Endocrine Functions of the Kidney

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Vitamin D[edit]

  • Vitamin D is inactive, and the activation process begins in the liver and ends in the proximal tubular cells within the kidneys with hydroxylation via the 1α-hydroxylase enzyme
  • Because of this, the kidneys are major regulators of calcium homeostasis in the GI tract and bone as well as regulators via urinary excretion
  • Vitamin D stimulates active absorption of calcium and phosphate by the intestine
  • Decreased gut calcium absorption causes decreased availability of calcium for bone formation or reformation. This causes rickets in children.
  • It also stimulates renal-tubular reabsorption of calcium and phospate, although this is much less important than the GI effects
  • Low calcium causes PTH secretion - secondary hyperparathyroidism, causing:
  • Rapid effects: increased renal calcium absorption, increased bone membrane release
  • Slow effects: Increased osteoclastic bone resorption and increased 1,25 OH Vit D causing increased Ca absorption
  • Hyperphosphataemia occurs almost always in renal failure due to loss of nephrons to excrete phosphate

The Renin-Angiotensin System[edit]


  • Renin - an acid protease secreted by the the JG cells of the kidneys into the bloodstream, converting angiotensinogen (produced in liver) to angiotensin I
  • Circulating level of angiotensinogen is increased by glucocorticoids, thyroid hormones, estrogens, cytokines and angiotensin II
  • Angiotensin I is then converted to angiotensin II by ACE (angiotensin-converting enzyme)
  • Most ACE is found in endothelial cells
  • ACE also inactivates bradykinin. Increased bradykinin produced when ACE is inhibited
  • Angiotensin II is a glycoprotein made up of 2 lobes with a deep active site in the middle
  • Angiotensin II is rapidly metabolized, with a circulating half-life of 1-2mins. It is metabolized by various peptidases.
  • Angiotensin-metabolising activity is found in red cells and many tissues including the lungs
  • Actions of Angiotensin II:
  • Angiotensin II causes arteriolar constriction and a rise in systolic and diastolic blood pressure, and is one of the most potent vasoconstrictors known - 4 to 8x more potent than noradrenaline
  • Its pressor activity is decreased in patients with cirrhosis and Na+ depletion due to downregulation of angiotensin receptors on vascular smooth muscle
  • Angiotensin II also acts on adrenal cortex to increase secretion of aldosterone
  • Angiotensin II also facilitates:
  • Noradrenaline release by direct action on post-ganglionic sympathetic neurons
  • Contraction of mesangial cells to decrease GFR
  • Increases Na+ reabsorption by direct effect on renal tubules
  • Acts on brain to decrease baroreflex sensitivity, potentiating the pressor effect of angiotensin II
  • Acts on the brain to increase water intake via thirst, and increase vasopressin and ACTH secretion
  • Many tissues have components of the renin-angiotensin system in them, and it may be involved as a growth factor in vessels and heart
  • Angiotensin II receptors:
  • AT1 - serpentine G protein coupled receptors which increase cytosolic free Ca2+ levels causing vasoconstriction
  • AT2 - act via G proteins which act via phosphatases to antagonise growth effects and open K+ channels
  • Also cause increased production of NO and therefore cGMP
  • The Juxtaglomerular Apparatus is made up of juxtaglomerular cells, macula densa and lacis cells. JG cells are the site of renin production.
  • Renin secretion is determined by:
  • Intra-renal baroreceptor mechanism which causes decreased renin secretion when arteriolar pressure in the JG cells increases
  • Macula densa sensing Na+ and Cl- entering the distal renal tubules in the loop of Henle
  • Direct feedback on JG cells by angiotensin II
  • Increased sympathetic nervous system activity increases renin secretion
  • Conditions leading to renin secretion include: Na+ depletion, diuretics, hypotension, haaemorrhage, dehydration, upright posture, cardiac failure, cirrhosis


  • Increases production of red blood cells from bone marrow
  • 85% produced in kidneys, 15% in liver. The liver cannot compensate enough when renal production is lost, and anaemia develops
  • Produced by interstitial cells in the peritubular capillary bed of the kidneys and by perivenous hepatocytes
  • Recombinant EPO given to renal failure patients, as well as to stimulate red cell production in individuals banking autologous transfusions during elective surgery
  • Secretion is regulated by hypoxia acting on heme protein in liver which activates the EPO gene in its reduced form