Efficacy of combination therapy of furosemide and hydrochlorothiazide in patients with end stage renal disease

Background: Diuretic resistance is encountered in patients with chronic renal failure because of reduced number of nephrons, diminished delivery to loop, and increased distal Na reabsorption. To overcome the resistance, combination therapy of loop diuretics and thiazides has been recommended. But, there were few studies for combination therapy in patients with end stage renal disease(Ccr<10 ml/min/1.73m²). Methods: In a randomized crossover study, we compared the natriuretic and chloruretic effect of the loop diuretics, furosemide(160 mg i.v.), given alone or in combination with thiazide diuretics, hydrochlorothiazide (100 mg p.o.), in 10 patients with end stage renal disease(Ccr<10 ml/min/1.73m², before dialysis therapy). Results: Administration of furosemide alone significantly(p<0.05) increased 24-hour excretion of sodium (from 89.6 ± 28.2 to 149.4 ± 59.5 mmol/24hr), and chloride(from 87.2 ± 41.1 to 154.6 ± 66.5 mmol/24hr) as compared with baseline. Also, combination therapy significantly(p<0.05) increased (urine sodium: from 75.8 ± 39.9 to 151.7 ± 60.8 mmol/24hr, urine chloride: from 64.6 ± 35.3 to 142.8 ± 61.2 mmol/24hr). But, there was no difference between furosemide alone and combination therapy. No significant differences in pharmacokinetic parameters of furosemide were found when furosemide was infused with alone or in combination with hydrochlorothiazide. Conclusion: There is no additive or synergistic effect in combination therapy of furosemide and hydrochlorothiazide in patients with end stage renal disease.