Identification of hyponatremia as a risk factor for the development of functional renal insufficiency during converting enzyme inhibition in severe chronic heart failure

To identify patients with severe chronic heart failure who are at greatest risk of developing functional renal insufficiency during converting enzyme inhibition, creatinine clearance was measured in 59 patients before and after long-term therapy with Captopril (39 patients) or enalapril (20 patients), while digitalis and diuretic therapy was kept constant. Creatinine clearance increased or remained constant in 33 of the 59 patients (Group I), but declined in the remaining 26 patients (Group II). The two groups were similar with respect to the cause of heart failure, pretreatment renal function and all pretreatment hemodynamic variables. Patients in Group II, however, had lower values for serum sodium concentration (134.8 ± 1.0 versus 137.0 ± 0.6 mmol/liter) and higher values for plasma renin activity (10.6 ± 3.4 versus 3.0 ± 0.5 ng/ml per hour), received larger doses of furosemide (108 ± 11 versus 84 ± 6 mg/day), were more frequently diabetic (42 versus 15%) and were more frequently treated with enalapril (50 versus 21 %) than were patients in Group I (all p < 0.05). By stepwise logistic analysis, only hyponatremia (or an elevated plasma renin activity) and enalapril therapy independently predicted the decline in creatinine clearance during converting enzyme inhibition. These observations could not be explained by changes in systemic blood pressure. In patients with a normal serum sodium concentration (≥137 mmol/liter), creatinine clearance increased with Captopril (+21%, p < 0.05), but not with enalapril (−6%, p = NS). In contrast, in hyponatremic patients, creatinine clearance did not change significantly with Captopril (−13%, p = NS), but decreased with enalapril (−24%, p < 0.05). In addition, patients who were diabetic and who received large doses of furosemide (>80 mg daily) showed a decrease in creatinine clearance only if they were also hyponatremic, but not if they had a normal pretreatment serum sodium concentration. These findings indicate that hyponatremic patients with heart failure are not only at risk of symptomatic hypotension, but are likely to develop functional renal insufficiency during treatment with converting enzyme inhibitors.