the most important paired excretory organs of vertebrates, including man. The kidneys participate in water and salt homeostasis; that is, they help maintain a constant concentration of osmotically active substances in internal fluids, the constant volume and ionic composition of these fluids, and acid-base equilibrium. They excrete the end products of nitrogen metabolism, heterologous and toxic compounds, and excess organic and inorganic matter. The kidneys participate in carbohydrate and protein metabolism and in the formation of biologically active substances that regulate blood pressure, the rate of aldosterone secretion by the adrenal glands, and the rate at which red blood cells are formed.

Comparative morphology. Three successive types of kidneys appeared in the course of vertebrate evolution: the primitive, or head, kidney (pronephros); the primary, or truncal, kidney (mesonephros); and the secondary, or pelvic, kidney (metanephros). These types of kidney also succeed one another in the course of embryological development in higher vertebrates. All three arise from the nephrotome, the pedicel of a somite. From the postembryonic period until the attainment of sexual maturity, the primary kidney is an excretory organ in cyclostomes, fishes, amphibians, young lizards, monotremes, and marsupials. In all other vertebrates including man, the pronephros and mesonephros are replaced by the metanephros in the embryo.

The principal morphological and functional unit of the kidneys is the nephron. The structures of the nephron developed and changed in vertebrates during evolution as animals adapted to a variety of environments. In petromyzons and other cyclostomes, all the nephrons originate in the general cavity of the glomus, where ultrafiltration from blood-carrying capillaries occurs. Fishes and other vertebrates have Malpighian corpuscles, which constitute the beginnings of the nephrons. Only in a few species of marine teleosts are the nephrons lacking in glomeruli. The nephron in all vertebrates has a proximal segment and, except in the case of some species of marine teleosts, a distal segment as well. Birds and mammals acquired a new morphological structure, the loop of Henle, whose tubules constitute the main element of the renal medulla.

The human kidneys are bean-shaped organs situated on the posterior abdominal wall on both sides of the spinal column, usually extending from the level of the 12th thoracic vertebra to the level of the third lumbar vertebra. As a result of developmental anomalies there may be one or three kidneys. The adult kidney weighs 120–200 g and is 10–12 cm long, 5–6 cm wide, and 3–4 cm thick. The anterior surface is covered by the peritoneum, but the kidney proper is outside the peritoneal cavity. The kidneys are covered by fascia, under which is a fatty capsule; the kidney parenchyma is directly surrounded by a fibrous capsule. The kidney has a smooth and convex external margin and a concave internal margin. In the center of the kidney is the hilum, which provides access to the renal sinus, which contains the renal pelvis and calyces; the renal pelvis continues into the ureter. The hilum is the point where an artery and nerves enter the kidney and from which the veins and lymphatics leave.

A distinguishing feature of the mammalian kidney is the pronounced division into an external (cortical) part, which is red-brown in color, and an internal (medullary) part, which is lilac-red. The medulla of the kidney forms eight to 18 pyramids, above and between which extend layers of cortical substance called the renal columns of Bertin. Each pyramid has a wide base next to the cortex and a blunted and narrower apex—the renal papilla—projecting into a minor calyx. Minor calyces open into a major calyx, from which urine enters the renal pelvis and subsequently the ureter. One human kidney has about 1 million nephrons, each of which consists of several parts that have a characteristic structure and perform a distinct function. The structure of a nephron begins with the glomerulus, which sits in a cup-shaped Bowman’s capsule; the glomerulus and Bowman’s capsule together form the Malpighian, or renal, corpuscle. Bowman’s capsule extends to the proximal convoluted uriniferous tubule and passes into the straight part of the proximal tubule. It is followed by the thin descending part of the loop of Henle, which drops into the medulla. There it bends 180° and becomes the thin ascending limb of the loop of Henle, later becoming the thick ascending limb of the loop and returning to the level of the glomerulus. The ascending part of the loop joins the distal convoluted tubules; it is joined by a connecting section to the collecting tubules in the cortex. The tubules pass through the cortex and medulla and coalesce to form in the papilla Bellini’s ducts, which open into the renal pelvis.

Mammals, including man, have several types of nephrons, which differ with respect to both the arrangement of the glomeruli in the cortex and the function of the tubules: subcortical, intercortical, and juxtamedullary. The glomeruli of the subcortical nephrons are in the surface zone of the cortex, whereas the juxtamedullary glomeruli are at the boundary between the cortex and medulla. The juxtamedullary nephrons have a long loop of Henle, which descends deep into the renal papilla and keeps the osmotic concentration of urine at a high level. A strict zonal distribution of the various types of tubules is characteristic of the kidneys. The cortex contains all the glomeruli, proximal and distal convoluted tubules, and cortical sections of the collecting tubules. The loop of Henle and collecting tubules are in the medulla. The efficiency of renal osmoregulation depends on the way the various elements of the nephron are arranged.

The cells of each section of the tubules differ in structure. Numerous microvilli (brush border) on the surface facing the lumen of the nephron are characteristic of the cubical epithelium of the proximal convoluted tubule. On the basal surface the cell membrane forms narrow folds, between which are numerous mitochondria. In the cells of the straight portion of the proximal tubule, the brush border and folds of the basement membrane are less pronounced and there are few mitochondria. The thin part of the loop of Henle is smaller in diameter and is lined with squamous cells containing a few mitochondria. Several features are characteristic of the epithelium of the distal segment of the nephron, which includes the thick ascending limb of the loop of Henle and the distal convoluted tubule with the connecting section. The features include few microvilli on the tubule surface facing the lumen of the nephron, distinct folds in the basement plasma membrane, and numerous large mitochondria with many cristae. The proximal sections of the collecting tubules have alternating light and dark cells, the latter cells containing more mitochondria. Bellini’s ducts consist of tall cells with a few mitochondria.

Blood enters the kidneys from the abdominal aorta via the renal artery, which separates into interlobar, arcuate, and interlobular arteries. The afferent glomerular arterioles arise from these arteries. The arterioles separate into capillaries and then reunite to form efferent arterioles. The afferent arteriole is almost twice as thick as the efferent arteriole, thus facilitating glomerular filtration. The efferent arteriole again separates into capillaries, and these capillaries are twined around the tubules of the same nephron. Venous blood enters the interlobular, arcuate, and interlobar veins. These veins form the renal vein, which empties into the inferior vena cava. The medulla is supplied with blood by the straight arterioles. The sympathetic neurons of the three inferior thoracic and two superior lumbar segments of the spinal cord innervate the kidneys. Parasympathetic fibers proceed to the kidneys from the vagus nerve. Sensory innervation of the kidneys as part of the splanchnic nerves reaches the inferior thoracic and superior lumbar ganglia.

Comparative physiology. The main functions of the kidneys, including excretion, osmoregulation, and ionoregulation, are performed by the processes controlling uropoiesis. These processes include the ultrafiltration of fluid and dissolved substances from blood by the glomeruli and reabsorption of some substances into the blood and secretion of other substances from the blood into the lumen by the tubule. As kidneys evolved, the filtration and reabsorption mechanism of uropoiesis assumed greater importance than the secretory mechanism. The excretion of most ions in terrestrial vertebrates is regulated by change in the level of ionic reabsorption. A characteristic feature of renal evolution is an increase in the volume of glomerular filtration, which is 10 to 100 times greater in mammals than in fishes and amphibians. The rate of reabsorption of substances by the tubular cells is considerably higher, because the ratio of kidney mass to body mass is almost the same in these animals. Renal function intensifies to keep the composition of the substances dissolved in blood stable. The secretory apparatus is more developed in some lower vertebrates, allowing them to excrete some substances at the same rate as mammals. In marine fishes, the kidney secretes magnesium, sulfates, and phosphates. In all vertebrates except mammals and cyclostomes, the kidneys have a remportai circulation, which brings venous blood from the lower extremities directly to the tubules, bypassing the glomeruli. The tubular cells extract many substances from the blood and secrete them into the lumen of the nephron.

The development of osmoregulation by the kidneys is closely related to the type of nitrogen metabolism. In amphibians and mammals, the end product of nitrogen metabolism is urea, an osmotically highly active substance that cannot be excreted without a large quantity of water in amphibians; mammals, however, have the capacity to concentrate urine osmotically. In reptiles and birds, the end product of metabolism is uric acid, which is secreted by cells of the uriniferous tubules. Supersaturated solutions are formed during the reabsorption of water. Uric acid, poorly soluble in water, is precipitated into the cloaca, thus enabling the organism to save water. The excretion of urea formed from 1 g of protein requires 20 ml of water if the osmotic concentrations of urine and blood plasma remain equal, whereas the excretion of the corresponding amount of uric acid requires 0.5 ml of water.

In human beings at rest, about one-fourth of the blood pumped into the aorta by the left ventricle of the heart enters the renal arteries. Renal blood flows at the rate of 1,300 ml/min in males and somewhat slower in females. Ultrafiltration of blood plasma from the cavity of the capillaries into the lumen of Bowman’s capsule occurs in the glomeruli; this results in the formation of primary urine, in which there is virtually no protein. About 120 ml of fluid a minute enters the lumen of the tubules. Under ordinary conditions, however, about 119 ml of the filtrate returns to the blood and only 1 ml is excreted from the body in the form of final urine. Ultrafiltration of liquid occurs because the hydrostatic pressure of blood in the glomerular capillaries exceeds the total colloidal-osmotic pressure of blood plasma proteins and the intrarenal tissue pressure. The diameter of the particles filtered from the blood is determined by the size of the pores in the filtering membrane, which in turn apparently depends on the diameter of the pores in the central layer of the basement membrane of the glomerulus. In most cases, the radius of the pores is less than 28 Å; electrolytes, low-molecular none-lectrolytes, and water can therefore pass freely through the lumen of the basement membrane into the lumen of the nephron, but the proteins pass into the ultrafiltrate.

The functional significance of the individual renal tubules in uropoiesis varies. Cells of the proximal segment of the nephron absorb and reabsorb the glucose, amino acids, and vitamins from the filtrate, as well as most of the electrolytes. The wall of this tubule is always permeable to water; the volume of fluid decreases by two-thirds toward the end of the proximal tubule, but the osmotic concentration of the fluid remains the same as that of blood plasma. Cells of the proximal tubule are capable of secretion, that is, the discharge of certain organic acids (such as penicillin, iodopyracet, para-aminohippuric acid, and fluorescein) and organic bases (such as choline and guanidine) from the peritubular fluid into the lumen of the tubule. Cells of the distal segment of the nephron and collecting tubules participate in the reabsorption of electrolytes against a considerable electrochemical gradient. Potassium, ammonia, hydrogen ions, and other substances can be secreted into the lumen of the nephron. The walls of the distal convoluted tubule and collecting tubules become more permeable to water under the influence of the antidiuretic hormone vasopressin, causing absorption of water by the osmotic gradient.

Osmoregulation maintains a constant concentration of osmotically active substances in blood under different water conditions in the body. If there is too much water, hypotonic urine is excreted; if there is too little water, osmotically concentrated urine is formed. The mechanism of osmotic dilution and concentration of urine was discovered in the 1950’s–60’s. In mammalian kidneys, the tubules and medullary vessels form a counterflow-reversible multiplying system. The descending and ascending limbs of the loops of Henle, the straight blood vessels, and the collecting tubules run parallel to one another in the medulla. Sodium salts, which accumulate in the medulla as a result of active sodium transport by cells of the ascending limb, are retained in this part of the kidney together with urea. When blood moves into the deeper parts of the medulla, urea and sodium salts enter the vessels. When blood moves in the reverse direction toward the cortex, urea and sodium salts leave the vessels and are retained in the tissue by the counterflow principle.

Vasopressin causes a high osmotic concentration of blood, intercellular fluid, tubular fluid, and all fluids at every level of the medulla, except for the contents of the ascending limbs of the loops of Henle. The walls of these tubules are comparatively impermeable to water, but the cells actively reabsorb sodium salts into the surrounding interstitial tissue, causing the osmotic concentration to decrease. The walls of the collecting tubules are impermeable to water in the absence of vasopressin. Vasopressin causes the walls to become permeable to water, allowing water to be reabsorbed from the lumen by the osmotic gradient into the surrounding tissue. In human kidneys, urine can be four or five times more osmotically concentrated than blood. In desert rodents with especially developed internal renal medullae, the osmotic pressure of urine is 18 times higher than that of blood.

Scientists have studied the molecular mechanisms of reabsorption and secretion by tubular cells. During Na reabsorption, Na may enter the cell from the lumen passively by the electrochemical gradient. After entrance into the cell, Na flows to the region of the basement membrane and passes into the extracellular fluid by means of the sodium pump (Na-K ion-exchange pump, electrogenic Na pump). These pumps may be suppressed by special inhibitors. Because diuretics affect various elements of the system of Na reabsorption, they are used clinically in the treatment of edema. Unlike Na, K can be reabsorbed by the nephron cell and secreted as well. During secretion, K flows from the interstitial fluid into the cell through the basement membrane through the operation of the Na-K pump and is discharged passively into the lumen of the nephron through the apical cellular membrane. This is caused by an increase in potassium permeability of the membranes and high intracellular concentration of K.

Reabsorption of various substances is regulated by neural and hormonal factors. The reabsorption of water increases under the influence of vasopressin. The reabsorption of Na is increased by aldosterone and decreased by natriuretic factors. The absorption of Ca and phosphates is altered by parathyroid hormone and thyrocalcitonin. The molecular mechanisms regulating the transport of substances by the nephron vary. Vasopressin and various other hormones stimulate the intracellular formation of cyclic AMP from ATP, which represents the effect of the hormone. Other hormones, such as aldosterone, act on the genetic apparatus of the cell, resulting in an intensification of protein synthesis in the ribosomes. These proteins alter the transport of substances through the tubular cell.

The kidneys are important incretory organs. Renin is produced in the cells of the juxtaglomerular apparatus, which is situated near the vascular pole of the glomerulus between the afferent and efferent arterioles; erythropoietin may be produced as well. The secretion of renin increases when renal arterial pressure and Na concentration decrease. The kidneys produce erythropoietin and, apparently, a substance that inhibits the formation of red blood cells. These substances help regulate the concentration of red blood cells. The kidneys have been found to synthesize prostaglandins, substances that lower blood pressure and change the sensitivity of the renal cell to vasopressin and certain other hormones.

Diseases. Kidney diseases may be manifested by edema, hypertension, changes in urine, and other symptoms. Congenital and acquired kidney diseases are classified separately. Among the former are anomalies of number (single, accessory, bifid), position (prolapse, high position, one-side position), shape (horseshoe, disk, S-shaped, L-shaped), and structure (aplasia, hypoplasia, polycystic). There are various anomalies of the renal pelvis and ureters, affecting number, shape, and caliber. Genetically determined defects in anatomical development and structure of the renal parenchyma are often accompanied by congenital defects of other organs; for example, familial nephropathy is often accompanied by deafness. Diseases of the renal tubules are mainly related to metabolic disorders having to do with amino acids and enzymes, such as familial cystinuria and vitamin D-resistant rickets.

The most common acquired kidney diseases are autoimmune diseases, such as glomerulonephritis and nephropathy of pregnancy, and infectious diseases, such as pyelonephritis and tuberculosis. Kidney lesions of a toxic nature are frequent in cases of poisoning by heavy metals and their compounds (such as mercury and bismuth), pesticides, or organic solvents (such as carbon tetrachloride and tetrachloroethylene). Drug nephropathies may occur after taking sulfanilamides, diuretics, or other substances. Injuries may result from radiation and trauma. Kidney tumors may be malignant (hypernephroma, sarcoma) or benign (fibroma, myxoma, adenoma). Tumors may be primary or metastatic. Nephrolithiasis, or the formation of kidney stones, is common. Kidney disorders may be concurrent, that is, secondary to diseases of other organ systems, such as collagen diseases, systemic vasculitis, and diabetes mellitus. The accompanying nephropathies often determine the severity and outcome of the main disease.

The basic functions of the kidneys may become suddenly impaired as a result of certain renal and extrarenal disorders, such as shock, poisoning, and acute infection. The disorders may produce acute renal insufficiency, which is characterized by high nitrogen levels in the blood and disturbance of the water-electrolyte and acid-base balances. Chronic renal insufficiency may be due to many uncured diseases of the kidneys. Kidney diseases of varying origins and types may produce similar symptoms, and a single kidney disease may produce various symptoms. This has served as the basis for identifying a number of syndromes: acute and chronic renal insufficiency, nephrotic syndrome, renal hypertension, and tubulopathies, which lead to disruption of homeostasis. Treatment of kidney diseases takes into account the cause, nature, and stage of the disease.

N. R. PALEEV