N-acetylcysteine does not prevent contrast induced nephropathy after cardiac catheterisation with an ionic low osmolality contrast medium: a multicentre clinical trial.

OBJECTIVE: To evaluate oral N-acetylcysteine in the prevention of contrast induced nephropathy (CIN) in patients at low to moderate risk undergoing cardiac catheterisation with ionic low osmolality contrast medium. METHODS: In a multicentre double blind clinical trial 156 patients undergoing coronary angiography or percutaneous coronary intervention with serum creatinine > or = 106.08 micromol/l or creatinine clearance < 50 ml/min or diabetes mellitus were randomly assigned to receive N-acetylcysteine 600 mg orally twice daily for two days or placebo. Only low osmolality ionic contrast medium was used. RESULTS: Sixteen patients developed CIN, defined as an increase of 44.2 micromol/l in creatinine in 48 hours: eight of 77 patients (10.4%) in the N-acetylcysteine group and eight of 79 patients (10.1%) in the placebo group (p = 1.00). The mean (SD) change in serum creatinine was similar in both groups: 7.96 (35.36) micromol/l in the N-acetylcysteine group and 6.19 (25.64) micromol/l in the placebo group (p = 0.67). No difference was observed in the change in endogenous creatinine clearance (-0.54 (10.4) ml/min v -2.52 (12.3) ml/min, N-acetylcysteine and placebo, respectively, p = 0.28). CONCLUSION: Oral N-acetylcysteine did not prevent CIN in patients at low to moderate risk undergoing cardiac catheterisation with ionic low osmolality contrast medium.

Bradykinin B1 receptor stimulates the proximal tubule Na(+)-ATPase activity through protein kinase C pathway.

Recently, our group described a B1-mediated stimulatory effect of des-Arg(9)-bradykinin (DABK) on the Na(+)-ATPase activity of proximal tubule basolateral membranes (BLM) [Biochim. Biophys. Acta 1431 (1999) 483.]. Data in the present report suggest the participation of a phosphatidylinositol-specific PLC (PI-PLC)/protein kinase C (PKC) pathway as the molecular mechanism of DABK-mediated stimulation of the Na(+)-ATPase activity since (i) 10(-8) M DABK activates PI-PLC activity; (ii) 10(-9) M U73122, a PI-PLC inhibitor, abolishes the effect of 10(-8) M DABK on the Na(+)-ATPase activity; (iii) 10(-8) M DABK increases phosphoprotein formation by 34%. This effect is completely reversed by 10(-7) M calphostin C, an inhibitor of PKC; (iv) 20 ng/ml TPA, an activator of PKC, and 10(-8) M DABK stimulate the Na(+)-ATPase activity in a similar and nonadditive manner. Furthermore, the effect of 10(-8) M DABK is completely reversed by calphostin C; (v) 10(-8) M DABK increases phosphoserine residue levels by 54%. This effect is completely reversed by 10(-7) M calphostin C.