on compounds that individuals are likely to be exposed to as a consequence of normal consumer activities or medical treatment, namely phthalates, bisphenol A, polyfluorinated alkyl acids, dioxins and furans, polycyclic aromatic hydrocarbons and polychlorinated biphenyls. Environmental exposure to these chemicals during everyday life could have adverse consequences on renal function and might contribute to progressive cumulative renal injury over a lifetime. Regulatory efforts should be made to limit individual exposure to environmental chemicals in an attempt to reduce the incidence of cardiorenal disease.

The effects of environmental chemicals on renal function

PubMed Central

Kataria, Anglina; Trasande, Leonardo; Trachtman, Howard

2015-01-01

The global incidence of chronic kidney disease (CKD) is increasing among individuals of all ages. Despite advances in proteomics, genomics and metabolomics, there remains a lack of safe and effective drugs to reverse or stabilize renal function in patients with glomerular or tubulointerstitial causes of CKD. Consequently, modifiable risk factors that are associated with a progressive decline in kidney function need to be identified. Numerous reports have documented the adverse effects that occur in response to graded exposure to a wide range of environmental chemicals. This Review summarizes the effects of such chemicals on four aspects of cardiorenal function: albuminuria, glomerular filtration rate, blood pressure and serum uric acid concentration. We focus on compounds that individuals are likely to be exposed to as a consequence of normal consumer activities or medical treatment, namely phthalates, bisphenol A, polyfluorinated alkyl acids, dioxins and furans, polycyclic aromatic hydrocarbons and polychlorinated biphenyls. Environmental exposure to these chemicals during everyday life could have adverse consequences on renal function and might contribute to progressive cumulative renal injury over a lifetime. Regulatory efforts should be made to limit individual exposure to environmental chemicals in an attempt to reduce the incidence of cardiorenal disease. PMID:26100504

[Renal risks of dietary complements: a forgotten cause].

PubMed

Dori, Olympia; Humbert, Antoine; Burnier, Michel; Teta, Daniel

2014-02-26

The use of dietary complements like vitamins, minerals, trace elements, proteins, aminoacids and plant-derived agents is prevalent in the general population, in order to promote health and treat diseases. Dietary complements are considered as safe natural products and are easily available without prescription. However, these can lead to severe renal toxicity, especially in cases of unknown pre-existing chronic kidney disease (CKD). In particular, Chinese herbs including aristolochic acid, high doses of vitamine C, creatine and protein complements may lead to acute and chronic renal failure, sometimes irreversible. Dietary complement toxicity should be suspected in any case of unexplained renal impairement. In the case of pre-existing CKD, the use of potentially nephrotoxic dietary complements should be screened for.

Renal arteriography

MedlinePlus

Renal angiogram; Angiography - kidney; Renal angiography; Renal artery stenosis - arteriography ... an artery by a blood clot Renal artery stenosis Renal cell cancer Angiomyolipomas (noncancerous tumors of the ...

Urinary Elimination of Bile Acid Glucuronides under Severe Cholestatic Situations: Contribution of Hepatic and Renal Glucuronidation Reactions.

PubMed

Perreault, Martin; Wunsch, Ewa; Białek, Andrzej; Trottier, Jocelyn; Verreault, Mélanie; Caron, Patrick; Poirier, Guy G; Milkiewicz, Piotr; Barbier, Olivier

2018-01-01

Biliary obstruction, a severe cholestatic complication, causes accumulation of toxic bile acids (BAs) in liver cells. Glucuronidation, catalyzed by UDP-glucuronosyltransferase (UGT) enzymes, detoxifies cholestatic BAs. Using liquid chromatography coupled to tandem mass spectrometry, 11 BA glucuronide (-G) species were quantified in prebiliary and postbiliary stenting serum and urine samples from 17 patients with biliary obstruction. Stenting caused glucuronide- and fluid-specific changes in BA-G levels and BA-G/BA metabolic ratios. In vitro glucuronidation assays with human liver and kidney microsomes revealed that even if renal enzymes generally displayed lower K M values, the two tissues shared similar glucuronidation capacities for BAs. By contrast, major differences between the two tissues were observed when four human BA-conjugating UGTs 1A3, 1A4, 2B4, and 2B7 were analyzed for mRNA and protein levels. Notably, the BA-24G producing UGT1A3 enzyme, abundant in the liver, was not detected in kidney microsomes. In conclusion, the circulating and urinary BA-G profiles are hugely impacted under severe cholestasis. The similar BA-glucuronidating abilities of hepatic and renal extracts suggest that both the liver and kidney may contribute to the urine BA-G pool.

Urinary Elimination of Bile Acid Glucuronides under Severe Cholestatic Situations: Contribution of Hepatic and Renal Glucuronidation Reactions

PubMed Central

Perreault, Martin; Białek, Andrzej; Trottier, Jocelyn; Verreault, Mélanie; Caron, Patrick; Poirier, Guy G.

2018-01-01

Biliary obstruction, a severe cholestatic complication, causes accumulation of toxic bile acids (BAs) in liver cells. Glucuronidation, catalyzed by UDP-glucuronosyltransferase (UGT) enzymes, detoxifies cholestatic BAs. Using liquid chromatography coupled to tandem mass spectrometry, 11 BA glucuronide (-G) species were quantified in prebiliary and postbiliary stenting serum and urine samples from 17 patients with biliary obstruction. Stenting caused glucuronide- and fluid-specific changes in BA-G levels and BA-G/BA metabolic ratios. In vitro glucuronidation assays with human liver and kidney microsomes revealed that even if renal enzymes generally displayed lower KM values, the two tissues shared similar glucuronidation capacities for BAs. By contrast, major differences between the two tissues were observed when four human BA-conjugating UGTs 1A3, 1A4, 2B4, and 2B7 were analyzed for mRNA and protein levels. Notably, the BA-24G producing UGT1A3 enzyme, abundant in the liver, was not detected in kidney microsomes. In conclusion, the circulating and urinary BA-G profiles are hugely impacted under severe cholestasis. The similar BA-glucuronidating abilities of hepatic and renal extracts suggest that both the liver and kidney may contribute to the urine BA-G pool. PMID:29850459

Alterations in blood pressure, antioxidant status and caspase 8 expression in cobalt chloride-induced cardio-renal dysfunction are reversed by Ocimum gratissimum and gallic acid in Wistar rats.

PubMed

Akinrinde, A S; Oyagbemi, A A; Omobowale, T O; Asenuga, E R; Ajibade, T O

2016-07-01

The protective abilities of the chloroform extract of Ocimum gratissimum (COG) and gallic acid against cobalt chloride (CoCl2) - induced cardiac and renal toxicity were evaluated. Rats were exposed to CoCl2 (350ppm) for 7 days, either alone, or in combination with COG (100 and 200mg/kg) or gallic acid (120mg/kg). CoCl2 given alone, caused significant increases (p<0.05) in oxidative stress parameters (hydrogen peroxide, H2O2 and malondialdehyde, MDA) and increased expression of the apoptotic initiator caspase 8 in the heart and kidneys. There was significant reduction (p<0.05) in reduced glutathione (GSH) in cardiac and renal tissues; reduction in superoxide dismutase (SOD) activity in the kidneys and adaptive increases in Glutathione S-transferase (GST) and catalase (CAT). CoCl2 also produced significant reduction (p<0.05) in systolic (SBP), diastolic (DBP) and mean arterial (MAP) blood pressures. Oral COG and gallic acid treatment significantly reduced (p<0.05) the levels of H2O2 and MDA; with reduced expression of caspase 8 and restoration of GSH levels, GPx, SOD and CAT activities, howbeit, to varying degrees in the heart and kidneys. COG (200mg/kg) was most effective in restoring the blood pressures in the rats to near control levels. CoCl2-induced histopathological lesions including myocardial infarction and inflammation and renal tubular necrosis and inflammation were effectively ameliorated by the treatments administered. This study provides evidence for the protective roles of O. gratissimum and gallic acid by modulation of CoCl2-induced alterations in blood pressure, antioxidant status and pro-apoptotic caspase 8 in Wistar rats. Copyright © 2016 Elsevier GmbH. All rights reserved.

Effect of Renal Impairment on the Pharmacokinetics and Pharmacodynamics of Verinurad, a Selective Uric Acid Reabsorption Inhibitor.

PubMed

Smith, William B; Hall, Jesse; Berg, Jolene K; Kazimir, Michal; Yamamoto, Amy; Walker, Susan; Lee, Caroline A; Shen, Zancong; Wilson, David M; Zhou, Dongmei; Gillen, Michael; Marbury, Thomas C

2018-06-11

BACKGROUND AND OBJECTIVE: Verinurad (RDEA3170) is a high-affinity, selective URAT1 transporter inhibitor in development for treating gout and asymptomatic hyperuricemia. This Phase I, single-dose study investigated the pharmacokinetics, pharmacodynamics, and safety of verinurad in adults with renal impairment and controls with normal renal function. Males aged 18-85 years were enrolled with serum urate (sUA) 4.5-10 mg/dl and creatinine clearance 60- < 90, 30- < 60, 15- < 30, or ≥ 90 ml/min (mild, moderate, severe renal impairment and controls, respectively; n = 7/8). Verinurad 15 mg was administered orally under fasted conditions. Serial plasma/serum and urine samplings were 30 min pre-dose to 72 h post-dose. Compared to controls, verinurad maximum observed plasma concentration increased by 53, 73, and 128% and area under the concentration-time curve increased by 24, 148, and 130%, in subjects with mild, moderate, and severe renal impairment, respectively; renal clearance decreased by 5, 42, and 79%. Exposures of major verinurad metabolites also increased with increasing renal impairment. Verinurad decreased sUA in all groups, with greater maximal changes in control and mild renal impairment than moderate and severe impairment groups (- 38.3, - 36.9, - 20.5, - 12.6%, respectively). There were no adverse event-related withdrawals or clinically meaningful changes in laboratory values. Exposures of verinurad and metabolites increased with decreasing renal function. Consistent with the renal-dependent mechanism of action of verinurad, increasing severity of renal impairment was associated with decreased sUA lowering. Verinurad safety assessments were similar regardless of renal impairment. Continued investigation of verinurad is warranted in patients with gout and renal impairment. CLINICALTRIALS. NCT02219516.

Distal renal tubular acidosis and hepatic lipidosis in a cat.

PubMed

Brown, S A; Spyridakis, L K; Crowell, W A

1986-11-15

Clinical and laboratory evidence of hepatic failure was found in a chronically anorectic cat. Simultaneous blood and urine pH determinations established a diagnosis of distal renal tubular acidosis. The cat did not respond to treatment. Necropsy revealed distal tubular nephrosis and hepatic lipidosis. The finding of distal renal tubular acidosis in a cat with hepatic lipidosis emphasizes the importance of complete evaluation of acid-base disorders in patients.

Persistent Increase in Blood Pressure After Renal Nerve Stimulation in Accessory Renal Arteries After Sympathetic Renal Denervation.

PubMed

de Jong, Mark R; Hoogerwaard, Annemiek F; Gal, Pim; Adiyaman, Ahmet; Smit, Jaap Jan J; Delnoy, Peter Paul H M; Ramdat Misier, Anand R; van Hasselt, Boudewijn A A M; Heeg, Jan-Evert; le Polain de Waroux, Jean-Benoit; Lau, Elizabeth O Y; Staessen, Jan A; Persu, Alexandre; Elvan, Arif

2016-06-01

Blood pressure response to renal denervation is highly variable, and the proportion of responders is disappointing. This may be partly because of accessory renal arteries too small for denervation, causing incomplete ablation. Renal nerve stimulation before and after renal denervation is a promising approach to assess completeness of renal denervation and may predict blood pressure response to renal denervation. The objective of the current study was to assess renal nerve stimulation-induced blood pressure increase before and after renal sympathetic denervation in main and accessory renal arteries of anaesthetized patients with drug-resistant hypertension. The study included 21 patients. Nine patients had at least 1 accessory renal artery in which renal denervation was not feasible. Renal nerve stimulation was performed in the main arteries of all patients and in accessory renal arteries of 6 of 9 patients with accessory arteries, both before and after renal sympathetic denervation. Renal nerve stimulation before renal denervation elicited a substantial increase in systolic blood pressure, both in main (25.6±2.9 mm Hg; P<0.001) and accessory (24.3±7.4 mm Hg; P=0.047) renal arteries. After renal denervation, renal nerve stimulation-induced systolic blood pressure increase was blunted in the main renal arteries (Δ systolic blood pressure, 8.6±3.7 mm Hg; P=0.020), but not in the nondenervated renal accessory renal arteries (Δ systolic blood pressure, 27.1±7.6 mm Hg; P=0.917). This residual source of renal sympathetic tone may result in persistent hypertension after ablation and partly account for the large response variability. © 2016 American Heart Association, Inc.

Association of renal tubular damage with cardio-renal anemia syndrome in patients with heart failure.

PubMed

Otaki, Yoichiro; Watanabe, Tetsu; Takahashi, Hiroki; Narumi, Taro; Kadowaki, Shinpei; Honda, Yuki; Arimoto, Takanori; Shishido, Tetsuro; Miyamoto, Takuya; Konta, Tsuneo; Kubota, Isao

2014-05-01

Cardio-renal anemia syndrome (CRAS) has begun to gather attention as a vicious circle since chronic heart failure (CHF), chronic kidney disease (CKD), and anemia are all able to be caused and exacerbated by each other. However, it remains unclear whether renal tubular damage (RTD), another type of kidney dysfunction, is associated with this vicious circle. The aim of the present study was to assess the association of RTD with CRAS in patients with CHF. We included 300 consecutive patients with CHF. RTD was defined as a urinary β2-microglobulin to creatinine ratio ≥ 300 μg/g. Patients with RTD had lower serum iron and higher levels of high sensitivity C-reactive protein than those without it. Multivariate logistic analysis showed that RTD was closely associated with anemia in patients with CHF, after adjustment for confounding factors. During a median period of 1,098 days, there were 86 cardiac events, including 14 cardiac deaths and 72 re-hospitalizations for worsening heart failure. Net reclassification improvement was significantly improved by addition of RTD to the model including age, New York Heart Association functional class, brain natriuretic peptide, anemia, and CKD. All patients were divided into 3 groups: CRAS+RTD group, CRAS group, and control group. Kaplan-Meier analysis demonstrated that CRAS+RTD had the greatest risk in patients with CHF. RTD was associated with normocytic anemia, accompanying iron deficiency and inflammation. RTD added prognostic information to conventional CRAS, suggesting the importance of RTD in cardio-renal anemia interaction. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Application of physiologically-based pharmacokinetic modeling to explore the role of kidney transporters in renal reabsorption of perfluorooctanoic acid in the rat

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

Worley, Rachel Rogers, E-mail: idz7@cdc.gov; Interdisciplinary Toxicology Program, University of Georgia, 341 Pharmacy South, Athens, GA 30602; Fisher, Jeffrey

ABSTRACT: Renal elimination and the resulting clearance of perfluorooctanoic acid (PFOA) from the serum exhibit pronounced sex differences in the adult rat. The literature suggests that this is largely due to hormonally regulated expression of organic anion transporters (OATs) on the apical and basolateral membranes of the proximal tubule cells that facilitate excretion and reabsorption of PFOA from the filtrate into the blood. Previously developed PBPK models of PFOA exposure in the rat have not been parameterized to specifically account for transporter-mediated renal elimination. We developed a PBPK model for PFOA in male and female rats to explore the rolemore » of Oat1, Oat3, and Oatp1a1 in sex-specific renal reabsorption and excretion of PFOA. Descriptions of the kinetic behavior of these transporters were extrapolated from in vitro studies and the model was used to simulate time-course serum, liver, and urine data for intravenous (IV) and oral exposures in both sexes. Model predicted concentrations of PFOA in the liver, serum, and urine showed good agreement with experimental data for both male and female rats indicating that in vitro derived physiological descriptions of transporter-mediated renal reabsorption can successfully predict sex-dependent excretion of PFOA in the rat. This study supports the hypothesis that sex-specific serum half-lives for PFOA are largely driven by expression of transporters in the kidney and contribute to the development of PBPK modeling as a tool for evaluating the role of transporters in renal clearance. - Highlights: • The PBPK model for PFOA in the rat explores the role of OATs in sex-specific clearance. • Descriptions of OAT kinetics were extrapolated from in vitro studies. • Model predictions showed good fit with experimental data for male and female rats.« less

Uric acid and chronic kidney disease: which is chasing which?

PubMed Central

Johnson, Richard J.; Nakagawa, Takahiko; Jalal, Diana; Sánchez-Lozada, Laura Gabriela; Kang, Duk-Hee; Ritz, Eberhard

2013-01-01

Serum uric acid is commonly elevated in subjects with chronic kidney disease (CKD), but was historically viewed as an issue of limited interest. Recently, uric acid has been resurrected as a potential contributory risk factor in the development and progression of CKD. Most studies documented that an elevated serum uric acid level independently predicts the development of CKD. Raising the uric acid level in rats can induce glomerular hypertension and renal disease as noted by the development of arteriolosclerosis, glomerular injury and tubulointerstitial fibrosis. Pilot studies suggest that lowering plasma uric acid concentrations may slow the progression of renal disease in subjects with CKD. While further clinical trials are necessary, uric acid is emerging as a potentially modifiable risk factor for CKD. Gout was considered a cause of CKD in the mid-nineteenth century [1], and, prior to the availability of therapies to lower the uric acid level, the development of end-stage renal disease was common in gouty patients. In their large series of gouty subjects Talbott and Terplan found that nearly 100% had variable degrees of CKD at autopsy (arteriolosclerosis, glomerulosclerosis and interstitial fibrosis) [2]. Additional studies showed that during life impaired renal function occurred in half of these subjects [3]. As many of these subjects had urate crystals in their tubules and interstitium, especially in the outer renal medulla, the disease became known as gouty nephropathy. The identity of this condition fell in question as the presence of these crystals may occur in subjects without renal disease; furthermore, the focal location of the crystals could not explain the diffuse renal scarring present. In addition, many subjects with gout also had coexistent conditions such as hypertension and vascular disease, leading some experts to suggest that the renal injury in gout was secondary to these latter conditions rather than to uric acid per se [4]. Indeed, gout was

Renal Oxidative Stress Induced by Long-Term Hyperuricemia Alters Mitochondrial Function and Maintains Systemic Hypertension

PubMed Central

Cristóbal-García, Magdalena; García-Arroyo, Fernando E.; Arellano-Buendía, Abraham S.; Madero, Magdalena; Rodríguez-Iturbe, Bernardo; Pedraza-Chaverrí, José; Zazueta, Cecilia; Johnson, Richard J.; Sánchez Lozada, Laura-Gabriela

2015-01-01

We addressed if oxidative stress in the renal cortex plays a role in the induction of hypertension and mitochondrial alterations in hyperuricemia. A second objective was to evaluate whether the long-term treatment with the antioxidant Tempol prevents renal oxidative stress, mitochondrial alterations, and systemic hypertension in this model. Long-term (11-12 weeks) and short-term (3 weeks) effects of oxonic acid induced hyperuricemia were studied in rats (OA, 750 mg/kg BW), OA+Allopurinol (AP, 150 mg/L drinking water), OA+Tempol (T, 15 mg/kg BW), or vehicle. Systolic blood pressure, renal blood flow, and vascular resistance were measured. Tubular damage (urine N-acetyl-β-D-glucosaminidase) and oxidative stress markers (lipid and protein oxidation) along with ATP levels were determined in kidney tissue. Oxygen consumption, aconitase activity, and uric acid were evaluated in isolated mitochondria from renal cortex. Short-term hyperuricemia resulted in hypertension without demonstrable renal oxidative stress or mitochondrial dysfunction. Long-term hyperuricemia induced hypertension, renal vasoconstriction, tubular damage, renal cortex oxidative stress, and mitochondrial dysfunction and decreased ATP levels. Treatments with Tempol and allopurinol prevented these alterations. Renal oxidative stress induced by hyperuricemia promoted mitochondrial functional disturbances and decreased ATP content, which represent an additional pathogenic mechanism induced by chronic hyperuricemia. Hyperuricemia-related hypertension occurs before these changes are evident. PMID:25918583

Diclofenac toxicity in Gyps vulture is associated with decreased uric acid excretion and not renal portal vasoconstriction.

PubMed

Naidoo, V; Swan, G E

2009-04-01

Diclofenac (DF), a non-steroidal anti-inflammatory drug (NSAID), is largely regarded as one of the most devastating environmental toxicant in recent times, after accidental exposure via their food-chain lead to massive mortalities in three vulture species on the Asian subcontinent. Although the use of diclofenac was recently banned on the Indian subcontinent, following the favourable safety profile of meloxicam, its mechanism of toxicity remains unknown. In an attempt to establish this mechanism, we test three hypotheses using models established from either the domestic chicken (Gallus domesticus) or the African White-backed vulture (Gyps africanus). We demonstrate that both DF and meloxicam are toxic to renal tubular epithelial (RTE) cells following 12 h of exposure, due to an increase in production of reactive oxygen species (ROS), which could be temporarily ameliorated by pre-incubation with uric acid (UA). When cultures were incubated with either drug for only 2 h, meloxicam showed no toxicity in contrast to diclofenac. In both cases no increase in ROS production was evident. In addition, diclofenac decreased the transport of uric acid, by interfering with the p-amino-hippuric acid (PAH) channel. We conclude that vulture susceptibility to diclofenac results from a combination of an increased ROS, interference with UA transport and the duration of exposure.

Horizontal ichthyoplankton tow-net system with unobstructed net opening

USGS Publications Warehouse

Nester, Robert T.

1987-01-01

The larval fish sampler described here consists of a modified bridle, frame, and net system with an obstruction-free net opening and is small enough for use on boats 10 m or less in length. The tow net features a square net frame attached to a 0.5-m-diameter cylinder-on-cone plankton net with a bridle designed to eliminate all obstructions forward of the net opening, significantly reducing currents and vibrations in the water directly preceding the net. This system was effective in collecting larvae representing more than 25 species of fish at sampling depths ranging from surface to 10 m and could easily be used at greater depths.

Determination of glomerular function in advanced renal failure.

PubMed Central

Manz, F; Alatas, H; Kochen, W; Lutz, P; Rebien, W; Schärer, K

1977-01-01

In 15 children with advanced chronic renal failure, glomerular filtration rate was determined by different methods. Inulin clearance correlated well with the mean of creatinine and urea clearance, and also with 51-chromium edetic acid (EDTA) clearance measured over 24 hours. The absolute values of creatinine clearance and of 51Cr-EDTA clearance measured up to 8 hours were higher than inulin clearance. In advanced renal failure both the 51Cr-EDTA clearance measured over 24 hours, and the mean of creatinine and urea clearance, provide acceptable estimates of true glomerular filtration rate. PMID:411426

Renal albumin absorption in physiology and pathology.

PubMed

Birn, H; Christensen, E I

2006-02-01

Albumin is the most abundant plasmaprotein serving multiple functions as a carrier of metabolites, hormones, vitamins, and drugs, as an acid/base buffer, as antioxidant and by supporting the oncotic pressure and volume of the blood. The presence of albumin in urine is considered to be the result of the balance between glomerular filtration and tubular reabsorption. Albuminuria has been accepted as an independent risk factor and a marker for renal as well as cardiovascular disease, and during the past decade, evidence has suggested that albumin itself may cause progression of renal disease. Thus, the reduction of proteinuria and, in particular, albuminuria has become a target in itself to prevent deterioration of renal function. Studies have shown albumin and its ligands to induce expression of inflammatory and fibrogenic mediators, and it has been hypothesized that increased filtration of albumin causes excessive tubular reabsorption, resulting in inflammation and fibrosis, resulting in the loss of renal function. In addition, it is known that tubular dysfunction in itself may cause albuminuria owing to decreased reabsorption of filtered albumin, and, recently, it has been suggested that significant amounts of albumin fragments are excreted in the urine as a result of tubular degradation. Thus, although both tubular and glomerular dysfunction influences renal handling of albumin, it appears that tubular reabsorption plays a central role in mediating the effects of albumin on renal function. The present paper will review the mechanisms for tubular albumin uptake and the possible implications for the development of renal disease.

Use of nonimaging nuclear medicine techniques to assess the effect of flunixin meglumine on effective renal plasma flow and effective renal blood flow in healthy horses.

PubMed

Held, J P; Daniel, G B

1991-10-01

The effect of flunixin meglumine on renal function was studied in 6 healthy horses by use of nonimaging nuclear medicine techniques. Effective renal plasma flow (ERPF) and effective renal blood flow (ERBF) were determined by plasma clearance of 131I-orthoiodohippuric acid before and after administration of flunixin meglumine. Mean ERPF and ERBF was 6.03 ml/min/kg and 10.7 ml/min/kg, respectively, before treatment and was 5.7 ml/min/kg and 9.7 ml/min/kg, respectively, after treatment. Although ERPF and ERBF decreased after flunixin meglumine administration, the difference was not statistically significant.

Ω3 fatty acids may reduce hyperlipidemia in pediatric renal transplant recipients.

PubMed

Filler, Guido; Weiglein, Geneva; Gharib, Mireille Tina; Casier, Shelley

2012-12-01

Life expectancy after pediatric renal transplantation remains lower than that of the normal population largely due to cardiovascular morbidity and mortality. Hyperlipidemia is a potentially modifiable risk factor for cardiovascular morbidity. Retrospective chart review of all available pediatric renal transplant patients (26) in a single center with assessment of anthropometry, renal function, steroid, calcineurin or mTOR inhibitor exposure and Ω3 FA supplementation. Eighteen transplant recipients without Ω3 FA supplementation served as control. Nutrition and supplement surveys were conducted with standardized questionnaires. Fasting cholesterol values were compared using the latest value prior to start of Ω3 FA and at last follow-up. Eight patients (five receiving mTOR inhibitor) started Ω3 FA supplementation at a mean dose of 29.2 ± 12 mg of EPA/kg and 16.1 ± 7.4 mg DHA/kg body weight. Median duration of treatment was 2.5 yr (range 0.8-5.9 yr) and their total fasting cholesterol at last follow-up dropped significantly from 5.08 ± 0.97 (control group 3.77 ± 0.81, p = 0.0084) to 4.17 ± 0.54 mm (p = 0.0158). High-density lipoprotein cholesterol increased not significantly from 1.74 ± 0.49 to 2.02 ± 0.93 mm. No patient had increased bleeding. Supplementation of omega-3 FAs may reduce hyperlipidaemia after pediatric renal transplantation. © 2012 John Wiley & Sons A/S.

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.

Enteral nutrition in patients with acute renal failure.

PubMed

Fiaccadori, Enrico; Maggiore, Umberto; Giacosa, Roberto; Rotelli, Carlo; Picetti, Edoardo; Sagripanti, Sibilla; Melfa, Luigi; Meschi, Tiziana; Borghi, Loris; Cabassi, Aderville

2004-03-01

Systematic studies on safety and efficacy of enteral nutrition in patients with acute renal failure (ARF) are lacking. We studied enteral nutrition-related complications and adequacy of nutrient administration during 2525 days of artificial nutrition in 247 consecutive patients fed exclusively by the enteral route: 65 had normal renal function, 68 had ARF not requiring renal replacement therapy, and 114 required renal replacement therapy. No difference was found in gastrointestinal or mechanical complications between ARF patients and patients with normal renal function, except for high gastric residual volumes, which occurred in 3.1% of patients with normal renal function, 7.3% of patients with ARF not requiring renal replacement therapy, 13.2% of patients with ARF on renal replacement therapy (P= 0.02 for trend), and for nasogastric tube obstruction: 0.0%, 5.9%, 14%, respectively (P < 0.001). Gastrointestinal complications were the most frequent cause of suboptimal delivery; the ratio of administered to prescribed daily volume was well above 90% in all the three groups. Definitive withdrawal of enteral nutrition due to complications was documented in 6.1%, 13.2%. and 14.9% of patients, respectively (P= 0.09 for trend). At regimen, mean delivered nonprotein calories were 19.8 kcal/kg (SD 4.6), 22.6 kcal/kg (8.4), 23.4 kcal/kg (6.5); protein intake was 0.92 g/kg (0.21), 0.87 g/kg (0.25), and 0.92 g/kg (0.21), the latter value being below that currently recommended for ARF patients on renal replacement therapy. Median fluid intake with enteral nutrition was 1440 mL (range 720 to 1960), 1200 (720 to 2400), and 960 (360 to 1920). Enteral nutrition is a safe and effective nutritional technique to deliver artificial nutrition in ARF patients. Parenteral amino acid supplementation may be required, especially in patients with ARF needing renal replacement therapy.

Estimated net acid excretion inversely correlates with urine pH in vegans, lacto-ovo vegetarians, and omnivores.

PubMed

Ausman, Lynne M; Oliver, Lauren M; Goldin, Barry R; Woods, Margo N; Gorbach, Sherwood L; Dwyer, Johanna T

2008-09-01

Diet affects urine pH and acid-base balance. Both excess acid/alkaline ash (EAA) and estimated net acid excretion (NAE) calculations have been used to estimate the effects of diet on urine pH. This study's goal was to determine if free-living vegans, lacto-ovo vegetarians, and omnivores have increasingly acidic urine, and to assess the ability of EAA and estimated NAE calculations to predict urine pH. This study used a cross-sectional design. This study assessed urine samples of 10 vegan, 16 lacto-ovo vegetarian, and 16 healthy omnivorous women in the Boston metropolitan area. Six 3-day food records from each dietary group were analyzed for EAA content and estimated NAE, and correlations with measured urine pH were calculated. The mean (+/- SD) urine pH was 6.15 +/- 0.40 for vegans, 5.90 +/- 0.36 for lacto-ovo vegetarians, and 5.74 +/- 0.21 for omnivores (analysis of variance, P = .013). Calculated EAA values were not significantly different among the three groups, whereas mean estimated NAE values were significantly different: 17.3 +/- 14.5 mEq/day for vegans, 31.3 +/- 8.5 mEq/day for lacto-ovo vegetarians, and 42.6 +/- 13.2 mEq/day for omnivores (analysis of variance, P = .01). The average deattenuated correlation between urine pH and EAA was 0.333; this value was -0.768 for estimated NAE and urine pH, with a regression equation of pH = 6.33 - 0.014 NAE (P = .02, r = -0.54). Habitual diet and estimated NAE calculations indicate the probable ranking of urine pH by dietary groups, and may be used to determine the likely acid-base status of an individual; EAA calculations were not predictive of urine pH.

Mechanism of Aluminum Inhibition of Net 45Ca2+ Uptake by Amaranthus Protoplasts 1

PubMed Central

Rengel, Zdenko; Elliott, Daphne C.

1992-01-01

Calcium ions serve as a second messenger in signal transduction and metabolic regulation. Effects of Al on calcium homeostasis remain to be elucidated. Short-term net 45Ca2+ uptake by Amaranthus tricolor protoplasts was monitored from uptake media prepared to test the influence of pH, Al, and various inhibitors. Accumulation of 45Ca2+ increased during the first 3 to 6 minutes and then leveled off or declined. Al and Ca2+ channel blockers (verapamil and bepridil) decreased net 45Ca2+ uptake. This decrease was more pronounced when Al and bepridil were both present in uptake media, but Al did not aggravate verapamil-induced reduction of net 45Ca2+ uptake. Erythrosin B and calmidazolium each increased net 45Ca2+ uptake, probably by interfering with Ca2+ efflux. This effect was undetectable in the presence of Al. Mycophenolic acid decreased net 45Ca2+ uptake; guanosine alleviated this effect. Al-induced reduction of net 45Ca2+ uptake was not aggravated by mycophenolic acid. Net 45Ca2+ uptake was generally less at pH 4.5 than at 5.5 for all treatments. It is concluded that Al ions affect net 45Ca2+ uptake by binding to the verapamil-specific channel site that is different from the bepridil-specific one, as well as by interfering with the action of guanosine 5′-triphosphate-binding proteins. PMID:16668688

Sectorial technetium-99m-dimercaptosuccinic acid scintigraphy for monitoring the effect of extracorporeal piezoelectric lithotripsy for calyceal calculi on regional renal function.

PubMed

Al-Tawheed, A; Al-Awadi, K A; Kehinde, E O; Loutfi, I; Abdul-Haleem, H; Al-Mohannadi, S

2003-01-01

To apply a semiquantitative method for analysis of technetium-99m-dimercaptosuccinic acid ((99m)Tc-DMSA) renal scintigraphy for monitoring the effect of extracorporeal piezoelectric lithotripsy (EPL) in patients with calyceal stones on regional kidney function and to check whether EPL had caused any deleterious effect on the target calyceal renal parenchymal function. Forty patients (mean age 35 years) suffering from calyceal stones documented by abdominal plain radiography, intravenous urogram or abdominal ultrasound were studied. All patients were treated by EPL. (99m)Tc-DMSA scan was performed before and 4 weeks after EPL. Sector analysis involved calculation of the relative function of the target calyx to the function of the ipsilateral kidney and the relative function of the treated kidney to global renal function. The stone sizes were 6-11 mm in diameter and 11 were located in the upper, 13 in the middle and 16 in the lower calyx. After EPL, the overall stone clearance rate was 85% (100% for calculi in the upper and middle calyces, 62% for lower calyces). The sector analysis did not show statistically significant change of the relative regional (calyceal) or whole kidney function between the pre- and post-EPL (99m)Tc-DMSA scans. Using sector analysis, EPL appeared to be a safe modality and its usage was not associated with any untoward effect on calyceal or whole kidney function. Sector analysis of (99m)Tc-DMSA renal scan is a simple semiquantitative method for monitoring regional changes of kidney function after EPL for treatment of calyceal stone. Copyright 2003 S. Karger AG, Basel

Glutaric Aciduria type I and acute renal failure - Coincidence or causality?

PubMed

Pode-Shakked, Ben; Marek-Yagel, Dina; Rubinshtein, Marina; Pessach, Itai M; Paret, Gideon; Volkov, Alexander; Anikster, Yair; Lotan, Danny

2014-01-01

Glutaric Aciduria type I (GA-I) is a rare organic acidemia, caused by mutations in the GCDH gene, and characterized by encephalopathic crises with neurological sequelae. We report herein a patient with GA-I who presented with severe acute renal failure requiring dialysis, following an acute diarrheal illness. Histopathological evaluation demonstrated acute tubular necrosis, and molecular diagnosis revealed the patient to be homozygous for a previously unreported mutation, p.E64D. As renal impairment is not part of the clinical spectrum typical to GA-I, possible associations of renal failure and the underlying inborn error of metabolism are discussed, including recent advancements made in the understanding of the renal transport of glutaric acid and its derivatives during metabolic disturbance in GA-I.

Impact of Febuxostat on Renal Function in Gout Patients With Moderate-to-Severe Renal Impairment.

PubMed

Saag, Kenneth G; Whelton, Andrew; Becker, Michael A; MacDonald, Patricia; Hunt, Barbara; Gunawardhana, Lhanoo

2016-08-01

Renal impairment is a risk factor for gout and a barrier to optimal gout management. We undertook this exploratory study to obtain data that have been heretofore limited regarding the safety and efficacy of febuxostat in patients with moderate-to-severe renal impairment (estimated glomerular filtration rate [GFR] 15-50 ml/minute/1.73 m(2) ). Ninety-six gout patients with moderate-to-severe renal impairment were enrolled in a 12-month multicenter, randomized, double-blind, placebo-controlled study. Patients were randomly assigned at a 1:1:1 ratio to receive 30 mg febuxostat twice daily, 40/80 mg febuxostat once daily, or placebo. The primary efficacy end point was the change in serum creatinine (Cr) level from baseline to month 12. Secondary end points included the change in estimated GFR from baseline to month 12 and the proportion of patients with a serum uric acid (UA) level of <6.0 mg/dl at month 12. At month 12, there were no significant differences in the change in serum Cr level from baseline, or in the change in estimated GFR from baseline, in either febuxostat group compared to the placebo group. The proportion of patients with a serum UA level of <6.0 mg/dl at month 12 was significantly greater in both febuxostat groups compared to the placebo group (both P < 0.001). At least 1 treatment-emergent adverse event (TEAE) occurred in 78.1% of patients receiving 30 mg febuxostat twice daily, 87.5% of patients receiving 40/80 mg febuxostat once daily, and 78.1% of patients receiving placebo. TEAEs most frequently involved the categories of renal failure and impairment and renal function analyses. Febuxostat proved to be efficacious in serum UA reduction and was well tolerated in gout patients with moderate-to-severe renal impairment. Patients randomly assigned to receive febuxostat demonstrated significantly lower serum UA levels and no significant deterioration in renal function. © 2016, American College of Rheumatology.

Novel Omega-3 Fatty Acid Epoxygenase Metabolite Reduces Kidney Fibrosis

PubMed Central

Sharma, Amit; Khan, Md. Abdul Hye; Levick, Scott P.; Lee, Kin Sing Stephen; Hammock, Bruce D.; Imig, John D.

2016-01-01

Cytochrome P450 (CYP) monooxygenases epoxidize the omega-3 polyunsaturated fatty acid (PUFA) docosahexaenoic acid into novel epoxydocosapentaenoic acids (EDPs) that have multiple biological actions. The present study determined the ability of the most abundant EDP regioisomer, 19,20-EDP to reduce kidney injury in an experimental unilateral ureteral obstruction (UUO) renal fibrosis mouse model. Mice with UUO developed kidney tubular injury and interstitial fibrosis. UUO mice had elevated kidney hydroxyproline content and five-times greater collagen positive fibrotic area than sham control mice. 19,20-EDP treatment to UUO mice for 10 days reduced renal fibrosis with a 40%–50% reduction in collagen positive area and hydroxyproline content. There was a six-fold increase in kidney α-smooth muscle actin (α-SMA) positive area in UUO mice compared to sham control mice, and 19,20-EDP treatment to UUO mice decreased α-SMA immunopositive area by 60%. UUO mice demonstrated renal epithelial-to-mesenchymal transition (EMT) with reduced expression of the epithelial marker E-cadherin and elevated expression of multiple mesenchymal markers (FSP-1, α-SMA, and desmin). Interestingly, 19,20-EDP treatment reduced renal EMT in UUO by decreasing mesenchymal and increasing epithelial marker expression. Overall, we demonstrate that a novel omega-3 fatty acid metabolite 19,20-EDP, prevents UUO-induced renal fibrosis in mice by reducing renal EMT. PMID:27213332

Intracellular Acid-Extruding Regulators and the Effect of Lipopolysaccharide in Cultured Human Renal Artery Smooth Muscle Cells

PubMed Central

Loh, Shih-Hurng; Lee, Chung-Yi; Tsai, Yi-Ting; Shih, Shou-Jou; Chen, Li-Wei; Cheng, Tzu-Hurng; Chang, Chung-Yi; Tsai, Chein-Sung

2014-01-01

Homeostasis of the intracellular pH (pHi) in mammalian cells plays a pivotal role in maintaining cell function. Thus far, the housekeeping Na+-H+ exchanger (NHE) and the Na+-HCO3 − co-transporter (NBC) have been confirmed in many mammalian cells as major acid extruders. However, the role of acid-extruding regulators in human renal artery smooth muscle cells (HRASMCs) remains unclear. It has been demonstrated that lipopolysaccharide (LPS)-induced vascular occlusion is associated with the apoptosis, activating calpain and increased [Ca2+]i that are related to NHE1 activity in endothelia cells. This study determines the acid-extruding mechanisms and the effect of LPS on the resting pHi and active acid extruders in cultured HRASMCs. The mechanism of pHi recovery from intracellular acidosis (induced by NH4Cl-prepulse) is determined using BCECF-fluorescence in cultured HRASMCs. It is seen that (a) the resting pHi is 7.19±0.03 and 7.10±0.02 for HEPES- and CO2/HCO3 −- buffered solution, respectively; (b) apart from the housekeeping NHE1, another Na+-coupled HCO3 − transporter i.e. NBC, functionally co-exists to achieve acid-equivalent extrusion; (c) three different isoforms of NBC: NBCn1 (SLC4A7; electroneutral), NBCe1 (SLC4A4; electrogenic) and NBCe2 (SLC4A5), are detected in protein/mRNA level; and (d) pHi and NHE protein expression/activity are significantly increased by LPS, in both a dose- and time- dependent manner, but NBCs protein expression is not. In conclusion, it is demonstrated, for the first time, that four pHi acid-extruding regulators: NHE1, NBCn1, NBCe1 and NBCe2, co-exist in cultured HRASMCs. LPS also increases cellular growth, pHi and NHE in a dose- and time-dependent manner. PMID:24587308

ABCG8 polymorphisms and renal disease in type 2 diabetic patients.

PubMed

Nicolas, Anthony; Fatima, Sehrish; Lamri, Amel; Bellili-Muñoz, Naima; Halimi, Jean-Michel; Saulnier, Pierre-Jean; Hadjadj, Samy; Velho, Gilberto; Marre, Michel; Roussel, Ronan; Fumeron, Frédéric

2015-06-01

Sterols, bile acids and their receptors have been involved in diabetic nephropathy. The ATP-binding cassette transporters G5 and G8 (ABCG5 and ABCG8) play an important role in intestinal sterol absorption and bile acid secretion. The aim of our study was to assess the associations between two ABCG8 coding polymorphisms, T400K and D19H, and the incidence of renal events in type 2 diabetic subjects. Participants were the 3137 French type 2 diabetic subjects with micro- or macro-albuminuria from the genetic substudy of the DIABHYCAR trial. The mean duration of follow-up was 4years. Renal events were defined as a doubling of serum creatinine concentration or end-stage renal disease at follow-up. We then used a second population (DIAB2NEPHROGENE) of 2140 type 2 diabetic patients for the purpose of validation. In DIABHYCAR, the 400K allele was significantly associated with a higher risk of incident renal events in a multiple adjusted model (HR: 1.75 [95% CI 1.20-2.56], P=0.003). This association was still significant after further adjustments for baseline values of estimated glomerular filtration rate and urinary albumin excretion. In the validation population, the 400K allele was associated with the prevalence of end-stage renal disease (OR=2.01 [95% CI 1.15-3.54], P=0.015). No significant association was found between the D19H polymorphism and the risk of diabetic nephropathy. A polymorphism of the sterol transporter ABCG8 has been associated with the prevalence of end-stage renal disease and with the incidence of new renal events in type 2 diabetic patients. Copyright © 2015. Published by Elsevier Inc.

Limitation on the use of amiloride in early renal failure.

PubMed

Knauf, H; Reuter, K; Mutschler, E

1985-01-01

The effect of a single oral dose of 10 mg amiloride was studied on urinary excretion of Na+, K+, Ca++ and Mg++ in healthy subjects and in patients with varying degrees of renal impairment. Amiloride produced a moderate diuresis and sodium excretion, and a slight calciuresis. Urinary excretion of potassium was significantly reduced as compared to the controls. Despite its diuretic and natriuretic effects, amiloride did not change the excretion of Mg++ as compared to the pretreatment period. When the creatinine clearance was below 50 ml/min, the net excretion of Na+ and Ca++ was drastically reduced. However, K+ retention and neutrality of Mg++ excretion were maintained down to end-stage renal disease. In the healthy volunteers the mean elimination half-life of amiloride was 20 h, and it rose to about 100 h in end-stage renal disease. This was because about 3/4 of native amiloride was eliminated through the kidney. Nonrenal elimination of amiloride was calculated to amount to only 1/4 of the total elimination. Therefore, the anticaliuretic amiloride is a valuable comedication in subjects with normal kidney function to prevent K+ and Mg++ loss. However, its use is hazardous if plasma creatinine is raised.

Proximal tubule glutamine synthetase expression is necessary for the normal response to dietary protein restriction.

PubMed

Lee, Hyun-Wook; Osis, Gunars; Handlogten, Mary E; Verlander, Jill W; Weiner, I David

2017-07-01

Dietary protein restriction has multiple benefits in kidney disease. Because protein intake is a major determinant of endogenous acid production, it is important that net acid excretion changes in parallel during changes in dietary protein intake. Dietary protein restriction decreases endogenous acid production and decreases urinary ammonia excretion, a major component of net acid excretion. Glutamine synthetase (GS) catalyzes the reaction of [Formula: see text] and glutamate, which regenerates the essential amino acid glutamine and decreases net ammonia generation. Because renal proximal tubule GS expression increases during dietary protein restriction, this could contribute to the decreased ammonia excretion. The purpose of the current study was to determine the role of proximal tubule GS in the renal response to protein restriction. We generated mice with proximal tubule-specific GS deletion (PT-GS-KO) using Cre-loxP techniques. Cre-negative (Control) and PT-GS-KO mice in metabolic cages were provided 20% protein diet for 2 days and were then changed to low-protein (6%) diet for the next 7 days. Additional PT-GS-KO mice were maintained on 20% protein diet. Dietary protein restriction caused a rapid decrease in urinary ammonia excretion in both genotypes, but PT-GS-KO blunted this adaptive response significantly. This occurred despite no significant genotype-dependent differences in urinary pH or in serum electrolytes. There were no significant differences between Control and PT-GS-KO mice in expression of multiple other proteins involved in renal ammonia handling. We conclude that proximal tubule GS expression is necessary for the appropriate decrease in ammonia excretion during dietary protein restriction.

An evaluation of longitudinal changes in serum uric acid levels and associated risk of cardio-metabolic events and renal function decline in gout.

PubMed

Desai, Rishi J; Franklin, Jessica M; Spoendlin-Allen, Julia; Solomon, Daniel H; Danaei, Goodarz; Kim, Seoyoung C

2018-01-01

Gout patients have a high burden of co-morbid conditions including diabetes mellitus (DM), chronic kidney disease (CKD), and cardiovascular disease (CVD). We sought to evaluate the association between changes in serum uric acid (SUA) levels over time and the risk of incident DM, CVD, and renal function decline in gout patients. An observational cohort study was conducted among enrollees of private health insurance programs in the US between 2004 and 2015. Gout patients were included on the index date of a SUA measurement ≥6.8 mg/dl. The exposure of interest was cumulative change in SUA levels from baseline. Hazard ratios (HR) and 95% confidence intervals (CI) for incident DM, incident CVD, and renal function decline (≥30% reduction in glomerular filtration rate) were derived using marginal structural models with stabilized inverse probability weights accounting for baseline confounders (age, gender, co-morbidities, co-medications) and time-varying confounders (serum creatinine, blood urea nitrogen, glycated hemoglobin). Among 26,341 patients with gout, the average age was 62, 75% were men, and the median baseline SUA was 8.6 mg/dl (interquartile range 7.7 to 9.5). The incidence rates/100 person-years (95% CI) were 1.63 (1.51-1.75) for DM, 0.77 (0.70-0.84) for CVD, and 4.32 (4.14-4.49) for renal function decline. The adjusted HR (95% CI) per 3 mg/dl reduction in SUA, corresponding on average to achieving the target level of <6 mg/dl in this population, was 1.04 (0.92-1.17) for DM, 1.07 (0.89-1.29) for CVD, and 0.85 (0.78-0.92) for renal function decline. Reduction in SUA in patients with gout may be associated with a reduced risk of renal function decline, but not with DM or CVD.

Evaluation of Renal Toxicity by Combination Exposure to Melamine and Cyanuric Acid in Male Sprague-Dawley Rats

PubMed Central

Son, Ji Yeon; Kang, Yoon Jong; Kim, Kyeong Seok; Kim, Tae Hyung; Lim, Sung Kwang; Lim, Hyun Jung; Jeong, Tae Cheon; Choi, Dal Woong; Chung, Kyu Hyuck; Lee, Byung Mu

2014-01-01

Melamine-induced nephrotoxicity is closely associated with crystal formation in the kidney caused by combined exposure to melamine (Mel) and cyanuric acid (CA). However, there are few dosage-finding studies for toxicological evaluation of chronic co-exposure to Mel and CA. The objective of this study was to investigate the possible mechanism by which a Mel and CA mixture lead to renal toxicity in rats. Mel and CA were co-administered to rats via oral gavage for 50 days. Nephrotoxicity was determined by measuring blood urea nitrogen (BUN) and serum creatinine (sCr) levels. Relative kidney weights were significantly increased in rats after co-exposure to Mel+CA (63/6.3 or 630/6.3 mg/kg) mixtures. BUN and sCr levels were significantly increased after Mel and CA co-exposure. Taken together, significant increase in KIM-1, NGAL, and calbindin levels were observed in the urine of rats exposed to Mel+CA (63/6.3 or 630/6.3 mg/kg) compared with the corresponding control group. Histological analysis revealed epithelial degeneration and necrotic cell death in the proximal tubules of the kidney after co-exposure to Mel+CA (63/6.3 or 630/6.3 mg/kg). Our data suggest that Mel-mediated renal toxicity may be influenced by CA concentrations in Mel-contaminated milk or foods. PMID:25071919

Predictors of post-hospitalization recovery of renal function among patients with acute kidney injury requiring dialysis.

PubMed

Pajewski, Russell; Gipson, Patrick; Heung, Michael

2018-01-01

Acute kidney injury (AKI) requiring dialysis complicates 1% of all hospital admissions, and up to 30% of survivors will still require dialysis at hospital discharge. There is a paucity of data to describe the postdischarge outcomes or to guide evidence-based dialysis management of this vulnerable population. Single-center, retrospective analysis of 100 consecutive patients with AKI who survived to hospital discharge and required outpatient dialysis. Data collection included baseline characteristics, hospitalization characteristics, and outpatient dialysis treatment variables. Primary outcome was dialysis independence 90 days after discharge. Overall, 43% of patients recovered adequate renal function to discontinue dialysis, with the majority recovering within 30 days post discharge. Worse baseline renal function was associated with lower likelihood of renal recovery. In the first week postdischarge, patients with subsequent nonrecovery of renal function had greater net fluid removal (5.3 vs. 4.1 L, P = 0.037), higher ultrafiltration rates (6.0 vs. 4.7 mL/kg/h, P = 0.041) and more frequent intradialytic hypotension (24.6% vs. 9.3% with 3 or more episodes, P = 0.049) compared to patients that later recovered. A significant proportion of AKI survivors will recover renal function following discharge. Outpatient intradialytic factors may influence subsequent renal function recovery. © 2017 International Society for Hemodialysis.

The Role of Hydrogen Sulfide in Renal System.

PubMed

Cao, Xu; Bian, Jin-Song

2016-01-01

Hydrogen sulfide has gained recognition as the third gaseous signaling molecule after nitric oxide and carbon monoxide. This review surveys the emerging role of H 2 S in mammalian renal system, with emphasis on both renal physiology and diseases. H 2 S is produced redundantly by four pathways in kidney, indicating the abundance of this gaseous molecule in the organ. In physiological conditions, H 2 S was found to regulate the excretory function of the kidney possibly by the inhibitory effect on sodium transporters on renal tubular cells. Likewise, it also influences the release of renin from juxtaglomerular cells and thereby modulates blood pressure. A possible role of H 2 S as an oxygen sensor has also been discussed, especially at renal medulla. Alternation of H 2 S level has been implicated in various pathological conditions such as renal ischemia/reperfusion, obstructive nephropathy, diabetic nephropathy, and hypertensive nephropathy. Moreover, H 2 S donors exhibit broad beneficial effects in renal diseases although a few conflicts need to be resolved. Further research reveals that multiple mechanisms are underlying the protective effects of H 2 S, including anti-inflammation, anti-oxidation, and anti-apoptosis. In the review, several research directions are also proposed including the role of mitochondrial H 2 S in renal diseases, H 2 S delivery to kidney by targeting D-amino acid oxidase/3-mercaptopyruvate sulfurtransferase (DAO/3-MST) pathway, effect of drug-like H 2 S donors in kidney diseases and understanding the molecular mechanism of H 2 S. The completion of the studies in these directions will not only improves our understanding of renal H 2 S functions but may also be critical to translate H 2 S to be a new therapy for renal diseases.

Impact on creatinine renal clearance by the interplay of multiple renal transporters: a case study with INCB039110.

PubMed

Zhang, Yan; Warren, Mark S; Zhang, Xuexiang; Diamond, Sharon; Williams, Bill; Punwani, Naresh; Huang, Jane; Huang, Yong; Yeleswaram, Swamy

2015-04-01

Serum creatinine is commonly used as a marker of renal function, but increases in serum creatinine might not represent changes in glomerular filtration rate (GFR). INCB039110 (2-(3-(4-(7H-pyrrolo[2,3-day]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(1-(3-fluoro-2-(trifluoromethyl)isonicotinoyl)piperidin-4-yl)azetidin-3-yl)acetonitrile) is an inhibitor of the Janus kinases (JAKs) with selectivity for JAK1. In a phase 1 study, a modest and reversible increase in serum creatinine was observed after treatment with INCB039110. However, a dedicated renal function study with INCB039110, assessed by iohexol plasma clearance, conducted in healthy volunteers indicated no change in GFR. In vitro studies were therefore conducted to investigate the interaction of INCB039110 with five transporters that are likely involved in the renal clearance of creatinine. Cell systems expressing individual or multiple transporters were used, including a novel quintuple-transporter model OAT2/OCT2/OCT3/MATE1/MATE2-K. INCB039110 potently inhibited OCT2-mediated uptake of creatinine as well as MATE1-/MATE2-K-mediated efflux of creatinine. Given the interactions of INCB039110 with multiple transporters affecting creatinine uptake and efflux, an integrated system expressing all five transporters was sought; in that system, INCB039110 caused a dose-dependent decrease in transcellular transport of creatinine with weaker net inhibition compared with the effects on individual transporters. In summary, a molecular mechanism for the increase in serum creatinine by INCB039110 has been established. These studies also underline the limitations of using serum creatinine as a marker of renal function. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

[May renal lithiasis be really prevented? New trends and therapeutic tools.

PubMed

Grases, Félix; Costa-Bauzá, Antonia; Prieto, Rafael M

2017-01-01

Renal calculi are generally formed as a result of the combination of certain factors, some related to urine composition (concentration of lithogenic substances, deficiency of crystallization inhibitors, presence of heterogeneous nucleants) and others with renal morphology and anatomy (urinary tract stasis, low urodynamic efficiency cavities, morpho-anatomic deformations, renal papillary tissue lesions). In fact, the composition, macrostructure and microstructure of the calculus will clearly depend on the factors that have induced it. For this reason, the appropriate study and classification of the renal calculi simplifies the diagnosis and allows a more effective therapeutic approach since it can be oriented to directly correct the etiological factors responsible for stone formation. In this article, we review the main etiological factors involved in the formation of each type of calculus and the prophylactic measures that can be adopted for proper correction. The most frequent kidney stones have been classified into the following types: calcium oxalate monohydrate papillary calculi, calcium oxalate monohydrate non-papillary calculi, calcium oxalate dihydrate calculi, mixed hydroxyapatite/ calcium oxalate calculi, carboxyapatite/hydroxyapatite calculi, brushite calculi, struvite/carboxyapatite calculi, uric acid calculi, uric acid/calcium oxalate monohydrate calculi, and cystine calculi. Occasionally, however, the calculus is not available for study, in which case the only way forward is to use all available information (clinical history, life habits, radiological data), together with basic biochemical information, to identify and correct all etiological factors related to renal lithiasis that have been identified.

Amino acid contribution to protein solubility: Asp, Glu, and Ser contribute more favorably than the other hydrophilic amino acids in RNase Sa.

PubMed

Trevino, Saul R; Scholtz, J Martin; Pace, C Nick

2007-02-16

Poor protein solubility is a common problem in high-resolution structural studies, formulation of protein pharmaceuticals, and biochemical characterization of proteins. One popular strategy to improve protein solubility is to use site-directed mutagenesis to make hydrophobic to hydrophilic mutations on the protein surface. However, a systematic investigation of the relative contributions of all 20 amino acids to protein solubility has not been done. Here, 20 variants at the completely solvent-exposed position 76 of ribonuclease (RNase) Sa are made to compare the contributions of each amino acid. Stability measurements were also made for these variants, which occur at the i+1 position of a type II beta-turn. Solubility measurements in ammonium sulfate solutions were made at high positive net charge, low net charge, and high negative net charge. Surprisingly, there was a wide range of contributions to protein solubility even among the hydrophilic amino acids. The results suggest that aspartic acid, glutamic acid, and serine contribute significantly more favorably than the other hydrophilic amino acids especially at high net charge. Therefore, to increase protein solubility, asparagine, glutamine, or threonine should be replaced with aspartic acid, glutamic acid or serine.

Amino acid contribution to protein solubility: Asp, Glu, and Ser contribute more favorably than the other hydrophilic amino acids in RNase Sa

PubMed Central

Trevino, Saul R.; Scholtz, J. Martin; Pace, C. Nick

2009-01-01

SUMMARY Poor protein solubility is a common problem in high resolution structural studies, formulation of protein pharmaceuticals, and biochemical characterization of proteins. One popular strategy to improve protein solubility is to use site-directed mutagenesis to make hydrophobic to hydrophilic mutations on the protein surface. However, a systematic investigation of the relative contributions of all twenty amino acids to protein solubility has not been done. Here, twenty variants at the completely solvent-exposed position 76 of Ribonuclease (RNase) Sa are made to compare the contributions of each amino acid. Stability measurements were also made for these variants, which occur at the i+1 position of a type II β-turn. Solubility measurements in ammonium sulfate solutions were made at high positive net charge, low net charge, and high negative net charge. Surprisingly, there was a wide range of contributions to protein solubility even among the hydrophilic amino acids. The results suggest that aspartic acid, glutamic acid, and serine contribute significantly more favorably than the other hydrophilic amino acids especially at high net charge. Therefore, to increase protein solubility, asparagine, glutamine, or threonine should be replaced with aspartic acid, glutamic acid or serine. PMID:17174328

The role of platelets and ε-aminocaproic acid in arthrogryposis, renal dysfunction and cholestasis (ARC) syndrome associated hemorrhage

PubMed Central

Weyand, Angela C.; Lombel, Rebecca M.; Pipe, Steven W.; Shavit, Jordan A.

2015-01-01

Arthrogryposis, renal dysfunction and cholestasis (ARC) syndrome is a rare disorder associated with platelet abnormalities resembling Gray Platelet Syndrome. Affected patients have normal platelet numbers but abnormal morphology and function. Bleeding symptomatology ranges from post-procedural to spontaneous life-threatening hemorrhage. We report a patient with ARC syndrome and compound heterozygous mutations in VPS33B who presented with significant bleeding requiring numerous admissions and transfusions. She was treated with prophylactic platelet transfusions and ε-aminocaproic acid. This was well tolerated and significantly decreased transfusion requirements and admissions for bleeding. Our experience provides support for consideration of prophylactic measures in these patients as well as the possibility of using prophylaxis in related disorders. PMID:26505894

The feasibility of using microwave-induced thermoacoustic tomography for detection and evaluation of renal calculi.

PubMed

Cao, Caijun; Nie, Liming; Lou, Cunguang; Xing, Da

2010-09-07

Imaging of renal calculi is important for patients who suffered a urinary calculus prior to treatment. The available imaging techniques include plain x-ray, ultrasound scan, intravenous urogram, computed tomography, etc. However, the visualization of a uric acid calculus (radiolucent calculi) is difficult and often impossible by the above imaging methods. In this paper, a new detection method based on microwave-induced thermoacoustic tomography was developed to detect the renal calculi. Thermoacoustic images of calcium oxalate and uric acid calculus were compared with their x-ray images. The microwave absorption differences among the calcium oxalate calculus, uric acid calculus and normal kidney tissue could be evaluated by the amplitude of the thermoacoustic signals. The calculi hidden in the swine kidney were clearly imaged with excellent contrast and resolution in the three orthogonal thermoacoustic images. The results indicate that thermoacoustic imaging may be developed as a complementary method for detecting renal calculi, and its low cost and effective feature shows high potential for clinical applications.

Proteinuria Impairs Podocyte Regeneration by Sequestering Retinoic Acid

PubMed Central

Peired, Anna; Angelotti, Maria Lucia; Ronconi, Elisa; la Marca, Giancarlo; Mazzinghi, Benedetta; Sisti, Alessandro; Lombardi, Duccio; Giocaliere, Elisa; Della Bona, Marialuisa; Villanelli, Fabio; Parente, Eliana; Ballerini, Lara; Sagrinati, Costanza; Wanner, Nicola; Huber, Tobias B.; Liapis, Helen; Lazzeri, Elena; Lasagni, Laura

2013-01-01

In CKD, the risk of kidney failure and death depends on the severity of proteinuria, which correlates with the extent of podocyte loss and glomerular scarring. We investigated whether proteinuria contributes directly to progressive glomerulosclerosis through the suppression of podocyte regeneration and found that individual components of proteinuria exert distinct effects on renal progenitor survival and differentiation toward a podocyte lineage. In particular, albumin prevented podocyte differentiation from human renal progenitors in vitro by sequestering retinoic acid, thus impairing retinoic acid response element (RARE)-mediated transcription of podocyte-specific genes. In mice with Adriamycin nephropathy, a model of human FSGS, blocking endogenous retinoic acid synthesis increased proteinuria and exacerbated glomerulosclerosis. This effect was related to a reduction in podocyte number, as validated through genetic podocyte labeling in NPHS2.Cre;mT/mG transgenic mice. In RARE-lacZ transgenic mice, albuminuria reduced retinoic acid bioavailability and impaired RARE activation in renal progenitors, inhibiting their differentiation into podocytes. Treatment with retinoic acid restored RARE activity and induced the expression of podocyte markers in renal progenitors, decreasing proteinuria and increasing podocyte number, as demonstrated in serial biopsy specimens. These results suggest that albumin loss through the damaged filtration barrier impairs podocyte regeneration by sequestering retinoic acid and promotes the generation of FSGS lesions. Our findings may explain why reducing proteinuria delays CKD progression and provide a biologic rationale for the clinical use of pharmacologic modulators to induce regression of glomerular diseases. PMID:23949798

Effect of renal denervation on dynamic autoregulation of renal blood flow.

PubMed

DiBona, Gerald F; Sawin, Linda L

2004-06-01

Vasoconstrictor intensities of renal sympathetic nerve stimulation elevate the renal arterial pressure threshold for steady-state stepwise autoregulation of renal blood flow. This study examined the tonic effect of basal renal sympathetic nerve activity on dynamic autoregulation of renal blood flow in rats with normal (Sprague-Dawley and Wistar-Kyoto) and increased levels of renal sympathetic nerve activity (congestive heart failure and spontaneously hypertensive rats). Steady-state values of arterial pressure and renal blood flow before and after acute renal denervation were subjected to transfer function analysis. Renal denervation increased basal renal blood flow in congestive heart failure (+35 +/- 3%) and spontaneously hypertensive rats (+21 +/- 3%) but not in Sprague-Dawley and Wistar-Kyoto rats. Renal denervation significantly decreased transfer function gain (i.e., improved autoregulation of renal blood flow) and increased coherence only in spontaneously hypertensive rats. Thus vasoconstrictor intensities of renal sympathetic nerve activity impaired the dynamic autoregulatory adjustments of the renal vasculature to oscillations in arterial pressure. Renal denervation increased renal blood flow variability in spontaneously hypertensive rats and congestive heart failure rats. The contribution of vasoconstrictor intensities of basal renal sympathetic nerve activity to limiting renal blood flow variability may be important in the stabilization of glomerular filtration rate.

Uric acid lowering to prevent kidney function loss in diabetes: the preventing early renal function loss (PERL) allopurinol study.

PubMed

Maahs, David M; Caramori, Luiza; Cherney, David Z I; Galecki, Andrzej T; Gao, Chuanyun; Jalal, Diana; Perkins, Bruce A; Pop-Busui, Rodica; Rossing, Peter; Mauer, Michael; Doria, Alessandro

2013-08-01

Diabetic kidney disease causes significant morbidity and mortality among people with type 1 diabetes (T1D). Intensive glucose and blood pressure control have thus far failed to adequately curb this problem and therefore a major need for novel treatment approaches exists. Multiple observations link serum uric acid levels to kidney disease development and progression in diabetes and strongly argue that uric acid lowering should be tested as one such novel intervention. A pilot of such a trial, using allopurinol, is currently being conducted by the Preventing Early Renal Function Loss (PERL) Consortium. Although the PERL trial targets T1D individuals at highest risk of kidney function decline, the use of allopurinol as a renoprotective agent may also be relevant to a larger segment of the population with diabetes. As allopurinol is inexpensive and safe, it could be cost-effective even for relatively low-risk patients, pending the completion of appropriate trials at earlier stages.

Prenatal Phthalate, Perfluoroalkyl Acid, and Organochlorine Exposures and Term Birth Weight in Three Birth Cohorts: Multi-Pollutant Models Based on Elastic Net Regression

PubMed Central

Lenters, Virissa; Portengen, Lützen; Rignell-Hydbom, Anna; Jönsson, Bo A.G.; Lindh, Christian H.; Piersma, Aldert H.; Toft, Gunnar; Bonde, Jens Peter; Heederik, Dick; Rylander, Lars; Vermeulen, Roel

2015-01-01

Background Some legacy and emerging environmental contaminants are suspected risk factors for intrauterine growth restriction. However, the evidence is equivocal, in part due to difficulties in disentangling the effects of mixtures. Objectives We assessed associations between multiple correlated biomarkers of environmental exposure and birth weight. Methods We evaluated a cohort of 1,250 term (≥ 37 weeks gestation) singleton infants, born to 513 mothers from Greenland, 180 from Poland, and 557 from Ukraine, who were recruited during antenatal care visits in 2002‒2004. Secondary metabolites of diethylhexyl and diisononyl phthalates (DEHP, DiNP), eight perfluoroalkyl acids, and organochlorines (PCB-153 and p,p´-DDE) were quantifiable in 72‒100% of maternal serum samples. We assessed associations between exposures and term birth weight, adjusting for co-exposures and covariates, including prepregnancy body mass index. To identify independent associations, we applied the elastic net penalty to linear regression models. Results Two phthalate metabolites (MEHHP, MOiNP), perfluorooctanoic acid (PFOA), and p,p´-DDE were most consistently predictive of term birth weight based on elastic net penalty regression. In an adjusted, unpenalized regression model of the four exposures, 2-SD increases in natural log–transformed MEHHP, PFOA, and p,p´-DDE were associated with lower birth weight: –87 g (95% CI: –137, –340 per 1.70 ng/mL), –43 g (95% CI: –108, 23 per 1.18 ng/mL), and –135 g (95% CI: –192, –78 per 1.82 ng/g lipid), respectively; and MOiNP was associated with higher birth weight (46 g; 95% CI: –5, 97 per 2.22 ng/mL). Conclusions This study suggests that several of the environmental contaminants, belonging to three chemical classes, may be independently associated with impaired fetal growth. These results warrant follow-up in other cohorts. Citation Lenters V, Portengen L, Rignell-Hydbom A, Jönsson BA, Lindh CH, Piersma AH, Toft G, Bonde JP

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.

A case report of massive acute boric acid poisoning.

PubMed

Corradi, Francesco; Brusasco, Claudia; Palermo, Salvatore; Belvederi, Giulio

2010-02-01

Boric acid comes as colourless, odourless white powder and, if ingested, has potential fatal effects including metabolic acidosis, acute renal failure and shock. An 82-year-old male was brought to the emergency room 3 h after unintentional ingestion of a large amount of boric acid. Clinical course was monitored by collecting data at admittance, 12 h after admission, every 24 h for 5 days and again 1 week after admission. During the first 132 h, serum and urinary concentrations of boric acid were measured. Serum boric acid levels decreased from 1800 to 530 microg/ml after haemodialysis and from 530 to 30 microg/ml during the forced diuresis period. During dialysis, boric acid clearance averaged 235 ml/min with an extraction ratio of 70%. The overall patient's condition steadily improved over 84 h after admission. In conclusion, early treatment with forced diuresis and haemodialysis may be considered for boric acid poisoning, even if signs of renal dysfunction are not apparent, to prevent severe renal damage and its complications.

The utility of uric acid assay in dogs as an indicator of functional hepatic mass.

PubMed

Hill, J M; Leisewitz, A L; Goddard, A

2011-06-01

Uric acid was used as a test for liver disease before the advent of enzymology. Three old studies criticised uric acid as a test of liver function. Uric acid, as an end-product of purine metabolism in the liver, deserved re-evaluation as a liver function test. Serum totalbile acids are widely accepted as the most reliable liver function test. This study compared the ability of serum uric acid concentration to assess liver function with that of serum pre-prandial bile acids in dogs. In addition, due to the renal excretion of uric acid the 2 assays were also compared in a renal disease group. Using a control group of healthy dogs, a group of dogs with congenital vascular liver disease, a group of dogs with non-vascular parenchymal liver diseases and a renal disease group, the ability of uric acid and pre-prandial bile acids was compared to detect reduced functional hepatic mass overall and in the vascular or parenchymal liver disease groups separately. Sensitivities, specificities and predictive value parameters were calculated for each test. The medians of uric acid concentration did not differ significantly between any of the groups, whereas pre-prandial bile acids medians were significantly higher in the liver disease groups compared with the normal and renal disease group of dogs. The sensitivity of uric acid in detecting liver disease overall was 65% while the specificity of uric acid in detecting liver disease overall was 59%. The sensitivity and specificity of uric acid in detecting congenital vascular liver disease was 68% and 59%, respectively. The sensitivity and specificity of uric acid in detecting parenchymal liver disease was 63% and 60%, respectively. The overall positive and negative predictive values for uric acid in detecting liver disease were poor and the data in this study indicated uric acid to be an unreliable test of liver function. In dogs suffering from renal compromise serum uric acid concentrations may increase into the abnormal range due

NetCDF-U - Uncertainty conventions for netCDF datasets

NASA Astrophysics Data System (ADS)

Bigagli, Lorenzo; Nativi, Stefano; Domenico, Ben

2013-04-01

To facilitate the automated processing of uncertain data (e.g. uncertainty propagation in modeling applications), we have proposed a set of conventions for expressing uncertainty information within the netCDF data model and format: the NetCDF Uncertainty Conventions (NetCDF-U). From a theoretical perspective, it can be said that no dataset is a perfect representation of the reality it purports to represent. Inevitably, errors arise from the observation process, including the sensor system and subsequent processing, differences in scales of phenomena and the spatial support of the observation mechanism, lack of knowledge about the detailed conversion between the measured quantity and the target variable. This means that, in principle, all data should be treated as uncertain. The most natural representation of an uncertain quantity is in terms of random variables, with a probabilistic approach. However, it must be acknowledged that almost all existing data resources are not treated in this way. Most datasets come simply as a series of values, often without any uncertainty information. If uncertainty information is present, then it is typically within the metadata, as a data quality element. This is typically a global (dataset wide) representation of uncertainty, often derived through some form of validation process. Typically, it is a statistical measure of spread, for example the standard deviation of the residuals. The introduction of a mechanism by which such descriptions of uncertainty can be integrated into existing geospatial applications is considered a practical step towards a more accurate modeling of our uncertain understanding of any natural process. Given the generality and flexibility of the netCDF data model, conventions on naming, syntax, and semantics have been adopted by several communities of practice, as a means of improving data interoperability. Some of the existing conventions include provisions on uncertain elements and concepts, but, to our

[Renal patient's diet: Can fish be included?].

PubMed

Castro González, M I; Maafs Rodríguez, A G; Galindo Gómez, C

2012-01-01

Medical and nutritional treatment for renal disease, now a major public health issue, is highly complicated. Nutritional therapy must seek to retard renal dysfunction, maintain an optimal nutritional status and prevent the development of underlying pathologies. To analyze ten fish species to identify those that, because of their low phosphorus content, high biological value protein and elevated n-3 fatty acids EPA and DHA, could be included in renal patient's diet. The following fish species (Litte tunny, Red drum, Spotted eagleray, Escolar, Swordfish, Big-scale pomfret, Cortez flounder, Largemouth blackbass, Periche mojarra, Florida Pompano) were analyzed according to the AOAC and Keller techniques to determine their protein, phosphorus, sodium, potassium, cholesterol, vitamins D(3) and E, and n-3 EPA+DHA content. These results were used to calculate relations between nutrients. The protein in the analyzed species ranged from 16.5 g/100 g of fillet (Largemouth black bass) to 27.2 g/100 g (Red drum); the lowest phosphorus value was 28.6 mg/100 g (Periche mojarra) and the highest 216.3 mg/100 g (Spotted eagle ray). 80% of the fish presented > 100 mg EPA + DHA in 100 g of fillet. By its Phosphorus/gProtein ratio, Escolar and Swordfish could not be included in the renal diet; Little tunny, Escolar, Big-scale pomfret, Largemouth black-bass, Periche mojarra and Florida Pompano presented a lower Phosphorus/EPA + DHA ratio. Florida pompano is the most recommended specie for renal patients, due to its optimal nutrient relations. However, all analyzed species, except Escolar and Swordfish, could be included in renal diets.

Protective propensity of bacoside A and bromelain on renal cholinesterases, γ-Aminobutyric acid and serotonin level of Mus musculus intoxicated with dichlorvos.

PubMed

Agarwal, Sonam; Chaudhary, Bharti; Bist, Renu

2017-01-05

Current study established a protective action of bacoside A and bromelain against the toxic effects of dichlorvos in kidneys of mice. Experimental design included five groups. The first group was control. Mice of groups II, III and IV were administered doses of dichlorvos, bromelain and bacoside A respectively. In group V, mice were treated with both the antioxidants (bacoside A and bromelain) and dichlorvos. After 21 days of exposure of different doses, levels of acetylcholinesterase (AChE), butyrylcholinesterase (BChE), γ-aminobutyric acid (GABA) and serotonin were measured in renal tissues. Dichlorvos significantly reduced the kidney AChE (p < 0.001), BChE (p < 0.01) and GABA level (p < 0.01) compared to control. A simultaneous significant elevation in the serotonin level (p < 0.01) was recorded after dichlorvos exposure. Concomitant exposure of bacoside A and bromelain followed by dichlorvos treatment in group V not only restored, but increased the renal cholinesterases and GABA level. Meanwhile, a significant decline in serotonin level (p < 0.001) was revealed, compared to dichlorvos exposed mice. Bacoside A and bromelain occupy a tremendous antioxidant action in the mice kidneys and a combination of the same ameliorates the renal toxicity induced by dichlorvos. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Potentials and limitations of microorganisms as renal failure biotherapeutics

PubMed Central

Jain, Poonam; Shah, Sapna; Coussa, Razek; Prakash, Satya

2009-01-01

Renal insufficiency leads to uremia, a complicated syndrome. It thus becomes vital to reduce waste metabolites and regulate water and electrolytes in kidney failure. The most common treatment of this disease is either dialysis or transplantation. Although these treatments are very effective, they are extremely costly. Recently artificial cells, microencapsulated live bacterial cells, and other cells have been studied to manage renal failure metabolic wastes. The procedure for microencapsulation of biologically active material is well documented and offers many biomedical applications. Microencapsulated bacteria have been documented to efficiently remove urea and several uremic markers such as ammonia, creatinine, uric acid, phosphate, potassium, magnesium, sodium, and chloride. These bacteria also have further potential as biotherapeutic agents because they can be engineered to remove selected unwanted waste. This application has enormous potential for removal of waste metabolites and electrolytes in renal failure as well as other diseases such as liver failure, phenylketonuria, and Crohn’s disease, to name a few. This paper discusses the various options available to date to manage renal failure metabolites and focuses on the potential of using encapsulated live cells as biotherapeutic agents to control renal failure waste metabolites and electrolytes. PMID:19707412

Bilateral renal oncocytoma in a Greyhound dog.

PubMed

Buergelt, C D; Adjiri-Awere, A

2000-03-01

A bilateral, locally invasive renal oncocytoma was diagnosed in a 10-year-old spayed female Greyhound dog. The diagnosis was based on positive staining of the tumor with the periodic acid-Schiff reaction prior to diastase treatment, on the immunohistochemical expression of cytoplasmic cytokeratin, and on the prominence of mitochondria in the tumor cells.

Extracellular acidosis and very low [Na+ ] inhibit NBCn1- and NHE1-mediated net acid extrusion from mouse vascular smooth muscle cells.

PubMed

Bonde, L; Boedtkjer, E

2017-10-01

The electroneutral Na + , HCO3- cotransporter NBCn1 and Na + /H + exchanger NHE1 regulate acid-base balance in vascular smooth muscle cells (VSMCs) and modify artery function and structure. Pathological conditions - notably ischaemia - can dramatically perturb intracellular (i) and extracellular (o) pH and [Na + ]. We examined effects of low [Na + ] o and pH o on NBCn1 and NHE1 activity in VSMCs of small arteries. We measured pH i by 2',7'-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein-based fluorescence microscopy of mouse mesenteric arteries and induced intracellular acidification by NH4+ prepulse technique. NBCn1 activity - defined as Na + -dependent, amiloride-insensitive net base uptake with CO 2 /HCO3- present - was inhibited equally when pH o decreased from 7.4 (22 mm HCO3-/5% CO 2 ) by metabolic (pH o 7.1/11 mm HCO3-: 22 ± 8%; pH o 6.8/5.5 mm HCO3-: 61 ± 7%) or respiratory (pH o 7.1/10% CO 2 : 35 ± 11%; pH o 6.8/20% CO 2 : 56 ± 7%) acidosis. Extracellular acidosis more prominently inhibited NHE1 activity - defined as Na + -dependent net acid extrusion without CO 2 /HCO3- present - at both pH o 7.1 (45 ± 9%) and 6.8 (85 ± 5%). Independently of pH o , lowering [Na + ] o from 140 to 70 mm reduced NBCn1 and NHE1 activity <20% whereas transport activities declined markedly (25-50%) when [Na + ] o was reduced to 35 mm. Steady-state pH i decreased more during respiratory (ΔpH i /ΔpH o  = 71 ± 4%) than metabolic (ΔpH i /ΔpH o  = 30 ± 7%) acidosis. Extracellular acidification inhibits NBCn1 and NHE1 activity in VSMCs. NBCn1 is equivalently inhibited when pCO 2 is raised or [HCO3-] o decreased. Lowering [Na + ] o inhibits NBCn1 and NHE1 markedly only below the typical physiological and pathophysiological range. We propose that inhibition of Na + -dependent net acid extrusion at low pH o protects against cellular Na + overload at the cost of intracellular acidification. © 2017 Scandinavian Physiological Society. Published by

Correlation between differential renal function estimation using CT-based functional renal parenchymal volume and (99m)Tc - DTPA renal scan.

PubMed

Sarma, Debanga; Barua, Sasanka K; Rajeev, T P; Baruah, Saumar J

2012-10-01

Nuclear renal scan is currently the gold standard imaging study to determine differential renal function. We propose helical CT as single modality for both the anatomical and functional evaluation of kidney with impaired function. In the present study renal parenchymal volume is measured and percent total renal volume is used as a surrogate marker for differential renal function. The objective of this study is to correlate between differential renal function estimation using CT-based renal parenchymal volume measurement with differential renal function estimation using (99m)TC - DTPA renal scan. Twenty-one patients with unilateral obstructive uropathy were enrolled in this prospective comparative study. They were subjected to (99m)Tc - DTPA renal scan and 64 slice helical CT scan which estimates the renal volume depending on the reconstruction of arterial phase images followed by volume rendering and percent renal volume was calculated. Percent renal volume was correlated with percent renal function, as determined by nuclear renal scan using Pearson coefficient. RESULTS AND OBSERVATION: A strong correlation is observed between percent renal volume and percent renal function in obstructed units (r = 0.828, P < 0.001) as well as in nonobstructed units (r = 0.827, P < 0.001). There is a strong correlation between percent renal volume determined by CT scan and percent renal function determined by (99m)TC - DTPA renal scan both in obstructed and in normal units. CT-based percent renal volume can be used as a single radiological tests for both functional and anatomical assessment of impaired renal units.

Validity and reliability of a novel immunosuppressive adverse effects scoring system in renal transplant recipients.

PubMed

Meaney, Calvin J; Arabi, Ziad; Venuto, Rocco C; Consiglio, Joseph D; Wilding, Gregory E; Tornatore, Kathleen M

2014-06-12

After renal transplantation, many patients experience adverse effects from maintenance immunosuppressive drugs. When these adverse effects occur, patient adherence with immunosuppression may be reduced and impact allograft survival. If these adverse effects could be prospectively monitored in an objective manner and possibly prevented, adherence to immunosuppressive regimens could be optimized and allograft survival improved. Prospective, standardized clinical approaches to assess immunosuppressive adverse effects by health care providers are limited. Therefore, we developed and evaluated the application, reliability and validity of a novel adverse effects scoring system in renal transplant recipients receiving calcineurin inhibitor (cyclosporine or tacrolimus) and mycophenolic acid based immunosuppressive therapy. The scoring system included 18 non-renal adverse effects organized into gastrointestinal, central nervous system and aesthetic domains developed by a multidisciplinary physician group. Nephrologists employed this standardized adverse effect evaluation in stable renal transplant patients using physical exam, review of systems, recent laboratory results, and medication adherence assessment during a clinic visit. Stable renal transplant recipients in two clinical studies were evaluated and received immunosuppressive regimens comprised of either cyclosporine or tacrolimus with mycophenolic acid. Face, content, and construct validity were assessed to document these adverse effect evaluations. Inter-rater reliability was determined using the Kappa statistic and intra-class correlation. A total of 58 renal transplant recipients were assessed using the adverse effects scoring system confirming face validity. Nephrologists (subject matter experts) rated the 18 adverse effects as: 3.1 ± 0.75 out of 4 (maximum) regarding clinical importance to verify content validity. The adverse effects scoring system distinguished 1.75-fold increased gastrointestinal adverse

Does Altered Uric Acid Metabolism Contribute to Diabetic Kidney Disease Pathophysiology?

PubMed

Gul, Ambreen; Zager, Philip

2018-03-01

Multiple experimental and clinical studies have identified pathways by which uric acid may facilitate the development and progression of chronic kidney disease (CKD) in people with diabetes. However, it remains uncertain if the association of uric acid with CKD represents a pathogenic effect or merely reflects renal impairment. In contrast to many published reports, a recent Mendelian randomization study did not identify a causal link between uric acid and CKD in people with type 1 diabetes. Two recent multicenter randomized control trials, Preventing Early Renal Function Loss in Diabetes (PERL) and FEbuxostat versus placebo rAndomized controlled Trial regarding reduced renal function in patients with Hyperuricemia complicated by chRonic kidney disease stage 3 (FEATHER), were recently designed to assess if uric acid lowering slows progression of CKD. We review the evidence supporting a role for uric acid in the pathogenesis of CKD in people with diabetes and the putative benefits of uric acid lowering.

Intake of Marine-Derived Omega-3 Polyunsaturated Fatty Acids and Mortality in Renal Transplant Recipients

PubMed Central

Gomes Neto, António W.; Sotomayor Campos, Camilo G.; Pranger, Ilse G.; van den Berg, Else; Gans, Rijk O. B.; Soedamah-Muthu, Sabita S.; Navis, Gerjan J.; Bakker, Stephan J. L.

2017-01-01

The effect of marine-derived omega-3 polyunsaturated fatty acids (n-3 PUFA) on long-term outcome in renal transplant recipients (RTR) remains unclear. We investigated whether marine-derived n-3 PUFA intake is associated with all-cause and cardiovascular (CV) mortality in RTR. Intake of eicosapentaenoic acid plus docosahexaenoic acid (EPA-DHA) was assessed using a validated Food Frequency Questionnaire. Cox regression analyses were performed to evaluate the associations of EPA-DHA intake with all-cause and CV mortality. We included 627 RTR (age 53 ± 13 years). EPA-DHA intake was 102 (42–215) mg/day. During median follow-up of 5.4 years, 130 (21%) RTR died, with 52 (8.3%) due to CV causes. EPA-DHA intake was associated with lower risk of all-cause mortality (Hazard Ratio (HR) 0.85; 95% confidence interval (95% CI) 0.75–0.97). Age (p = 0.03) and smoking status (p = 0.01) significantly modified this association, with lower risk of all-cause and CV mortality particularly in older (HR 0.75, 95% CI 0.61–0.92; HR 0.68, 95% CI 0.48–0.95) and non-smoking RTR (HR 0.80, 95% CI 0.68–0.93; HR 0.74, 95% CI 0.56–0.98). In conclusion, marine-derived n-3 PUFA intake is inversely associated with risk of all-cause and CV mortality in RTR. The strongest associations were present in subgroups of patients, which adds further evidence to the plea for EPA-DHA supplementation, particularly in elderly and non-smoking RTR. PMID:28379169

Renal function in juvenile rats subjected to prenatal malnutrition and chronic salt overload.

PubMed

Magalhães, João Carlos G; da Silveira, Alex B; Mota, Diogenes L; Paixão, Ana Durce O

2006-05-01

Dietary sodium may contribute to hypertension and to cardiovascular and renal disease if a primary deficiency of the kidney to excrete sodium exists. In order to investigate whether chronic 1% NaCl in the drinking water changes blood pressure and renal haemodynamics in juvenile Wistar rats subjected to prenatal malnutrition, an evaluation of plasma volume, oxidative stress in the kidney, proteinuria and renal haemodynamics was carried out. Malnutrition was induced by a multideficient diet. Mean arterial pressure, renal blood flow and glomerular filtration rate (GFR) were measured using a blood pressure transducer, a flow probe and inulin clearance, respectively. Plasma volume and oxidative stress were measured by means of the Evans Blue method and by monitoring thiobarbituric acid reactive substances (TBARS) in the kidneys, respectively. Urinary protein was measured by precipitation with 3% sulphosalicylic acid. It was observed that prenatally malnourished rats presented higher values of plasma volume (26%, P < 0.05), kidney TBARS (43%, P < 0.01) and blood pressure (10%, P < 0.01) when compared with the control group. However, they showed no change in renal haemodynamics or proteinuria. Neither prenatally malnourished nor control rats treated with sodium overload presented plasma volume or blood pressure values different from their respective control groups, but both groups presented elevated proteinuria (P < 0.01). The prenatally malnourished group treated with sodium overload presented higher values of kidney TBARS, GFR and filtration fraction (58, 87 and 72% higher, respectively, P < 0.01) than its respective control group. In summary, sodium overload did not exacerbate the hypertension in juvenile prenatally malnourished rats, but induced renal haemodynamic adjustments compatible with the development of renal disease.

Handling of the homocysteine S-conjugate of methylmercury by renal epithelial cells: role of organic anion transporter 1 and amino acid transporters.

PubMed

Zalups, Rudolfs K; Ahmad, Sarfaraz

2005-11-01

Recently, the activity of the organic anion transporter 1 (OAT1) protein has been implicated in the basolateral uptake of inorganic mercuric species in renal proximal tubular cells. Unfortunately, very little is known about the role of OAT1 in the renal epithelial transport of organic forms of mercury, such as methylmercury (CH(3)Hg(+)). Homocysteine (Hcy) S-conjugates of methylmercury [(S)-(3-amino-3-carboxypropylthio)(methyl)mercury (CH(3)Hg-Hcy)] have been identified recently as being potentially important biologically relevant forms of mercury. Thus, the present study was designed to characterize the transport of CH(3)Hg-Hcy in Madin-Darby canine kidney (MDCK) cells (which are derived from the distal nephron) that were transfected stably with the human isoform of OAT1 (hOAT1). Data on saturation kinetics, time dependence, substrate specificity, and temperature dependence demonstrated that CH(3)Hg-Hcy is a transportable substrate of hOAT1. However, substrate-specificity data from the control MDCK cells also showed that CH(3)Hg-Hcy is a substrate of one or more transporter(s) that is/are not hOAT1. Additional findings indicated that at least one amino acid transport system was probably responsible for this transport. It is noteworthy that the activity of amino acid transporters accounted for the greatest level of uptake of CH(3)Hg-Hcy in the hOAT1-expressing cells. Furthermore, rates of survival of the hOAT1-transfected MDCK cells were significantly lower than those of corresponding control MDCK cells when they were exposed to cytotoxic concentrations of CH(3)Hg-Hcy. Collectively, the present data indicate that CH(3)Hg-Hcy is a transportable substrate of OAT1 and amino acid transporters and, thus, is probably a transportable mercuric species taken up in vivo by proximal tubular epithelial cells.

Effects of water immersion on renal hemodynamics in normal man

NASA Technical Reports Server (NTRS)

Epstein, M.; Levinson, R.; Loutzenhiser, R.

1976-01-01

The present study was undertaken to delineate the effects of water immersion to the neck (NI) on renal plasma flow and glomerular filtration rate as assessed by the clearance of p-aminohippuric acid (PAH) and inulin, respectively. Nine normal male subjects were studied on two occasions, control and NI. The conditions of seated posture and time of day were identical. Immersion did not alter either clearance at a time when sodium excretion was increasing markedly. The constancy of PAH clearance during NI suggests that renal blood flow is unaltered and that the natriuresis of NI is mediated independently of alterations in overall renal perfusion. The sluggish decline of a natriuresis during recovery is consistent with the presence of a humoral factor contributing to the encountered natriuresis.

Glutaric Aciduria Type 1 and Acute Renal Failure: Case Report and Suggested Pathomechanisms.

PubMed

du Moulin, Marcel; Thies, Bastian; Blohm, Martin; Oh, Jun; Kemper, Markus J; Santer, René; Mühlhausen, Chris

2018-01-01

Glutaric aciduria type 1 (GA1) is caused by deficiency of the mitochondrial matrix enzyme glutaryl-CoA dehydrogenase (GCDH), leading to accumulation of glutaric acid (GA) and 3-hydroxyglutaric acid (3OHGA) in tissues and body fluids. During catabolic crises, GA1 patients are prone to the development of striatal necrosis and a subsequent irreversible movement disorder during a time window of vulnerability in early infancy. Thus, GA1 had been considered a pure "cerebral organic aciduria" in the past. Single case reports have indicated the occurrence of acute renal dysfunction in children affected by GA1. In addition, growing evidence arises that GA1 patients may develop chronic renal failure during adulthood independent of the previous occurrence of encephalopathic crises. The underlying mechanisms are yet unknown. Here we report on a 3-year-old GA1 patient who died following the development of acute renal failure most likely due to haemolytic uraemic syndrome associated with a pneumococcal infection. We hypothesise that known GA1 pathomechanisms, namely the endothelial dysfunction mediated by 3OHGA, as well as the transporter mechanisms for the urinary excretion of GA and 3OHGA, are involved in the development of glomerular and tubular dysfunction, respectively, and may contribute to a pre-disposition of GA1 patients to renal disease. We recommend careful differential monitoring of glomerular and tubular renal function in GA1 patients.

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.

The Role of Platelets and ε-Aminocaproic Acid in Arthrogryposis, Renal Dysfunction, and Cholestasis (ARC) Syndrome Associated Hemorrhage.

PubMed

Weyand, Angela C; Lombel, Rebecca M; Pipe, Steven W; Shavit, Jordan A

2016-03-01

Arthrogryposis, renal dysfunction, and cholestasis (ARC) syndrome is a rare disorder associated with platelet abnormalities resembling gray platelet syndrome. Affected patients have normal platelet numbers but abnormal morphology and function. Bleeding symptomatology ranges from postprocedural to spontaneous life-threatening hemorrhage. We report a patient with ARC syndrome and compound heterozygous mutations in VPS33B (vacuolar protein sorting 33B) who presented with significant bleeding requiring numerous admissions and transfusions. She was treated with prophylactic platelet transfusions and ε-aminocaproic acid. This was well-tolerated and significantly decreased transfusion requirements and admissions for bleeding. Our experience provides support for consideration of prophylactic measures in these patients as well as the possibility of using prophylaxis in related disorders. © 2015 Wiley Periodicals, Inc.

The equivalency between logic Petri workflow nets and workflow nets.

PubMed

Wang, Jing; Yu, ShuXia; Du, YuYue

2015-01-01

Logic Petri nets (LPNs) can describe and analyze batch processing functions and passing value indeterminacy in cooperative systems. Logic Petri workflow nets (LPWNs) are proposed based on LPNs in this paper. Process mining is regarded as an important bridge between modeling and analysis of data mining and business process. Workflow nets (WF-nets) are the extension to Petri nets (PNs), and have successfully been used to process mining. Some shortcomings cannot be avoided in process mining, such as duplicate tasks, invisible tasks, and the noise of logs. The online shop in electronic commerce in this paper is modeled to prove the equivalence between LPWNs and WF-nets, and advantages of LPWNs are presented.

The Equivalency between Logic Petri Workflow Nets and Workflow Nets

PubMed Central

Wang, Jing; Yu, ShuXia; Du, YuYue

2015-01-01

Logic Petri nets (LPNs) can describe and analyze batch processing functions and passing value indeterminacy in cooperative systems. Logic Petri workflow nets (LPWNs) are proposed based on LPNs in this paper. Process mining is regarded as an important bridge between modeling and analysis of data mining and business process. Workflow nets (WF-nets) are the extension to Petri nets (PNs), and have successfully been used to process mining. Some shortcomings cannot be avoided in process mining, such as duplicate tasks, invisible tasks, and the noise of logs. The online shop in electronic commerce in this paper is modeled to prove the equivalence between LPWNs and WF-nets, and advantages of LPWNs are presented. PMID:25821845

Effect of photo-selective nettings on post-harvest quality and bioactive compounds in selected tomato cultivars.

PubMed

Selahle, Maphoko Kamogelo; Sivakumar, Dharini; Soundy, Puffy

2014-08-01

Photo-selective coloured netting is referred to as a 'new agro-technological' concept adopted to manipulate light quality changes that can induce favourable responses in plants. Tomato (Solanum lycopersicum L.) cultivars AlvaV, Irit and SCX 248 grown under the black net (commercial net, 25% shading) showed higher weight loss, loss of firmness, ascorbic acid content and decline in the ratio of soluble solids content/titrable acidity during post-harvest storage (low-temperature storage at 10°C and 90% relative humidity for 21 days followed by market shelf conditions at 25°C for 2 days). During post-harvest storage, lycopene, β-carotene, total phenolic content and antioxidant scavenging activity were higher in cvs AlfaV and Irit grown under the black or pearl nets. However, the β-carotene, total phenolic content and antioxidant scavenging activity were higher in SCX 248 grown under the red net during post-harvest storage. Cultivar AlfaV grown under the red and pearl nets had a higher number of odour active aroma compounds during post-harvest storage. Panellists preferred cv. AlfaV grown under the pearl nets after storage based on taste, overall appearance and firm textured fruits. Pearl photo-selective nets retained the overall fruit quality and bioactive components in cvs AlfaV and Irit during post-harvest storage. Red photo-selective nets, however, showed greater influence on retention of overall fruit quality and bioactive compounds in cv. SCX 248 during post-harvest storage. © 2013 Society of Chemical Industry.

Boldine prevents renal alterations in diabetic rats.

PubMed

Hernández-Salinas, Romina; Vielma, Alejandra Z; Arismendi, Marlene N; Boric, Mauricio P; Sáez, Juan C; Velarde, Victoria

2013-01-01

Diabetic nephropathy alters both structure and function of the kidney. These alterations are associated with increased levels of reactive oxygen species, matrix proteins, and proinflammatory molecules. Inflammation decreases gap junctional communication and increases hemichannel activity leading to increased membrane permeability and altering tissue homeostasis. Since current treatments for diabetic nephropathy do not prevent renal damage, we postulated an alternative treatment with boldine, an alkaloid obtained from boldo with antioxidant, anti-inflammatory, and hypoglycemic effects. Streptozotocin-induced diabetic and control rats were treated or not treated with boldine (50 mg/Kg/day) for ten weeks. In addition, mesangial cells were cultured under control conditions or in high glucose concentration plus proinflammatory cytokines, with or without boldine (100 µmol/L). Boldine treatment in diabetic animals prevented the increase in glycemia, blood pressure, renal thiobarbituric acid reactive substances and the urinary protein/creatinine ratio. Boldine also reduced alterations in matrix proteins and markers of renal damage. In mesangial cells, boldine prevented the increase in oxidative stress, the decrease in gap junctional communication, and the increase in cell permeability due to connexin hemichannel activity induced by high glucose and proinflammatory cytokines but did not block gap junction channels. Thus boldine prevented both renal and cellular alterations and could be useful for preventing tissue damage in diabetic subjects.

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

Mathematical Modeling of Renal Hemodynamics in Physiology and Pathophysiology

PubMed Central

Sgouralis, Ioannis; Layton, Anita T.

2015-01-01

In addition to the excretion of metabolic waste and toxin, the kidney plays an indispensable role in regulating the balance of water, electrolyte, acid-base, and blood pressure. For the kidney to maintain proper functions, hemodynamic control is crucial. In this review, we describe representative mathematical models that have been developed to better understand the kidney's autoregulatory processes. We consider mathematical models that simulate glomerular filtration, and renal blood flow regulation by means of the myogenic response and tubuloglomerular feedback. We discuss the extent to which these modeling efforts have expanded the understanding of renal functions in health and disease. PMID:25765886

Vitamin U has a protective effect on valproic acid-induced renal damage due to its anti-oxidant, anti-inflammatory, and anti-fibrotic properties.

PubMed

Gezginci-Oktayoglu, Selda; Turkyilmaz, Ismet Burcu; Ercin, Merve; Yanardag, Refiye; Bolkent, Sehnaz

2016-01-01

The aim of present study was to investigate the effect of vitamin U (vit U, S-methylmethionine) on oxidative stress, inflammation, and fibrosis within the context of valproic acid (VPA)-induced renal damage. In this study, female Sprague Dawley rats were randomly divided into four groups: Group I consisted of intact animals, group II was given vit U (50 mg/kg/day, by gavage), group III was given VPA (500 mg/kg/day, intraperitonally), and group IV was given VPA + vit U. The animals were treated by vit U 1 h prior to treatment with VPA every day for 15 days. The following results were obtained in vit U + VPA-treated rats: (i) the protective effect of vit U on renal damage was shown by a significant decrease in histopathological changes and an increase in Na(+)/K(+)-ATPase activity; (ii) anti-oxidant property of vit U was demonstrated by a decrease in malondialdehyde levels and xanthine oxidase activity and an increase in glutathione levels, catalase and superoxide dismutase activities; (iii) anti-inflammatory property of vit U was demonstrated by a decrease in tumor necrosis factor-α, interleukin-1β, monocyte chemoattractant protein-1 levels, and adenosine deaminase activity; (iv) anti-fibrotic effect of vit U was shown by a decrease in transforming growth factor-β, collagen-1 levels, and arginase activity. Collectively, these data show that VPA is a promoter of inflammation, oxidative stress, and fibrosis which resulted in renal damage. Vit U can be proposed as a potential candidate for preventing renal damage which arose during the therapeutic usage of VPA.

Correlation analysis of renal ultrasound elastography and clinical and pathological changes in patients with chronic kidney disease
.

PubMed

Peng, Lingyan; Zhong, Tingting; Fan, Qiuling; Liu, Yanjun; Wang, Xuemei; Wang, Lining

2017-06-01

To analyze the correlations of renal tissue elastography with clinical biochemical indicators and pathological changes in patients with chronic kidney disease (CKD) as well as to explore the potential for renal tissue elastography as a new, noninvasive method for the dynamic monitoring of renal disease progression, efficacy assessment, and prognosis evaluation. Patients admitted to the Department of Nephrology of the First Affiliated Hospital of China Medical University from August 2014 to January 2015 who had undergone renal biopsies were selected. A total of 113 patients with CKD and 16 healthy controls were enrolled in this study, including 61 males and 52 females. In total, 23 cases of IgA nephropathy, 39 cases of membranous nephropathy, 15 cases of minimal-change nephropathy (MCN), and 7 cases of focal segmental glomerulosclerosis were included. The Young's moduli (YM) of the renal cortex and medulla were measured using an AixPlorer Doppler ultrasound with full digital color from Supersonic Imagine. The correlations between the YM of renal tissue and clinical biochemical indicators of blood and urine and the differences in Young's moduli among the different pathological changes in the patients with CKD were analyzed. The YM of the CKD patients was significantly higher than that of the control group (p < 0.05), and the YM of the renal cortex and medulla gradually increased with the progression of CKD. The YM of the renal cortex in the stage-G5 CKD patients was significantly higher than that of the CKD patients in stages G1 - G3 (p < 0.05). The YM of the renal medulla of the CKD patients in stages G3 - 5 was significantly higher than that of the CKD patients in stages G1 - G2. On univariate analysis, the YM of the renal cortex was correlated with systolic blood pressure, serum creatinine, cystatin C, serum albumin, serum phosphorus, calcium and phosphorus products, uric acid, iPTH, urinary N-acetyl-glucosaminidase (NAG), eGFR, and hemoglobin levels. And

Dietary acid load, trabecular bone integrity, and mineral density in an ageing population: the Rotterdam study.

PubMed

de Jonge, E A L; Koromani, F; Hofman, A; Uitterlinden, A G; Franco, O H; Rivadeneira, F; Kiefte-de Jong, J C

2017-08-01

We studied the relation between a diet that is high in acid-forming nutrients (e.g. proteins) and low in base-forming nutrients (e.g. potassium) and bone structure. We showed a negative relation, which was more prominent if proteins were of animal rather than of vegetable origin and if intake of dietary fibre was high. Studies on dietary acid load (DAL) and fractures have shown inconsistent results. Associations between DAL, bone mineral density (BMD) and trabecular bone integrity might play a role in these inconsistencies and might be influenced by renal function and dietary fibre intake. Therefore, our aim was to study (1) associations of DAL with BMD and with the trabecular bone score (TBS) and (2) the potential influence of renal function and dietary fibre in these associations. Dutch individuals aged 45 years and over (n = 4672) participating in the prospective cohort of the Rotterdam study were included. Based on food frequency questionnaires, three indices of DAL were calculated: the net endogenous acid production (NEAP) and the ratios of vegetable or animal protein and potassium (VegPro/K and AnPro/K). Data on lumbar spinal TBS and BMD were derived from dual-energy X-ray absorptiometry measurements. Independent of confounders, NEAP and AnPro/K, but not VegPro/K, were associated with low TBS (standardized β (95%) = -0.04 (-0.07, -0.01) and -0.08 (-0.11, -0.04)) but not with BMD. Associations of AnPro/K and VegPro/K with TBS were non-linear and differently shaped. Unfavourable associations between NEAP, BMD and TBS were mainly present in subgroups with high fibre intake. High NEAP was associated with low TBS. Associations of AnPro/K and VegPro/K and TBS were non-linear and differently shaped. No significant associations of DAL with BMD were observed, nor was there any significant interaction between DAL and renal function. Mainly in participants with high intake of dietary fibre, DAL might be detrimental to bone.

Renal perfusion scintiscan

MedlinePlus

... Radionuclide renal perfusion scan; Perfusion scintiscan - renal; Scintiscan - renal perfusion Images Kidney anatomy Kidney - blood and urine flow Intravenous pyelogram References Rottenberg G, Andi AC. Renal ...

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.

Net one, net two: the primary care network income statement.

PubMed

Halley, M D; Little, A W

1999-10-01

Although hospital-owned primary care practices have been unprofitable for most hospitals, some hospitals are achieving competitive advantage and sustainable practice operations. A key to the success of some has been a net income reporting tool that separates practice operating expenses from the costs of creating and operating a network of practices to help healthcare organization managers, physicians, and staff to identify opportunities to improve the network's financial performance. This "Net One, Net Two" reporting allows operations leadership to be held accountable for Net One expenses and strategic leadership to be held accountable for Net Two expenses.

Evaluation of interobserver variability of parenchymal phase of Tc-99m mercaptoacetyltriglycine and Tc-99m dimercaptosuccinic acid renal scintigraphy

PubMed Central

Erdoğan, Zeynep; Abdülrezzak, Ümmühan; Silov, Güler; Özdal, Ayşegül; Turhal, Özgül

2014-01-01

Objective: The aim of this study was to investigate the variability in the interpretation of parenchymal abnormalities and to assess the differences in interpretation of routine renal scintigraphic findings on posterior view of technetium-99m dimercaptosuccinic acid (pvDMSA) scans and parenchymal phase of technetium-99m mercaptoacetyltriglycine (ppMAG3) scans by using standard criterions to make standardization and semiquantitative evaluation and to have more accurately correlation. Materials and Methods: Two experienced nuclear medicine physicians independently interpreted pvDMSA scans of 204 and ppMAG3 scans of 102 pediatric patients, retrospectively. Comparisons were made by visual inspection of pvDMSA scans, and ppMAG3 scans by using a grading system modified from Itoh et al. According to this, anatomical damage of the renal parenchyma was classified into six types: Grade 0-V. In the calculation of the agreement rates, Kendall correlation (tau-b) analysis was used. Results: According to our findings, excellent agreement was found for DMSA grade readings (DMSA-GR) (tau-b = 0.827) and good agreement for MAG3 grade readings (MAG3-GR) (tau-b = 0.790) between two observers. Most of clear parenchymal lesions detected on pvDMSA scans and ppMAG3 scans identified by observers equally. Studies with negative or minimal lesions reduced correlation degrees for both DMSA-GR and MAG3-GR. Conclusion: Our grading system can be used for standardization of the reports. We conclude that standardization of criteria and terminology in the interpretations may result in higher interobserver consistency, also improve low interobserver reproducibility and objectivity of renal scintigraphy reports. PMID:24761059

Dysregulation of renal aquaporins and epithelial sodium channel in lithium-induced nephrogenic diabetes insipidus.

PubMed

Nielsen, Jakob; Kwon, Tae-Hwan; Christensen, Birgitte Mønster; Frøkiaer, Jørgen; Nielsen, Søren

2008-05-01

Lithium is used commonly to treat bipolar mood disorders. In addition to its primary therapeutic effects in the central nervous system lithium has a number of side effects in the kidney. The side effects include nephrogenic diabetes insipidus with polyuria, mild sodium wasting, and changes in acid/base balance. These functional changes are associated with marked structural changes in collecting duct cell composition and morphology, likely contributing to the functional changes. Over the past few years, investigations of lithium-induced renal changes have provided novel insight into the molecular mechanisms that are responsible for the disturbances in water, sodium, and acid/base metabolism. This includes dysregulation of renal aquaporins, epithelial sodium channel, and acid/base transporters. This review focuses on these issues with the aim to present this in context with clinically relevant features.

Renal-Stone Risk Assessment During Space Shuttle Flights

NASA Technical Reports Server (NTRS)

Whitson, Peggy A.; Pietrzyk, Robert A.; Pak, Charles Y. C.

1996-01-01

The metabolic and environmental factors influencing renal stone formation before, during, and after Space Shuttle flights were assessed. We established the contributing roles of dietary factors in relationship to the urinary risk factors associated with renal stone formation. 24-hr urine samples were collected prior to, during space flight, and following landing. Urinary factors associated with renal stone formation were analyzed and the relative urinary supersaturation ratios of calcium oxalate, calcium phosphate (brushite), sodium urate, struvite and uric acid were calculated. Food and fluid consumption was recorded for a 48-hr period ending with the urine collection. Urinary composition changed during flight to favor the crystallization of stone-forming salts. Factors that contributed to increased potential for stone formation during space flight were significant reductions in urinary pH and increases in urinary calcium. Urinary output and citrate, a potent inhibitor of calcium-containing stones, were slightly reduced during space flight. Dietary intakes were significantly reduced for a number of variables, including fluid, energy, protein, potassium, phosphorus and magnesium. This is the first in-flight characterization of the renal stone forming potential in astronauts. With the examination of urinary components and nutritional factors, it was possible to determine the factors that contributed to increased risk or protected from risk. In spite of the protective components, the negative contributions to renal stone risk predominated and resulted in a urinary environment that favored the supersaturation of stone-forming salts. The importance of the hypercalciuria was noted since renal excretion was high relative to the intake.

Renal stone risk assessment during Space Shuttle flights

NASA Technical Reports Server (NTRS)

Whitson, P. A.; Pietrzyk, R. A.; Pak, C. Y.

1997-01-01

PURPOSE: The metabolic and environmental factors influencing renal stone formation before, during, and after Space Shuttle flights were assessed. We established the contributing roles of dietary factors in relationship to the urinary risk factors associated with renal stone formation. MATERIALS AND METHODS: 24-hr. urine samples were collected prior to, during space flight, and following landing. Urinary and dietary factors associated with renal stone formation were analyzed and the relative urinary supersaturation of calcium oxalate, calcium phosphate (brushite), sodium urate, struvite and uric acid were calculated. RESULTS: Urinary composition changed during flight to favor the crystallization of calcium-forming salts. Factors that contributed to increased potential for stone formation during space flight were significant reductions in urinary pH and increases in urinary calcium. Urinary output and citrate, a potent inhibitor of calcium-containing stones, were slightly reduced during space flight. Dietary intakes were significantly reduced for a number of variables, including fluid, energy, protein, potassium, phosphorus and magnesium. CONCLUSIONS: This is the first in-flight characterization of the renal stone forming potential in astronauts. With the examination of urinary components and nutritional factors, it was possible to determine the factors that contributed to increased risk or protected from risk. In spite of the protective components, the negative contributions to renal stone risk predominated and resulted in a urinary environment that favored the supersaturation of stone-forming salts. Dietary and pharmacologic therapies need to be assessed to minimize the potential for renal stone formation in astronauts during/after space flight.

Stanniocalcin 1 effects on the renal gluconeogenesis pathway in rat and fish.

PubMed

Schein, Vanessa; Kucharski, Luiz C; Guerreiro, Pedro M G; Martins, Tiago Leal; Morgado, Isabel; Power, Deborah M; Canario, Adelino V M; da Silva, Roselis S M

2015-10-15

The mammalian kidney contributes significantly to glucose homeostasis through gluconeogenesis. Considering that stanniocalcin 1 (STC1) regulates ATP production, is synthesized and acts in different cell types of the nephron, the present study hypothesized that STC1 may be implicated in the regulation of gluconeogenesis in the vertebrate kidney. Human STC1 strongly reduced gluconeogenesis from (14)C-glutamine in rat renal medulla (MD) slices but not in renal cortex (CX), nor from (14)C-lactic acid. Total PEPCK activity was markedly reduced by hSTC1 in MD but not in CX. Pck2 (mitochondrial PEPCK isoform) was down-regulated by hSTC1 in MD but not in CX. In fish (Dicentrarchus labrax) kidney slices, both STC1-A and -B isoforms decreased gluconeogenesis from (14)C-acid lactic, while STC1-A increased gluconeogenesis from (14)C-glutamine. Overall, our results demonstrate a role for STC1 in the control of glucose synthesis via renal gluconeogenesis in mammals and suggest that it may have a similar role in teleost fishes. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Evaluation of anti-apoptotic activity of different dietary antioxidants in renal cell carcinoma against hydrogen peroxide

PubMed Central

Garg, Neeraj K; Mangal, Sharad; Sahu, Tejram; Mehta, Abhinav; Vyas, Suresh P; Tyagi, Rajeev K

2011-01-01

Objective To evaluate the anti-apoptotic and radical scavenging activities of dietary phenolics, namely ascorbic acid,α-tocopherol acetate, citric acid, salicylic acid, and estimate H2O2-induced apoptosis in renal cell carcinoma cells. Methods The intracellular antioxidant potency of antioxidants was investigated. H2O2-induced apoptosis in RCC-26 was assayed with the following parameters: cell viability (% apoptosis), nucleosomal damage and DNA fragmentation, bcl-2 levels and flow cytometery analysis (ROS production evaluation). Results The anticancer properties of antioxidants such as ascorbic acid, α-tocopherol acetate, citric acid, salicylic acid with perdurable responses were investigated. It was observed that these antioxidants had protective effect (anti-apoptotic activity) against hydrogen peroxide (H2O2) in renal cell carcinoma (RCC-26) cell line. Conclusions This study reveals and proves the anticancer properties. However, in cancer cell lines anti-apoptotic activity can indirectly reflect the cancer promoter activity through radicals scavenging, and significantly protect nucleus and bcl-2. PMID:23569726

[The degree of chronic renal failure is associated with the rate of pro-inflammatory cytokines, hyperhomocysteinemia and with oxidative stress].

PubMed

Tbahriti, H F; Messaoudi, A; Kaddous, A; Bouchenak, M; Mekki, K

2014-06-01

To evaluate pro-inflammatory cytokines, homocysteinemia and markers of oxidative status in the course of chronic renal failure. One hundred and two patients (male/female: 38/64; age: 45±07 years) with chronic renal failure were divided into 4 groups according to the National Kidney Foundation classification. They included 28 primary stage renal failure patients, 28 moderate stage renal failure, 28 severe stage renal failure and 18 end stage renal failure. The inflammatory status was evaluated by the determination of pro-inflammatory cytokines (tumor necrosis factor-α, interleukin-1β, interleukin-6) and total homocysteine. Pro-oxidant status was assessed by assaying thiobarbituric acid reactive substances, hydroperoxides, and protein carbonyls. Antioxidant defence was performed by analysis of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase. Inflammatory markers were elevated in the end stage renal failure group compared to the other groups (P<0.001). Indeed, an increase in thiobarbituric acid reactive substances, hydroperoxides and protein carbonyls was noted in the end stage renal failure group in comparison with the other groups (P<0.001), while the levels of antioxidants enzymes activity were decreased in the study population (P<0.001). Impaired renal function is closely associated with the elevation of inflammatory markers leading to both increased markers of oxidative stress and decreased antioxidant defense. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Silymarin protects against renal injury through normalization of lipid metabolism and mitochondrial biogenesis in high fat-fed mice.

PubMed

Bin Feng; Meng, Ran; Bin Huang; Bi, Yan; Shen, Shanmei; Zhu, Dalong

2017-09-01

Obesity is associated with an increased risk of chronic kidney diseases and the conventional treatment with renin-angiotensin-aldosterone system (RAAS) inhibitors is not enough to prevent renal injury and prolong the progression of disease. Recently, silymarin has shown protective effects on renal tissue injury, but the underlying mechanisms remain elusive. The goal of this study was to investigate the potential capacity of silymarin to prevent renal injury during obesity induced by high fat diet (HFD) in mice. In vivo, male C57BL/6 mice received HFD (60% of total calories) for 12 weeks, randomized and treated orally with vehicle saline or silymarin (30mg/kg body weight/d) for 4 weeks. In vitro, human proximal tubular epithelial cells (HK2) were exposed to 300μM palmitic acid (PA) for 36h followed by silymarin administration at different concentrations. The administration of silymarin significantly ameliorated HFD induced glucose metabolic disorders, oxidative stress and pathological alterations in the kidney. Silymarin significantly mitigated renal lipid accumulation, fatty acid β-oxidation and mitochondrial biogenesis in HFD mice and PA treated HK2 cells. Furthermore, silymarin partly restored mitochondrial membrane potential of HK2 cells after PA exposure. In conclusion, silymarin can improve oxidative stress and preserve mitochondrial dysfunction in the kidney, potentially via preventing accumulation of renal lipids and fatty acid β-oxidation. Copyright © 2017. Published by Elsevier Inc.

Structural and functional correlations in stable renal allografts.

PubMed

Fulladosa, Xavier; Moreso, Francesc; Torras, Joan; Hueso, Miquel; Grinyó, Josep M; Serón, Daniel

2003-05-01

Renal functional reserve (RFR) has been proposed as a surrogate marker of renal mass, but its significance in well-functioning renal transplants is controversial. Thus, we used early protocol biopsies to analyze structural and functional correlations in stable grafts. We studied 32 cyclosporine (CsA)-treated stable cadaveric transplants at 5 months. Biopsies were evaluated according to Banff criteria and histomorphometry. Inulin and p-aminohippurate clearances were used to calculate glomerular filtration rate (GFR) and effective renal plasma flow (ERPF). RFR after an amino acid infusion (RFR-AA) and after a combined amino acid and dopamine infusion (RFR-AA-DOPA) was evaluated. Baseline GFR was 54 +/- 16 mL/min/1.73 m2, and ERPF was 219 +/- 55 mL/min/1.73 m2. RFR-AA was 9% +/- 13%, and RFR-AA-DOPA was 22% +/- 20%. RFR-AA correlated with CsA dose (R = 0.39; P = 0.02), whereas RFR-AA-DOPA correlated with CsA dose (R = 0.36; P = 0.04) and CsA levels (R = 0.40; P = 0.02). The only histological parameter associated with RFR was the presence of arteriolar hyalinosis (AH). Patients showing an AH score of 1 or greater (n = 7) had lower RFR-AA (0% +/- 9% versus 11% +/- 13%; P = 0.02) and lower RFR-AA-DOPA (9% +/- 17% versus 26% +/- 19%; P = 0.03). Multivariate analysis showed that an AH score of 1 or greater, but not CsA dose or levels, was associated with RFR-AA (R = 0.42; P = 0.01). RFR-AA-DOPA was associated with hyaline arteriolar damage (R = 0.43; P = 0.01), as well as CsA levels (R = 0.54; P = 0.006). The presence of AH is the only histological parameter associated with impaired RFR in well-functioning grafts.

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 cortical thickness and PON1 activity both decrease in chronic renal failure.

PubMed

Ak, Gülçin; Ozgönül, Mert; Sözmen, Eser Y; Aslan, S Leyla; Sözmen, Bülent

2002-01-01

Chronic renal failure (CRF) is associated with a tendency to atherosclerosis due to the enhanced oxidative stress and insufficient antioxidant enzyme activities such as superoxide dismutase (SOD), catalase (CAT) and paraoxonase (PON 1), together with abnormalities in lipid parameters. We determined the in vitro susceptibility of low-density lipoprotein (LDL) to oxidation and PON1 activities in patients with chronic renal insufficiency to see how PON1 affected the progression of the disease and whether hemodialysis influenced these parameters. Thirty-seven patients (21 men, 16 women, mean age 43.9 +/- 16) with CRF were included, 23 were receiving hemodialysis treatment. Exclusion criteria were diabetes mellitus and acute coronary disease. Eighteen healthy subjects (9 men and 9 women, mean age 39.9 +/- 10.5) volunteered to participate as controls. All patients were evaluated by renal ultrasound (USG) and two-dimensional echography, and their lipid profiles, PON1 activity, basal and Cu-induced LDL oxidation were determined. PON1 activities of patients were lower than controls (14.4 +/- 11 vs 30.9 +/- 19 U/L, p < 0.05) while basal ox-LDL levels determined by the thiobarbituric acid reactive substances (TBARS) method were higher (0.6 +/- 0.4 vs 0.4+/- 0.2 nmol/mg LDL protein, p<0.01). There was no significant difference between the groups treated with hemodialysis or not. There was a positive correlation between renal cortical thickness and HDL levels (r=0.47, p=0.006) and PON1 activity (r=0.45, p=0.01). Our data showed that HDL cholesterol levels and PON1 activities were both lower in patients, indicating depletion of the protective antioxidant capacity. PON1 activities and phenotypes were no different in patients with coronary disease and others so it does not appear to be a significant indicator of coronary artery disease in patients with CRF.

SGLT2 inhibitor lowers serum uric acid through alteration of uric acid transport activity in renal tubule by increased glycosuria

PubMed Central

Chino, Yukihiro; Samukawa, Yoshishige; Sakai, Soichi; Nakai, Yasuhiro; Yamaguchi, Jun-ichi; Nakanishi, Takeo; Tamai, Ikumi

2014-01-01

Sodium glucose cotransporter 2 (SGLT2) inhibitors have been reported to lower the serum uric acid (SUA) level. To elucidate the mechanism responsible for this reduction, SUA and the urinary excretion rate of uric acid (UEUA) were analysed after the oral administration of luseogliflozin, a SGLT2 inhibitor, to healthy subjects. After dosing, SUA decreased, and a negative correlation was observed between the SUA level and the UEUA, suggesting that SUA decreased as a result of the increase in the UEUA. The increase in UEUA was correlated with an increase in urinary d-glucose excretion, but not with the plasma luseogliflozin concentration. Additionally, in vitro transport experiments showed that luseogliflozin had no direct effect on the transporters involved in renal UA reabsorption. To explain that the increase in UEUA is likely due to glycosuria, the study focused on the facilitative glucose transporter 9 isoform 2 (GLUT9ΔN, SLC2A9b), which is expressed at the apical membrane of the kidney tubular cells and transports both UA and d-glucose. It was observed that the efflux of [14C]UA in Xenopus oocytes expressing the GLUT9 isoform 2 was trans-stimulated by 10 mm d-glucose, a high concentration of glucose that existed under SGLT2 inhibition. On the other hand, the uptake of [14C]UA by oocytes was cis-inhibited by 100 mm d-glucose, a concentration assumed to exist in collecting ducts. In conclusion, it was demonstrated that the UEUA could potentially be increased by luseogliflozin-induced glycosuria, with alterations of UA transport activity because of urinary glucose. PMID:25044127

Advances in the Urinary Exosomes in Renal Diseases.

PubMed

Chen, Pei-Pei; Qin, Yan; Li, Xue-Mei

2016-08-01

Cells secrete around 30- 100 nm membrane-enclosed vesicles that are released into the extracellular spaceis termed exosomes(EXs). EXs widely present in body fluids and incorporated proteins,nucleic acids that reflect the physiological state of their cells of origin and they may play an important role in cell-to-cell communication in various physiological and disease processes. In this article we review the recent basic and clinical studies in urinary EXs in renal diseases,focusing on their biological characteristics and potential roles as new biological markers,intervention treatment goals,and targeted therapy vectors in renal diseases.However,some issues still exist;in particular,the clinical application of EXs as a liquid biopsy technique warrants further investigations.

Bioactive Compounds and Fruit Quality of Green Sweet Pepper Grown under Different Colored Shade Netting during Postharvest Storage.

PubMed

Mashabela, Madonna N; Selahle, Kamogelo M; Soundy, Puffy; Crosby, Kevin M; Sivakumar, Dharini

2015-11-01

In this study, influence of 3 types of photo-selective nets (pearl, red and yellow) and a standard black net on marketable yield, fruit quality and bioactive compounds after postharvest storage was investigated. Percentage marketable fruits were higher in green sweet peppers produced under the pearl nets. Fruits produced under the pearl nets showed higher fruit mass, firmness, chlorophyll content, ascorbic acid content, antioxidant scavenging activity after postharvest storage. Red/far red photon ratio under the pearl net could have improved the ascorbic acid content and the antioxidant scavenging activity in green peppers. Green sweet peppers grown under the pearl nets had higher hue values and maintained green color longer. Our results showed the impact of modified light quality on the bioactive compounds of green sweet pepper during postharvest storage. Green sweet peppers are rich in phytochemicals. Marketability of green sweet peppers is affected partially due to ripening after postharvest storage and decay. Maintenance of green color, fruit mass, firmness, and nutritional composition are important parameters that attract consumers. This research shows the influence of light quality during production on the fruit quality parameters and bioactive compounds after postharvest storage. © 2015 Institute of Food Technologists®

Value of imaging studies after a first febrile urinary tract infection in young children: data from Italian renal infection study 1.

PubMed

Montini, Giovanni; Zucchetta, Pietro; Tomasi, Lisanna; Talenti, Enrico; Rigamonti, Waifro; Picco, Giorgio; Ballan, Alberto; Zucchini, Andrea; Serra, Laura; Canella, Vanna; Gheno, Marta; Venturoli, Andrea; Ranieri, Marco; Caddia, Valeria; Carasi, Carla; Dall'amico, Roberto; Hewitt, Ian

2009-02-01

We examined the diagnostic accuracy of routine imaging studies (ultrasonography and micturating cystography) for predicting long-term parenchymal renal damage after a first febrile urinary tract infection. This study addressed the secondary objective of a prospective trial evaluating different antibiotic regimens for the treatment of acute pyelonephritis. Data for 300 children < or =2 years of age, with normal prenatal ultrasound results, who completed the diagnostic follow-up evaluation (ultrasonography and technetium-99m-dimercaptosuccinic acid scanning within 10 days, cystography within 2 months, and repeat technetium-99m-dimercaptosuccinic acid scanning at 12 months to detect scarring) were analyzed. Outcome measures were sensitivity, specificity, and negative and positive predictive values for ultrasonography and cystography in predicting parenchymal renal damage on the 12-month technetium-99m-dimercaptosuccinic acid scans. The kidneys and urinary tracts were mostly normal. The acute technetium-99m-dimercaptosuccinic acid scans showed pyelonephritis in 54% of cases. Renal scarring developed in 15% of cases. The ultrasonographic and cystographic findings were poor predictors of long-term damage, showing minor sonographic abnormalities for 12 and reflux for 23 of the 45 children who subsequently developed scarring. The benefit of performing ultrasonography and scintigraphy in the acute phase or cystourethrography is minimal. Our findings support (1) technetium-99m-dimercaptosuccinic acid scintigraphy 6 months after infection to detect scarring that may be related to long-term hypertension, proteinuria, and renal function impairment (although the degree of scarring was generally minor and did not impair renal function) and (2) continued surveillance to identify recurrent urinary tract infections that may warrant further investigation.

Extrarenal citrulline disposal in mice with impaired renal function

USDA-ARS?s Scientific Manuscript database

The endogenous synthesis of arginine, a semiessential amino acid, relies on the production of citrulline by the gut and its conversion into arginine by the kidney in what has been called the "intestinal-renal axis" for arginine synthesis. Although the kidney is the main site for citrulline disposal,...

Dental Aspect of Distal Tubular Renal Acidosis with Genu Valgum Secondary to Rickets: A Case Report

PubMed Central

Bahadure, Rakesh N.; Thosar, Nilima; Kriplani, Ritika; Baliga, Sudhindra; Fulzele, Punit

2012-01-01

Distal renal tubular acidosis is a disease that occurs when the kidneys do not remove acid properly into the urine, leaving the blood too acidic (called acidosis). Distal renal tubular acidosis (type I RTA) is caused by a defect in the kidney tubes that causes acid to build up in the bloodstream. It ultimately results rickets which include chronic skeletal pain, in skeletal deformities, skeletal fractures. Rickets is among the most frequent childhood diseases in many developing countries. Dental problems in rickets include delayed eruption of permanent teeth, premature fall of deciduous teeth, defects in structure of teeth, enamel defects in permanent teeth (hypoplastic), pulp defects, intraglobular dentine, and caries tooth. Herewith, reported a case of distal tubular renal acidosis with genu valgum secondary to rickets, with pain and extraoral swelling associated with right and left mandibular 1st permanent molars. Teeth were infected with pulp without being involved with caries. Radiographically cracks in enamel and dentin were observed. Pulp revascularization with 46 and root canal treatment was done for 36 with followup of 1 year. PMID:22567455

A new pathological scoring system by the Japanese classification to predict renal outcome in diabetic nephropathy.

PubMed

Hoshino, Junichi; Furuichi, Kengo; Yamanouchi, Masayuki; Mise, Koki; Sekine, Akinari; Kawada, Masahiro; Sumida, Keiichi; Hiramatsu, Rikako; Hasegawa, Eiko; Hayami, Noriko; Suwabe, Tatsuya; Sawa, Naoki; Hara, Shigeko; Fujii, Takeshi; Ohashi, Kenichi; Kitagawa, Kiyoki; Toyama, Tadashi; Shimizu, Miho; Takaichi, Kenmei; Ubara, Yoshifumi; Wada, Takashi

2018-01-01

The impact of the newly proposed pathological classification by the Japan Renal Pathology Society (JRPS) on renal outcome is unclear. So we evaluated that impact and created a new pathological scoring to predict outcome using this classification. A multicenter cohort of 493 biopsy-proven Japanese patients with diabetic nephropathy (DN) were analyzed. The association between each pathological factor-Tervaert' and JRPS classifications-and renal outcome (dialysis initiation or 50% eGFR decline) was estimated by adjusted Cox regression. The overall pathological risk score (J-score) was calculated, whereupon its predictive ability for 10-year risk of renal outcome was evaluated. The J-scores of diffuse lesion classes 2 or 3, GBM doubling class 3, presence of mesangiolysis, polar vasculosis, and arteriolar hyalinosis were, respectively, 1, 2, 4, 1, and 2. The scores of IFTA classes 1, 2, and 3 were, respectively, 3, 4, and 4, and those of interstitial inflammation classes 1, 2, and 3 were 5, 5, and 4 (J-score range, 0-19). Renal survival curves, when dividing into four J-score grades (0-5, 6-10, 11-15, and 16-19), were significantly different from each other (p<0.01, log-rank test). After adjusting clinical factors, the J-score was a significant predictor of renal outcome. Ability to predict 10-year renal outcome was improved when the J-score was added to the basic model: c-statistics from 0.661 to 0.685; category-free net reclassification improvement, 0.154 (-0.040, 0.349, p = 0.12); and integrated discrimination improvement, 0.015 (0.003, 0.028, p = 0.02). Mesangiolysis, polar vasculosis, and doubling of GBM-features of the JRPS system-were significantly associated with renal outcome. Prediction of DN patients' renal outcome was better with the J-score than without it.

Idiopathic recurrent calcium urolithiasis (IRCU): an acid meal challenge uncovers inappropriate pH of postprandial, fasting and daily urine: a cross-sectional study of male patients providing insight into post- and pre-load urinary stone substances, crystallization risk, presence of stones, renal transport and systemic metabolic factors.

PubMed

Schwille, Paul O; Wipplinger, J

2008-07-28

In IRCU the possible role of urinary pH (U-pH) as risk factor of calcium (Ca) stones is poorly understood. To evaluate in IRCU the response to an oral acid load, focussing on post- and pre-load U-pH, other urinary, renal and extra-renal factors, and linkage with Ca stones. - 237 male patients, either Ca stone-free (SF) or -bearing (SB), but without overt signs of systemic metabolic acidosis underwent a standardized laboratory programme that included, besides collection of urine and blood, the intake of an oxalate-free acid test meal (proton content 120 mM). Established analytical methods were used. In 79 patients the post-meal load U-pH was < or = 5.30 (in healthy individuals accepted as the upper limit after the same proton load), but >5.30 in 158; in these two subsets the mean fasting pre-load U-pH was 5.84 and 6.37 (p <0.001), the mean U-pH in 24 h urine 5.70 and 6.03 (p <0.001), the mean score of stone formation activity 32 and 42 (p = 0.12), the SF/SB ratio 35/44 and 76/82 (not significant). However, when in pre-load urine undissociated uric acid concentration was low due to the high pH, the SF/SB ratio was 53/66 (p = 0.038), whereas isolated increase of U-pH with SF/SB ratio 54/65 (p = 0.059), urinary supersaturation with Ca phosphate (hydroxyapatite), Ca oxalate, uric acid, and isolated decrease of concentration of total protein, total uric acid and the crystallization inhibitors magnesium and citrate failed to affect significantly the frequency distribution of SF and SB patients. Pre-load U-pH was positively associated with urinary ratio sodium/proton excretion, renal reclaim of sodium and protein, negatively associated with body mass index, fasting insulinemia and uricemia, urinary protein concentration, renal reclaim of phosphate. In IRCU 1) inappropriately high U-pH combined with increase of proteinuria and alteration of renal-tubular transport are frequent; 2) disturbed interactions of renal proton generation with sodium handling, urinary physico

Altered levels of acid, basic, and neutral peptidase activity and expression in human clear cell renal cell carcinoma.

PubMed

Varona, Adolfo; Blanco, Lorena; López, José I; Gil, Javier; Agirregoitia, Ekaitz; Irazusta, Jon; Larrinaga, Gorka

2007-02-01

Peptides play important roles in cell regulation and signaling in many tissues and are regulated by peptidases, most of which are highly expressed in the kidney. Several peptide convertases have a function in different tumor stages, and some have been clearly characterized as diagnostic and prognostic markers for solid tumors, including renal cancer; however, little is known about their in vivo role in kidney tumors. The present study compares the activity of a range of peptidases in human tumor samples and nontumor tissue obtained from clear cell renal cell carcinoma (CCRCC) patients. To cover the complete spectrum and subcellular distribution of peptide-converting activity, acid, neutral, basic, and omega activities were selected. CCRCC displays a selective and restricted pattern of peptidase activities. Puromycin-sensitive aminopeptidase activity in the tumor increases [tumor (t) = 10,775 vs. nontumor (n) = 7,635 units of peptidase (UP)/mg protein; P < 0.05], whereas aminopeptidase N decreases (t = 6,664 vs. n = 33,381 UP/mg protein; P < 0.001). Aminopeptidase B activity of the particulate fraction in tumors decreases (t = 2,399 vs. n = 13,536 UP/mg protein; P < 0.001) compared with nontumor tissues, and aspartyl-aminopeptidase activity decreases significantly in CCRCC (t = 137 vs. n = 223 UP/mg protein; P < 0.05). Soluble and particulate pyroglutamyl peptidase I activities, aminopeptidase A activity, and soluble aminopeptidase B activity do not vary in renal cancer. The relative expression for the aforementioned peptidases, assayed using quantitative RT-PCR, increases in CCRCC for aminopeptidases B (1.5-fold) and A (19-fold), aspartyl-aminopeptidase (3.9-fold), puromycin-sensitive aminopeptidase (2.5-fold), and pyroglutamyl peptidase I (7.6-fold). Only aminopeptidase N expression decreases in tumors (1.3-fold). This peptidase activity profile in the neoplastic kidney suggests a specific role for the studied convertases and the possible involvement of an

Association of four genetic loci with uric acid levels and reduced renal function: the J-SHIPP Suita study.

PubMed

Tabara, Yasuharu; Kohara, Katsuhiko; Kawamoto, Ryuichi; Hiura, Yumiko; Nishimura, Kunihiro; Morisaki, Takayuki; Kokubo, Yoshihiro; Okamura, Tomonori; Tomoike, Hitonobu; Iwai, Naoharu; Miki, Tetsuro

2010-01-01

Recent genome-wide association studies have identified several genetic variants as susceptibility loci for serum uric acid (UA) levels. We also identified a common nonsense mutation, W258X, responsible for renal hypouricemia. Here, we investigated clinical implications of these genetic variants by cross-sectional and longitudinal genetic epidemiological analysis. The study enrolled 5,165 Japanese subjects aged 64 ± 12 years from the general population. Clinical parameters were obtained from the personal health records, evaluated at medical checkups. Serum UA levels were significantly different between the SLC22A12 rs11231825 (CC/CT/TT: 4.5 ± 1.6, 5.0 ± 1.4, 5.3 ± 1.4 mg/dl; p = 7.6 × 10(-20)), SLC2A9 rs1014290 (TT/TG/GG: 4.9 ± 1.4, 5.1 ± 1.4, 5.3 ± 1.4 mg/dl; p = 3.1 × 10(-11)) and ABCG2 rs2231142 (TT/TG/GG: 5.3 ± 1.5, 5.2 ± 1.4, 5.1 ± 1.4 mg/dl; p = 2.0 × 10(-5)) genotypes. During 9.4 years of follow-up, 87 new cases of hyperuricemia were diagnosed. Multiple logistic regression analysis identified the accumulation of risk alleles as a significant determinant of future development of hyperuricemia (OR = 7.94; 95% CI: 1.97-53.6). In contrast, subjects with nonsense mutation predominantly showed lower UA levels (XX/XW/WW: 1.3 ± 1.7, 3.6 ± 1.0, 5.2 ± 1.4 mg/dl; p = 9.3 × 10(-82)). However, these subjects showed significantly reduced renal function (β = -0.111; p < 0.001) independently of possible covariates. Accumulation of risk genotypes was an independent risk factor for future development of hyperuricemia. Genetically developed hypouricemia was an independent risk factor for decreased renal function. Copyright © 2010 S. Karger AG, Basel.

Betulinic acid ameliorates experimental diabetic-induced renal inflammation and fibrosis via inhibiting the activation of NF-κB signaling pathway.

PubMed

Wang, Shaogui; Yang, Zhiying; Xiong, Fengxiao; Chen, Cheng; Chao, Xiaojuan; Huang, Junying; Huang, Heqing

2016-10-15

Diabetic nephropathy (DN) is the leading cause of end-stage renal failure and is characterized by excessive deposition of extracellular matrix (ECM) proteins such as fibronectin (FN), in the glomerular mesangium and tubulointerstitium. Betulinic acid (BA), a pentacyclic triterpene derived from the bark of the white birch tree, has been demonstrated to have many pharmacological activities. However, the effect of BA on DN has not been fully elucidated. To explore the possible anti-inflammatory effects of BA and their underlying mechanisms, we used streptozotocin-induced diabetic rat kidneys and high glucose-treated glomerular mesangial cells. Our study showed BA could inhibit the degradation of IκBα and the activity of NF-κB in diabetic rat kidneys and high glucose-induced mesangial cells, resulting in reduction of FN expression. In addition, BA suppressed the DNA binding activity and transcriptional activity of NF-κB in high glucose-induced glomerular mesangial cells (GMCs). Furthermore, BA enhanced the interaction between IκBα and β-arrestin2 in mesangial cells. Taken together, our data suggest BA inhibits NF-κB activation through stabilizing NF-κB inhibitory protein IκBα, thereby preventing diabetic renal fibrosis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Renal Response to Acid Load after Phenformin

PubMed Central

Rooth, Gösta; Bandman, Ulf

1973-01-01

Normally the kidneys respond to an acid load by increased ammonia production. In six patients with adult-type diabetes this response was reduced by a mean 50% after a therapeutic dose of phenformin. The reduced ability to compensate for acid loads may be one factor leading to metabolic acidosis and lactoacidosis sometimes associated with phenformin therapy. PMID:4753235

Acidity and alkalinity in mine drainage: Theoretical considerations

USGS Publications Warehouse

Kirby, Carl S.; Cravotta,, Charles A.

2004-01-01

Acidity, net acidity, and net alkalinity are widely used parameters for the characterization of mine drainage, but these terms are not well defined and are often misunderstood. Incorrect interpretation of acidity, alkalinity, and derivative terms can lead to inadequate treatment design or poor regulatory decisions. We briefly explain derivations of theoretical expressions of three types of alkalinities (caustic, phenolphthalein, and total) and acidities (mineral, CO2, and total). Theoretically defined total alkalinity is closely analogous to measured alkalinity and presents few practical interpretation problems. Theoretically defined “CO2- acidity” is closely related to most standard titration methods used for mine drainage with an endpoint pH of 8.3, but it presents numerous interpretation problems, and it is unfortunately named because CO2 is intentionally driven off during titration of mine-drainage samples. Using the proton condition/massaction approach and employing graphs for visualization, we explore the concept of principal components and how to assign acidity contributions to solution species, including aqueous complexes, commonly found in mine drainage. We define a comprehensive theoretical definition of acidity in mine drainage on the basis of aqueous speciation at the sample pH and the capacity of these species to undergo hydrolysis to pH 8.3. This definition indicates the computed acidity in milligrams per liter (mg L-1 ) as CaCO3 (based on pH and analytical concentrations of dissolved FeIII , FeII , Mn, and Al in mg L-1 ): Aciditycomputed = 50. (10(3-pH) + 3.CFeIII/55.8 + 2.CFeII/55.8 + 2.CMn/54.9 + 3.CAl/27.0) underestimates contributions from HSO4 - and H+ , but overestimates the acidity due to Fe3+. These errors tend to approximately cancel each other. We demonstrate that “net alkalinity” is a valid mathematical construction based on theoretical definitions of alkalinity and acidity. We demonstrate that, for most mine-drainage solutions, a

Predictors of Recoverability of Renal Function after Pyeloplasty in Adults with Ureteropelvic Junction Obstruction.

PubMed

Li, Xiao-Dong; Wu, Yu-Peng; Wei, Yong; Chen, Shao-Hao; Zheng, Qing-Shui; Cai, Hai; Xue, Xue-Yi; Xu, Ning

2018-01-01

This study aimed to identify factors predicting the recoverability of renal function after pyeloplasty in adult patients with ureteropelvic junction obstruction. We retrospectively reviewed 138 adults with unilateral renal obstruction-induced hydronephrosis and who underwent Anderson-Hynes dismembered pyeloplasty from January 2013 to January 2016. Hydronephrosis was classified preoperatively according to the Society for Fetal Urology (SFU) grading system. All patients underwent Doppler ultrasonography, excretory urography, computed tomography, and technetium-99m-diethylenetriamine pentaacetic acid radioisotope (99mTc DTPA) renography before and after surgery. Renal resistive index (RRI) and 99mTc DTPA renography were repeated at 1, 3, 6, and 12 months. Multivariate analysis identified age, renal pelvic type, SFU grade, preoperative RRI, decline of RRI, and renal parenchyma to hydronephrosis area ratio (PHAR) as independent predictors of renal function recoverability after pyeloplasty. However, preoperative RRI and RRI decline were not significantly associated with recoverability of renal function in patients aged >35 years. Lower preoperative RRI, greater decline in RRI, higher PHAR, lower SFU grade, and extrarenal pelvis were associated with greater improvements in postoperative renal function. Preoperative differential renal function cannot independently predict the recoverability of postoperative renal function in adult patients with unilateral renal obstruction-induced hydronephrosis. SFU grade, renal pelvic type, PHAR, preoperative RRI, and decline in RRI were significantly associated with the recoverability of renal function in adult patients aged <35 years, while only SFU grade, renal pelvic type, and PHAR were significantly associated with renal function recoverability in patients aged ≥35 years. Renal function recovery was better in patients younger than 35 years when compared with older patients. © 2018 S. Karger AG, Basel.

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

Mathematical modeling of renal hemodynamics in physiology and pathophysiology.

PubMed

Sgouralis, Ioannis; Layton, Anita T

2015-06-01

In addition to the excretion of metabolic waste and toxin, the kidney plays an indispensable role in regulating the balance of water, electrolyte, acid-base, and blood pressure. For the kidney to maintain proper functions, hemodynamic control is crucial. In this review, we describe representative mathematical models that have been developed to better understand the kidney's autoregulatory processes. We consider mathematical models that simulate glomerular filtration, and renal blood flow regulation by means of the myogenic response and tubuloglomerular feedback. We discuss the extent to which these modeling efforts have expanded the understanding of renal functions in health and disease. Copyright © 2015 Elsevier Inc. All rights reserved.

Urea and Ammonia Metabolism and the Control of Renal Nitrogen Excretion

PubMed Central

Mitch, William E.; Sands, Jeff M.

2015-01-01

Renal nitrogen metabolism primarily involves urea and ammonia metabolism, and is essential to normal health. Urea is the largest circulating pool of nitrogen, excluding nitrogen in circulating proteins, and its production changes in parallel to the degradation of dietary and endogenous proteins. In addition to serving as a way to excrete nitrogen, urea transport, mediated through specific urea transport proteins, mediates a central role in the urine concentrating mechanism. Renal ammonia excretion, although often considered only in the context of acid-base homeostasis, accounts for approximately 10% of total renal nitrogen excretion under basal conditions, but can increase substantially in a variety of clinical conditions. Because renal ammonia metabolism requires intrarenal ammoniagenesis from glutamine, changes in factors regulating renal ammonia metabolism can have important effects on glutamine in addition to nitrogen balance. This review covers aspects of protein metabolism and the control of the two major molecules involved in renal nitrogen excretion: urea and ammonia. Both urea and ammonia transport can be altered by glucocorticoids and hypokalemia, two conditions that also affect protein metabolism. Clinical conditions associated with altered urine concentrating ability or water homeostasis can result in changes in urea excretion and urea transporters. Clinical conditions associated with altered ammonia excretion can have important effects on nitrogen balance. PMID:25078422

[Acute renal failure in a 75-year-old woman with a high-output ileostoma].

PubMed

Teege, S; Wiech, T; Steinmetz, O M

2017-05-01

We report on a 75-year old woman who presented with acute oliguric renal failure. The kidney biopsy revealed calcium oxalate depositions in the tubular lumen, caused by an overload of intravenous ascorbic acid (cumulative dose of 240 g). Due to a lack of specific therapeutic interventions, the patient remained dialysis-dependent. Iatrogenic causes of kidney failure play an important role in the pathogenesis of kidney diseases and should always be considered in patients with acute renal failure. Detailed evaluation of the patient history is often suggestive, while renal biopsy can establish the diagnosis.

Boldine Prevents Renal Alterations in Diabetic Rats

PubMed Central

Hernández-Salinas, Romina; Vielma, Alejandra Z.; Arismendi, Marlene N.; Boric, Mauricio P.; Sáez, Juan C.; Velarde, Victoria

2013-01-01

Diabetic nephropathy alters both structure and function of the kidney. These alterations are associated with increased levels of reactive oxygen species, matrix proteins, and proinflammatory molecules. Inflammation decreases gap junctional communication and increases hemichannel activity leading to increased membrane permeability and altering tissue homeostasis. Since current treatments for diabetic nephropathy do not prevent renal damage, we postulated an alternative treatment with boldine, an alkaloid obtained from boldo with antioxidant, anti-inflammatory, and hypoglycemic effects. Streptozotocin-induced diabetic and control rats were treated or not treated with boldine (50 mg/Kg/day) for ten weeks. In addition, mesangial cells were cultured under control conditions or in high glucose concentration plus proinflammatory cytokines, with or without boldine (100 µmol/L). Boldine treatment in diabetic animals prevented the increase in glycemia, blood pressure, renal thiobarbituric acid reactive substances and the urinary protein/creatinine ratio. Boldine also reduced alterations in matrix proteins and markers of renal damage. In mesangial cells, boldine prevented the increase in oxidative stress, the decrease in gap junctional communication, and the increase in cell permeability due to connexin hemichannel activity induced by high glucose and proinflammatory cytokines but did not block gap junction channels. Thus boldine prevented both renal and cellular alterations and could be useful for preventing tissue damage in diabetic subjects. PMID:24416726

Acid-base metabolism: implications for kidney stones formation.

PubMed

Hess, Bernhard

2006-04-01

The physiology and pathophysiology of renal H+ ion excretion and urinary buffer systems are reviewed. The main focus is on the two major conditions related to acid-base metabolism that cause kidney stone formation, i.e., distal renal tubular acidosis (dRTA) and abnormally low urine pH with subsequent uric acid stone formation. Both the entities can be seen on the background of disturbances of the major urinary buffer system, NH3+ <--> NH4+. On the one hand, reduced distal tubular secretion of H+ ions results in an abnormally high urinary pH and either incomplete or complete dRTA. On the other hand, reduced production/availability of NH4+ is the cause of an abnormally low urinary pH, which predisposes to uric acid stone formation. Most recent research indicates that the latter abnormality may be a renal manifestation of the increasingly prevalent metabolic syndrome. Despite opposite deviations from normal urinary pH values, both the dRTA and uric acid stone formation due to low urinary pH require the same treatment, i.e., alkali. In the dRTA, alkali is needed for improving the body's buffer capacity, whereas the goal of alkali treatment in uric acid stone formers is to increase the urinary pH to 6.2-6.8 in order to minimize uric acid crystallization.

Acid, basic, and neutral peptidases present different profiles in chromophobe renal cell carcinoma and in oncocytoma.

PubMed

Blanco, Lorena; Larrinaga, Gorka; Pérez, Itxaro; López, José I; Gil, Javier; Agirregoitia, Ekaitz; Varona, Adolfo

2008-04-01

Renal cell carcinomas (RCCs) are neoplasias with high prevalence and mortality. We previously reported that several peptidases may be involved in the pathophysiology of clear cell renal cell carcinoma (CCRCC). Now, to gain insight into the reasons that lead the various RCC types to behave very differently with regard to aggressiveness and response to anticancer treatments, we analyzed subsets of chromophobe renal cell carcinoma (ChRCC), and renal oncocytoma (RO), a benign tumor; as well as different grades and stages of CCRCCs. Particulate APN, APB, and APA activities were decreased in both ChRCC and RO (tumor vs. nontumor tissues). Interestingly, activities were downregulated in a tumor-type specific way and the intensities of the decreases were stronger in the benign tumor than in the malignant type. Moreover, when two key histopathological parameters for tumor prognosis (high vs. low stage and grade) were analyzed, increases of activity were also observed in several of these cell surface peptidases (APN, APB). Some soluble activities (APB, Asp-AP) were also downregulated in the RCCs. With respect to genetic expression, PSA and APN were in a positive correlation related to their activities in both ChRCC and RO; but not APB, Asp-AP, APA, and PGI. These results may suggest an involvement of several peptidases in the pathophysiology of renal cancer, since they presented different patterns of activity and expression in tumors with different behaviors.

Estimated Net Endogenous Acid Production and Serum Bicarbonate in African Americans with Chronic Kidney Disease

PubMed Central

Appel, Lawrence J.; Astor, Brad C.; Miller, Edgar R.; Beddhu, Srinivasan; Woodward, Mark; Parekh, Rulan S.; Anderson, Cheryl A.M.

2011-01-01

Summary Background and objectives Metabolic acidosis may contribute to morbidity and disease progression in patients with chronic kidney disease (CKD). The ratio of dietary protein, the major source of nonvolatile acid, to dietary potassium, which is naturally bound to alkali precursors, can be used to estimate net endogenous acid production (NEAP). We tested the association between estimated NEAP and serum bicarbonate in patients with CKD. Design, setting, participants, & measurements NEAP was estimated among 462 African American adults with hypertensive CKD using published equations: NEAP (mEq/d) = −10.2 + 54.5 (protein [g/d]/potassium [mEq/d]). Dietary protein and potassium intake were estimated from 24-hour urinary excretion of urea nitrogen and potassium, respectively. All of the eligible measurements during follow-up were modeled using generalized linear regression clustered by participant and adjusted for demographics, 24-hour urinary sodium, kidney function, and selected medications. Results Higher NEAP was associated with lower serum bicarbonate in a graded fashion (P trend < 0.001). Serum bicarbonate was 1.27 mEq/L lower among those in the highest compared with the lowest quartile of NEAP (P < 0.001). There was a greater difference in serum bicarbonate between the highest and lowest quartiles of NEAP among patients with stage 4/5 CKD (−2.43 mEq/L, P < 0.001) compared with those with stage 2/3 disease (−0.77 mEq/L, P = 0.01; P-interaction = 0.02). Conclusions Reducing NEAP, through reduction of dietary protein and increased intake of fruits and vegetables, may prevent metabolic acidosis in patients with CKD. PMID:21700817

Cerebro-renal interactions: impact of uremic toxins on cognitive function.

PubMed

Watanabe, Kimio; Watanabe, Tsuyoshi; Nakayama, Masaaki

2014-09-01

Cognitive impairment (CI) associated with chronic kidney disease (CKD) has received attention as an important problem in recent years. Causes of CI with CKD are multifactorial, and include cerebrovascular disease, renal anemia, secondary hyperparathyroidism, dialysis disequilibrium, and uremic toxins (UTs). Among these causes, little is known about the role of UTs. We therefore selected 21 uremic compounds, and summarized reports of cerebro-renal interactions associated with UTs. Among the compounds, uric acid, indoxyl sulfate, p-cresyl sulfate, interleukin 1-β, interleukin 6, TNF-α, and PTH were most likely to affect the cerebro-renal interaction dysfunction; however, sufficient data have not been obtained for other UTs. Notably, most of the data were not obtained under uremic conditions; therefore, the impact and mechanism of each UT on cognition and central nervous system in uremic state remains unknown. At present, impacts and mechanisms of UT effects on cognition are poorly understood. Clarifying the mechanisms and establishing novel therapeutic strategies for cerebro-renal interaction dysfunction is expected to be subject of future research. Copyright © 2014 Elsevier Inc. All rights reserved.

Transport of amino acids in the kidney.

PubMed

Makrides, Victoria; Camargo, Simone M R; Verrey, François

2014-01-01

Amino acids are the building blocks of proteins and key intermediates in the synthesis of biologically important molecules, as well as energy sources, neurotransmitters, regulators of cellular metabolism, etc. The efficient recovery of amino acids from the primary filtrate is a well-conserved key role of the kidney proximal tubule. Additionally, renal metabolism participates in the whole body disposition of amino acids. Therefore, a wide array of axially heterogeneously expressed transporters is localized on both epithelial membranes. For transepithelial transport, luminal uptake, which is carried out mainly by active symporters, is coupled with a mostly passive basolateral efflux. Many transporters require partner proteins for appropriate localization, or to modulate transporter activity, and/or increase substrate supply. Interacting proteins include cell surface antigens (CD98), endoplasmic reticulum proteins (GTRAP3-18 or 41), or enzymes (ACE2 and aminopeptidase N). In the past two decades, the molecular identification of transporters has led to significant advances in our understanding of amino acid transport and aminoacidurias arising from defects in renal transport. Furthermore, the three-dimensional crystal structures of bacterial homologues have been used to yield new insights on the structure and function of mammalian transporters. Additionally, transgenic animal models have contributed to our understanding of the role of amino acid transporters in the kidney and other organs and/or at critical developmental stages. Progress in elucidation of the renal contribution to systemic amino acid homeostasis requires further integration of kinetic, regulatory, and expression data of amino acid transporters into our understanding of physiological regulatory networks controlling metabolism. © 2014 American Physiological Society.

Downflow limestone beds for treatment of net-acidic, oxic, iron-laden drainage from a flooded anthracite mine, Pennsylvania, USA: 2. Laboratory evaluation

USGS Publications Warehouse

Cravotta, C.A.; Ward, S.J.; Hammarstrom, J.M.

2008-01-01

Acidic mine drainage (AMD) containing elevated concentrations of dissolved iron and other metals can be neutralized to varying degrees by reactions with limestone in passive treatment systems. We evaluated the chemical and mineralogical characteristics and the effectiveness of calcitic and dolomitic limestone for the neutralization of net-acidic, oxic, iron-laden AMD from a flooded anthracite mine. The calcitic limestone, with CaCO3 and MgCO3 contents of 99.8 and <0.1 wt%, respectively, and the dolomitic limestone, with CaCO3 and MgCO3 contents of 60.3 and 40.2 wt%, were used to construct a downflow treatment system in 2003 at the Bell Mine, a large source of AMD and baseflow to the Schuylkill River in the Southern Anthracite Coalfield, in east-central Pennsylvania. In the winter of 2002-2003, laboratory neutralization-rate experiments evaluated the evolution of effluent quality during 2 weeks of continuous contact between AMD from the Bell Mine and the crushed calcitic or dolomitic limestone in closed, collapsible containers (cubitainers). The cubitainer tests showed that: (1) net-alkaline effluent could be achieved with detention times greater than 3 h, (2) effluent alkalinities and associated dissolution rates were equivalent for uncoated and Fe(OH)3-coated calcitic limestone, and (3) effluent alkalinities and associated dissolution rates for dolomitic limestone were about half those for calcitic limestone. The dissolution rate data for the cubitainer tests were used with data on the volume of effuent and surface area of limestone in the treatment system at the Bell Mine to evaluate the water-quality data for the first 1.5 years of operation of the treatment system. These rate models supported the interpretation of field results and indicated that treatment benefits were derived mainly from the dissolution of calcitic limestone, despite a greater quantity of dolomitic limestone within the treatment system. The dissolution-rate models were extrapolated on a

The role of the renal specialist nurse in prevention of renal failure.

PubMed

Hurst, J

2002-01-01

This article will investigate the care required for those with reduced renal function before renal replacement therapy (RRT) commences. Renal nurses are often involved with the technical, monitoring and evaluative aspects of RRT for those with end stage renal failure. However, many patients may experience reduced renal function many years before reaching the stage of needing RRT. Renal nurses are already involved in the preparation of patients for RRT, but are not presently exercising their specialist skills in the period before this time by contributing to the prevention of end stage renal failure (ESRF). Screening programmes carried out in various parts of the world demonstrate that many members of the population have undetected renal insufficiency, and may benefit from intervention from the nephrology team to prevent further renal dysfunction. It is for this group of patients that this article will consider the potential for the renal nurse to expand their scope of practice.

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.

Catamaran Nets

NASA Technical Reports Server (NTRS)

1990-01-01

West Coast Netting, Inc.'s net of Hyperester twine, is made of three strands of fiber twisted together by a company-invented sophisticated twisting machine and process that maintain precisely the same tension on each strand. The resulting twine offers higher strength and improved abrasion resistance. The technology that created the Hyperester supertwine has found spinoff applications, first as an extra-efficient seine for tuna fishing, then as a capture net for law enforcement agencies. The newest one is as a deck for racing catamarans. Hyperester twine net has been used on most of the high performance racing catamarans of recent years, including the America's Cup Challenge boats. They are tough and hold up well in the continual exposure to sunlight and saltwater.

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.

[Renal response to intravenous administration of sodium bicarbonate in newborn infants of different gestational ages].

PubMed

Jasso-Gutiérrez, L; Araujo, B; Fuse-Moteji, R; del Castillo, E D

1976-01-01

The study comprised a series of 16 neonates made up of 5 patients of 33 weeks of gestation, 5 infants of 35 weeks and 6 more of 40 weeks of gestation. Blood pH, PaCO2 and HCO3- were measured together with bicarbonate, ammonium, titrable acidity and hydrogen ions in urine before and after intravenous infusion of sodium bicarbonate. Before infusion of bicarbonate, titrable acidity, ammonium and net acidity in urine were higher in accordance with a greater gestational age. As the administration of bicarbonate elapsed, titrable acidity, ammonium and net acidity dropped with increase in concentration of bicarbonate. A hypothesis is set forth that the differences found in the factors evaluated in urine before administration of bicarbonate depend on the physiologic characteristics set in the newborn by gestational age.

A microperfusion study of sucrose movement across the rat proximal tubule during renal vein constriction

PubMed Central

Bank, Norman; Yarger, William E.; Aynedjian, Hagop S.

1971-01-01

Constriction of the renal vein has been shown to inhibit net sodium and water reabsorption by the rat proximal tubule. The mechanism is unknown but might be the result of inhibition of the active sodium pump induced by changes in the interstitial fluid compartment of the kidney, or to enhanced passive backflux of sodium and water into the cell or directly into the tubular lumen. Since passive movement of solutes across epithelial membranes is determined in part by the permeability characteristics of the epithelium, an increase in the permeability of the proximal tubule during venous constriction would suggest that enhanced passive flux is involved in the inhibition of reabsorption. In the present experiments, isolated segments of rat proximal convoluted tubules were microperfused in vivo with saline while the animals were receiving 14C-labeled sucrose intravenously. In normal control animals, no sucrose was detected in the majority of the collected tubular perfusates. In rats with renal vein constriction (RVC), however, sucrose consistently appeared in the tubular perfusates. The rate of inflow of sucrose correlated with the length of the perfused segment, estimated by fractional water reabsorption. In another group of animals with renal vein constriction, inulin-14C was given intravenously and the proximal tubules similarly microperfused. Inulin did not appear in the majority of collected perfusates in these animals. These observations indicate that a physiological alteration in the permeability of the proximal tubule occurs during RVC. Such an increase in permeability is consistent with the view that enhanced passive extracellular back-flux plays a role in the reduction of net sodium and water reabsorption in this experimental condition. PMID:5540167

Dual-energy dual-source CT with additional spectral filtration can improve the differentiation of non-uric acid renal stones: An ex vivo phantom study

PubMed Central

Qu, Mingliang; Ramirez Giraldo, Juan C.; Leng, Shuai; Williams, James C.; Vrtiska, Terri J.; Lieske, John C.; McCollough, Cynthia H.

2014-01-01

Purpose To determine the ex vivo ability of dual-energy, dual-source computed tomography (DE-DSCT) with additional tin filtration to differentiate between five groups of human renal stone types. Methods Forty-three renal stones of ten types were categorized into five primary groups based on effective atomic numbers, which were calculated as the weighted average of the atomic numbers of constituent atoms. Stones were embedded in porcine kidneys and placed in a 35cm water phantom. DE-DSCT scans were performed with and without tin filtration at 80/140kV. The CT number ratio [CTR=CT(low)/CT(high)] was calculated on a volumetric voxel-by-voxel basis for each stone. Statistical analysis was performed and receiver operating characteristic (ROC) curves were plotted to compare the difference in CTR with and without tin filtration, and to measure the discrimination between stone groups. Results CTR of non-uric acid stones increased on average by 0.17 (range 0.03–0.36) with tin filtration. The CTR values for non-uric acid stone groups were not significantly different (p>0.05) between any of the two adjacent groups without tin filtration. Use of the additional tin filtration on the high-energy x-ray tube significantly improved the separation of non-uric acid stone types by CTR (p<0.05). The area under the ROC curve increased from 0.78–0.84 without fin filtration to 0.89–0.95 with tin filtration. Conclusion Our results demonstrated better separation between different stone types when additional tin filtration was used on DE-DSCT. The increased spectral separation allowed a 5-group stone classification scheme. Some overlapping between particular stone types still exists, including brushite and calcium oxalate. PMID:21606290

Icariin protects rats against 5/6 nephrectomy-induced chronic kidney failure by increasing the number of renal stem cells.

PubMed

Huang, Zhongdi; He, Liqun; Huang, Di; Lei, Shi; Gao, Jiandong

2015-10-21

Chronic kidney disease poses a serious health problem worldwide with increasing prevalence and lack of effective treatment. This study aimed to investigate the mechanism of icariin in alleviating chronic renal failure induced by 5/6 nephrectomy in rats. The chronic renal failure model was established by a two-phased 5/6 nephrectomy procedure. The model rats were given daily doses of water or icariin for 8 weeks. The kidney morphology was checked by HE staining. The levels of blood urea nitrogen, serum creatinine, and serum uric acid were measured by colometric methods. The expression of specified genes was analyzed by quantitative real-time PCR and immunohistochemical staining. The number of renal stem/progenitor cells was analyzed by CD133 and CD24 immunohistochemical staining. Icariin protected against CDK-caused damages to kidney histology and improved renal function, significantly reduced levels of BUN, creatinine, and uric acid. Icariin inhibited the expression level of TGF-β1 whereas upregulated HGF, BMP-7, WT-1, and Pax2 expression. Moreover, ccariin significantly increased the expression of CD24, CD133, Osr1, and Nanog in remnant kidney and the numbers of CD133(+)/CD24(+) renal stem/progenitor cells. These data demonstrated that icariin effectively alleviated 5/6 nephrectomy induced chronic renal failure through increasing renal stem/progenitor cells.

Renal perfusion index reflects cardiac systolic function in chronic cardio-renal syndrome.

PubMed

Lubas, Arkadiusz; Ryczek, Robert; Kade, Grzegorz; Niemczyk, Stanisław

2015-04-17

Cardiac dysfunction can modify renal perfusion, which is crucial to maintain sufficient kidney tissue oxygenation. Renal cortex perfusion assessed by dynamic ultrasound method is related both to renal function and cardiac hemodynamics. The aim of the study was to test the hypothesis that Renal Perfusion Index (RPI) can more closely reflect cardiac hemodynamics and differentiate etiology of chronic cardio-renal syndrome. Twenty-four patients with hypertension and chronic kidney disease (CKD) at 2-4 stage (12 with hypertensive nephropathy and 12 with CKD prior to hypertension) were enrolled in the study. Blood tests, 24-h ABPM, echocardiography, and ultrasonography with estimation of Total renal Cortical Perfusion intensity and Renal Perfusion Index (RPI) were performed. In the group of all patients, RPI correlated with left ventricular stoke volume (LVSV), and cardiac index, but not with markers of renal function. In multiple stepwise regression analysis CKD-EPI(Cys-Cr) (b=-0.360), LVSV (b=0.924) and MAP (b=0.376) together independently influenced RPI (R2=0.74; p<0.0001). RPI<0.567 allowed for the identification of patients with chronic cardio-renal syndrome with sensitivity of 41.7% and specificity of 83.3%. Renal perfusion index relates more strongly to cardiac output than to renal function, and could be helpful in recognizing chronic cardio-renal syndrome. Applicability of RPI in diagnosing early abnormalities in the cardio-renal axis requires further investigation.

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.

Application of deconvolution interferometry with both Hi-net and KiK-net data

NASA Astrophysics Data System (ADS)

Nakata, N.

2013-12-01

Application of deconvolution interferometry to wavefields observed by KiK-net, a strong-motion recording network in Japan, is useful for estimating wave velocities and S-wave splitting in the near surface. Using this technique, for example, Nakata and Snieder (2011, 2012) found changed in velocities caused by Tohoku-Oki earthquake in Japan. At the location of the borehole accelerometer of each KiK-net station, a velocity sensor is also installed as a part of a high-sensitivity seismograph network (Hi-net). I present a technique that uses both Hi-net and KiK-net records for computing deconvolution interferometry. The deconvolved waveform obtained from the combination of Hi-net and KiK-net data is similar to the waveform computed from KiK-net data only, which indicates that one can use Hi-net wavefields for deconvolution interferometry. Because Hi-net records have a high signal-to-noise ratio (S/N) and high dynamic resolution, the S/N and the quality of amplitude and phase of deconvolved waveforms can be improved with Hi-net data. These advantages are especially important for short-time moving-window seismic interferometry and deconvolution interferometry using later coda waves.

Multiple Renal Artery Pseudoaneurysms in Patients Undergoing Renal Artery Embolization Following Partial Nephrectomy: Correlation with RENAL Nephrometry Scores

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

Gupta, Nakul; Patel, Anish; Ensor, Joe

PurposeTo describe the incidence of multiple renal artery pseudoaneurysms (PSA) in patients referred for renal artery embolization following partial nephrectomy and to study its relationship to RENAL nephrometry scores.Materials and MethodsThe medical records of 25 patients referred for renal artery embolization after partial nephrectomy were retrospectively reviewed for the following parameters: size and number of tumors, RENAL nephrometry scores, angiographic abnormalities, technical and clinical outcomes, and estimated glomerular filtration rates (eGFRs) after embolization.ResultsTwenty-four patients had primary renal tumors, while 1 patient had a pancreatic tumor invading the kidney. Multiple tumors were resected in 4 patients. Most patients (92 %) were symptomatic,more » presenting with gross hematuria, flank pain, or both. Angiography revealed PSA with (n = 5) or without (n = 20) AV fistulae. Sixteen patients (64 %) had multiple PSA involving multiple renal vessels. Higher RENAL nephrometry scores were associated with an increasing likelihood of multiple PSA. Multiple vessels were embolized in 14 patients (56 %). Clinical success was achieved after one (n = 22) or two (n = 3) embolization sessions in all patients. Post-embolization eGFR values at different time points after embolization were not significantly different from the post-operative eGFR.ConclusionA majority of patients requiring renal artery embolization following partial nephrectomy have multiple pseudoaneurysms, often requiring selective embolization of multiple vessels. Higher RENAL nephrometry score is associated with an increasing likelihood of multiple pseudoaneurysms. We found transarterial embolization to be a safe and effective treatment option with no long-term adverse effect on renal function in all but one patient with a solitary kidney.« less

Diet and renal stone formation.

PubMed

Trinchieri, A

2013-02-01

The relationship between diet and the formation of renal stones is demonstrated, but restrictive diets do not take into account the complexity of metabolism and the complex mechanisms that regulate the saturation and crystallization processes in the urine. The restriction of dietary calcium can reduce the urinary excretion of calcium but severe dietary restriction of calcium causes hyperoxaluria and a progressive loss of bone mineral component. Furthermore urinary calcium excretion is influenced by other nutrients than calcium as sodium, potassium, protein and refined carbohydrates. Up to 40% of the daily excretion of oxalate in the urine is from dietary source, but oxalate absorption in the intestine depends linearly on the concomitant dietary intake of calcium and is influenced by the bacterial degradation by several bacterial species of intestinal flora. A more rational approach should be based on the cumulative effects of foods and different dietary patterns on urinary saturation rather than on the effect of single nutrients. A diet based on a adequate intake of calcium (1000-1200 mg per day) and containment of animal protein and salt can decrease significantly urinary supersaturation for calcium oxalate and reduce the relative risk of stone recurrence in hypercalciuric renal stone formers. The DASH-style diet that is high in fruits and vegetables, moderate in low-fat dairy products and low in animal proteins and salt is associated with a lower relative supersaturation for calcium oxalate and a marked decrease in risk of incident stone formation. All the diets above mentioned have as a common characteristic the reduction of the potential acid load of the diet that can be correlated with a higher risk of recurrent nephrolithiasis, because the acid load of diet is inversely related to urinary citrate excretion. The restriction of protein and salt with an adequate calcium intake seem to be advisable but should be implemented with the advice to increase the intake

A novel antioxidant agent caffeic acid phenethyl ester prevents long-term mobile phone exposure-induced renal impairment in rat. Prognostic value of malondialdehyde, N-acetyl-beta-D-glucosaminidase and nitric oxide determination.

PubMed

Ozguner, Fehmi; Oktem, Faruk; Ayata, Ali; Koyu, Ahmet; Yilmaz, H Ramazan

2005-09-01

Caffeic acid phenethyl ester (CAPE), a flavonoid like compound, is one of the major components of honeybee propolis. It has been used in folk medicine for many years in Middle East countries. It was found to be a potent free radical scavenger and antioxidant recently. The aim of this study was to examine long-term applied 900 MHz emitting mobile phone-induced oxidative stress that promotes production of reactive oxygen species (ROS) and, was to investigate the role of CAPE on kidney tissue against the possible electromagnetic radiation (EMR)-induced renal impairment in rats. In particular, the ROS such as superoxide and nitric oxide (NO) may contribute to the pathophysiology of EMR-induced renal impairment. Malondialdehyde (MDA, an index of lipid peroxidation) levels, urinary N-acetyl-beta-D-glucosaminidase (NAG, a marker of renal tubular injury) and nitric oxide (NO, an oxidant product) levels were used as markers of oxidative stress-induced renal impairment and the success of CAPE treatment. The activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) in renal tissue were determined to evaluate the changes of antioxidant status. The rats used in the study were randomly grouped (10 each) as follows: i) Control group (without stress and EMR), ii) Sham-operated rats stayed without exposure to EMR (exposure device off), iii) Rats exposed to 900 MHz EMR (EMR group), and iv) A 900 MHz EMR exposed + CAPE treated group (EMR + CAPE group). In the EMR exposed group, while tissue MDA, NO levels and urinary NAG levels increased (p < 0.0001), the activities of SOD, CAT, and GSH-Px in renal tissue were reduced (p < 0.001). CAPE treatment reversed these effects as well (p < 0.0001, p < 0.001 respectively). In conclusion, the increase in NO and MDA levels of renal tissue, and in urinary NAG with the decrease in renal SOD, CAT, GSH-Px activities demonstrate the role of oxidative mechanisms in 900 MHz mobile phone-induced renal tissue damage

Factors associated with mosquito net use by individuals in households owning nets in Ethiopia

PubMed Central

2011-01-01

Background Ownership of insecticidal mosquito nets has dramatically increased in Ethiopia since 2006, but the proportion of persons with access to such nets who use them has declined. It is important to understand individual level net use factors in the context of the home to modify programmes so as to maximize net use. Methods Generalized linear latent and mixed models (GLLAMM) were used to investigate net use using individual level data from people living in net-owning households from two surveys in Ethiopia: baseline 2006 included 12,678 individuals from 2,468 households and a sub-sample of the Malaria Indicator Survey (MIS) in 2007 included 14,663 individuals from 3,353 households. Individual factors (age, sex, pregnancy); net factors (condition, age, net density); household factors (number of rooms [2006] or sleeping spaces [2007], IRS, women's knowledge and school attendance [2007 only], wealth, altitude); and cluster level factors (rural or urban) were investigated in univariate and multi-variable models for each survey. Results In 2006, increased net use was associated with: age 25-49 years (adjusted (a) OR = 1.4, 95% confidence interval (CI) 1.2-1.7) compared to children U5; female gender (aOR = 1.4; 95% CI 1.2-1.5); fewer nets with holes (Ptrend = 0.002); and increasing net density (Ptrend < 0.001). Reduced net use was associated with: age 5-24 years (aOR = 0.2; 95% CI 0.2-0.3). In 2007, increased net use was associated with: female gender (aOR = 1.3; 95% CI 1.1-1.6); fewer nets with holes (aOR [all nets in HH good] = 1.6; 95% CI 1.2-2.1); increasing net density (Ptrend < 0.001); increased women's malaria knowledge (Ptrend < 0.001); and urban clusters (aOR = 2.5; 95% CI 1.5-4.1). Reduced net use was associated with: age 5-24 years (aOR = 0.3; 95% CI 0.2-0.4); number of sleeping spaces (aOR [per additional space] = 0.6, 95% CI 0.5-0.7); more old nets (aOR [all nets in HH older than 12 months] = 0.5; 95% CI 0.3-0.7); and increasing household altitude

Transport characteristics of L-citrulline in renal apical membrane of proximal tubular cells.

PubMed

Mitsuoka, Keisuke; Shirasaka, Yoshiyuki; Fukushi, Akimasa; Sato, Masanobu; Nakamura, Toshimichi; Nakanishi, Takeo; Tamai, Ikumi

2009-04-01

L-Citrulline has diagnostic potential for renal function, because its plasma concentration increases with the progression of renal failure. Although L-citrulline extracted by glomerular filtration in kidney is mostly reabsorbed, the mechanism involved is not clearly understood. The present study was designed to characterize L-citrulline transport across the apical membranes of renal epithelial tubular cells, using primary-cultured rat renal proximal tubular cells, as well as the human kidney proximal tubular cell line HK-2. L-Citrulline was transported in a Na(+)-dependent manner from the apical side of both cell types cultured on permeable supports with a microporous membrane. Kinetic analysis indicated that the transport involves two distinct Na(+)-dependent saturable systems and one Na(+)-independent saturable system in HK-2 cells. The uptake was competitively inhibited by neutral and cationic, but not anionic amino acids. Relatively large cationic and anionic compounds inhibited the uptake, but smaller ones did not. In HK-2 cells, mRNA expression of SLC6A19 and SLC7A9, which encode B(0)AT1 and b(0,+)AT, respectively, was detected by RT-PCR. In addition, L-citrulline transport was significantly decreased in HK-2 cells in which either SLC6A19 or SLC7A9 was silenced. Hence, these results suggest that amino acid transporters B(0)AT1 and b(0,+)AT are involved in the reabsorption of L-citrulline in the kidney, at least in part, by mediating the apical membrane transport of L-citrulline in renal tubule cells.

Adaptations of hepatic amino acid uptake and net utilisation contributes to nitrogen economy or waste in lambs fed nitrogen- or energy-deficient diets.

PubMed

Kraft, G; Ortigues-Marty, I; Durand, D; Rémond, D; Jardé, T; Bequette, B; Savary-Auzeloux, I

2011-04-01

We investigated the effect of relative changes in dietary nitrogen (N) and energy supply and the subsequent variations in net portal appearance (NPA) of nitrogenous and energy nutrients on the net amino acid (AA) uptake by the liver and net N supply to the peripheral tissues. Six lambs were catheterised across the splanchnic tissues and received, in a replicated Latin square, one of three dietary treatments. The diets were formulated to either match the requirements of N and energy (C), or supply only 0.8 of the N requirement (LN) or 0.8 of the energy requirement (LE). Net fluxes of AA and urea-N were measured across the portal-drained viscera, and estimation of arterial hepatic flow allowed the estimation of hepatic fluxes. Catheters were implanted into the portal and hepatic veins as well as in the abdominal aorta for the measurement of AA fluxes. Animals fed the LN diet showed more efficient N retention (0.59 of digested N) than did the C and LE diet (0.50 and 0.33, respectively; P < 0.001). The NPA of total AA-N for the LN diet was only 0.60 of the value measured for the control (C) diet (P < 0.01). Despite this, the total estimated AA-N net splanchnic fluxes were not significantly different across the three diets (3.3, 1.9 and 2.6 g total AA-N/day for C, LN and LE, respectively, P = 0.52). Thus, different metabolic regulations must have taken place across the liver between the three experimental diets. A combination of decreased net uptake of total AA-N by the liver of animals in the LN diet (0.61 of the C diet; P = 0.002) and reduced urinary urea-N production (0.52 of the C diet; P = 0.001) spared AA from catabolism in the LN diet relative to the other two diets. For the LE diet, the urinary urea-N output was 1.3 times the value of the C diet (P = 0.01). This may relate to an increased catabolism of AA by the muscle and/or, to a lesser extent, to an increased utilisation of AA for gluconeogenesis in the liver. These effects may explain the reduced whole body

Evidence Report: Risk of Renal Stone Formation

NASA Technical Reports Server (NTRS)

Sibonga, Jean D.; Pietrzyk, Robert

2017-01-01

The formation of renal stones poses an in-flight health risk of high severity, not only because of the impact of renal colic on human performance but also because of complications that could potentially lead to crew evacuation, such as hematuria, infection, hydronephrosis, and sepsis. Evidence for risk factors comes from urine analyses of crewmembers, documenting changes to the urinary environment that are conducive to increased saturation of stone-forming salts, which are the driving force for nucleation and growth of a stone nidus. Further, renal stones have been documented in astronauts after return to Earth and in one cosmonaut during flight. Biochemical analysis of urine specimens has provided indication of hypercalciuria and hyperuricemia, reduced urine volumes, and increased urine saturation of calcium oxalate and calcium phosphate. A major contributor to the risk for renal stone formation is bone atrophy with increased turnover of the bone minerals. Dietary and fluid intakes also play major roles in the risk because of the influence on urine pH (more acidic) and on volume (decreased). Historically, specific assessments on urine samples from some Skylab crewmembers indicated that calcium excretion increased early in flight, notable by day 10 of flight, and almost exceeded the upper threshold for normal excretion (300mg/day in males). Other crewmember data documented reduced intake of fluid and reduced intake of potassium, phosphorus, magnesium, and citrate (an inhibitor of calcium stone formation) in the diet. Hence, data from both short-duration and long-duration missions indicate that space travel induces risk factors for renal stone formation that continue to persist after flight; this risk has been documented by reported kidney stones in crewmembers.

Identification of key metabolic changes in renal interstitial fibrosis rats using metabonomics and pharmacology.

PubMed

Zhao, Liangcai; Dong, Minjian; Liao, Shixian; Du, Yao; Zhou, Qi; Zheng, Hong; Chen, Minjiang; Ji, Jiansong; Gao, Hongchang

2016-06-03

Renal fibrosis is one of the important pathways involved in end-stage renal failure. Investigating the metabolic changes in the progression of disease may enhance the understanding of its pathogenesis and therapeutic information. In this study, (1)H-nuclear magnetic resonance (NMR)-based metabonomics was firstly used to screen the metabolic changes in urine and kidney tissues of renal interstitial fibrotic rats induced by unilateral ureteral obstruction (UUO), at 7, 14, 21, and 28 days after operation, respectively. The results revealed that reduced levels of bioenergy synthesis and branched chain amino acids (BCAAs), as well as elevated levels of indoxyl sulfate (IS) are involved in metabolic alterations of renal fibrosis rats. Next, by pharmacological treatment we found that reduction of IS levels could prevent the renal fibrotic symptoms. Therefore, we suggested that urinary IS may be used as a potential biomarker for the diagnosis of renal fibrosis, and a therapeutic target for drugs. Novel attempt combining metabonomics and pharmacology was established that have ability to provide more systematic diagnostic and therapeutic information of diseases.

Renal Stone Risk During Space Flight: Assessment and Countermeasure Validation

NASA Technical Reports Server (NTRS)

Whitson, P. A.; Sams, C. F.; Jones, J. A.; Pietrzke, R. A.; Nelman-Gonzalez, M. A.; Hudson, E. K.

2007-01-01

NASA has focused its future on exploration class missions including the goal of returning to the moon and landing on Mars. With these objectives, humans will experience an extended exposure to the harsh environment of microgravity and the associated negative effects on all the physiological systems of the body. Exposure to microgravity affects human physiology and results in changes to the urinary chemical composition during and after space flight. These changes are associated with an increased risk of renal stone formation. The development of a renal stone would have health consequences for the crewmember and negatively impact the success of the mission. As of January 2007, 15 known symptomatic medical events consistent with urinary calculi have been experienced by 13 U.S. astronauts and Russian cosmonauts. Previous results from both MIR and Shuttle missions have demonstrated an increased risk for renal stone formation. These data have shown decreased urine volume, urinary pH and citrate levels and increased urinary calcium. Citrate, an important urinary inhibitor of calcium-containing renal stones binds with calcium in the urine, thereby reducing the amount of calcium available to form calcium oxalate stones. Urinary citrate also prevents calcium oxalate crystals from aggregating into larger crystals and into renal stones. In addition, citrate makes the urine less acidic which inhibits the development of uric acid stones. Potassium citrate supplementation has been successfully used to treat patients who have formed renal stones. The evaluation of potassium citrate as a countermeasure has been performed during the ISS Expeditions 3-6, 8, 11-13 and is currently in progress during the ISS Expedition 14 mission. Together with the assessment of stone risk and the evaluation of a countermeasure, this investigation provides an educational opportunity to all crewmembers. Individual urinary biochemical profiles are generated and the risk of stone formation is estimated

Atheroembolic renal disease

MedlinePlus

Renal disease - atheroembolic; Cholesterol embolization syndrome; Atheroemboli - renal; Atherosclerotic disease - renal ... disorder of the arteries. It occurs when fat, cholesterol, and other substances build up in the walls ...

Inhibiting aerobic glycolysis suppresses renal interstitial fibroblast activation and renal fibrosis.

PubMed

Ding, Hao; Jiang, Lei; Xu, Jing; Bai, Feng; Zhou, Yang; Yuan, Qi; Luo, Jing; Zen, Ke; Yang, Junwei

2017-09-01

Chronic kidney diseases generally lead to renal fibrosis. Despite great progress having been made in identifying molecular mediators of fibrosis, the mechanism that governs renal fibrosis remains unclear, and so far no effective therapeutic antifibrosis strategy is available. Here we demonstrated that a switch of metabolism from oxidative phosphorylation to aerobic glycolysis (Warburg effect) in renal fibroblasts was the primary feature of fibroblast activation during renal fibrosis and that suppressing renal fibroblast aerobic glycolysis could significantly reduce renal fibrosis. Both gene and protein assay showed that the expression of glycolysis enzymes was upregulated in mouse kidneys with unilateral ureter obstruction (UUO) surgery or in transforming growth factor-β1 (TGF-β1)-treated renal interstitial fibroblasts. Aerobic glycolysis flux, indicated by glucose uptake and lactate production, was increased in mouse kidney with UUO nephropathy or TGF-β1-treated renal interstitial fibroblasts and positively correlated with fibrosis process. In line with this, we found that increasing aerobic glycolysis can remarkably induce myofibroblast activation while aerobic glycolysis inhibitors shikonin and 2-deoxyglucose attenuate UUO-induced mouse renal fibrosis and TGF-β1-stimulated myofibroblast activation. Furthermore, mechanistic study indicated that shikonin inhibits renal aerobic glycolysis via reducing phosphorylation of pyruvate kinase type M2, a rate-limiting glycolytic enzyme associated with cell reliance on aerobic glycolysis. In conclusion, our findings demonstrate the critical role of aerobic glycolysis in renal fibrosis and support treatment with aerobic glycolysis inhibitors as a potential antifibrotic strategy. Copyright © 2017 the American Physiological Society.

Effects of Renal Denervation from the Intima and the Adventitia of Renal Arteries on Renal Sympathetic Nerve Activity in Dogs: A Comparative Study.

PubMed

Bai, Minfu; Yang, Chaokuan; Gao, Chuanyu; Wang, Xianpei; Liu, Hongzhi; Zhang, You; Liu, Jun; Wu, Jintao; Jian, Dongdong; Zhu, Lijie; Zhao, Wenli; Ma, Peiyao; Han, Yaqi

2015-01-01

This study was designed to observe the efficacy and safety of renal denervation from the inside and outside of renal arteries. Fourteen beagles were randomly divided into a control group (n = 4) and treatment group (n = 10). One renal artery in every beagle of the treatment group was randomly assigned to an intimal group (10 renal arteries) which underwent percutaneous renal denervation from the inside, and another renal artery was assigned to an adventitial group (10 renal arteries) which underwent renal denervation from the outside by laparotomy. Compared with the intimal group, the renal norepinephrine (NE) concentration in the adventitial group had significantly decreased (p = 0.003) at 3 months postsurgery. Renal artery HE staining showed that the perineurium from the adventitial group appeared thickened. Western blotting showed that renal tissue tyrosine hydroxylase (TH) protein expression in the adventitial group was significantly lower than that in the intimal group (p < 0.01) at 3 months postsurgery. There was a renal artery stenosis and a renal atrophy in the intimal group after 1 month of follow-up. The inhibitory effect on renal sympathetic nerve activity was more effective in the adventitial group than the intimal group, and renal denervation in the former group was safe. © 2015 S. Karger AG, Basel.

Coral reefs will transition to net dissolving before end of century

NASA Astrophysics Data System (ADS)

Eyre, Bradley D.; Cyronak, Tyler; Drupp, Patrick; De Carlo, Eric Heinen; Sachs, Julian P.; Andersson, Andreas J.

2018-02-01

Ocean acidification refers to the lowering of the ocean’s pH due to the uptake of anthropogenic CO2 from the atmosphere. Coral reef calcification is expected to decrease as the oceans become more acidic. Dissolving calcium carbonate (CaCO3) sands could greatly exacerbate reef loss associated with reduced calcification but is presently poorly constrained. Here we show that CaCO3 dissolution in reef sediments across five globally distributed sites is negatively correlated with the aragonite saturation state (Ωar) of overlying seawater and that CaCO3 sediment dissolution is 10-fold more sensitive to ocean acidification than coral calcification. Consequently, reef sediments globally will transition from net precipitation to net dissolution when seawater Ωar reaches 2.92 ± 0.16 (expected circa 2050 CE). Notably, some reefs are already experiencing net sediment dissolution.

Renal cell carcinoma

MedlinePlus

Renal cancer; Kidney cancer; Hypernephroma; Adenocarcinoma of renal cells; Cancer - kidney ... 2016:chap 57. National Cancer Institute website. Renal cell cancer treatment (PDQ) - health professional version. February 23, 2018. ...

Can MR Measurement of Renal Artery Flow and Renal Volume Predict the Outcome of Percutaneous Transluminal Renal Angioplasty?

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

Binkert, Christoph A.; Debatin, Jorg F.; Schneider, Ernst

2001-07-15

Purpose: Predicting therapeutic benefit from percutaneous transluminal renal angioplasty (PTRA) in patients with renal artery stenosis (RAS) remains difficult. This study investigates whether magnetic resonance (MR)-based renal artery flow measurements relative to renal parenchymal volume can predict clinical outcome following PTRA.Methods: The data on 23 patients (13 men, 10 women; age range 47-82 years, mean age 64 years) were analyzed. The indication for treatment was hypertension (n = 18) or renal insufficiency (n = 5). Thirty-four cases of RAS were identified: bilateral disease was manifest in 11 and unilateral disease in 12 patients. The MR imaging protocol included a breath-hold,more » cardiac-gated cine phase-contrast sequence for renal flow measurement and a fast multiplanar spoiled gradient-echo sequence for renal volume measurement. MR measurements were performed on the day prior to and the day following PTRA. Clinical success was defined as (a) a reduction in diastolic blood pressure > 15% or (b) a reduction in serum creatinine > 20%. Kidneys were categorized as normal volume or low volume. A renal flow index (RFI) was calculated by dividing the renal flow (ml/min) by the renal volume (cm{sup 3}).Results: Clinical success was observed in 11 patients. Twelve patients did not benefit from angioplasty. Normal kidney volume was seen in 10 of 11 responders and in 8 of 12 nonresponders, resulting in a sensitivity of 91%, specificity of 33%, a positive predictive value (PPV) of 56% and a negative predictive value (NPV) of 80%. A RFI below a threshold of 1.5 ml/min/cm{sup 3} predicted successful outcome with 100% sensitivity, 33% specificity, 58% PPV, and 100% NPV. The combination of normal renal volume and a RFI below 1.5 ml/min/cm{sup 3} identified PTRA responders with a sensitivity of 91%, a specificity of 67%, a PPV of 71%, and a NPV of 89%. PTRA resulted in a greater increase in renal flow in responders compared with nonresponders (p < 0.001).Conclusion

Urea and Ammonia Metabolism and the Control of Renal Nitrogen Excretion.

PubMed

Weiner, I David; Mitch, William E; Sands, Jeff M

2015-08-07

Renal nitrogen metabolism primarily involves urea and ammonia metabolism, and is essential to normal health. Urea is the largest circulating pool of nitrogen, excluding nitrogen in circulating proteins, and its production changes in parallel to the degradation of dietary and endogenous proteins. In addition to serving as a way to excrete nitrogen, urea transport, mediated through specific urea transport proteins, mediates a central role in the urine concentrating mechanism. Renal ammonia excretion, although often considered only in the context of acid-base homeostasis, accounts for approximately 10% of total renal nitrogen excretion under basal conditions, but can increase substantially in a variety of clinical conditions. Because renal ammonia metabolism requires intrarenal ammoniagenesis from glutamine, changes in factors regulating renal ammonia metabolism can have important effects on glutamine in addition to nitrogen balance. This review covers aspects of protein metabolism and the control of the two major molecules involved in renal nitrogen excretion: urea and ammonia. Both urea and ammonia transport can be altered by glucocorticoids and hypokalemia, two conditions that also affect protein metabolism. Clinical conditions associated with altered urine concentrating ability or water homeostasis can result in changes in urea excretion and urea transporters. Clinical conditions associated with altered ammonia excretion can have important effects on nitrogen balance. Copyright © 2015 by the American Society of Nephrology.

Mangiferin Inhibits Renal Urate Reabsorption by Modulating Urate Transporters in Experimental Hyperuricemia.

PubMed

Yang, Hua; Gao, Lihui; Niu, Yanfen; Zhou, Yuanfang; Lin, Hua; Jiang, Jing; Kong, Xiangfu; Liu, Xu; Li, Ling

2015-01-01

Mangiferin, a natural glucosyl xanthone from the leaves of Mangifera indica L., was previously shown to exert potent hypouricemic effects associated with inhibition of the activity of xanthine dehydrogenase/oxidase. The present study aimed to evaluate its uricosuric effect and possible molecular mechanisms underlying the renal urate transporters responsible for urate reabsorption in vivo. Mangiferin (1.5-24.0 mg/kg) was administered intragastrically to hyperuricemic mice and rats induced by the intraperitoneal injection of uric acid and potassium oxonate, respectively. The uricosuric effect was evaluated by determining the serum and urinary urate levels as well as fractional excretion of uric acid (FEUA). The mRNA and protein levels of renal urate-anion transporter 1 (URAT1), organic anion transporter 10 (OAT10), glucose transporter 9 (GLUT9), and PDZ domain-containing protein (PDZK1) were analyzed. The administration of mangiferin significantly decreased the serum urate levels in hyperuricemic mice in a dose- and time-dependent manner. In hyperuricemic rats, mangiferin also reduced the serum urate levels and increased the urinary urate levels and FEUA. These results indicate that mangiferin has uricosuric effects. Further examination showed that mangiferin markedly inhibited the mRNA and protein expression of renal URAT1, OAT10, and GLUT9 in hyperuricemic rats, but did not interfere with PDZK1 expression. Taken together, these findings suggest that mangiferin promotes urate excretion by the kidney, which may be related to the inhibition of urate reabsorption via downregulation of renal urate transporters.

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.

Impact of feline AIM on the susceptibility of cats to renal disease

PubMed Central

Sugisawa, Ryoichi; Hiramoto, Emiri; Matsuoka, Shigeru; Iwai, Satomi; Takai, Ryosuke; Yamazaki, Tomoko; Mori, Nobuko; Okada, Yuki; Takeda, Naoki; Yamamura, Ken-ichi; Arai, Toshiro; Arai, Satoko; Miyazaki, Toru

2016-01-01

Renal failure is one of the most important social problems for its incurability and high costs for patients’ health care. Through clarification of the underlying mechanism for the high susceptibility of cats to renal disease, we here demonstrates that the effective dissociation of serum AIM protein from IgM is necessary for the recovery from acute kidney injury (AKI). In cats, the AIM-IgM binding affinity is 1000-fold higher than that in mice, which is caused by the unique positively-charged amino-acid cluster present in feline AIM. Hence, feline AIM does not dissociate from IgM during AKI, abolishing its translocation into urine. This results in inefficient clearance of lumen-obstructing necrotic cell debris at proximal tubules, thereby impairing AKI recovery. Accordingly, mice whose AIM is replaced by feline AIM exhibit higher mortality by AKI than in wild-type mice. Recombinant AIM administration into the mice improves their renal function and survival. As insufficient recovery from AKI predisposes patients to chronic, end-stage renal disease, feline AIM may be involved crucially in the high mortality of cats due to renal disease. Our findings could be the basis of the development of novel AKI therapies targeting AIM-IgM dissociation, and may support renal function in cats and prolong their lives. PMID:27731392

Predictors of renal scar in children with urinary infection and vesicoureteral reflux.

PubMed

Soylu, Alper; Demir, Belde Kasap; Türkmen, Mehmet; Bekem, Ozlem; Saygi, Murat; Cakmakçi, Handan; Kavukçu, Salih

2008-12-01

We evaluated the predictors of renal scar in children with urinary tract infections (UTIs) having primary vesicoureteral reflux (VUR). Data of patients who were examined by dimercaptosuccinic acid (DMSA) scintigraphy between 1995 and 2005 were evaluated retrospectively. Gender, age, reflux grade, presence/development of scarring, breakthrough UTIs, and resolution of reflux, were recorded. The relation of gender, age and VUR grade to preformed scarring and the relation of gender, age, VUR grade, presence of preformed scarring, number of breakthrough UTIs and reflux resolution to new scarring were assessed. There were 138 patients [male/female (M/F) 53/85]. Multivariate analysis showed that male gender [odds ratio (OR) 2.5], age > or = 27 months in girls (OR 4.2) and grades IV-V reflux (OR 12.4) were independent indicators of renal scarring. On the other hand, only the presence of previous renal scarring was found to be an independent indicator for the development of new renal scar (OR 13.4). In conclusion, while the most predictive variables for the presence of renal scarring among children presenting with a UTI were male gender, age > or = 27 months in girls, and grades IV-V reflux, the best predictor of new scar formation was presence of previous renal scarring.

Impact of feline AIM on the susceptibility of cats to renal disease.

PubMed

Sugisawa, Ryoichi; Hiramoto, Emiri; Matsuoka, Shigeru; Iwai, Satomi; Takai, Ryosuke; Yamazaki, Tomoko; Mori, Nobuko; Okada, Yuki; Takeda, Naoki; Yamamura, Ken-Ichi; Arai, Toshiro; Arai, Satoko; Miyazaki, Toru

2016-10-12

Renal failure is one of the most important social problems for its incurability and high costs for patients' health care. Through clarification of the underlying mechanism for the high susceptibility of cats to renal disease, we here demonstrates that the effective dissociation of serum AIM protein from IgM is necessary for the recovery from acute kidney injury (AKI). In cats, the AIM-IgM binding affinity is 1000-fold higher than that in mice, which is caused by the unique positively-charged amino-acid cluster present in feline AIM. Hence, feline AIM does not dissociate from IgM during AKI, abolishing its translocation into urine. This results in inefficient clearance of lumen-obstructing necrotic cell debris at proximal tubules, thereby impairing AKI recovery. Accordingly, mice whose AIM is replaced by feline AIM exhibit higher mortality by AKI than in wild-type mice. Recombinant AIM administration into the mice improves their renal function and survival. As insufficient recovery from AKI predisposes patients to chronic, end-stage renal disease, feline AIM may be involved crucially in the high mortality of cats due to renal disease. Our findings could be the basis of the development of novel AKI therapies targeting AIM-IgM dissociation, and may support renal function in cats and prolong their lives.

Furan fatty acids - Beneficial or harmful to health?

PubMed

Xu, Long; Sinclair, Andrew J; Faiza, Muniba; Li, Daoming; Han, Xianlin; Yin, Huiyong; Wang, Yonghua

2017-10-01

Furan fatty acids are found in plants, algae, and fish, and reported to have some positive health benefits, including anti-oxidant and anti-inflammatory activities, and inhibition of non-enzymatic lipid peroxidation. A major metabolite of furan fatty acids, 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF), has been reported to be increased in patients who progress from prediabetes to type 2 diabetes, although CMPF is not necessarily associated with impaired glucose metabolism. Other studies report that CMPF levels are lower in subjects with diabetes than control subjects. Plasma CMPF levels increase in subjects who consume fish or fish oil, and in patients with renal failure. It is not known where furan fatty acids are converted to CMPF and it is speculated that this might be a result of microbiome activity. The plasma levels reported for CMPF in healthy, diabetic and patients with renal disease vary by factors of more than 100-fold within each of these three groups, so measurement error appears to be limiting the ability to interpret studies. This review explores these controversies and raises questions about whether CMPF is a marker for healthy diets or indeed associated with diabetes and renal health. The review concludes that, on balance, furan fatty acids are beneficial for health. Copyright © 2017 Elsevier Ltd. All rights reserved.

[Aortic dissection spread to the renal arteries: role of renal volumetry after angioplasty].

PubMed

Vautrin, E; Thony, F; Chavanon, O; Hannachi, I; Barone-Rochette, G; Pierre, H; Baguet, J-P

2012-06-01

Type A or B aortic dissection can extend to renal arteries, causing a renal ischemia which treatment is usually endovascular. The aim of our study is to show the interest of the renal volumetry in the follow-up of these patients. Twenty-two patients (16 men, mean age 63.4±11.8years, BMI 25.2±3.4kg/m(2)) with a type A or B aortic dissection spread to one or to both renal arteries and followed at Grenoble university hospital were consecutively included. All patients underwent renal angiography with aorto-renal pressure gradients measurements and follow-up by renal volumetry (scanner Siemens(®)). A renal ischemia was defined by a decrease of 20% or more of the volumetry. Sixteen patients (73%) were hypertensive before the aortic dissection among which ten (62%) were treated. Eight patients (36%) have a significant renal pressure gradient among which five (62%) underwent renal endovascular therapy. The renal volumetry of these five patients remained unchanged while six of 17 patients (36%) without angioplasty have a decreasing volumetry. Renal volumetry appeared an effective and attractive option for the follow-up of the patients with aortic dissection spread to the renal arteries. These results should be taken into account to put the indication of an endovascular treatment. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Functions of the Renal Nerves.

ERIC Educational Resources Information Center

Koepke, John P.; DiBona, Gerald F.

1985-01-01

Discusses renal neuroanatomy, renal vasculature, renal tubules, renin secretion, renorenal reflexes, and hypertension as related to renal nerve functions. Indicates that high intensitites of renal nerve stimulation have produced alterations in several renal functions. (A chart with various stimulations and resultant renal functions and 10-item,…

Endothelin-A Receptor Antagonism after Renal Angioplasty Enhances Renal Recovery in Renovascular Disease

PubMed Central

Tullos, Nathan; Stewart, Nicholas J.; Surles, Bret

2015-01-01

Percutaneous transluminal renal angioplasty/stenting (PTRAS) is frequently used to treat renal artery stenosis and renovascular disease (RVD); however, renal function is restored in less than one half of the cases. This study was designed to test a novel intervention that could refine PTRAS and enhance renal recovery in RVD. Renal function was quantified in pigs after 6 weeks of chronic RVD (induced by unilateral renal artery stenosis), established renal damage, and hypertension. Pigs with RVD then underwent PTRAS and were randomized into three groups: placebo (RVD+PTRAS), chronic endothelin-A receptor (ET-A) blockade (RVD+PTRAS+ET-A), and chronic dual ET-A/B blockade (RVD+PTRAS+ET-A/B) for 4 weeks. Renal function was again evaluated after treatments, and then, ex vivo studies were performed on the stented kidney. PTRAS resolved renal stenosis, attenuated hypertension, and improved renal function but did not resolve renal microvascular rarefaction, remodeling, or renal fibrosis. ET-A blocker therapy after PTRAS significantly improved hypertension, microvascular rarefaction, and renal injury and led to greater recovery of renal function. Conversely, combined ET-A/B blockade therapy blunted the therapeutic effects of PTRAS alone or PTRAS followed by ET-A blockade. These data suggest that ET-A receptor blockade therapy could serve as a coadjuvant intervention to enhance the outcomes of PTRAS in RVD. These results also suggest that ET-B receptors are important for renal function in RVD and may contribute to recovery after PTRAS. Using clinically available compounds and techniques, our results could contribute to both refinement and design of new therapeutic strategies in chronic RVD. PMID:25377076

Effect of acute acid-base disturbances on ErbB1/2 tyrosine phosphorylation in rabbit renal proximal tubules.

PubMed

Skelton, Lara A; Boron, Walter F

2013-12-15

The renal proximal tubule (PT) is a major site for maintaining whole body pH homeostasis and is responsible for reabsorbing ∼80% of filtered HCO3(-), the major plasma buffer, into the blood. The PT adapts its rate of HCO3(-) reabsorption (JHCO3(-)) in response to acute acid-base disturbances. Our laboratory previously showed that single isolated perfused PTs adapt JHCO3(-) in response to isolated changes in basolateral (i.e., blood side) CO2 and HCO3(-) concentrations but, surprisingly, not to pH. The response to CO2 concentration can be blocked by the ErbB family tyrosine kinase inhibitor PD-168393. In the present study, we exposed enriched rabbit PT suspensions to five acute acid-base disturbances for 5 and 20 min using a panel of phosphotyrosine (pY)-specific antibodies to determine the influence of each disturbance on pan-pY, ErbB1-specific pY (four sites), and ErbB2-specific pY (two sites). We found that each acid-base treatment generated a distinct temporal pY pattern. For example, the summated responses of the individual ErbB1/2-pY sites to each disturbance showed that metabolic acidosis (normal CO2 concentration and reduced HCO3(-) concentration) produced a transient summated pY decrease (5 vs. 20 min), whereas metabolic alkalosis produced a transient increase. Respiratory acidosis (normal HCO3(-) concentration and elevated CO2 concentration) had little effect on summated pY at 5 min but produced an elevation at 20 min, whereas respiratory alkalosis produced a reduction at 20 min. Our data show that ErbB1 and ErbB2 in the PT respond to acute acid-base disturbances, consistent with the hypothesis that they are part of the signaling cascade.

Effect of acute acid-base disturbances on ErbB1/2 tyrosine phosphorylation in rabbit renal proximal tubules

PubMed Central

Skelton, Lara A.

2013-01-01

The renal proximal tubule (PT) is a major site for maintaining whole body pH homeostasis and is responsible for reabsorbing ∼80% of filtered HCO3−, the major plasma buffer, into the blood. The PT adapts its rate of HCO3− reabsorption (JHCO3−) in response to acute acid-base disturbances. Our laboratory previously showed that single isolated perfused PTs adapt JHCO3− in response to isolated changes in basolateral (i.e., blood side) CO2 and HCO3− concentrations but, surprisingly, not to pH. The response to CO2 concentration can be blocked by the ErbB family tyrosine kinase inhibitor PD-168393. In the present study, we exposed enriched rabbit PT suspensions to five acute acid-base disturbances for 5 and 20 min using a panel of phosphotyrosine (pY)-specific antibodies to determine the influence of each disturbance on pan-pY, ErbB1-specific pY (four sites), and ErbB2-specific pY (two sites). We found that each acid-base treatment generated a distinct temporal pY pattern. For example, the summated responses of the individual ErbB1/2-pY sites to each disturbance showed that metabolic acidosis (normal CO2 concentration and reduced HCO3− concentration) produced a transient summated pY decrease (5 vs. 20 min), whereas metabolic alkalosis produced a transient increase. Respiratory acidosis (normal HCO3− concentration and elevated CO2 concentration) had little effect on summated pY at 5 min but produced an elevation at 20 min, whereas respiratory alkalosis produced a reduction at 20 min. Our data show that ErbB1 and ErbB2 in the PT respond to acute acid-base disturbances, consistent with the hypothesis that they are part of the signaling cascade. PMID:24133121

Reactivation of Mucosal and Cutaneous Leishmaniasis in a Renal Transplanted Patient

PubMed Central

Tuon, Felipe F.; Bombonatto, Giovana Marina; Battaglin, Eveline Roesler; Sakumoto, Marcus Henrique; Amato, Valdir Sabbaga; de Camargo, Raphael Abegão; Nicodemo, Antônio Carlos

2014-01-01

Mucosal leishmaniasis (ML) is a chronic form of tegumentary leishmaniasis, which causes destructive lesions of nasal, pharyngeal, and laryngeal mucosa. We describe a case of leishmaniasis reactivation with simultaneous cutaneous and mucosal forms in a renal transplanted patient with no history of prior leishmaniasis. Reactivation after renal transplantation was not reported in Brazil. A 67-year-old woman receiving prednisone 20 mg/day, tacrolimus 1 mg/day, and mycophenolic acid 360 mg/day presented with nose edema with erythema and cutaneous lesions. Amastigotes were identified on biopsies and the polymerase chain reaction confirmed Leishmania (Viannia) braziliensis. The patient was treated with liposomal amphotericin B but died 3 weeks after as a result of bacterial septic shock. In conclusion, tegumentary leishmaniasis can reactivate with simultaneous cutaneous and mucosal forms in a renal transplanted patient during the immunosuppressant therapy. PMID:24732458

Characteristics of renal papillae in kidney stone formers.

PubMed

Marien, Tracy P; Miller, Nicole L

2016-12-01

The mechanism of kidney stone formation is not well understood. In order to better understand the pathophysiology for specific kidney stone compositions and systemic diseases associated with kidney stones, endoscopic papillary mapping studies with concurrent biopsies have been conducted. This review will summarize the findings of these studies and proposed mechanisms for thirteen disease processes associated with kidney stones. A review of the literature was performed identifying thirteen studies that endoscopically mapped and biopsied renal papillae of different stone formers. These studies characterized renal papillae based on amount of Randall's plaque, Bellini's duct pathology, papillary contour changes, presence of attached stones, pitting, and frequently papillary and cortical biopsies. The groups studied and reviewed here are kidney stone formers who have a history of idiopathic calcium oxalate stone formation, cystinuria, brushite stones, gastric bypass, ileostomy, small bowel resection, primary hyperparathyroidism, distal renal tubular acidosis (dRTA), primary hyperoxaluria, idiopathic calcium phosphate stone formation, medullary sponge kidney (MSK), uric acid stones, and struvite stones. A proposed standardized scoring system for papillary pathology was also reviewed. The series showed various degrees and types of changes to the renal papillae and corresponding histopathologic changes for each type of stone former reviewed. Those with predominantly alone Randall's plaque pathology had less tissue damage versus those with extensive Bellini's duct lesions who had more interstitial fibrosis and cortical pathology. Randall's plaques are associated with stone formers who have low urinary volume, high urinary calcium, and acidic urine and thus are frequently seen in those with brushite stones, primary hyperparathyroidism, small bowel resection, and idiopathic calcium phosphate stone formers. Bellini's duct plugging and pathology is theorized to occur via free

Neutrophil extracellular traps contribute to the pathogenesis of acid-aspiration-induced ALI/ARDS.

PubMed

Li, Haitao; Zhou, Xiaoting; Tan, Hongyi; Hu, Yongbin; Zhang, Lemeng; Liu, Shuai; Dai, Minhui; Li, Yi; Li, Qian; Mao, Zhi; Pan, Pinhua; Su, Xiaoli; Hu, Chengpin

2018-01-05

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is a manifestation of systemic inflammation in the lungs, but the factors that trigger inflammation in ALI/ARDS are unclear. We hypothesized that neutrophil extracellular traps (NETs) contribute to the pathogenesis of acid aspiration-induced ALI/ARDS. Analysis of bronchial aspirates from ARDS patients showed that NETs were significantly correlated with the degree of ARDS (r = -0.5846, p = 0.0359). NETs in bronchoalveolar lavage fluid of acid-aspiration mice were significantly higher (141.6 ± 23.08) at 3 h after injury than those in the sham group (1234 ± 101.9; p = 0.003, n = 5 per group). Exogenous NETs aggravated lung injury, while alvelestat and DNase markedly attenuated the intensity of ARDS. We investigated whether NETs are involved in the severity of gastric aspiration-induced ARDS. Then, a hydrochloric acid aspiration-induced ALI murine model was used to assess whether NETs are pathogenic and whether targeting NETs is protective. Exogenous NETs were administered to mice. Alvelestat can inhibit neutrophil elastase (NE), which serves an important role in NET formation, so we investigated whether alvelestat could protect against ALI in cell and mouse models. NETs may contribute to ALI/ARDS by promoting tissue damage and systemic inflammation. Targeting NETs by alvelestat may be a potential therapeutic strategy.

Antiurolithiatic Effect of Sirupeelai Samoola Kudineer: A Polyherbal Siddha Decoction on Ethylene Glycol-induced Renal Calculus in Experimental Rats

PubMed Central

Vasanthi, A. Hannah Rachel; Muthulakshmi, V.; Gayathri, V.; Manikandan, R.; Ananthi, S.; Kuruvilla, Sarah

2017-01-01

Background: Sirupeelai Samoola Kudineer (SK), a polyherbal decoction containing four medicinal plants has been used in Siddha system of medicine, practiced in Southern parts of India for the management of urolithiasis. Objective: The present study is carried out to scientifically validate the traditional claim and to study the mechanism of action of the drug. Materials and Methods: In the present study, anti-urolithiatic effect of SK was evaluated in Sprague-Dawley rats using ethylene glycol through drinking water and intraperitoneal injection of sodium oxalate. Renal damage was confirmed by the increased production of thiobarbituric acid reactive substance (TBARS). Results: Co-treatment with SK to urolithiatic rats for 21 days significantly prevented the elevation of renal and urinary stone biomarkers in plasma and renal tissue thereby preventing renal damage and the formation of renal calculi. Administration of SK at all doses and cystone restored the antioxidant (glutathione) levels by preventing the elevation of TBARS in the kidney tissue, which was further confirmed by histological sections. Conclusions: SK treatment promotes diuresis which leads to flushing of the renal stones and maintains the alkaline environment in the urinary system which probably mediates the antilithiatic activity. SK provides structural and functional protection to the kidneys by enhancing its physiological function against stone formation and validates its clinical use. SUMMARY SK exhibited antilithiatic and diuretic potential in ethylene glycol and sodium oxalate induced urolithiasis in ratsElevated urinary stone markers (Calcium, oxalate, uric acid, magnesium and phosphates) in plasma and renal tubular enzymes (LDH, GGT, ALP, AST ALT) in urolithiatic rats were reversed by SK treatmentSK administration significantly reduced the level of renal stress markers like Urea, Creatinine, LPO and elevated SOD, GPx, GSH levels aiding in nephroprotectionSK also provides structural and

[Renal elastography].

PubMed

Correas, Jean-Michel; Anglicheau, Dany; Gennisson, Jean-Luc; Tanter, Mickael

2016-04-01

Renal elastography has become available with the development of noninvasive quantitative techniques (including shear-wave elastography), following the rapidly growing field of diagnosis and quantification of liver fibrosis, which has a demonstrated major clinical impact. Ultrasound or even magnetic resonance techniques are leaving the pure research area to reach the routine clinical use. With the increased incidence of chronic kidney disease and its specific morbidity and mortality, the noninvasive diagnosis of renal fibrosis can be of critical value. However, it is difficult to simply extend the application from one organ to the other due to a large number of anatomical and technical issues. Indeed, the kidney exhibits various features that make stiffness assessment more complex, such as the presence of various tissue types (cortex, medulla), high spatial orientation (anisotropy), local blood flow, fatty sinus with variable volume and echotexture, perirenal space with variable fatty content, and the variable depth of the organ. Furthermore, the stiffness changes of the renal parenchyma are not exclusively related to fibrosis, as renal perfusion or hydronephrosis will impact the local elasticity. Renal elastography might be able to diagnose acute or chronic obstruction, or to renal tumor or pseudotumor characterization. Today, renal elastography appears as a promising application that still requires optimization and validation, which is the contrary for liver stiffness assessment. Copyright © 2016 Association Société de néphrologie. Published by Elsevier SAS. All rights reserved.

Uptake of free amino acids by bacteria-free larvae of the sand dollar Dendraster excentricus.

PubMed

Davis, J P; Stephens, G C

1984-10-01

Larvae of Dendraster excentricus were produced by collecting gametes and carrying out fertilization under aseptic conditions. Since gametes are free of bacteria in the gonad, bacteria-free (axenic) suspensions of larvae result. Net rates of entry of 14 amino acids and the rate of production of ammonia were simultaneously determined by high-performance liquid chromatography. The net rates of uptake of neutral amino acids were an order of magnitude greater than rates for basic and acidic amino acids. Influx of 14C-labeled leucine, arginine, and glutamate accurately reflects the net entry rate of these substrates. Uptake of amino acids by axenic suspensions of larvae was compared with uptake by suspensions prepared without aseptic precautions. There was no significant difference in net uptake of the 14 amino acids or in the pattern of oxidation and assimilation of [14C]leucine during short-term experiments of 4-h duration or less.

Functional renal imaging: new trends in radiology and nuclear medicine.

PubMed

Durand, Emmanuel; Chaumet-Riffaud, Philippe; Grenier, Nicolas

2011-01-01

The objective of this work is to compare the characteristics of various techniques for functional renal imaging, with a focus on nuclear medicine and magnetic resonance imaging. Even with low spatial resolution and rather poor signal-to-noise ratio, classical nuclear medicine has the advantage of linearity and good sensitivity. It remains the gold standard technique for renal relative functional assessment. Technetium-99m ((99m)Tc)-labeled diethylenetriamine penta-acetate remains the reference glomerular tracer. Tubular tracers have been improved: (123)I- or (131)I-hippuran, (99m)Tc-MAG3 and, recently, (99m)Tc-nitrilotriacetic acid. However, advancement in molecular imaging has not produced a groundbreaking tracer. Renal magnetic resonance imaging with classical gadolinated tracers probably has potential in this domain but has a lack of linearity and, therefore, its value still needs evaluation. Moreover, the advent of nephrogenic systemic fibrosis has delayed its expansion. Other developments, such as diffusion or blood oxygen level-dependent imaging, may have a role in the future. The other modalities have a limited role in clinical practice for functional renal imaging. Copyright © 2011 Elsevier Inc. All rights reserved.

Traditional and emerging cardiovascular and renal risk factors: an epidemiologic perspective.

PubMed

Zoccali, C

2006-07-01

Patients with chronic kidney disease (CKD) represent an important segment of the population (7-10%) and, mostly because of the high risk of cardiovascular complications associated with renal insufficiency, detection and treatment of CKD is now a public health priority. Traditional risk factors can incite renal dysfunction and cardiovascular damage as well. As renal function deteriorates, non-traditional risk factors play an increasing role both in glomerular filtration rate (GFR) loss and cardiovascular damage. Secondary analyses of controlled clinical trials suggest that inflammation may be a modifiable risk factor both for cardiac ischemia and renal disease progression in patients with or at risk of coronary heart disease. Homocysteine predicts renal function loss in the general population and cardiovascular events in end-stage renal disease (ESRD), but evidence that this sulfur amino acid is directly implicated in the progression of renal disease and in the high cardiovascular mortality of uremic patients is still lacking. High sympathetic activity and raised plasma concentration of asymmetric dimethylarginine (ADMA) have been associated to reduced GFR in patients with CKD and to cardiovascular complications in those with ESRD but again we still lack clinical trials targeting these risk factors. Presently, the clinical management of CKD patients remains largely unsatisfactory because only a minority of these attain the treatment goals recommended by current guidelines. Thus, in addition to research into new and established risk factors, it is important that nephrologists make the best use of knowledge already available to optimize the follow-up of these patients.

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

Renal Tumors

PubMed Central

Tan, Puay Hoon; Cheng, Liang; Rioux-Leclercq, Nathalie; Merino, Maria J.; Netto, George; Reuter, Victor E.; Shen, Steven S.; Grignon, David J.; Montironi, Rodolfo; Egevad, Lars; Srigley, John R.; Delahunt, Brett; Moch, Holger

2016-01-01

The International Society of Urological Pathology convened a consensus conference on renal cancer, preceded by an online survey, to address issues relating to the diagnosis and reporting of renal neoplasia. In this report, the role of biomarkers in the diagnosis and assessment of prognosis of renal tumors is addressed. In particular we focused upon the use of immunohistochemical markers and the approach to specific differential diagnostic scenarios. We enquired whether cytogenetic and molecular tools were applied in practice and asked for views on the perceived prognostic role of biomarkers. Both the survey and conference voting results demonstrated a high degree of consensus in participants’ responses regarding prognostic/predictive markers and molecular techniques, whereas it was apparent that biomarkers for these purposes remained outside the diagnostic realm pending clinical validation. Although no individual antibody or panel of antibodies reached consensus for classifying renal tumors, or for confirming renal metastatic disease, it was noted from the online survey that 87% of respondents used immunohistochemistry to subtype renal tumors sometimes or occasionally, and a majority (87%) used immunohistochemical markers (Pax 2 or Pax 8, renal cell carcinoma [RCC] marker, panel of pan-CK, CK7, vimentin, and CD10) in confirming the diagnosis of metastatic RCC. There was consensus that immunohistochemistry should be used for histologic subtyping and applied before reaching a diagnosis of unclassified RCC. At the conference, there was consensus that TFE3 and TFEB analysis ought to be requested when RCC was diagnosed in a young patient or when histologic appearances were suggestive of the translocation subtype; whereas Pax 2 and/or Pax 8 were considered to be the most useful markers in the diagnosis of a renal primary. PMID:24025522

Experimental drug-induced changes in renal function and biodistribution of /sup 99m/Tc-MDP

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

McAfee, J.G.; Singh, A.; Roskopf, M.

Increased renal uptake of /sup 99m/Tc methylene diphosphonate (MDP) was observed irregularly in rats after methotrexate, vincristine or gentamicin, administered separately. Cisplatin regularly induced a dose-related increased MDP uptake which correlated with the degree of tubular damage histologically. The augmented MDP renal uptake was not consistently accompanied by a decreased clearance of simultaneously injected I-131 Hippuran, particularly at lower drug dose levels. This observation agreed with previous evidence that the mechanisms of tubular transport of diphosphonates and organic acids like Hippuran are different. At higher dose levels, the augmented MDP uptake was accompanied by increased renal calcium, hypophosphatemia, elevated serummore » urea nitrogen and creatinine, and only occasional, mild hypercalcemia. The magnitude of the increased renal uptake of MDP observed could not be explained by alterations in iron metabolism or by dehydration. Drug-induced renal retention of MDP by a factor of 2 or more above normal appears to be a useful indicator of tubular damage when other parameters of renal function are sometimes normal.« less

Modeling and Simulation for Estimating the Influence of Renal Dysfunction on the Hypouricemic Effect of Febuxostat in Hyperuricemic Patients Due to Overproduction or Underexcretion of Uric Acid.

PubMed

Hirai, Toshinori; Kimura, Toshimi; Echizen, Hirotoshi

2016-01-01

Whether renal dysfunction influences the hypouricemic effect of febuxostat, a xanthine oxidase (XO) inhibitor, in patients with hyperuricemia due to overproduction or underexcretion of uric acid (UA) remains unclear. We aimed to address this question with a modeling and simulation approach. The pharmacokinetics (PK) of febuxostat were analyzed using data from the literature. A kinetic model of UA was retrieved from a previous human study. Renal UA clearance was estimated as a function of creatinine clearance (CLcr) but non-renal UA clearance was assumed constant. A reversible inhibition model for bovine XO was adopted. Integrating these kinetic formulas, we developed a PK-pharmacodynamic (PK-PD) model for estimating the time course of the hypouricemic effect of febuxostat as a function of baseline UA level, febuxostat dose, treatment duration, body weight, and CLcr. Using the Monte Carlo simulation method, we examined the performance of the model by comparing predicted UA levels with those reported in the literature. We also modified the models for application to hyperuricemia due to UA overproduction or underexcretion. Thirty-nine data sets comprising 735 volunteers or patients were retrieved from the literature. A good correlation was observed between the hypouricemic effects of febuxostat estimated by our PK-PD model and those reported in the articles (observed) (r=0.89, p<0.001). The hypouricemic effect was estimated to be augmented in patients with renal dysfunction irrespective of the etiology of hyperuricemia. While validation in clinical studies is needed, the modeling and simulation approach may be useful for individualizing febuxostat doses in patients with various clinical characteristics.