Endocrine Functions of the Kidney

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

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

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

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

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

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