Kidney Endocrine Functions

Introduction

• The kidneys are also involved in promoting erythropoiesis and producing activated vitamin D
  • erythropoiesis (red blood cell production)
    • the kidneys produce a glycoprotein growth factor called erythropoietin (EPO)
      • in hypoxia, there is less O2 being delivered to the kidneys
        • this in turn causes the production of hypoxia-inducible factor-1α (HIF-1α) which acts on the fibroblasts in the renal cortex to transcribe EPO (increased EPO mRNA)
          • EPO promotes the differentiation of proerythroblasts to eventually form into erythrocytes (red blood cells)
            • note that one can commonly see anemia in patients with chronic renal failure since the functioning renal mass is decreased
              • this is why recombinant human EPO is a treatment for anemia of chronic renal failure
  • vitamin D production
    • the kidneys contain an enzyme called 1α-hydroxylase
      • 1α-hydroxylase catalyzes the hydroxylation (at the C1 position) of 25-hydroxycholecalciferol into 1,25-dihydroxycholecalciferol
        • 1,25-dihydroxycholecalciferol is a physiologically active form of vitamin D
          • in the kidney, 25-hydroxycholecalciferol can also be hydroxylated (at the C24 position) into 24,25-hydroxycholecalciferol, an inactive form of vitamin D
        • 1α-hydroxylase is regulated by a number of factors such as
          • plasma Ca²⁺ concentration
            • a decrease in plasma Ca²⁺ increases 1α-hydroxylase activity
          • parathyroid hormone
            • increases 1α-hydroxylase activity
          • plasma phosphate concentration
            • a decrease in plasma phosphate increases 1α-hydroxylase activity
• Prostaglandins 
  • the kidneys locally produce prostaglandins (e.g., PGE2) that result in vasodilation of the afferent arteriole
    • this in turn increases renal blood flow
    • nonsteroidal antiinflammatory drugs (NSAIDs) impair prostaglandin synthesis
      • the renoprotective effects of prostaglandins are loss in low blood volume states (e.g., hemorrhage)
• Dopamine
  • low levels of dopamine dilates the renal arterioles and thus increases renal blood flow
    • secreted by proximal tubular cells to promote natriuresis