5
RENAL SYSTEM
Michelle A. Dokas
DEVELOPMENTAL ANATOMY OF THE RENAL SYSTEM
A. Anatomic Location
The kidneys are positioned within the retroperitoneal space and are surrounded by adipose tissue and loose connective tissue. The kidneys lie along the lower two thoracic vertebrae and the first four lumbar vertebrae. They are not fixed but move with the diaphragm and are supported by the surrounding vascular system, adipose tissue, and fibrous tissue called the renal fascia. The right kidney lies slightly lower than the left.
B. Anatomic Structure
1. Development. All nephrons are formed by 28 weeks gestation. Kidney weight doubles in the first month of life. Filtration and absorption capabilities are not developed until the epithelial cells of the nephrons mature. As the loop of Henle matures and elongates, the ability to concentrate urine improves. Infants are more vulnerable to dehydration and fluid overload because of their inability to concentrate or to excrete urine in response to changes in fluid status. Bladder capacity is age dependent: infants, 15 to 20 mL; adults, 600 to 800 mL. The kidneys of infants and children are relatively large for their body size and age, making them more susceptible to trauma.
2. Gross Structures (Figure 5.1)
a. The capsule is the thin, fibrous, tough outer covering of the kidney.
b. The structural unit of the kidney is the lobe. Each lobe is composed of a pyramid and the overlying cortex. On average, there are 14 lobes in each kidney.
c. The outer portion of the kidney is the cortex. It contains all the glomeruli, the proximal and distal convoluted tubules, the first portions of the loop of Henle, and the collecting ducts.
d. The inner region contains the medulla and the pelvis. The medulla has a pyramidal shape and contains primarily the collecting ducts and loops of Henle. The pelvis forms the upper end of the ureter. It is formed by the merging of the collecting ducts and tubular structures. It provides the pathway of urine from the kidney to the ureter. The fluid in the pelvis is identical to urine.
3. Gross Renal Vasculature. About 20% to 25% of the total cardiac output is delivered to the kidneys. Two renal arteries branch from the descending aorta, and each renal artery branches repeatedly into arterioles.
4. Microscopic Structure
a. The nephron is the functional unit of the kidney. Each mature kidney has about 1 million nephrons. Formation of nephrons is completed at birth, new ones cannot be formed. The nephron wall is composed of a single layer of epithelial cells. The top end (origin) of the nephron is called Bowman’s capsule, which is found in the cortex of the kidney. The fluid in Bowman’s capsule is a filtrate of blood plasma.
b. There are two types of nephrons. Cortical nephrons (85% of nephrons) originate in the outer portion of the cortex and have short loops of Henle that reach only the outer region of the medulla. Juxtaglomerular nephrons originate closer to the medulla, have very long loops of Henle that reach deep into the medulla, and are important for water conservation in the body.
c. The nephron can be divided into three parts: vascular components, tubular components, and collecting ducts.
i. Vascular components of the nephron. Afferent arterioles originate from the medulla and cortex and leads to the capillary bed, which is called the glomerulus (Bowman’s capsule and the glomerulus may be referred to collectively as the glomerulus). Afferent arterioles bring blood to the glomerulus. Efferent arterioles take blood as it exits the glomerulus to the second capillary bed of peritubular capillaries, which supply the proximal and distal tubules in the cortex. Efferent arterioles of juxtaglomerular nephrons send off branches to create the vasa recta, a loop of straight vessels that stretch deep down to supply the medulla, extending alongside the descending limbs of the loop of Henle and back up toward the cortex.
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FIGURE 5.1 Gross structure of bisected kidney.
Source: From Curley, M. A. Q., & Moloney-Harmon, P. (Eds.). (2001). Critical care nursing of infants and children (2nd ed., p. 733). Philadelphia, PA: W. B. Saunders.
ii. Tubular components of the nephron (Figure 5.2). The proximal tubule leads to Bowman’s capsule. The tubule begins as coiled and convoluted (proximal convoluted tubule) and then straightens as it extends into the medulla. The descending limb of the loop of Henle is a long, thin tubule that extends deep into the medulla. At its deepest point in the medulla, it turns sharply upward toward the cortex. The ascending limb of the loop of Henle is considerably thicker than the descending limb. It becomes continuous with the distal tubule. The distal tubule is a coiled, convoluted structure responsible for final adjustments of filtrate.
iii. Collecting ducts gather fluid from several nephrons and drain into larger ducts, which drain into the minor calyces, then into the renal pelvis, then to the ureter.
DEVELOPMENTAL PHYSIOLOGY AND CLINICAL ASSESSMENT OF KIDNEY FUNCTION
A. Basic Transport Mechanisms
The following concepts are integral to the formation of urine in the kidney:
1. During active transport, substances combine with a carrier and diffuse against the concentration gradient through the tubular membrane with the help of adenosine triphosphate (ATP). Sodium, glucose, amino acids, calcium, potassium, chloride, bicarbonate, and phosphate are reabsorbed from the tubule by active transport.
2. Passive transport involves movement of substances in response to changes in the concentration gradient, without the assistance of ATP or a carrier. Diffusion is the spontaneous movement of solutes across a semipermeable membrane from a high concentration to a lesser concentration. For example, as water reabsorbs out of the tubule and the urea concentration in the tubule increases, urea diffuses out of the tubule. Osmosis is the spontaneous movement of water across a semipermeable membrane from an area of lesser solute concentration to an area of greater solute concentration. For example, as sodium is reabsorbed from the tubule and its concentration increases outside the tubule, water moves out of the tubule to balance the concentration gradient. Serum colloid osmotic pressure is the opposing pressure preventing free water from moving out of the vascular space.
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FIGURE 5.2 Tubular components of the nephron.
ADH, antidiuretic hormone.
Source: From Wong, D. L., Hockenberry-Eaton, M., Wilson, D., Winkelstein, M. L., Ahmann, E., & DiVito-Thomas, P. (1999). Whaley & Wong’s nursing care of infants and children (6th ed.). St. Louis, MO: Mosby.
B. Urine Formation
Urine formation involves the following physiologic processes: filtration, reabsorption, and secretion.
1. Filtration
a. Fluid and various substances, known as the glomerular filtrate, are filtered from the plasma through the porous walls of the glomerular capillaries into Bowman’s capsule and on to the renal tubules. Glomerular filtrate is primarily composed of water; it is essentially the same substance as blood plasma except for the larger protein molecules, such as albumin, because they are largely unable to move through the filtration barrier.
b. The pathway for filtration is through capillary fenestrations across the basement membrane and through slit passages. The ability to resist passing and to pass through filtration pathways depend on size, shape, and electrical charge of the molecules. Albumin (protein) molecules are too large to permeate the glomerular membrane, creating a high osmotic pressure that opposes orthostatic filtration from the vascular space.
c. The “forcing” pressure, or filtration pressure, is the net pressure acting to force substances out of the glomerulus.
i. The primary force is the hydrostatic pressure of the blood inside the capillaries generated by the pumping action of the heart.
ii. The secondary forces are the oncotic pressure of the plasma in the glomerular capillaries and the hydrostatic pressure in Bowman’s capsule.
448d. Regulation of glomerular filtration rate (GFR)
i. Renal blood flow (RBF) and GFR must remain relatively constant over a wide range of perfusion pressures and in various physiological states such as disease. This is referred to as autoregulation. Numerous neural and hormonal factors can alter RBF, such as renal vasoconstrictors that decrease RBF, including endothelin, angiotensin II, thromboxane, alpha-adrenergic receptor stimulators, vasopressin, and catecholamines. Vasodilators that may relax renal vascular smooth muscle include prostaglandins, atrial peptides, bradykinin, fenoldopam, and nitric oxide. Failure of these mechanisms can lead to renal dysfunction in all of the disease states discussed in this chaper.
ii. Changes in filtration pressure can directly affect GFR. Factors affecting filtration pressure, and thus the GFR, include vasoconstriction or vasodilation of afferent and efferent arterioles, blood flow rate, tubule obstruction, and changes in serum osmotic pressure. RBF is controlled by sympathetic nerve impulses that constrict arterioles. The effect on GFR depends on which arteriole (afferent or efferent) is constricted (Table 5.1).
iii. Vasodilation and vasoconstriction are autoregulatory responses to changes in systemic arterial pressure. They occur to maintain constant RBF and a stable GFR. A distal tubular feedback mechanism ensures constant delivery of filtrate to the distal tubule. Failure of this autoregulatory response can be due to obstruction, trauma, dehydration, or disease.
TABLE 5.1 Factors Affecting GFR
Factors | Physiologic Response | Net Effect on GFR |
Afferent arteriole vasoconstriction, efferent arteriole vasodilation, or both | Decreased blood flow Decreased glomerular hydration pressure | Decrease |
Afferent arteriole vasodilation or efferent arteriole vasoconstriction | Blood backs up in the glomerulus Increased hydrostatic pressure | Increase |
Decrease in plasma protein concentration | Decreased plasma osmotic pressure | Increase |
Slow blood flow | Larger proportions of the plasma filter out of the glomerulus Plasma osmotic pressure rises | Decrease |
Rapid blood flow | Less change in plasma osmotic pressure | Increase |
Tubular obstruction | Fluid backs up in the renal tubules Hydrostatic pressure increases in Bowman’s capsule | Decrease |
GFR, glomerular filtration rate.
iv. The effect of shock on GFR and renal function is detailed in Figure 5.3.
e. Measuring filtration. Clearance is the volume of a specific substance filtered from the plasma over a designated time, generally:
Clearance (mL/min/1.73m) =
Concentration of substance in urine ×
Volume of urine collected/plasma
concentration of that substance
i. Substances used to assess GFR include creatinine, inulin (nonmetabolizable sugar), radioisotopes, radiocontrast agents, and cystatin-C.
ii. GFR as estimated by creatinine clearance alone is less accurate. Creatinine is an endogenous waste product that is produced by the muscles and excreted by the kidneys. Estimates of GFR using creatinine clearance and cystatin-C together are more accurate, especially in children (Traynor, Mactier, Geddes, & Fox, 2006).
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FIGURE 5.3 Renal response to shock.
iii. GFR as measured by creatinine clearance
1) First week of life. GFR = 15 to 20 mL/min/1.73 m2
2) At the second week of life. GFR = 35 to 40 mL/min/1.73 m2
3) At 6 months. GFR = 60 mL/min/1.73 m2
4) At 1 year. GFR = 80 to 120 mL/min/1.73 m2
iv. The filtration fraction (FF) is the percentage of fluid filtered into Bowman’s capsule by the glomerulus in relationship to the total renal plasma flow (normal = 20%).
v. Alteration in GFR occurs with decreased renal perfusion, changes in glomerular perfusion pressures (e.g., shock, glomerular nephritis), and decreases in plasma oncotic pressure (e.g., nephrotic syndrome).
2. Tubular Reabsorption. As fluid flows along the nephron, past the cells of the tubular wall, substances are reabsorbed from the renal tubule and returned to the blood via the peritubular capillaries.
a. Most of tubular reabsorption occurs in the proximal tubule. By the time the filtrate reaches the end of the proximal tubule, two thirds of the water and virtually all the nutrients have been reabsorbed and returned to the blood. The proximal tubules play a role in acid–base balance and regulation of calcium, magnesium, and phosphorus. The proximal tubules have active transport systems for secretion of organic acids and bases from blood to tubule lumen.
b. The tubular cells lining the walls of the proximal tubules are surrounded by two different membranes that aid in water and solute reabsorption. The convoluted portion of the proximal tubule has a brush-like border of microvilli that greatly increases surface area exposed to glomerular filtrate and enhances reabsorption. The basolateral membrane has no microvilli but has an abundance of sodium and potassium pumps and other diffusion transport systems for glucose and amino acids.
c. Segments of the renal tubule use particular modes of transport to reabsorb certain substances. Substances reabsorbed by active transport depend on carriers. If the amount of substance exceeds the number of carriers (renal tubular threshold), the remaining substance will remain in the filtrate and be excreted in urine (e.g., glucosuria). Glucosuria only occurs when plasma glucose levels exceed 180 mg/dL.
d. Fluid reabsorption is determined by the net sodium reabsorption. If the GFR decreases, net sodium reabsorption decreases and fluid reabsorption decreases. If the GFR increases, net sodium reabsorption increases and fluid reabsorption increases.
e. Several factors enhance the rate of fluid reabsorption from the renal tubule. The efferent arteriole is narrower than the peritubular capillary; therefore, blood flowing from the efferent arteriole to the peritubular capillary is under relatively low pressure. The wall of the renal capillary is more permeable than other capillaries.
450f. The prime “mover” for most of the proximal tubular transport is the active transport of sodium. Water is reabsorbed by osmosis in response to the reabsorption of sodium ions by active transport. Amino acids and glucose are cotransported (reabsorbed) with sodium into the interstitial fluid and eventually to capillaries. When sodium is reabsorbed from the tubule, it takes chloride with it, changing the osmotic gradient and favoring the reabsorption of water into the interstitium and eventually to the capillaries. When water is absorbed from the tubule, the concentration of the remaining solutes increases, therefore increasing the diffusion of other solutes into the interstitial space and eventually to the capillaries.
g. Measuring reabsorption. The amount of solute reabsorbed is the difference between the amount of solute filtered into the glomerulus and the amount of solute excreted in the urine (assuming the amount filtered is greater than the amount excreted).
3. Tubular secretion is the process by which certain substances are removed from the blood or plasma of the peritubular capillary and added to the fluid of the renal tubule through active or passive transport.
a. Certain organic compounds (such as penicillin, creatinine, and histamine) are actively secreted into tubular fluid by the epithelium of the proximal convoluted segment.
b. Hydrogen ions are secreted by the distal segment and the collecting ducts. Hydrogen ion secretion plays an important role in acid–base balance.
c. Potassium ions are secreted into tubular fluid because of the electrochemical attraction created by sodium reabsorption.
d. Measuring secretion. The amount of solute secreted is the difference between the amount of solute filtered into the glomerulus and the amount of solute excreted in the urine (assuming the amount filtered is less than the amount excreted).
C. Water and Sodium Balance
1. Measuring Water Balance and Regulation of Urine Concentration. Normal serum osmolarity is 272 to 290 mOsm/L. The calculation for serum osmolarity is (2 × serum NA) + (serum glucose/18) + (blood urea nitrogen [BUN]/2.8). Normal urine osmolarity is approximately 300 mOsm/L. This usually correlates with a urine-specific gravity of 1.010 to 1.015.
2. Role of Countercurrent Mechanism in Concentrating and Diluting
a. Filtrate concentration changes as it flows from the proximal tubule to the collecting ducts. Filtrate becomes increasingly concentrated as it moves from the proximal tubule through the descending limb to the loop of Henle. Maximum concentration occurs at the tip of the loop of Henle. Filtrate becomes less concentrated as it moves up the ascending limb of the loop and on to the collecting duct.
b. Juxtamedullary nephrons and the medullary portion of the kidney play a major role in this countercurrent mechanism. Sodium and chloride are actively reabsorbed out of the thick portion of the ascending limb into the interstitial space and peritubular capillaries, creating an osmotic gradient between the interstitium and the tubule. This segment of the tubule is impermeable to water, and water cannot be reabsorbed with sodium. In response to this osmotic gradient, water is passively reabsorbed out of the descending limb into the interstitium and peritubular capillaries. A concentration gradient is created, and filtrate is more dilute as it enters the collecting duct. As this dilute urine enters the distal tubule and collecting ducts, antidiuretic hormone (ADH) controls the amount of water reabsorption according to the need for dilute or concentrated urine. ADH is released from the hypothalamus. If dilute urine is needed, ADH is inhibited. If water conservation or concentrated urine is needed, ADH is secreted.
3. Hormonal Control of Water Balance
a. Vasopressin, or ADH, plays a role in water balance. The distal convoluted tubule and collecting duct are impermeable to water; so water may be excreted as dilute urine. If ADH is present, the distal tubule and collecting ducts become permeable, water is reabsorbed, and urine is more concentrated. A rise in the solute concentration of the extracellular fluids and blood plasma stimulates cells in the hypothalamus to increase production of ADH and to cause release of ADH from the posterior pituitary. In the kidney, ADH initiates retention of water and decrease in solute concentration. Decreased solute concentration causes decreased ADH release, which causes dilute urine. Increased solute concentration causes increased ADH release, which causes concentrated urine.
b. Aldosterone is responsible for virtually all sodium and water reabsorption in the 451collecting duct. This region of the renal tubule fine-tunes sodium excretion. The adrenal cortex releases aldosterone in response to angiotensin II, hyperkalemia, hyponatremia, decreased pulse pressure, or decreased right atrial distention. Aldosterone increases sodium reabsorption by increasing the number of sodium channels in the apical plasma membrane of the principal cell. Aldosterone stimulates the secretion of potassium and hydrogen and decreases potassium reabsorption.
c. Other factors also control renal sodium excretion. Hormones that lead to retention of sodium include growth hormone, cortisol, insulin, and estrogen. These act at the tubular level. Parathyroid hormone (PTH), progesterone, and glycogen inhibit tubular reabsorption of sodium. Atrial natriuretic peptide, a 28-amino peptide produced and secreted in the atria of the heart, is released in response to atrial stretch, for example, in response to expansion of central blood volume. This peptide then enhances sodium excretion in part by inhibiting sodium reabsorption on the collecting duct.
4. Sodium and Water Reabsorption
a. Sodium concentration is higher in the lumen of the tubule than in the cells lining the tubule, so sodium moves into the tubular cells. Because the proximal tubule’s brush border has no sodium pump, the sodium cannot be pumped back into the lumen. Only the basolateral membrane can pump out sodium into the interstitial spaces and then diffuse into the peritubular capillaries. When sodium (positively charged) is reabsorbed, it leaves the tubule and moves into the tubular wall, which is followed by negatively charged ions, such as, chloride, phosphate, and bicarbonate.
b. Every sodium or chloride ion that leaves the tubule means the loss of osmotically active particles from the tubule to the interstitium. The movement of particles creates a change in osmotic gradient favoring water reabsorption, and water follows the sodium and chloride into the interstitium. With less sodium in the tubule, the concentration of solutes in the tubule increases, thereby increasing diffusion of other solutes out of the tubule and into the interstitial space. As water is reabsorbed from the filtrate into the peritubular capillaries, substances remaining in the tubule become more concentrated. As a result, water moves into the tubules. As sodium reabsorption increases, water reabsorption increases and vice versa.
c. Alteration in the GFR influences the amount of sodium reabsorbed or secreted. When the GFR decreases (e.g., dehydration, sepsis), sodium and water reabsorption increases. Decreased volume decreases venous, atrial, and arterial pressures. Pressoreceptors decrease the number of impulses to the brainstem, which activates sympathetic impulses to stimulate renin release from the juxtaglomerular cells in the afferent arterioles. Renin is converted to angiotensin I, which is converted to angiotensin II, which causes vasoconstriction and secretion of aldosterone. This creates “thirst” in an effort to increase volume. As water volume increases, ADH is secreted to maintain water and solute balance.
D. Electrolyte Balance
1. Potassium Ion (K+)
a. The kidney is chiefly responsible for maintaining potassium homeostasis. Potassium has a normal serum value of approximately 3.5 to 5 mEq/L. It is the most abundant solute inside cells (145 mEq/L); a very small amount is present in the serum. Potassium is an important factor in the performance of many enzyme systems, playing a role in the maintenance of cell volume, pH, and cell excitability (membrane potentials). Decreasing serum potassium depolarizes membranes and raises excitability (e.g., cardiac rhythm deterioration leading to fibrillation). Increasing serum potassium hyperpolarizes membranes and decreases excitability (e.g., skeletal and smooth-muscle weakness and decreased reflexes). Acid–base balance changes; hormone imbalance and pharmacologic agents frequently cause postassium shifts.
b. Potassium excretion is regulated mainly by the collecting duct, but is a complex regulating mechanism that is intertwined with sodium and hydrogen transport. The secretion and excretion of potassium are also influenced by plasma concentration of postassium, dietary potassium, aldosterone, angiontensin II, and delivery of sodium to prinicpal cells (Eaton & Pooler, 2013). Most potassium is reabsorbed in the proximal tubule and the loop of Henle. The distal tubule and collecting ducts have a high concentration of intracellular potassium owing to the action of the sodium–potassium pumps. Changes in renal regulation of potassium are due to changes in potassium secretion in the distal tubule and collecting duct. Increases in intracellular potassium increase the secretion and excretion of potassium. Increases in plasma potassium stimulate 452the adrenal cortex to secrete aldosterone, which promotes secretion and excretion of potassium.
c. Any drug that interferes with aldosterone activity (e.g., angiotensin-converting enzyme [ACE] inhibitors, angiotensin II receptor blockers, spironolactone, heparin, and beta-blockers) will inhibit potassium secretion and increase serum potassium levels.
d. Drugs that block the principal cell sodium channel also inhibit potassium secretion (e.g., trimethoprim, pentamidime, amiloride) and may lead to increased serum potassium levels (Daly & Farrington, 2013).
e. In acidosis, potassium excretion decreases. Distal tubular and collecting-duct cells lose potassium to the plasma, leakage and secretion of potassium into tubules decrease, and potassium shifts from the cells into the plasma. In alkalosis, potassium excretion increases. Potassium increases in the distal tubule and collecting duct. Leakage and secretion of potassium increase. Potassium shifts into the cells. With a shift from acidosis to alkalosis, serum potassium decreases because of the shift into the cells.
2. Sodium
a. The normal serum value is approximately 135 to 145 mEq/L. Hyponatremia may lead to seizure activity. Excess of sodium leads to edema and hypertension. Dilutional hyponatremia occurs secondary to hypotonic fluid intake and impaired free water excretion. The hyponatremia corrects slowly with free water diuresis.
b. Management may include dialysis or continuous renal replacement therapy (CRRT) for severe or symptomatic hyponatremia (serum Na+ <125 mEq/L) in the oliguric, hypervolemic patient or oliguric, hypernatremic patient (Na+ >150 mEq/L). Hyponatremic metabolic acidosis may be treated with administration of sodium, partly in the form of sodium bicarbonate. Administration of isotonic saline 0.9% is indicated for fluid loss and dehydration, whereas administration of hypertonic 3% saline is indicated if the patient is fluid overloaded and has significant hyponatremia. Hypertonic saline is used until the serum sodium is corrected to a “safe” level, often considered to be greater than 125 mEq/L, and then transitioned to a less hypertonic intravenous (IV) solution.
3. Phosphate (Phosphorus, Inorganic)
a. Normal serum values in the newborn are 4.2 to 6.5 mg/dL. Normal values in children aged 1 to 5 years are 3.5 to 6.5 mg/dL and in older children range from 2.5 to 4.5 mg/dL. Renal excretion of phosphate is the body’s primary mechanism for regulation of phosphate; therefore, patients in renal failure are at high risk for hyperphosphatemia.
b. PTH indirectly affects serum phosphate levels by affecting calcium. Phosphate and calcium are reabsorbed from bone. Tubular reabsorption of phosphate is decreased as tubular reabsorption of sodium increases. PTH enhances intestinal absorption of calcium and phosphate. Vitamin D is converted to its active form by the liver and kidneys, thereby regulating phosphate and calcium balance. Active absorption of phosphate (and calcium) by the intestine is stimulated by vitamin D. Reabsorption of phosphate and calcium from bone to extracellular fluid is facilitated by vitamin D. Vitamin D stimulates renal tubular reabsorption of phosphate and calcium.
4. Calcium
a. The normal serum value is 9 to 11 mg/dL (total calcium) and 1.00 to 1.4 mmol/dL (ionized calcium). Calcium exists in two forms: ionized and nonionized. About 45% to 50% is ionized, meaning “free” and not bound to albumin. Ionized calcium is the physiologically active form of calcium. Albumin-bound calcium is not filtered at the glomerulus. Decreased serum albumin levels may affect serum calcium levels.
b. PTH is the most important regulator of calcium. Hypocalcemia stimulates the release of PTH, which decreases renal excretion of calcium and increases urinary excretion of phosphorus. Hypercalcemia inhibits the release of PTH.
5. Magnesium. The normal serum values are 1.8 to 2.3 mEq/L. Magnesium is an essential cofactor for many metabolic enzymatic processes in the body. Eighty percent of plasma magnesium is filtered at the glomerulus, and only a small amount of this filtrate is excreted.
E. Regulation of Acid–Base Balance
1. Definitions. An acid is a source of hydrogen ions. A base takes up or absorbs hydrogen ions. A buffer combines with an acid or base to maintain a stable pH.
2. In an effort to achieve an acid–base balance, the lungs regulate carbon dioxide and the kidneys regulate bicarbonate. With normal digestion, metabolic 453acids (hydrogen ions) are produced. Metabolic hydrogen ions are picked up by serum bicarbonate and form carbon dioxide. An increased level of carbon dioxide and hydrogen ions stimulates increased respiration, which helps to eliminate carbon dioxide and reverse acidosis. Respiratory regulation of acid–base balance is generally inadequate in severe metabolic acidosis and alkalosis.
3. The kidney regulates acid–base balance through hydrogen secretion and bicarbonate reabsorption. Hydrogen ions are secreted (removed from the blood and plasma of the peritubular capillary and added to the fluid of the renal tubule) at the distal tubule and the collecting duct. Bicarbonate is filtered at the glomerulus and is not readily reabsorbed because the peritubular capillary membrane is not highly permeable to the molecule. HCO3– combines with H+ in the tubular cell to form carbonic acid (H2CO3). The carbonic acid rapily dissociates and is diffused into the tubular cell where carbonic anhydrase catalizes the reaction between CO2 and H2O to form HCO3– and H+. In the distal tubule, hydrogen also combines with nonbicarbonate buffers for the elimination of excess acids in the urine. The end effect is alkalinity of the plasma (McCance & Huether, 2010).
a. Renal response in alkalotic conditions. Potassium excretion increases, chloride is reabsorbed with sodium, and bicarbonate is excreted. If an increase in filtrate bicarbonate is secondary to increased serum concentration, bicarbonate excretion increases. If an increase in filtrate bicarbonate is secondary to hypovolemia (e.g., in persistent vomiting), hydrogen ion secretion and bicarbonate reabsorption from the tubules increase, preventing excretion of excess bicarbonate. Alkalosis is corrected as volume status is restored.
b. Renal response in acidotic conditions. Potassium excretion decreases. Bicarbonate is reabsorbed with sodium, and chloride is excreted. Bicarbonate diffuses into the extracellular compartment and ultimately into the plasma (via the renal vein), resulting in reabsorption of hydrogen ions. Renal excretion of acid (ammonium excretion) increases.
F. Regulation of Arterial Blood Pressure
1. Maintenance of Circulating Blood Volume. Circulating blood volume is maintained by sodium and water balance. A countercurrent mechanism plays a role in concentrating and diluting. Hormonal control of water balance is mediated by ADH and aldosterone, initiated by hypothalamic osmoreceptors and cardiopulmonary baroreceptors. Large decreases in plasma volume elicit significant concentrations of ADH to exert direct vasoconstrictor effects on arteriolar smooth muscle to increase total peripheral resistance. Renal arterioles and mesangial cells also respond to a high plasma concentration of ADH, prompting retention of both sodium and water by lowering GFR (Eaton & Pooler, 2013).
2. Regulation of peripheral vascular resistance is via the renin–angiotensin–aldosterone system and the central nervous system (CNS) (Figure 5.4). Juxtaglomerular cells release renin in response to a decrease in glomerular pressure (kidney perfusion pressure), an increase in sympathetic nervous system stimulation, decreased sodium in the distal tubule, or 454vasoconstrictive agents. Renin diffuses into the circulatory system and converts angiotensinogen into angiotensin I. As angiotensin I circulates to the lungs, it converts to angiotensin II (and also produces aldosterone). Angiotensin II is a powerful vasoconstrictor of the peripheral vascular system. Angiotensin II stimulates aldosterone secretion, which causes an increase in water and sodium reabsorption. The sympathetic nervous system also regulates peripheral vascular resistance by causing vasoconstriction.
FIGURE 5.4 Renin–angiotensin aldosterone cascade to maintain systemic perfusion pressure.
Source: From Curley, M. A. Q., & Moloney-Harmon, 2nd ed., P. (Eds.). (2001). Critical care nursing of infants and children (2nd ed., p. 735). Philadelphia, PA: W. B. Saunders.
G. Regulation of RBF
1. Prostaglandins are vasoactive substances that act by either dilating or constricting renal vessels. Their effect is limited to the renal vasculature.
2. Three prostaglandins are produced by cells in the kidney’s cortical and medullary structures. Thromboxane A2 is a vasoconstrictor. Prostacyclin (PGI2) and prostaglandin E2 (PGE2) are vasodilators. PGI2 and PGE2 produce direct vasodilation of afferent arterioles, which helps to maintain RBF and glomerular perfusion. PGE2 increases urine output by counteracting the actions of ADH. PGE2 increases sodium excretion by inhibiting its reabsorption from the renal tubules.
H. Elimination of Toxins and Metabolic Wastes
1. Urea is produced in the liver as a by-product of amino acid metabolism. Amino acids and proteins are metabolized in the liver and yield ammonia, which is very toxic until the liver rapidly detoxifies it into urea. Urea production proceeds continuously and constitutes about half of the usual solute content of urine. It is freely filtered by the kidney; about 50% of urea is passively reabsorbed, and 50% is excreted in the urine.
2. Uric acid is a by-product of metabolism of certain organic bases in nucleic acids. Ninety percent is reabsorbed in the glomerular filtrate, and 10% is secreted into the renal tubule.
3. Creatinine is the end product of protein metabolism. Under normal conditions, creatinine is completely filtered by the proximal tubules and excreted in the urine. Its complete elimination makes it an excellent marker of renal function. The creatinine level is proportional to the BUN level. The normal BUN-to-creatinine ratio is 10:1 to 15:1. An increase in both BUN and creatinine signals renal dysfunction. An increase in BUN without an increase in creatinine may be an indication of dehydration, decreased renal perfusion, or catabolism.
I. Stimulation of Bone Marrow Erythrocyte Production
1. Erythropoietin is a hormone produced in the kidneys that stimulates red blood cell (RBC) production from the bone marrow, and a deficiency of production leads to anemia. The anemia associated with chronic kidney disease (CKD) is due mainly to a deficiency of erythropoietin. In renal failure, production of erythropoietin is insufficient. However, often the anemia of CKD can be improved with iron supplementation. Some children with CKD have iron depletion even when taking iron supplements.
2. IV and subcutaneous recombinant human erythropoietin are available for treatment of anemia secondary to CKD. Side effects include hypertension, seizures, and vascular access thrombus formation. This is often administered at the time of dialysis if the patient is receiving intermittent dialysis therapy.
3. Uremia shortens the life span of RBCs and is a significant contributor to anemia. It also decreases platelet function.
4. Transfusions should be avoided as much as possible, not only because of risks, such as communicable disease and fluid overload, but also to avoid further decrease of the significantly inhibited positive feedback loop stimulating erythropoeitin production.
5. Other possible deficiencies should be assessed before therapy is initiated, including vitamin B12 deficiency, folate deficiency, or aluminum intoxication (the latter leading to microcytic anemia). Throughout the course of therapy, iron stores (serum iron, ferritin, and total iron-binding capacity [TIBC]) should be evaluated frequently because the rapid proliferative response may not be accompanied by an adequate availability of iron. If iron stores prove insufficient during the course of therapy, replacement should be implemented (Table 5.2).
INVASIVE AND NONINVASIVE DIAGNOSTIC STUDIES
A. Imaging
1. Renal ultrasound with doppler (RUS) is readily available, accurate, reliable, and noninvasive. It can show size, shape, and anatomical variants. Asymmetry indicates unilateral disease process. RUS avoids radiation and contrast media, which may be nephrotoxic. Increased echogenicity of the renal parenchyma is a common nonspecific indicator of intrinsic renal disease. In some cases of acute tubular necrosis (ATN), renal parenchymal echogenicity may be normal. RBF is generally reduced in ARF, and Doppler flow ultrasound can detect low blood flow. Low RBF or abnormal blood flow associated with renal artery stenosis can also be detected. Low RBF can also be indicative of pyelonephritis and may show small renal calculi (Wu, Bellah, & Snyder, 2016). Complete absence of flow suggests complete thrombosis of the renal circulation (Toto, 2004).
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2. Voiding cystourethorography (VCUG) is the most sensitive and effective way to assess for the prescence of urinary reflux.
3. Dimercaptosuccinic acid scanning (DMSA) is the critical test for renal scarring associated with reflux as well as detection of urinary obstruction and urine leak. It is more sensitive than intravenous pyelogram (IVP) and is noninvasive.
4. A MAG3 renal scan looks at functional renal function and the collecting system. It is useful in assessing for hydronephrosis and can distinguish ATN from prerenal or other intrinsic renal disease.
5. CT and helical CT show more detailed anatomy than ultrasound. Helical CT is the gold standard for diagnosing renal calculi. Evaluation of cystic structures is more precise with CT (Lerma, 2009). It is also preferred in any child with abdominal trauma. Most currently, the use of CT angiography (CTA) can evaluate for renal hypertension, vasculitis, vascular malformations, and renal trauma (Wu et al., 2016).
6. MRI and magnetic renal angiography (MRA) are useful tests for patients with a contrast allergy. MRI shows more specific anatomic details. MRA is now the standard of care for renal vessels and thrombotic disorders. Use of contrast is not recommended when estimated GFR is ≤30 mL/min (Lerma, 2009).
7. Kidney angiogram is helpful in patients with acute kidney injury (AKI) caused by vascular disorders, including renal artery stenosis and renal artery 456emboli, but should be used cautiously in patients with compromised renal function.
B. Laboratory Evaluation
1. Urinalysis is the most important noninvasive test and is easily obtainable. It shows:
a. pH. Normal 6 to 8. pH <6.0 is suggestive of metabolic acidosis. pH >8 is suspicious for renal tubular acidosis.
b. Specific gravity. Demonstrates hydration status.
c. Leukocyte esterase. Tests for the prescence of white blood cells (WBCs) and is indicitative of infection.
d. Red cells. May indicate trauma, glomerulonephritis, nephrolithiasis.
e. Protein. Is specific for albumin and should not be present. More than 1+ protein is consistent with nephrotic syndrome.
f. Ketones and glucose. Ketones in the presence of normal serum glucose would suggest renal tubular dysfunction as well as presence of poorly controlled diabetes (although not reliable for the diagnosis of diabetes) or Fanconi syndrome.
2. Complete blood count (CBC) assesses for anemia (see Table 5.2).
3. Serum chemistries with BUN and creatinine. Normal creatinine varies with age (Table 5.3).
4. Urine electrolyte measurement in AKI is performed to test functional integrity of the renal tubules.
5. The most informative urine test is the fractional excretion of sodium (FENa); results are inaccurate if the patient is on diuretics or prior infusion of saline (Lerma, 2009).
TABLE 5.3 Normal Serum Creatinine Based on Age
Age | Normal Creatinine Levels (mg/dL) |
1 month and younger | 1 |
Second month of life | <0.5 |
3 months–6 years | <0.6 |
6–15 years | <1.0 |
a. Results. Less than 1%—prerenal renal failure such as intravascular volume depletion due to fluid losses or sequestration, hypotension, sepsis, and so on; greater than 2%—intrinsic or chronic renal failure.
C. Kidney biopsy should be performed only when clinical, biochemical, and noninvasive imaging studies are insufficient for diagnosis and there is reasonable belief that the test results will alter therapy.
ACUTE KIDNEY INJURY
A. Definitions
1. AKI is the sudden loss of renal capacity for filtration and tubular reabsorption, resulting in accumulation of wastes, fluid and electrolyte imbalance, and acid–base imbalances. AKI had previously been termed acute renal failure, however, with advancements in understanding that kidney injury is an independant risk factor for mortality, develeopment of standardized definitions, and discovery of AKI biomarkers, the nomenclature has changed. Several nephrology groups developed the RIFLE critiera for AKI. RIFLE stratifies for risk, injury, failure, and outcomes of loss and end-stage kidney disease.
a. Risk is defined as 50% rise in serum creatinine over baseline or less than 0.5 mL/kg/hr of urine output for 6 hours.
b. Injury is defined as two- to three-times rise in baseline creatinine or urine output <0.5 mL/kg/hr for 16 hours
c. Failure is defined as rise in serum creatinine more than three times baseline or urine output <0.5 mL/kg/hr for 24 hours or <0.3 mL/kg/hr for 12 hours (Fortenberry, Paden, & Goldstein, 2013).
457B. Causes
1. There are many causes of AKI in children, including prerenal causes, intrinsic renal failure, (also known as ATN), and postrenal failure.
2. Prerenal causes, the most common cause of AKI, are usually caused by poor perfusion (Table 5.4). A decrease in renal perfusion causes decreased glomerular perfusion and GFR. Prerenal causes, by definition, are not associated with any intrinsic parenchymal disease. Impaired RBF may be secondary to impaired cardiac performance, intravascular volume depletion, renal vasoconstriction, or renal artery thrombosis. When reduction of RBF is mild to moderate, kidney blood flow and GFR are maintained by autoregulatory response. This is accomplished by autoregulation of afferent arteriolar dilation and efferent arteriolar vasoconstriction. Prerenal AKI will occur when adaptive mechanisms fail and GFR falls. There is a good prognosis for kidney function if prompt recognition and restoration of adequate RBF is achieved. Two common classes of medications, nonsteroidal anti-inflammatory drugs (NSAIDs) and ACE inhibitors, can cause prerenal AKI by impairing renal autoregulation. Hypoxic/ischemic and nephrotoxic acute kidney failure are the most common causes of hospital-acquired kidney failure. In more current studies, cardiopulmonary bypass has been associated with a 20% to 40% AKI rate (Fortenberry et al., 2013).
3. Intrinsic renal failure is also known as ATN and is related to decreased perfusion to the renal parenchyma as in hemolytic uremic syndrome (HUS), acute glomerulonephritis, or acute interstitial nephritis. The condition is typically reversible except when ischemia is severe enough to cause cortical necrosis producing oliguria (rare). ATN is the death of tubular cells, which may result when tubular cells are deprived of oxygen (ischemic ATN) or when they have been exposed to a toxic drug or molecule (nephrotoxic ATN). When mean arterial blood pressure drops significantly, renal autoregulatory processes are no longer functional, often leading to development of ATN and uremic syndrome. Multiple factors, including systemic maldistribution of volume and decrease in blood flow secondary to circulating mediators, affect blood and oxygen delivery to the kidneys. Fortunately, new tubular cells usually replace those that have died. The tubular cells of the kidneys undergo a continuous cycle of cell death and renewal, much like the cells of the skin (Lerma, 2009).
a. Etiology
i. Nephrotoxic ATN is a toxic insult to the renal tubules secondary to nephrotoxic drugs, radiographic contrast dye, organic solvents, or inappropriate levels of hemoglobin or myoglobin. Tubular epithelium necrosis occurs. The healing process and prognosis are better than that for ischemic ATN because the supporting basement membrane is not affected. The most freqeuntly used nephrotoxic medications that have been associated with ATN in the pediatric population include lasix, gentamycin, vancomycin, and gancyclovir (Slater et al., 2017).
458ii. Ischemic ATN (hemodynamically mediated renal failure) is a sudden and sustained decline of GFR and necrosis of the tubule cells secondary to nephrotoxic injury. Compensatory and autoregulatory mechanisms are exhausted. Renal oxygen delivery is critically impaired, causing tubular and cellular damage. The body attempts to compensate and maintain adequate RBF and GFR by sodium and water retention, which results in decreased urine output. Oliguric ATN has a much worse prognosis than nonoliguric ATN. Common complications of AKI are noted in Table 5.5.
b. Pathophysiology
i. Vasoactive factors. Arteriolar vasoconstriction is induced.
ii. Tubular factors. As the hydrostatic pressure increases, there is back leak from the tubular lumen to the vasa recta. Cellular sloughing and casts cause tubular obstruction.
iii. Vascular factors. In low blood flow states, nephrotoxins are concentrated in the renal tubular cells. Glomerular capillary permeability increases for proteins and decreases for potassium.
iv. Metabolic factors. Damage to the cell membrane and impaired cellular function occur as the calcium flux is altered and oxygen free radicals are formed.
c. The clinical course of ATN can be divided into four phases
i. The onset, or initiating phase, is the time from the precipitating event until cell injury occurs. The duration is hours to days. It may correspond with prerenal failure. Renal failure is reversible at this point. The time course may be hours for postischemic ATN compared with days for nephrotoxic ATN.
ii. The oliguric phase is the time from cell injury to the development of uremia. Duration is 1 to 2 weeks. Oliguria (urine output of less than 1 mL/kg/hr) is more common in postischemic ATN. Anuria (no urine output) is uncommon in ATN, which is more common in postrenal obstruction. The following events characterize development of severe nephron dysfunction and uremia or uremic syndrome during this phase:
• GFR is significantly decreased.
• Hypervolemia occurs.
• BUN and plasma creatinine increase.
459• Electrolyte imbalances occur.
• Metabolic acidosis is present.
• Side effects of the accumulation of uremic toxins are evident (sluggishness, insomnia, itching, slurring of speech, anorexia, nausea, vomiting, confusion, asterixis, seizures, coma).
iii. The diuretic phase is the beginning of recovery characterized by improved urine output, increased urea excretion, and solute excretion. Duration is 7 to 14 days. Signs of gradual improvement of overall renal function are seen. In the early part of the phase, urine output dramatically increases each day. In the beginning of the diuretic phase, “dumb” urine is excreted; “dumb” urine is similar to filtrate and shows little function of reabsorption or secretion. Throughout the diuretic phase, urea excretion and solute reabsorption and secretion improve. By the end of this phase, the BUN has fallen and stabilized, electrolyte balance and acidosis are improved, and GFR begins to return to normal. Renal replacement therapy may be indicated during this phase until kidney function has returned enough to control fluid and electrolyte balance. Administration of fluid to replace urine output may be necessary if the patient’s volume status and assessment indicate.
iv. During the recovery phase, renal function slowly reoccurs. It may take years for renal function to return to normal. There may be residual damage and a certain percentage of unrecoverable renal function. Children may have some degree of chronic renal failure for months or years after the insult but generally have steadily improving renal function as months and years pass. Intermittent monitoring of renal function will be required (Lerma, 2009).
TABLE 5.6 Diagnostic Laboratory Values (Urine and Serum)
Diagnostic Labs | Prerenal | ATN |
Urine output | Decreased | Decreased or normal |
Urine sediment | Normal | Red blood cell casts, cellular debris |
Specific gravity | High (>1.020) | Low (≤1.010) |
Osmolality (urine-to-plasma ratio) | >1.5 (>1.2 in neonates) | <1.2 |
Urine sodium | Low (<10 mEq/L) | High (>30 mEq/L) (>25 mEq/L in neonates) |
Creatinine (urine-to-plasma ratio) | >15:1 | <10:1 |
FENa (%) | <1 (<2.5 in neonates) | >2 (>3 in neonates) |
Creatinine | Normal or slowly increasing | High and increasing |
BUN | High | High and increasing |
ATN, acute tubular necrosis; BUN, blood urea nitrogen; FENa, excreted fraction of filtered sodium.
Note: Diuretic administration may affect results or measurement of urine sodium.
4. Postrenal failure is usually associated with obstruction of urine flow at any point in the ureters, bladder, or urethral meatus and is caused by such conditions as Wilms’ tumor, renal calculi, blood clots, or edema. AKI secondary to postrenal failure is a relatively small percentage of the cases of AKI, but it is an important cause of renal failure in newborn males with posterior urethral valve. Hydronephrosis is a key finding indicating the presence of obstruction.
C. Laboratory Findings in AKI
1. Urinalysis. Common findings in AKI. Diagnostic laboratory values (urine and serum) are detailed in Table 5.6.
a. Urinary sediment
i. Intrinsic kidney failure
b. Color
i. “Dirty” brown. Intrinsic kidney failure
ii. Reddish brown. Acute glomerulone-phritis
iii. Bilious tinge. Mixed hepatic and renal failure
460c. Proteinuria
i. Glomerulonephritis
ii. Interstitial nephritis
iii. Toxic and infectious causes
d. Casts
i. RBC casts. Glomerulonephritis or vasculitis
ii. WBC casts. Interstitial nephritis
iii. Granular casts. Glomerulonephritis
iv. Uric acid crystals. Tumor lysis syndrome (TLS)
v. Calcium oxylate crystals. Ethylene glycol ingestion
vi. Acetaminophen crystals. Acetaminophen toxicity (acute)
2. Serum Chemistries
a. Hyperkalemia
i. Hyperkalemia occurs secondary to decreased renal excretion. Oliguric patients do not excrete sufficient potassium to maintain a normal balance. Hyperkalemia may be exacerbated by metabolic acidosis, which causes a shift of potassium from the intracellular space. Continued acid production occurs from catabolic cellular metabolism, despite loss of renal excretory function. Multiple blood transfusions and RBC hemolysis release potassium. The longer the blood is stored, the higher the potassium content of the blood as a result of cell lysis and potassium release. Blood banks generally release the oldest unit of blood first. In an infant or child with hyperkalemia requiring blood transfusion, a specific request should be made for a fresh unit of blood.
ii. ECG changes secondary to hyperkalemia can range from peaked T waves, prolonged PR interval, and complete heart block to ventricular fibrillation as the potassium level increases.
iii. Other clinical manifestations may include muscle cramps, muscle weakness, muscle twitching, abdominal cramps, diarrhea, and ileus.
iv. Management of hyperkalemia depends on the severity of electrolyte imbalance. Patients with a serum potassium level greater than 7 mEq/L and evidence of myocardial toxicity are at an extremely high risk for lethal arrhythmias. Prompt, aggressive intervention is critical for survival.
1) Treatment measures include the administration of insulin (0.1 units/kg regular insulin) and hypertonic glucose (0.5 to 1 mL/kg 50% dextrose) to promote cellular uptake of potassium. These medications essentially “move” the potassium around in the body and are not causing true potassium excretion. The effects of cellular shifts on serum potassium are short lived and require frequent monitoring of serum sodium and potassium. These medications may need to be redosed until potassium excretion occurs.
2) Albuterol is another pharmacologic strategy used to shift serum potassium into the cellular space, although it is not as potent as IV strategies. Its peak action is 90 to 120 minutes. Patients with hyperkalemia may be placed on continuous inhaled albuterol.
3) Movement of the potassium into the cells can be facilitated by administration of sodium bicarbonate (1–3 mEq/kg) in the absense of acidosis. (Caution: Do not mix calcium and bicarbonate in IV solutions because precipitation will occur.)
4) Stabilize the myocardium with IV calcium (10–20 mg/kg per dose calcium chloride [infants and children] or 50–100 mg/kg per dose calcium gluconate [infants and children]).
5) Eliminate exogenous sources of potassium (potassium-free hydration).
6) Remove potassium from the patient using resin exchange via the gastrointestinal tract with a sodium polystyrene sulfonate (Kayexalate) enema (1 g/kg per dose). (Note: Repeat the enema two or three times per 24-hour period if necessary.) Sodium polystyrene sulfonate (Kayexalate) exchanges sodium for potassium in the gastrointestinal tract. It must be retained in the gastrointestinal tract to cause the renin exchange and ultimate removal of potassium. If it is not retained, the dose should be repeated. It may be instilled high in the rectum using a red rubber tube. Full effect is usually seen in 4 hours.
7) If kidney function is absent or severely impaired, or if hyperkalemia is severe, consider hemodialysis. Hemodialysis against a potassium-free dialysate can decrease serum potassium as rapidly as 1.5 mEq/hr. CRRT without potassium in the 461replacement fluid or dialysate is also an option if the patient is too hemodynamically unstable to tolerate hemodialysis.
b. Hyperphosphatemia
i. Hyperphosphatemia occurs primarily as a result of the kidney’s inability to excrete phosphate in mild to moderate renal insufficiency. Phosphorus homeostasis is maintained by an increase in phosphorus excretion per nephron through the action of PTH. As renal failure progresses and GFR is less than 30 mL per minute, elevated phosphorus level will ensue. Hyperphosphatemia may also be secondary to TLS, rhabdomyolysis, bowel infarction, ileus, or the use of oral phosphates and/or sodium phosphate enemas in the presence of gastrointestinal tract abnormalities.
ii. Hyperphosphatemia may not produce signs and symptoms until levels are very high (>10 mEq/L); however, a secondary hypocalcemia may develop as an attempt to compensate. See clinical manifestations in the discussion of hypocalcemia.
iii. Management of hyperphosphatemia may include IV fluid therapy to increase phosphorus excretion or administration of IV calcium. Use of enteral calcium-based phosphate binders should be considered. Administration of phosphorus-containing agents and dietary phosphorus intake should be minimized. Acute situations can be managed initially with the administration of insulin and glucose by shifting phosphorus from the extracellular space to the intracellular space. Management of severe hyperphosphatemia (greater than 10–12 mEq/L) may include hemodialysis or renal replacement therapy to decrease phosphate levels.
iv. Long-term sequelae include increased risk of mortality, cardiovascular disease, bone disease, and extraskeletal calcification of soft tissues, including blood vessels, lungs, kidneys, and joints.
c. Hypocalcemia
i. Pathophysiology. Serum calcium declines reciprocally as phosphorus rises. Alterations in calcium most often occur secondary to hyperphosphatemia. Other reasons for hypocalcemia include induced resistance to the action of PTH, crush injury (occurs early), severe muscle damage, large transfusions of citrate-containing blood products, sepsis, and hypomagnesemia.
ii. Clinical manifestations of calcium or phosphate imbalance include CNS changes (anxiety, tetany, and seizures), muscle cramps, hypotension, and Trousseau’s and Chvostek’s signs.
iii. Management of hypocalcemia includes decreasing the serum phosphate levels and replacing magnesium, if indicated, to increase PTH release. If the patient is symptomatic, administer IV 10% calcium gluconate (50–100 mg/kg per dose; maximum dose, 2 g). If a more rapid response is required, use calcium chloride (10–20 mg/kg per dose [infants and children] and 37–74 mg/kg per dose [neonates]; maximum dose, 1 g). Infuse slowly (do not exceed 1 mL/min), and monitor for bradycardia and asystole with IV calcium infusion. Because of high osmolar content, extravasation with IV administration can cause severe tissue damage.
iv. In AKI, PTH’s ability to serve as a regulator of phosphorus and calcium balance is compromised because of the alteration in the renal absorption of calcium and excretion of phosphate. Decreased synthesis of the active form of vitamin D results in hypocalcemia.
d. Hypermagnesemia
i. Mild hypermagnesemia may occur in AKI secondary to decreased renal excretion of magnesium. It may be secondary to the use of magnesium-containing antacids (Maalox) or total parenteral nutrition (TPN).
ii. Clinical manifestations. Acute elevations may depress the CNS, peripheral neuromuscular junction, and deep-tendon reflexes. There is an increased potential for hypotension, hypoventilation, and cardiac arrhythmias.
iii. Management of hypermagnesemia usually does not require intervention other than discontinuing magnesium-containing substances (e.g., Maalox). Calcium acts as a direct antagonist to magnesium. In life-threatening situations, IV calcium may be administered. Dialysis may be used for removal of magnesium because loop diuretics in particular enhance magnesium excretion. PTH stimulates reabsorption of magnesium from the tubules.
e. Glucose intolerance may develop secondary to decreased peripheral sensitivity to insulin when renal excretion is decreased. Renal replacement therapy can remove glucose.
462f. Uremia is related to the accumulation of toxins and waste products normally excreted in the urine and is measured as BUN.
i. Azotemia refers to a high serum concentration of nitrogenous wastes. Buildup of creatinine is not harmful to the body; however, uremia can have deleterious effects. Uremic pericarditis occurs only in the presence of prolonged severe renal failure and results from chemical irritation of the pericardium secondary to the metabolic abnormalities. It may culminate in cardiac tamponade or cause recurrent hypotension during hemodialysis. If adequate relief of uremic pericarditis does not occur with hemodialysis, pericardiectomy is recommended.
ii. Clinical manifestations are due to toxic effects of substances such as urea and ammonia. Neurologic symptoms include lethargy, confusion, seizures, and coma. Gastrointestinal tract symptoms include anorexia, nausea, vomiting, diarrhea, and gastrointestinal tract bleeding. Cardiovascular symptoms include hypervolemia and hypotension secondary to shifts of fluid into the extracellular space. Hematologic compromise involves normochromic, normocytic anemia, thrombocytopenia, platelet dysfunction, and increased bleeding time. Skin symptoms include pruritus and discoloration. Immunosuppression may result. Bone manifestations include osteodystrophies such as osteomalacia, adynamic bone disease, and growth retardation in children. Endocrine manifestations include sexual dysfunction, hyperprolactinemia contributing to amenorrhea and galactorrhea in women, low total T4 and T3 and free T3, but normal free T4, reverse T3, and thyroid-stimulating hormone (TSH), suggesting a normal thyroid state. In early CKD, increased insulin resistance and glucose intolerance (azotemic pseudodiabetes), elevated triglycerides and very low-density lipoprotein (VLDL) and decreased high-density lipoprotein (HDL), and decreased protein synthesis and increased catabolism (Lerma, 2009).
iii. Initial management includes conservative therapies related to diet and medications. The goals of conservative treatment are to treat the cause of CKD if possible and detect/treat any reversible cause of decreased kidney function, prevent/slow progression of CKD, prevent/treat complications of CKD, prevent/treat complications associated with other comorbid conditions such as diabetes and cardiovascular disease, and prepare for replacement therapy. Referral to a nephrologist should occur when estimated GFR is less than 30 mL/min (Stage IV; Lerma, 2009). Management for symptomatic patients may include renal replacement therapy (either dialysis or transplantation).
g. Acid–Base Imbalance
i. Metabolic acidosis occurs in AKI because of alterations in renal function, including a decrease in GFR, decreased hydrogen ion secretion, decreased bicarbonate reabsorption, decreased ammonia (NH3) synthesis, and ammonium (NH4) excretion. Acidosis in ARF results in an increase in the anion gap.
Anion gap = Sodium – (Chloride + Bicarbonate)
ii. Clinical manifestations of acidosis secondary to AKI include increased minute ventilation, a change in mental status as ammonium excretion decreases, and hyperkalemia as potassium excretion decreases, causing an increased potential for lethal dysrhythmias. Other manifestations can include decreased cardiac output, decreased tissue perfusion, and altered oxygen delivery.
iii. Management involves the correction of metabolic acidosis. Minor adjustments may be made by hyperventilation. IV administration of bicarbonate in the form of sodium bicarbonate or THAM may be necessary for significant correction (Table 5.7).
h. Hematologic changes include anemia and abnormal platelet function. Anemia is related to decreased erythrocyte production, changes secondary to volume status (i.e., hemoconcentration or hemodilution), frequent blood sampling, and bleeding. Patients with chronic renal failure require erythropoietin supplementation because of decreased erythrocyte production. Although platelet number is generally normal in uremia, the bleeding time is prolonged because of defective platelet activation and adhesiveness. Coagulation tests are normal in AKI. Skin bleeding time is the best predictor of clinical bleeding. Uremic bleeding is usually mild mucocutaneous bleeding. If a uremic patient bleeds, consider a structural or other hemostatic abnormality. If the hemostatic defect is thought to be related solely to the renal failure, peritoneal or hemodialysis can usually reverse the hemostatic disorder. Uremic patients who undergo surgery are always at risk for bleeding. Consider administration of desmopressin (DDAVP) before surgery.
463TABLE 5.7 Renal Response to Changes in Acid–Base Balance
Change in Acid–Base Balance | Renal Response |
Respiratory Acidosis | |
Carbon dioxide and bicarbonate are retained | Increase bicarbonate in plasma to take up hydrogen ions |
Plasma hydrogen ions rise | Acid excreted in urine |
Respiratory Alkalosis | |
Elimination or blowing off of carbon dioxide increases | Increase excretion of bicarbonate to conserve dioxide hydrogen ions |
Plasma hydrogen ion concentration decreases | |
Metabolic Acidosis | |
Plasma bicarbonate decreases and plasma hydrogen ion concentration increases | Replenish bicarbonate |
Metabolic Alkalosis | |
Plasma bicarbonate increases | Fewer intracellular hydrogen ions available for secretion |
Plasma and intracellular hydrogen ion concentration decreases | Some bicarbonate escapes into the urine (alkaline urine) |
Chronic Acidosis | |
Increase production of ammonia (NH3) to bind with hydrogen ions and excrete ammonium (NH4+) in urine | |
TABLE 5.8 Clinical Manifestations of Potential Multisystem Complications Secondary to AKI
System | Clinical Manifestations |
Cardiovascular | ECG changes secondary to hyperkalemia |
Respiratory | Pneumonia, pulmonary edema |
Gastrointestinal | Hemorrhage, abdominal cramping, nausea and vomiting, diarrhea, malnutrition |
Neurologic | Altered mental status |
Metabolic | Acidosis, hypercalcemia, hyperkalemia, uremia, hypermagnesemia, hyperphosphatemia, hyperuricemia |
Hematologic | Anemia, coagulopathy |
Infection | Sepsis, pneumonia |
AKI, acute kidney injury.
i. Infection is a risk for AKI patients, who have an altered immune response secondary to the suppression of macrophages by uremic toxins. Invasive lines increase the risk. Prophylactic antibiotic therapy is generally not indicated.
j. Complications include potential multisystem complications (Table 5.8).
D. Management of AKI
1. Response to treatment is related to the extent of nephron damage and ATN.
a. In prerenal failure, there is no actual nephron damage and the kidneys respond well to treatment for symptoms of decreased urine output, electrolyte abnormalities, or both.
464b. In true intrinsic ATN, actual nephron damage has occurred and response to therapy to treat the underlying problem of renal dysfunction is variable. Some function may return, or it may not.
2. The plan of care to support renal function includes eliminating the cause of AKI, if known, and discontinuing or altering the dose of potentially nephrotoxic medications. All drugs excreted by the kidneys require an alteration of the dosage based on the level of renal function. Serum concentrations of potentially toxic drugs should be closely monitored. Creatinine clearance and serum creatinine should be monitored when using potentially nephrotoxic agents. Drug-dosage alteration is indicated with increased levels of serum creatinine. If a patient is receiving renal replacement therapy, drug supplementation may be necessary to restore the drug that is removed or filtrated.
3. Maintain adequate intravascular volume and maintain adequate blood pressure. Administer inotropic agents as needed to support cardiac output and perfusion to the kidneys.
4. Pharmacologic support includes diuretics and other agents. Common indications for diuretic therapy include pulmonary edema, hypertension, hypercalcemia, hyperkalemia, generalized edema, hypervolemia, and increased intracranial pressure. Diuretics promote renal excretion of water, either directly or indirectly by acting on different segments of the tubules.
a. Loop diuretics inhibit reabsorption of sodium and chloride in the ascending loop of Henle and distal renal tubule, interfering with the chloride-binding cotransport system. This leads to increased excretion of water, potassium, sodium, chloride, magnesium, and calcium. Furosemide (Lasix) and bumetanide (Bumex) are two of the most potent loop diuretics. Lasix can be given as bolus doses of 1 mg/kg/dose or as a continuous drip with a starting dose of 0.05–0.1 mg/kg/hr. Potential complications include hypovolemia, hypokalemia, hyponatremia, metabolic alkalosis, hypercalciuria, hypomagnesemia, hyperglycemia, ototoxicity, renal calculi, and thrombocytopenia.
b. Thiazide diuretics inhibit sodium reabsorption in the distal tubules, leading to excretion of sodium, chloride, potassium, bicarbonate, magnesium, phosphate, calcium, and water. Chlorothiazide (Diuril; dose is 2 mg/kg/dose IV every 8–12 hours) or hydrochlorothiazide (HydroDIURIL) is frequently used as a secondary or adjunct agent in diuretic therapy. Potential complications are similar to loop diuretics. Potassium supplemental therapy may be indicated.
c. Nonthiazide, sulfonamide diuretics inhibit sodium reabsorption in the cortical diluting site and proximal tubules, leading to increased excretion of sodium and water as well as potassium and hydrogen ions. Metolazone (Zaroxolyn) is frequently used as a secondary agent in conjunction with loop diuretics.
d. Potassium-sparing diuretics compete with aldosterone for binding sites in the distal tubule, increasing sodium chloride and water excretion while conserving potassium and hydrogen ions. Spironolactone (aldosterone antagonist) is the most commonly used agent. Potassium-sparing diuretics are used in conjunction with a potassium-depleting diuretic agent to decrease the occurrence of hypokalemia. They also have minimal side effects but may block the effect of aldosterone on arteriolar smooth muscle.
e. Osmotic diuretics increase the osmotic pressure in the glomerular filtrate, which inhibits tubular reabsorption of water and electrolytes, thus increasing urinary output. Mannitol is a sugar that is relatively inert and freely filtered by the glomerulus; however, it is not greatly reabsorbed by the renal tubule. The transient pulling of fluid into the intravascular space can increase the intravascular volume significantly; therefore, mannitol should not be used with patients in congestive heart failure and hypervolemia or in those with renal failure.
f. Acetazolamide (Diamox) acts by competitively inhibiting carbonic anhydrase, resulting in increased excretion of sodium, potassium, bicarbonate, and water. It also results in a decrease in the formation of aqueous humor. Metabolic acidosis can result secondary to the limitation of secretion of hydrogen ions from the tubule and subsequent decreased reabsorption of bicarbonate and sodium.
g. Fenoldopam is a continuous infusion that is a dopamine 1 receptor agonist. It contains both renal vasodilatory and naturetic properties secondary to tubular sodium excretion (Moffett, Mott, Nelson, Goldstein, & Jeffries, 2008). Dose is 0.3 to 0.5 mcg/kg/min. Therefore, in critically ill children, it can both improve urine output and decrease blood pressure in hypertensive patients at higher doses.
E. Replacement Therapy
Consider renal replacement therapy if function cannot be adequately supported using the preceding measures.
465F. Complications
Complications of end-stage renal disease (ESRD) include hypertensive disease, hyperlipidemia, and hyperparathyroidism because of poor control of calcium and phosphate levels.
HEMOLYTIC UREMIC SYNDROME
A. Definition
HUS is the simultaneous occurrence of hemolytic anemia, thrombocytopenia, and renal failure. It is the most common cause of acute renal failure in young children (Kliegman, Stanton, St. Geme, & Schor, 2016).
B. Pathophysiology
Pathophysiology is characterized by microangiopathy with platelet aggregation and fibrin deposition in small vessels in the kidney, gut, and CNS. Hemolytic anemia is believed to be a result of the shearing of red cells as they pass through narrowed vessels.
C. Types of HUS
1. Typical HUS peaks from June to September with gastrointestinal prodromes (vomiting, diarrhea, abdominal pain) during the days to weeks preceding onset. HUS is characteristically a disease of young children. Escherichia coli 0157:H7 causes a large number of cases of typical HUS.
2. Atypical HUS is an extremely rare group of disorders of the kidneys and is distinctly different from the HUS syndrome caused by E. coli 0157:H7. It occurs year round and there is generally no gastrointestinal prodrome. It is rare in children younger than 2 years. Relapses can occur, and these cases may evolve to terminal renal failure. Children with atypical HUS are much more likely to develop chronic complications such as kidney failure and severe high blood pressure. Familial occurrence is possible. There is substantial evidence that atypical HUS is a genetic disorder.
D. Clinical Symptoms
Clinical symptoms of HUS include bloody diarrhea (more common in typical HUS), mild to moderate hypertension, fever, lethargy, decreased urine output, and paleness, petechia, dehydration.
E. Laboratory Findings
Laboratory findings reveal increased schistocyte number on peripheral smear, anemia (age specific), and an elevated reticulocyte count. Other indicators of intravascular hemolysis include elevated lactate dehydrogenase (LDH), increased indirect bilirubin level, and low haptoglobin level. The Coomb’s test is negative. Mild leukocytosis may accompany hemolytic anemia. Thrombocytopenia is uniformly present, and the platelet count is generally less than 60,000/mm3. Prothrombin time, partial thromboplastin time, fibrinogen level, and coagulation factors are normal (Swartz, 2008).
F. Management and Treatment
Management and treatment are primarily focused on general supportive care and treatment of complications such as AKI, anemia, CNS symptoms, and abdominal symptoms. Platelet transfusion is warranted if the patient is actively bleeding. Peritoneal dialysis (PD) is the treatment of choice until renal function returns.
G. Outcomes
1. Prognosis—Mortality is less than 10% with typical HUS. Hypertension, proteinuria, and low GFR effects 25% of patients. Prognosis is worse with patients who have neurological involvement.
2. Significant renal failure is seen in more than 90% of patients with HUS. Dialysis is required for many of these patients.
NEPHROTIC SYNDROME
A. Nephrotic syndrome is a pediatric disorder that is characterized by proteinuria greater than 40 mg/m2/hr, hypoalbuminemia, edema, and hyperlipidemia that occurs secondary to glomerular damage. It can be a primary or secondary disease.
1. Nephrotic syndrome in children is primarily “idiopathic” (90%), and its presentation and relapses are often associated with a recent upper respiratory infection. It usually presents between 2 and 6 years of age and affects males more often than females. Idiopathic nephrotic syndrome can be divided into three morphologic patterns: (1) minimal-change disease (85%), (2) mesangial proliferation (5%), or (3) focal sclerosis (10%). Presenting signs and symptoms include periorbital edema, dependent edema, ascites, foamy appearance of the urine, weight gain, irritability, pleural effusions, and decreased appetite.
2. Secondary nephrotic syndrome can be induced by membranous nephropathy, glomerulonephritis, lupus nephritis, malaria, hepatitis B, and HIV. It has also been associated with malignancy and can occur as a result of exposure to numerous renal toxic drugs and chemicals.
3. Diagnosis. Urinalysis that reveals +3 or +4 protein with occasional microscopic hematuria, decreased creatinine clearance, low serum albumin, elevated cholesterol, and triglycerides.
4664. Treatment includes diuretics, antihypertensive medications, and dietary salt restriction to manage symptoms. Patients with minimal-change disease may be responsive to corticosteroid therapy; however, if the proteinuria persists for longer than a month, a renal biopsy may be indicated to determine the precise cause of the disease. Many patients require low-dose steroid therapy for 3 to 6 months and if a relapse occurs. Patients who are resistant to steroids or have frequent relapse may be treated with cyclophosphamide.
OTHER DISEASES CAUSING AKI
A. Acute Glomerulonephritis
Acute glomerulonephritis refers to a specific set of renal diseases (such as lupus nephritis and poststreptococcal nephritis) that result from immunologic mechanisms triggering inflammation and proliferation of glomerular tissue.
1. Acute glomerulonephritis is currently described as a clinical syndrome that frequently manifests as a sudden onset of hematuria, proteinuria, and red cell casts. With the exception of poststreptococcal glomerulonephritis, the exact triggers for the formation of the immune complexes are unclear. In streptococcal infection, involvement of derivatives of streptococcal proteins has been reported. A streptococcal neuraminidase may alter host immunoglobulin G (IgG). IgG combines with host antibodies. IgG/anti-IgG immune complexes are formed and then collect in the glomeruli. In addition, antibody titers to other antigens, such as antistreptolysin O or antihyaluronidase, DNAase-B, and streptokinase, provide evidence of a recent streptococcal infection and may be elevated. Antigen–antibody complexes mediate glomerular injury. Hypofiltration occurs as a result of decreased glomerular blood flow. Glomerular blood flow decreases as a result of arteriolar vasoconstriction, capillary obstruction by thrombi, and endothelial cell edema from proliferation of endothelial cells and WBC infiltration.
2. Clinical signs and symptoms include salt and water retention secondary to decreased GFR, RBC, or granular casts in the urine, declining renal function, hypertension, hematuria, oliguria, and other nonspecific symptoms such as fever, malaise, abdominal discomfort, nausea, or vomiting.
3. Management includes sodium and water restriction and treatment of underlying disease as well as management of declining renal function.
4. Outcome. Sporadic cases of acute nephritis progress to a chronic form. This progression occurs in as many as 30% of adult and 10% of pediatric patients. The mortality rate of acute glomerulonephritis has been reported at 0% to 7%. The male-to-female ratio is 2:1. Most cases of acute glomerulonephritis occur in patients aged 5 to 15 years.
B. Hepatorenal Syndrome
Hepatorenal syndrome is renal failure that develops in the presence of end-stage liver disease in absence of intrinsic kidney disease. Hepatorenal failure may accompany liver failure related to fulminant hepatic failure, hepatic malignancy, liver resection, hepatitis, or biliary tract obstruction.
1. Kidney dysfunction results from renal hypoperfusion characterized by intense constriction of the renal cortical vasculature resulting in decreased GFR leading to oliguria and avid sodium retention. Portal hypertension and resultant splanchnic sequestration increase cardiac output and decrease peripheral vascular resistance, termed hyperdynamic circulation. In response, vasoconstrictor systems (including the renin-angiotensin system) are activated and direct the kidneys to retain water and sodium in order to maintain hemodynamic stability. As cirrhosis worsens, increased systemic vasodilation and accompanying compensatory vasoconstriction further compromise renal perfusion leading to renal failure.
2. Signs and symptoms include increased renal vascular resistance, decreased glomerular filtration, increased sodium and water retention (secondary to hyperaldosteronism), decreased urine output, and electrolyte and coagulation abnormalities. Symptoms are marked by rapid and progressive deterioration of renal function and the patient typically demonstrates severely decompensated liver cirrhosis, jaundice, and hyponatremia. Oliguria and rising creatinine develop over a few days. In approximately 50% of patients, it is difficult to pinpoint a cause triggering the event. For the remainder, onset of hepatrorenal syndrome follows a readily apparent precipitating event such as infection, significant gastrointestinal hemorrhage, overaggressive diuresis, or large volume paracentesis (>5 L) without replacement of the intravascular volume (Lerma, 2009).
3. After exclusion of other causes of renal disease, management includes treatment of the hepatic failure and support of renal function. Intravascular volume depletion and nephrotoxic agents should also be avoided. Sepsis should be considered in the patient with cirrhosis with acute renal deterioration 467and a full septic workup should be completed even in the absence of symptoms such as leukocytosis and fever. Pharmacological interventions are aimed at improving systemic hemodynamics by increasing systemic or splanchnic vasoconstriction in order to improve renal perfusion pressure and glomerular filtration (Lerma, 2009).
4. Prognosis is poor for patients without subsequent liver transplant as it is the only established therapy that improves renal failure.
C. Tumor Lysis Syndrome
TLS typically occurs after effective chemotherapy or radiation, but it may occur after treatment with glucocorticoids, antiestrogen tamoxifen, and interferon. It is most likely to occur in patients with poorly differentiated leukemias and lymphomas, a high WBC count, or bulky lymphoma. During tumor lysis, rapid release of intracellular metabolites exceeds the excretory capacity of the kidneys.
1. Potential effects of tumor lysis include hyperuricemia, hypocalcemia, hyperphosphatemia, hyperkalemia, and hyperxanthinemia. These electrolyte imbalances lead to crystallization, tubular obstruction, decreased urine output, and renal failure. The severity of the condition is proportional to the tumor burden, rapid proliferation kinetics (such as Burkitt’s lymphoma or acute lymphocytic leukemia), extensive bone marrow involvement, LDH levels above 1,500 IU/mL, and with tumors highly sensitive to chemotherapy or radiation. Patients are at increased risk of developing TLS when there is a previous history of renal impairment, volume depletion, concomitant nephrotoxic medication use, and an acidic urine pH that can facilitate uric acid crystal formation (Lerma, 2009). Prevention of complications from cell breakdown is the optimal goal.
2. Prevention is paramount. At-risk patients should receive vigorous hydration and allopurinol before cancer treatment is begun. Urate oxidases and urinary alkalinization should be considered. Electrolyte imbalances should be treated promptly. Hypocalcemia should not be treated unless the patient is symptomatic because administration of calcium may precipitate metastatic calcifications in a patient with hyperphosphatemia. PD is not as effective as hemodialysis because the clearance rates for phosphate and uric acid are significantly lower. Severe electrolyte disturbances may require hemodialysis or CRRT and may be required in up to 30% of patients of AKI associated with TLS. Left untreated, TLS may lead to severe, life-threatening cardiac arrhythmias, seizures, muscle paralysis, and death (Lerma, 2009).
D. Cardiac Failure and Cardiopulmonary Bypass
Changes in renal function may be attributed to hypovolemia or hypervolemia, hypotension, and electrolyte imbalance. Worsening cardiac function in patients with heart failure leads to decreased cardiac output, which may lead to decreased renal flow and decreased GFR, decreased flow to the parenchyma, and ATN. AKI incidence ranges from 1% to 82% in ICU and postoperative cardiopulmonary bypass patients admitted to the ICU (Fortenberry et al., 2013).
E. Rhabdomyolysis
Rhabdomyolysis can be caused directly by muscle injury or indirectly by several medical conditions (Table 5.9). It results in lysis of the cell membrane and leakage of its contents, including myoglobin, potassium, phosphorus, and enzymes, into the bloodstream.
1. Diagnosis. Myoglobin is a small, bright-red protein that is common in muscle cells. It gives the muscle much of its red coloration. Myoglobin stores oxygen for use when muscles are exercised. The cellular release of myoglobin is often accompanied by an increase of creatine kinase (CK). Myoglobin is readily filtered by the kidney and, when excreted into the urine, it is called myoglobinuria. Myoglobin can precipitate, causing tubular obstruction and acute renal insufficiency. Myoglobinuria is often minimally present in most individuals after intense exertion. Factors, such as volume depletion, exercising in the heat, eccentric muscle contractions, and fasting, are potentiating factors. Increased mortality is associated with rhabdolyolysis caused by severe trauma and crush injuries. Other causes of rhabdomylysis include metablolic myopathies, hypoxia/ischemia, certain licit and illicit drugs, congestive heart failure, malignant hyperthermia, and snake bites. Clinical features of myoglobinuria are typically suffucient to recognize the condition and include weakness, discomfort, pain, tenderness, swelling, tea-colored urine, kidney dysfunction, fever, and leukocytosis. It can be recognized clinically by urinalysis with a dipstick strongly positive for heme and urine sediment with few or no red cells. A more sensitive and diagnostic finding is an elevated creatine phosphokinase (CPK). CK peaks at 12 to 36 hours after muscle injury and acute rhabdomyolysis is seen with levels exceeding 5,000 IU/L. Although transient elevations of serum creatinine disproportionate to elevation of BUN is often seen in early acute rhabdmyolysis, ARF seldom occurs until CPK levels exceed 15,000 to 20,000. Hypoalbuminuria, hyperkalemia, hyperphosphatemia, hypocalcemia, and hyperuricemia may also be observed (Lerma, 2009).
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2. Renal failure may ensue from myoglobinuria resulting from ferrihemate toxicity, tubular obstruction, altered GFR, hypotension, and crystal formations. Aspartate aminotransferase and alanine aminotransferase may also be elevated as they are released from necrotic muscle.
3. Prevention of renal failure hinges on prompt and aggressive treatment that includes volume depletion and maintenance of high urine output. Mannitol and alkalinization of the urine may also be considered. Hyperkalemic cardiotoxicity may occur in patients with hypocalcemia and should be monitored for electrocardiographic changes associated with hyperkalemia despite observing modest serum hyperkalemia. Calcium infusions, as well as frequent or near constant hemodialysis, may be necessary if cardiotoxicity is observed.
RENAL REPLACEMENT THERAPIES
Renal replacement therapies for infants and children include PD, hemodialysis, and CRRT.
A. Methods of Solute Clearance and Water Removal: Convection, Diffusion, Ultrafiltration
1. Convective transport occurs when water and small particles are carried through membrane pores into ultrafiltrate by the hydrostatic pressure created by a moving stream of fluid containing large protein molecules. The important determinants of convective transport are the direction and rate of the solvent flux across the membrane. Unlike diffusion, it is not influenced by any solute concentration gradient.
2. Diffusion is the removal of a solute from a higher concentration to a lower concentration to establish equilibrium. If adequate clearance is not obtained by convection alone, it may be necessary to influence clearance by diffusion as well.
3. Ultrafiltration is the removal of extracellular fluid via convection. The rate of removal is determined by the surface area of the filter membrane, the permeability coefficient of the membrane to water, and the transmembrane pressure gradient.
B. Peritoneal Dialysis
1. Indications for PD include an inability to tolerate anticoagulation, ATN, renal cortical necrosis, renal agenesis, bilateral renal dysplasia, and other renal dysfunction requiring long-term, nonemergent therapy. PD is often used for infants and children in either AKI or chronic renal failure. Selection of this modality is influenced by considerations such as availability, convenience, medical factors, and socioeconomic factors. One absolute contraindication is an unsuitable peritoneum secondary to adhesions, fibrosis, or malignancy.
2. Types of PD include continuous ambulatory PD (CAPD), manual PD, or continuous-cycling PD using a computerized cycler device. Access is via a soft catheter placed in the peritoneal space. Catheter placement can be performed in the operating room or at the bedside.
a. Process. An ordered amount of dialysate is instilled via a catheter into the peritoneal cavity. The removal of water and solutes (ultrafiltrate) is adjusted by raising the osmolarity of the 469dialysate (increasing the glucose concentration) or increasing the dwell time. Dwell times impact waste and fluid removal. Long dwell times may achieve good waste and solute clearance but poor fluid removal. Short dwell times have poor waste and solute clearance but remove a significant amount of fluid. Solutes are transported by diffusion and ultrafiltration. Smaller solutes, such as creatinine, urea, and potassium, diffuse down a concentration gradient into the peritoneal dialysate and removal is maximal at the start of the dwell. Glucose, lactate, and calcium diffuse in the opposite direction into the blood. The amount of dialysate placed into the peritoneal space (inflow volume) is determined by gradually increasing volumes from 15 to 50 mL/kg of body weight as tolerated. Standard dialysate solution contains dextrose, sodium, calcium, magnesium, chloride, and lactate (which is metabolized to produce bicarbonate). Potassium, heparin, or antimicrobial medications can be added to the dialysate fluid as needed. CAPD or manual PD may be needed in infants and small children when inflow volumes are less than 50 mL. Excessive inflow volume can be assessed by monitoring for signs of pain, discomfort, or respiratory compromise on inflow. The dialysate solution must be warmed to or near body temperature to prevent hypothermia.
b. Manual PD is more time-consuming than the cycler method. It involves manual timing of fluid dwell within the abdomen, exact measurement of inflow and outflow volumes, calculation of net ultrafiltration after each dwell time, and cumulative ultrafiltrate tabulation. Inflow is initiated, the catheter is clamped, and a timer is set to mark dwell time completion. Clots, kinks, and catheter position can affect the ability to inflow adequately. Dwell cycles generally range from 30 to 120 minutes and include fill, dwell, and drain times. On completion of the dwell time, the catheter is unclamped and the outflow drains to a urine collection bag to be measured. Drain times are dependent on catheter patency. The net ultrafiltrate is calculated (outflow volume minus inflow volume). The cycle is repeated at ordered intervals.
c. CAPD via a cycler utilizes the same principles as manual PD, but it requires less hands-on nursing time, has a decreased incidence of infection because of having a closed system, provides a programmable automated ultrafiltrate calculation, and has a built-in mechanism for dialysate warming.
3. Potential complications of PD include peritonitis, which can be indicated by cloudy dialysate, abdominal pain, tenderness, or sepsis. Mechanical and iatrogenic catheter problems may also occur and include leakage at the insertion site, bowel perforation, retroperitoneal hemorrhage, increased intraabdominal pressure resulting from obstruction of the catheter, and hernia. Ultrafiltration failure may occur as the result of the failure of PD fluid removal to match the volume balance needs of the patient. Patients present with signs and symptoms of volume overload and reversible causes should be addresed before considering alteration in peritoneal membrane function. Other complications include impaired pulmonary function related to abdominal distention or fluid overload, decreased cardiac output and stroke volume related to fluid status, hypoproteinemia resulting from protein losses in the dialysate, and hyperglycemia related to absorption of dextrose from the dialysate. Hyperglycemia may require treatment with insulin. Delayed growth and development have also been shown in children undergoing PD (Zaritsky & Warady, 2011).
C.