[Effect of angiotensin II receptor antagonist (losartan) on renal function, serum potassium and blood pressure in patients with advanced renal failure: differences between patients with a serum creatinine (SCr) level higher than 3 mg/dl and those with a lower SCr level].

The administration of angiotensin II receptor antagonist(AIIA) to patients with advanced chronic renal failure(CRF) is not actively recommended. This study was performed to verify the appropriateness of this situation and to determine if there are any substantial differences between patients with a serum creatinine(SCr) level higher than 3 mg/dl and those with a lower SCr level in terms of the clinical effects such as renal function, serum potassium level and systemic blood pressure(BP) after the administration of AIIA. Sixteen patients with advanced CRF who were admitted to the out-patient clinic in Jikei University Hospital(1998/1-1999/12) were enrolled(average age: 65 years, underlying renal disease: diabetic nephropathy 6, CGN 5, and other 1). They had never been administered AIIA before. The patients were classified into two groups in accordance with their level of SCr: group A(SCr lower than 3.0 mg/dl; n = 11), and Group B(SCr higher than 3.0 mg/dl; n = 5). Losartan(50 mg/day) administration was started in order to examine parameters such as the SCr, potassium, BP at the out-patient clinic, and urinary protein excretion at the 0, 1, 3, 6, 9, and 12 month time points. Although the 1/SCr values provided negative slopes with time in both groups, no significant difference was found between the two slopes. There were no changes in the serum potassium levels or urinary protein excretion during the study period in either group, and no statistical difference was found between the two groups. Although the serum potassium level exceeded 5.5 mEq/l in two patients each in both groups, the level was controlled by diet therapy with restricted potassium. BP was reduced significantly in both groups during the study period, and no statistical difference in BP reduction was observed between the two groups. In conclusion, the results indicate there were no differences in the effect on renal function, serum potassium levels or systemic BP between the patients with a SCr level higher than 3.0 mg/dl and those with a lower level. The results also support the notion that patients with advanced renal dysfunction are not precluded from AIIA administration.

Plasma pteridine concentrations in patients with chronic renal failure.

BACKGROUND: Pteridine metabolism is impaired in the uraemic state. This may affect cardiovascular function and contribute to malnutrition. We wished to clarify further the impact of impaired pteridine metabolism. METHODS: Using the HPLC method, the plasma concentrations of endogenous pteridines were determined in 64 patients with chronic renal failure (33 on intermittent haemodialysis (HD) treatment vs 31 not yet on renal replacement therapy), and in 18 healthy controls. The patients were classified into three groups on the basis of creatinine clearance (Ccr): group (a), Ccr >60 ml/min; group (b), Ccr=10-60 ml/min; group (c), all patients receiving HD. RESULTS: Total neopterin (NP) and biopterin (BP) levels and the NP/BP ratio (a biomarker for macrophage activity) were significantly higher, whereas tetrahydrobiopterin (BH(4))/dihydrobiopterin (BH(2)) ratio (a biomarker for nitric oxide synthase and phenylalanine hydroxylase activities) was significantly lower in group (c) (118.9+/-11.7 ng/ml, 18.8+/-1.2 ng/ml, 6.79+/-0.53, and 0.26+/-0.06) than in healthy subjects (5.17+/-0.29 ng/ml, 2.83+/-0.19 ng/ml, 1.92+/-0.13, and 1.15+/-0.11; P<0.01). These significant differences were also observed between control and group (b) (12.4+/-2.20 ng/ml, 4.48+/-0.36 ng/ml, 2.81+/-0.48, and 0.74+/-0.08; P<0.01). In groups (a) and (b), significant negative correlations were found between Ccr and the total NP level (r=-0.663, P<0.01), the total BP level (r=-0.492, P<0.01), the BH(2) level (r=-0.677, P<0.01), and the NP/BP ratio (r=-0.493, P<0.01). Conversely, significant positive correlations were found between Ccr and the BH(4)/BH(2) ratio (r=0.602, P<0.01). CONCLUSION: The reduction of quinoid-type BH(2) to BH(4) is modified in patients with advanced chronic renal failure, before and after the initiation of regular HD treatment. These metabolic alterations may play a role in the impaired macrophage, endothelial constitutive nitric oxide synthase, or phenylalanine hydroxylase (PH) activities observed in such patients.