bluuebunny/crossref_metadata_2025 huggingface dataset:
Relationship between Urinary Albumin Excretion and Glomerular Filtration Rate in Normotensive, Nonproteinuric Patients with Type 2 Diabetes mellitus
Authors: Taniwaki Hiromichi , Ishimura Eiji , Emoto Masanori , Kawagishi Takahiko , Matsumoto Naoki , Shoji Tetsuo , Okamura Terue , Inaba Masaaki , Nishizawa Yoshiki
Published: April 2003

Background/Aim: In patients with type 2 diabetes mellitus, the relationship between glomerular filtration rate (GFR) and urinary albumin excretion remains an unresolved issue. In order to investigate the early renal function abnormalities, GFR and urinary albumin excretion were assessed, and their relationship was examined in normotensive patients with type 2 diabetes mellitus. Methods: In a cross-sectional study of 85 nonhypertensive Japanese patients with type 2 diabetes mellitus not showing overt proteinuria, the GFR was measured using 99mTc-diethylenetriamine pentaacetate renography. Fifty-one diabetic patients lacked microalbuminuria (albumin excretion <30 mg/day), while 34 patients showed microalbuminuria (between 30 and 300 mg/day). Fifteen healthy subjects served as controls. Results: The three groups were well matched with regard to gender, age, and body mass index. The GFR in microalbuminuric patients (134 ± 23 ml/min/1.48 m2) was significantly higher than in patients without microalbuminuria (108 ± 21 ml/min/1.48 m2) and in controls (109 ± 18 ml/min/1.48 m2; p < 0.0001). In type 2 diabetic patients, the GFR positively correlated with the logarithmically transformed urinary albumin excretion. Multiple regression analysis showed that the urinary albumin excretion was significantly and independently affected by GFR (β = 0.548), duration of diabetes (β = 0.297), and systolic blood pressure (β = 0.232; R2 = 0.409; p < 0.0001). Conclusion: It is suggested that one of the mechanisms underlying increased urinary albumin excretion in early nephropathy in normotensive type 2 diabetes is glomerular hyperfiltration.
Diabetes mellitus Worsens Intrarenal Hemodynamic Abnormalities in Nondialyzed Patients with Chronic Renal Failure
Authors: Matsumoto Naoki , Ishimura Eiji , Taniwaki Hiromichi , Emoto Masanori , Shoji Tetsuo , Kawagishi Takahiko , Inaba Masaaki , Nishizawa Yoshiki
Published: April 2003

Duplex Doppler sonography has been reported to be useful in examining the intrarenal hemodynamic abnormalities in various renal diseases. We investigated the impact of diabetes on intrarenal hemodynamics in patients with chronic renal failure (CRF). The resistive index and pulsatility index of the renal interlobar arteries were measured using duplex Doppler sonography in 90 CRF patients (serum creatinine >130 and <800 mmol/l, mean age 59 ± 11 years). Forty-eight patients had type 2 diabetes and 42 did not. Twenty-nine age-matched, healthy subjects served as controls. Both resistive index and pulsatility index were greater in CRF patients than in the controls (p < 0.0001). No significant differences existed in age, sex, body mass index, total serum cholesterol, serum creatinine, estimated creatinine clearance, or mean blood pressure between the diabetic CRF and nondiabetic CRF groups. Resistive index and pulsatility index were significantly increased in the diabetic CRF patients compared to the nondiabetic CRF patients (p < 0.0001). Multiple regression analysis of all CRF patients revealed that resistive index was independently affected by the presence of type 2 diabetes (F = 44.535), as well as decreased creatinine clearance (F = 18.157) and age (F = 15.160) (R2 = 0.559, p < 0.0001). These results clearly demonstrated that intrarenal arterial resistance is significantly increased in CRF patients with type 2 diabetes compared to similar patients without diabetes. The impact of diabetes mellitus and advanced age on intrarenal hemodynamics may be due to intrarenal arteriosclerosis and interstitital lesions. Measurements of RI values in addition to conventional ultrasound imaging may add further information on such renal lesions.
Effects of Chronic Hypoxia on Renal PDGF-A, PDGF-B, and VEGF Gene Expression in Rats
Authors: Schweda Frank , Blumberg Friedrich C. , Schweda Annette , Nabel Caroline , Holmer Stephan R. , Riegger Günter A.J. , Pfeifer Michael , Krämer Bernhard K.
Published: April 2003

Background: There is evidence from in vitro studies to suggest that the genes of platelet-derived growth factor (PDGF), and vascular endothelial growth factor (VEGF) are, like the erythropoietin gene, regulated by oxygen tension. Hypoxia-induced stimulation of, for example, PDGF or VEGF might be involved in the pathogenesis of acute or chronic renal failure and in renal ‘inflammatory’ diseases (glomerulonephritis, vasculitis, allograft rejection). Methods: Male Wistar rats were exposed to chronic normobaric hypoxia (10% O2, 90% N2) for 4 weeks. Additional groups of rats were treated with the endothelin receptor antagonist LU13525 and the NO donor molsidomine. Renal mRNA levels of PDGF-A, PDGF-B, and VEGF were semiquantitated using RNase protection assays. Results: Renal gene expression of PDGF-A and PDGF-B was neither affected by 2 or 4 weeks of hypoxia nor by concomitant treatment with LU135252 or molsidomine. Chronic hypoxia did also not change VEGF gene expression; however, concomitant treatment with LU135252 increased all VEGF subtypes (188, 164, 120). Conclusions: The findings of the present study suggest that renal PDGF and VEGF gene expression in vivo during chronic hypoxia for 2 and 4 weeks is not sensitive to tissue hypoxia in contrast to cell culture experiments. During chronic hypoxia with concomitant blockade of endothelin receptors, all VEGF subtypes were increased, suggesting an inhibitory action of endothelins with regard to renal VEGF gene expression.
Investigation of the Localization of Dehydroepiandrosterone Sulphotransferase in Adult Rat Kidney
Authors: Aldred S. , Foster J.J.R. , Lock E.A. , Waring R.H.
Published: April 2003

Sulphotransferases are a family of enzymes involved in the metabolism and detoxification of many compounds. Dehydroepiandrosterone (DHEA) sulphotransferase (DHEA-ST), which catalyzes the sulphation of steroids such as DHEA, is present in rat liver and adrenals. Sulphated steroids are present in urine, and many other enzymes which catalyze detoxification reactions are found in the kidney. There are not previous reports of DHEA-ST localization in adult kidney. The activity of DHEA-ST was investigated in adult rat kidney by a radio-isotope assay with DHEA as the substrate. Western blotting was used to assess protein expression, and the localization of DHEA-ST was investigated by immunohistochemistry. The DHEA-ST activity in rat kidney was found to be approximately four times less than that in rat liver. In female kidney, the activity was 1.46 ± 0.06 nmol/min/µg, and in male kidney the activity was 1.29 ± 0.09 nmol/min/µg. Investigation of protein expression gave a single band at 35 kDa which signified the presence of this enzyme in both male and female adult rat kidneys. Localization studies showed positive staining at high intensity in the collecting ducts of the medulla and in the S3 portion of the proximal convoluted tubule in the cortex. The distribution within the proximal tubules was restricted to the brush border. Reverse-transcriptase polymerase chain reaction showed DHEA-ST RNA expression in adult rat kidney and liver. The presence of this enzyme and its location in the kidney may suggest that in situ sulphation via DHEA-ST may play an important role in the excretion of endogenous and exogenous compounds.
Effect of Dilazep Hydrochlorideon the Im munohistopathology of IgA Nephropathy in ddY Mice
Authors: Hayashi Takeshi , Kaneko Shougo , Thang Nguyen Tat , Shou Ichiyu , Shirato Isao , Tomino Yasuhiko
Published: April 2003

We determined the clinical and immunopathological effects of dilazep hydrochloride (dilazep) on IgA nephropathy of ddY mice. Group I (early-treatment group, n = 10) was orally treated with 300 mg/kg body weight of this drug from 12 weeks of age until 60 weeks of age, and group II (late-treatment group, n = 10) was also treated with the same dosage of this drug from 20 weeks of age until 60 weeks of age. Group III (control group, n = 10) received drinking water. On immunofluorescence, distribution and intensity of IgA and C3 depositions in glomeruli of group I and group II animals were significantly decreased as compared with those in group III. The expression of fibronectin, laminin, or type IV collagen in glomeruli was basically similar in the three groups treated with or without dilazep. On light microscopy, the expansion of glomerular mesangial areas and the average number of intraglomerular cells were markedly decreased as compared with those in group III. The levels of urinary protein excretion in groups I and II were significantly lower than those in group III (p < 0.01 and p < 0.05). These findings suggest that treatment with dilazep might improve the clinical and immunopathological findings in IgA nephropathy of ddY mice.
Survival of Balkan Endemic Nephropathy Patients
Authors: Bukvić Danica , Janković Slavenka , Ðukanović Ljubica , Marinković Jelena
Published: April 2003

The retrospective cohort study comprised 97 Balkan endemic nephropathy (BEN) and BEN-suspected patients discovered in 1971 in the field examination in the village of Šopić, one of the regions most frequently affected by the disease. Our aim was to determine the outcome of the disease in patients and to compare the survival of BEN-suspected and BEN-manifested patients and the survival of their kidneys. The mean survival time was 16.4 years for all patients (95% CI 14.51–18.21) and 23.1 years for suspected and 13.3 years for manifested patients (log-rank = 19.46; d.f. = 1; p < 0.001). According to our results, it can be concluded that BEN is characterized by slow course and prolonged evolution and that the prognosis was consistently better for BEN-suspected than for BEN-manifested patients.
Vasopressin and Diabetes mellitus
Authors: Bankir Lise , Bardoux Pascale , Ahloulay Mina
Published: April 2003

In diabetes mellitus (DM), the urine flow rate is increased, and the fluid turnover in the body is accelerated because of the glucose-induced osmotic diuresis. On the other hand, plasma vasopressin (VP) is elevated in both type 1 and type 2 DM. This elevation seems to be due to a resetting of the osmostat. A high VP level is beneficial in the short term because it limits to some extent the amount of water required for the excretion of a markedly enhanced load of osmoles (mainly glucose). However, in the long run, it may have adverse effects by favoring the developement of diabetic nephropathy. VP has been shown in normal rats to induce kidney hypertrophy, glomerular hyperfiltration, and an increase in urinary albumin excretion (features also occurring in association in the period preceding diabetic nephropathy). Moreover, VP has been shown to participate in the progression of renal failure in rats with five-sixths reduction in renal mass. In recent studies, we have shown (1) that creatinine clearance, albuminuria and renal mass increased much less during experimental DM in Brattleboro rats unable to secrete VP than in their VP-replete Long-Evans controls, and (2) that albuminuria was prevented during experimental DM in Wistar rats when a VP nonpeptidic, highly selective V2 receptor antagonist was administered chronically for 9 weeks. Taken together, these results strongly suggest that VP plays a crucial role in the onset and aggravation of the renal complications of DM. The mechanisms by which VP exerts these adverse V2-dependent effects are not yet elucidated. They are most likely indirect and may involve several intermediate steps comprising VP-induced changes in the composition of the tubular fluid in the loop of Henle (due to solute recycling in the renal medulla associated with improved concentrating activity of the kidney), inhibition of the tubuloglomerular feedback control of glomerular function, and alterations in glomerular hemodynamics by the intrarenal renin-angiotensin system.
Prognosis of Renal Amyloidosis: A Clinicopathological Study Using Cluster Analysis
Authors: Sasatomi Yoshie , Kiyoshi Yasuhiro , Uesugi Noriko , Hisano Satoshi , Takebayashi Shigeo
Published: April 2003

Progression of renal amyloidosis is associated with severe proteinuria or nephrotic syndrome, and various mechanisms have been postulated to explain these complications. We studied the acceleration of proteinuria and reduced renal function by cluster analysis using clinical parameters, renal histological findings, type of renal amyloidosis and follow-up data. We divided 97 cases into three groups of renal amyloidosis. Accelerated progression correlated with serum creatinine (s-Cr) levels at renal biopsy and histological grade of renal damage by amyloid deposition (p < 0.0001). The most influential prognostic factors (s-Cr level ≧2.0 mg/dl) were tubulointerstitial and vascular damage induced by amyloid deposition at biopsy (odds ratio 96.9 and 69.2, respectively). In addition, we found amyloidosis type amyloid associated (AA) correlated with more amyloid-mediated vascular and tubulointerstitial damage than amyloidosis type amyloid light chain (AL) (p < 0.001, p < 0.01, respectively). Proteinuria and nephrotic syndrome were more severe in cases of amyloidosis AL than in amyloidosis AA (p = 0.076). In conclusion, less tubulointerstitial and vascular damage was caused by amyloid deposition; this was slowly progressive. Amyloid AA was detected in tubulointerstitial tissue and vessels more frequently than amyloid AL. Heavy proteinuria and/or nephrosis were not indicators of rapid progression.
Renal and Vascular Injury Induced by Exogenous Angiotensin II Is AT1 Receptor-Dependent
Authors: Lombardi Donna M. , Viswanathan Mohan , Vio Carlos P. , Saavedra Juan M. , Schwartz Stephen M. , Johnson Richard J.
Published: April 2003

Angiotensin II (Ang II) infusion in rats augments vascular injury in balloon-injured carotid arteries and induces marked vascular and tubulointerstitial injury in kidneys. We examined how the AT1 receptor is modulated and whether blockade of the receptor with losartan could prevent the phenotypic and cellular changes. We also examined the role of the local renin-angiotensin system (RAS) by examining the expression of angiotensin-converting enzyme (ACE) and the effect of treatment with the ACE inhibitor, ramipril. Ang II infusion resulted in systemic hypertension and accelerated intimal and medial thickening in balloon-injured carotid arteries. Renal injury was manifested by proteinuria, glomerular phenotypic changes (mesangial expression of α-actin and podocyte expression of desmin), and tubulointerstitial injury with the tubular upregulation of the macrophage-adhesive protein, osteopontin, the interstitial accumulation of macrophages and myofibroblasts, and the deposition of collagen types III and IV. Ang II infusion decreased AT1 receptor number in the renal interstitium but not in glomeruli. Losartan completely blocked the Ang II-mediated hypertension, proteinuria, and injury to both carotid and kidney. Ang II infusion was also associated with an increase in ACE protein in both the proximal tubular brush border as well as at interstitial sites of injury, but despite evidence for activation of the local RAS, treatment with ramipril was without effect. These studies demonstrate that the renal and vascular injury induced by Ang II infusion is mediated by the AT1 receptor despite downregulation of the receptor in the interstitium. In addition, although there is evidence for local RAS activation, the injury appears to be mediated solely by the exogenous Ang II.
Urinary Prostaglandin D Synthase (β-Trace) Excretion Increases in the Early Stage of Diabetes mellitus
Authors: Hirawa Nobuhito , Uehara Yoshio , Ikeda Toshio , Gomi Tomoko , Hamano Kumiko , Totsuka Yasuo , Yamakado Minoru , Takagi Masao , Eguchi Naomi , Oda Hiroshi , Seiki Kousuke , Nakajima Hiroshi , Urade Yoshihiro
Published: April 2003

Objective: Circulating levels of lipocalin-type prostaglandin D synthase (L-PGDS)/β-trace reportedly increase in renal failure as well as in cardiovascular injuries. We investigated the alterations of L-PGDS in urine and plasma in the early stage of type-2 diabetic patients. Method: Thirty-six type-2 diabetic patients and 29 normal subjects were studied. Overnight spot urine and plasma samples were obtained in the morning. L-PGDS was measured by ELISA method using anti-L-PGDS antibody. Variables indicating renal function were determined. Results: Plasma L-PGDS concentration was slightly higher in the patients with diabetes mellitus than in the control subjects, whereas the urinary L-PGDS excretion almost doubled in the diabetic patients as compared with that in the control subjects. Plasma L-PGDS was determined by plasma creatinine (Cr) concentration while urinary L-PGDS excretion was correlated solely with urinary protein excretion. There was no relationship between plasma L-PGDS concentration and urinary L-PGDS excretion. The averaged plasma concentration of L-PGDS in the diabetics with a normal Cr level in plasma, corresponding to that in the controls, was determined by the plasma Cr concentration. On the other hand, the urinary L-PGDS excretion was determined by the amount of proteinuria and greater in the diabetics with a normal Cr level in plasma than in the controls even when the patients exhibited urinary protein excretion equal to that in the control subjects. Conclusions: Urinary L-PGDS excretion increased in the early stage of kidney injury in patients with type-2 diabetes mellitus. The urinary excretion was correlated independently with urinary protein excretion even when there was no difference in urinary protein or albumin excretions, thereby suggesting that urinary L-PGDS excretion is possibly a more sensitive indicator of renal injuries than proteinuria. Urinary L-PGDS may thus predict the progression of renal injuries in diabetic patients.
Virological and Histological Responses to One Year Alpha-Interferon-2a in Hemodialyzed Patients with Chronic Hepatitis C
Authors: Hanrotel Catherine , Toupance Olivier , Lavaud Sylvie , Thiefin Gérard , Brodard Véronique , Ingrand Didier , Diebold Marie-Danièle , Wynckel Alain , Chanard Jacques
Published: April 2003

Background: α-Interferon-2a (IFNα) alone is a therapy of limited proven benefit for non-uremic patients with chronic hepatitis C virus (HCV) infection. In dialyzed patients, such an effect is suggested on small short-term studies without sufficient clinical and virologic follow-up to document any sustained effect. Protocol: Twelve chronically hemodialyzed patients with chronic hepatitis C and waiting for renal transplantation were included in a prospective open study of treatment with IFNα. We used, as did others, doses of 3 million units (MU), three times a week, but for a longer period of treatment of 12 months. Follow-up was continued for 6 months after the end of IFNα in order to document any sustained biochemical, virological and histological responses. Results: Aminotransferase levels returned to the normal range within 1–2 months of treatment in all patients in whom they had been elevated at baseline. At 1 month of treatment, serum HCV-RNA was not detected in 5 (41%) patients and in 9 (75%) at 12 months. A sustained virological response was documented in 4 (33%) patients 6 months after the end of treatment. Relapse occurred in 5 patients within 2 months after IFNα withdrawal. HCV genotype was not predictive of any sustained response. At inclusion, using the histologic Metavir scoring system, half of the patients had low-grade cytolytic activity and none had cirrhosis. After IFNα, liver biopsy specimens were available from 9 patients and showed histologic improvement in 3. IFNα tolerance was poor, inducing a 5% mean weight loss and the acute rejection of two nonfunctioning kidney grafts. Conclusion: This study documents that administration of IFNα at 3 MU three times a week, for 12 months, in hemodialysis patients with chronic hepatitis C was efficient for clearing the serum of HCV-RNA in 75% of the patients. A sustained response was maintained in one third of these patients after cessation of IFNα, and was predicted by the early serum clearance of the virus within the first 2 months of treatment. We confirm that a 12-month treatment period carries a higher sustained response rate than shorter treatment periods. These encouraging results call for larger studies in uremic patients, using IFNα alone or in association with new antiviral drugs.
Studies on Calcium Oxalate Binding Proteins: Effect of Lipid Peroxidation
Authors: Selvam Ramasamy , Kalaiselvi Periandavan
Published: April 2003

Objective: Urolithiasis and free radicals have long been associated. In this study, we have isolated calcium oxalate monohydrate (COM) binding proteins from rat kidney before and after lipid peroxidation (LPO) and studied its properties on calcium oxalate crystal growth. Materials and Methods: LPO was carried out using t-butyl hydroperoxide, cumene hydroperoxide and an ascorbate system. The COM binding proteins from control and peroxidised tissues were isolated using a modified procedure. Protein was extracted using 25 mM EDTA, and the extract was loaded onto a DEAE cellulose column and eluted with Tris-HCl buffer (pH 6.5), 0.05 M NaCl in the above buffer and 0.3 M NaCl in the same buffer. Three major protein fractions were obtained, and they were designated as fractions I, II and III according to their order of elution. The proteins were subjected to calcium oxalate crystal nucleation and aggregation. Results: A positive correlation was observed between LPO and COM adsorption, while a negative correlation was observed between reduced glutathione and COM adsorption. Peroxidised protein did not show any alteration in the elution profile on the DEAE cellulose column. The –SH content of the peroxidised fractions were lower than that of the control fractions, but their oxalate binding activities were increased. Peroxidised fraction I promoted crystal growth to a greater extent than the control fraction I. Peroxidised fractions II and III were less inhibitory in nature compared to their control fractions. Light-microscopic examination of the crystals formed in the presence of the peroxidised fractions showed the formation of large aggregates of COM. Conclusion: Peroxidation of the renal proteins favoured their adsorption to COM crystals. –SH depletion increased the oxalate binding activity and also their affinity to the COM crystals. The peroxidised fraction I was found to favour the formation of large aggregates, suggesting that peroxidation may be one of the mechanisms altering the crystal inhibitory activity of the proteins in hyperoxaluria.
Membranoproliferative Glomerulonephritis Associated with Hypocomplementemic Urticarial Vasculitis after Complete Remission of Membranous Nephropathy
Authors: Saeki Takako , Ueno Mitsuhiro , Shimada Hisaki , Nishi Shinichi , Imai Naoshi , Miyamura Shouji , Gejou Fumitake , Arakawa Masaaki
Published: April 2003

A 49-year-old-man developed proteinuria in 1978. He was diagnosed as having membranous nephropathy by renal biopsy and was treated with prednisolone. The proteinuria disappeared completely and the treatment was stopped. In 1995, after complete remission, he developed nephrotic syndrome with chronic urticaria and hypocomplementemia. Renal biopsy revealed membranoproliferative glomerulonephritis (type I) and skin biopsy showed leukocytoclastic vasculitis, which was compatible with hypocomplementemic vasculitis syndrome. Steroid therapy was very effective.
Evaluation of i-STAT Creatinine Assay
Authors: Gault M. Henry , Seymour M. Elizabeth , Howell Wanda E.
Published: April 2003

Background: We evaluated a new, 2-min blood creatinine method using the hand-held i-STAT analyzer. Good results have already been reported using this analyzer for 10 methods including electrolytes, TCO2, pH, PCO2, bicarbonate, glucose, hemoglobin and urea for uremic blood, hemodialysate and peritoneal effluent. Methods: Evaluation included study of imprecision and accuracy. Results: Imprecision studies gave excellent results, including those for reproducibility of 6 solutions with a mean of 10 repeats and coefficients of variation (CVs) of 0.4–3.4%, and also the mean of the differences between 33 duplicate blood specimens which was 2.2% of the specimen mean. To assess accuracy, we compared results of 149 tests by i-STAT and Beckman Synchron CX7 methods. The difference between the two means was 2.6% and the mean of all differences was 10.9% with i-STAT results higher, especially when blood creatinine values were <100 µmol/l (1.1 mg/dl) indicating the need for a slightly higher upper limit of the normal range. The correlation coefficient between the two methods was 0.99, the slope 1.0 and the intercept –5.0 µmol/l (–0.06 mg/dl). We assessed the recommended creatinine correction for variation in PCO2 above and below 40 mm Hg, but our results did not suggest the need for such a correction in our range of 27–64 mm Hg; omission would remove a major method disadvantage. Assays of hemodialysate and peritoneal effluent were also satisfactory. Conclusions: The i-STAT creatinine method is simple and rapid and our evaluation showed satisfactory accuracy and precision. However, results were on average slightly higher than for the Beckman Synchron CX7 method.
Up-Regulated TGF-β mRNA Expression in Splenic T Cells of High IgA-Prone Mice: A Murine Model of IgA Nephropathy with Glomerulosclerosis
Authors: Oyama Atsushi , Muso Eri , Ono Takahiko , Matsushima Hiroyuki , Yashiro Masatomo , Suyama Katsuo , Kamata Tadashi , Nogaki Fumiaki , Kobayashi Ikei , Miyawaki Shigeki , Yoshida Haruyoshi , Sasayama Shigetake
Published: April 2003

Background/Aims: Recently, we established a high serum IgA-prone inbred (HIGA) mouse strain as a murine model of spontaneous IgA nephropathy by selective mating of high serum IgA ddY mice, and found that they showed enhanced production of glomerular extracellular matrix components with increased expression of TGF-β mRNA and protein in the kidneys. In this study, we examined the roles of lymphocytes in the development of high serum IgA in this strain. Methods: We performed flow cytometric analyses of T and B cells in splenic mononuclear cells (SMNCs) from these mice using BALB/c mice as normal controls. We also compared serum TGF-β1 concentrations and TGF-β mRNA expression levels in the B-cell-depleted (T-cell-rich) fraction of SMNCs in these mice. Results: HIGA mice showed significantly fewer CD3-positive cells compared with BALB/c mice when young, but not when aged. The CD4/CD8 ratio of HIGA mice was lower than that of BALB/c mice, but this difference was not significant. Although the number of B220-positive cells did not vary significantly, the ratio of surface IgA-positive B cells was significantly increased in both young and adult HIGA mice. The B-cell-depleted SMNCs from HIGA mice exhibited higher levels of expression of TGF-β and TGF-β1 mRNA than controls from a young age, which were maintained throughout life, but there were no differences in PDGF, MCP-1 or bFGF expression between these two strains. In contrast to local mRNA expression, serum TGF-β1 concentration was decreased in HIGA mice compared with BALB/c controls. Conclusion: These findings suggest that the mating procedure performed to establish HIGA mice selected for a unique phenotype of local up-regulation of TGF-β production in the kidneys, as well as T cells that may contribute to both the early and consistently high serum IgA expression and enhanced production of renal extracellular matrix components in HIGA mice. Additionally, TGF-β1 may act locally, not systemically, in a paracrine or autocrine manner.
Pharmacokinetics of Cetirizine in Chronic Hemodialysis Patients: Multiple-Dose Study
Authors: Noiri Eisei , Ozawa Hisashi , Fujita Toshiro , Nakao Akihide
Published: April 2003

The serum concentration-time profiles of cetirizine were measured in 8 male end-stage renal failure (ESRF) patients on chronic hemodialysis (HD). Cetirizine (5 mg) was ingested three times a week during the predialysis period. Blood samples were drawn for basal level evaluation, before and after dialysis on 3 days per week, and before HD the following week. The serum levels of cetirizine were measured using a validated atmospheric-pressure ionization liquid chromatography-tandem mass spectrometry method. Basal levels of cetirizine in HD patients were confirmed to be 0 ng/ml. The predialysis levels of cetirizine on days 1, 3, 5, and 8 were (mean ± SD) 2.74 ± 7.76, 34.16 ± 21.55, 35.58 ± 13.43, and 22.47 ± 12.92 ng/ml, respectively. The postdialysis levels of cetirizine 4–5 h after ingestion were as follows (ng/ml): day 1, 103.11 ± 37.27; day 3, 131.34 ± 51.18, and day 5, 136.48 ± 48.72. Between dialysis sessions, no supplemental dosage was required to keep the therapeutic range of 14 ng/ml. In addition, the predialysis levels on day 8 were not statistically different from the basal levels. Evidence from the multiple-dose study supports the clinical use of cetirizine for ESRF patients on HD. Thus, it is concluded that a prescription of 5 mg cetirizine three times a week during the predialysis period will be the effective and safety renal dosage for ESRD patients on HD.
The Risk of Renal Stone Formation during and after Long Duration Space Flight
Authors: Whitson Peggy A. , Pietrzyk Robert A. , Morukov Boris V. , Sams Clarence F.
Published: April 2003

Background: The formation of a renal stone during space flight may have serious negative effects on the health of the crewmember and the success of the mission. Urinary biochemical factors and the influence of dietary factors associated with renal stone development were assessed during long duration Mir Space Station missions. Methods: Twenty-four-hour urine samples were collected prior to, during and following long duration space flight. The relative urinary supersaturation of calcium oxalate, calcium phosphate (brushite), sodium urate, struvite and uric acid were determined. Results: Changes in the urinary biochemistry of crewmembers during long duration spaceflight demonstrated increases in the supersaturation of the stone-forming salts. In-flight hypercalciuria was evident in a number of individual crewmembers and 24-hour dietary fluid intake and urine volume were significantly lower. During flight, there was a significant increase in brushite supersaturation. Conclusions: These data suggest acute effects of space flight and postflight changes in the urinary biochemistry favoring increased crystallization in the urine. The effects of dietary intake, especially fluid intake, may have a significant impact on the potential for renal stone formation. Efforts are now underway to assess the efficacy of a countermeasure to mitigate the increased risk.
Parathyroidectomy in Chronic Renal Failure: Has Medical Care Reduced the Need for Surgery?
Authors: Cohen Eric P. , Moulder John E.
Published: April 2003

Subtotal or total parathyroidectomy is sometimes required for the management of severe secondary or tertiary hyperparathyroidism. Advances in medical and dialysis care may have a beneficial effect on hyperphosphatemia and vitamin D status, which could, in turn, reduce the need for parathyroidectomy. We used the United States Renal Data System to test this hypothesis. We found that the percentage of prevalent end-stage renal disease patients undergoing subtotal or total parathyroidectomy has declined significantly from 1988 to 1998. It is likely that improved medical and dialysis care has enabled this result.
Associations of Micro-Albuminuria with Intra-Uterine Growth Retardation
Authors: Yudkin John S. , Martyn Christopher N. , Phillips David I.W. , Gale Catherine R.
Published: April 2003

Background/Aim: Micro-albuminuria is associated with insulin resistance and a high blood pressure and predicts an increased risk of cardiovascular disease in both diabetic and non-diabetic populations. Relationships have been described for micro-albuminuria with both low birth weight and short stature in adulthood. We have tested the hypothesis that micro-albuminuria in non-diabetic adults may be associated with markers of intra-uterine growth retardation. Methods: We measured the urinary albumin excretion rate in 818 men and women from three populations, in whom detailed records of birth weight were available, of whom 354 had records of length at birth to provide an estimate of the ponderal index. Results: The albumin excretion rates were higher in men than in women (5.1 vs. 3.8 µg/min) and were related to age (r = 0.23, p < 0.001) and body mass index (r = 0.08, p = 0.02) as well as fasting plasma glucose and blood pressure. Considered as a continuous variable, the albumin excretion rate was not related to any measure of size at birth or to adult height. Fifty-four subjects (6.6%) were micro-albuminuric (albumin excretion rate ≧ 20 µg/ min), and these subjects were thinner at birth than normo-albuminuric subjects (12.9 vs. 13.8 oz/in3, p = 0.09). Compared to those subjects whose ponderal index had been in the upper third of the distribution, people whose ponderal index had been in the lower third of the distribution had an odds ratio for micro-albuminuria of 3.1 (p for trend 0.05). Conclusion: The association between micro-albuminuria, insulin resistance, and coronary heart disease may be a consequence of growth retardation representing a common antecedent.
Management of Hyperinsulinemia with Diazoxide in an Elderly Hemodialysis Patient
Authors: Shaer Andrea J.
Published: April 2003

An elderly, nondiabetic, chronic hemodialysis patient is described here who had profound hypoglycemia for a myriad of reasons including renal failure, malnutrition, and quinine use. Furthermore, by biochemical parameters the patient had hyperinsulinemia, which was consistent with the diagnosis of an insulinoma. However, a tumor was not identified by noninvasive radiologic imaging as is often the case and the patient was not a candidate for surgical exploration. Diazoxide at a dose of 225 mg/day was used to successfully manage this patient’s hypoglycemia. Previous experience with the use of diazoxide for hyperinsulinism in the hemodialysis population is limited and this case is the second report of its use for this purpose.
Sodium and Fluid Modulation in Dialysis: New Approach
Authors: Splendiani G. , Costanzi S. , Passalacqua S. , Fulignati P. , Sturniolo A.
Published: April 2003

Hypotension during hemodialysis is still an unsolved problem. The treatment of patients with cardiovascular instability is efficaciously carried out with the use of ‘profiled dialysis’ (PD) with computerized modulation of ultrafiltration and conductivity. We tested a new profile model which involves progressive decrease of ultrafiltration associated with variable conductivity (‘bell pattern’). We observed 8 stable long-term patients receiving hemodialysis (4 men and 4 women, mean age 63.5 years) for 4 h three times a week. Before our test, sodium balance had reached a steady state in all patients and remained stable during the entire observation period. The sodium balance was established by means of a simple pattern suggested by Ursino and coworkers. The patients were observed for two periods of 1 month each (protocols A and B). The intradialytic mean arterial pressure was studied, checking every hour of dialysis. Statistical analysis was done by ANOVA for repeated measures. We compared standard dialysis with constant ultrafiltration rate and conductivity (protocol A) with sessions performed involving a progressive decrease of ultrafiltration together with a variable conductivity of –0.2, +0.2, +0.6, +0.6, 0, –0.4, –0.4, and –0.4 mS/s (protocol B). We found a lower incidence of hypotension (p < 0.01) with better cardiovascular stability during and after treatment in ‘profiled dialysis’.
Prolonged Dietary Calcium Restriction: A Diagnostic Approach in Idiopathic Hypercalciuria
Authors: Müller Dominik , Eggert Paul
Published: April 2003

Background: Although frequently observed, the etiology of idiopathic hypercalciuria (IHC) remains largely unknown. A common hypothesis postulates intestinal hyperabsorption and/or a primary renal leak as the pathophysiological basis. The aim of our study was to investigate the regulation pattern of calcium homeostasis in patients with IHC by using a prolonged period of calcium restriction. Methods: Twenty-seven patients with IHC were investigated. After a 3-week run-in period (dietary calcium content 700–1,000 mg/24 h), a standard calcium reduced diet (300 mg/24 h) was given for 4 weeks. Thereafter, the participants received again a normal calcium-containing diet. Values for urinary calcium, PTH and calcitriol levels of all participants were obtained at different phases of the study. Forty-three healthy persons served as controls. Results: During calcium restriction, two distinct groups were identified. One group displayed an increase (n = 12) in urinary calcium excretion, the second (n = 15) a marked reduction, respectively. In both groups, the values during calcium restriction were significantly different from baseline (p < 0.01). In the first group, the increase of urinary calcium excretion was accompanied by an increase of PTH and calcitriol. These values were also significantly different from baseline values (p < 0.01). The control group showed decreasing calcium excretion during oral restriction (p < 0.01). Conclusion: Prolonged calcium restriction proved to be useful in distinguishing apparently two major forms of IHC. The fact that one group displayed the same excretion pattern as the control group raises the question if this group just represents the upper limit of a physiological range. These findings may shed new light on diagnosis, pathogenesis and treatment of patients with IHC.
Localization and Roles of CD44, Hyaluronic Acid and Osteopontin in IgA Nephropathy
Authors: Sano Nami , Kitazawa Kozo , Sugisaki Tetsuzo
Published: April 2003

An important function of CD44 is to act as a cellular receptor for hyaluronic acid and osteopontin. Cell-matrix interactions mediated by the CD44/hyaluronic acid receptor-ligand pair are involved in the regulation of leukocyte migration and activation. Osteopontin is a molecule associated with cell adhesion and migration and functions through binding to CD44. This study examined whether CD44, hyaluronic acid and osteopontin participate in the progression of IgA nephropathy. CD44 was expressed in mesangial cells, crescents, tubular cells and interstitial infiltrating cells in areas of tubulointerstitial injury. Hyaluronic acid was deposited in the capillary tuft of adhesion, crescents and the periglomerular area, and around damaged tubules. Osteopontin was expressed in tubular cells and interstitial infiltrating cells in areas of tubulointerstitial injury. The glomerular and interstitial deposition of hyaluronic acid correlated with the glomerular and interstitial expression of CD44. The interstitial expression of CD44 correlated with the interstitial expression of osteopontin. The expression of both CD44 and osteopontin in the interstitium correlated with the extent of tubulointerstitial damage. The expression of CD44 in the interstitium correlated with the severity of chronic glomerular lesions. The glomerular and interstitial CD44 and hyaluronic acid expression correlated with proteinuria, and interstitial CD44 and hyaluronic acid expression correlated with creatinine clearance rate. In summary, this study suggests that CD44 participates in the progression of IgA nephropathy by binding hyaluronic acid and osteopontin.
Variant Frequency in Flap Production
Authors: Patterson David , Connine Cynthia M.
Published: April 2003

This study examined the distribution of allophonic variants [t], [I] or [U], of medial /t/ using a corpus of conversational speech. We utilized a large conversational speech database to generate statistics about the frequency of occurrence of medial flaps. Results confirmed the prevalence of flapping in American English. Low frequency words showed a redistribution of variants from [U] to [t] compared to dominant flapping in high frequency words. A similar redistribution of variant production occurred for morphologically complex words (e.g. dirty) compared with morphologically simple words (e.g. water). A second analysis examining vowel length prior to medial /t/ and medial /d/ showed that, while both stops were pronounced as a flap, the vowel preceding medial /d/ tended to the longer. These results were discussed in reference to potential processes in recognizing spoken words.
Embryonic Submandibular Gland Morphogenesis: Stage-Specific Protein Localization of FGFs, BMPs, Pax6 and Pax9 in Normal Mice and Abnormal SMG Phenotypes in FgfR2-IIIc+/Δ, BMP7–/– and Pax6–/–Mice
Authors: Jaskoll Tina , Zhou Yan Min , Chai Yang , Makarenkova Helen P. , Collinson J. Martin , West John D. , Hajihosseini Mohammad K. , Lee Jina , Melnick Michael
Published: April 2003

Embryonic submandibular salivary gland (SMG) initiation and branching morphogenesis are dependent on cell-cell communications between and within epithelium and mesenchyme. Such communications are typically mediated in other organs (teeth, lung, lacrimal glands) by growth factors in such a way as to translate autocrine, juxtacrine and paracrine signals into specific gene responses regulating cell division and histodifferentiation. Using Wnt1-Cre/R26R transgenic mice, we demonstrate that embryonic SMG mesenchyme is derived exclusively from cranial neural crest. This origin contrasts to that known for tooth mesenchyme, previously shown to be derived from both neural crest and nonneural crest cells. Thus, although both SMGs and teeth are mandibular derivatives, we can expect overlap and differences in the details of their early inductive interactions. In addition, since embryonic SMG branching morphogenesis is analogous to that seen in other branching organs, we also expect similarities of expression regarding those molecules known to be ubiquitous regulators of morphogenesis. In this study, we performed an analysis of the distribution of specific fibroblast growth factors (FGFs), FGF receptors, bone morphogenetic proteins (BMPs) and Pax transcription factors, previously shown to be important for tooth development and/or branching morphogenesis, from the time of initiation of embryonic SMG development until early branching morphogenesis. In addition, we report abnormal SMG phenotypes in FgfR2- IIIc+/Δ, BMP7–/–and Pax6–/– mice. Our results, in comparison with functional studies in other systems, suggest that FGF-2/FGFR-1, FGF-8/FGFR-2(IIIc) and FGF-10/FGFR-2(IIIb) signaling have different paracrine and juxtacrine functions during SMG initial bud formation and branching. Finally, our observations of abnormal SMGs in BMP7–/– and Pax6–/–indicate that both BMP7 and Pax6 play important roles during embryonic SMG branching morphogenesis.
Neurobrucellosis – A Rare Complication of Renal Transplantation
Authors: Yousif Bedri , Nelson Jeff
Published: April 2003

Brucellosis is an intracellular bacterial infection contracted by consuming raw milk or by contact with infected cattle. Neurobrucellosis is a rather rare manifestation of brucellosis and has protean clinical presentations characterized by meningoencephalitis, myelitis, myelopathies, subarachnoid hemorrhage and psychiatric manifestations. A depressed immune status is believed to be a risk factor for developing neurobrucellosis. We report a case of neurobrucellosis in a patient 13 years after a cadaveric renal transplantation. Even though a Brucella organism was not isolated from body fluids she satisfied other criteria for establishing the diagnosis. Treatment with doxycycline and rifampin led to a clinical cure as well as to marked improvement in the Brucella titer.
Short-Term Small-Dose Intravenous Iron Trial to Detect Functional Iron Deficiency in Dialysis Patients
Authors: Lin Ja-Liang , Chang Ming-Yang , Tan Dan-Tzu , Leu Mei-Ling
Published: April 2003

Background/Aim: Management of renal anemia in end-stage renal disease requires careful evaluation of the iron status before and in particular during erythropoietin treatment. However, there is no simple and practical iron index accurately predictive of functional iron deficiency in these patients till now. The purpose of this prospective study, therefore, is to evaluate whether a short course of low-dose intravenous iron challenge can detect functional iron deficiency in hemodialysis patients. Methods: Twenty-four patients with baseline serum ferritin levels between 100 and 500 ng/ml were treated with intravenous saccharated ferric oxide, 960 mg over 24 hemodialysis treatments, and the hemoglobin level was checked every week. Results: Patients whose hemoglobin value increased at least by 1 g/dl within the 8-week period were classified as having functional iron deficiency or as responders (n = 26; 81.2%). All other subjects were classified as having adequate iron levels or as nonresponders (n = 6; 18.8%). There were no significant differences in age, sex, dialysis years, Kt/V, dialyzers, hemoglobin, and basal and final trasferrin saturation and ferritin between responders and nonresponders. In addition, there were no iron indices with acceptable levels of sensitivity and specificity. On the contrary, the cutoff value of increments of hemoglobin of at least 0.2 g/dl after a 2-week intravenous iron trial had a sensitivity of 96.2% and a specificity of 100% in all patients (n = 32) and a sensitivity of 100% and a specificity of 100% after patients with transferrin saturation <20% were excluded (n = 24). These values had the greatest utility of the tests studied in this work. Conclusion: A 240-mg intravenous iron challenge during a 2-week period may be a simple, accurate, and straightforward method to detect a functional iron deficiency status in hemodialysis patients undergoing erythropoietin therapy.
Parathyroid Hormone-Related Protein as a Renal Regulating Factor
Authors: Esbrit Pedro , Santos Soledad , Ortega Arantxa , Fernández-Agulló Teresa , Vélez Esperanza , Troya Soraya , Garrido Pedro , Peña Antonio , Bover Jordi , Bosch Ricardo J.
Published: April 2003

Parathyroid hormone (PTH) and PTH-related protein (PTHrP) produce similar biological effects through the PTH/PTHrP receptor. Less is known about the physiological role of PTHrP, which was first identified as the agent of the humoral hypercalcemia of malignancy. Despite the widespread production of PTHrP in healthy individuals, the concentration of the protein is below the detectable limit of current assays, suggesting that PTHrP normally functions locally in an autocrine or paracrine manner. Thus, some differences in their biological activities have been described and they may be related to the presence of different receptors. In this regard, a second receptor that binds selectively to PTH has also been found. Recent studies have demonstrated the expression of both PTH/PTHrP receptor and protein in the renal glomeruli. Moreover, there are convincing data that support a direct role of PTH and PTHrP in modulating renal blood flow and glomerular filtration rate. This multifunctional protein, PTHrP, also has a proliferative effect on both glomerular mesangial cells and tubular epithelial cells. Increases in the expression of PTHrP have been observed in several experimental models of nephropathies, suggesting that PTHrP upregulation is a common event associated with the mechanism of renal injury and repair.