Takayasu Taira

Immediate Effect of Shakuyaku-kanzo-to on Muscle Cramp in Hemodialysis Patients

We administered 2.5 g of Shakuyaku-kanzo-to granule to 61 patients who had muscle cramp during hemodialysis (HD) sessions and examined its immediate effects. We selected 10 patients who wanted to take the drug at home, out of cases, for whom the drug was effective on the study described above and had them take the drug in the same way at the beginning of muscle cramp at home examined the effects. In the study during HD sessions, muscle cramp and its associated pain disappeared in 5.3 ± 3.9 min on average in 54 out of 61 cases. In the study of patients who took the drug at home, muscle cramp disappeared within 10 min in all cases. Shakuyaku-kanzo-to is thought to be very useful for muscle cramp during HD sessions of hemodialized patients because it has immediate effects by its oral administration on the occasion of cramp. With regard to the muscle cramp, which appears at home after HD sessions, the patients can cope with it by taking the drug by themselves. This is an epoch-making therapy, for it was impossible to cope with muscle cramp except in hospitals because the therapy of muscle cramp was limited to intravenous infusion of hypertonic solutions of dextrose, mannitol, and saline during HD sessions.

The Immediate Effect of Shakuyaku-kanzo-to, Traditional Japanese Herbal Medicine, for Muscular Cramps during Maintenance Hemodialysis

Accessible online at: www.karger.com/journals/nef Dear Sir, Muscular cramps in patients with chronic renal failure undergoing hemodialysis are very common and the incidence reportedly reaches 20% in all patients [1]. Shakuyaku-kanzo-to is a traditional Japanese herbal medicine which is composed of Paeonia root (Shakuyaku) and Glycyrrhiza root (Kanzo) and is used for the treatment of muscular cramps in patients with normal renal function in Japan. We elucidated the effect of this herbal medicine for muscular cramps in hemodialysis patients. The subjects included 23 hemodialysis patients who experienced muscular cramps during hemodialysis (10 males and 13 females; 3 diabetics and 20 nondiabetics; mean age, 57.2 B 9.0 years; mean duration of dialysis, 8.2 B 6.6 years), with a total of 61 episodes of muscular cramps. Shakuyakukanzo-to Extract Granules for Ethical Use (TJ68: Tsumura & Co., Japan) were administered at a single dose of 2.5 g immediately after the complaint of muscular cramps during hemodialysis. Muscular cramps disappeared in 54 (88.5%) of the 61 episodes. The mean time to disappearance of muscular cramps and associated pain was 5.4 B 3.9 min. No adverse reaction occurred at the single use of Shakuyaku-kanzo-to during hemodialysis.

Expression of epidermal growth factor and its receptor in rabbits with ischaemic acute renal failure

Urinary immunoreactive epidermal growth factor (EGF) levels decrease, and renal immunoreactive EGF levels increase in rats with ischaemic acute renal failure (ARF). We investigated the immunohistochemical localization of EGF and EGF receptor in rabbits with ischaemic ARF to clarify the significance of renal EGF. Male New Zealand White rabbits underwent right nephrectomy prior to a 60 min renal artery clamp. At 3, 6, 24, 48, 72 and 96 h after ischaemia, serum urea nitrogen and serum creatinine were determined. Guinea pig anti-rabbit EGF antibody and monoclonal anti-EGF receptor antibody were used for the primary incubation. EGF was immunolocalized to the ascending limb of Henle and the distal convoluted tubule in the normal right kidneys. However, in the post ischaemic left kidneys at 6, 24, 48 and 72 h, immunoreactivity of EGF was associated with proximal tubules. In the normal kidneys, antibody to EGF receptor reacted with distal tubules and collecting ducts. In the ischaemic kidneys, EGF receptor was localized in the basolateral membrane in the proximal tubules. The expression of EGF and EGF receptor in renal tubules may play an important role in repair following ischaemic renal damage.

Mesangial Proliferative Nephritis in Man Is Associated with Increased Expression of the Cell Survival Factor, Bcl-2

Although most studies suggest that the hypercellularity in mesangial proliferative nephritis is due to increased cell proliferation, we hypothesized that it may also be due to increased expression of survival factors that may block their removal (apoptosis). We therefore studied the expression of apoptosis preventing/delaying the bcl-2 gene product in the glomerulus with various human glomerulonephritides. Immunohistochemistry for Bcl-2, proliferating cell associated protein (Ki-67) and α-smooth muscle actin (α-SMA) was performed on 55 biopsied kidney tissues: 6 cases of orthostatic proteinuria as a control (OP); 6 cases of diffuse proliferative lupus nephritis (WHO type IV, LN-MPGN); 24 cases of IgA nephropathy (IgA); 9 cases of minimal change nephrosis and 10 cases of idiopathic membranous nephropathy. The number of Ki-67-positive cells and the expression of α-SMA in the glomerulus were significantly higher in LN-MPGN and IgA. There was a significant positive correlation between glomerular Bcl-2 expression and glomerular cell proliferation evaluated by the number of Ki-67-positive cells (r = 0.605, p < 0.01) or glomerular α-SMA expression (r = 0.674, p < 0.01). Glomerular expression of Bcl-2 in IgA or LN-MPGN was significantly higher than that in OP (p < 0.01 and p < 0.05 vs. OP, respectively). The Bcl-2-positive cells were present in mesangial locations and demonstrated a perinuclear pattern. These results suggest that maintenance of glomerular hypercellularity in human glomerular diseases is partly due to the prevention of mesangial cell death via Bcl-2 expression.

Urinary Epidermal Growth Factor Levels in Patients With Acute Renal Failure

To investigate the importance of epidermal growth factor (EGF) in patients with renal dysfunction, urinary human EGF (hEGF) levels were determined by radioimmunoassay in 16 patients with acute renal failure (ARF) and in 12 healthy controls. Seven patients with chronic renal failure also were studied. Urinary hEGF levels, corrected for urine creatinine concentrations, were significantly decreased in patients with ARF in the acute phase compared with normal control subjects (0.98 +/- 0.20 v 13.74 +/- 1.18 ng/mg creatinine, P < 0.001), and subsequently increased during the recovery phase (6.10 +/- 0.73 ng/mg creatinine, P < 0.001 v acute phase). A significant positive correlation existed between urinary hEGF levels and creatinine clearance in patients with ARF (r = 0.66, P < 0.001). Serum hEGF levels also were significantly lower in patients with ARF compared with normal control subjects (0.10 +/- 0.01 v 0.30 +/- 0.03 ng/mL, P < 0.001). No significant correlation was found between hEGF concentrations in serum and urine. In conclusion, measurement of urinary hEGF may be useful in the diagnosis of ARF and for following the recovery of the kidney after severe tubular injury.

Individual application of the kidney disease quality of life (KDQOL) instrument to monitor the health status of dialysis patients.

Accessible online at: www.karger.com/journals/nef Dear Sir, Recently, the Kidney Disease Quality of Life (KDQOL®) Instrument, consisting of SF-36 and the kidney disease targeted scales, was developed and has been accepted among many countries because of the scientific and statistical accuracy. Originally, these scales were developed for the group comparisons and not for the individual use [1]. Nevertheless, Meyer et al. [2] reported that the SF-36 was useful in monitoring individual dialysis patients’ health status. We speculated that KDQOL questionnaire might be also as useful as the SF-36 for the individual use. Here, we collect individual KDQOL scores and monitor 1 case before and after a medical intervention, as Meyer et al. [2] had tried. 108 seminight hemodialysis patients, mostly socially rehabilitated responded to

Kidney Disease Quality of Life of Japanese Dialysis Patients Who Desire Administration of Sildenafil and the Treatment of Erectile Dysfunction Using Sildenafil

Abstract:  Erectile dysfunction (ED) is common among patients on dialysis therapy. In the present study, we attempted administration of sildenafil to Japanese patients undergoing dialysis. In order to diagnose ED before prescribing sildenafil, we assessed the hemodialysis patients who desired sildenafil by using the five items version of the International Index of Erectile Function (IIEF‐5). In addition, the characteristics of the quality of life in Japanese hemodialysis patients who desired sildenafil were assessed using the kidney disease quality of life (KDQOL). To all 37 male subjects (mean age of 53.8 ± 10.4 years) attending the Outpatient Hemodialysis Unit at Atsugi Clinic (Atsugi City, Japan), it was explained by their primary doctor that the treatment of ED with sildenafil was possible. As a result, 10 patients (27.0%) desired the treatment. For eight patients, ED was diagnosed by IIEF‐5 prior to prescription of sildenafil. The mean IIEF‐5 scores were 6.13 ± 4.67 points. Sildenafil was prescribed to five patients (three diabetic, two non‐diabetic) and sexual function was improved in three cases. The main adverse effect was found to be ventricular arrhythmia in one case. As for KDQOL, the group desiring sildenafil showed significantly high values in Dialysis Staff Encouragement and Patient Satisfaction. Among the other nine dialysis patients (five diabetic, four non‐diabetic; mean age of 58.1 ± 8.9 years) who visited the ED department of Ishida Hospital (Asahikawa City, Japan), sildenafil was effective for all non‐diabetic patients (100%) and for only one diabetic patient (20%). Among all 14 patients at Atsugi Clinic and Ishida Hospital, sildenafil efficacy rates were 83.3% for non‐diabetic patients and 37.5% for diabetic patients. Non‐diabetic patients without the side‐effects were all responders for the sildenafil treatment. The patients who relied on the dialysis staff and were more satisfied with the general treatment in the dialysis institute desired the administration of sildenafil under the present circumstances wherein the dialysis population had few experiences of sildenafil treatment. Diabetic status is thought to be a negative factor for the response of sildenafil treatment in dialysis patients.

Immunochemical Study of Epidermal Growth Factor in Rats with Mercuric Chloride-Induced Acute Renal Failure

Urine contains high concentrations of epidermal growth factor (EGF), and EGF is a potent growth promoter for proximal tubular cells. In the present study, urinary and whole-kidney EGF levels were investigated in rats with mercuric chloride (HgCl2)-induced acute renal failure (ARF) using a specific radioimmunoassay for rat EGF to clarify changes in EGF after toxic injury. Male Wistar rats were given HgCl2 (2 mg/kg, subcutaneously) or saline. Serum urea nitrogen and creatinine levels were measured for 4 days after toxin administration. Forty-eight hours after toxic injury, urinary immunoreactive EGF levels in HgCl2-treated rats decreased significantly compared with control rats (1.62 +/- 0.15 versus 3.78 +/- 0.21 ng/mg creatinine; p < 0.01). Urinary immunoreactive EGF was at its lowest level 96 h after toxic injury (0.64 +/- 0.06 ng/mg creatinine; p < 0.001). Twenty-four hours after toxic injury, renal immunoreactive EGF levels increased significantly compared with control rats (22.04 +/- 2.12 versus 4.84 +/- 0.70 ng/g wet weight tissue; p < 0.001), and the increase persisted for as long as 48 h (13.36 +/- 1.61 ng/g wet weight tissue; p < 0.05). In summary, urinary immunoreactive EGF levels decreased and renal EGF levels increased in rats with HgCl2-induced ARF. These findings suggest that there is an impairment in the excretion of EGF in rats with HgCl2-induced ARF and that local paracrine production of EGF continues in ARF.

Performance of the Newer Type (Lixelle Type S-15) on Direct Hemoperfusion Beta-2-Microglobulin Adsorption Column for Dialysis-Related Amyloidosis

Accessible online at: www.karger.com/journals/nef Dear Sir, Dialysis-related amyloidosis (DRA) is a common complication associated with longterm hemodialysis therapy [1]. There is no effective therapy to prevent and/or treat DRA. However, the elimination of ß2-microglobulin (ß2-MG), the major constituent of the amyloid fibrils in DRA that accumulates in uremic patients [2], from the circulation has been expected to bring some clinical benefit [3]. The direct hemoperfusion ß2-MG adsorption column (Lixelle Model Type S35, KANEKA Corp., Japan) was developed under this background. This column is a blood purification system that adsorbs ß2MG for patients with dialysis-related amyloidosis. This column has been commercially available in Japan in combination with hemodialysis since 1996. The adsorbent mainly absorbs peptides or proteins whose molecular weight (MW) ranged from 4,000 to 20,000 daltons [3]. The adsorbent does not significantly adsorb low-MW substances and electrolytes whose MW are lower than 1,000 daltons. Table 1. ß2-MG removal volume (mg) and rate (%)

The Distribution of 3H-Labeled Endotoxin in the Kidney of Liver Cirrhotic Rats

Although the etiology and pathogenesis of progressive renal failure is largely unknown, endotoxin is supposed to be one of the contributory factors. However, the distribution of endotoxin in liver cirrhosis has not been clarified. Therefore we studied the distribution of 3H-labeled endotoxin in the kidney in rats with CCl4-induced liver injury. Daily inhalations of CCl4 on rats for 6 and 10 weeks produced liver fibrosis (LF group, N = 5) and cirrhosis (LC group, N = 5), respectively. At 6 or 10 weeks, animals were sacrificed 24 hours after an intravenous injection of endotoxin labeled with 3H at the galactose moiety (12,000 cpm/1 g body weight). In the liver, 3H-labeled endotoxin was taken up mainly by Kupffer cells as determined by autoradiography. Compared to control rats, in rats of the LC or LF group the measured amount of 3H-labeled endotoxin per gram kidney or ml blood increased, while that of the liver was significantly decreased. A positive correlation of the amount of 3H-labeled endotoxin per weight or volume respectively was shown between kidney and blood, but not between lung or spleen and blood. These results suggest that overflow of endotoxin due to decreased inactivation in the liver causes endotoxemia in liver injury and that the resulting endotoxemia may directly affect the kidney. The resulting endotoxin-induced vasoconstriction may be a contributory factor for the progressive renal failure frequently observed in liver cirrhosis.