bluuebunny/crossref_metadata_2025 huggingface dataset:
Atraumatic Loss of a Kidney in a Patient with Alpha1-Antitrypsin Deficiency
Authors: Randers Else , Jønler Morten , Lund Allan M. , Danielsen Henning
Published: April 2003

α1-Antitrypsin (α1AT) deficiency is characterized by a high risk of developing pulmonary emphysema and liver disease. Arteriopathy may be associated with α1AT deficiency. We present a patient with only one kidney and α1AT deficiency, but only mild pulmonary symptoms and no signs of liver disease, and atraumatic loss of the remaining kidney. Histological examination of the renal artery showed desposits of a mucoid ground substance in the arterial media, as has been demonstrated in other patients with α1AT deficiency. After dialysis treatment for 15 months, the patient underwent an uneventful kidney transplantation. The case draws attention to the awareness of complications of α1AT deficiency even in cases with only mild pulmonary manifestations of the disorder. To our knowledge, atraumatic loss of a kidney in a patient with α1AT deficiency has not previously been reported.
Evidence of Hepatitis C Virus Passage Across Dialysis Membrane
Authors: Valtuille R. , Fernández J.L. , Berridi J. , Moretto H. , del Pino N. , Rendo P. , Lef L.
Published: April 2003

The passage of hepatitis C virus (HCV) across the dialysis membrane is a controversial issue. We performed a study applying extreme conditions of permeability to the dialysis membrane and avoiding the use of heparin and dialysis bath that might interfere with polymerase chain reaction (PCR) results. We obtained samples from the ultrafiltrate at the beginning of 18 hemodialysis sessions carried out in 6 HCV RNA-positive patients. HCV RNA was detected by PCR in 3 (16.7%) ultrafiltrate samples belonging to 1 of the patients. HCV genotype was the same as that found in positive ultrafiltrate samples and in the serum corresponding to this patient. The viral load of this patient was under the levels detectable by the assay employed. Therefore, contamination of the ultrafiltrate may constitute a potential risk for HCV transmission in hemodialysis units.
Dissociated Expression of Collagen Type IV Subchains in Diabetic Kidneys of KKAy Mice
Authors: Funabiki Kazuhiko , Makita Yuichiro , Yamamoto Masatoshi , Shike Toshihide , Fukui Mitsumine , Sumiyoshi Yuko , Tomino Yasuhiko
Published: April 2003

Diabetic nephropathy is characterized by thickening of the glomerular basement membrane and expansion of the mesangial matrix. The glomerular basement membrane is assembled from at least five genetically distinct collagen IV chains. In patients with diabetic nephropathy, differential distribution of these components has been demonstrated. In order to clarify the relationship between progression of diabetic nephropathy and altered type IV collagen assembly in the renal cortex, we examined steady state mRNA levels encoding collagen IV subchains in the kidney cortices of spontaneously diabetic KKAy mice and nondiabetic C57black mice as controls. They were sacrificed at 4, 8, 16, and 24 weeks of age. Northern and dot blot analyses were performed using 32P-labeled mouse probes for classical α1(IV) and α2(IV) and for α3(IV), α4(IV), and α5(IV) minor chains. The mRNA levels for all collagen IV chains peaked at 4 weeks of age and declined rapidly thereafter in the nondiabetic mice. At all times, α1(IV) and α2(IV) mRNA expressions were abundant and almost unchanged in KKAy mice. In contrast, mRNA levels for α3(IV), α4(IV), and α5(IV) progressively changed with age. It appears that the expression of minor collagen IV chains is dissociated from the α1(IV) and α2(IV) chains in diabetic nephropathy. Moreover, an unbalanced increase in the production may affect collagen IV assembly and contribute to basement membrane thickening in diabetic nephropathy of KKAy mice.
Morbidity and Mortality on Maintenance Haemodialysis
Authors: Locatelli Francesco , Del Vecchio Lucia , Manzoni Celestina
Published: April 2003

Despite the many technical advances in medical care and dialysis delivery, mortality and morbidity remain high in end-stage renal disease (ESRD) patients. A number of factors seem to contribute. Cardiovascular diseases are the leading cause of death: volume overload, anaemia, hypertension, arteriovenous fistula, uraemia-related myocardial cell injury all contribute to the development of ischaemic heart disease and congestive heart failure. The underlying disease is determinant for prognosis, with diabetics displaying an excess cardiovascular mortality. Elderly are also more likely to experience intercurrent medical conditions, vascular disease and diabetes, thus increasing the risk of death. Protein-energy malnutrition and wasting also contribute to the higher mortality in renal replacement therapy. Although nowadays high-risk patients are dialysed too, the rate of acceptance of ESRD patients still varies widely in different countries, possibly because of hidden selection criteria. The patients in the registries with a higher acceptance rate are more likely to be affected by co-morbid conditions and greater disease severity; the assessment of these co-morbid conditions is extremely important when comparing outcomes in different haemodialysis populations. Dialysis adequacy, obtained by means of longer duration of the treatment, is also of paramount importance; it allows minimizing the clinical effects of ultrafiltration and ensure that correct dry weight is reached. This means decreasing the incidence of intradialytic hypotensive episodes, but also improving blood pressure control, a strong predictor of survival. Family and social support, together with adequate medical care, greatly affect the quality of life of patients and can improve compliance to dialysis, diet and drugs and therefore survival.
Measurement of Glomerular FiltrationRate by the 99m< /sup>Tc-DTPA Renogram Is Less Precise than Measured and Predicted Creatinine Clearance
Authors: De Santo Natale G.G. , Anastasio Pietro , Cirillo Massimo , Santoro Domenico , Spitali Lucia , Mansi Luigi , Celentano Luigi , Capodicasa Dorotea , Cirillo Eleonora , Del Vecchio Enrico , Pascale Carmen , Capasso Giovanbattista
Published: April 2003

The work was devised to compare measurements of glomerular filtration rate (GFR) by technetium-99m-diethylenetriaminepentacetic acid (99mTc-DTPA) renogram to those by creatinine clearance (measured and predicted by Cockroft and Gault) and by inulin clearance. A total number of 65 individuals were enrolled: 15 healthy controls and 50 patients with renal disease. Compared to inulin clearance used as the gold standard, 99mTc-DTPA overestimated at low and underestimated at high GFRs. 99mTc-DTPA measurements were less precise than creatinine clearance except for individuals with GFR >100 ml/min × 1.73 m2. Measured creatinine clearance had the highest correlation coefficient with inulin clearance, 99mTc-DTPA clearance the lowest. In correlation analyses, 81.5% of the interindividual variability for measured creatinine clearance could be explained by true differences in inulin clearance; this value dropped to 59.1 and 57.4% for predicted creatinine clearance and 99mTc-DTPA, respectively. In patients with GFR <25 ml/min × 1.73 m2, all 99mTc-DTPA measurements were out of the 95% confidence interval for the inulin measurement. It can be inferred that 99mTc-DTPA clearance from the renogram is less precise than measured and predicted creatinine clearance.
Effects of Human Alpha-1-Acid Glycoprotein on Aminonucleoside- Induced Minimal Change Nephrosis in Rats
Authors: Muchitsch Eva-Maria , Pichler Ludwig , Schwarz Hans Peter , Ulrich Walter
Published: April 2003

A minimal change nephrosis was induced in rats by a single intraperitoneal injection of puromycin aminonucleoside (100 mg/kg). This resulted in increased urine protein output, plasma creatinine, blood urine nitrogen, and relative kidney weight. Electronoptically, there was a retraction of the glomerular podocytic foot processes. When human α1-acid glycoprotein was injected at 600 mg/kg intravenously on experimental days 6, 7, 8, and 9 into these animals, urine protein output decreased significantly, and the number of podocytic foot processes increased significantly. α1-Acid glycoprotein is rich in sialic acid and largely negatively charged. Its therapeutic role in nephrosis, which is characterized by a loss of sialic acid and a loss of negative charge, thereby leading to a loss of permselectivity, is discussed.
Activation of Epidermal Growth Factor Receptor in the Early Phase after Renal Ischemia-Reperfusion in Rat
Authors: Yano Tomohiro , Yazima Shoko , Hagiwara Kiyokazu , Ozasa Hisashi , Ishizuka Shino , Horikawa Saburo
Published: April 2003

In order to estimate a regenerative response in the early phase after renal ischemia-reperfusion in rat, we examined the time course of the activation of epidermal growth factor receptor (EGFR) as a response of signal transduction pathway after 45 min ischemia in kidney. The activation of EGFR was observed 5–30 min after the start of reperfusion. Simultaneously, superoxide anion/hydrogen peroxide generated in the mitochondrial fraction was elevated during the same period. On the other hand, the level of EGF decreased in a time-dependent manner. These results suggested that superoxide anion/hydrogen peroxide generated during the ischemia-reperfusion other than EGF could act as an activator for the EGFR. In summary, the activation of EGFR is important as a regenerative response at an early stage after the start of reperfusion in ischemic kidney.
Molecular Analysis of the Carboxy Terminus of the Beta and Gamma Subunits of the Epithelial Sodium Channel in Patients with End-Stage Renal Disease
Authors: Födinger Manuela , Schedler Dagmar , Fritsche-Polanz Robert , Hörl WalterH. , Sunder-Plassmann Gere
Published: April 2003

Background: Mutations in the carboxy termini of the beta subunit (hβENaC) and the gamma subunit (hγENaC) of the human epithelial sodium channel have been identified in patients with Liddle syndrome. Moreover polymorphisms have been described in these genes, the clinical relevance of which for progression to end-stage renal disease (ESRD) is unknown. We, therefore, have screened ESRD patients for putative variants of these genes. Methods: We investigated 256 chronic hemodialysis patients, including 123 patients with a history of hypertension as a cause of ESRD. Screening for mutations in the carboxy termini of hβENaC and hγENaC was accomplished by polymerase chain reaction amplification followed by single-strand conformation polymorphism analysis. Results: In 231 patients single-strand conformation polymorphism analysis of the polymerase chain reaction fragments of the hβENaC and hγENaC genes showed a similar migration pattern as compared with negative control subjects. In 25 patients a band shift was observed. However, sequence analysis in all these patients revealed wild-type sequence. Conclusions: The present study demonstrates the absence of genetic variants in the carboxy terminus of the hβENaC and hγENaC genes in Austrian patients with ESRD maintained on chronic hemodialysis treatment. Thus, mutations in these genes are unlikely to be associated with ESRD.
Effect of FK 506 in the Treatment of Autoimmune Glomerulonephritis in Brown Norway Rats
Authors: Nakahama H. , Obata K. , Sugita M. , Horio M. , Oka K. , Moriyama T.
Published: April 2003

Mercuric chloride (HgCl2) induces a lymphoproliferative disorder and autoimmune glomerulonephritis in Brown Norway (BN) rats. The effects of a new immunosuppressant, FK 506, on this model of glomerulonephritis were studied. BN rats were treated with HgCl2 according to a standard protocol (HgCl2 1 mg/kg s.c. 3 times/week). FK 506 was inoculated subcutaneously daily from day 15 to day 28. Animals were divided into 4 groups: group 1, rats were treated with normal saline alone and sacrificed on day 28; group 2, rats were treated with HgCl2 alone and sacrificed on day 14; group 3, rats were treated with HgCl2 alone and sacrificed on day 28, and group 4, rats were treated with HgCl2 and FK 506 (from day 15 to day 28) and sacrificed on day 28. Rats developed proteinuria by day 7, which reached a plateau level by day 14. On day 14, renal histology showed prominent mesangial cellular proliferation and the expansion of mesangial matrix. Electron microscopic study showed the effacement of visceral epithelial foot processes and the microvillous transformation of the visceral epithelium. Immunofluorescence study showed strong linear staining for IgG and the adhesion molecule ICAM-1 in all glomeruli. Treatment with FK 506 (1 mg/kg s.c. daily) resulted in a remarkable reduction in proteinuria on day 28 (493.5 ± 48.3 vs. 24.4 ± 13.5 mg/day) and an improvement in the morphological lesions. These findings suggest that FK 506 could be useful in the treatment of some human glomerulonephritides.
The Role of α-Glutathione S-Transferase in the Monitoring of Hemodialysis Patients with Hepatitis C Virus Infection Undergoing High-Dose Interferon-α-2b Therapy
Authors: Boran Mediha , Çetin Selahattin
Published: April 2003

The study aimed to evaluate the behavior of α-glutathione S-transferase (α-GST) in the serum of hemodialysis patients with hepatitis C virus (HCV) infection following treatment with high-dose IFN-α-2b. Ten patients with detected anti-HCV antibodies and HCV RNA by RT-PCR were selected and treated with high-dose interferon (IFN)-α-2b, 10 million units s.c. daily for 2 weeks followed by 3 times per week for 6 additional weeks. Blood samples were obtained from these patients at baseline for plasma α-GST and hepatic aminotransferases. Patients were monitored with weekly blood counts and monthly liver enzymes. Biochemical (normal α-GST and ALT) and virologic (negative HCV RNA by RT-PCR) responses were observed in 3 (30%) of the 10 patients. At the end of the follow-up (follow-up duration 44 weeks), 3 patients demonstrated long-term biological and virologic responses and 7 had relapses. In the nonresponders plasma AST and ALT approached normal levels on some occasions despite persistent viral RNA. In contrast to transaminases α-GST remained distinctly elevated in nonresponders and provided a more clear distinction between the responders and nonresponders. In conclusion, plasma α-GST, as a sensitive and reliable marker of response, may have a role in the monitoring of hemodialyzed patients undergoing IFN-α-2b therapy.
Effects of Interleukin-15 on Vascular Permeability Factor Release by Peripheral Blood Mononuclear Cells in Normal Subjects and in Patients with Minimal-Change Nephrotic Syndrome
Authors: Matsumoto Koichi , Ohi Hiroyuki , Kanmatsuse Katsuo
Published: April 2003

The characteristic function of interleukin (IL)-15 appears to be its ability to mimic the stimulatory action of IL-2 on lymphocytes by utilizing part of the IL-2 receptor complex. To gain insight into the immunoregulatory properties of this cytokine in patients with minimal-change nephrotic syndrome (MCNS), we analyzed effects of IL-15 on vascular permeability factor (VPF) release in vitro. Peripheral blood mononuclear cells (PBMC) were isolated from 16 patients with MCNS, 16 patients with IgA nephropathy (IgAN) and 16 healthy controls. Cells were stimulated with concanavalin A (Con A) and the VPF was assessed using the method of Lagrue with minor modifications. PBMC secreted significantly increased amounts of VPF under stimulation with Con A in patients with MCNS and IgAN patients with the nephrotic syndrome as compared with normal controls. Here we have demonstrated, for the first time, that addition of IL-15 to PBMC obtained from nephrotic patients as well as from normal controls increased Con A-induced release of VPF by 250%. This stimulatory effect was found highly significant and was dose-dependent. The effect of IL-15 on the secretion of VPF was specific, since a complete reversion was obtained with a neutralizing antibody to human IL-15. Our findings reveal that IL-15 has the potential to function as an immunoregulatory molecule of PBMC VPF release. In addition, IL-15 had similar effects to IL-2 in terms of its capacity to upregulate VPF release. Taken together, our data emphasize a positive regulatory role for IL-15 in inducing the release of VPF when present at optimal levels. Therefore, IL-15 antagonists may provide a basis for immune intervention in the pathophysiology of VPF.
A New Chemical Preservative That Permits Analysis of Urine Sediment for Light Microscopic Examination 12 h after Emission
Authors: del Rosario Rodríguez Moreno M. , Rodríguez Moreno Irene , León M. Teresa Miranda , Boy Monique , Cowdry Agnieszka Nina
Published: April 2003

Introduction: Urine diagnosis by light microscopy is considerably more difficult when specimens are analyzed after a certain period of time. Objectives: (1) To investigate whether this change effectively exists at a significant level of 12 h. (2) To apply measures, once the above has been done, allowing for the analysis of samples beyond 12 h in similar conditions. Materials and Methods: Both freshly produced urine and pathological samples were used under certain experimental conditions: initial, 12 h, 12 h + fridge at 4°C (F), 12 h + chemical preservation (S) and 12 h + SF. The chemical preservative was prepared at a 50/50 ratio with 3% formaldehyde and 2.5% glutaraldehyde by the addition of a buffer of pH 7.2–7.4, resulting in a solution of pH 7.35 at 25°C room temperature. Urinalysis was carried out on all samples: glucose (enzymatic method of hexokinase) and total protein in liquid (red pyrogallol method). Centrifugation was followed by sediment analysis with light microscopy. Statistical analysis was done with the Kolmogorov-Smirnov normality test, Friedman nonparametric test and multiple comparisons. Results and Conclusion: Urine samples tested 12 h after having been produced changed significantly (p < 0.0001), making it necessary to adopt certain measures to maintain their initial conditions. In our case, after the addition of the chemical preservative, samples did not present any changes (p > 0.10) in relation to the initial conditions and were seen to be reliable, therefore indicating the suitability and effectiveness of the analytical conditions (urinalysis in particular, sediment analysis).
Potassium Removal Increases the QTc Interval Dispersion during Hemodialysis
Authors: Cupisti Adamasco , Galetta Fabio , Caprioli Raffaele , Morelli Ester , Tintori Gian Carlo , Franzoni Ferdinando , Lippi Alberto , Meola Mario , Rindi Paolo , Barsotti Giuliano
Published: April 2003

This study was planned to clarify the mechanism(s) by which hemodialysis increases the QTc dispersion, a marker of risk of ventricular arrhythmias. To this aim, 10 uremic patients, without any relevant heart diseases, underwent two different types of hemodialysis schedules. In the first, 1 h of isolated high rate ultrafiltration preceded the standard diffusive procedure. In the second, during the first hour of standard bicarbonate hemodialysis, the decrease of plasma potassium concentration was prevented by increasing K+ concentration in the dialysate, according to its pre dialysis plasma levels. During the high rate ultrafiltration period, together with ECG signs of increased sympathetic nervous system activity and catecholamines secretion, the QTc dispersion did not change significantly. Instead, an evident increment was observed 1 h after the start of the diffusive hemodialysis, then slowly progressing until the end of the dialysis and finally returning to the pre dialysis values within 2 h after the end of the session. To the contrary, the increase of the QTc dispersion was totally blunted during a standard hemodialysis procedure in absence of plasma K+ decrease, but appeared again when the K+ dialysate fluid concentration was restored to 2 mmol/l. This study provides evidence that the increase of QTc dispersion occurring on hemodialysis is mainly related to the diffusive process, more precisely to the K+ removal. This is one more reason to focus attention on K+ removal rate especially when hemodialysis treatment is given in uremics affected by cardiac diseases with high risk of arrhythmias.
Renal Cell Carcinoma and Paraneoplastic IgA Nephropathy
Authors: Magyarlaki T. , Kiss B. , Buzogány I. , Fazekas A. , Sükösd F. , Nagy J.
Published: April 2003

Paraneoplastic nephropathy is rarely associated with human tumors. Little is known about the pathogenetic background of this relationship. To our knowledge, no conclusive study of the association of potentially ‘immunogenic’ renal cell carcinoma (RCC) and paraneoplastic nephropathy has been published. For this reason, we performed an immunohistochemical analysis of native resected kidneys of 60 patients with RCC, paying special attention to their pre- and postoperative records. Sixteen (27%) of the 60 tumor patients had immune complex nephropathy (11 IgA nephropathy [IgA NP] and 5 focal segmental glomerulosclerosis [FSGS]). Preoperative proteinuria and/or hematuria observed in 11 of 16 cases disappeared in 6 IgA NP patients within a 2- to 3-month follow-up after nephrectomy. Eleven of 16 tumors stained with the anti human immunoglobulin (IgA or IgM) of the same isotype as that present in glomerular immune complexes. In 3 IgA NP patients RCC-associated von Hippel-Lindau (VHL) protein and IgA staining were found simultaneously in the tumor and glomeruli, with the clinical and laboratory findings disappearing after nephrectomy. Immune injury of the glomeruli due to a tumor-induced antigen-antibody response was demonstrated in these 3 IgA NP patients.
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

Background/Aims: 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. Methods: 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. Results: 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 m2) than in Bostonians (112 ± 3 ml/min/1.73 m2; p < 0.001). Conclusion: 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.
Expression and Localization of the Neuronal Glycine Receptor Beta-Subunit in Human, Rabbit and Rat Kidneys
Authors: Sarang Satinder S. , Miller Gary W. , Grant David F. , Schnellmann Rick G.
Published: April 2003

The glycine receptor (GlyR) is a ligand-gated Cl– channel composed of two transmembrane subunits, α and β, and gephyrin. The goal of this study was to determine whether the α- and/or β-subunits of the GlyR are expressed in human, rabbit and/or rat kidneys. Screening of human and rat kidney cortex cDNA libraries identified polymerase chain reaction products that were identical to the neuronal GlyR β-subunit. Sequencing revealed that rat kidney cortex and neuronal GlyR β-subunits were identical. RNA isolated from the S2 segment of rabbit renal proximal tubules (RPT) and rat and rabbit kidney cortex was amplified following reverse transcription and gave similar results to that of human and rat kidney cDNA libraries. Degenerate primers against all GlyR α-subunits did not yield a product from rat and rabbit kidney cortex RNA, or from human and rat kidney cortex cDNA libraries. Immunofluorescence studies localized the β-subunit and gephyrin to the basolateral membrane of rabbit RPT. These results provide compelling evidence for the GlyR β-subunit, but not the α-subunit, in human, rabbit and rat kidney cortex.
Metallothioneins in Human Kidneys and Associated Tumors
Authors: Hellemans Godelieve , Soumillion Ann , Proost Paul , van Damme Jo , van Poppel Hein , Baert Luc , De Ley Marc
Published: April 2003

Human kidneys and their associated tumors (nonneoplastic kidney tissues from patients with a transitional cell carcinoma or an adenocarcinoma and the adenocarcinomas themselves) were evaluated for their Zn, Cd, and Cu contents as well as for their metallothionein (MT) level. The total Cd content was correlated with the MT content, and both values were significantly decreased in the adenocarcinomas in comparison with the other tissues. After extraction and separation by anion-exchange chromatography, MT-0 was identified in the nonneoplastic tissues from both the adenocarcinomas as well as the transitional cell carcinomas. Since until now MT-0 protein was only found in human fetal liver and in Zn-stimulated human monocytes, a possible role for this isoform as an oncofetal marker is hypothesized. Separation of the isoforms of MT by reversed-phase high-performance liquid chromatography and sequence analysis showed besides MT-1e and MT-1l the isoform-MT-1g, which is not expressed in the healthy kidney, and MT-1k, an isoform which is not yet demonstrated in renal tissues. We conclude that the expression profile of the MT isoforms in the kidney changes due to the presence of a tumor.
The Plasma Levels of Homocysteine Are Elevated in Moderate Renal Insufficiency but Do Not Predict the Rate of Progression
Authors: Samuelsson O. , Lee D.M. , Attman P.-O. , Knight-Gibson C. , Mullen J.K. , Larsson R. , Mulec H. , Weiss L. , Alaupovic P.
Published: April 2003

Background: Chronic renal failure is characterized by specific alterations of the lipoprotein metabolism. It is also characterized by elevated plasma levels of total homocysteine (tHcy). Hyperhomocysteinemia has been shown to be a risk factor for atherosclerosis in both the general population and in patients with end-stage renal disease. Aim: To analyze whether elevated tHcy levels also may contribute to a higher rate of progression of renal insufficiency in patients with moderately advanced renal failure. Methods: To investigate whether tHcy concentrations are associated with an accelerated rate of progression of renal insufficiency, we have correlated baseline plasma concentrations of tHcy with the progressive decline of renal function in an observational study of human chronic renal disease. Results: Sixty-three nondiabetic patients (49 men, 14 women) were studied as part of an observational study of patients with moderately advanced renal insufficiency. The average follow-up time of the patient population was 3.0 years, and the mean rate of decline in glomerular filtration rate (51Cr- EDTA clearance) was –3.2 ± (SD) 3.9 ml/min × 1.73 m2 body surface area. The mean plasma concentration of tHcy at the beginning of the study was 28.3 ± 12.0 µmol/l. Plasma tHcy concentrations correlated significantly with the glomerular filtration rate (r = –0.32, p < 0.01). However, there was no association between the initial plasma level of tHcy and the rate of progression as assessed by linear regression analysis (r = 0.02; NS). In contrast, increased levels of apolipoprotein B, low-density lipoprotein cholesterol, and proteinuria were all significantly associated with a more rapid decline in renal function. Conclusions: Patients with moderately advanced chronic renal insufficiency have elevated plasma levels of homocysteine. The tHcy plasma levels increase in parallel with the degree of reduction in renal function. However, the hyperhomocysteinemia is not prospectively associated with a higher rate of progression of the renal functional impairment. Hence, there is no indication that elevated homocysteine levels play a contributing role for an accelerated glomerulosclerotic process.
Suppressive Effects of Perilla frutescens on Spontaneous IgA Nephropathy in ddY Mice
Authors: Makino Toshiaki , Ono Takahiko , Muso Eri , Honda Gisho , Sasayama Shigetake
Published: April 2003

Perilla frutescens (perilla) is a common herb used in Japan for garnishing raw seafood to protect the alimentary tract from inflammatory diseases. The present study was performed to investigate whether or not perilla prevents the development of lesions of IgA nephropathy in ddY mice which spontaneously develop this disease. After orally administering perilla extract to ddY mice from 8 to 42 weeks of age, the changes in urine, serum, and kidneys were evaluated. Perilla extract significantly suppressed proteinuria and glomerular IgA deposition (p < 0.01 and p < 0.05, respectively). The decreased serum IgA concentration in perilla-treated mice showed a significant correlation with glomerular IgA deposition. Such findings suggest that perilla reduced glomerular IgA deposition via suppression of IgA production in the serum. On the other hand, the nitric oxide concentration in the serum of perilla-treated mice was significantly higher than that observed in the controls. The addition of the sera of perilla-treated mice to quiescent cultured murine mesangial cells resulted in a cell proliferation which was less than in controls, suggesting that perilla might either directly prevent mesangial cell proliferation or prevent proliferation by regulating circulating cytokines. Such results indicate that perilla should prevent IgA nephropathy, thus representing a promising herbal medicine for glomerulonephritis.
Importance of Residual Renal Function in Continuous Ambulatory Peritoneal Dialysis: Its Influence on Different Parameters of Renal Replacement Treatment
Authors: López-Menchero R. , Miguel A. , García-Ramón R. , Pérez-Contreras J. , Girbés V.
Published: April 2003

Objective: To study the influence of residual renal function (RRF) on different parameters of the renal substitutive treatment offered by peritoneal dialysis. Methods: We analyzed the impact of RRF on dialysis dose, nutrition parameters, anemia and phosphocalcic metabolism in 37 patients with end-stage renal disease (ESRD) treated by continuous ambulatory peritoneal dialysis (CAPD). Analytical controls were done every 6 months after an initial assessment at the end of the first month of treatment. Multiple lineal regression models were used as the statistical method to analyze the influence of RRF on different theoretically dependent factors. RRF was calculated as a mean of creatinine and urea clearances. Three observations per patient were used: one at the end of the first month of treatment; a final one at the end of follow-up (mean time 24.2 ± 11.4 months), and at a mean time between them (13.4 ± 6.7 months), with a final number of 111 observations. Results: Dialysis dose: RRF was the most important factor in terms of creatinine clearance (r2 = 0.94; β = 0.999), KT/V (r2 = 0.68; β = 0.819) and β2-microglobulin levels (r2 = 0.46; β = –0.489). Nutrition parameters: RRF was a determinant factor for normalized protein catabolic rate (r2 = 0.53; β = 0.471), percent lean body mass (r2 = 0.45; β = 0.446) and albumin levels (r2 = 0.25; β = 0.229). Anemia: RRF was the most important factor when studying hemoglobin levels (r2 = 0.28; β = 0.407). Phosphocalcic metabolism: Between the analyzed factors, RRF was the only one which reached significance on serum phosphate levels (r2 = 0.19; β = –0.594). RRF did not show any relationship with either calcium or PTH levels. Conclusions: Independent of other factors, RRF in CAPD is positively and directly related to dialysis dose, β2-microglobulin levels, nutrition parameters (albumin, normalized protein catabolic rate and percent lean body mass, hemoglobin and serum phosphate levels.
Obstructive Nephropathy: Lessons from Cystic Kidney Disease
Authors: Chevalier Robert L.
Published: April 2003

Obstructive nephropathy is one of the most important causes of renal failure in infants and children, while polycystic kidney disease (PKD) is a major cause of renal failure in the adult population. This review summarizes the evidence that there may be a number of mechanisms common to the pathophysiology of both conditions. In animal models of obstructive nephropathy and PKD, the renal tubular expression of epidermal growth factor is suppressed, and expression of clusterin is increased, both of which suggest arrested maturation or dedifferentiation of the tubular cell. There is a marked increase in apoptosis of epithelial cells in dilated tubules, associated with an increase in apoptotic stimuli. The renin-angiotensin system is activated in both obstructive nephropathy and PKD, which may contribute to tubular atrophy and interstitial fibrosis, which characterize the progression of both conditions. Focal cystic dilatation of the tubule is found in obstructive nephropathy, while tubular obstruction is present in cystic kidney disease. It is therefore likely that elucidation of the effects of mechanical stretch on renal tubular epithelial cells will contribute to our understanding of both conditions.
Selenium Depletion in Hemodialysis Patients Treated with Polysulfone Membranes
Authors: Bogye Gabor , Tompos Gabor , Alfthan Georg
Published: April 2003

Background/Aims: Epidemiological, animal and human studies have indicated that selenium deficiency is a risk factor for death from malignant diseases. The mechanisms that could modify selenium status may, therefore, be of particular interest in hemodialysis patients, considering their high cancer mortality rates. We aimed at evaluating the effect of hemodialysis with polysulfone membranes on selenium status. Methods: Twenty- eight chronically dialyzed patients and 32 age-matched healthy controls were enrolled in the study. Serum and dialysis fluid selenium concentrations, serum total protein, and hemoglobin concentrations and serum glutathione peroxidase activity were determined before and after the hemodialysis procedure. Results: The (mean ± SD) serum selenium and total protein concentrations and glutathione peroxidase activities were significantly (p < 0.05) higher in healthy controls (75.9 ± 8.3 µg/l, 78 ± 6 g/l, and 23.8 ± 4.8 mU/20 µl, respectively) than in the patients. There was no significant difference between serum selenium concentration before (63.6 ± 11.6 µg/l) and after (64.4 ± 11.4 µg/l) hemodialysis sessions, although hemoglobin and total serum protein concentrations and serum glutathione peroxidase activities increased (from 98.5 ± 1.3 to 114.8 ± 1.5 g/l, from 64 ± 8 to 71 ± 9 g/l, and from 16.8 ± 1.8 to 18.9 ± 1.9 mU/20 µl, respectively) significantly (p < 0.05) during hemodialysis, indicating hemoconcentration. The selenium concentration doubled, and protein appeared in the dialysates during dialysis session. The correlation of the selenium concentrations with the protein concentrations in the dialysate is significant (p < 0.01) with a Spearman R value of 0.97. Conclusion: The results of the present study suggest that selenium is lost through the pores of polysulfone membranes during hemodialysis which is associated with their protein permeability.
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.
Increased Serum IL-10 and Endothelin Levels in Hemolytic Uremic Syndrome Caused by Escherichia coli O157
Authors: Yamamoto Takehisa , Nagayama Ken-ichi , Satomura Ken-ichi , Honda Takeshi , Okada Shintaro
Published: April 2003

Background: Shiga toxin, produced by Escherichia coli O157:H7, is important for the pathogenicity of the epidemic form of hemolytic uremic syndrome (HUS). This toxin has recently been found to stimulate endothelin-1 synthesis in cultured endothelial cells in vitro. Methods: We investigated endothelin and cytokine levels in sera during a large outbreak of E. coli O157:H7 infection in Osaka, Japan, in 1996. Eleven patients with HUS and 9 patients with hemorrhagic colitis at the onset of E. coli O157:H7 infection were studied. Results: Serum IL-6 (p < 0.01), IL-8 (p < 0.05), IL-10 (p < 0.001) and endothelin (p < 0.001) levels were significantly increased in patients with HUS compared to those with colitis only. The serum thrombomodulin level, a molecular marker of endothelial damage, also showed a significant positive correlation with serum IL-6 (p < 0.01), IL-8 (p < 0.01), IL-10 (p < 0.01) and endothelin (p < 0.001) levels. In a HUS patient, the increase in serum IL-10 and endothelin levels reached a plateau prior to the peak of serum creatinine levels. Conclusion: Increased serum endothelin synthesis by Shiga toxin in vivo was proven in HUS secondary to E. coli O157:H7 infection. Increased serum endothelin and IL-10 levels were speculated to be associated with the development of HUS through vascular endothelial damage caused by E. coli O157:H7 infection.
Interleukin-18 and Interleukin-12 Synergize to Stimulate the Production of Vascular Permeability Factor by T Lymphocytes in Normal Subjects and in Patients with Minimal-Change Nephrotic Syndrome
Authors: Matsumoto Koichi , Kanmatsuse Katsuo
Published: April 2003

Background/Aim: In a previous study, we reported that interleukin (IL)-12 could upregulate the production of vascular permeability factor (VPF) derived from activated human peripheral blood mononuclear cells. Since IL-18, a novel immunoregulatory cytokine with potent interferon-γ inducing activities, has been shown to be a strong cofactor for T helper type 1 cell development, we tested the hypothesis that IL-18 in combination with IL-12 can act synergistically to modulate the production of VPF. Methods: For this purpose, T cells were isolated from heparinized venous blood, stimulated with concanavalin A, and incubated in the presence of IL-18 or IL-12, and the production of VPF was determined by the method of Lagrue. Results: There was a significant increase in VPF production from concanavalin A-stimulated T cells following incubation with IL-18 or IL-12. More importantly, the combination of the cytokines was found to give a potent synergistic stimulation of VPF by concanavalin A-activated T cells from normal subjects. To determine the specificity of the stimulatory effect, neutralizing anti-IL-18 and anti-IL-12 antibodies were preincubated with IL- 18 and IL-12, respectively, prior to the addition of responder cells. The antibodies completely inhibited the effects of IL-18 and IL-12. Thus, these data show that IL-18 can synergize with IL-12 to selectively increase the production of VPF from T cells. The present study further demonstrates that IL-18 and IL-12 are in fact acting in synergy in patients with minimal-change nephrotic syndrome. Conclusions: Taken together, our results indicate that both IL-18 and IL-12 contribute to the VPF production in vitro and suggest that they play key roles in the complexity of cytokine regulation in the pathophysiology of VPF.
Chronic Unilateral Ureteral Obstruction Represented as Renin-Dependent Hypertension
Authors: Ishidoya Shigeto , Fukuzaki Atsushi , Kaneto Hiroyuki , Takeda Atsushi , Ogata Yukihiko , Sasaki Toru , Suzuki Ken-ichi , Watanabe Ryuji , Hoshi Senji , Kikuya Masahiro , Takeuchi Kazuhisa , Ito Sadayoshi , Orikasa Seiichi
Published: April 2003

A 50-year-old woman developed renin-dependent hypertension immediately after accidental unilateral ureteral ligation during hysterectomy, and the hypertension lasted for 5 months. Surgical release of the obstruction was carried out 157 days after the ligation. Then, her blood pressure was normalized. However, the obstructed kidney showed intensive tubulointerstitial fibrosis and functional recovery was not obtained. This case suggests that the renin-angiotensin system may be upregulated in human kidney during unilateral ureteral obstruction for a long duration.
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 a allele (31.2 ± 1.76 µmol/l) was significantly lower than in those without the a 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 a/a, b/a and b/b 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 a allele (b/a + a/a) 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 (Ca2+) is reabsorbed by the luminal membrane of the proximal and distal nephron. Ca2+ enters cells across apical plasma membranes along a steep electrochemical gradient, through Ca2+ 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 Ca2+ 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 45Ca2+ uptake by these membrane vesicles was measured in the presence and absence of 100 mM NaCl. In the absence of Na+, intravesicular GTPγs significantly enhanced 0.5 mM Ca2+ 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+, however, this effect disappeared. In the distal tubules, intravesicular GTPγs increased 0.5 mM Ca2+ 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+. The action of GTPγs, when present, was dose dependent with a half-maximal effect at 20 µM. The distal luminal membrane is the site of two Ca2+ channels with different kinetics parameters. GTPγs increased the Vmax value of the low-affinity component exclusively, in the presence as in the absence of Na+. Finally, Ca2+ 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 Ca2+ channels differs in the proximal and distal luminal membranes: Ca2+ channels present in the proximal tubule and the low-affinity Ca2+ channels present in the distal tubule membranes are directly regulated by Gs and Gi proteins respectively, whereas the high-affinity Ca2+ channel in the distal tubule membrane is insensitive to any of them.
Expression Pattern in a Modified Equalized Kidney cDNA Library of Hypertensive Rat
Authors: Chern Tser-Haw , Chiang Fu-Tien , Wu Kwan-Dun , Hsu Kwan-Lih , Lo Huey-Ming , Tseng Chuen-Den , Tseng Yung-Zu
Published: April 2003

Background: Genes with important functions and rarely expressed would probably more easily be cloned from a modified equalized kidney cDNA library for further investigation. Methods: A kidney cDNA library of a spontaneously hypertensive rat was synthesized by a modified equalization method. Inserts of random clones were amplified by PCR and sequenced. Sequences were compared against a nonredundant database in GenBank. The cDNA profile was compared with an expression profile of a mouse renal proximal tubule cDNA library. Seven clones were analyzed by Northern blot analysis. The cDNA ends of two novel genes were amplified by PCR, sequenced and analyzed. Results: 336 cDNA clones were analyzed and grouped into 323 species of transcript with 77 species similar to previously reported genes. Northern blot analysis identified one kidney-specific, one rarely expressed and lung-specific, and another relatively testis-specific gene. Two novel genes were cloned. One was 4.1 kb in length and encoded a 390-amino acid zinc-finger protein. Another was 2.5 kb and encoded a 474-amino acid protein of unknown function. Compared with the expression profile of a mouse renal proximal tubule cDNA library, this kidney library had a lower proportion of ribosomal genes and had a greater proportion of genes for signal transduction and DNA or RNA binding. Conclusions: Rare or novel genes could be more easily isolated from this library for molecular study of hypertension and renal pathophysiology.