Does the inhibition of renin-angiotensin system decrease inter-dialytic weight gain in anuric hemodialysis patients?

OBJECTIVE: Knowledge about the inhibition of centrally located angiotensin-I (AT-I) receptors by highly lipophilic AT-I receptor blockers and its' effect are limited with experimental studies. Thus, we aimed to investigate the effect of Telmisartan on Inter-dialytic weight gain (IDWG) % and echocardiographic measurements in anuric hemodialysis (HD) patients. PATIENTS AND METHODS: A total of forty-one anuric HD patients with ≥ 6 months maintenance on HD were included in this prospective, randomized and self-controlled study. Four weeks prior the study, angiotensin converting enzyme blockers and AT-I receptor blocker drugs were stopped. Patients were assessed three times during the study protocol. These are baseline, three months later (without Telmisartan period) and three months after Telmisartan therapy. RESULTS: IDWG % was significantly decreased in the period of with Telmisartan compared to period without Telmisartan (5.6 ± 1.0% vs 5.3 ± 1.0%, p = 0.03). After the administration of Telmisartan left ventricule end-diastolic diameter (LVEDD) (p = 0.001) and inferior vena cava diameter (IVCD) (19.1 ± 3.8 mm vs 17.3 ± 4.2 mm, p = 0.001) were significantly decreased compared to the period of without Telmisartan. Despite of significantly changes observed in IVCD and LVEDD measurements in a period without Telmisartan, there was no significantly difference in left ventricular mass index (LVMI) measurements in this period. However, LVMI was significantly regressed after the administration of Telmisartan (269.3 ± 82.7 g vs 256.3 ± 70.3 g, p = 0.003 respectively). CONCLUSIONS: Treatment of anuric HD patients with Telmisartan at a dose of 40 mg a day reduces IDWG%, LVEDD and IVCD measurements. Further studies investigating the long-term effect of these beneficial effects on clinical outcomes are necessary.

In vitro metabolic N- and C-oxidation of phenanthridine.

The in vitro microsomal metabolism of phenanthridine has been studied to establish as to whether phenanthridine produces the corresponding N-oxide and lactam as metabolites and the mechanism involved. We now report our preliminary findings using rat hepatic microsomal preparations (control and induced with phenobarbitone) fortified with NADPH. The potential metabolite, phenanthridine-N-oxide, was prepared by m-CPBA oxidation of substrate; the lactam was commercially available. The substrate and metabolites were extracted and analysed by HPLC and TLC. Five metabolites, i.e. the corresponding N-oxide, lactam and three other products, were detected. Both N-oxide and lactam metabolites showed identical chromatographic behaviour and UV spectrum--using a multi-array UV detector linked to a HPLC system--as the authentic compounds. The uncharacterised metabolites are proposed to be phenolic because of their chromatographic behaviour and response to detection reagents. The amount of N-oxide and lactam formed was significantly increased when phenobarbitone induced rat microsomes were used as enzyme source. The results indicate that these latter metabolites are probably formed by a phenobarbitone inducible CYP450 isozyme. It may be that the lactam was produced via the N-oxide and experiments are under way to investigate the proposed pathway.