Urinary excretion of aquaporin-2 after furosemide and felodipine in healthy humans.

OBJECTIVE: Furosemide inhibits renal sodium and chloride reabsorption in the loop of Henle. A compensatory increased reabsorption of sodium and water takes place in the collecting duct. It is not known whether aquaporin-2 (AQP2) renal water channels are involved in this compensatory reabsorption. In animals, dihydropyridine derivatives of calcium channel blockers down-regulate AQP2 in the collecting duct, but the effect has not been studied in humans. We sought to test the hypotheses that urinary excretion of aquaporin-2 (U-AQP2) increases after a single intravenous dose of furosemide, and that U-AQP2 decreases after a single oral dose of felodipine. MATERIAL AND METHODS: In two randomized, single-blind, placebo-controlled, cross-over studies, we measured the effect of furosemide and felodipine on U-AQP2, urine volume, free water clearance (CH2O), and fractional excretion of sodium (FENa) in 13 healthy subjects in each study. Plasma concentrations of vasopressin (AVP), renin (PRC), angiotensin II (ang II), aldosterone (aldo), atrial (ANP), and brain natriuretic peptides (BNP) were measured during the study. Glomerular filtration rate (GFR) was measured by constant infusion technique. U-AQP2 and hormones were determined by radioimmunoassay. RESULTS: Furosemide treatment increased U-AQP2 (202%), urine volume (214%), and FENa by a factor of 11, (p < 0.001 for all), whereas CH2O and GFR were unchanged. After treatment with placebo, no differences were seen. Furosemide treatment increased AVP (18%), PRC (60%), ang II (100%), and aldo (98%) (p < 0.032); ANP was decreased by 29% (p < 0.001), whereas there was no change in BNP. The hormones were unchanged after placebo except for a minor decrease in ANP after placebo. Felodipine tended to increase U-AQP2, to decrease CH2O and urine volume and GFR, and to increase FENa, but the effect was not significantly different from placebo. Felodipine increased PRC (82%) (p < 0.003) and ang II, but decreased aldo, and increased AVP. After placebo, PRC was unchanged, whereas ang II, aldo and AVP were changed as after felodipine. CONCLUSIONS: Furosemide treatment increased U-AQP2, AVP, and the activity of the renin-angiotensin-aldosterone system. These changes are most likely compensatory phenomena, which prevent an excess loss of sodium and water. Felodipine tended to increase U-AQP2.

Hypochromic reticulocytes, hypochromic erythrocytes and p-transferrin receptors in diagnosing iron-deficient erythropoiesis.

BACKGROUND: The purpose of this study was to test the hypothesis that hypochromic reticulocytes, hypochromic erythrocytes and p-transferrin receptors are sensitive variables in detecting iron-deficient erythropoiesis in healthy subjects and hemodialysis patients. METHODS: Study 1: Twenty-one blood donors donated 450 mL blood. During the following 2 weeks blood samples were analyzed for the variables mentioned above. Study 2: Twenty-eight blood donors received 10,000 U recombinant human erythropoietin (rHuEPO) twice in the first week or placebo, after they had donated 450 mL blood. During the following 3 weeks the blood samples were analyzed for the variables mentioned in Study 1. Study 3: Eighteen hemodialysis patients receiving rHuEPO and iron treatment had either iron treatment discontinued for 4 weeks, after which iron was resumed, or received unchanged treatment. During 8 weeks blood samples were analyzed for the variables mentioned in Study 1. RESULTS: Study 1: Blood donation induced an increase in hypochromic reticulocytes of 178%, in hypochromic erythrocytes the increase was 267%, and in p-transferrin receptors 32%. Study 2: Treatment with rHuEPO induced a more pronounced increase than placebo in hypochromic reticulocytes (232% vs. 158%) and hypochromic erythrocytes (1240% vs. 300%), but not in p-transferrin receptors. Study 3: Discontinuation of iron treatment did not cause any significant differences in the variables mentioned above between the two groups, but caused a 25% decrease in p-ferritin. When iron treatment was resumed, p-ferritin increased by 19%. We found no significant changes in the control group. CONCLUSIONS: Hypochromic reticulocytes, hypochromic erythrocytes and p-transferrin receptors are sensitive variables in the early detection of iron-deficient erythropoiesis in healthy subjects, but in this study the iron withdrawal period was too short to show the value of these variables in the detection of iron-deficient erythropoiesis in hemodialysis patients.