Abstract. Diepeveen SHA, Verhoeven GWHE, van der Palen J, Dikkeschei LD, van Tits LJ, Kolsters G, Offerman JJG, Bilo HJG, Stalenhoef AFH (Isala Clinics, location Weezenlanden, Zwolle; Medical Spectrum Twente, Enschede; and Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands). Effects of atorvastatin and vitamin E on lipoproteins and oxidative stress in dialysis patients: a randomised-controlled trial. Objectives. The objective of this study was to examine the effects of treatment with atorvastatin, a-tocopherol and the combination of both, on lipoproteins and oxidative stress in dialysis patients. Design and setting. This double-blind randomised placebo-controlled trial was performed at the dialysis department of a non-university hospital. Subjects, intervention and measurements. A total of 44 clinically stable, non-diabetic patients on dialysis therapy (23 on haemo-and 21 on peritoneal-dialysis) without manifest cardiovascular disease were included in this study. They were randomised for treatment during a period of 12 weeks with 40 mg atorvastatin + placebo a-tocopherol (group 1) once daily, 800 IU a-tocopherol + placebo atorvastatin once daily (group 2), 40 mg atorvastatin + 800 IU a-tocopherol once daily (group 3), or placebo atorvastatin + placebo a-tocopherol once daily (group 4). Assessment of lipid profile and oxidative stress was performed at the start of the study and after 12 weeks of treatment.Results. Treatment with atorvastatin reduced total cholesterol, triglycerides (TG), low-density lipoprotein (LDL) cholesterol, apolipoprotein B (apoB) and levels of oxidised LDL (oxLDL) with 30-43%. It had no influence on LDL oxidisability. Additional supplementation with a-tocopherol had no effect on lipid profile and oxLDL levels but decreased in vitro LDL oxidisability. No side-effects were observed. Conclusions. Treatment with atorvastatin is effective in lowering plasma total cholesterol, TG, LDL, apoB and oxLDL in a population of stable dialysis patients and might therefore be an effective tool in improving the poor cardiovascular outcome in these patients. Supplementation of a-tocopherol to atorvastatin had beneficial effects on in vitro LDL oxidisability and might therefore be of additional value. Further research on the clinical effects of treatment with atorvastatin in combination with a-tocopherol is necessary.

Ten previously untreated patients with metastatic non-seminomatous testicular carcinoma received cis-diamminedichloroplatinum (CDDP). Renal function studies were performed before and following the first CDDP infusion. A decrease in effective renal plasma flow (ERPF) and an increase in filtration fraction (FF) was found in all patients. These findings suggest primary changes in renal hemodynamics during CDDP infusion.

Nine patients (Group A) with histologically proven, nonseminomatous testicular cancer were treated with cisplatin (CDDP) according to the Einhorn regimen. Renal function studies including the measurement of the effective renal plasma flow (ERPF) and the glomerular filtration rate (GFR) were performed prior to the chemotherapy and then after treatment on days 10 and 21 of the first course. In order to prevent CDDP-induced nephrotoxicity, verapamil (a calcium entry blocker) and cimetidine were given along with CDDP. The results were compared with others from another group of nine patients (Group B) treated with CDDP, but without verapamil and cimetidine. In Group A there was much less of a decrease in ERPF as compared to Group B on day 21. In addition, the decrease in GFR on days 10 and 21 was totally prevented in the verapamil- and cimetidine-treated group.

Background/Aim: In patients with end-stage renal disease (ESRD), cardiovascular complications are the main cause of death. Increased oxidative stress is one of the risk factors for enhanced atherosclerosis in this population. Literature data vary partially dependent on differences in methodology. The present study compares three different methods: plasma lipid peroxides, the newly developed measurement of circulating oxidized LDL (Ox-LDL) particles and the frequently used copper-induced LDL oxidation lag time. Methods: We assessed plasma lipid peroxides, circulating Ox-LDL and in vitro copper-induced LDL oxidation lag time in 47 non-diabetic patients with ESRD, at the start of renal replacement therapy, and compared these with 41 age- and sex-matched controls. Results: In ESRD, total cholesterol (4.6 ± 1.1 vs. 5.6 ± 0.9 mmol/l; p < 0.001), LDL cholesterol (2.8 ± 0.8 vs. 3.5 ± 0.7 mmol/l; p < 0.001) and HDL cholesterol (1.0 ± 0.3 vs. 1.4 ± 0.4 mmol/l; p < 0.001) were lower compared to controls. Plasma lipid peroxides were higher (1.1 ± 0.5 vs. 0.8 ± 0.5 µmol/l; p = 0.003) in ESRD. No differences were observed in plasma Ox-LDL (63.1 ± 62.0 vs. 55.3 ± 48.0 mg/l). However, due to the lower plasma LDL cholesterol in ESRD, LDL oxidation level was increased in ESRD (7.1 ± 0.1 vs. 4.2 ± 0.3%; p = 0.03). LDL lag time was slightly longer (89 ± 11 vs. 84 ± 11 min; p = 0.04) in ESRD. There were no significant differences regarding the amount and rate of dienes produced. Conclusions: Elevated levels of lipid peroxides and higher LDL oxidation levels support the theory that ESRD is associated with increased oxidative stress, which may explain the accelerated atherosclerosis. The measured amount of oxidative stress is not reflected by in vitro oxidizability of LDL.

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Renal function studies were performed in 18 patients with nonseminomatous testicular cancer during four platinum-containing chemotherapy courses. The first 9 patients received chemotherapy alone, the second 9 also captopril, an angiotensin I converting enzyme inhibitor, in order to prevent cis-diamminedichloroplatinum-induced nephrotoxicity. In the first group a decrease in glomerular filtration rate, that was preceded by a fall in effective renal plasma flow, was observed. In the second group, captopril was able to prevent the initial decrease in effective renal plasma flow, but failed to prevent the ultimate decrease in glomerular filtration rate.

On the assumption that hemodynamic changes in renal blood flow are the initial expression of cis-diamminedichloroplatinum (CDDP)-related nephrotoxicity, we treated patients with metastatic non-seminomatous testicular carcinoma during CDDP infusion with captopril. This angiotensin-converting enzyme inhibitor significantly attenuated the initial decrease in effective renal plasma flow and can probably be used to protect the kidneys against CDDP-induced nephrotoxicity.