Yoshiki Matsushita

In vivo Effect of 1α-Hydroxyvitamin D3 on Interleukin-2 Production in Hemodialysis Patients

The immunoregulatory effect of 1α-OHD3, a precursor form of active vitamin D3 1,25 (OH)2D3, was examined in hemodialysis patients. Peripheral blood mononuclear cells (PBM) from hemodialysis patients produced significantly less interleukin-2 (IL-2) than those from normal controls. Four weeks of oral administration of 0.5 µg/day of 1α-OHD3 enhanced the IL-2 production of PBM from the patients. This fact suggests that 1α-OHD3 therapy may be useful for the restoration of IL-2 production in hemodialysis patients, and that the vitamin D3 deficiency may be responsible for the impairment of cellular immunity associated with IL-2 production disorder in hemodialysis patients.

Clinical implications of coinfection with a novel DNA virus (TTV) in hepatitis C virus carriers on maintenance hemodialysis

A novel hepatitis‐associated DNA virus, designated as transfusion‐transmitted virus (TTV), was identified recently. We investigated the frequency of TTV viremia in hepatitis C virus (HCV) carriers on maintenance hemodialysis to determine whether TTV coinfection has any clinical relevance. The subjects were 50 hemodialysis patients who had been followed over 4 years after diagnosis of HCV infection. Stored serum samples derived from each patient every 12th month after enrollment were subjected to polymerase chain reaction to amplify TTV DNA and HCV RNA. At enrollment, TTV viremia was detected in 24 (48%) HCV‐positive patients irrespective of the number of previous blood transfusions and the duration of hemodialysis. The presence of TTV viremia had no relation to serum alanine aminotransferase (ALT) levels, HCV viremic levels or HCV genotypes. After enrollment, HCV infection persisted in all patients over the 4‐year follow‐up period, whereas spontaneous resolution of TTV infection was observed in 7 (29%) of the 24 TTV viremic cases (annual rate 7.3%, 95% confidence interval [CI] 0.8–25.5%). Evidence for TTV infection was found in 4 (15%) of the 26 TTV nonviremic patients (annual incidence 3.9%, 95% CI 0.1–19.6%). The relationship between the ALT profile and TTV infection during follow up was not evident. Active TTV coinfection occurs frequently in HCV carriers undergoing hemodialysis but exerts no biochemical or virological influence on the underlying hepatitis C. Lack of disease association and the frequent spontaneous resolution of infection suggest that the clinical significance of TTV infection remains unclear. J. Med. Virol. 59:431–436, 1999.

Reappraisal of Biochemical Hepatitis C Activity in Hemodialysis Patients

We reappraised biochemical hepatitis C activity in hemodialysis patients in comparison with normal controls. A total of 111 hemodialysis patients and 66 healthy volunteer blood donors with hepatitis C virus (HCV) infection were consecutively enrolled. Serum alanine aminotransferase (ALT) levels were normal (< or =45 U/L) in 103 (93%) hemodialysis patients and 34 (52%) donors (p < 0.001). HCV viremic levels were lower in the hemodialysis group (p = 0.044), with no difference in the HCV genotype prevalence. During two-year follow-up, 60 (67%) of 90 hemodialysis patients and 13 (26%) of 50 donors showed persistently normal ALT levels (p < 0.001). For hemodialysis patients, however, the upper normal limit of ALT activity was reset at 25 U/L corresponding to the mean + 2 x SD for the normalized ALT distribution in 400 control patients. The adjusted ALT levels were initially normal in 73 (66%) hemodialysis patients and persistently normal in 19 (21%). Thus, ALT levels were the same for the two groups. GB virus C (GBV-C)/hepatitis G virus (HGV) coinfection found only in the hemodialysis group (10/111) had no influence on the disease. A relationship was noted between low disease activity and female gender in both groups. These findings indicate that biochemical hepatitis C activity in hemodialysis patients is similar to that in normal controls and should be monitored based on adjusted ALT levels.

Abnormal Calcium Metabolism in Hemodialyzed Patients with Diabetic Nephropathy

Calcium metabolism was studied in hemodialyzed patients with diabetes mellitus nephropathy (HD/DM) and in hemodialyzed nondiabetic patients with chronic glomerulonephritis (HD/non-DM). Incidence of bone changes visible in X-ray films, assessed by changes in the lamina dura and trabecular patterns of mandibulae, was less in HD/DM than in HD/non-DM patients. Serum c-terminal parathyroid hormone was significantly lower in HD/DM than that in HD/non-DM. Serum calcitonin was higher in HD/DM than that in HD/non-DM. The lower level of c-terminal parathyroid hormone would be a reason that bone changes were less in HD/DM than in HD/non-DM patients.

Effects of the Nicotinic Acid Analogue Niceritrol on Lipoprotein Lp(a) and Coagulation-Fibrinolysis Status in Patients with Chronic Renal Failure on Hemodialysis

Effects of the Nicotinic Acid Analogue Niceritrol on Lipoprotein Lp(a) and Coagulation-Fibrinolysis Status in Patients with Chronic Renal Failure on Hemodialysis T. Tetsuo Shoji Y. Yoshiki Nishizawa K. Koichi Kawasaki T. Tsutomu Tabata Y. Yoshiki Matsushita T. Takashi Inoue H. Hirotoshi Moriia Second Department of Internal Medicine, Osaka City University Medical School, and Division of Internal Medicine, Inoue Hospital, Osaka, Japan

Changes in parathyroid hormone in diabetic patients on long-term hemodialysis.

Changes in parathyroid hormone (PTH) and osteocalcin over 3 years were studied in hemodialyzed patients with diabetic nephropathy (HD/DM) and hemodialyzed patients without diabetes (HD/non-DM). In HD/DM patients, concentrations of the carboxyl terminal regions of PTH and osteocalcin in the serum did not change significantly, but in HD/non-DM patients, both concentrations increased significantly. In patients in both groups, the mean concentration of the mid-region of PTH increased significantly. Secondary hyperparathyroidism in HD/DM develops slower than in HD/non-DM.

Hepatitis C biochemical remission and viral replication in haemodialysis patients

The natural course of non‐A, non‐B (type C) hepatitis was studied in 62 haemodialysis patients. From the onset of the disease, serum alanine aminotransferase levels were monitored monthly for 9‐218 mon (median 115). After fluctuation of aminotransferase levels for 1‐206 mon (median 39), 57 (92%) patients showed normalization of these levels lasting until the end of the follow‐up, which was for >2 yr in 31 (50%) cases and for >5 yr in 15 (24%) cases. At the end of follow‐up, hepatitis C viraemia was assessed by reverse transcription‐polymerase chain reaction (RT‐PCR) and branched DNA (bDNA) assay. Viraemic levels were significantly lower in the 15 patients with normal aminotransferase for >5 yr (median RT‐PCR + ve/bDNA‐ve, range RT‐PCR‐ve to 106.7 Eq/mL) than in the 47 cases with normal levels for <5 yr (median 106.6, range RT‐PCR + ve/bDNA‐ve to 107.6 Eq/mL) (P < 0.01). Moreover, a significant inverse relation was observed between viraemic levels and the duration of aminotransferase normalization (r = −0.46, P < 0.01). These findings indicate that biochemical remission of hepatitis C may be frequent in haemodialysis patients and may be related to viral attenuation.

Acute Renal Failure in McArdle’s Disease

This is a report of a case of acute renal failure associated with McArdles disease. A 45-year-old man had acute renal failure that required dialysis. His case was subsequently diagnosed as rhabdomyolysis secondary to McArdles disease, a primary myopathy due to myophosphorylase deficiency. History-taking revealed nothing suspected to be responsible for precipitating the renal failure.

Clinical Availability of Serum Fructosamine Measurement in Diabetic Patients with Uremia

Serum fructosamine levels were investigated in patients with uremia undergoing various modes of treatment. The serum fructosamine levels correlated positively with the blood glucose levels determined a week or two earlier. The fructosamine levels were significantly affected by the protein concentration, and those corrected for protein concentrations had a closer correlation to the blood glucose levels than did the uncorrected levels. The corrected fructosamine levels were not significantly different between healthy volunteers and nondiabetic patients with uremia on conservative treatment. In an in vitro system, fructosamine concentrations were hardly affected by urea, which is known to influence the level of hemoglobin A1. These results suggest that serum fructosamine measurement can provide us with reliable information on a short-term glycemic condition, even in azotemic patients. To be more precise, the serum level of fructosamine corrected for protein concentration can be an excellent glycemic index which is not susceptible to over- or dehydration and is of high clinical value, especially in the management of diabetic patients with chronic renal failure.

Clinical effects of 1α-hydroxyvitamin D3 on calcium metabolism in hemodialysis patients

著者らは昭和53年以降慢性血液透析患者のカルシウム代謝異常に対して活性型ビタミンD3である1α-OH-D3を投与してきた. 過去10年間におけるその効果を経年的に評価するために, 慢性血液透析患者217名を対象とし, 透析期間によって5群に分け, カルシウム代謝異常に対する1α-OH-D3の効果を主に次の項目に関して検討した.1) 手指骨骨X線上の骨膜下吸収所見1α-OH-D3内服率が高い群では骨膜下吸収所見の陽性率は低下していた. 投与前に陽性を呈していた26例中17例 (65%) は1α-OH-D3内服により改善した.2) 低カルシウム血症 (4.0mEq/l以下) の頻度1α-OH-D3内服率の上昇につれて低カルシウム血症の頻度は明らかに低下したが, 血清カルシウム4.5mEq/l以上の頻度は必ずしも高くなく, 1α-OH-D3内服によって4.0-4.5mEq/lに維持されている例が多かった.3) 高c-PTH血症 (10.0ng/ml以上) の頻度透析導入1年以内に1α-OH-D3を投与開始した群では, 短期的 (3年以内) には血中c-PTHは抑制される傾向にあるが, 長期的には高c-PTH者の頻度は1α-OH-D3投与によっても漸増傾向であった.以上の結果より, 現状での1α-OH-D3投与は長期的にみた場合PTH抑制という面で不十分と考えられた. その効果をさらに高めるためには, 透析導入早期からの投与開始と血清カルシウムを4.5-5.0mEq/lに維持するように投与量を調節することが重要であると認識した.