Tadao Endo

De novo Development of Hypercholesterolemia and Elevated High-Density Lipoprotein Cholesterol: Apoprotein A-I Ratio in Patients with Chronic Renal Failure following Kidney Transplantation

Serum lipids, apoprotein and lecithin-cholesterol acyltransferase activities were studied in 27 renal transplant recipients with stable and normal renal function (serum creatinine 0.16 mM/l or less) sustained for more than 1 year following grafting. Hypertriglyceridemia, which was characteristic of hyperlipidemia in 18 hemodialyzed patients with chronic renal failure, was no longer manifest in transplant recipients. On the other hand, de novo hypercholesterolemia was observed posttransplant with mean serum levels of 5.82 +/- 1.34 versus 5.01 +/- 0.88 mM/l in 575 normal controls. As to the high-density lipoprotein metabolism, the cholesterol content (1.72 +/- 0.56 mM/l) was significantly higher in transplant patients than in hemodialyzed patients (0.82 +/- 0.31 mM/l). In contrast, no variation in apoprotein A-I levels was found between both groups of patients, which produced an elevated high-density lipoprotein cholesterol:apoprotein A-I ratio. Thus, derangement in the serum lipid profile, although qualitatively different, continued to be present following transplantation, and its relevance to the cardiovascular morbidity in these patients remains to be evaluated.

15-Deoxyspergualin "rescue therapy" for methylprednisolone-resistant rejection of renal transplants as compared with anti-T cell monoclonal antibody (OKT3).

A randomized trial with OKT3, an anti—T cell monoclonal antibody or with 15-deoxyspergualin against methylprednisolone-resistant rejection crisis was performed in 25 posttransplant patients immunosuppressed with prednisolone and cyclosporine. At least temporary reversal of rejection was observed in 58.3% of patients treated with 15-deoxyspergualin. This reversal rate may be quite comparable to 61.5% seen in patients treated with OKT3. Adverse effects with 15-deoxyspergualin were related to bone marrow suppression, while those with OKT3 were pyrexia, gastrointestinal symptoms, and herpes infection. In contrast to OKT3, which may act by modulating T cell surface antigen, 15-deoxyspergualin may be effective somewhere in the later stages of the rejection cascade.

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.

A Non‐Randomized Comparative Study of Visual laser Ablation and Transurethral Resection of the Prostate in Benign Prostatic Hyperplasia

Background: Transurethral resection of the prustate (TURP) haz been the ‐preferred surgical treatment for benign prostatic hyperplasia (BPH) for the past 50 years. Alternative methods for treating BPH such as visual laser ablation (VLAP) have been established during the past decade. In order to assess the safety and efficacy of VLAP, this alternative method was performed using a Urolase fiber and neodymium: yttrium‐aluminum‐garnet laser and compared to results obtained in patients treated with TURP for BPH Methods: In this non‐randomized comparative study, 100 BPH patients were equally split between treatment with VLAP or TURP, and their cases compared. The efficacy was assessed using an International Prostate Symptom Score, urinary flow rates, post‐void residual urinary volume and an estimated prostate volume.

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.

Factors contributing to long graft survival in non-heart-beating cadaveric renal transplantation in Japan: a single-center study at Kitasato University.

Yoshida K, Endo T, Saito T, Iwamura M, Ikeda M, Kamata K, Sato K, Baba S. Factors contributing to long graft survival in non‐heart‐beating cadaveric renal transplantation in Japan: a single‐center study at Kitasato University. Clin Transplant 2002: 16: 397–404.

Cause of Death in Renal Transplant Patients: A Comparison Between Azathioprine and Ciclosporin

Abstract The results of renal transplantation have improved due to advances in immunosuppression techniques of preservation, and pre- and postoperative treatments; however, both morbidity and mortality remain serious problems. To decrease the morbidity and mortality rates we analyzed the causes of death after renal transplantation in our hospital. Between 1972 and 1999, we performed 364 renal transplantations, 257 of which were living-related and 107, cadaveric. There were 178 patients given azathioprine and 186 given ciclosporin. The survival rate of the patients on ciclosporin therapy was much better than that of those on azathioprine therapy. Of the total 364 renal transplant patients, 59 (16.2%) died, and 28 (47.5%) of these 59 deaths occurred within 1 year after renal transplantation. The causes of death were infection in 19 (32.2%) patients, gastrointestinal diseases in 16 (27.1%), cardiovascular diseases in 11 (18.6%), cerebrovascular diseases in 6 (10.2%), suicide in 3 (5.1%), and other causes in 4 (6.8%). These findings reinforce that early diagnosis and treatment are essential to decrease the morbidity and mortality rates assoiated with renal transplantation.

T-cell receptor variable gene analysis of renal allograft-infiltrating cells in biopsy specimens using a nonradioisotopic micromethod.

BACKGROUND A sensitive micromethod for T-cell receptor (TCR) analysis is needed for clonality analysis of renal allograft-infiltrating T cells (RAITs) obtained by needle biopsy. METHODS TCR cDNA was amplified by the anchored polymerase chain reaction and was hybridized with 28 different TCR beta variable (TCRBV) genes fixed on nylon membranes, and the percentage of each TCRBV gene was measured spectrophotometrically. RESULTS The specificity and linearity of the hybridization technique and the constancy of the TCRBV percentages over a wide range of sample amounts were demonstrated by control experiments. Analysis of RAITs of biopsy specimens from four patients showed broad or skewed TCRBV usage, indicating the presence of polyclonal and oligoclonal RAIT populations, respectively. In one patient who received OKT3 immunosuppressive treatment, the TCRBV skewness was dramatically reduced after the treatment. CONCLUSION We have established a powerful method for analyzing RAIT clonality, which is especially useful for monitoring RAIT dynamics after immunosuppression therapy.

Comparative study of population pharmacokinetics upon switching of cyclosporine formulation from Sandimmune to Neoral in stable renal transplant patients.

CYCLOSPORINE A (CyA) is the most commonly used immunosuppressant in renal transplantation. Because of its narrow therapeutic window, therapeutic drug monitoring by measuring the trough level is widely employed. However, the original formulation of CyA, Sandimmune (SIM), has considerable interand intrapatient variability because of its variable absorption. Neoral (MEPC), a new microemulsion form of CyA, has been reported to have improved interand intrapatient variability, but it may need different TDM than the trough level, such as AUC0–4 or C2 level. In this report we performed a population pharmacokinetic study before and after switching from SIM to MEPC in 69 stable renal transplant patients, thereby determining the population pharmacokinetic parameters for a comparison of the bioequivalence of the two different CyA formulations, using the nonlinear mixed-effects model (NONMEM with first-order method) population pharmacokinetic program.

Cadaveric renal transplantation from non-heart-beating donors with graft survival for more than 10 years.

THE number of cadaveric renal transplantations has not increased in Japan; this is due to a difference in social acceptance of brain death. Moreover, as the shortage of donor kidneys is a big issue not only in Japan but all over the world, it is important to obtain longer graft survival in cadaveric renal transplantation. We have performed 107 cadaveric renal transplantations from non-heart-beating donors in Kitasato University Hospital from 1974 until the present. We have analyzed the factors that contribute to longer graft survival among twenty of 107 cadaveric grafts that have survived longer than 10 years.