Erythropoietin is reduced by combination of diuretic therapy and RAAS blockade in proteinuric renal patients with preserved renal function.

Background: Renin-angiotensin-aldosterone system (RAAS) blockade improves prognosis in renal patients, but usually requires diuretic co-treatment. RAAS blockade can decrease erythropoietin (EPO) and/or haemoglobin (Hb) levels. Diuretics decrease EPO in rodents, but their effect on EPO and Hb in humans is unknown.
Methods: Proteinuric renal patients with preserved renal function were treated during 6-week periods with placebo, losartan 100 mg/day (LOS) and LOS plus hydrochlorothiazide 25 mg/day (LOS/HCT), in random order.
Results: Hb was inversely related to proteinuria, and EPO levels were inappropriately low in relation to Hb. Hb was lowered by LOS with and without HCT. EPO was decreased by LOS/HCT, but not by LOS.
Conclusions: EPO and Hb are reduced by HCT added to LOS in proteinuric renal patients with preserved renal function. We hypothesize that EPO reduction by HCT is caused by a decrease in renal oxygen requirement, which is the main stimulus for EPO production, due to the inhibition of active tubular sodium reabsorption. Further studies should explore the exact mechanism of this phenomenon and its clinical impact.