Direct effect of methylprednisolone on renal sodium and water transport via the principal cells in the kidney

作者：Lauridsen Thomas G^*; Vase Henrik; Bech Jesper N; Nielsen Soren; Pedersen Erling B

来源：European Journal of Endocrinology, 2010, 162(5): 961-969.

DOI：10.1530/EJE-10-0030

Background: Glucocorticoids influence renal concentrating and diluting ability. We tested the hypothesis that methylprednisolone treatment increased renal water and sodium absorption by increased absorption via the aquaporin-2 (AQP2) water channels and the epithelial sodium channels (ENaCs) respectively.
Methods: The effect of methylprednisolone was measured during fasting in a randomized, placebo-controlled, single-blinded cross-over study of 15 healthy humans. The subjects received a standardized diet on day 1, fasted on day 2, and received 500 mg methylprednisolone intravenously on day 3. The effect variables were urinary excretions of AQP2 (u-AQP2), urinary excretion of the beta-fraction of the ENaC (u-ENaC(beta)), cAMP (u-cAMP), prostaglandin E(2) (u-PGE(2)), free water clearance (C(H2O)), and fractional excretion of sodium (FE(Na)), and plasma vasopressin (p-AVP), angiotensin II (p-Ang II), aldosterone (p-Aldo), atrial natriuretic peptide (p-ANP), and brain natriuretic peptide (p-BNP).
Results: Methylprednisolone treatment increased u-AQP2, u-ENaC(beta), and p-AVP significantly, but did not change u-cAMP, C(H2O), and FE(Na). P-ANP increased during methylprednisolone treatment, but after the increase in u-AQP2 and u-ENaC(beta). U-PGE(2), p-Ang II, and p-BNP were unchanged. Heart rate increased and diastolic blood pressure fell.
Conclusions: Methylprednisolone increased u-AQP2 and u-ENaC. Neither the AVP-cAMP axis nor changes in the renin-angiotensin-Aldo system, or the natriuretic peptide system seems to bear a causal relationship with the increase in either u-AQP2 or u-ENaC. Most probably, the effect is mediated via a direct effect of methylprednisolone on the principal cells. The lack of decrease in urinary output and sodium reabsorption most likely can be attributed to the diuretic and natriuretic properties of the increased secretion of ANP.

• 出版日期2010-5