RENAL ENDOCRINOLOGY 

INTRODUCTION 

• The function of the kidney is not just limited to maintaining fluid or salt balance; it also plays a crucial role in preserving the body’s hormonal balance.
• Renal endocrinology comprises the physicochemical, pharmacological, physiological, and pathological aspects of the hormones and autacoids secreted by the kidney.
• In addition, non-renal hormones directly or indirectly impact renal function.
• The kidney produces several hormones, including calcitriol, the renin-angiotensin system, and erythropoietin.
• Moreover, the kidney makes enzymes like kallikreins that break prohormones in other peripheral sites and local hormones like prostaglandins and adrenomedullin.
• In addition, numerous hormones, including natriuretic peptides, or ANP, aldosterone, and angiotensin, have the kidney as a critical target.
• Some other diseases, including urolithiasis and other hereditary disorders, share similarities between endocrinology and nephrology.
• Chronic and acute kidney diseases and many other illnesses, including diabetes mellitus, cause disturbances in the endocrine system.
•  Noteworthy hormonal imbalances that can impact renal structure and function include thyroid, parathyroid, and acromegaly problems.

Renin

• It is an enzyme that aids in maintaining normal levels of potassium and sodium in the body and blood pressure.
• There is sodium depletion, or low blood volume, when blood pressure falls too low. Particular kidney cells produce renin, which is then released into the bloodstream.
•  Aldosterone, a hormone produced by kidneys, is also regulated by renin. 
• Aldosterone supports proper potassium and sodium levels in the body and blood pressure management.
• Angiotensinogen, a precursor of renin released into the blood, is converted into angiotensin I by renin. 
• A protein in the capillaries of the lungs then changes angiotensin I into angiotensin II. Angiotensin II, which combines renal and cardiovascular functioning to control arterial pressure and sodium and volume homeostasis, is produced at a rate limited by renin.
• Four major stimuli cause the JG cells’ granules, which store mature renin, to release it into the bloodstream
• High and low renin levels Essential hypertension is a term used to describe some hypertensive patients. In about 20% of hypertensive individuals, plasma renin activity is inhibited. 
• A high renin level might result from overactive adrenal glands, bleeding (hemorrhage), or heart failure.
• Pressure transducer mechanisms in afferent arterioles monitor changes in renal perfusion.
• Renin activity in the blood has a 10- to 15-minute half-life.
• Angiotensin II has a relatively short half-life in circulation—less than 60 seconds.
• Blood pressure, volume control, and aldosterone secretion are all mediated by angiotensin II.
• It has been demonstrated that angiotensin III has 100% of angiotensin II’s aldosterone-stimulating action but only 40% of its pressor effects. In contrast, angiotensin IV has a reduced systemic impact.
• The adrenal cortex’s zona glomerulosa is where aldosterone is primarily made. Renin-angiotensin-aldosterone, ACTH, and extracellular potassium levels are principally 
• responsible for controlling the production and elimination of this hormone.

Aldosterone

• The adrenal cortex, the adrenal gland’s outer layer, produces the steroid hormone aldosterone. 
• Retaining sodium inside and releasing potassium from the body aids in maintaining the proper equilibrium between water and the salts in the kidney.
• Aldosterone causes the kidneys to reabsorb water and salt, which raises blood volume and blood pressure.
• Aldosterone has a plasma half-life of about 20 minutes.
• Excess aldosterone can result in high blood pressure and fluid buildup in body tissues. Fluid retention, lethargy, and, in rare cases, paralysis can result from this. 
• A tumor in the adrenal gland or disease can cause the overproduction of aldosterone.
• Because angiotensin one is converted to angiotensin 2 in the lungs, the adrenal glands, kidneys, and lungs are the organs involved in generating, using, and regulating aldosterone.
•  Medication, such as captopril, spironolactone, eplerenone, and telmisartan, increases renal perfusion and reduces vasoconstriction. Furthermore, RAAS component blockade reduces fibrosis, hypertrophy, and inflammation. As a result, the heart and kidney tissues undergo less tissue remodeling.

Renin-Angiotensin-Aldosteron System or RAAS 

• The system consists of renin, angiotensin II, and aldosterone hormones. One of the most essential systems in renal endocrinology
• Apart from the Renal System, the pulmonary, adrenal cortex, circulatory system, and brain are other organ systems involved in the renin-angiotensin-aldosterone system.
• The function of RAAS is to raise arterial pressure when renal blood pressure is decreased, transport sodium to the convoluted tubule at the distal end, and, due to beta-agonism,
•  Play a significant role in the physiological function of the circulatory and other systems. 
• Many cardiovascular and renal disorders have been linked to overactivity of the renin-angiotensin-aldosterone pathway.

Antidiuretic Hormone or Vasopressin 

• The body’s blood pressure, salt balance, and kidney function are all regulated by the hormone known as antidiuretic hormone (ADH) or Arginine vasopressin (vasopressin), which are other names for ADH (AVP). 
• It is formed in the brain’s hypothalamus and kept in the posterior part of the pituitary gland.
• ADH aids the kidneys in regulating the body’s salt and water levels, which helps control heart rate and the volume of urine produced.
• ADH also stimulates the kidneys to reabsorb water.
• ADH is released in response to plasma osmotic pressure alterations, fluid volume changes, activity, angiotensinogen, and emotional states like pain.
• Since they can result in fluid imbalances that trigger seizures or cerebral edema, extremely high ADH levels may be harmful. A person with heart failure may also have elevated ADH levels.
• ADH has also been used to treat von Willebrand disease and hemophilia, two significant bleeding disorders. 

Calcitriol

• A synthetic, hormonally active version of vitamin D is called calcitriol.
• Also called 1,25-dihydroxycholecalciferol.
• Renal diseases can lead to decreased calcium levels, which can be treated with calcitriol. 
• It helps control parathyroid levels and raises the body’s calcium levels. Hypocalcemia, fractures, and bone disease can all be treated with calcitriol.
• The half-life of calcitriol is considered to be a few hours or so. 
• If your blood contains excessive amounts of calcium or vitamin D, or if you’ve ever experienced an allergic reaction to calcitriol or other forms of vitamin D, you should avoid using calcitriol.
• According to studies, calcitriol suppresses the gene expression of essential chemokines and epidermal proteins involved in psoriasis. It dramatically reduces the proliferation of healthy human keratinocytes and Leukocytes by inducing death.
• The mode of administration is with a catheter; calcitriol is delivered intravenously, orally regardless of mealtime, and topically solely for external usage. No dilution is required for intravenous delivery, and a bolus dosage is administered after a dialysis session. 
• Lab technicians check serum calcium and phosphorus levels twice weekly during the first titration phase.
• Consuming Calcitriol tablets orally, with or without food, would be best. Still, they must be kept out of direct sunlight for an extended period. 
• Another application of calcitriol is Applying a thin coating with gentle rubbing to the affected area is how topical administration is carried out; take care not to get any on your face or eyes.
• Side effects include Headaches, skin rashes, nausea, diarrhea, stomach pain, infections of the urinary tract, Anorexia, constipation, lymphocytosis, elevated neutrophils, hypertension, increased hematocrit, elevated hemoglobin, sleepiness, overheating, and ocular problems such as conjunctivitis and photophobia.
• Hypercalcemia and nephrolithiasis have been encountered in patients receiving system-wide calcitriol therapy.
• Additional laboratory abnormalities linked to late signs of hypercalcemia include elevated levels of transaminase (AST), aspartate transaminase (ALT), and blood nitrogen levels (BUN) 
• Because calcitriol enhances phosphorous absorption, hyperphosphatemia can develop in people with renal failure.
• This condition may also produce ectopic mineralization, secondary hyperparathyroidism, renal osteodystrophy, and high serum creatinine levels.
• The relative contraindications for taking systemic calcitriol include hypercalcemia, vitamin D toxicity, and allergy to calcitriol or any vitamin D analog.
• Those with higher susceptibility to calcium dysregulation, such as arteriosclerosis, heart disease, hyperphosphatemia, kidney failure, and sarcoidosis, have additional contraindications to calcitriol. 
• Digoxin should be administered cautiously to patients with cardiac illness since they are more likely to experience cardiac arrhythmias due to hypercalcemia.

Erythropoietin or EPO

• They are also known as hemopoietin, hemopoietin, and erythropoietin.
• The EPO levels fall into a typical range of 4 to 26 mU/mL.
• The kidneys are primarily responsible for producing the hormone erythropoietin.
• The kidneys’ specialized cells often boost the production of EPO when they see low blood oxygen levels.
• Our body uses erythropoietin (EPO) to keep a healthy number of red blood cells in circulation (erythrocytes).
• Usually, Artificial erythropoietin is used to treat anemia caused by chronic kidney disease.
• Many conditions influence the kidney’s production of Erythropoietin.
• Bone marrow helps produce extra red blood cells upon signaling from erythropoietin. 
• The kidneys lower erythropoietin production when they determine that the blood contains enough oxygen.
• Low EPO levels are most frequently caused by chronic kidney disease (CKD). 
• EPO levels fall as a result of decreased production due to damaged kidneys. 
• Synthetic injectable shots (erythropoietin-stimulating agents, or ESAs) are prescribed for patients with uncommon cancer types.  
• Because EPO makes more oxygen available to muscles, its misuse enhances their performance.
• Local hormones or autocrine or paracrine molecules

Kallikrein

• Kallikrein is a serine protease enzyme
• It is also called tissue kallikrein.
• The kidneys, pancreas, and salivary glands are examples of exocrine glands that are essential suppliers of tissue kallikrein.
• The kallikrein-kinin system may control renal blood flow, affect tubular water and sodium transport, and contribute to the etiology of several human disorders, including hypertension. Also, there is some evidence that urinary kinins play a part in the distal nephron’s ability to transport water and other substances.
• The development of hypertension, renal disorders, and the antihypertensive action of medications like diuretics and ACE inhibitors have all been linked to the renal kallikrein-kinin system.

Prostaglandins 

• Prostaglandins, made by the kidney, may help control the renin-angiotensin system, salt and water elimination, and renal hemodynamics. 
• Moreover, prostaglandins might shield the kidneys from toxic and ischemia-related damage.
• PGE2 and prostacyclin are prostaglandins (PGI2). 
• These vasodilatory prostaglandins boost the glomerular filtration rate and renal blood flow, which can lead to higher capillary flow and potassium secretion.
• Prostaglandins may counteract the antidiuretic hormone’s hydro-osmotic impact by changing the collecting ducts’ water permeability.
• Prostaglandins are synthesized from collecting ducts, interstitial cells, and afferent and efferent arterioles of the kidney.

Endothelins

• Endothelin is a 21-amino acid-long peptide. 
• Endothelial and tubular cells are responsible for production.
• Endothelin can work in the kidney as a paracrine-autocrine factor, controlling blood flow to the kidneys, glomerular blood oxygenation, and sodium and water balance. 
• Kidney damage can result from endoplasmic reticulum stress and apoptosis caused by endothelin-1 in renal tubular cells.
• It is produced from Endothelial cells, vascular smooth muscle cells, macrophages, and the renal medulla. 
• Endothelin tightens blood vessels, which lowers blood pressure. Endothelin levels that are too high cause blood vessels to constrict more than they ought to, resulting in issues with blood pressure and lung and cardiac disorders.

Adrenomedullin or AM

• AM was first found in tissue from human pheochromocytomas. In polycystic ovarian syndrome patients, increased AM is linked to insulin resistance. 
• Many cardiovascular systems, including the kidney, express AM and AM genes.
• The 52-amino acid peptide hormone adrenomedullin is found in the kidney and other tissues, including the blood. 
• Both endothelium-dependent and endothelium-independent mechanisms are used to cause vasodilation. 
• Adrenomedullin may boost cell division and control stem cells’ fate. 
• Involved in kidney protection, it can also decrease ER stress-induced tubular cell death.

Frequently asked questions