bluuebunny/crossref_metadata_2025 huggingface dataset:
Prosthetic Graft Placement Using the Deep Forearm Veins in Hemodialysis Patients: A Preliminary Report
Authors: Skandalos Ioannis , Chatzibaloglou Ananias , Tsalis Kostas , Tourlis Theodoros , Kalpakidis Vasilis , Anagnostopoulos Theodoros , Dadoukis Ioannis , Sombolos Kostas
Published: April 2003

When the superficial arm veins are not suitable for the creation of a conventional endogenous arteriovenous (A-V) fistula or the placement of a prosthetic graft in the forearm, the use of the deep forearm veins as an outflow system to construct an A-V graft access seems to be a reasonable alternative. Using this approach, we placed 6 prosthetic grafts in 6 hemodialysis patients in whom conventional methods had failed. Adequate functioning of this ‘deep vein’-type vascular access in these 6 patients has been maintained for 3, 6, 11, 15, 19 and 24 months, respectively, without complications or any need for further interventions. Only one graft failed after 6 months. Our preliminary results indicate that this technique can be used successfully when the superficial forearm veins have been exhausted, thus avoiding the use of upper-arm or axillary veins.
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 Xanthomonas maltophilia 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.
Renal Antioxidant Enzymes and Fibrosis-Related Markers in the Rat Adriamycin Model
Authors: van den Branden Christiane , Ceyssens Bart , De Craemer Dirk , Pauwels Marina , Vanden Houte Katherina , De Bleser Pieter , Hellemans Karine , Geerts Albert , Verbeelen Dierik
Published: April 2003

Excessive generation of reactive oxygen intermediates can induce changes in the cellular antioxidant defence system. In this study we examine the antioxidant enzyme status and the expression of fibrosis-related marker proteins in the Adriamycin model of chronic renal failure in the rat. Twenty weeks after Adriamycin treatment, rats have overt nephrotic syndrome and renal failure with development of tubulo-interstitial fibrosis and glomerulosclerosis. Lipids accumulate in blood and in both glomeruli and tubulo-interstitial tissue. Desmin and α-smooth muscle actin expression increases in glomeruli and in the tubulo-interstitial area. Renal cortex antioxidant enzyme activities are decreased 20 weeks after Adriamycin injection (to 41% for catalase, to 56% for total superoxide dismutase and to 69% for glutathione peroxidase). The mRNA levels of catalase, Cu/Zn-superoxide dismutase and glutathione peroxidase-1 evaluated by Northern blot are decreased by more than 50% for catalase, Cu/Zn-superoxide dismutase and glutathione peroxidase-1. We conclude that in the rat Adriamycin-induced model of chronic renal failure with fibrosis, the combination of decreased antioxidant enzyme status in renal cortex with high concentrations of lipids in blood and renal tissue facilitates oxidative damage. Development of fibrosis is paralleled by increased expression of desmin and α-smooth muscle actin.
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

Background: 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. Methods: After a first set of experiments to investigate the renal hemodynamic effects of CyA (20 mg·kg–1, i.v. bolus), we studied four additional conditions where acute CyA treatment was followed by the administration of: (2) ANP alone (10 µg·kg–1 i.v. as bolus and a maintenance infusion of 1 µg·kg–1·min–1); (3) thiorphan alone (5 mg·kg–1 i.v. as bolus and a maintenance infusion of 0.5 mg·kg–1· min–1); (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–1. The GFR was measured as the clearance of 3H-methoxyinulin (ml·min–1·100 g–1 body weight). Results: The data show: (1) the GFR fell from 1.06 ± 0.15 to 0.59 ± 0.09 ml·min–1·100 g–1 (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–1·100 g–1 (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–1·100 g–1 (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–1·100 g–1 (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. Conclusion: 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.
Differential Changes of CDK Activities in Glomeruli and Tubules during the Active DNA Synthetic Period after Ischemic Injury
Authors: Park Sung Kwang , Kim Won , Lee Chang Hwan , Koh Gou Young
Published: April 2003

The present study was designed to determine the spatial correlation among extent of DNA synthetic activity, expressions of G1/S phase cyclins, cyclin-dependent kinases (CDKs) and CIP/KIP family of CDK inhibitors (CKIs), and activities of G1/S phase CDKs in glomeruli and outer medullae of kidneys during the active regeneration period after ischemic injury. DNA synthetic activity was measured using [3H]-thymidine autoradiogram in the kidney sections. Cyclin, CDK, and CKI proteins were determined by Western blot analysis. CDK activities were determined by phosphorylation amount using specific substrate. The protein levels of cyclins (D1, D3, E, A) and activities of CDK4 and CDK2 were increased concomitant with the induction of DNA synthetic activity in outer medullae, but not in glomeruli, in adult kidneys during DNA synthetic period after ischemic injury. The p27KIP1 protein, but not the p21CIP1 protein, increased equally in total kidney, glomeruli, and outer medullae after ischemic injury. These results indicate that renal tubules have an active cyclin/CDK system, while glomeruli, do not have a cyclin/CDK system during active regeneration of kidneys after ischemic injury.
Heat Shock Protein 47 in Renal Scarring
Authors: Razzaque M.S. , Ahsan N. , Taguchi T.
Published: April 2003

Heat shock protein 47 (HSP47) is a collagen-binding protein, thought to play an essential mechanistic role in the assembly and processing of procollagens. HSP47 is increasingly being implicated in the pathogenesis of several human and experimental fibrotic diseases. HSP47 could mediate increased accumulation of collagens in the fibrotic mass, possibly by regulating increased assembly of procollagens. Therefore, modulation of HSP47 might be a valuable tool for manipulation of some fibrotic diseases, including renal scarring
Enalaprilat Directly Ameliorates in vitro Cyclosporin Nephrotoxicity in Human Tubulo-Interstitial Cells
Authors: Johnson David W. , Saunders Heather J. , Vesey David A. , Qi Weier , Field Michael J. , Pollock Carol A.
Published: April 2003

Background/Aims: Several recent studies have suggested that angiotensin-converting enzyme (ACE) inhibitors ameliorate chronic cyclosporin A (CyA) tubulo-interstitial disease by mechanisms independent of their antihypertensive effects. The aim of the present study was to determine whether ACE inhibition exerts a direct beneficial effect on the tubulo-interstitium in an in vitro model of chronic CyA nephropathy. Methods: Primary cultures of human proximal tubular cells (PTC) and renal cortical fibroblasts (CF) were exposed for 24 h to CyA in the presence or absence of enalaprilat. Parameters of tubulo-interstitial nephrotoxicity were then measured including collagen synthesis (proline incorporation), tubular viability and function (thymidine incorporation, lactate dehydrogenase release, and apical sodium-hydrogen exchange), and secretion of insulin-like growth factor I, transforming growth factor beta 1 (TGFβ1), and platelet-derived growth factor. Results: CyA promoted CF collagen synthesis, PTC cytotoxicity (suppressed viability, growth and sodium transport), and tubulo-interstitial fibrogenic cytokine release (CF secretion of insulin-like growth factor I and PTC secretion of TGFβ1 and platelet-derived growth factor). Enalaprilat completely reversed the stimulatory effects of CyA on CF collagen synthesis (CyA + enalaprilat 6.40 ± 0.50% vs. CyA alone 8.33 ± 0.56% vs. control 6.57 ± 0.62% vs. enalaprilat alone 5.55 ± 0.93%, p < 0.05) and PTC secretion of TGFβ1 (0.71 ± 0.11, 1.13 ± 0.09, 0.89 ± 0.07, and 0.67 ± 0.09 ng/mg protein/day, respectively, p < 0.05). However, the other manifestations of CyA toxicity were not significantly reversed by concomitant enalaprilat administration. Conclusions: ACE inhibition directly prevents CyA-induced interstitial fibrosis, but not proximal tubule cytotoxicity, independently of haemodynamic and systemic renin-angiotensin system effects. Renoprotection may be partially afforded by directly preventing the tubular secretion of TGFβ1.
Prevalence of a Novel DNA Virus (TTV) among Patients on Maintenance Hemodialysis
Authors: Schröter Matthias , Feucht Heinz-Hubert , Zöllner Bernhard , Schäfer Peter , Laufs Rainer
Published: April 2003

Background/Aims: A recently detected DNA virus (TTV) has been assumed to be responsible for posttransfusion hepatitis in humans. Until now it is unclear whether patients on maintenance hemodialysis are at increased risk of acquiring TTV. Methods: Serum samples derived from 143 chronically hemodialyzed patients were examined for TTV viremia by nested PCR. All serum specimens were also investigated for viremia and for the presence of antibodies of hepatitis C virus (HCV) and GB virus C/hepatitis G virus (GBV-C/HGV) by PCR and serological assays, respectively. Results: The prevalence of TTV was determined to be 18.8% (n = 27), for HCV a prevalence of 15.4% (n = 22) and for GBV-C/HGV of 8.4% (n = 12) could be demonstrated. Parallel infection by TTV and HCV was detected in only 1.4% (n = 2) of the patients. In no serum sample could TTV and GBV-C/HGV be detected in parallel. None of the solely TTV-viremic individuals had clinical or biochemical signs of liver disease. Conclusion: From our data we conclude that TTV viremia is widespread among hemodialysis patients and can be detected in 18.8%. Since no viremic patient had clinical or biochemical signs of liver disease, the hepatitis-inducing capacity of TTV remains unclear.
Effects of Allopurinol on Renal Stone Formation and Osteopontin Expression in a Rat Urolithiasis Model
Authors: Yasui Takahiro , Sato Motohiko , Fujita Keiji , Ito Yasunori , Nomura Shintaro , Kohri Kenjiro
Published: April 2003

Background: The inhibitory effect of allopurinol on calcium oxalate urolithiasis has been reported, but its effect on stone matrix proteins has not been studied in vivo. To clarify the effect of allopurinol on the matrix, we investigated its effect on the expression of osteopontin (OPN), which we previously identified as an important stone matrix protein. Methods: Control rats were not treated. Rats of the stone group were given ethylene glycol (EG) and vitamin D3, while the allopurinol groups (low-dose group and high-dose group) were treated with allopurinol in addition to receiving EG and vitamin D3. Results: The rate of renal stone formation was lower in the allopurinol groups than in the stone group. This was associated with a low expression of OPN mRNA in allopurinol-treated rats relative to that in the stone group. Conclusion: Allopurinol was effective in preventing calcium oxalate stone formation and reduced OPN expression in rats. Our results suggest that allopurinol prevents renal stone formation by acting against not only the control of oxalate but also OPN expression.
Twelve Weeks of Exercise TrainingIncreases Muscle Function and Walking Capacity in Elderly Predialysis Patients and Healthy Subjects
Authors: Heiwe S. , Tollbäck A. , Clyne N.
Published: April 2003

Muscle function declines with age and progressive uraemia. We examined whether elderly predialysis patients could improve thigh muscle function, walking capacity, and functional mobility to the same extent as elderly healthy subjects when participating in 12 weeks of individual muscle endurance exercises for the thigh as well as in a low-intensive group programme. The uraemic exercise and comparison groups comprised 16 patients (age 76 ± 7 years, glomerular filtration rate 18 ± 5 ml/min) and 9 patients (age 72 ± 6 years, glomerular filtration rate 16 ± 5 ml/min), respectively. The healthy exercise and comparison groups comprised 18 subjects (age 75 ± 7 years) and 5 subjects (age 79 ± 4 years), respectively. Muscular strength, dynamic endurance, walking capacity, and functional mobility increased significantly in both the uraemic and the healthy exercise groups after 12 weeks of regular muscle endurance exercise training, whereas there was no significant change in static muscle endurance and quality of life in either group. None of the values changed for the uraemic comparison group nor the healthy comparison group during the observation period. Elderly predialysis patients had lower muscle function and mobility as compared with elderly healthy subjects, but were able to improve both after 12 weeks of exercise training to the same extent as elderly healthy subjects.
Control of the Epidermal Growth Factor Receptor and Its Ligands during Renal Injury
Authors: Hise Michael K. , Salmanullah Muhammad , Liu Li , Drachenberg Cinthia I. , Papadimitriou John C. , Rohan Richard M.
Published: April 2003

Aim: We studied control of the epidermal growth factor (EGF) receptor and its ligands during kidney injury, since they may be importantly involved in repair. Methods: The folic acid model of renal injury was used in these studies. Messenger RNA (mRNA) was evaluated by solution hybridization. Immunohistochemistry of transforming growth factor alpha (TGF-α) was also performed. Results: Twenty-four hours after folic acid induced acute renal injury, creatinine increased from 0.3 ± 0.03 mg/dl in controls to 2.0 ± 0.8 mg/dl in folic acid injured kidneys (n = 4, p < 0.03). mRNA for the EGF receptor was increased nearly sevenfold by 24 h, and mRNA for the receptor was increased as early as 1 h following folic acid treatment. EGF receptor ligand caused a profound downregulation of the receptors in proximal tubule basolateral membranes, but receptors returned rapidly to the membrane surface in injured kidneys. The mRNA levels for heparin-binding EGF and TGF-α, two EGF receptor ligands, increased within 1 h of injury. TGF-α mRNA increased from 1.0 ± 0.09 (relative densitometry units) in control animals to 2.9 ± 0.13 in folic acid treated rats at 24 h (n = 4, p < 0.01), and immunohistochemical staining for TGF-α increased in injured kidneys at distal nephron sites. Conclusions: These studies indicate that upregulation of the EGF receptor is related to an increase in mRNA. The rapid return of receptors to the membrane surface following ligand stimulation may be useful in maintaining a mitogenic stimulus. Multiple EGF-like ligands may be important in activating the upregulated EGF receptor during repair from renal injury.
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.
Differential Effects of Circulating IgA Isolated from Patients with IgA Nephropathy on Superoxide and Fibronectin Production of Mesangial Cells
Authors: Chen H.C. , Guh J.Y. , Chang J.M. , Lai Y.H.
Published: April 2003

Background: IgA nephropathy (IgAN) is characterized by predominant deposition of IgA in the glomerular mesangium. Serum IgA is often elevated in patients with IgAN, and it has been postulated that it is responsible for the mesangial lesions. However, the direct effect of circulating IgA on mesangial cells is not clear. Methods: We investigated the effects of sera and IgA which were isolated from patients with IgAN on thymidine uptake, superoxide and fibronectin production and fibronectin mRNA expression of cultured rat mesangial cells, and we compared the findings to the effects of IgA isolated from patients with non-IgA mesangial proliferative glomerulonephritis (MsPGN) and normal controls. IgA was isolated with affinity chromatography using cyanogen bromide activated Sepharose 4B coupled to sheep antihuman IgA antiserum. Results: Our results demonstrated that both sera and IgA from patients with IgAN dose-dependently increased mitogenesis of mesangial cells as measured by 3H-labeled thymidine uptake. The thymidine uptake by sera and IgA isolated from patients with IgAN was significantly higher than that of sera and IgA isolated from patients with MsPGN and normal controls. Sera and IgA from patients with IgAN significantly enhanced superoxide and fibronectin production and fibronectin mRNA expression of mesangial cells. The superoxide and fibronectin production was also significantly higher as compared with patients with MsPGN and normal controls. Conclusions: Our results indicate that circulating IgA isolated from patients with IgAN is different from that of patients with MsPGN and normal controls and may potentially induce oxidative injury and production of extracellular matrix of glomerular mesangial cells in IgAN.
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 3H-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.
Elevation of Blood (1→3)-Beta-D-Glucan Concentrations in Hemodialysis Patients
Authors: Kato Akihiko , Takita Takako , Furuhashi Mitsuyoshi , Takahashi Toshiyuki , Maruyama Yukitaka , Hishida Akira
Published: April 2003

Determination of the blood (1→3)-β-D-glucan (β-DG) concentration is a sensitive marker to detect the presence of deep mycosis and fungal infections. Although cellulose material is known to contain β-DG, the influence of a cellulose dialyzer membrane on the blood β-DG level remains to be elucidated. In this study, we determined the plasma β-DG levels in dialysis outpatients using either a modified regenerated cellulose (MRC) or a synthetic polysulfone (PS) membrane for more than 3 months. Plasma β-DG levels were extremely high in patients using the MRC (2,778 ± 549 pg/ml, n = 9) but not the PS membrane (18.8 ± 3.7 pg/ml, n = 8) compared to normal ranges (<20 pg/ml). A single dialysis session using the MRC membrane further increased blood β-DG values to 5,561 ± 722 pg/ml (p < 0.01). After changing the membranes from MRC to PS, the blood β-DG levels gradually decreased and reached 29.6 ± 6.0 pg/ml at 6 months. In contrast, the PS membrane did not affect plasma β-DG levels after a single dialysis session (16.0 ± 3.9 pg/ml) or 4 months later (24.0 ± 4.9 pg/ml). These findings suggested that a cellulose membrane could influence the measurement of blood β-DG concentrations in the long-term. Careful assessment is required to diagnose the presence of fungal infection in HD patients using a cellulose membane.
Plasma Adrenomedullin Levels in Patients on Hemodialysis
Authors: Yamasaki Hiroko , Nagake Yoshio , Akagi Shigeru , Sugimoto Taro , Ichikawa Haruo , Makino Hirofumi
Published: April 2003

Adrenomedullin (AM) is a hypotensive peptide that has recently been isolated from human pheochromocytoma. In this study, we measured plasma AM concentrations in 54 patients on hemodialysis (HD) and examined the clinical significance. We also evaluated the effects of high-flux and low-flux dialysis membranes on plasma AM levels. The average value of plasma AM at pre-HD (4.44 ± 0.16 fmol/ml) was significantly elevated compared with that in 44 healthy volunteers (1.31 ± 1.41 fmol/ml) (p < 0.0001). The plasma AM concentrations at pre-HD showed a negative correlation with age and mean blood pressure (MBP) at pre-HD. The plasma AM concentrations at post-HD showed a negative correlation with MBP at post-HD and a negative correlation with the reduction rate of AM. Multiple regression analysis showed that age and MBP were independent factors associated with plasma AM at pre-HD and that MBP and reduction rate of AM were independent factors associated with plasma AM at post-HD. We investigated the differences between high-flux dialyzers (PS-UW, PS-N and FB-F) and a low-flux dialyzer (AM-BC-F), and we found that high-flux dialyzers removed plasma AM more efficiently than a low-flux dialyzer did. In addition, in 3 patients on HD, plasma AM levels decreased significantly during isovolumic dialysis using a high-flux dialyzer, despite the fact that there were no significant changes in MBP and ANP. In conclusion, elevation in plasma AM level causes a fall in MBP in patients on HD, therefore, removal of AM by HD treatment using a high-flux dialyzer contributes to the stability of blood pressure during HD.
Correlation between Peritoneal Mesothelial Cell Cytology and Peritoneal Histopathology with Respect to Prognosis in Patients on Continuous Ambulatory Peritoneal Dialysis
Authors: Izumotani Tsuyoshi , Ishimura Eiji , Yamamoto Tadashi , Otoshi Tatsuyuki , Okuno Senji , Inaba Masaaki , Kim Masao , Nishizawa Yoshiki
Published: April 2003

Background: Sclerosing encapsulating peritonitis (SEP) is a serious complication seen in patients on long-term continuous ambulatory peritoneal dialysis (CAPD). We have previously reported that mesothelial cells in effluent dialysate significantly increased in size as the duration of CAPD progressed. In this study, we investigated the relationship between mesothelial cytology, histopathology of the peritoneum, and clinical outcomes of 34 CAPD patients. Methods: When peritoneal dialysis catheters were inserted (n = 7) or removed (n = 27), a peritoneal biopsy was performed and results compared with mesothelial cytology in effluent dialysate. Results: A significant positive correlation was noted between the duration of CAPD and the surface area of peritoneal mesothelial cells (r = 0.721, p < 0.0001). The surface area of mesothelial cells in peritoneal sclerosis (n = 9; 584 ± 97 µm2) was significantly greater than in peritoneal fibrosis (n = 14; 389 ± 26 µm2, p < 0.05), pathologic acute peritonitis (n = 3; 223 ± 10 µm2, p < 0.005), and normal peritoneum (n = 7; 247 ± 12 µm2, p < 0.001). The surface area in sclerosing peritonitis (n = 1; 1,200 µm2) was greater than that of all the others. Giant cells were found in the 1 case with sclerosing peritonitis and in 3 of 9 cases with peritoneal sclerosis, although they were found in only 1 of 14 patients with peritoneal fibrosis and in none of those with pathologic acute peritonitis or normal peritoneum. As the surface area of mesothelial cells increased to more than 400 µm2 and giant cells appeared in the effluent, the frequency of peritoneal sclerosis and/or clinical SEP increased. Conclusion: An increase in the mesothelial cell surface area and the emergence of giant cells in the effluent indicate advanced peritoneal histopathology, and may be useful indicators to determine appropriate timing of discontinuation of CAPD to prevent the development of SEP.
Pharmacokinetics of Abacavir in HIV-1-Infected Patients with Impaired Renal Function
Authors: Izzedine Hassane , Launay-Vacher Vincent , Aymard Guy , Legrand Mayeule , Deray Gilbert
Published: April 2003

Background: Abacavir is a potent, novel 2′-deoxyguanosine analogue reverse transcriptase inhibitor (NRTI) which effectively suppresses HIV-1 replication. To date, there is no pharmacokinetic study in patients with renal impairment. Methods: Five HIV-1-infected patients with various degrees of renal dysfunction (creatinine clearance 60, 40, 25, 20 and 1 haemodialyzed patient) were evaluated after being treated for at least 2 months with multi-antiretroviral therapy including abacavir. After an overnight fast, the subjects received their abacavir dosage (600 or 300 mg). Blood samples were withdrawn and plasma concentrations determined. A nonparametric pharmacokinetic analysis was then performed. The dialysability of abacavir was also evaluated. Results: Time of maximum plasma concentration (Tmax) was constant among the subjects with a mean value of 0.7 ± 0.27 h (range 0.33–1). Maximum plasma concentration (Cmax) ranged from 2.76 to 4.15 mg/l (mean 3.44 ± 0.59). The elimination half-life ranged from 1.31 to 2.67 h (mean 2.08 ± 0.51). Normalized Cmax/dose ranged from 0.007 to 0.014 mg/l and normalized AUC(0-inf)/dose ranged from 0.014 to 0.035 mg·h/l. In haemodialysis the dialysance was 60–80 ml/min with a fractional drug removal of 24% during a 4-hour haemodialysis session with a high permeability membrane. Discussion: In our patients, absorption, elimination and distribution phases were not altered by renal insufficiency. Furthermore, our pharmacokinetic data are similar to those obtained in patients with normal renal function. Therefore, dosage adjustment is not necessary in patients with renal insufficiency. In haemodialyzed patients, treatment can be administered independently to the dialysis session because of the negligible elimination of abacavir in the dialysate.
Effect of Weekly or Successive Iron Supplementation on Erythropoietin Doses in Patients Receiving Hemodialysis
Authors: Kato Akihiko , Hamada Mayumi , Suzuki Takayuki , Maruyama Takanori , Maruyama Yukitaka , Hishida Akira
Published: April 2003

Aims: To conduct a 3-month prospective study to determine the optimal way for intravenous iron supplementation in hemodialysis (HD) patients with resistance to recombinant human erythropoietin (rHuEPO) therapy due to deficient iron storage. Methods: Thirty-five HD patients with iron deficiency were divided into three groups: (1) patients receiving an intravenous infusion of 40 mg of iron during the first ten HD sessions (n = 12); (2) patients receiving 40 mg of iron injected once a week for 10 weeks (n = 12), and (3) patients without any iron supplementation (n = 11). The rHuEPO dosage was adjusted to maintain hemoglobin levels >10.0 g/dl, and the degree of anemia was assessed 3 months later. Results: In group 1, the hemoglobin levels were significantly increased after 4 weeks and remained increased until the end of the study (p < 0.01). In group 2, the hemoglobin levels were gradually increased until the end of the study (p < 0.01). There was no difference in the final hemoglobin values between both groups. The rHuEPO dosage was significantly decreased from 131 ± 18 to 90 ± 17 U/kg/week in group 1 (p < 0.01), but could not be changed in group 2 during the observation period despite a similar elevation of the serum ferritin level. In group 3, the rHuEPO doses were rather increased at the end of the study (p < 0.05).  Conclusion: Aggressive iron supplementation for the short term may be effective to restore rHuEPO hyporesponsiveness in HD patients with functional iron deficiency.
Oral and Parenteral Essential Amino Acid Therapy in Malnourished Hemodialysis Patients
Authors: Oğuz Yusuf , Bulucu Fatih , Vural Abdülgaffar
Published: April 2003

Background/Aims: Malnutrition has been encountered more frequently than expected and is associated with increased morbidity and mortality in hemodialysis (HD) patients. Until the last few years, only oral and enteral nutritional supplies have been used in the treatment of malnutrition in HD patients. However, intradialytic parenteral essential amino acid (EAA) nutrition has recently been introduced to treat these patients. The present study was conducted to compare both methods of EAA nutrition, oral and parenteral, in malnourished HD patients. Methods: Half of the 20 malnourished HD patients in this study received 0.9 g/kg/week of oral EAA (oral group), while the other half of the patients were treated with the same dose of parenteral EAA (parenteral group) for 4 months. However, at the very beginning of the study, 4 patients from the oral group were transferred to the parenteral group because of complaints such as nausea and vomiting. Therefore, this study was completed with 6 patients in the oral group and 14 patients in the parenteral group. Some biochemical parameters, including blood lymphocyte counts and anthropometric measurements as indicators of the nutritional status, were obtained from both of the groups in the pre- and posttreatment periods. Results: Following the treatment, there were no statistically significant differences between the groups with respect to anthropometric measurements. However, statistically significant increases were observed in serum albumin (p = 0.048) and creatinine (p = 0.006) levels and blood lymphocyte counts (p = 0.006) in the parenteral group, while there were statistically significant increases only in serum calcium (p = 0.028) levels and blood lymphocyte counts (p = 0.038) in the oral group following the treatment when compared to pretreatment values. Conclusion: These results show that parenteral EAA therapy is more comfortable and effective than oral EAA therapy in the treatment of malnourished HD patients.
Lipid Formulations of Polyene Antifungal Drugs and Attenuation of Associated Nephrotoxicity
Authors: Razzaque M.S. , Hossain M.A. , Ahsan N. , Taguchi T.
Published: April 2003

Amphotericin B is an effective broad-spectrum antifungal agent, but various side effects, especially nephrotoxicity, have restricted its use. Recently, lipid formulations of amphotericin B have been developed in order to reduce its toxic side effects. Clinical trials, although in the early stages, suggest promising results, and that some of these lipid formulations are potent and less toxic, even at higher doses. We summarize herein the existing information about newer lipid formulations of polyene antifungal drugs, which could attenuate associated nephrotoxicity.
Mesangiocapillary Glomerulonephritis Caused by Puumala Hantavirus Infection
Authors: Mustonen Jukka , Mäkelä Satu , Helin Heikki , Helanterä Antero , Miettinen Marja , Partanen Jukka , Pasternack Amos
Published: April 2003

Nephropathia epidemica induced by Puumala hantavirus typically causes acute reversible renal function impairment. A typical renal biopsy finding is acute tubulointerstitial nephritis with slight glomerular mesangial changes. We describe here 5 patients who developed the nephrotic syndrome during the convalescent phase of an otherwise typical acute febrile nephropathia epidemica. Renal biopsy of all patients disclosed type I mesangiocapillary glomerulonephritis (MCGN). A clinical remission of the nephrotic syndrome was observed in 4 patients during the follow-up period, and 1 entered into chronic renal failure. Three patients had microscopic hematuria and proteinuria and 2 elevated blood pressure at the latest assessment visit. No patient had clinical or laboratory findings compatible with chronic bacterial, parasitic or viral infections (hepatitis B or C), malignancies, or other disorders known to be associated with MCGN. In conclusion, Puumala hantavirus has to be added to the list of potential agents associated with type I MCGN. Further studies are necessary to establish the incidence of MCGN caused by various hantavirus infections.
Perinatal Hypoxia-Ischemia Induces Apoptotic and Excitotoxic Death of Periventricular White Matter Oligodendrocyte Progenitors
Authors: Ness Jennifer K. , Romanko Michael J. , Rothstein Raymond P. , Wood Teresa L. , Levison Steven W.
Published: April 2003

Hypoxia-ischemia (HI) is a leading cause of white matter damage, a major contributor to cerebral palsy in premature infants. Preferential white matter damage is believed to result from vulnerability of the immature oligodendrocyte (the pro-OL) to factors elevated during ischemic damage, such as oxygen free radicals and glutamate. In order to determine whether pro-OLs undergo apoptotic death after HI, we analyzed periventricular white matter OLs in P7 rats 4, 12 and 24 h after HI to analyze the time course and mode of cell death. DNA fragmentation was seen at 12 and 24 h of recovery after HI, representing a 17-fold increase over control. In addition, caspase-3 activation was found in NG2+ pro-OLs at 12 h. Electron-microscopic analysis of cell death in the white matter revealed a transition from early necrotic deaths to hybrid cell deaths to classical apoptosis between 4 and 24 h of recovery from HI. The delayed time course of apoptosis in pro-OLs supports the feasibility of interventions to improve clinical outcomes for newborns surviving birth asphyxia.
Age-Dependent Consequences of Seizures and the Development of Temporal Lobe Epilepsy in the Rat
Authors: Dubé Céline , da Silva Fernandes Maria José , Nehlig Astrid
Published: April 2003

The age-related functional changes underlying epileptogenesis remain to be clarified. In the present study, we explored the correlation between metabolic changes, neuronal damage and epileptogenesis during the acute, silent and chronic phases following status epilepticus (SE) induced by lithium-pilocarpine (Li-Pilo) in 10- (P10), 21-day-old (P21) and adult rats. Local cerebral metabolic rates for glucose (LCMRglcs) were measured by the [14C]2-deoxyglucose method during SE, the silent period and the interictal phase of the chronic period. Neurodegeneration was assessed by cresyl violet staining. During SE, LCMRglcs dramatically increased at all ages mainly in forebrain vulnerable regions. During the silent phase, in P21 and adult rats, metabolic decreases were recorded in damaged forebrain regions involved in the genesis and propagation of seizures 14 days after SE. At the end of the silent phase, P21 and adult rats exhibited metabolic increases in intact brainstem areas involved in the remote control of epilepsy. During the interictal phase of the chronic period, LCMRglcs decreased in damaged forebrain areas of adult and P21 rats that were not spontaneously epileptic, while LCMRglcs were similar to control levels in epileptic P21 rats. In P10 rats, there was no damage and no metabolic consequences at any time after SE. In conclusion, the process of epileptogenesis and its functional consequences differ in P21 and adult rats. The factors underlying these age-related differences remain to be explored.
Effects of Maturation on Mechanisms of cGMP-Induced Cerebral Vasodilatation
Authors: Nauli S.M. , Williams J.M. , Pearce W.J.
Published: April 2003

In light of observations that cerebrovascular levels of cGMP vary during maturation, the present study examines the possibility that the mechanisms mediating cGMP-induced cerebral vasodilatation also change during maturation. Specifically, these experiments explore age-related changes in the ability of cGMP to both: (1) depress cytosolic calcium concentration, and (2) attenuate contractile protein calcium sensitivity in α-toxin and β-escin permeabilized preparations as well as fura-2 loaded arteries. The present data demonstrate that: (1) cGMP attenuates cytosolic calcium concentration at lower concentrations than required to reduce myofilament calcium sensitivity; (2) both potassium-induced and 5HT-induced contractions were more sensitive to cGMP in fetal than adult arteries; (3) all potassium-induced increases in cytosolic calcium were resistant to the effects of cGMP, but those produced by 5HT were sensitive to attenuation by cGMP, and more so in fetal than in adult basilar arteries, and (4) cGMP attenuated both basal and agonist-enhanced myofilament calcium sensitivity. Overall, these data demonstrate that the mechanisms mediating the multiple vasoactive effects of cGMP are more potent in immature than in mature cerebral arteries and are heavily influenced by both the artery type and the method of contraction.
Sieve Plugs in Fenestrae of Glomerular Capillaries – Site of the Filtration Barrier?
Authors: Rostgaard Jørgen , Qvortrup Klaus
Published: April 2003

The exact location of the filtration barrier of the glomerular capillary wall, which consists of an endothelium, a basement membrane and a visceral epithelium, has not yet been determined. Apparent discrepancies between different investigators in the past could be explained if postmortem artifactual tissue changes, due to subnormal blood pressure or anoxia, have taken place in the endothelium before the tissue and tracers have been sufficiently fixed and immobilized by the fixative. To test this supposition, a new method of fixation, which includes a technique to maintain a physiological perfusion pressure and a fixative composed of an oxygen-carrying blood substitute fluid containing glutaraldehyde, was employed combined with contrast enhancement. New observations of the glomerular capillary wall revealed that filamentous plugs (about 90 nm in height) filled the capillary fenestrae and a filamentous surface coat about 60 nm thick covered the interfenestral domains of the endothelial cell. Based on these purely morphological data, we dare to suggest that the fenestral plugs are the primary site of the glomerular filtration barrier – albeit highly speculative, nevertheless a logical location – and consequently that the glomerular filtration process is a ‘tangential-flow’ as opposed to a ‘dead-end’ filtration process. A tangential-flow filtration would minimize ‘clogging’ and ‘concentration polarization’ in the ‘filter’.
Transverse Cervical Artery Pseudoaneurysm: A Rare Complication of Internal Jugular Vein Cannulation
Authors: Cuhaci Bulent , Khoury Paul , Chvala Robert
Published: April 2003

Internal jugular vein cannulation has become the preferred approach for temporary hemodialysis catheter placement following reports of an increased incidence of subclavian vein stenosis due to subclavian vein catheterization. Internal jugular vein catheterization is associated with a high rate of successful catheter placement. However, significant complications such as internal carotid artery (ICA) puncture, pneumothorax, vessel erosion, thrombosis, airway obstruction and infection can occur. The most common complication is ICA puncture. More recently a few cases of thyrocervical trunk pseudoaneurysm and fistula following internal jugular vein and subclavian vein catheterization attempts have been reported. Patients with renal failure who are on hemodialysis may have to undergo multiple catheter placements and vascular access interventions. This, along with their comorbid conditions, increases the risk of such complications. Here we report a patient on hemodialysis who developed transverse cervical artery pseudoaneurysm following an attempted right internal jugular vein catheterization. We report this case because of its rarity, to raise awareness of such a complication and to discuss different treatment options, in particular endovascular coil occlusion. A review of relevant literature is also presented.
Renal Transplant Dysfunction due to Severe Aorto-Iliac Atherosclerosis in the Presence of Patent Renal Transplant Artery
Authors: Tovbin David , Feldman Leonid , Basok Anna , Shnaider Alla , Hertzanu Yancu , Lantsberg Sophie , Mostoslavsky Markus , Zlotnik Moshe
Published: April 2003

We report a case of progressive deterioration in renal function and decreased renal graft perfusion induced by extensive aorto-iliac atherosclerotic lesions proximal to a patent renal graft artery. Significant improvement in kidney graft function followed left axillo-femoral bypass graft surgery, which to the best of our knowledge, has never been performed previously for permanent maintenance of renal transplant perfusion.
Primary Antiphospholipid Antibody Syndrome and Mesangial IgA Glomerulonephritis
Authors: Sinniah Raja , Gan Hwa Chau , Yoon Kam Hon
Published: April 2003

The antiphospholipid antibody syndrome (APS) is characterized by recurrent thrombosis, fetal loss, multiorgan involvement, and the presence of lupus anticoagulant and/or anticardiolipin antibody. When not associated with systemic lupus erythematosus, other collagen diseases, or ingestion of medications, the condition is called primary APS. The kidney may be involved in the APS syndrome with acute nephritis and renal failure. The cases with renal biopsy studies have shown variable glomerular morphology, ranging from mild mesangial changes to a diffuse endocapillary proliferative glomerulonephritis. The most frequent lesion is thrombotic microangiopathy or features seen in the hemolytic uremic syndrome. Apart from fibrin thrombus deposition, only a few cases have shown focal and segmental deposits of IgG and/or IgM and/or C3. We describe a patient with primary APS who had thrombosis with lower limb amputation and acute renal failure. The renal biopsy specimen showed a focal proliferative glomerulonephritis with endothelial proliferation and damage, with diffuse heavy mesangial deposits of IgA and fibrinogen. This case with diabetes mellitus, but without diabetic nephropathy, represents the occurrence of primary APS and mesangial IgA nephropathy which potentiated the renal injury, leading to acute renal failure. The relationship to the Henoch-Schönlein syndrome is discussed.
Ultrastructure of Glomerular Basement Membrane in Active Heymann Nephritis Rats Revealed by Tissue-Negative Staining Method
Authors: Hayashi Yoshiko , Hironaka Kazue , Shikata Kenichi , Ogawa Saeko , Ota Kosuke , Wada Jun , Kamata Kouju , Ota Zensuke , Makino Hirofumi
Published: April 2003

Recently, we have developed a tissue-negative staining method, and successfully visualized fine meshwork structure of the glomerular basement membrane (GBM). To clarify the mechanism of proteinuria in active Heymann nephritis, we performed tissue-negative staining and investigated the ultrastructural alterations of the GBM. Active Heymann nephritis, the animal model of human membranous nephropathy, was induced in Lewis rats by the injection of proximal tubular brush border antigen, i.e. Fx1A. Urinary protein excretion was measured and histological studies were performed over 15 weeks following the Fx1A injection. Proteinuria developed at 10 weeks after injection (38.2 ± 7.4 mg/day) and progressively increased (160.2 ± 20.6 mg/day at 15 weeks). Capillary fine deposits of IgG and C3 were seen by immunofluorescence, and subepithelial electron dense deposits (EDD) by transmission electron microscopy (TEM). Using the tissue-negative staining method, regular meshwork structure consisted of fine fibrils and pores (2.5 ± 0.7 nm in short dimension) was observed in the GBM of control rats. At 10 and 15 weeks after injection, the GBM, directly facing the endothelial side of EDD, contained enlarged pores and nephrotic tunnels. Mean values of the short dimension of enlarged pores were 2.9 ± 0.5 nm at 10 weeks and 3.1 ± 0.4 nm at 15 weeks, which were significantly larger than that of control rats (p < 0.01). The rest area of the GBM, including newly produced GBM covering the epithelial side of EDD, had no significant difference in size of the pores from control GBM and no tunnels. Although there was no significant difference in the size of enlarged pores between 10 and 15 weeks, the percentage area of GBM with impaired size barrier increased at 15 weeks (51.4 ± 8.1%) compared with 10 weeks (24.0 ± 8.3%) and related to severity of proteinuria. The density of the tunnels also increased at 15 weeks. In conclusion, immune deposits may affect the GBM biosynthesis and induce the defect of size barrier of the GBM, which is responsible for proteinuria in active Heymann nephritis.