bluuebunny/crossref_metadata_2025_split huggingface dataset:
Age, Renal Perfusion and Function in Island-Dwelling Indigenous Kuna Amerinds of Panama
Authors: Hollenberg Norman K. , Rivera Alicio , Meinking Terri , Martinez Gregorio , McCullough Marji , Passan Diane , Preston Mack , Taplin David , Vicaria-Clement Maureen 
Published: April 2003

<i>Background/Aims:</i> Among possible contributors to a progressive fall in renal perfusion and function with increasing age, some hypotheses have invoked the rise in blood pressure that occurs with age, and a high-protein diet typical of urban cultures. Kuna Amerinds residing in isolated islands off the Panamanian Coast have a very low protein intake and show no tendency for blood pressure to rise with age, thus providing an opportunity to test these hypotheses. <i>Methods:</i> We measured renal plasma flow and glomerular filtration rate (PAH and inulin clearance) in 16 Kuna Indians ranging in age from 18 to 86 years (51 ± 6 years) who have resided on Ailigandi, an isolated Panamanian island for all of their lives. Inulin and PAH were infused with a battery-driven pump for 60 min, and a metabolic clearance rate used to calculate inulin and PAH clearance. For comparison, we employed identical techniques in 29 residents of Boston, ranging in age from 19 to 79 years (52 ± 4 years), all normotensive and free of disease or medication use. Twenty-four were Caucasian. <i>Results:</i> The Bostonian controls showed the anticipated fall in PAH clearance with age (y = 806 – 4.9x; r = –0.82; f = 38.0; p < 0.0001). Our hypothesis was that the absence of a blood pressure rise with age and the low protein intake would flatten the slope relating renal perfusion to Kuna age. Our finding was a numerically steeper slope relating age and renal plasma flow in the Kuna (y = 936 – 6.48x; r = –0.81; p < 0.001). Filtration fraction rose with age in both populations, and again the rise was steeper in the Kuna. GFR in the Kuna, on the other hand, was very much higher at any age (139 ± 4 ml/min/1.73 m<sup>2</sup>) than in Bostonians (112 ± 3 ml/min/1.73 m<sup>2</sup>; p < 0.001). <i>Conclusion:</i> The findings are not in accord with the hypothesis that age-related changes in renal perfusion and glomerular filtration rate reflect an important contribution from blood pressure rise and a high protein intake, typical of modern, urban life.
Effect of Vitamin E and Pentoxifylline on Glycerol-Induced Acute Renal Failure
Authors: Akpolat Tekin , Akpolat Ilkser , Öztürk Hamit , Sarıkaya Şaban , Coşar Arif Mansur , Bedir Abdülkerim , Kandemir Bedri 
Published: April 2003

The pathogenesis of acute renal failure may involve, among other causes, ischemia, vascular congestion, arachidonic acid pathways, and reactive oxygen metabolites. The aim of this study is to evaluate the effects of pentoxifylline and vitamin E on the prevention of experimental acute renal failure induced by glycerol. Eighty-five Sprague-Dawley rats weighing 170–230 g were included in the study. The rats were randomly divided into four groups: group 1 was given 1 ml saline; group 2, glycerol; group 3, glycerol plus vitamin E, and group 4, glycerol plus pentoxifylline. Extent of histological renal tubular necrosis and regeneration in each animal were graded. Blood urea nitrogen, serum creatinine, and creatine kinase concentrations were measured. Mean blood urea nitrogen and serum creatinine concentrations and tubular injury scores were significantly lower in group 1 than in groups 2–4 (p < 0.001), but there were no significant differences among groups 2–4. We conclude that postinsult administration of vitamin E and pentoxifylline does not have a beneficial effect on prevention and severity of acute renal failure and that controlled, multicenter studies involving a large number of patients are needed to clarify this subject.
An Intron 4 Gene Polymorphism in Endothelial Cell Nitric Oxide Synthase Might Modulate Volume-Dependent Hypertension in Patients on Hemodialysis
Authors: Yokoyama Keitaro , Tsukada Toshihiko , Nakayama Masaaki , Hara Sigeko , Yamada Akira , Kawaguchi Yoshindo , Hosoya Tatsuo 
Published: April 2003

Nitric oxide (NO) has some relevance to the pathophysiology of hypertension. We examined the distribution of endothelial nitric oxide synthase (ecNOS4) gene polymorphism in patients with essential hypertension (n = 107) in comparison with healthy subjects (n = 362), and then studied the possibility that ecNOS4 gene polymorphism affects changes in blood pressure (BP) due to water load in hemodialysis patients. Though the NO metabolite (NOx) level in subjects with the <i>a</i> allele (31.2 ± 1.76 µmol/l) was significantly lower than in those without the <i>a</i> allele (35.6 ± 0.90 µmol/l) (p = 0.0263), we found no association between this gene polymorphism and essential hypertension. However, there still remains the possibility that the NO response to elevation of BP might be suppressed in patients with hypertension. In order to examine the association between ecNOS4 gene polymorphism and volume-dependent hypertension, 181 hemodialysis patients with complete anuria were recruited. Depending on the increase in mean BP (mm Hg) divided by percent increase in body weight (ΔBP/ΔBW), patients were divided into high responders (High-R: ΔBP/ΔBW >2.0 mm Hg; n = 90) and low responders (Low-R: ΔBP/ΔBW <2.0 mm Hg; n = 91). In the High-R group, the frequencies of <i>a/a</i>, <i>b/a</i> and <i>b/b</i> genotypes were 1.1, 32.1 and 66.8%, respectively, and in the Low-R group, these frequencies were 1.1, 9.4 and 89.5%, respectively. The relative risk for those in the High-R group conferred by the ecNOS4 <i>a</i> allele (<i>b/a</i> + <i>a/a</i>) was 3.64 (95% confidence intervals: 1.60–8.24, p = 0.0089). This study did not show a strong involvement of ecNOS4 gene polymorphism, at least in the basal NO production in patients with essential hypertension, however, it indicated that ecNOS4 gene polymorphism might modulate changes in BP due to water load in patients on hemodialysis, thus indicating that these polymorphisms may be involved in the pathophysiology of volume-dependent hypertension.
G Proteins Regulate Calcium Channels in the Luminal Membranes of the Rabbit Nephron
Authors: Brunette M.G. , Hilal G. , Mailloux J. , Leclerc M. 
Published: April 2003

The filtered calcium (Ca<sup>2+</sup>) is reabsorbed by the luminal membrane of the proximal and distal nephron. Ca<sup>2+</sup> enters cells across apical plasma membranes along a steep electrochemical gradient, through Ca<sup>2+</sup> channels. Regulation by various hormones implies several steps, including binding of these hormones to the basolateral membrane, interaction with G proteins, liberation of messengers, activation of kinases and finally opening of the channels at the opposite pole of the cells. In the present study, we examined whether the Ca<sup>2+</sup> entry through the luminal membranes of proximal and distal tubules is also regulated by G proteins, by a membrane-limited process. Luminal membranes were purified from rabbit proximal and distal tubule suspensions, and their vesicles were loaded with GTPγs or the carrier. Then, the <sup>45</sup>Ca<sup>2+</sup> uptake by these membrane vesicles was measured in the presence and absence of 100 m<i>M</i> NaCl. In the absence of Na<sup>+</sup>, intravesicular GTPγs significantly enhanced 0.5 m<i>M</i> Ca<sup>2+</sup> uptake by the proximal membrane vesicles from 0.53 ± 0.06 to 0.72 ± 0.06 pmol/µg/10 s (p < 0.05). In the presence of Na<sup>+</sup>, however, this effect disappeared. In the distal tubules, intravesicular GTPγs increased 0.5 m<i>M</i> Ca<sup>2+</sup> uptake in the absence (from 0.57 ± 0.02 to 0.79 ± 0.02 pmol/µg/10 s, p < 0.02) and in the presence (from 0.36 ± 0.03 to 0.55 ± 0.03 pmol/µg/10 s, p < 0.02) of Na<sup>+</sup>. The action of GTPγs, when present, was dose dependent with a half-maximal effect at 20 µ<i>M</i>. The distal luminal membrane is the site of two Ca<sup>2+</sup> channels with different kinetics parameters. GTPγs increased the V<sub>max</sub> value of the low-affinity component exclusively, in the presence as in the absence of Na<sup>+</sup>. Finally, Ca<sup>2+</sup> uptake by the membranes of the two segments was differently influenced by toxins: cholera toxin slightly stimulated transport by the proximal membrane, but had no influence on the distal membrane, whereas pertussis toxin decreased the cation uptake by the distal tubule membrane exclusively. We conclude that the nature of Ca<sup>2+</sup> channels differs in the proximal and distal luminal membranes: Ca<sup>2+</sup> channels present in the proximal tubule and the low-affinity Ca<sup>2+</sup> channels present in the distal tubule membranes are directly regulated by Gs and Gi proteins respectively, whereas the high-affinity Ca<sup>2+</sup> channel in the distal tubule membrane is insensitive to any of them.
Use of ‘Locked-In’ Antibiotic to Treat an Unusual Gram-Negative Hemodialysis Catheter Infection
Authors: Shah Jirgis , Feinfeld Donald A. 
Published: April 2003

A 37-year-old woman on maintenance hemodialysis for 3 years had multiple vascular access failures due to antiphospholipid syndrome. She was dialyzed via a tunneled left subclavian catheter, but after 1 year developed chills and fever during each dialysis session. Blood cultures grew out <i>Xanthomonas maltophilia</i> sensitive to ceftazidime and ciprofloxacin. Intravenous administration of both antibiotics failed to eradicate infection. We added ‘locked-in’ ceftazidime, instilling it daily into the catheter along with heparinized saline for 3 weeks. Within 24 h the patient was dialyzed uneventfully, and all subsequent blood cultures have been negative. This case shows the successful use of a ‘locked-in’ antibiotic to treat an unusual gram-negative catheter infection. Two prior series have reported similar good results in infections with more common organisms. Such treatment may permit continued use of tunneled hemodialysis catheters for longer periods.
Inhibition of Neutral Endopeptidase Potentiates the Effects of Atrial Natriuretic Peptide on Acute Cyclosporin-Induced Nephrotoxicity
Authors: Capasso Giovambattista , Unwin Robert , Ciani Francesca , Rizzo Amato , Russo Ferdinando , Pica Angelo , De Santo Natale Gaspare 
Published: April 2003

<i>Background:</i> The use of cyclosporin A (CyA) is limited by its significant nephrotoxicity. Atrial natriuretic peptide (ANP) has been shown to ameliorate the reduction in glomerular filtration rate (GFR) induced by CyA, but its effect is transient. One explanation may be the rapid breakdown of this hormone by neutral endopeptidase (NEP) which is highly active in the kidney. In the present study, we examined the effect of the NEP inhibitor thiorphan on the acute fall in GFR induced by CyA. <i>Methods:</i> After a first set of experiments to investigate the renal hemodynamic effects of CyA (20 mg·kg<sup>–1</sup>, i.v. bolus), we studied four additional conditions where acute CyA treatment was followed by the administration of: (2) ANP alone (10 µg·kg<sup>–1</sup> i.v. as bolus and a maintenance infusion of 1 µg·kg<sup>–1</sup>·min<sup>–1</sup>); (3) thiorphan alone (5 mg·kg<sup>–1</sup> i.v. as bolus and a maintenance infusion of 0.5 mg·kg<sup>–1</sup>· min<sup>–1</sup>); (4) ANP plus thiorphan (as in 2 and 3), and (5) an infusion of 0.9% saline, increased from 1.2 to 3 ml·h<sup>–1</sup>. The GFR was measured as the clearance of <sup>3</sup>H-methoxyinulin (ml·min<sup>–1</sup>·100 g<sup>–1</sup> body weight). <i>Results:</i> The data show: (1) the GFR fell from 1.06 ± 0.15 to 0.59 ± 0.09 ml·min<sup>–1</sup>·100 g<sup>–1</sup> (p < 0.01) 60 min after CyA and remained depressed for at least 2 h; (2) ANP caused a marked initial rise in GFR from 0.49 ± 0.07 to 1.23 ± 0.18 ml·min<sup>–1</sup>·100 g<sup>–1</sup> (p < 0.005 vs. CyA) which declined rapidly to the value seen after CyA injection alone, despite continuing ANP infusion; (3) thiorphan caused a modest, but significant increase in GFR within 15 min from 0.48 ± 0.04 to 0.69 ± 0.10 ml·min<sup>–1</sup>·100 g<sup>–1</sup> (p < 0.05 vs. CyA) which was sustained during infusion and for at least 30 min after stopping infusion; (4) ANP plus thiorphan produced a marked increase in GFR from 0.58 ± 0.09 to 1.39 ± 0.44 ml·min<sup>–1</sup>·100 g<sup>–1</sup> (p < 0.05 vs. CyA) which then decreased, but remained above the post-CyA injection value, until infusion of both drugs ended; (5) more than doubling the saline infusion rate per se had no significant effect on the GFR response to CyA. The blood pressure decreased significantly during ANP infusion, but more so when combined with thiorphan. <i>Conclusion:</i> These data indicate that the inhibition of NEP by thiorphan is able to ameliorate partially the reduction in GFR induced by CyA and to enhance, and prolong, the vasodilator and diuretic effects of ANP.
Effect of Dilazep Dihydrochloride on Urinary Albumin Excretion in Patients with Autosomal Dominant Polycystic Kidney Disease
Authors: Nakamura Tsukasa , Ushiyama Chifuyu , Takahashi Yutaka , Tanaka Araki , Shimada Noriaki , Ebihara Isao , Koide Hikaru 
Published: April 2003

Proteinuria and microalbuminuria occur with a highly variable severity and are associated with progression of autosomal dominant polycystic kidney disease (ADPKD). Dilazep dihydrochloride, an antiplatelet drug, is effective in patients with immunoglobulin A nephropathy or diabetic nephropathy. We studied whether dilazep dihydrochloride affects the urinary albumin excretion (UAE) in normotensive and hypertensive patients with ADPKD. Twelve normotensive ADPKD patients with microalbuminuria were randomly assigned to two groups: a dilazep (300 mg/day) treatment group (n = 6, group A) and a placebo group (n = 6, group B). In addition, 10 hypertensive ADPKD patients with microalbuminuria were randomly assigned to two groups: a dilazep (300 mg/day) treatment group (n = 5, group C) and a placebo group (n = 5, group D). Treatment with dilazep was continued for a period of 6 months, at the end of which the UAE was reduced form 130 ± 52 to 46 ± 26 µg/min (p < 0.01) in group A. There was no reduction in group C. There were no changes in UAE in placebo groups B and D. These results suggest that dilazep dihydrochloride may be effective in reducing UAE in normotensive ADPKD patients with microalbuminuria.
Hyaluronan and Rat Renal Fibroblasts: In vitro Studies
Authors: Pedagogos Eugenia , Hewitson Timothy D. , Nicholls Kathleen M. , Becker Gavin J. 
Published: April 2003

Hyaluronic acid (HA) is a ubiquitous component of extracellular matrix. After tissue injury, HA appears in greater abundance during the inflammatory response and the phase of clearance of cell and matrix debris, before collagen production and matrix degradation. The aim of this study was to examine whether normal rat renal fibroblasts were capable of HA synthesis and to determine the effect of HA on in vitro collagen production in a series of normal rat cortical fibroblast cultures. Fibroblast cultures from both renal cortex and medulla were established from adult Sprague-Dawley rats. HA synthesis was measured by radioimmunoassay, and incorporation of <sup>3</sup>H-proline into collagen was used to determine collagen synthesis. Fibroblasts were defined on the basis of morphology and alpha smooth muscle actin immunohistochemistry. HA synthesis was measured in both renal cortical and medullary fibroblasts at passage 3 for both 24 and 48 h in 5 animals and expressed as a fraction of protein content. HA was synthesized by both cortical and medullary fibroblasts; however, cortical fibroblasts produced less HA than medullary fibroblasts at both 24 h (p = 0.05) and 48 h (p = 0.02). In normal cortical fibroblasts, exogenous HA suppressed overall total (cell and media) collagen production after a 22-hour labelling period (p = 0.002 compared to controls). Decreased collagen production was also found individually in cell (p = 0.02) and media fractions (p = 0.01). Both cortical and medullary fibroblasts are capable of synthesizing HA in vitro. Furthermore, the findings in this study suggest that HA may be an important mediator in reducing renal cortical fibroblast collagen production and may play an important role in limiting renal interstitial scarring.
Influence of Prolonged Corticosteroid Therapy on the Outcome of Steroid-Responsive Nephrotic Syndrome
Authors: Matsukura Hiro , Inaba Susumu , Shinozaki Kentaro , Yanagihara Toshio , Hara Masanori , Higuchi Akira , Takada Tsuneo , Tanizawa Takakuni , Miyawaki Toshio 
Published: April 2003

Eighty-six patients (59 males and 27 females) diagnosed with steroid-responsive nephrotic syndrome during childhood were identified. The patients were 20–40 years of age (mean 27.0 ± 5.0) with a mean follow-up period of 19.5 ± 5.9 years. All patients had been treated with a long-term tapering corticosteroid therapy. Thirty patients had also received a course of cyclophosphamide (2 mg/kg/day for 12 weeks). Sixty-six had achieved sustained remission off corticosteroids, while 20 were still receiving corticosteroids to maintain remission. None of the 86 patients had proteinuria or renal insufficiency at the time of the study. Mean final heights in males and females were similar (–0.51 ± 1.21 and –0.23 ± 1.16 standard deviation score). Mean final height of 20 steroid-dependent patients was significantly less than that of 66 in remission off corticosteroids (p < 0.005). Ten cyclophosphamide-treated patients got married and 9 had at least 1 healthy child. In children with steroid-responsive nephrotic syndrome, the need for corticosteroid therapy to maintain remission may be associated with decreased adult height. Patients who received a 12-week course of cyclophosphamide are likely to be normally fertile as adults.
Downregulation of Vascular Endothelial Growth Factor and Its Receptors in the Kidney in Rats with Puromycin Aminonucleoside Nephrosis
Authors: Fan Liying , Wakayama Tomohiko , Yokoyama Shigeru , Amano Osamu , Iseki Shoichi 
Published: April 2003

<i>Aim:</i> We aimed to examine the possible involvement of vascular endothelial growth factor (VEGF) in the pathogenesis of puromycin aminonucleoside nephrosis (PAN). <i>Methods:</i> The expression and localization of the mRNA of VEGF and its receptors, flt-1 and flk-1, were analyzed in the kidneys of puromycin aminonucleoside-injected rats by use of Northern blotting and in situ hybridization. <i>Results:</i> In association with the induction of proteinuria, VEGF mRNA underwent decrease in amount from 3 days after the injection, reaching the minimum level at 7 days, followed by a gradual recovery by 28 days. The levels of flk-1 and flt-1 mRNA showed similar transient decrease in PAN kidney, whereas the mRNA of von Willebrand factor, a marker of endothelial cells, showed no change in amount. In the normal rat kidney, VEGF mRNA was localized primarily to podocytes, and flk-1 mRNA was localized exclusively to endothelial cells with much higher intensity in glomeruli than in peritubular capillaries. In PAN kidney, the intensities of both VEGF and flk-1 signals in podocytes and glomerular endothelial cells, respectively, appeared much lower at 7 days than in normal kidney. <i>Conclusion:</i> These results indicate that the VEGF-VEGF receptor system is downregulated in PAN, implying that it is not involved in the mechanism of proteinuria in PAN.
Effect of Cerivastatin on Urinary Albumin Excretion and Plasma Endothelin-1 Concentrations in Type 2 Diabetes Patients with Microalbuminuria and Dyslipidemia
Authors: Nakamura Tsukasa , Ushiyama Chifuyu , Hirokawa Kaoru , Osada Shiwori , Shimada Noriaki , Koide Hikaru 
Published: April 2003

<i>Background/Aims:</i> To determine whether cerivastatin, a newly developed novel synthetic potent statin, exerts a renoprotective effect, we assessed urinary albumin excretion (UAE) and plasma and urinary endothelin (ET)-1 concentrations in normotensive microalbuminuric type 2 diabetes patients with dyslipidemia. <i>Methods:</i> Sixty normotensive type 2 diabetic patients (38 men and 22 women; mean age 56.5 years) with microalbuminuria (20–200 µg/min) and dyslipidemia (total cholesterol >200 mg/dl, LDL cholesterol >160 mg/dl, HDL cholesterol <35 mg/dl, and triglyceride >150 mg/dl) were enrolled in a double-blind study for 6 months, receiving either cerivastatin (0.15 mg/day) or placebo. Plasma and urinary ET-1 concentrations were measured by radioimmunoassay. <i>Results:</i> Cerivastatin did not affect serum creatinine and HbA<sub>1c</sub> levels, and reduced systolic blood pressure slightly, but not significantly. Plasma levels of total cholesterol and LDL cholesterol were significantly reduced (p < 0.01), and plasma triglyceride levels were also reduced significantly (p < 0.05) after 6 months of cerivastatin treatment. A concomitant significant decrease in UAE (p < 0.01), and urinary and plasma ET-1 concentrations (p < 0.01) were found during this period. <i>Conclusion:</i> The use of cerivastatin is associated with decreased microalbuminuria and plasma and urinary ET-1 levels in microalbuminuric patients with type 2 diabetic mellitus and speculate that this may represent an amelioration of renal injury.
Homocysteine-Lowering Effect of 500 μg Folic Acid Every Other Day versus 250 μg/Day
Authors: Brouwer I.A. , van Rooij I.A.L.M. , van Dusseldorp M. , Thomas C.M.G. , Blom H.J. , Hautvast J.G.A.J. , Eskes T.K.A.B. , Steegers-Theunissen R.P.M. 
Published: April 2003

<i>Background/Aims:</i> Elevated plasma total homocysteine (tHcy) concentrations are a risk factor for neural tube defects and vascular diseases. Supplementation with folic acid decreases tHcy. We investigated whether supplementation with 500 µg folic acid every other day is as effective in lowering tHcy as 250 µg folic acid each day. <i>Methods:</i> In a 4-week intervention study, 22 healthy young women (18–40 years old) took either 500 µg folic acid every other day (500-µg/2d group) or 250 µg folic acid each day (250-µg/d group). Fasting blood was collected on days 0 and 28. <i>Results:</i> Plasma folate concentrations increased by 11.4 nmol/l (6.8–15.9) in the 250-µg/d group and by 9.1 nmol/l (95% Cl 1.9–16.3) in the 500-µg/2d group. These increases were not significantly different from each other. THcy concentrations decreased by 1.52 µmol/l (95% Cl –2.09 to –0.95; p < 0.001) in the 250-µg/d group and by 0.88 µmol/l (–1.53 to –0.23; p < 0.05) in the 500-µg/2d group. The difference in decrease between the 250-µg/d group and the 500-µg/2d group was 0.64 µmol/l (p = 0.11). <i>Conclusion:</i> Although not conclusive, this study suggests that supplying subjects with folic acid each day decreases tHcy more effectively than a double dose every other day.