Non-technical summary Recombinant human erythropoietin (rHuEPO) decreases circulating levels of renin and aldosterone, two hormones regulating water and salt homeostasis, but the effect of rHuEPO on renal function is unknown. This study demonstrates that rHuEPO reduces the reabsorption of water and sodium in the proximal renal tubules and, probably by activation of the tubuloglomerular feedback mechanism, also causes a fall in glomerular filtration rate. Thus, the decrease in plasma concentrations of renin and aldosterone may be secondary to increased end-proximal tubular delivery of water and sodium. In conclusion, the fall in proximal reabsorption together with a reduced filtered load and a decrease in angiotensin II and aldosterone-dependent tubular reabsorption are expected to increase the oxygen tension in the renal tissue. This may serve to down-regulate the endogenous renal synthesis of EPO in the presence of high levels of circulating rHuEPO.Abstract Recombinant human erythropoietin (rHuEPO) elevates haemoglobin concentration both by increasing red blood cell volume and by a decrease in plasma volume. This study delineates the association of rHuEPO-induced changes in blood volumes with changes in the renin-aldosterone system and renal function. Sixteen healthy males were given rHuEPO for 28 days in doses raising the haematocrit to 48.3 ± 4.1%. Renal clearance studies with urine collections (N = 8) were done at baseline and at days 4, 11, 29 and 42. Glomerular filtration rate (GFR) was measured by 51 Cr-EDTA. Renal clearance of lithium (C Li ) was used as an index of proximal tubular outflow and to assess segmental renal tubular handling of sodium and water. rHuEPO-induced increases in haematocrit occurred from day 10 onwards and was caused by both an increase in red cell volume and a fall in plasma volume. Well before that (from day 2 and throughout the treatment time), rHuEPO decreased plasma levels of renin and aldosterone (N = 8) by 21-33% (P < 0.05) and 15-36% (P < 0.05), respectively. After cessation of rHuEPO, values returned to baseline. On days 11 and 29, C Li increased (P < 0.02) indicating a significant 10-16% decrease in absolute proximal reabsorption of sodium and water (APR = GFR − C Li , P < 0.05). GFR decreased slightly, albeit significantly, on day 4 (P < 0.05). In conclusion, rHuEPO promptly, and before any changes in blood volumes and haematocrit can be detected, causes a down-regulation of the renin-aldosterone system. The results are compatible with a rHuEPO-induced reduction in proximal reabsorption rate leading to activation of the tubuloglomerular feedback mechanism and a fall in GFR. Therefore, treatment with rHuEPO may result in suppression of endogenous EPO synthesis secondary to a decrease in intrarenal oxygen consumption.

ObjectiveIn a recent study, we found that Greenlandic Inuit children had a more adverse metabolic profile than Danish children. Aerobic fitness and adiposity could only partly account for the differences. Therefore, we set out to evaluate and compare plasma leptin and adiponectin levels in Danish and Inuit children.MethodsIn total, 187 Inuit and 132 Danish children (5.7–17.1 years) had examinations of anthropometrics, body fat content, pubertal staging, fasting blood and aerobic fitness.ResultsPlasma leptin was higher in Danish boys [3,774 (4,741–3,005)] [pg/mL unadjusted geometric mean (95% CI)] compared to both northern [2,076 (2,525–1,706)] (p<0.001) and southern (2,515 (3,137–2,016)) (p<0.001) living Inuit boys and higher in Danish girls [6,988 (8,353–5,847)] compared to southern living Inuit girls [4,910 (6,370–3,785)] (p=0.021) and tended to be higher compared to northern living Inuit girls [5,131 (6,444–4,085)] (p=0.052). Plasma adiponectin was higher for both Danish boys [22,359 (2,573–19,428)] [ng/mL unadjusted geometric mean (95% CI)] and girls [26,609 (28,994–24,420)] compared to southern living Inuit boys [15,306 (18,406–12,728)] and girls [18,864 (22,640–15,717)] (both p<0.001), respectively. All differences remained after adjustment for body fat percentage (BF%), aerobic fitness, age and puberty. The leptin/adiponectin ratio was higher in Danish boys and tended to be higher in Danish girls compared to northern living Inuit boys and girls, respectively. These differences were eliminated after adjustment for BF%, aerobic fitness, age and puberty.ConclusionsIn contrast to our hypothesis, plasma leptin was higher in Danish children despite a more healthy metabolic profile compared to Inuit children. As expected, plasma adiponectin was lowest in Inuit children with the most adverse metabolic profile.

In recognition of the policies of Diabetes, specifically that "[a]t the time of submission, authors should disclose details of related papers they have authored [.], similar papers in press, and any closely related papers previously published or currently under review at another journal," we hereby inform the readers of the journal that we did not disclose that one article based on part of the same study cohort was previously accepted for publication (1) and that another article based on the same study cohort was in review for publication (2) when the above-listed paper was submitted to Diabetes. This has led to republication in the above-listed article of data on three anthropometric parameters and one physiological parameter describing the study cohort (body weight, percent whole body fat, leg muscle mass, and VO 2max) without reference to these articles. Taking this opportunity, we also disclose that a fourth article was later published using the same study cohort (3).