Jun Shiota

Plasma Atrial Natriuretic Peptide during Hemodialysis with or without Fluid Removal

Plasma immunoreactive human atrial natriuretic peptide (hANP) levels were measured in 9 patients with chronic renal failure treated with maintenance hemodialysis in order to evaluate the effects of fluid removal and osmotic pressure. Under hemodialysis without fluid removal plasma hANP levels remained unchanged, but the levels were significantly decreased during extra-corporeal ultrafiltration (p less than 0.01). The present study provided strong evidence that the fall in plasma hANP levels in hemodialysis patients is mainly due to the reduction in circulating plasma volume.

Two distinct monoclonal natural thymocytotoxic autoantibodies from New Zealand black mouse.

Autoimmune-prone NZB and NZB x NZW F1 mice have a large amount of autoantibodies cytotoxic for thymocytes (natural thymocytotoxic autoantibodies, NTA). We established two distinct monoclonal NTAs (NTA260 and NTA204) from a NZB mouse that react with the majority, but not all of these thymocytes. Flow cytometry analysis showed that NTA260 is positive on subpopulations of peripheral T cells from young mice, in which approximately 65% of CD4+ and 85% of CD8+ T cells were NTA260+. NTA260 also reacted with brain tissues of mice and rats, including Purkinje cells in the cerebellum. Western blot analysis showed that the molecular weight of NTA260 antigen was 55 kDa. In contrast to NTA260, NTA204 reacted with peripheral B cells but not with peripheral T cells in mice. NTA204 also reacted with peripheral blood granulocytes and bone marrow myeloid cells from both mice and rats. An immunofluorescence inhibition assay revealed the presence of autoantibodies with specificities of each NTA260 and NTA204 in the sera from NZB mice. As a selective decline in the subset of NTA260+ T cells but not NTA204+ B cells was observed with aging of NZB and NZB x NZW F1 hybrid mice, NTA260 is at least partly related to the observed immunological abnormalities of T cells in these autoimmune-prone New Zealand mice.

Effect of zinc supplementation on bone formation in hemodialysis patients with normal or low turnover bone

Abstract Zinc (Zn) is an essential trace element, which has been shown to stimulate osteoblastic bone formation and to inhibit osteoclastic bone resorption in vitro. In thalassemia, major patients Zn supplementation was reported to increase whole-body bone mineral content and areal bone mineral density. Therefore, we investigated the effect of Zn supplementation on bone formation in hemodialysis (HD) patients. Nine male patients with age of 66 (35–78) years indicated by median (range), HD vintage of 57 (4–97) months and serum intact parathyroid hormone (PTH) of 113 (6–310) pg/mL were supplemented with polaprezinc containing 34 mg Zn/day for 18 months. Doses of vitamin D were not changed during supplementation. Blood was collected at baseline, 3, 6, 12 and 18 months. Serum Zn increased significantly from 58 (52–65) μg/dL to 71 (57–93) μg/dL at three months and remained unchanged until 18 months. No changes were observed in serum intact PTH during supplementation. Although we found no changes in serum bone alkaline phosphatase (BAP) during Zn supplementation analyzed by Friedman test and Scheffe post hoc test, a significant trend of increase in serum BAP was verified by Jonckheere–Terpstra test (p = 0.0409). On the contrary, there was no trend in serum TRACP5b by Jonckheere–Terpstra test. Therefore, we suggested the effect of Zn supplementation on promoting bone formation, not affected by the status of PTH and vitamin D, in HD patients with normal or low turnover bone.

Lupus Nephritis in Autoimmune‐prone NZBxNZW F1 Mice and Mechanisms of Transition of the Glomerular Lesions

The pattern of renal glomerular lesions in systemic lupus erythematosus (SLE)‐prone NZBxNZW (B/W) F, mice shows an age‐associated transition, as is often seen in human lupus nephritis during the clinical course of the disease. Observations revealed that the earliest lesions were confined to the mesangium associated mainly with IgM deposits, and to a lesser degree with IgG. In mice over 5 months of age, the lesions extended gradually to the capillary wall with fine granular subepithelial deposits of IgG, but not of IgM. The ultimate pattern of the glomerular lesion was one of diffuse proliferation with diffusely distributed deposits of both IgG and IgM in the mesangium and along the capillary wall. Even at this stage, subepithelial deposits were composed of IgG, but not of IgM. The pattern of glomerular deposits of endogenous retroviral envelope glycoprotein gp70, which is highly anionic, virtually coincided with that of IgG. Taking these findings collectively, it is suggested that the progression of glomerular lesions in B/W F, mice depends largely on the age‐associated appearance of retroviral gp70 IgG anti gp70 immune complexes in the circulation and their deposition along peripheral subepithelial, and eventually subendothelial areas. Acta Pathol Jpn 41: 1–11, 1991.

Plasma Atrial Natriuretic Peptide Levels in Continuous Ambulatory Peritoneal Dialysis Patients

Hikaru Koide, MD, Division of Nephrology, Department of Medicine, Koto Hospital, 6-8-5 Ojima, Koto-ku, Tokyo 136 (Japan) Dear Sir, The cardiothoracic ratio (CTR) as determined from the chest x-ray is a simple and noninvasive method for determining the presence of volume overload, although it is not consistently reliable. The present study showed the plasma level of atrial natriuretic peptide (hANP) to be a more reliable method for determining the volume overload status in patients undergoing continuous ambulatory peritoneal dialysis (CAPD). We studied 73 CAPD patients (46 males, 27 females) aged 15-68 years (mean 45.2) without overt edema or uncontrolled hypertension (mean blood pressure ≥ 110 mm Hg). The duration of CAPD ranged from 2 to 64 months (mean 25.6). All patients received standard peritoneal dialysis fluid (Dianeal® PD-2; Baxter Healthcare), 1.5, 2.5 or 4.25%, and four exchanges of 2 liters of dialysate daily. None of the patients had peritonitis at the time of the study or in the previous 4 weeks. Dietary sodium intake was restricted to 7 g/day. Blood samples were collected in the morning for plasma hANP assay from the 73 CAPD patients and from 39 age-matched healthy control subjects (26 males, 13 females) after they had rested in the supine position for approximately 30 min. Plasma hANP was measured by a specific and sensitive radioimmunoassay [ 1 ]. Recovery of synthetic hANP by this method was 96.7%. Results are presented as the mean ± SD. The significance of differences was analyzed by Student’s t test for unpaired data. A level of p < 0.05 was accepted as statistically significant.

DOWN-REGULATION OF CD43 MOLECULE EXPRESSION ON INTRAPERITONEAL NEUTROPHILS IN CAPD PATIENTS WITH PERITONITIS

To assess the release of proteases from neutrophils infiltrated into the peritoneal cavity in continuous ambulatory peritoneal dialysis (CAPD), we investigated the regulation of CD43, LAM-1 and Mac-1 expression on the neutrophil plasma membrane using FACS analysis in CAPD patients with peritonitis. Five CAPD patients with peritonitis and five CAPD patients without peritonitis were studied. CD43 expression was immunohistochemically determined in both groups of patients using flow cytometry, and comparisons were made between the two groups. Down-regulation of CD43 and LAM-1, and up-regulation of Mac-1 were demonstrated on neutrophils obtained from CAPD dialysate of peritonitis patients after 1-h dwell time. Further up-regulation of Mac-1 developed until a dwell time of 4 h. Immunoblot analysis for neutrophil lysate from dialysate showed the presence of the asialo form of CD43 molecules and their fragments, which may be produced by cleavage of the CD43 molecule at extracellular sites. The intraperitoneal neutrophils in dialysate from CAPD patients with peritonitis are continuously activated during dwell time, and proteases may be released from neutrophils into dialysate after only a short dwell time.

Effect of Acarbose on Blood Glucose and Proteinuria in Patients with Diabetic Nephropathy

Accessible online at: www.karger.com/journals/nef Dear Sir, A study of the effect of Acarbose on decreases in the levels of fasting blood glucose and urinary protein excretion in patients with diabetic nephropathy is described. The importance of strict control of hyperglycemia in diabetes mellitus is now well accepted. Acarbose (·-glucosidase inhibitor), a complex oligosaccharide, is a potent competitive inhibitor of sucrase and decreases postprandial hyperglycemia when administered with food [1, 2]. Lee [3] reported that glomerular mesangial thickening and mesangial immunoglobulin deposition were significantly reduced in ab/ab mice receiving highdose Acarbose (40 mg/100 g food). We recently determined the levels of fasting blood glucose, glycohemoglobin A1c (HbA1c) and urinary protein excretion after treatment with Acarbose (Glucobay®) for 24 months in diabetic patients with or without nephropathy. Non-insulin-dependent diabetes mellitus type 2 was diagnosed according to the criteria of the 75-gram oral glucose tolerance test of the Japanese Diabetic Research Council [4]. Blood and urine samples were obtained from 33 diabetic patients with or without nephropathy in our outpatient clinic. Thirteen patients who showed more than 300 mg of urinary albumin per gram creatinine (Cr) were included in this study. Levels of fasting glucose and HbA1c in the peripheral blood were measured by ordinary laboratory examination before and 24 months after initiation of the treatment. Oral doses of 150–300 mg/day of Acarbose (Glucobay) were administered for 24 months. Levels of fasting glucose 24 months after initiation of treatment with Acarbose (152 B 44 mg/dl; mean B SD) were significantly lower than those before treatment (212 B 96 mg/dl; p ! 0.001). The levels of HbA1c 24 months after initiation of treatment (7.7 B 0.9%) were also significantly lower than those before treatment (9.8 B 2.6%; p ! 0.001). The mean levels of urinary protein excretion 24 months after initiation (400 mg/g Cr) were lower than those before the treatment (540 mg/g Cr), but the difference was not statistically significant. It appears that mild glycemic control, rather than strict control, might not improve proteinuria in patients with diabetic nephropathy. It is necessary to decrease markedly the levels of blood glucose to improve proteinuria and vice versa. References