Renal hormone

In addition to their involvement in excretion and metabolism, the kidneys also have endocrine functions. They produce the hormones erythropoietin and calcitriol and play a decisive part in producing the hormone angiotensin II by releasing the enzyme renin. Renal prostaglandins (see p. 390) have a local effect on Na resorption. 

Calcitriol (vitamin D hormone, lo,25-dihy-droxycholecalciferol) is a hormone closely related to the steroids that is involved in Ca homeostasis (see p. 342). In the kidney, it is formed from calcidiol by hydroxylation at C-1. The activity of calcidiol-1-monooxygenase [1] is enhanced by the hormone parathyrin (PTH). 

Erythropoietin is a peptide hormone that is formed predominantly by the kidneys, but also by the liver. Together with other factors known as colony-stimulating factors (CSF see p.392), it regulates the differentiation of stem cells in the bone marrow. 

Erythropoietin release is stimulated by hypoxia (low PO2). Within hours, the hormone ensures that erythrocyte precursor cells in the bone marrow are converted to erythrocytes, so that their numbers in the blood increase. Renal damage leads to reduced erythropoietin release, which in turn results in anemia. Forms of anemia with renal causes can now be successfully treated using erythropoietin produced by genetic engineering techniques. The hormone is also administered to dialysis patients. Among athletes and sports professionals, there have been repeated cases of erythropoietin being misused for doping purposes. 

The peptide hormone angiotensin II is not synthesized in a hormonal gland, but in the blood. The kidneys take part in this process by releasing the enzyme renin. 

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Physiologically, oxygen transport to metabolising tissues is provided by haemoglobin contained within erythrocytes. This pathway starts in the bone marrow with immunohaematopoietic stem cells that differentiate to progenitors which proliferate to yield the recognisable normoblasts. The latter mature to reticulocytes, which are then released into the circulation. Overall regulation is primarily mediated by the renal hormone called erythropoietin. 

The metabolic changes observed in uremia result from the decline in renal excretory function, hence the retention of a legion of substances the loss of vital renal hormones (e.g., erythropoietin) and enzymes (e.g., la-hydroxylase) the effect of the uremic environment on organ function, intermediary metabolism, and transport processes dialysis-related problems and exogenous toxins. 

Olsen UB, Ahnfelt-Ronne I. Bumetanide induced increase of renal blood flow in conscious dogs and its relation to local renal hormones (PGE, kallikrein and renin). Acta Pharmacol Toxicol 1976 38 219-228. 

The calcium homeostatic system, originally attributed exclusively to the parathyroid hormone, now includes the renal hormone la,25-di-hydroxyvitamin D3. Calcium is the fifth most abundant element in vertebrate systems and is the most important structural component of the body 45, 72). Calcium is also required for the following purposes ... 

Parathyroid hormone, a polypeptide of 83 amino acid residues, mol wt 9500, is produced by the parathyroid glands. Release of PTH is activated by a decrease of blood Ca " to below normal levels. PTH increases blood Ca " concentration by increasing resorption of bone, renal reabsorption of calcium, and absorption of calcium from the intestine. A cAMP mechanism is also involved in the action of PTH. Parathyroid hormone induces formation of 1-hydroxylase in the kidney, requited in formation of the active metabolite of vitamin D (see Vitamins, vitamin d). 

Although it is being found that vitamin D metaboUtes play a role ia many different biological functions, metaboHsm primarily occurs to maintain the calcium homeostasis of the body. When calcium semm levels fall below the normal range, 1 a,25-dihydroxy-vitainin is made when calcium levels are at or above this level, 24,25-dihydroxycholecalciferol is made, and 1 a-hydroxylase activity is discontiaued. The calcium homeostasis mechanism iavolves a hypocalcemic stimulus, which iaduces the secretion of parathyroid hormone. This causes phosphate diuresis ia the kidney, which stimulates the 1 a-hydroxylase activity and causes the hydroxylation of 25-hydroxy-vitamin D to 1 a,25-dihydroxycholecalciferol. Parathyroid hormone and 1,25-dihydroxycholecalciferol act at the bone site cooperatively to stimulate calcium mobilization from the bone (see Hormones). Calcium blood levels are also iafluenced by the effects of the metaboUte on intestinal absorption and renal resorption. 

It is well accepted that hypertension is a multifactorial disease. Only about 10% of the hypertensive patients have secondary hypertension for which causes, ie, partial coarctation of the renal artery, pheochromacytoma, aldosteronism, hormonal imbalances, etc, are known. The hallmark of hypertension is an abnormally elevated total peripheral resistance. In most patients hypertension produces no serious symptoms particularly in the early phase of the disease. This is why hypertension is called a silent killer. However, prolonged suffering of high arterial blood pressure leads to end organ damage, causing stroke, myocardial infarction, and heart failure, etc. Adequate treatment of hypertension has been proven to decrease the incidence of cardiovascular morbidity and mortaUty and therefore prolong life (176—183). 

Fig. 2. Schematic representation of relevant electrolyte transport through the renal tubule, depicting the osmolar gradient ia medullary iaterstitial fluid ia ywOj yW where represents active transport, —passive transport, hoth active and passive transport, and passive transport of H2O ia the presence of ADH, ia A, the cortex, and B, the medulla. An osmole equals a mole of solute divided by the number of ions formed per molecule of the solute. Thus one mole of sodium chloride is equivalent to two osmoles, ie, lAfNaCl = 2 Osm NaCl. ADH = antidiuretic hormone.

Historically the only melanocortin peptide to be used clinically is the parent hormone from which all these peptides are derived from namely ACTH (see above). It has also been used in the treatment infantile spasms for epilepsy, where it is administered as an intramuscular injection only over a 2-12 weeks period. Obvious side effects include weight gain, puffy face, high blood pressure and an increased risk of infection and should never be administered to patients with diabetics, renal or heart failure. ACTH is also used as a stimulation test to measure adrenal cortex activity, i.e. production of cortisol and is used to ascertain whether someone has Addison s disease. 

A major regulator of bone metabolism and calcium homeostasis, parathyroid hormone (PTH) is stimulated through a decrease in plasma ionised calcium and increases plasma calcium by activating osteoclasts. PTH also increases renal tubular calcium re-absorption as well as intestinal calcium absorption. Synthetic PTH (1-34) has been successfully used for the treatment of osteoporosis, where it leads to substantial increases in bone density and a 60-70% reduction in vertebral fractures. 

AVP plays a central role in water homeostasis of terrestrial mammals, leading to water conservation by the kidney. OT is primarily involved in milk ejection, parturition and in sexual and maternal behaviour. Both hormones are pqDtides secreted by the neurohypophysis, and both act also as neurotransmitters in the central nervous system (CNS). The major hormonal targets for AVP are the renal tubules and vascular myocytes. The hormonal targets for OT are the myoepithelial cells... 

These dragp are contraindicated in patients who are hypersensitive to the bisphosphonates. Alendronate and risedronate are contraindicated in patients with hypocalcemia Alendronate is a pregnancy Category C drug and is contraindicated during pregnancy. These drugp are contraindicated in patients with renal impairment with serum creatinine less than 5 mg/dL. Concurrent use of these dm with hormone replacement therapy is not recommended. 

Anemia may occur in patients with chronic renal failure as tlie result of the inability of the kidney to produce erythropoietin. Erythropoietin is a glycoprotein hormone synthesized mainly in the kidneys and used to stimulate and regulate the production of erythrocytes or red blood cells (RBCs). Failure to produce the needed erythrocytes results in anemia Two examples of drug used to treat anemia associated with chronic renal failure are epoetin alfa (Epogen) and darbepoetin alfa (Aranesp). 

Vasopressin (Rtressin Synthetic) and its derivatives, namely lypressin (Diapid) and desmopressin (DDAVP), regulate the reabsorption of water by the kidneys. Vasopressin is secreted by the pituitary when body fluids must be conserved. An example of this mechanism may be seen when an individual has severe vomiting and diarrhea with little or no fluid intake. When this and similar conditions are present, die posterior pituitary releases the hormone vasopressin, water in die kidneys is reabsorbed into die blood (ie, conserved), and die urine becomes concentrated. Vasopressin exhibits its greatest activity on die renal tubular epithelium, where it promotes water resoqition and smooth muscle contraction throughout die vascular bed. Vasopressin has some vasopressor activity. 

The availability of a cDNA for erythropoietin has made it possible to produce substantial amounts of this hormone for analysis and for therapeutic purposes previously the isolation of erythropoietin from human urine yielded very small amounts of the protein. The major use of recombinant erythropoietin has been in the treatment of a small number of anemic states, such as that due to renal failure. 

KONTESSIS P, JONES S, DODDS R, TREVISAN R, NOSADINI R, FIORETTO P, BORSATO M, SACERDOTI D and viBERTi G (1990) Renal, metabolic and hormonal responses to ingestion of animal and vegetable proteins. Kidney Int. 38 (1) 136-44. 

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