bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Colchicine on Chronic Ciclosporin Nephrotoxicity in Sprague-Dawley Rats
Authors: Sobh Mohamed , Sabry Alaa , Moustafa Fatma , Foda Mohamed A. , Sally Samir , Ghoneim Mohamed
Published: April 2003

Thirty male Sprague-Dawley rats were given ciclosporin (Cs) orally, 15 mg/kg daily for 80 days. Fifteen served as positive controls, while the other 15 were given daily colchicine at a dose of 30 µg/kg in addition to Cs. Additional 15 rats were given olive oil only and served as negative controls. The animals were subjected every other week to laboratory assessment of serum creatinine, sodium, potassium, and Cs whole-blood trough levels; also urine samples were examined for creatinine, sodium, potassium, and protein concentrations. At the end point, the animals were sacrificed, and kidney tissue was examined for histopathological changes. Comparing negative control versus Cs-treated and Cs-plus-colchicine-treated rats, there were no significant differences in serum creatinine, creatinine clearance, and serum and urine values of sodium and potassium as well as urinary protein/creatinine ratios. Yet histopathological examination of kidney tissues showed focal tubular atrophy and interstitial fibrosis in inner medulla and inner stripe of the outer medulla in all Cs-treated animals and in only 1 of the colchicine-treated group, but in none of the negative controls. Histological changes in other kidney zones in different animal groups were minor and not different. From this study, we may conclude that colchicine is of protective value against chronic Cs nephrotoxicity in Sprague-Dawley rats.
Resolution of Hepatitis B Viremia in a Renal Transplant Recipient Treated with Alpha-2b Interferon
Authors: Post Anthony B. , Hricik Donald E. , Sterling Richard K. , Bartucci Marilyn R. , Jacobs Gretta H. , Schulak James A.
Published: April 2003

A renal transplant patient developed symptomatic hepatitis after withdrawal from corticosteroids. Tests for hepatitis B e antigen and hepatitis B viral DNA were both positive prior to treatment with 1 million units alpha interferon three times weekly for 3 weeks followed by an increase to 3 million units alpha interferon three times weekly for a total of 16 weeks. At the end of treatment, hepatitis had clinically resolved with conversion to a hepatitis B e antibody positive and hepatitis B e antigen and viral DNA negative state. The renal allograft function remained excellent throughout the course of therapy with interferon.
Low Prevalence of Hepatitis G Virus Antibodies in Glomerular Diseases
Authors: Cengiz Kuddusi , Günaydιn Murat , Bedir Abdulkerim , Pekbay Ayhan
Published: April 2003

A possible agent for human non-A–E hepatitis has been identified and named hepatitis G virus (HGV). HGV is also a flavivirus, and the clinical characteristics and risk factors of HGV infection may be similar to those of hepatitis C virus infection. Hepatitis C virus infection may manifest as a primary glomerulonephritis. The aim of this study is to evaluate the prevalence of serum HGV RNA in 98 adult patients with biopsy-proven glomerular diseases. We found that only 3 patients (3%) out of 98 with primary glomerulonephritis had HGV RNA. One of 59 (1.7%) healthy controls was serum HGV RNA positive (p > 0.05). The prevalence of serum HGV RNA was low in the patients with primary glomerulonephritis.
Renal Disease in the Elderly
Authors: Davison Alex M.
Published: April 2003

There are structural and functional changes which take place in the kidney with age. These changes have an impact on patient management, particularly with respect to drug therapy. It is unlikely that glomerulonephritis is less common in the elderly, and any apparent difference with respect to younger patients most likely reflects clinical practice rather than any inherent difference in the aged kidney. Tubulointerstitial nephritis may be more common and is most likely linked to drug therapy. The management of end-stage renal failure in the elderly should not be significantly different from that in younger patients and should be based on the capacity for rehabilitation rather than any arbitrary age.
Discordance between Retinopathy and Nephropathy in Type 2 Diabetes
Authors: Kanauchi Masao , Kawano Takahiro , Uyama Hideto , Shiiki Hideo , Dohi Kazuhiro
Published: April 2003

The aim of this study was to investigate the relationship between the grade of retinopathy and the severity of glomerular lesions in patients with type 2 diabetes and to describe 5 patients without diabetic retinopathy for whom renal biopsy specimens demonstrated advanced diabetic nephropathy. A total of 221 patients with type 2 diabetes (139 males and 82 females) who consectively underwent renal biopsy between 1982 and 1996 were investigated. The severity of diffuse glomerular lesions was graded using the criteria of Gellman and coworkers, and diabetic retinopathy was classified as absent, nonproliferative, or proliferative. The incidence of advanced nephropathy without retinopathy for all 221 cases was 2.3%. Advanced nephropathy was present in 5 of the 122 (4.1%) patients without retinopathy. These 5 patients were all males and aged 50–70 (mean 61) years. Their clinical characteristics were not uniform, and no special clinical features distinguished the patients who were regarded as having possible advanced nephropathy without retinopathy. In our study, although concordance of retinopathy and nephropathy is relatively common, a little discordance was pronounced in Japanese type 2 diabetic patients. Our findings are consistent with the hypothesis that there are important differences in some aspects of the pathogenesis of retinopathy and nephropathy.
Apo(a) Phenotypes and Lp(a) Concentrations in Renal Transplant Patients
Authors: Kandoussi A.M. , Hugue V. , Cachera C. , Hazzan M. , Dracon M. , Tacquet A. , Noël C.
Published: April 2003

Plasma lipoprotein (a) (LP(a)) concentrations are increased in patients with end-stage renal disease. Considering the influence of the apolipoprotein (a) (Apo(a)) polymorphism and the mode of dialysis in this prospective longitudinal study, we compared Lp(a) concentrations before and after the first 6 months of a successful kidney transplantation in 125 recipient patients. Apo(a) phenotyping was performed by using SDS-PAGE and SDS-agarose, isoforms were classified into high molecular weight (HMW) and low molecular weight (LMW). Before the graft, the Lp(a) concentrations were significantly higher in CAPD than in hemodialysis patients (p = 0.021). Six months after transplantation, Lp(a) fell in both treatment groups. This decrease occurred within both LMW and HMW but to a different extent: median relative variations were –35 and –50%, respectively (p = 0.048). Among patients with Lp(a) concentration >30 mg/dl 6 months after transplantation, 74% had LMW Apo(a) isoform while the remaining 26% had HMW isoform. Successful renal transplantation leads rapidly to a correction of Lp(a) concentrations, especially in patients treated with CAPD who have higher Lp(a) levels. The most important factor seems to be the LMW status corresponding to high Lp(a) levels.
Platelet-Leukocyte Activation during Hemodialysis Detected with a Monoclonal Antibody to Leukocyte Integrin CD11b
Authors: Hernández M.R. , Galán A.M. , Lozano M. , Bozzo J. , Cases A. , Escolar G. , Calls J. , Ordinas A.
Published: April 2003

Platelet activation is commonly monitored with a battery of monoclonal antibodies against different platelet epitopes with controversial results. The transient expression of platelet markers and their role mediating interactions with other cells could easily explain these discrepancies. The present study has evaluated whether the analysis of a leukocyte activation antigen (CD11b) could provide more reliable results than detection of platelet activation markers. Cytometric techniques with specific monoclonal antibodies were used to compare the reliability of platelet and leukocyte markers to detect activation. Modifications in the presence of platelet glycoproteins GPIb (CD42b), GPIIIa (CD41) and GPIV (CD36), expression of specific platelet markers (P-selectin (CD62P) and lysosomal protein (CD63)) and leukocyte integrin (CD11b) were assessed during hemodialysis. Platelet antigens remained in uremic patients at levels similar or slightly above those detected in a group of healthy subjects. Modifications of platelet antigens during hemodialysis produced inconclusive results. However, numbers of leukocytes expressing CD11b increased progressively during hemodialysis (17.2 ± 5.1% at 15 min and 21.3 ± 6.6% at 2 h, p < 0.05, vs. baseline 6.9 ± 0.2%). The hemodialysis procedure caused an increased formation of leukocyte-platelet aggregates. Detection of leukocyte CD11b may be a useful marker of overall cellular activation during the hemodialysis procedure.
Transient Renal Glucosuria in Patients with Tetanus
Authors: Rezaian Gholam-Reza , Khajehdehi Parviz , Beheshti Shohreh
Published: April 2003

Background/Aims: During our early years of experience with patients suffering from tetanus, some of them were found to have unexplained renal glucosuria. Methods: Thus, all the normoglycemic patients with tetanus who were consecutively encountered over the subsequent 8 years were studied for the presence of renal glucosuria. Results: From 92 cases of tetanus admitted to the intensive-care unit, 63 patients had normal blood sugar in the course of their illness. The quantitative measurement of 24-hour urine confirmed the presence of significant renal glucosuria in 52% (n = 33) of these cases. The renal glucosuria was of transient nature and decreased to normal levels in the recovery stage (4 weeks after discharge from the hospital). There was no significant difference in age, sex, severity of disease and site of entry between the two groups of the patients with and without renal glucosuria. Conclusion: Significant but transient glucosuria of renal origin possibly induced by tetanospasmin is common in patients with tetanus.
Characteristic Matrix and Tubular Basement Membrane Abnormalities in the CBA/Ca-kdkd Mouse Model of Hereditary Tubulointerstitial Disease
Authors: Sibalic Vladimir , Sun Li-kang , Sibalic Anita , Oertli Beat , Ritthaler Theresia , Wüthrich Rudolf P.
Published: April 2003

CBA/CaH-kdkd mice develop hereditary tubulointerstitial disease with mononuclear cell infiltration and cyst formation, possibly representing a model of human nephronophthisis. The purpose of the present investigation was to examine the components of the fibrotic changes which typically develop in the kidneys of these mice. By conventional histology, kdkd mice displayed progressive interstitial fibroblast and matrix accumulation. Immunohistological analysis of kdkd kidneys showed marked deposition of fibronectin in the tubulointerstitial space and revealed prominent irregularities for laminin and collagen type IV in the tubular basement membrane (TBM), including thickening, widening and folding. Electron microscopy confirmed the TBM abnormalities and showed marked undulation and thickening in areas of proximal tubular (PT) degeneration. Immunofluorescence staining analysis for the fibronectin receptors VLA-4 and VLA-5 showed no expression on injured proximal tubules, whereas the expression of the laminin receptor VLA-6 was increased and irregular on altered PT. Analysis of RNA derived from kdkd kidneys revealed marked upregulation of steady-state mRNA levels for the fibrogenic growth factor TGF-β. We conclude that TBM alterations, matrix accumulation and changes in integrin expression together with enhanced TGF-β production are typical features of kdkd tubulointerstitial disease and suggest that characteristic TBM or matrix alterations could contribute to the pathogenesis of the disease in these mice.
IgA Glomerulonephritis with Irregular IntramembranousDense Deposits
Authors: Katz Allan , Chan Patricia
Published: April 2003

A 30-year-old white male presented with hematuria, proteinuria and normal renal function following a flu-like illness. IgA was mildly elevated but C3 and C4 levels were normal in serum. Renal biopsy showed a mesangial proliferative nephritis with immunohistochemical features of IgA nephritis but with an unusual pattern and distribution of deposits in glomerular, tubular and Bowman’s capsular basement membranes.
Prevalence and Renal Prognosis of Diagnosed Autosomal Dominant Polycystic Kidney Disease in Japan
Authors: Higashihara Eiji , Nutahara Kikuo , Kojima Masayo , Tamakoshi Akiko , Yoshiyuki Ohno , Sakai Hideto , Kurokawa Kiyoshi
Published: April 2003

The prevalence and renal prognosis of diagnosed autosomal dominant polycystic kidney disease (ADPKD) in Japan were estimated. Hospital-based nationwide surveys were conducted in 1995. The number of ADPKD patients who visited hospitals but were not on chronic dialysis was estimated to be 10,000 (95% confidence interval: 8,200–11,900) and that of ADPKD patients on dialysis was 4,590, yielding a prevalence of ADPKD of 117 per million population at the end of 1994 (95% confidence interval: 102–132). The prevalence increased with age and reached a peak value of 261 per million population at the age group of 55–59 years. The rate of end-stage renal disease among living patients was calculated based on the assumption that the prevalence of ADPKD in the population under the age of 55 years was 261 per million population. The rate of end-stage renal disease increased with the progression of the patients’ age, reaching 49% at the age of 65–69 years and declining thereafter. Conclusion: The hospital-based prevalence of ADPKD is lower than the autopsy-based prevalence, suggesting that a fairly large number of these patients do not receive medical care in their lifetime. The probability of end-stage renal disease is at most 50% among ADPKD patients who visit a hospital.
Glomerular and Tubular Function in Renal Transplant Patients Treated with and without Ciclosporin A
Authors: Hansen Jesper Melchior , Fogh-Andersen Niels , Leyssac Paul Peter , Strandgaard Svend
Published: April 2003

The present study evaluated whether chronically administered low-dose (<5 mg/kg) ciclosporin A (CsA) affects renal haemodynamics and tubular function in renal transplant recipients (RTx) when studied at nadir CsA blood levels. The renal clearance of lithium was used as an index of proximal tubular outflow of sodium and water. Effective renal plasma flow, glomerular filtration rate, and renal clearance of lithium were studied in 67 stable non-diabetic RTx and 44 healthy controls. Forty-eight of the RTx were treated with CsA, prednisone, and azathioprine. Nineteen were treated exclusively with prednisone and azathioprine. In RTx with a good graft function (serum-creatinine <125 µmol/l), no specific CsA-induced renal haemodynamic and tubular dysfunctions were evident. In CsA-treated RTx with a slightly reduced renal function (serum creatinine 125–180 µmol/l) a decrease in fractional proximal tubular reabsorption was found. The renal clearances of urate and magnesium were comparable between RTx treated with or without CsA, and a significant correlation between glomerular filtration rate and renal clearance of urate was found. CsA-treated RTx had a significantly higher blood pressure, independent of glomerular filtration rate and segmental tubular function. In conclusion, at nadir CsA blood levels, no specific CsA-induced tubular dysfunction evaluated by the renal lithium clearance method could be demonstrated in RTx receiving chronically low-dose CsA. The hyperuricaemia commonly seen in RTx seems to be mainly caused by the reduced glomerular filtration rate.
Chemokines, Renal Disease, and HIV Infection
Authors: Wenzel U.O. , Stahl R.A.K.
Published: April 2003

Renal disease is characterized by the influx of leukocytes into the injured tissue. Before leukocytes can exert their effects on renal damage or repair, they have to reach the site of injury. To recruit specific populations of leukocytes during inflammation is the role of a family of cytokines called chemokines. The characterization of this family has emerged within the past years, yet chemokines have already been the subject of thousands of scientific reports and promise to have many clinical applications. There is good evidence that chemokines contribute to leukocyte infiltration in glomeruli and interstitium and that they play a pivotal role in various renal diseases. The fact that there exist so many chemokines suggests the biological need for redundancy to effect recruitment of immune cells. Although they were originally defined as host defense proteins, chemokines clearly have other functions that extend well beyond the regulation of leukocyte migration. The recent suggestion that chemokines may contribute to a slow progression of the human immunodeficiency virus (HIV) infection and the very recent identification of chemokine receptors as docking molecules for HIV infection add another aspect to chemokine research. The speed at which researchers are exploring the HIV-chemokine connection is evident in the large number of publications on this topic as well as the rapid translation of publications into possible therapeutic applications. Delineating a precise role for chemokines in mediating pathologic changes is an area of fruitful investigation.
Significance of Platelet-Derived Microparticles and Activated Platelets in Diabetic Nephropathy
Authors: Omoto Seitaro , Nomura Shosaku , Shouzu Akira , Hayakawa Takashi , Shimizu Hidekazu , Miyake Yutaka , Yonemoto Toshiyoshi , Nishikawa Mitsushige , Fukuhara Shirou , Inada Mitsuo
Published: April 2003

We measured levels of platelet-derived microparticles (PMP), which have coagulative activity and are produced by platelet activation or physical stimulation, and CD62P/CD63-positive platelets in patients with diabetes mellitus to determine their clinical significance and effects on complications of diabetes including diabetic nephropathy. We also compared these levels before and after administration of the antiplatelet drug cilostazol. Plasma PMP and CD62P/CD63-positive platelet levels were significantly higher in patients with diabetes mellitus than normal controls. CD62P-positive platelet levels were significantly higher in patients with nephropathy than in patients without complications. After administration of cilostazol, PMP and CD62P/CD63-positive platelet levels were significantly decreased. The increases in platelet activity and its related procoagulant activity appear to account in part for the hypercoagulability observed in diabetes mellitus. Our findings suggest that activated platelets might play a role in the development of diabetic nephropathy. Furthermore, antiplatelet therapy with cilostazol for diabetic patients may be useful as antithrombin therapy including antiplatelet therapy, since it suppresses the production of intrinsic coagulants produced by platelet activation.
Abnormal Distribution of Mesangium-Specific Laminin in Glomeruli of Patients with Idiopathic Membranous Nephropathy
Authors: Horikoshi Satoshi , Ebihara Isao , Nakamura Tsukasa , Koide Hikaru
Published: April 2003

Using a monoclonal antibody, the distribution of the mesangium-specific laminin that binds only to the mesangium in normal kidney, was studied immunohistochemically in renal tissues obtained from patients with different glomerulonephritides including idiopathic membranous nephropathy. In minimal change nephrotic syndrome and IgA nephropathy, the mesangium-specific laminin staining was restricted to the mesangium, as is observed in the normal kidney. However, in patients with idiopathic membranous nephropathy, the monoclonal antibody against the mesangium-specific laminin reacted with the glomerular peripheral capillary walls including subepithelial protrusions or ‘spikes’, as well as with the mesangium. These results suggest that the quality of laminin produced in response to the challenge of immune deposits in the peripheral capillary walls may be different from that in the rest of the glomerular basement membrane in idiopathic membranous nephropathy.
Immunochemical Localization of Transforming Growth Factor-α-Related Protein in the Rat Kidney
Authors: Díaz-Ruiz Carmen , Asbert Mónica , Pérez-Tomás Ricardo
Published: April 2003

Transforming growth factor-α (TGF-α) is a 50-amino acid polypeptide synthesized as part of a larger precursor of 159 amino acids. Its expression has been reported in normal and neoplastic kidney. In this report, we characterized a renal TGF-α-immunoreactive protein, which we named TGF-α-related protein (TGF-α-RP). It was found to be present in the final part of the collecting tubules of the normal rat kidney. Western blotting analysis of kidney samples revealed a protein of 38 kD and pI = 5.5. In nonreducing conditions immunoreaction for this protein decreased and a TGF-α-immunoreactive protein of 150 kD was observed. The expression of TGF-α-RP seems to be highly conserved in the kidney of mammals and chickens. Therefore, TGF-α-RP may have an important role in the normal development and function of the kidney.
Effects of Protein Meals on the Urinary Excretion of Various Plasma Proteins in Healthy Subjects
Authors: Narita Takuma , Kitazato Hiroji , Koshimura Jun , Suzuki Katsunori , Murata Masahiko , Ito Seiki
Published: April 2003

To examine whether hemodynamic changes in response to acute protein loadings with different protein sources cause increases in urinary excretion of plasma proteins in healthy subjects, urinary excretions of various plasma proteins with various molecular radii and isoelectric points, namely albumin (Alb), IgG, IgG4, ceruloplasmin (CRL), and α2-macroglobulin (A2), were measured in healthy subjects after ingestion of a beef meal or of a tuna fish meal. Significant increases in urinary excretions of the negatively charged IgG4 and CRL and of the neutrally charged IgG were found in parallel with enhanced creatinine clearances after each protein ingestion. These renal responses returned to basal levels 9 h after the test. This finding suggests that in healthy subjects, the increase in glomerular filtration rate after acute protein loading caused selective enhancement of urinary excretions of plasma proteins with a molecular radius of approximately 55 Å (the radius of IgG, IgG4, and CRL), irrespective of the charge barrier of the glomerulus. The increases in these three plasma proteins may be induced by leakage via the shunt pathway in the glomerulus, as proposed earlier (see text). In contrast, increases in urinary excretions of A2 and Alb were not found. The former finding may be explained by the possibility that A2 would not pass through this pathway, since the molecular radius of A2 (88 Å) is larger than that of IgG, although the latter finding may be partially explained by preferential renal tubular reabsorption of Alb.
Sympathetic Skin Response in Hemodialysis Patients: Correlation with Nerve Conduction Studies and Adequacy of Dialysis
Authors: Robles N.R. , Solis M. , Albarran L. , Esparrago J.F. , Roncero F. , Sanchez-Casado E.
Published: April 2003

A sympathetic skin response (SSR) test was performed in diabetic and nondiabetic patients undergoing regular hemodialysis and the results correlated with nerve conduction studies (NCS): sensory conduction velocity (SCV) and motor conduction velocity (MCV). Comparisons were made between diabetic and nondiabetic patients and between cuprophane and polyacrylonitrile membrane dialyzed patients. Six nondiabetic uremic patients (30%) and all diabetic patients had no SSR. Eight nondiabetic uremic patients (40%) had a mildly impaired response. Nondiabetic patients with a normal response were younger (31.1 ± 16.4 years) than the patients with abnormal SSR, whether mildly impaired response (58.3 ± 20.3 years; p < 0.05, Anova) or absent response (65.3 ± 13.8 years; p < 0.01, Anova). SCV, MCV, and SSR values were reduced (p < 0.01) in uremic patients with respect to normal subjects. Severity and frequencies of sensory NCS abnormalities in nondiabetic patients were: normal 20%, mildly impaired 75%, and severely impaired 5%. Severity and frequencies of motor conduction abnormalities were: normal 80%, mildly impaired 20%, severely impaired 0%. The SSR abnormality incidence in patients with a normal NCS was similar to that in patients with either mildly or severely impaired NCS (chi-square test). There was a positive linear correlation between the SSR amplitude and SCV (r = 0.52, p < 0.01) and MCV (r = 0.49, p < 0.01). The SSR latency was also significantly related to SCV (r = 0.66, p < 0.01) and MCV (r = 0.61, p < 0.01). A significant negative correlation was found between age and SSR parameters, amplitude (r = –0.56, p < 0.01) and latency (r = –0.66, p < 0.01). No correlation was found between duration of hemodialysis or Kt/V and SSR. No differences were found in SSR, NCS, or Kt/V values between cuprophane membrane and polyacrylonitrile membrane dialyzed patients (Student’s t test). The relationship between NCS and SSR in uremic patients was confirmed. Old age and diabetes mellitus, but not the dialysisis membrane used, were confirmed as synergistic factors of neuropathic impairment. It appeared that SSR is more sensitive than NCS in detecting polyneuropathy in uremic patients on hemodialysis.
Disseminated Herpes simplex Virus Infection in a Renal Transplant Patient as Possible Cause of Repeated Urinary Extravasations
Authors: Gómez E. , Melón S. , de Oña M. , Alvarez R. , Laures A. , Alvarez-Grande J.
Published: April 2003

Disseminated herpes simplex virus type 2 (HSV-2) infections are infrequent in patients receiving organ transplants, but usually have a poor outcome. We describe the case of a renal transplant patient who developed a disseminated HSV-2 infection with repeated urinary extravasations. The diagnosis was carried out using a multiplex polymerase chain reaction nested assay and it suggested HSV-2 as a possible cause of repeated urinary fistulas.
Focal Segmental Glomerulosclerosis in a 32-Year-Old Kidney Allograft after7 Years without Immunosuppression
Authors: Trimarchi Hernan M. , Gonzalez Juan M. , Truong Luan D. , Brennan T. Stephen , Barrios Roberto , Suki Wadi N.
Published: April 2003

In kidney allografts, focal segmental glomerulosclerosis (FSGS) has been described as recurrent, de novo, or a histological variant of chronic transplant glomerulopathy. We describe a unique case of de novo FSGS in a renal transplant not accompanied by any feature of rejection in a patient who had not been immunosuppressed for several years. A 58-year-old woman received a histoidentical living-related kidney transplant for end-stage renal disease due to chronic pyelonephritis. Twenty-four years after the transplant she voluntarily discontinued all immunosuppressive medication. Seven years later she presented with nephrotic syndrome, mild renal failure, and positive serology for hepatitis C virus (HCV) antibody. The kidney transplant biopsy disclosed de novo FSGS. Features of acute or chronic rejection, including chronic transplant glomerulopathy, were not seen. The pathogenesis of this lesion is probably related to sustained and prolonged glomerular hyperfiltration; alternatively, HCV infection may have triggered or accelerated the appearance of FSGS.
A Definite Role for the Kallikrein-Kinin System in the Renal Hemodynamic Response to an Oral Protein Load during the Aging Process
Authors: Drummond Pecly Inah Maria , Genelhu de Abreu Fagundes Virginia , Francischetti Emilio Antonio
Published: April 2003

The effect of aging on the physiologic responses of renal plasma flow (RPF) and glomerular filtration rate to an acute oral protein load (renal reserve) is a poorly understood process. In this study of 37 healthy human volunteers, distributed among three groups (group 1: n = 13, age range 20–39 years; group 2: n = 13, age range 40–59 years; group 3: n = 11, age range 60–68 years), we evaluated the influence of age on some of the vasoactive systems such as plasma renin activity, urinary kallikrein, plasmatic prokallikrein, plasmatic kallikrein, and plasmatic kininogen on RPF and creatinine clearance (Ccr) in response to an acute oral protein load (1 g/kg body weight). The aging process diminished but did not cease the increments in RPF (group 1: 539.6 vs. 658.9 ml/min/1.73 m2, p < 0.001; group 2: 509.0 vs. 570.7 ml/min/ 1.73 m2, p < 0.001; group 3: 453.9 vs. 506.0 ml/min/ 1.73 m2, p < 0.001) and Ccr (group 1: 139.7 vs. 166.5 ml/ min/1.73 m2, p < 0.001; group 2: 126.6 vs. 142.2 ml/min/1.73 m2, p < 0.001; group 3: 112.6 vs. 121.4 ml/min/ 1.73 m2, p < 0.01) after a protein overload. The plasma renin activity did not change after a meat meal. On the other hand, all parameters regarding the kinin system changed significantly in the direction of increased bradykinin formation, despite aging (urinary kallikrein – group 1: 0.25 vs. 0.44 mU/ml, p < 0.005; group 2: 0.25 vs. 0.41 mU/ml, p < 0.005; group 3: 0.33 vs. 0.47 mU/ml, p < 0.005/plasmatic kininogen – group 1: 1.3 vs. 0.9 µg LBK/ml, p < 0.005; group 2: 1.1 vs. 0.7 µg LBK/ml, p < 0.005; group 3: 0.8 vs. 0.7 µg LBK/ml, p < 0.005). These findings indicate that: (1) the aging process narrows but does not cease the increment range in Ccr and RPF after acute oral protein ingestion; (2) increased bradykinin formation plays a definite role in the acute renal vasodilatory response, and (3) contrary to previous clinical studies, our results suggest that the renal reserve is progressively and significantly reduced during the aging process.
Adrenomedullin Inhibits Transmural Pressure Induced Mesangial Cell Proliferation through Activation of Protein Kinase A
Authors: Osajima Akihiko , Kato Hiroaki , Uezono Yasuhito , Suda Takeshi , Okazaki Masahiro , Oishi Yosuke , Tamura Masahito , Tanaka Hiroshi , Izumi Futoshi , Nakashima Yasuhide
Published: April 2003

Adrenomedullin (AM), a hypotensive peptide isolated from human pheochromocytoma, inhibits the proliferation of mesangial cells (MC) induced by mitogens such as platelet-derived growth factor. Quite recently, we have demonstrated that transmural pressure applied to cultured MC increased DNA synthesis and cell proliferation through protein kinase C and tyrosine kinase pathways. However, the modulatory effect of AM on pressure-induced cell proliferation is as yet unknown. In the present study, we examined the effect of AM on transmural pressure-induced DNA synthesis in cultured rat MC. Pressure was applied to cells placed in a sealed chamber using compressed helium. Application of pressure resulted in an increase in [3H]thymidine incorporation (approximately 2.0-fold). AM clearly inhibited pressure-induced DNA synthesis in a concentration-dependent manner. This inhibition was paralleled by an increase in cellular cAMP levels evoked by AM. Forskolin and dibutyryl cAMP mimicked the inhibitory effect of AM. The protein kinase A inhibitor H-89 significantly attenuated the effect of AM. Human AM(22–52)-NH2, a putative AM receptor antagonist, reversed the inhibitory effects of AM more potently than did human CGRP(8–37), a calcitonin gene related peptide receptor antagonist. Our results suggest that AM, by acting mainly on AM-sensitive receptors, inhibits pressure-induced DNA synthesis in cultured rat MC through activation of protein kinase A. AM may play a protective role against MC proliferation in certain pathological conditions.
The Outer Membrane Protein I of Pseudomonas aeruginosa PAO1, a Possible Pollutant of Dialysate in Hemodialysis, Induces Cytokines in Mouse Bone Marrow Cells
Authors: Ino Mitsuhiro , Nagase Sohji , Nagasawa Toshiro , Koyama Akio , Tachibana Shinro
Published: April 2003

The finding of outer membrane protein I (OprI) of Pseudomonas aeruginosa in hemodialyzers used by patients with end-stage renal failure led us to study the possible role of OprI as cytokine inducer. However, there are few reports on the biological activity of OprI, because it is difficult to obtain highly purified OprI. In this study, we attempt to establish a procedure for the efficient purification of OprI, which does not include lipopolysaccharide, from the bacterial culture broth, not hemodialyzers, to demonstrate that OprI is a potent cytokine inducer. From bacterial culture broth (1 liter), P. aeruginosa PAO1, which was confirmed previously by the sequence coding, was separated by centrifugation, high-performance liquid chromatography, and disk electrophoresis. Mouse bone marrow cells were stimulated by purified OprI, and the supernatants of the culture were analyzed by several enzyme-linked immunosorbent assay kits. The tumor necrosis factor alpha production stimulated by purified OprI was confirmed and degraded within 24 h. Furthermore, interleukin (IL) 1α, IL-1β, IL-6, and granulocyte-macrophage colony-stimulating factor were also induced by OprI despite the absence of lipopolysaccharide. We conclude that OprI has the potential to induce tumor necrosis factor alpha production in mouse bone marrow cells and that tumor necrosis factor alpha contributes to the induction of inflammatory cytokines, namely IL-1α, IL-1β, IL-6, and granulocyte/macrophage colony-stimulating factor, while lipopolysaccharide has little effect on these cells. These results suggest the presence of a pathway of inflammatory signal transduction triggered by OprI. In addition, OprI is possibly one of the harmful dialysate pollutants in hemodialysis patients besides the well-known lipopolysaccharide.
HIV-Associated Nephropathy
Authors: Cohen Arthur H. , Cohen Gail M.
Published: April 2003

HIV-associated nephropathy is manifested by heavy proteinuria and renal insufficiency and characterized pathologically by the collapsing variant of focal and segmental glomerulosclerosis with acute tubular necrosis and mild interstitial inflammation. Untreated, it may result in end-stage renal disease in as little as 4 months. It may present in patients with any manifestation of HIV infection, and affects predominantly black individuals. Insights into pathogenesis have come from a transgenic mouse model, renal cell cultures, and from study of human biopsy material. Although the pathogenesis is not completely understood, current considerations revolve around the role of HIV or protein in renal epithelium and the effects of cytokines, including transforming growth factor-β and basic fibroblast growth factor, on renal structures. Therapy with zidovudine, corticosteroids, or angiotensin-converting enzyme inhibitors has met with modest success; to date, protease inhibitors have not been assessed.
Ultrastructural Localization of Dominantly Increased Fibronectin in the Markedly Thickened Glomerular Basement Membrane in a Selectively Mated Murine High IgA Strain (HIGA Mice)
Authors: Kawamura Takahide , Muso Eri , Kamata Tadashi , Suyama Katsuo , Oyama Atsushi , Ono Takahiko , Yoshida Haruyoshi , Miyawaki Shigeki , Sasayama Shigetake
Published: April 2003

To clarify which matrix component(s) contributes to glomerular sclerosis with mesangial IgA deposits in a murine high serum IgA strain (HIGA) derived from ddY mice, morphological and immunopathological analyses of glomeruli were performed in comparison with original ddY and BALB/c mice as controls. Significantly increased thickness of the glomerular basement membrane (GBM), especially the lamina densa, was observed in HIGA mice. Immunofluorescent staining showed marked increases in levels of fibronectin and laminin in both the mesangium and capillary wall in aged HIGA mice. Analysis of the distribution of immunogold-labeled antibody in GBM revealed a significant increase (p < 0.0001) and specific orientation of fibronectin in the endothelial side, which suggested that mesangial fibronectin produced at high levels due to IgA deposition extended to the endothelial side of GBM and contributed to the thickening of GBM with further development to glomerulosclerosis in the HIGA mice.
Effect of Protamine on Ion Selectivity of Superficial and Juxtamedullary Proximal Straight Tubules
Authors: Takahashi Mitsuo , Taniguchi Junichi , Muto Shigeaki , Tsuruoka Shuichi , Imai Masashi
Published: April 2003

Protamine is known to inhibit cation selectivity of the paracellular shunt pathway in several leaky nephron segments. Ion permeability of the superficial (SF) proximal straight tubules (PST) is selective to Cl–, whereas that of the juxtamedullary (JM) PST is selective to Na+. Protamine was used to estimate the contribution of the paracellular shunt pathway to ion selectivity in these segments. PSTs were isolated from the kidneys of Japanese white rabbit and microperfused in vitro. The ratio of Na+ to Cl– permeability (PNa/PCl) was estimated from the diffusion potential (dVT) generated by NaCl gradients. When 300 µg/ml protamine was added to the lumen, PNa/PCl was decreased from 0.33 to 0.26 in SF-PST and from 1.80 to 1.29 in JM-PST, respectively, as the results of inhibition of cation selectivity. Addition of 30 U/ml heparin to the lumen, which neutralizes protamine, returned the ratios toward the control levels. Protamine exhibited similar effect on PNa/PCl in the presence or the absence of ouabain in the bath, indicating that the observed voltage deflections were independent of the transcellular active transport process. Although PNa/PCl was different between SF- and JM-PST, protamine inhibits Na+ permeability in both segments. Preferential Cl– permeability in the SF-PST may be intrinsic to the paracellular route of this segment. The mechanism of this anion selectivity remains to be established.
Antihypertensive Therapy in Renal Patients – Benefits and Difficulties
Authors: Schwenger V. , Zeier M. , Ritz E.
Published: April 2003

High blood pressure values, diastolic and systolic, are associated with decreased renal function. This is particularly true when the diastolic blood pressure is higher than 90 mm Hg. Several studies showed that lowering of the blood pressure within the range of normotension according to the WHO causes a reduction in the rate of progression to terminal renal failure. These studies have led to recommendations to aim at a target blood pressure of approximately 125/75 mm Hg in the treatment of patients with glomerular diseases and particularly diabetic nephropathy with proteinuria >1 g/day. In contrast to these results, blood pressure values corresponding to the recommendation (≤125/75 mm Hg) of the JNC VI (see text) were achieved in 15% of the patients only. It has also been shown that at any given level of an average 24-hour blood pressure, patients with an insufficient decrease of the blood pressure during nighttime have a higher risk to progress to terminal renal failure. Thus it is very important to lower the nighttime blood pressure and to detect nighttime blood pressure increases using ambulatory blood pressure measurements.
Exchange of Alkali Trace Elements in Hemodialysis Patients:A Comparison with Na+ and K+
Authors: Krachler Michael , Scharfetter Hermann , Wirnsberger Gerhard H.
Published: April 2003

Background: In the past, nephrologists have been troubled by electrolyte disturbances and consequently focused their attention on the importance of maintaining the concentrations of electrolytes within the normal range. However, information about the potential role of trace elements in chronic renal failure is scarce. Methods: During hemodialysis sessions, the concentrations of the five alkali metal cations lithium (Li), sodium (Na), potassium (K), rubidium (Rb), and cesium (Cs) have been determined in plasma and dialysis fluids of chronic hemodialysis patients by inductively coupled plasma mass spectrometry (Li, Rb, Cs) and by ion-sensitive electrodes (Na, K). Strict quality control schemes were applied to all analytical procedures to ensure accuracy and precision of the results. Results: The plasma concentrations of the elements Li, Cs, Rb, and K distinctly decreased to 29, 50, 69, and 71%, respectively, of their initial values during hemodialysis. Simultaneously, the concentrations of these elements in dialysis fluids at the outlet of the dialyzer increased approximately 13-fold for Rb, 11-fold for Li, 3-fold for Cs, and 2-fold for K as compared with the inlet values. The concentrations of Na in plasma and dialysis fluids were almost identical and did not change during hemodialysis. Conclusions: Li, Rb, and Cs were depleted in hemodialysis patients, although the plasma concentrations of these trace elements still remained within the reference ranges for healthy adults. Consequently, further studies are needed to elucidate the clinical importance and long-term effects of these trace element imbalances – for example, CNS disturbances associated with diminished concentrations of Rb – in hemodialysis patients.
Risk Factors for Chronic Renal Dysfunction in Cardiac Allograft Recipients
Authors: Esposito C. , Semeraro L. , Bellotti N. , Fasoli G. , Fornoni A. , Rampino T. , Klersy C. , Campana C. , Gavazzi A. , Viganò M. , Dal Canton A.
Published: April 2003

Renal dysfunction is one of the most common and threatening complications in heart transplant recipients. Even if ciclosporin seems to play a central role in inducing renal damage, other factors may concur or predispose to renal injury. In order to identify factors responsible for renal dysfunction, we retrospectively studied a cohort of 114 cardiac transplant recipients during a follow-up period of at least 3 years. The patients had a normal renal function before and 0.5 months after heart transplantation. Doubling of baseline serum creatinine or attainment of serum creatinine steadily above 176.8 µmol/l (2.0 mg/dl) was used as criterion to define the end-point renal dysfunction. A series of clinical and laboratory variables were obtained from the patients’ charts at different time intervals, and their prognostic value for the occurrence of renal dysfunction was calculated by Cox proportional hazards models. 23 out of 114 patients reached the end point after a median time period of 21 months. High serum triglyceride, alanine aminotransferase, alkaline phosphatase, ciclosporin, urea, glucose, and hemoglobin levels were shown to be associated with the development of renal dysfunction. Four variables, i.e., triglyceride, ciclosporin, urea, and alkaline phosphatase, had an independent prognostic value. Our results confirm a role for ciclosporin in inducing renal dysfunction and identify hyperlipidemia and an increased plasma urea level as risk factors for renal dysfunction in heart transplant recipients.
Renal Artery Stenosis Associated with Epidermal Nevus Syndrome
Authors: Aizawa Kenichi , Nakamura Tetsuya , Ohyama Yoshio , Saito Yuichiro , Hoshino Jin , Kanda Tsugiyasu , Sumino Hiroyuki , Nagai Ryozo
Published: April 2003

Epidermal nevus syndrome is an unusual neurocutaneous disorder in which epidermal nevi are associated with abnormalities of the skeleton and central nervous system, including the eyes and somtimes the cardiovascular system. We treated a patient in whom the latter included renal artery stenosis. An 18-year-old man with epidermal nevi was diagnosed as having the syndrome based on the additional presence of scoliosis, an arachnoid cyst in the middle cranial fossa, and microphthalmos. Hypertension was diagnosed when the patient was 15 years old. The plasma renin activity (9.7 ng/ml/h) was elevated. Right renal artery stenosis was demonstrated by angiography, and the abdominal aorta was narrowed distal to the ostium of the superior mesenteric artery. The plasma renin activity in the right renal vein (16 ng/ml/h) was higher than contralaterally (10 ng/ml/h). Several cardiovascular manifestations have been reported as a complication of epidermal nevus syndrome. Hypertension in an individual with epidermal nevi and congenital anomalies should prompt a search for a vascular anomaly.
The Ferroxidase Activity of Caeruloplasmin Is Reduced in Haemodialysis Patients
Authors: Roxborough Heather E. , Mercer Caroline , McMaster Dorothy , Maxwell A. Peter , Young Ian S.
Published: April 2003

Increased free-radical production leading to oxidative stress may contribute to the development of cardiovascular complications in haemodialysis patients. The ferroxidase activity of caeruloplasmin forms an important component of antioxidant defences in body fluids. The aim of this study was to assess ferroxidase activity in haemodialysis patients. Venous blood was collected from 83 haemodialysis patients immediately prior to and after dialysis and from 52 healthy controls. Immunoreactive caeruloplasmin was measured by rate nephelometry, and ferroxidase activity determined by measuring loading of ferrous iron onto iron-free transferrin. A significant reduction in ferroxidase activity was observed in dialysis patients when compared with controls (37 ± 1.20 and 46 ± 1.14 mU/l, respectively; p < 0.001). Following dialysis, ferroxidase activity rose significantly to 41 ± 1.16 mU/l, with a significant difference still remaining between control and patient ferroxidase activity (p < 0.005). Immunoreactive caeruloplasmin was found to be similar in all groups (before dialysis 0.40 ± 0.07 g/l, after dialysis 0.39 ± 0.07 g/l, control 0.42 ± 0.09 g/l: p = NS). A significant difference in caeruloplasmin-specific activity was therefore observed between predialysis, postdialysis and control samples (97 ± 2.31, 105 ± 1.74 and 112 ± 1.51 mU/g; p < 0.001, p < 0.01, respectively). Ferroxidase activity of caeruloplasmin is impaired in renal failure. Inhibition of caeruloplasmin ferroxidase activity in dialysis patients may contribute to increased oxidative stress in these patients.
Exacerbation of Renal Failure due to Hypothyroidism in a Patient with Ischemic Nephropathy
Authors: Makino Yuriko , Fujii Takashi , Kuroda Setsuko , Inenaga Takashi , Kawano Yuhei , Takishita Shuichi
Published: April 2003

A case of acute-on-chronic renal failure in a 70-year-old woman with ischemic nephropathy and primary hypothyroidism is presented. Her renal function became progressively worse as the level of serum creatinine increased from 283 to 628 µmol/l (3.2–7.1 mg/dl) within 8 months. Her thyroid function had been normal before the exacerbation of renal failure, but it was markedly reduced with a marked elevation of serum thyroid-stimulating hormone. Thyroid hormone replacement therapy resulted in rapid improvement of the renal function to 159 µmol/l (1.8 mg/dl) of serum creatinine. The development of primary hypothyroidism seemed to worsen the already impaired renal function in this case. We suggest the assessment of thyroid function in patients with unexplained deterioration of renal failure.
Cardiac Autonomic Neuropathy in Patients with Chronic Renal Failure on Hemodialysis
Authors: Kurata Chinori , Uehara Akihiko , Sugi Toshihiko , Ishikawa Akira , Fujita Kimio , Yonemura Katsuhiko , Hishida Akira , Ishikawa Keiko , Tawarahara Kei , Shouda Sakae , Mikami Tadashi
Published: April 2003

To characterize uremic cardiac autonomic neuropathy, we measured plasma catecholamines, analyzed the 24-hour heart rate variability (HRV), and acquired serial images with 123I-metaiodobenzylguanidine (MIBG) in 44 patients with chronic renal failure on hemodialysis and in 14 controls. Time-domain measures were calculated using the Marquette HRV program. MIBG clearance rates from the heart and lung were evaluated on planar images, and the regional MIBG uptake in the left ventricular myocardium was evaluated with single-photon emission computed tomography. Compared with controls, plasma dopamine and norepinephrine levels were elevated (p < 0.001 and p = 0.03, respectively), and all the time-domain measures of HRV were reduced in the patients (p < 0.001). The MIBG clearance rate from the heart was higher (p < 0.001), that from the lung was lower (p < 0.001), and the myocardial MIBG distribution was more heterogeneous in patients than in controls (total uptake score p ≤ 0.03). These variables were similar between 26 patients without and 18 patients with hypertension. Uremic cardiac autonomic neuropathy may be characterized by high plasma levels of dopamine and norepinephrine, reduced HRV, and abnormal MIBG kinetics in the heart with heterogeneous myocardial MIBG distribution, suggesting cardiac sympathetic overactivity and parasympathetic deterioration. In addition, abnormal MIBG kinetics in the lung may imply pulmonary sympathetic nervous dysfunction and/or endothelial dysfunction in uremic patients.