Endocrine Functions of the Kidney

Outline the endocrine functions of the kidney

The kidney is involved in a number of endocrine processes and produces or metabolises a number of hormones:

• RAAS
• Vitamin D
• EPO
• Prostaglandins

Renin-Angiotensin-Aldosterone System

The RAAS is a signaling pathway involved in blood pressure control. It involves a number of hormones:

• Angiotensinogen is produced by the liver in response to:
  • Glucocorticoids
  • Thyroid hormones
  • Oestrogens
  • Angiotensin II
  • Various inflammatory proteins

• Renin is a protease produced by the kidneys in response to β₁ stimulation or hypotension, and exists to cleave angiotensinogen to angiotensin I

• ACE cleaves angiotensin I to angiotensin II, and also cleaves bradykinin into inactive metabolites

• Angiotensin II increases blood pressure via a number of mechanisms:
  • Simulates aldosterone release from the adrenal cortex, increasing sodium and water retention
  • Vasoconstriction of efferent greater than the afferent arterioles
    Results in slight decrease in GFR at a lower perfusion pressure, but increases filtration fraction.
    • NB: Different sources quote different changes (increase or decrease) in GFR
      The final effect may vary depending on the contribution of other autoregulatory processes.
  • Reduces K_f through constriction of glomerular mesangial cells
  • Increased SNS activity and central and peripheral vasoconstriction
  • Increases thirst via hypothalamic stimulation
  • Stimulates ADH release, reducing renal water excretion
  • Stimulates release of angiotensinogen

• Aldosterone acts on the distal convoluted tubule to:
  • Increase reabsorption of Na⁺ and water
  • Increase elimination of K⁺ and H⁺

Vitamin D

Vitamin D has a complex metabolic pathway which meanders through a number of organ systems:

• Vitamin D₃ may be absorbed in diet or produced in skin by the action of UV light on 7-dehydrocholesterol
• Vitamin D₃ is then hydrolysed in the liver by CYP450 enzymes to form 25-hydroxycholecalciferol (25-OHD₃)
• 25-OHD₃ is then converted in the proximal tubule to calcitriol - the active form

Erythropoietin

Erythropoiesis is stimulated by EPO release:

• In adults, EPO is released from the:
  • Peritubular capillary fibroblasts (85%)
  • Liver (15%)
• EPO is released in response to:
  • Hypoxia
  • Hypotension
  • Low Hct
• Erythropoiesis is inhibited by:
  • High red cell volume
  • Renal failure
    Production of EPO is decreased in renal failure, which is why patients with end-stage renal disease require exogenous EPO.

References

1. Barrett KE, Barman SM, Boitano S, Brooks HL. Ganong's Review of Medical Physiology. 24th Ed. McGraw Hill. 2012.
2. Kam P, Power I. Principles of Physiology for the Anaesthetist. 3rd Ed. Hodder Education. 2012.