Shigeyuki Kushihata

Remnant-Like Particle Cholesterol May Indicate Atherogenic Risk in Patients on Chronic Hemodialysis

Recently, involvement of remnant-like particle cholesterol (RLP-C) in atherosclerosis was reported, but this parameter has not been adequately investigated in hemodialysis (HD) patients. The present study investigated the relationship between the RLP-C level and total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), lipid peroxides (malone dialdehyde, MDA), apolipoprotein (Apo) A-I, and ApoB. In addition, the fractions of very low density lipoprotein (VLDL), intermediate density lipoprotein (IDL), LDL, and HDL in serum lipoproteins were determined by disk polyacrylamide gel electrophoresis. The relationship between the RLP-C level and three atherogenic indices was also studied. The RLP-C level in HD patients (8.2 +/- 6.7 mg/dl) was significantly higher than that in normal controls (2.7 +/- 1.3 mg/dl). The RLP-C level showed a significant positive correlation with the levels of TC, TG, LDL-C, MDA, ApoB, VLDL(%), and IDL(%), as well as a negative correlation with HDL(%). However, there was no correlation with age or the duration of HD. RLP-C also showed significant positive correlations with the (TC -HDL-C)/HDL-C ratio and the (VLDL + LDL)/HDL ratio, as well as a negative correlation with the ApoA-I/ApoB ratio. These results suggest that RLP-C may be a potential indicator of atherogenic risk in HD patients.

Lipid-lowering therapy and coagulation/fibrinolysis parameters in patients on peritoneal dialysis.

Patients on continuous ambulatory peritoneal dialysis (CAPD) often have abnormalities of lipid metabolism or coagulation and fibrinolysis, these patients may thus be more susceptible to atherosclerosis than those on hemodialysis. It has been reported that hypercoagulability and hyperfibrinolysis are correlated with abnormalities of lipid metabolism. Therefore, we investigated the effect of a decrease in lipids on the coagulation and fibrinolysis system in CAPD patients with hyperlipidemia who received lipid-lowering therapy. The patients included 5 men and 13 women, with a mean age of 52.5 years. Pravastatin sodium (10 mg/day) and ethyl icosapentate (1800 mg/day) were administered concomitantly for 8 weeks. Lipid levels and coagulation/fibrinolysis parameters were measured before and after therapy. The patients were divided into two groups depending on their response to therapy: responders showed a decrease in total cholesterol or triglycerides by at least 20% and non-responders showed less improvement. In the responders, the levels of protein C, tissue plasminogen activator/plasminogen activator inhibitor-I complex, factor XIII, α2-plasmin inhibitor, and D-dimer were significantly lower after therapy than before therapy. Protein C, factor XIII, and α2-plasmin inhibitor were also significantly decreased after therapy in non-responders, but the extent of the decrease was smaller. The plasminogen level was significantly increased after therapy in non-responders. These findings suggest that a decrease in lipid levels and/or some other action by lipid-lowering agents may correct abnormalities of coagulation and fibrinolysis in CAPD patients. (Int J Artif Organs 2000; 23: 27–32)

Continuous Ambulatory Peritoneal Dialysis Is Superior to Hemodialysis in Chronic Dialysis Patients with Cerebral Hemorrhage

Continuous Ambulatory Peritoneal Dialysis Is Superior to Hemodialysis in Chronic Dialysis Patients with Cerebral Hemorrhage N. Noriaki Yorioka H. Hiroaki Oda T. Takahiko Ogawa Y. Yoshihiko Taniguchi S. Shigeyuki Kushihata A. Atsuo Takemasa K. Koji Usui K. Kenichiro Shigemoto S. Satoru Harada M. Michio Yamakido 2nd Department of Internal Medicine, Hiroshima University School of Medicine, and Ichiyokai Harada Hospital, Hiroshima, Japan

Nicardipine Hydrochloride Suppresses DNA Synthesis in Human Mesangial Cells Stimulated with Recombinant Human (rh) Platelet-Derived Growth Factor AA, rh lnterleukin-1 α, or rh Tumor Necrosis Factor-α

In order to define the role of cytokines in mesangial cell pathophysiology, we measured the mitogenic activity of recombinant human platelet-derived growth factor AA (rhPDGF-AA), rh interleukin-1 alpha (rhIL-1 alpha) and rh tumor necrosis factor-alpha (rhTNF-alpha) in cultured human mesangial cells, and investigated the effect of the calcium channel blocker nicardipine hydrochloride on their cell mitogenic activity. DNA synthesis in mesangial cells, stimulated by rhPDGF-AA, rhIL-1 alpha or rhTNF-alpha, was measured using [3H]TdR up take and similar investigations, with nicardipine hydrochloride added to the above, were conducted. The results showed DNA synthesis in cultured human mesangial cells were stimulated by rhPDGF-AA, rhIL-1 alpha and rhTNF-alpha, and this effect was reduced by the addition of nicardipine hydrochloride. Since rhPDGF-AA, rhIL-1 alpha and rhTNF-alpha are released by the inflammatory cells which infiltrate glomeruli, these cytokines may be involved in the mechanisms of mesangial cell proliferation observed in immune-mediated mesangial proliferative glomerulonephritis. Nicardipine hydrochloride reduced DNA synthesis in cultured human mesangial cells in response to these cytokines, suggesting possible application in medical therapy for immune-mediated mesangial proliferative glomerulonephritis.

Glomerulocystic Kidney Disease in a Young Adult

We report an 18-year old woman who had glomerulocystic kidney disease (GCKD) without a family history of renal disease or hypertension and no known congenital abnormalities. Her renal function was normal. Renal biopsy showed cystic dilatation of the Bowmans spaces and atrophy of the glomerular tufts. Electron microscopy revealed specific changes in the basement membranes of noncystic glomeruli, suggesting a congenital origin for her renal pathology. This relatively rare case contrasts with the usual presentation of GCKD in neonates or children.

PARENT AND CHILD CASES OF IGA NEPHROPATHY ASSOCIATED WITH VON RECKLINGHAUSEN'S DISEASE

Yoshihiko Taniguchi, MD, Second Department of Internal Medicine, Hiroshima University School of Medicine, 1-2-3 Kasumi, Minami-Ku, Hirsohima City 734 (Japan) Table 1. Serological typing for HLA-A, -B, -C, -DR, and -DQ antigens Dear Sir, We present parent and child cases of IgA nephropathy associated with von Recklinghausen’s disease. Case 1: In April 1987, a 41-year-old woman was referred to our department because of episodes of proteinuria and occult hematuria concomitant with febrile upper respiratory tract infections. A renal biopsy done at this time revealed IgA nephropathy, moderate degree. In 1988, she was diagnosed as having von Recklinghausen’s disease at the Dermatology Department of our hospital. In 1995, her renal function deteriorated gradually, so she was admitted for a second renal biopsy. Physical examination revealed multiple soft, small tumoral masses, which were pathologically diagnosed as being fibro-mas, along with café-au-lait spots and diffuse freckles. Her extremities were also slightly edematous. Abnormal laboratory findings were: urinary protein 2+, occult hematuria 3+, urinary protein excretion 0.8 g/day, BUN 19 mg/dl, serum creatinine 0.89 mg/dl, uric acid 6.0 mg/dl, creatinine clearance 58.5 ml/min, and serum ß2microglobulin 2.79 μg/ml. Her serum IgA level was normal. Microscopic examination of her renal biopsy tissues revealed sclerotic lesions such as global sclerosis or adhesions of Bowman’s capsule, and marked tubulointerstitial lesions were found. Immunofluorescent findings revealed IgA and C3 mesangial deposits. Electron microscopic examination showed slight dense deposits in the mesangial areas. Case 2: A 24-year-old man, the son of case 1 ‚ was referred to our hospital in January 1989 because of episodes of proteinuria and occult hematuria concomitant with upper respiratory tract infections. He was also diagnosed as having von Recklinghausen’s disease at the Dermatology Department of our hospital in 19 8 9. He was admitted to our hospital in September

Hepatocyte Growth Factor Localization in Primary Glomerulonephritis and Drug-Induced Interstitial Nephritis

Noriaki Yorioka, MD, 2nd Department of Internal Medicine, Hiroshima University School of Medicine, 1-2-3 Kasumi Minami-ku, Hiroshima City 734 (Japan) Table 1. Correlation between the distribution of HGF on tubule epithelial cells and primary glomerulonephritis, drug-induced interstitial nephritis and control tissue. Dear Sir, Hepatocyte growth factor (HGF) was initially identified as a mitogen for hepatocytes by Nakamura et al. [1] in 1984. Recently, HGF has been shown to be a mitogen for a variety of cell types, including renal tubular cells [2, 3]. Nagaike et al. [4] examined changes in HGF mRNA expression, HGF activity and HGF receptor in the rat kidney following unilateral nephrectomy or treatment with carbon tetrachloride, and suggested that HGF might function as a renotropic factor during renal regeneration after injury. In this study, we present the immunohis-tochemical localization of HGF in patients with primary glomerulonephritis and drug-induced interstitial nephritis. We examined 37 patients (18 males and 19 females; age: 15-74 years, mean ± SD; 40.9 ± 17.6) who underwent renal biopsy prior to treatment in the Second Department of Internal Medicine, Hiroshima University School of Medicine, Hiroshima, Japan. These patients were diagnosed as follows: primary glomerulonephritis, 25 patients (IgA nephropathy, 15 patients; membranous glomerulonephritis, 6 patients; focal glomer-ulosclerosis, 4 patients); druginduced interstitial nephritis, 9 patients (NSAIDs, 4 patients; anticancer agents, 2 patients; antibiotics, 2 patients; interferon-γ, 1 patient), and minimal changes, for control tissue, 3 patients. Kidney tissue fixed in formalin and embedded in paraffin was used to localize HGF. The sections were deparaffmized using xylene and alcohol, and the antigen was unmasked in 0.01% trypsin diluted with 0.06 M PBS, pH 7.2, for 30 min at 37 °C. The primary antibody (monoclonal anti-HGF antibody, Otsuka Pharmaceuticals, Japan) was applied overnight at 4 o C, followed by incubation with the secondary antibody for 30 min at room temperature. Immuno-products were visualized by applying DAB. The relationship between the presence of HGF and the histological stages of IgA nephropathy [5] was evaluated.

Effects of dialysis membranes on the kinetics of tumor necrosis factor-alpha production by peripheral mononuclear cells in chronic hemodialysis patients.

To evaluate the biocompatibility of dialysis membranes, blood samples were collected from 10 hemodialysis patients immediately before dialysis and peripheral blood mononuclear cells were isolated. The 3.0 x 105 cells/ml were then passed 30 times through modules made of a polyethylene glycolgrafted cellulose membrane, a polyacrylonitrile membrane, and a polysulfone membrane. Expression of messenger RNA for tumor necrosi factor-α (TNF-α) was determined. Cells were also cultured for 2 h with and without lipopolysaccharide and TNF-α levels in the supernatant were measured. TNF-α messenger RNA expression was significantly higher immediately after passage through the polyacrylonitrile membrane compared with the other membranes. Cells cultured without lipopolysaccharide, produced significantly less TNF-α after passage through the polysulfone membrane, while lipopolysaccharide significantly increased TNF-α production by cells passed through the polyacrylonitrile membrane. These results suggest that biocompatibility differs even among dialysis membranes believed to cause no complement activation.

CAPD CATHETER RUPTURE WITHOUT DETERIORATION

Quality assurance of platelet concentrates should include regular determinations on sampled units of platelet concentrate volume, platelet count, pH value and an indicator of maintenance of platelet discoid shape. In regard to the latter, recent investigations suggest that the visual assessment of platelet swirling may provide meaningful and reproducible information with limited staff training and efforts. Other laboratory assays provide useful data that may prove beneficial particulary when new procedures and products are examined. In addition to laboratory tests, it is of utmost importance to regularly monitor the effectiveness of platelet support therapy at clinical level. This can be done using a number of indicators including the proportion of patients who show febrile, allergic and septic reactions, who become and remain refractory to random-donor platelet support, who develop and/or die of hemorrhage not prevented or corrected by platelet support. (Int J Artif Organs 1998; 21 S-6: 95-7)

Dose Escalation Induces Tolerance to Side-Effects of Erythropoietin in a Patient with Dialysis Anaemia: Case Report

A 51-year-old woman began haemodialysis for chronic renal failure in February 1981. Symptomatic anaemia required treatment with recombinant human erythropoietin (rHuEPO) in February 1990 (3000 IU, twice weekly, intravenously). She developed influenza-like symptoms and treatment was withdrawn. In June 1994 rHuEPO was resumed at a very low dose of 100 IU subcutaneously three times weekly, and was increased gradually to 500 IU, without inducing any side-effects. At this dose the haematocrit was maintained at 22.0 – 25.0% and the symptoms of anaemia improved. In patients like ours, with influenza-like symptoms caused by rHuEPO therapy, dose escalation starting from an ultra-low dose may be effective in avoiding side-effects.