bluuebunny/crossref_metadata_2025 huggingface dataset:
No Association between Deletion-Type Angiotensin-Converting Enzyme Gene Polymorphism and Left-Ventricular Hypertrophy in Hemodialysis Patients
Authors: Yildiz Alaattin , Akkaya Vakur , Hatemi Ali Can , Çine Naci , Tükek Tufan , Görçin Bilal , Demirel Şeref , Türk Süleyman , Sever Mehmet S.
Published: April 2003

Left-ventricular hypertrophy (LVH), a bad prognostic sign, is a common finding in hemodialysis patients. The aim of the study was to analyze factors, including angiotensin-converting enzyme (ACE) genotype that may have an effect on the development of LVH in hemodialysis patients. Seventy-nine hemodialysis patients (42 males, 37 females, mean age 37.7 ± 13.1 years) and 82 age- and sex-matched normotensive healthy controls (40 males, 42 females, mean age 35.6 ± 5.7 years) were included. Left-ventricular mass index (LVMI) was higher in the hemodialysis group compared to controls (170.1 ± 69.3 versus 84.9 ± 15.7 g/m2, p < 0.001). Fourty-three hypertensive patients in the hemodialysis group had an increased LVMI compared to 36 normotensive hemodialysis patients (194.2 ± 75.5 versus 141.2 ± 48.0 g/m2, p < 0.001). On univariate analysis, LVMI was found to be correlated with blood pressure (r = 0.38, p < 0.001), time spent on dialysis (r = 0.22, p = 0.02) and hemoglobin levels (r = –0.21, p = 0.03). No correlation was found between LVMI and age (r = 0.09, p = 0.22), predialytic creatinine (r = 0.09, p = 0.21) and albumin (r = –0.10, p = 0.18). On multivariate analysis for the predictors of LVMI, blood pressure, time spent on dialysis and hemoglobin levels were also found to be significant. LVMI in DD, ID and II genotypes were 155.0 ± 71.2, 181.6 ± 60.6, and 163.6 ± 83.4 g/m2, respectively (p > 0.05). No association between LVMI and DD genotype was found. ACE genotype distribution was similar in hemodialysis patients and healthy controls. It was concluded that LVH in hemodialysis patients was mainly related to hypertension, anemia and time spent on dialysis and the DD genotype had no effect on LVMI in hemodialysis patients.
Renal Findings and Glomerular Pathology in Diabetic Subjects
Authors: Wirta Ole , Helin Heikki , Mustonen Jukka , Kuittinen Elina , Savela Tero , Pasternack Amos
Published: April 2003

Background: To describe the relationship between proteinuria, hematuria, and renal insufficiency, on one hand, and glomerular pathology, on the other hand, in a consecutive biopsy series of diabetic patients. Subjects and Methods: All diabetic subjects (n = 200) biopsied from 1979 to 1995 at Tampere University Hospital were identified in retrospect. The clinician-based indication (any unexplained renal finding) for renal biopsy was consistent during the years and was: proteinuria alone in 68%; combined with hematuria in 10%; with renal insufficiency in 10%; with both in 9%, and with isolated hematuria or renal failure in 3%. One third of the subjects had proteinuria of ≧3 g/24 h and 16% a serum creatinine level of ≧200 µM. Glomerulopathy was found in 171 specimens and defined as nodular diabetic (group A), diffuse diabetic (group B) and primary (group C). The 24-hour urinary protein excretion rate [mean (range)] was 3.5 (1.6–6.9), 1.0 (0.5–3.5), and 3.6 (1.1–6.6) g in groups A, B and C, respectively (ANOVA p = 0.001). The corresponding serum creatinine values [mean (SD)] were 175 (115), 105 (142) and 169 (138) µM (p = 0.001). Results: Nodular diabetic glomerulopathy was found in 40%, diffuse diabetic glomerulopathy in 42% and primary glomerulopathy in 18%. A primary glomerulopathy was found in any indication and in both types of diabetes (prevalence range 14–26%). The best multivariate logistic regression model obtained (χ2 = 13.5, p = 0.008) in predicting the presence of diabetic glomerulosclerosis (group A + B) in contrast to a primary glomerulopathy (group C) included retinopathy (p = 0.04), renal insufficiency (p = 0.03), hematuria (p = 0.12) and type of diabetes (p = 0.10). Conclusion: In this series of diabetic subjects, biopsied due to proteinuria, hematuria and not severe renal insufficiency, 18% had evidence of a primary glomerulopathy.
Effects of Potassium Citrate/Citric Acid Intake in a Mouse Model of Polycystic Kidney Disease
Authors: Tanner George A. , Vijayalakshmi Kodi , Tanner Judith A.
Published: April 2003

The kidney function in a model of autosomal dominant polycystic kidney disease (PKD), the Han:SPRD rat, is dramatically improved by chronic ingestion of a solution of potassium citrate and citric acid (KCitr). This study investigated whether this treatment would also be beneficial in the pcy/pcy mouse, a model of autosomal recessive PKD. Starting at 1 month of age, male CD-1 pcy/pcy and normal CD-1 mice were provided with a solution of 55 mM K3 citrate/67 mM citric acid or tap water to drink. The pcy/pcy mice on the KCitr solution failed to grow normally and showed elevated plasma urea levels when compared to water-drinking littermates. Growth of normal CD-1 mice was not affected by KCitr intake. The pcy/pcy mice were then provided with a more dilute solution of KCitr to drink: this resulted in greater kidney wet and dry weights and a higher kidney weight/body weight ratio, but no beneficial effects. We conclude that pcy/pcy mice cannot tolerate a high level of KCitr intake and that a lower level is of no benefit. Whether KCitr therapy would be helpful in patients with PKD is still an open question.
Cytomegalovirus Infection in a Seroendemic Renal Transplant Population: A Longitudinal Study of Virological Markers
Authors: Rao M. , Finny G.J. , Abraham P. , Juneja R. , Thomas P.P. , Jacob C.K. , Sridharan G.
Published: April 2003

Background/Aims: The detection of viremia by polymerase chain reaction (PCR) in cytomegalovirus (CMV) infection in renal allograft recipients has been shown to have a predictive value for disease. However, its diagnostic utility in a population with high background seropositivity has not been defined. This prospective study was undertaken to assess the relationship of CMV DNAemia, and/or IgM seropositivity to CMV disease in a seroendemic transplant population. Methods: Consecutive patients undergoing renal transplantation between August 1997 and February 1998 were enrolled. Blood was sampled before transplantation from the donors and recipients for CMV serology and nested PCR for CMV DNA, and after transplantation from the recipients only at monthly intervals until 6 months. Patients were observed for the development of any CMV-like illness during follow-up. CMV DNA was quantitated using limiting dilution PCR on samples obtained from symptomatic patients at the time of illness and from asymptomatic patients at the end of their 6-month follow-up. Results: A total of 57 recipient-donor pairs were recruited. Immunosuppression was cyclosporine-based in 55 of 57 (95.6%). The CMV serologic status was D+R+ in 55 of 57 and D+R– in 2 of 57 pairs. PCR positivity indicating viremia increased from 5% before transplantation to 95% at 6 months after transplantation. Similarly IgM positivity reached 80% at 3 months and thereafter; positivity for any marker was 100% by 6 months. Viremia was sustained in over half the patients. The incidence of CMV-attributable disease peaked at 3 months, and was predominantly mild and self-limiting. Tissue-invasive disease appeared later in 4 patients (7%). Asymptomatic viremia was seen in 60–70% of patients at each sampling point. The positive predictive value (PPV) of PCR positivity for disease was 35–40%, and the negative predictive value (NPV), 90–100%. However, the high NPV was of use only in the early post-transplant period, negativity for markers declining rapidly with time. Quantitative assay showed significantly higher levels of CMV DNA in symptomatic patients (p = 0.01). A cutoff of 0.001 µg had a specificity of 95% and a PPV of 92.3% for symptomatic CMV disease. Conclusion: Qualitative tests to detect CMV DNAemia and IgM, although useful markers of viremia and active infection, have limited utility for the diagnosis of disease in a seroendemic transplant population. Quantitation of CMV DNAemia may play an important role in diagnosis in such a setting.
Kidney Disease and Silicosis
Authors: Rosenman K.D. , Moore-Fuller M. , Reilly M.J.
Published: April 2003

Aim: To determine the prevalence of kidney disease in a cohort of individuals with silicosis. Methods: Review of medical records and questionnaires from patients reported to a state surveillance system for silicosis. Reporting of individuals with silicosis is required by state law. All individuals with silicosis reported as required by law to the State of Michigan. Individuals included in this article were reported from 1987 to 1995. Cases were reported by hospitals, physicians, the state workers’ compensation bureau, or from death certificates. Only individuals who met the criteria for silicosis developed by the National Institute for Occupational Safety and Health (NIOSH) were included. Results: Medical records were reviewed of 583 individuals with confirmed silicosis. This was mainly a population of elderly men. Ten percent of the 583 silicotics were found to have some mention of chronic kidney disease, and 33% of the 283 silicotics who we had laboratory tests on had a serum creatinine level >1.5 mg/dl. An association between kidney disease and age and between kidney disease and race was found among this cohort of 583 silicotics. Individuals with silicosis were more likely to have a serum creatinine level >1.5 mg/dl than age- and race-matched controls. However, no relationship between duration of exposure to silica or profusion of scarring on chest X-ray and prevalence of kidney disease or elevated creatinine levels was found. Conclusions: This study confirms previous case reports and epidemiologic studies of end-stage renal disease that found an association between kidney disease and exposure to silica. The epidemiologic data are conflicting on the mechanism by which silica causes kidney disease and are compatible with silica being able to cause kidney disease by both an autoimmune and direct nephrotoxic effect. Chronic kidney disease should be considered as a complication of silicosis.
An Increased Serum Level of Free Apo(a) in Renal Patients Is More Striking than that of Lp(a) and Is Influenced by Homocysteine
Authors: Herrmann Wolfgang , Quast Sabine , Ellgass Astrid , Wolter Kai , Kiessig Stefan T. , Molinari Ewald , Riegel Werner
Published: April 2003

Lipoprotein(a) [Lp(a)] excess combined with hyperhomocysteinaemia and hyperfibrinogenaemia may contribute to the high incidence of vascular diseases in dialysis patients. This study is aimed at investigating the role of free apolipoprotein(a) [fapo(a)] in renal patients. We have been able to show that, as compared with controls (0.53 mg/l), the median serum concentrations of fapo(a) in patients with nephrotic syndrome (2.58 mg/l) and with peritoneal dialysis (3.40 mg/l) were strongly elevated (5- to 7-fold), while the fapo(a) levels in patients undergoing haemodialyis (1.02 mg/l) and after renal transplantation (0.90 mg/l) were about doubled. The observed differences in fapo(a) levels indicate that several mechanisms may increase the level of fapo(a), i.e., reduced renal clearance, enhanced hepatic synthesis, or homocysteine releasing apolipoprotein(a) from Lp(a). In the study collective, the median total homocysteine levels were significantly elevated in all patient groups, stronger in patients on haemodialysis (31.4 µmol/l) and peritoneal dialysis (31.2 µmol/l) than in patients with nephrotic syndrome (19.7 µmol/l) and after renal transplantation (19.5 µmol/l). In transplant patients with adequate renal function and without other apolipoprotein(a)-increasing factors, fapo(a) was significantly increased when total homocysteine exceeded 22 µmol/l. In conclusion, our findings let us presume that an increased fapo(a) level in renal patients possibly could be one of the reasons contributing to the high incidence of vascular diseases in these patients, because fapo(a) not covalently linked with Lp(a) is even more easily able to inhibit the fibrinolytic system than the complete Lp(a). These preliminary results have to be confirmed by further investigations.
Fas-Fas Ligand System in the Peripheral Blood of Patients with Renal Diseases
Authors: Sato Masashi , Konuma Takako , Yanagisawa Naoki , Haizuka Hisatoshi , Asakura Hiroshi , Nakashima Yutaka
Published: April 2003

To clarify the role of the Fas-Fas ligand (FasL) system in the peripheral blood from patients with various renal diseases, the Fas and FasL expression on mononuclear cells (MNCs) and serum levels of soluble Fas (sFas) and soluble FasL were investigated. Patients were selected from those with various types of glomerular diseases showing various degrees of renal function. Fas expression on MNCs was analyzed by a FACScan, sFas and soluble FasL were measured with an ELISA kit, and FasL expression on MNCs was counted using a FACScan after a bioassay. Fas-positive MNCs and sFas increased with statistical significance concomitantly with deterioration in renal function. Moreover, there was a significant correlation between them. sFas- and FasL-positive MNCs were significantly correlated with proteinuria. However, the Fas expression percentage on MNCs and/or serum levels of sFas did not correlate with the number of TUNEL-positive cells in the glomeruli. Also, there was no disease specificity in the activation of Fas. These results indicate that Fas expression on MNCs is activated in accordance with the deterioration in renal function without disease specificity, corresponding to the elevation of serum sFas levels to protect against Fas-mediated apoptosis.
Hemodialysis-Induced Degranulation of Polymorphonuclear Cells: No Correlation between Membrane Markers and Degranulation Products
Authors: Grooteman M.P.C. , van Tellingen A. , van Houte A.J. , Bos J.C. , Schoorl M. , van Limbeek J. , Nubé M.J.
Published: April 2003

Background/Aims: Degranulation of polymorphonuclear leukocytes (PMN) during hemodialysis (HD) is usually assessed by measuring degranulation products. However, this process might also be estimated by the assessment of cell surface markers. In this study, the relationship between the expression of PMN degranulation markers (CD63 and CD66b) and the release of degranulation products [myeloperoxidase (MPO) and lactoferrin (LF)] was investigated during clinical HD in order to evaluate cell surface markers as a useful index of PMN degranulation. Methods: The expression of CD63 and CD66b on PMN and the release of MPO and LF were investigated in 10 chronic HD patients, during both heparin (HDhep) and trisodium citrate anticoagulation (HDcit), in a randomized order. Samples were drawn from both the efferent and afferent lines of the dialyzer at 0, 7.5, and 180 min. Results: During HDhep at first passage, a major increase in MPO (from 158 ± 32 to 448 ± 177 µg/l, p = 0.001) and LF (from 134 ± 52 to 260 ± 120 µg/l, p = 0.01) was found across the dialyzer, whereas marked changes were not observed during HDcit. The expression of CD63 and CD66b increased across the dialyzer during both anticoagulation modalities, but was only significant in the case of HDhep (CD63: mean fluorescence intensity from 247 ± 61 to 331 ± 118, p < 0.01; CD66b: mean fluorescence intensity from 340 ± 76 to 434 ± 103, p = 0.01). During HDhep a correlation was noted between the degranulation products and markers of both azurophilic and specific granules (MPO and CD63: r = 0.35; p < 0.01; LF and CD66b: r = 0.39, p < 0.01). Significant differences in the expression of CD63 and CD66b between HDhep and HDcit were not observed. When analyzing the combined data for both HDhep and HDcit, no correlation was observed between degranulation products and markers. Conclusion: Our data suggest that the measurements of cell surface markers may not be a reliable indicator of the degree of HD-induced PMN degranulation.
How to Improve Survival in Pre-Dialysis Patients
Authors: Macdougall Iain C.
Published: April 2003

Aims: This survey was performed to determine how anaemia in pre-dialysis patients is currently managed. Methods: A random sample of 200 nephrologists attending the 1999 ERA/EDTA Congress participated in an interactive survey session. Participants were questioned on their current prescribing attitudes and preferences, and asked to select a preferred answer from a number of alternatives by means of an electronic key-pad. Results: Three quarters of the audience treated their pre-dialysis patients with erythropoietin. However, approximately 50% treated ≤10% of patients and only 8% of respondents treated ≧75%. In addition, more than half of the respondents said that very few of their patients currently self-administer erythropoietin. Increased healthcare expenditure was the main reason given for limiting treatment. Conclusions: The survey highlighted important gaps in long-term treatment strategies for pre-dialysis patients. It indicated that new approaches to the treatment of renal anaemia are needed to minimise disease progression and to prevent cardiac dysfunction and associated mortality. Erythropoietin has already been shown to significantly improve the survival of dialysis patients with renal anaemia, and new strategies might, therefore, include the prevention of anaemia in pre-dialysis patients by earlier initiation of erythropoietin therapy.
Long-Term Knowledge Retention following Predialysis Psychoeducational Intervention
Authors: Devins Gerald M. , Hollomby David J. , Barré Paul E. , Mandin Henry , Taub Kenneth , Paul Leendert C. , Guttmann Ronald , Binik Yitzchak M.
Published: April 2003

Background/Aims: Early identification and predialysis psychoeducation are gaining acceptance. Although research supports the immediate value of predialysis interventions, long-term benefits remain unknown. We examined long-term knowledge retention following a psychoeducational intervention. Methods: 47 progressive renal failure patients completed the Kidney Disease Questionnaire at baseline and 18, 30, 42, and 54 months after initiating renal replacement therapy (RRT; the ‘longitudinal’ sample). A larger cohort provided data at one or more of these points (n = 132, 117, 101, and 70 at 18, 30, 42, and 54 months, respectively; the ‘cross-sectional’ sample). Results: Initial knowledge gains among psychoeducation recipients were followed by a significant knowledge advantage for three groups throughout follow-up. Patients who received predialysis psychoeducation either before or after starting dialysis demonstrated superior Kidney Disease Questionnaire scores as compared with those identified before the initiation of RRT who received the usual standard of practice. Patients identified after the initiation of RRT and who received standard education, however, demonstrated the same level of knowledge retention as produced by psychoeducation. The results were identical across the longitudinal and cross-sectional samples. Conclusions: Patient education produces important benefits in end-stage renal disease, but the incremental value of early intervention remains to be demonstrated.
Decreased Matrix Metalloproteinase Activity in the Kidneys of Hereditary Nephrotic Mice (ICGN Strain)
Authors: Uchio Kozue , Manabe Noboru , Tamura Kotaro , Miyamoto Makoto , Yamaguchi Misuzu , Ogura Atsuo , Yamamoto Yoshie , Miyamoto Hajime
Published: April 2003

Abnormalities of extracellular matrix (ECM) metabolism, i.e., overproduction and/or inhibition of ECM breakdown, may contribute to progression of fibrotic degeneration in the kidney. Earlier studies revealed that major ECM components, type I, III, and IV collagens, etc., were accumulated in glomeruli and tubulointerstitium in kidneys of Institute of Cancer Research (ICR) derived glomerulonephritis (ICGN) mice which are a novel inbred strain of mice with a hereditary nephrotic syndrome of unknown etiology and are considered to be a good model of human idiopathic nephrotic syndrome. In the present study, we compared the activities of matrix metalloproteinases (MMPs), a family of enzymes that degrade ECM components, in the kidneys of aged ICGN mice and age-matched ICR mice as normal controls. We biochemically measured interstitial collagenase (MMP-1), gelatinase (MMP-2 and MMP-9), and stromelysin (MMP-3) activities in the kidney tissues. Lower activities of MMP-1 and MMP-2 and MMP-9 were demonstrated in the kidneys of ICGN mice as compared with those of ICR mice, but there were no significant differences in the MMP-3 activities between these strains. These results show that decreased MMP activities cause abnormal accumulation of ECM in ICGN mouse kidneys.
Benidipine, a Long-Acting Calcium-Channel Blocker, Prevents the Progression to End-Stage Renal Failure in a Rat Mesangioproliferative Glomerulonephritis
Authors: Nakamura Takamichi , Obata Jun-ei , Onitsuka Makoto , Shimada Yuji , Yoshida Yoji , Kawachi Hiroshi , Shimizu Fujio
Published: April 2003

Background: Although the renoprotective effect of calcium-channel blockers (CCBs) has been examined in several models of hypertensive nephropathy, it remains unclear. It also remains to be clarified whether CCBs prevent the progression to end-stage renal failure in chronic progressive glomerulonephritis (GN). A new rat model of progressive mesangioproliferative GN was used to study the effect of benidipine hydrochloride, a long-acting dihydropyridine CCB, on the clinical features and morphological lesions. Methods: This animal model of progressive GN was induced by a single intravenous injection of anti-Thy-1 monoclonal antibody (MoAb 1-22-3) two weeks after unilateral nephrectomy. After 10 weeks of treatment with benidipine (1, 3, and 5 mg/kg body weight, p.o.) or hydralazine (5 mg/kg body weight, p.o.), systolic blood pressure (SBP), urinary protein excretion, creatinine clearance, glomerulosclerosis index, tubulointerstitial lesion index, glomerular cross-sectional area, and glomerular expression of transforming growth factor-β (TGF-β) and α-smooth muscle actin (α-SMA) were measured. Results: Untreated rats developed hypertension, massive proteinuria, renal dysfunction, severe glomerular and tubulointerstitial injury, higher glomerular size, and marked glomerular staining for TGF-β and α-SMA, while uninephrectomized control rats did not. Each dose of benidipine and hydralazine equally reduced SBP to uninephrectomized control levels. Three and five mg/kg/day of benidipine increased creatinine clearance, ameliorated glomerular and tubulointerstitial injury, and reduced glomerular staining for TGF-β and α-SMA, but 1 mg/kg/day of benidipine and hydralazine failed. Only a dose of 5 mg/kg/day of benidipine reduced glomerular size, although it did not reduce the size to control levels. Conclusion: These results indicate that in a rat model of progressive mesangioproliferative GN, benidipine prevents the progression to end-stage renal failure in a dose-dependent manner. This renoprotective action is associated with the suppression of glomerular expression of TGF-β and α-SMA.
Influence of Calcium on Regulatory Volume Decrease: Role of Potassium Channels
Authors: Pasantes-Morales H. , Morales Mulia S.
Published: April 2003

In most cell types, hyposmotic swelling consistently elicits an increase in the concentration of cytosolic Ca2+ – [Ca2+]i – with contributions of extracellular and intracellular sources. The mechanisms of Ca2+ entry and release from endogenous sources are not fully clarified and may be cell specific. The ubiquity of the swelling-evoked [Ca2+]i rise makes Ca2+ a likely candidate for a role as osmotransducing signal. However, the regulatory volume decrease (RVD) which follows swelling and the osmolyte fluxes involved in this process are not always Ca2+ dependent. It was found that, with a few exceptions, in most cell types the osmosensitive Cl– efflux pathway and the swelling-activated organic osmolyte fluxes are Ca2+ independent. In contrast, Ca2+-dependent or Ca2+-independent K+ fluxes activated by swelling are detected, depending on the cell type. The close correlation found in this review between the Ca2+ dependence of RVD and that of the K+ channels activated by swelling led to the conclusion that it is the type of osmosensitive K+ pathway which largely confers the Ca2+ dependence to RVD. Interestingly, this coincidence of Ca2+-dependent K+ efflux and RVD is found predominantly in epithelial cells, whereas in nonepithelial cells both processes are largely Ca2+ independent. In these cells, the [Ca2+]i rise elicited by swelling may be an epiphenomenon.
Cytokine Gene Expression in Adriamycin Nephropathy: Effects of Antioxidant Nuclear Factor κB Inhibitors in Established Disease
Authors: Rangan Gopala K. , Wang Yiping , Tay Yuet-Ching , Harris David C.H.
Published: April 2003

Background/Aim: Inhibition of nuclear factor ĸB with the antioxidant pyrrolidine dithiocarbamate (PDTC) reduced tubulointerstitial injury in Adriamycin nephropathy (AN), whereas N-acetylcysteine (NAC) was ineffective. Here we hypothesize that PDTC reduces the renal cortical expression of nuclear factor ĸB dependent cytokines in AN. Methods: Male Wistar rats received a single intravenous injection of doxorubicin hydrochloride (7.5 mg/kg). NAC (150 mg/kg twice daily i.p.), PDTC (50 mg/kg twice daily i.p.), or vehicle were commenced on day 14 and continued until day 30. Results: On day 30, mRNAs of selected cytokines were increased in AN (TNF-α 3.4-fold, MCP-1 5.1-fold, IL-10 2.7-fold, TGF-β1 3.5-fold, all p < 0.05) as determined by RT-PCR. PDTC reduced IL-10 and TGF-β1 mRNAs (p < 0.05), whereas the upregulation of MCP-1 and TNF-α mRNAs was not affected. In contrast, NAC increased TNF-α and IL-10 mRNAs (p < 0.05). Nuclear protein levels of activator protein-1 were increased in AN (4.4-fold, p < 0.01) and not significantly altered by PDTC (3.0-fold, p = 0.13) or NAC (5.2-fold, p = 0.18). Conclusions: The protective effects of PDTC in AN are not associated with a local reduction in TNF-α and MCP-1 gene expression. The latter may be due to continued transactivation by activator protein-1. These data also suggest that IL-10 and TGF-β1 mRNA expressions are PDTC dependent and have a role in mediating tubulointerstitial injury.
Peritonitis Increases MMP-9 Activity in Peritoneal Effluent from CAPD Patients
Authors: Fukudome Keiichi , Fujimoto Shouichi , Sato Yuji , Hisanaga Shuichi , Eto Tanenao
Published: April 2003

Patients undergoing long-term continuous ambulatory peritoneal dialysis (CAPD) sometimes experience ultrafiltration failure. Mesothelial basement membrane thickening and the accumulation of submesothelial fibrotic tissue are common features of the diseased peritoneum. Peritonitis can lead to ultrafiltration failure, but the precise mechanism is not clear. The key enzymes in extracellular matrix (ECM) remodeling, namely matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs), are produced by human peritoneal mesothelial cells. Using peritoneal effluent from 13 CAPD patients with peritonitis and 7 noninfected CAPD control individuals, we examined MMP and TIMP activities by gelatin and reverse zymography. Latent and activated types of MMP-2 and -9, and TIMP-1 and -2 were identified in peritoneal effluent (from all CAPD patients). Levels of latent and activated type MMP-9, as well as of TIMP-1 activities were higher at the onset of peritonitis than either during the recovery phase of peritonitis and/ or in control individuals. Activated MMP-9 activity positively correlated with leukocyte numbers and IL-6 levels in peritoneal effluent. Activities of MMP-2 and TIMP-2 in peritoneal effluent did not change between the onset of peritonitis and recovery. We concluded that increased MMP-9 and TIMP-1 levels might be associated with peritoneal ECM remodeling during peritonitis.
Acute Respiratory Failure due to ‘Pulmonary Calciphylaxis’ in a Maintenance Haemodialysis Patient
Authors: Matsuo Takatoshi , Tsukamoto Yusuke , Tamura Masato , Hanaoka Masato , Nagaoka Takashi , Kobayashi Yutaka , Higashihara Masaaki , Yokoyama Hiroyuki , Saegusa Nobuo
Published: April 2003

Calciphylaxis is a rapidly developing, fatal process of vascular calcium deposition with prominent cutaneous manifestation. We treated a long-term haemodialysis patient who developed an analogous disorder limited to the lungs. A 57-year-old man was admitted for initiation of peritoneal dialysis because limited cardiac reserve precluded further haemodialysis. He was treated successfully for pneumonia until hypoxia and progressive hypercalcaemia developed. 99mTc-methylene disphosphonate scintigraphy showed diffusely increased pulmonary uptake. Death supervened despite aggressive and successful treatment of hypercalcaemia. Autopsy studies included immunohistochemistry and morphometric studies of bone. Alveolar capillary walls showed diffuse calcium deposition. Both gross and microscopical findings differed from those of typical metastatic calcification in dialysis patients. Immunoreactivity for parathyroid hormone-related protein was present in the lesions. Bone histomorphometry indicated mild osteitis fibrosa. Pneumonia is believed to have caused local synthesis of parathyroid hormone-related protein that, along with high calcium × phosphorus product, contributed to calcium deposition. By analogy with the cutaneous process we termed the deposition ‘pulmonary calciphylaxis’.
Primary Hyperoxaluria Type 1 Causing End-Stage Renal Disease in a 45-Year-Old Patient
Authors: David-Walek T. , Niederstadt C. , Rob P.M. , Fricke L. , Latta K. , Steinhoff J. , Stange E.F.
Published: April 2003

Primary hyperoxaluria type 1 (PH1) is caused by deficiency of peroxisomal alanine-glyoxylate aminotransferase which is in humans exclusively expressed in liver cells. The disease is inherited as an autosomal recessive trait, and initial symptoms usually occur in early childhood. Up to the age of 25 years, 90% of the patients are symptomatic, and many patients develop end-stage renal failure. Pronounced medical care is necessary in PH1 patients to prevent generalized oxalosis with complications due to bone disease and peripheral gangrene. The rather short survival of patients on hemodialysis is caused by sudden arrhythmias and heart block. As no dialysis procedure is able to remove the daily produced oxalate, early transplantation is mandatory. Our 45-year-old patient is remarkable on the basis of the late manifestations of PH1. The diagnosis was delayed by unspecific symptoms of nephrolithiasis with recurrent pyelonephritis. Clinical course and diagnostic cornerstones of primary hyperoxaluria are outlined. The principles of conservative treatment and experiences with dialysis and transplantation are discussed.
Serum Uric Acid and Renal Prognosis in Patients with IgA Nephropathy
Authors: Ohno Iwao , Hosoya Tatsuo , Gomi Hideho , Ichida Kimiyoshi , Okabe Hideaki , Hikita Miho
Published: April 2003

Background/Aims: This study was designed to elucidate the clinical significance of serum uric acid (SUA) and the relationship between hyperuricemia and renal prognosis in IgA nepropathy. Methods: The correlation between SUA and other clinical parameters were examined in 748 IgA nephropathy patients (432 males and 316 females). Among these patients, 226 (144 males and 82 females) who were followed for more than 5 years were examined for the relationship between hyperuricemia and renal prognosis. Results: In IgA nephropathy, SUA correlated negatively with creatinine clearance (Ccr), and positively with urinary protein and tubulointerstitial damage. SUA was higher in patients with hypertension or diffuse proliferative glomerulonephritis. Hyperuricemia was a risk factor for renal prognosis, both in terms of serum creatinine (p = 0.0025) and Ccr (p = 0.0057). In 56 patients with normal Ccr at renal biopsy, the change of Ccr after more than 8 years was –22.3 ± 20.8% in 13 patients with hyperuricemia, compared with +2.6 ± 39.4% in 43 patients without hyperuricemia (p = 0.0238). Hyperuricemia was related independently to deterioration of Ccr (p = 0.0461). Conclusion: Hyperuricemia in IgA nephropathy is derived from both glomerular and tubulointerstitial damage, and correlated with hypertension. Hyperuricemia is a risk factor for renal prognosis in IgA nephropathy.
De novo Fibrillary Glomerulopathy in the Renal Allograft of a Patient with Systemic Lupus erythematosus
Authors: Isaac Jorge , Herrara Guillermo A. , Shihab Fuad S.
Published: April 2003

Lupus glomerulonephritis is a complication of systemic lupus erythematosus, with 10% of the patients developing end-stage renal disease. It is accepted that lupus patients are good candidates for kidney transplantation and that the disease activity is subdued after transplantation due to rigorous immunosuppression, with a low rate of graft loss due to recurrent glomerulonephritis. While recurrent fibrillary glomerulopathy has been reported in renal allografts, de novo disease has not. We report a patient with systemic lupus who underwent a renal transplantation and subsequently lost her allograft due to de novo fibrillary glomerulopathy. Four years after her first kidney transplant, the patient presented with acute deterioration of her renal function. A renal biopsy was performed, and it revealed a focal mesangioproliferative pattern with positive amorphous mesangial immunofluorescence staining for IgG and C3. Congo red staining was negative. Electron microscopy demonstrated the presence of randomly oriented nonamyloid fibrils in the mesangiun. The diagnosis of de novo fibrillary glomerulopathy was made. The patient lost her allograft and received a second cadaveric renal transplant 1 year later. She has had a stable renal function since then.
An Intron 4 Gene Polymorphism in Endothelial Cell Nitric Oxide Synthase Might Modulate Lipid Metabolism in Nondiabetic Patients on Hemodialysis
Authors: Asanuma Katsuhiko , Yokoyama Keitaro , Tsukada Toshihiko , Takemoto Fumi , Hara Shigeko , Yamada Akira , Tomino Yasuhiko
Published: April 2003

We investigated the relationship between endothelial constitutive nitric oxide synthase (ecNOS) gene polymorphism and lipid metabolism in patients with nondiabetic chronic renal failure on hemodialysis. Serum from 181 nondiabetic patients on hemodialysis were examined. A genomic DNA fragment was amplified by polymerase chain reaction (PCR) for determining the ecNOS genotype. The PCR products were designated as a and b alleles by electrophoresis. In hemodialysis patients, the frequency of the ecNOS4 for b/b, b/a and a/a genotype was 76.6, 22.8 and 0.6%, respectively. There was not significant difference in the levels of total cholesterol (TC), triglyceride (TG) and calculated low-density lipoprotein cholesterol (LDL-c) in sera between patients (aa and ba) with the a allele and patients (bb) without the a allele. On the other hand, the levels of serum high-density lipoprotein cholesterol (HDL-c) in patients with the a allele (51.9 ± 3.33 mg/dl) were significantly higher than those in patients without the a allele (43.05 ± 1.40 mg/dl) (p = 0.005). The frequency of patients with the a allele and low levels of serum HDL-c among patients with a long duration of dialysis (≧10 years) was significantly lower than that in patients with short duration of dialysis (<10 years) (p = 0.05). It appears that an intron 4 gene polymorphism in ecNOS may modulate lipid metabolism in nondiabetic patients on hemodialysis and the a allele of ecNOS gene polymorphism may affect the prognosis of hemodialysis patients with low levels of serum HDL-c.
Onset, Time Course, and Persistence of Increased Haemodialysis-Induced Breath Isoprene Emission
Authors: Trovarelli Gianfranco , Brunori Federica , De Medio Gianna Evelina , Timio Mario , Lippi Giorgio , Pelli Maria Antonietta , Capodicasa Enrico
Published: April 2003

Recent findings of increased isoprene emission in the exhaled breath of patients undergoing haemodialysis and experimental evidence of the potential toxic and cancerogenic effects of isoprene hydrocarbon led us to assess how long haemodialysis patients are exposed to how much isoprene after a single haemodialysis session. Patients with end-stage renal failure on regular 4-hour (from 08.00 to 12.00 h) maintenance haemodialysis three times weekly were monitored. The breath isoprene content was analyzed by gas chromatography. Intrapatient evaluations were performed by collecting samples before, during, and immediately after the haemodialysis session, during the following hours, and on the following nondialysis day. The breath isoprene content increased in all patients. Isoprene overproduction showing a biphasic pattern was first detected soon after the dialysis session ended. These data show that haemodialyzed patients seem to be consistently exposed to high endogenous isoprene concentrations. The mechanisms and implications of this endogenous isoprene overproduction need to be elucidated with regard to the mevalonic pathway and in the physiopathological setting of the uraemia-dialysis syndrome.
Evidence for Alterations in Circulating Low-Molecular-Weight Antioxidants and Increased Lipid Peroxidation in Smokers on Hemodialysis
Authors: Lim Paik-Seong , Wang Nan-Phong , Lu Tien-Chen , Wang Tsung-Hsiu , Hsu Wei-Ming , Chan Elsie C. , Hung Wang-Ru , Yang Chiu-Chin , Kuo I-Fang , Wei Yau-Huei
Published: April 2003

Background/Aim: Cardiovascular disease is the major cause of mortality in dialysis patients, accounting for about 40% of deaths in most large registries. Oxidative stress has been strongly implicated in the pathogenesis of these events. As end-stage renal disease is a state of elevated free radical activity, the aim of the present study was to investigate the negative impact of smoking in 57 male hemodialysis patients. Methods: The patients, who were 20–85 years of age (mean age 51.0 ± 14 years), had been on hemodialysis for at least 6 months before participating in this study. Fasting blood sampling for serum lipid, albumin, urate and lipophilic antioxidants such as tocopherols, carotenes, ascorbate and lipid peroxides was performed. Results: The plasma malondialdehyde (MDA) concentration was significantly higher in hemodialysis patients who smoked compared to hemodialysis patients who were nonsmokers (1.92 ± 0.52 vs. 1.59 ± 0.42 nmol/ml, p = 0.006). No association was found between levels of MDA in smokers and parameters such as body mass index, serum cholesterol, serum triglycerides and smoking index. There were no significant differences in the plasma levels of uric acid, α-tocopherol, γ-tocopherol, δ-tocopherol, α-carotene, β-carotene and retinol between the two groups. A significantly lower level of plasma ascorbate was observed in hemodialysis patients who smoked compared to the nonsmoking hemodialysis patients or healthy controls (4.59 ± 4.0 vs. 9.57 ± 4.0 and 10.16 ± 4.6 µg/ml, p < 0.05). Moreover, in smokers, the plasma levels of ascorbate were negatively correlated with the levels of plasma MDA (r = –0.43, p < 0.001) of each patient. Partial correlation analysis of the plasma levels of the measured antioxidants and the smoking index revealed a negative correlation between the plasma levels of lipid-normalized lycopene and the smoking index (r = –0.53, p < 0.05). Conclusion: Our data suggest that cigarette smoking further increases plasma-circulating products of lipid peroxidation, which are already increased in nonsmoking hemodialysis patients as compared to matched healthy controls. The lower plasma levels of ascorbate in hemodialysis patients who smoke suggest that these patients may be more susceptible to oxidative tissue damage caused by smoking.
The Complement System in Renal Diseases
Authors: Welch Thomas R.
Published: April 2003

The complement system has long been recognized as having a role in immune glomerular disease. This review provides an update on this association, some strategies for the clinical testing of complement in disease, and a brief commentary on current research directions. Evidence of complement activation in glomerulonephritis comes from characteristic patterns of a decrease in the serum concentrations of specific components, some of which are virtually diagnostic of certain nephritides. These patterns are often accompanied by the presence of complement components in the glomeruli and the detection of complement breakdown products in the circulation. In certain diseases, circulating complement-activating substances can be detected. Although there are over 20 complement proteins, clinical analysis is most often directed at C3 and C4, with occasional measurement of B and C5. Recently, a variety of mechanisms for complement-induced injury has been recognized. These mechanisms go far beyond simple passive lysis of erythrocytes, the earliest functional effect of complement studied. The role of such mechanisms in renal disease is just beginning to be studied. Local synthesis of complement components in the kidney may play a role both in host defense and in the promotion of interstitial inflammation and scarring. Such mechanisms will likely be defined more precisely with the availability of animals with specific complement deficiencies. Ultimately, an understanding of the role of complement in renal disease may permit specific targeted inhibition of one or more complement functions as a form of therapy.
Suppression of Experimental Membranous Glomerulonephritis in Rats by an Anti-MHC Class II Antibody
Authors: Hasegawa Yoshiyuki , Kaneoka Hidetoshi , Tanaka Tomoichiro , Ogahara Satoru , Matsumae Tomoji , Noda Ritsuya , Yoshitake Keisuke , Murata Toshiaki , Naito Setsuya
Published: April 2003

Background: We previously reported that idiopathic membranous nephropathy (IMN) strongly correlated with HLA-DRB1*1501-DRB5*0101-DQAI*0102-DQB1* 0602, a specific haplotype of human major histocompatibility complex (MHC), in Japanese patients. To investigate the role of MHC in the development of rat Heymann nephritis (HN), an animal model of membranous nephropathy, a monoclonal antibody (mAb) specific to rat MHC class II antigen (RT1B) was administered, and its effectiveness in inhibiting HN was assessed. Methods: Active HN was induced in HN-sensitive Lewis rats by administering brush border proteins of rat proximal uriniferous tubules (FX1A). Rats were divided into four groups: rats treated with 1,000 µg anti-rat MHC class II mAb, rats treated with 100 µg anti-rat MHC class II mAb, rats treated with murine myeloma IgG, and rats that did not receive either FX1A or any other mAb. We examined the differences in 24-hour urinary protein excretion and serum alloantibody titers against FX1A between groups at different time intervals, and the histologic features of kidneys at the end of the study. Results: HN was induced in Lewis rats by inoculation with FX1A antigen. Administration of anti-MHC class II mAb successfully lowered urinary proteins, production of anti-FX1A alloantibodies, and the development of glomerular lesions in a dose-dependent manner. Conclusion: The present results demonstrated that the MHC class II molecule itself is directly involved in the pathogenesis of HN, and suggest that this therapy would be any better (or less toxic) than nonselective immunosuppressants in the treatment of IMN.
Remission Achieved in Chronic Nephropathy by a Multidrug Approach Targeted at Urinary Protein Excretion
Authors: Ruggenenti Piero , Brenner Barry M. , Remuzzi Giuseppe
Published: April 2003

Regardless of the pattern of renal involvement, increased urinary protein excretion rate is the best independent predictor of progression of chronic nephropathies and short-term reduction in proteinuria has been reported to be renoprotective in the long term. Despite such evidence, however, the therapeutic target in renoprotection is almost exclusively on blood pressure control. We report the clinical course of a patient with chronic nephropathy after the institution of a multidrug treatment titrated against urinary protein excretion to achieve renoprotection. The present findings indicate that adjusting renoprotective therapy according to the decline in protein excretion in a multidrug strategy may stabilize or even reverse renal disease progression. This approach should be formally explored in prospective studies.
Membranous Glomerulonephritis after Haematopoietic Cell Transplantation for Multiple Myeloma
Authors: Rossi Licia , Cardarelli Francesca , Vampa Maria L. , Buzio Carlo , Olivetti Giorgio
Published: April 2003

Renal involvement during graft-versus-host disease following haematopoietic cell transplantation for multiple myeloma has never been described. We report a case of a recipient who developed nephrotic syndrome and membranous glomerulonephritis 22 months after the graft and 6 months after cyclosporine withdrawal. Symptoms resolved when immunosuppressive therapy was reinstituted.
Hypocomplementemic Type II Membranoproliferative Glomerulonephritis in a Male Patient with Familial Lecithin-Cholesterol Acyltransferase Deficiency due to Two Different Allelic Mutations
Authors: Sessa Adalberto , Battini Graziana , Meroni Mietta , Daidone Giuseppe , Carnera Ida , Brambilla Pier Luigi , Viganò Giovanni , Giordano Ferdinando , Pallotti Francesco , Torri Tarelli Laura , Calabresi Laura , Rolleri Marina , Bertolini Stefano
Published: April 2003

Patients with familial lecithin-cholesterol acyltransferase (LCAT) deficiency very often show progressive glomerulosclerosis with evolution to end-stage disease. High levels of an abnormal lipoprotein (lipoprotein X) cause glomerular capillary endothelial damage. The ultrastructural study of renal biopsy specimens shows characteristic glomerular deposits of membrane-like, cross-striated structures and vacuole structures. The gene encoding for LCAT has been mapped to chromosome 16q22.1, and several mutations of this gene cause LCAT deficiency which is inherited as an autosomal recessive trait and which is characterized by corneal opacities, normochromic normocytic anemia, and renal dysfunction. Herein we report clinical features and renal histological findings concerning a 24-year-old male patient with classical familial LCAT deficiency due to two different allelic mutations: a nonsense mutation inherited from the father and a missense mutation inherited from the mother. Moreover, the patient showed glomerular histological lesions and an immunofluorescent glomerular pattern typical of hypocomplementemic membranoproliferative type II glomerulonephritis (dense-deposit disease). The nature of electron-dense material that characterizes dense-deposit disease is still unkwown, but there are suggestions that some chemical modifications might occur in the renal basement membranes. Therefore, this clinical case might induce to consider possible relations between disorders of the lipoprotein metabolism and renal dense-deposit disease.
mRNA Expression of the IGF System in the Kidney of the Hypersomatotropic Rat
Authors: Hise Michael K. , Salmanullah Muhammad , Tannenbaum Gloria S. , Rohan Richard M.
Published: April 2003

Aim: To examine the response of the insulinlike growth factor (IGF) system in the kidney during a state of extreme growth. Methods: We studied the mRNA expression of IGF-I, IGF-I receptor, and IGF-binding proteins (BP) using sensitive RNase protection assays following subcutaneous implantation of growth hormone pituitary cells (GH3) in rats. Results: Within 5 weeks, the serum GH levels increased from 18.0 ± (SE) 5.0 ng/ml in control animals to 389.8 ± 30.3 ng/ml in GH3 rats (n = 5, p < 0.001). The circulating IGF-I levels were also elevated. The kidney weights increased from 0.74 ± 0.01 g in controls to 1.06 ± 0.03 g in GH3 animals (n = 5, p < 0.001). Similar changes were observed at week 10. The renal IGF-I mRNA averaged 1.0 ± (SD) 0.33 relative densitometry units in controls (n = 4) and increased to 2.11 ± 0.13 relative densitometry units in GH3 rats (n = 5, p < 0.001). On the other hand, mRNA for the type I IGF receptor decreased in hypersomatotropic rats. Messenger RNAs for IGFBP-1 and IGFBP-4, which have been localized to renal tubules, both decreased significantly following growth induction, while IGFBP-3, the mRNA of which has an interstitial localization, was increased at week 10. Conclusion: These data suggest that there is a dynamic relationship between tubular and interstitial compartments with regard to the IGF system in the kidney which may be important in the regulation of the cell mass.