Renal Function PDF

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7582_Ch04_105-123 24/06/20 5:38 PM Page 105 7582_Ch04_105-123 24/06/20 5:38 PM Page 106 106 Part One | Basic Principles CHAPTER 4 K E Y T E R M S —cont’d Osmolarity Passive transport Peritubular capillaries Renal threshold Renal tubular acidosis Renin Titratable acidity Tubular reabsorption Tubular secretion Renal Function Podocytes Proximal convoluted tubule Renal plasma flow Renin–angiotensin–aldosterone system (RAAS) Shield of negativity Vasa recta Vasopressin LEARNING OUTCOMES Introduction and flows slowly through the cortex and medulla of the kidney close to the tubules. The peritubular capillaries surround the Upon completing this chapter, the reader will be able to: This chapter reviews nephron anatomy and physiology and proximal and distal convoluted tubules, providing for the 4-1 Identify the components of the nephron, kidney, and 4-10 Given hypothetical laboratory data, calculate a creati- discusses their relationship to urinalysis and renal function immediate reabsorption of essential substances from the fluid excretory system. nine clearance and determine whether the result is testing. A section on laboratory assessment of renal function is in the proximal convoluted tubule and final adjustment of normal. included. the urinary composition in the distal convoluted tubule. The 4-2 Trace the flow of blood through the nephron, and state vasa recta are located adjacent to the ascending and descending the physiological functions that occur. 4-11 Discuss the clinical significance of the glomerular loops of Henle in juxtamedullary nephrons. In this area, the 4-3 Describe the process of glomerular ultrafiltration. filtration rate tests. Renal Physiology major exchanges of water and salts take place between the 4-12 Describe and contrast the Modification of Diet in Renal Each kidney contains approximately 1 to 1.5 million functional blood and the medullary interstitium. This exchange main- 4-4 Discuss the functions and regulation of the Disease (MDRD), cystatin C, and beta2-microglobulin units called nephrons. As shown in Figure 4-1, the human tains the osmotic gradient (salt concentration) in the medulla, renin–angiotensin–aldosterone system (RAAS). tests for performing estimated glomerular filtration kidney contains two types of nephrons. Cortical nephrons, which is necessary for renal concentration. Box 4-2 outlines 4-5 Differentiate between active and passive transport in rates (eGFR). which make up approximately 85% of nephrons, are situated the urinary filtrate flow. relation to renal concentration. primarily in the cortex of the kidney. They are responsible Based on an average body size of 1.73 m2 of surface, the 4-13 Define osmolarity, and discuss its relationship to urine primarily for removal of waste products and reabsorption of total renal blood flow is approximately 1200 mL/min, and the 4-6 Explain the function of antidiuretic hormone in the concentration. nutrients. Juxtamedullary nephrons have longer loops of Henle total renal plasma flow ranges from 600 to 700 mL/min. Nor- concentration of urine. 4-14 Describe the basic principles of freezing-point that extend deep into the medulla of the kidney. Their primary mal values for renal blood flow and renal function tests depend 4-7 Describe the role of tubular secretion in maintaining osmometers. function is concentration of the urine. on body size. When dealing with body sizes that vary greatly acid–base balance. The ability of the kidneys to clear waste products selec- from the average 1.73 m2 of body surface, a correction must 4-15 Given hypothetic laboratory data, calculate a tively from the blood and simultaneously to maintain the be calculated to determine whether the observed measure- 4-8 Identify the laboratory procedures used to evaluate free-water clearance and interpret the result. body’s essential water and electrolyte balances is controlled in ments represent normal function. This calculation is covered glomerular filtration, tubular reabsorption and secre- 4-16 Given hypothetic laboratory data, calculate a PAH the nephron by the following renal functions: in the discussion on tests for glomerular filtration rate (GFR) tion, and renal blood flow. clearance and relate this result to renal blood flow. Renal blood flow later in this chapter. Variations in normal values have been 4-9 Describe the creatinine clearance test. published for different age groups and should be considered 4-17 Describe the relationship of urinary ammonia and Glomerular filtration when evaluating renal function studies. titratable acidity to the production of an acidic urine. Tubular reabsorption Tubular secretion Glomerular Filtration The physiology, laboratory testing, and associated pathol- The glomerulus consists of a coil of approximately eight capil- KEY TERMS ogy of these four functions are discussed in this chapter. lary lobes, the walls of which are referred to as the glomerular filtration barrier. The glomerulus is located within Bowman Active transport Creatinine clearance Glomerular filtration rate (GFR) Renal Blood Flow capsule, which forms the beginning of the renal tubule. Afferent arteriole Cystatin C Glomerulus The renal artery supplies blood to the kidney. The human kid- Although the glomerulus serves as a nonselective filter of plasma substances with molecular weights less than 70,000, Aldosterone Density Juxtaglomerular apparatus neys receive approximately 25% of the blood pumped through the heart at all times. Blood enters the capillaries of the several factors influence the actual filtration process. These Antidiuretic hormone (ADH) Distal convoluted tubule Loops of Henle include the cellular structure of the capillary walls and Bowman nephron through the afferent arteriole. It then flows through Beta2-microglobulin (B2M) Endogenous procedure Macula densa the glomerulus and into the efferent arteriole. The varying capsule, hydrostatic pressure and oncotic pressure, and the feedback mechanisms of the renin–angiotensin–aldosterone Clearance tests Efferent arteriole Maximal reabsorptive capacity (Tm) sizes of these arterioles help create the hydrostatic pressure dif- ferential that is important for glomerular filtration and to main- system (RAAS). Collecting duct Exogenous procedure Metabolic acidosis tain consistency of glomerular capillary pressure and renal Concentration tests Fenestrated endothelium Nephron Cellular Structure of the Glomerulus blood flow within the glomerulus. Notice the smaller size of Countercurrent mechanism Free water clearance Osmolality the efferent arteriole in Figure 4-2. This increases the glomeru- Plasma filtrate must pass through three glomerular filtration lar capillary pressure. Renal blood flow is outlined in Box 4-1. barrier cellular layers: the capillary wall membrane, the base- Creatinine Glomerular filtration barrier Osmolar clearance Continued Before returning to the renal vein, blood from the efferent ment membrane (basal lamina), and the visceral epithelium of arteriole enters the peritubular capillaries and the vasa recta the Bowman capsule. The endothelial cells of the capillary wall 7582_Ch04_105-123 24/06/20 5:38 PM Page 107 7582_Ch04_105-123 24/06/20 5:38 PM Page 108 Chapter 4 | Renal Function 107 108 Part One | Basic Principles Glomerulus Juxtaglomerular Afferent apparatus arteriole Efferent arteriole Renal cortex Bowman capsule Cortical Glomerulus Renal nephron tubule Distal Cortex convoluted Renal Proximal Papilla of tubule medulla convoluted pyramid Loop of tubule Collecting Henle Juxtamedullary duct nephron Peritubular Collecting capillaries Renal duct artery Vasa recta Thick descending Medulla loop of Henle Calyx Thick ascending Renal Vasa recta loop of Henle vein Thin descending Thin ascending loop of Henle loop of Henle Cortex Figure 4–2 The nephron and its component Renal pelvis parts. Box 4–1 Renal Blood Flow Box 4–2 Urinary Filtrate Flow 1. Renal artery 1. Bowman capsule Ureter 2. Afferent arteriole 2. Proximal convoluted tubule 3. Glomerulus 3. Descending loop of Henle 4. Efferent arteriole 4. Ascending loop of Henle Figure 4–1 The relationship of the nephron to the 5. Peritubular capillaries 5. Distal convoluted tubule Urinary bladder kidney and excretory system. (From Scanlon, VC, and 6. Vasa recta 6. Collecting duct Sanders, T: Essentials of Anatomy and Physiology, 7. Renal vein 7. Renal calyces ed 3. FA Davis, Philadelphia, PA, 1999, p 405, with permission.) Urethra 8. Ureter 9. Bladder an autoregulatory mechanism within the juxtaglomerular ap- 10. Urethra paratus maintains the glomerular blood pressure at a relatively differ from those in other capillaries by containing pores and important because it is the place where albumin (the primary constant rate, regardless of fluctuations in systemic blood pres- are referred to as fenestrated endothelium. The pores increase protein associated with renal disease) has a negative charge and sure. Dilation of the afferent arterioles and constriction of the capillary permeability but do not allow the passage of large is repelled (Figs. 4-3B and 4-3C). efferent arterioles when blood pressure drops prevent a marked molecules and blood cells. Further restriction of large mole- decrease in blood flowing through the kidney, thus preventing Renin–Angiotensin–Aldosterone System cules occurs as the filtrate passes through the basement mem- Glomerular Pressure an increase in the blood level of toxic waste products. Likewise, The RAAS regulates the flow of blood to and within the glomeru- brane and the thin membranes covering the filtration slits an increase in blood pressure results in constriction of the lus. The system responds to changes in blood pressure and formed by the intertwining foot processes of the podocytes of As mentioned previously, the presence of hydrostatic pressure, afferent arterioles to prevent overfiltration or damage to the plasma sodium content that are monitored by the juxtaglomeru- the inner layer of the Bowman capsule (Fig. 4-3A). resulting from the smaller size of the efferent arteriole and the glomerulus. lar apparatus, which consists of the juxtaglomerular cells in the In addition to the structure of the glomerular filtration bar- glomerular capillaries, enhances filtration. This pressure is nec- rier that prohibits the filtration of large molecules, the barrier essary to overcome the opposition of pressures from the fluid afferent arteriole and the macula densa of the distal convoluted tubule (Fig. 4-4). Low plasma sodium content decreases water contains a shield of negativity that repels molecules with a within the Bowman capsule and the oncotic pressure of unfil- Technical Tip 4-1. If it were not for the shield of nega- negative charge even though they are small enough to pass tered plasma proteins in the glomerular capillaries. By increas- retention within the circulatory system, resulting in a decreased tivity, all routine urines would have positive readings through the three layers of the barrier. The shield is very ing or decreasing the size of the afferent and efferent arterioles, overall blood volume and subsequent decrease in blood pres- on reagent strips for protein and albumin. sure. When the macula densa senses such changes, a cascade of 7582_Ch04_105-123 24/06/20 5:38 PM Page 109 7582_Ch04_105-123 24/06/20 5:38 PM Page 110 Chapter 4 | Renal Function 109 110 Part One | Basic Principles Afferent Low blood pressure arteriole Low plasma sodium Efferent arteriole Hydrostatic Glomerular basement Renin secretion pressure membrane Oncotic Angiotensinogen Protein pressure Angiotensin I (unfiltered plasma Angiotensin- proteins) converting enzymes Glomerular B basement Angiotensin II membrane Foot Fenestrated processes Slit diaphragm epithelium of podocyte Vasoconstriction Proximal convoluted tubule Aldosterone ADH Podocyte foot Podocyte Sodium reabsorption process Bowman’s space Glomerular Proximal convoluted Distal convoluted tubule Collecting duct basement tubule Sodium reabsorption Water resorption Figure 4–5 Algorithm of the renin– Blood membrane A angiotensin–aldosterone system. Fenestrated C endothelium Figure 4–3 Factors affecting glomerular filtration in the renal corpuscle (A). Inset B, glomerular filtration barrier. Inset C, the shield of negativity. Box 4–3 Actions of the RAAS Table 4–1 Tubular Reabsorption 1. Dilates the afferent arteriole and constricts the efferent arteriole Substance Location 2. Stimulates sodium reabsorption in the proximal convoluted tubule Active Glucose, amino Proximal convo- reactions within the RAAS occurs (Fig. 4-5). Renin, an enzyme transport acids, salts luted tubule produced by the juxtaglomerular cells, is secreted and reacts 3. Triggers the adrenal cortex to release the sodium-retaining hor- mone aldosterone to cause sodium reabsorption and potassium Chloride Ascending loop of with the bloodborne substrate angiotensinogen to produce the Henle Distal tubule excretion in the distal convoluted tubule and collecting duct Afferent inert hormone angiotensin I. As angiotensin I passes through the arteriole 4. Triggers the hypothalamus to release antidiuretic hormone to Sodium Proximal and distal alveoli of the lungs, angiotensin-converting enzyme (ACE) stimulate water reabsorption in the collecting duct convoluted changes it to the active form angiotensin II. Angiotensin II Macula Efferent tubules densa corrects renal blood flow in the following ways: arteriole Passive Water Proximal convo- Causing vasodilation of the afferent arterioles and transport luted tubule constriction of the efferent arterioles Descending loop of Stimulating reabsorption of sodium and water in the Tubular Reabsorption Henle Juxtaglomerular proximal convoluted tubules cells The body cannot lose 120 mL of water-containing essential Collecting duct Triggering the release of the sodium-retaining hormone substances every minute. Therefore, when the plasma ultrafil- aldosterone by the adrenal cortex and antidiuretic hor- Urea Proximal convo- trate enters the proximal convoluted tubule, the nephrons, mone by the hypothalamus (Box 4-3). luted tubule through cellular transport mechanisms, begin reabsorbing As systemic blood pressure and plasma sodium content these essential substances and water (Table 4-1). Ascending loop of increase, the secretion of renin decreases. Therefore, the actions Henle of angiotensin II produce a constant pressure within the Reabsorption Mechanisms Sodium Ascending loop of nephron. The cellular mechanisms involved in tubular reabsorption are Henle As a result of the glomerular mechanisms just discussed, termed active transport and passive transport. For active every minute, approximately 2 to 3 million glomeruli filter ap- transport to occur, the substance to be reabsorbed must com- proximately 120 mL of water-containing low-molecular-weight bine with a carrier protein contained in the membranes of the Passive transport is the movement of molecules across a Glomerulus substances. Because this filtration is nonselective, the only dif- renal tubular epithelial cells. The electrochemical energy cre- membrane as a result of differences in their concentration or ference between the compositions of the filtrate and the plasma ated by this interaction transfers the substance across the cell electrical potential on opposite sides of the membrane. These is the absence of plasma protein, any protein-bound sub- membranes and back into the bloodstream. Active transport is physical differences are called gradients. Passive reabsorption stances, and cells. Analysis of the fluid as it leaves the glomeru- responsible for the reabsorption of the following substances: of water takes place in all parts of the nephron except the as- lus shows the filtrate to have a specific gravity of 1.010 and cending loop of Henle, the walls of which are impermeable to Glucose, amino acids, and salts in the proximal convo- Figure 4–4 Close contact of the distal tubule with the afferent arte- confirms that it is chemically an ultrafiltrate of plasma. This water. Urea is passively reabsorbed in the proximal convoluted luted tubule riole, macula densa, and the juxtaglomerular cells within the juxta- information provides a useful baseline for evaluating the renal tubule and the ascending loop of Henle, and passive reabsorp- glomerular apparatus. Note the smaller size of the afferent arteriole mechanisms involved in converting the plasma ultrafiltrate into Chloride in the ascending loop of Henle tion of sodium accompanies the active transport of chloride in indicating increased blood pressure. the final urinary product. Sodium in the distal convoluted tubule the ascending loop. 7582_Ch04_105-123 24/06/20 5:38 PM Page 111 7582_Ch04_105-123 24/06/20 5:38 PM Page 112 Chapter 4 | Renal Function 111 112 Part One | Basic Principles Active transport, like passive transport, can be influenced osmotic gradient in the medulla, as well as the hormone by the concentration of the substance being transported. When vasopressin (antidiuretic hormone [ADH]) that is released Cortex Blood (vein) the plasma concentration of a substance that is normally com- by the posterior pituitary gland when the amount of water in 300 mOsm/L pletely reabsorbed reaches a level that is abnormally high, the the body decreases. One would expect that as the dilute filtrate Efferent Proximal convoluted tubule arteriole filtrate concentration exceeds the maximal reabsorptive in the collecting duct comes in contact with the higher osmotic capacity (Tm) of the tubules, and the substance begins appear- concentration of the medullary interstitium, passive reabsorp- ing in the urine. The plasma concentration at which active tion of water would occur. However, the process is controlled 300 transport stops is termed the renal threshold. For glucose, the by the presence or absence of ADH, which renders the walls plasma renal threshold is 160 to 180 mg/dL, and glucose of the distal convoluted tubule and collecting duct permeable appears in the urine when the plasma concentration reaches or impermeable to water. A high level of ADH increases per- Na+Cl- H2O Glomerulus H2O 300 Na+ this level. Knowledge of the renal threshold and the plasma meability, resulting in increased reabsorption of water, and a concentration can be used to distinguish between excess solute low-volume concentrated urine. Likewise, absence of ADH 100 filtration and renal tubular damage. Active transport of more renders the walls impermeable to water, resulting in a large Descending Na+Cl- than two-thirds of the filtered sodium out of the proximal con- volume of dilute urine. Just as the production of aldosterone limb Thick voluted tubule is accompanied by the passive reabsorption of is controlled by the body’s sodium concentration, the produc- H2O ascending Na+ an equal amount of water. Therefore, as seen in Figure 4-6, the tion of ADH is determined by the state of body hydration. limb 600 fluid leaving the proximal convoluted tubule still maintains the Therefore, the chemical balance in the body is actually the final Na+Cl- same concentration as the ultrafiltrate. determinant of urine volume and concentration. The concept H2O H2O of ADH control can be summarized as follows: ↑ Body Hydration = ↓ ADH = ↑ Urine Volume Technical Tip 4-2. Glucose appearing in the urine of a ↓ Body Hydration = ↑ ADH = ↓ Urine Volume H2O 900 person with a normal blood glucose level is the result H2O of tubular damage and not diabetes mellitus. A non- Tubular Secretion H2O Loop of fasting patient with high glucose intake would not In contrast to tubular reabsorption, in which substances are Henle have a normal blood glucose. The plasma glucose removed from the glomerular filtrate and returned to the 1200 would reach the renal threshold and appear in blood, tubular secretion involves the passage of substances the urine. from the blood in the peritubular capillaries to the tubular filtrate (Fig. 4-7). Tubular secretion serves two major functions: Medulla Countercurrent mechanism eliminating waste products not filtered by the glomerulus and Tubular Concentration regulating the acid–base balance in the body through the Reabsorption Secretion Renal concentration begins in the descending and ascending secretion of hydrogen ions. Variable loops of Henle, where the filtrate is exposed to the high Many foreign substances, such as medications, cannot be reabsorption filtered by the glomerulus because they are bound to plasma Figure 4–6 Renal concentration. osmotic gradient of the renal medulla. Water is removed by osmosis in the descending loop of Henle, and sodium and proteins. When these protein-bound substances enter the per- chloride are reabsorbed in the ascending loop. Excessive reab- itubular capillaries, they develop a stronger affinity for the tu- Tubular Renal tubular Peritubular sorption of water as the filtrate passes through the highly con- bular cells and dissociate from their carrier proteins, which lumen cell plasma centrated medulla is prevented by the water-impermeable walls results in their transport into the filtrate by the tubular cells. Efferent HCO3– (filtered) of the ascending loop. This selective reabsorption process is The major site for removal of these nonfiltered substances is arteriole called the countercurrent mechanism and serves to maintain the proximal convoluted tubule. Afferent HCO3 + H+ H+ HCO3 – HCO3 – the osmotic gradient of the medulla (see Fig. 4-6). The sodium arteriole and chloride leaving the filtrate in the ascending loop prevent Acid–Base Balance H2CO3 dilution of the medullary interstitium by the water reabsorbed To maintain the normal blood pH of 7.4, the blood must buffer H2CO3 Carbonic anhydrase from the descending loop. Maintenance of this osmotic gradi- and eliminate the excess acid formed by dietary intake and ent is essential for the final concentration of the filtrate when body metabolism. The buffering capacity of the blood depends it reaches the collecting duct. on bicarbonate (HCO3–) ions, which are readily filtered by the H2O + CO2 H2O + CO2 CO2 In Figure 4-6, the actual concentration of the filtrate leaving glomerulus and must be returned to the blood expediently to the ascending loop is quite low due to the reabsorption of salt maintain the proper pH. As shown in Figure 4-8, the secretion Bowman’s Final urine and not water in that part of the tubule. Reabsorption of sodium of hydrogen ions (H+) by the renal tubular cells into the filtrate capsule Reabsorption To blood continues in the distal convoluted tubule, but now it is under prevents the filtered bicarbonate from being excreted in the Glomerular Figure 4–8 Reabsorption of filtered bicarbonate. the control of the hormone aldosterone, which regulates reab- filtrate Secretion urine and causes the return of a bicarbonate ion to the plasma. sorption in response to the body’s need for sodium (Fig. 4-5). Tubule This process, which occurs primarily in the proximal convo- Figures 4-9 and 4-10 are diagrams of the two primary methods luted tubule, provides for almost 100% reabsorption of filtered for the excretion of hydrogen ions in the urine. In Figure 4-9 Collecting Duct Concentration To urine bicarbonate. the secreted hydrogen ion combines with a filtered phosphate The final concentration of the filtrate through the reabsorption As a result of their small molecular size, hydrogen ions are ion instead of a bicarbonate ion and is excreted rather than of water begins in the late distal convoluted tubule and con- readily filtered and reabsorbed. Therefore, the actual excretion Figure 4–7 Summary of movement of substances in the reabsorbed. In the proximal convoluted tubule, ammonia is tinues in the collecting duct. Reabsorption depends on the of excess hydrogen ions also depends on tubular secretion. nephron. produced from the breakdown of the amino acid glutamine. 7582_Ch04_105-123 24/06/20 5:38 PM Page 113 7582_Ch04_105-123 24/06/20 5:38 PM Page 114 Chapter 4 | Renal Function 113 114 Part One | Basic Principles Tubular Renal tubular Peritubular Newer methods that do not require the collection of timed lumen cell plasma PAH HISTORICAL NOTE Osmolarity (24-hour) urine specimens have been developed using just the – HPO4 (filtered) serum creatinine, cystatin C, or B2M values. The results of GFR Inulin Clearance tests these tests are reported as estimated glomerular filtration rate HPO4– + H+ H+ HCO3– HCO3– (eGFR). The traditional procedure for creatinine clearance is Inulin, a polymer of fructose, is an extremely stable sub- included here because it is still being performed, and its H2CO3 stance that is neither reabsorbed nor secreted by the Ammonia principles apply to other clearance procedures using urine. tubules. It is not a normal body constituent, however, and H2PO4 Carbonic anhydrase must be infused by IV at a constant rate throughout the Procedure testing period. Therefore, although inulin was the original By far, the greatest source of error in any clearance procedure reference method for clearance tests, current methods are using urine is the use of urine specimens that are improperly H2O + CO2 CO2 available that are endogenous and can provide accurate Titratable Free water timed. The importance of using a specimen that is accurately clearance GFR results. timed (see Chapter 3) will become evident in the following acidity Final urine discussion of the calculations involved in converting isolated Figure 4–9 Excretion of secreted hydrogen ions combined with laboratory measurements to the GFR. The GFR is reported in phosphate. A test that requires an infused substance is termed an milliliters cleared per minute; therefore, it is necessary to Osmolarity exogenous procedure and is seldom the method of choice determine the number of milliliters of plasma from which the if a suitable test substance is already present in the body clearance substance (creatinine) is removed completely during Tubular Renal tubular Peritubular (endogenous procedure). lumen cell plasma 1 minute. To calculate this information, one must know urine volume in mL/min (V), urine creatinine concentration in NH3 Creatinine Clearance mg/dL (U), and plasma creatinine concentration in mg/dL (P). Figure 4–11 The relationship of nephron areas to renal Creatinine is a waste product of muscle metabolism that is pro- The urine volume is calculated by dividing the number of – – NH3 + H+ H+ HCO3 HCO3 function tests. duced enzymatically by creatine phosphokinase from creatine, milliliters in the specimen by the number of minutes used to H2CO3 which links with adenosine triphosphate (ATP) to produce collect the specimen. which the kidneys are able to remove (to clear) a filterable sub- adenosine diphosphate (ADP) and energy. Because creatinine stance from the blood. To ensure that glomerular filtration is is normally found at a relatively constant level in the blood, it EXAMPLE NH4+ Carbonic anhydrase being measured accurately, the substance analyzed must be one provides the laboratory with an endogenous procedure for evaluating glomerular function. The use of creatinine has sev- Calculate the urine volume (V) for a 2-hour specimen measur- that is neither reabsorbed nor secreted by the tubules. Other ing 240 mL: H2O + CO2 CO2 factors to consider in selecting a clearance test substance in- eral disadvantages, and careful consideration should be given clude the stability of the substance in urine during a possible to them: 2 hours × 60 minutes = 120 minutes Final urine 24-hour collection period, the consistency of the plasma level, 1. Some creatinine is secreted by the tubules, and secretion 240 mL/120 minutes = 2 mL/min the substance’s availability to the body, and the availability of increases as blood levels rise. V = 2 mL/min Figure 4–10 Excretion of secreted hydrogen ions combined with tests to analyze the substance. 2. Chromogens present in human plasma react in the The concentrations of plasma and urine are determined by ammonia produced by the tubules. chemical analysis. Their presence, however, may help chemical testing. The standard formula used to calculate the Clearance Tests counteract the falsely elevated rates caused by tubular milliliters of plasma cleared per minute (C) is: The ammonia reacts with the H+ to form the ammonium A variety of substances has been used to measure the GFR. secretion. UV ion (NH4+) (Fig. 4-10). The resulting ammonium ion is ex- Newer methods that eliminate many of the problems men- 3. Medications, including gentamicin, cephalosporins, and C = P creted in the urine. Should there be additional need for the tioned previously have replaced some of these tests. They are cimetidine (Tagamet), inhibit tubular secretion of creati- elimination of hydrogen ions, the distal convoluted tubule and summarized as Historical Notes. nine, thus causing serum levels that are falsely low.1 This formula is derived as follows: The milliliters of plasma the collecting duct are also able to produce ammonium ions. At present, creatinine, beta2-microglobulin (B2M), cleared per minute (C) times the mg/dL of plasma creatinine 4. Bacteria will break down urinary creatinine if specimens All three of these processes occur simultaneously at rates cystatin C, and, possibly, radioisotopes are the primary sub- (P) must equal the mg/dL of urine creatinine (U) times the are kept at room temperature for extended periods.2 determined by the acid–base balance in the body. A disruption stances used in clearance tests. Each procedure has its advan- urine volume in mL/min (V), because all of the filtered creati- in these secretory functions can result in metabolic acidosis or tages and disadvantages. 5. A diet heavy in meat consumed during collection of a nine will appear in the urine. Therefore: renal tubular acidosis, the inability to produce an acid urine. 24-hour urine specimen will influence the results if the plasma specimen is drawn before the collection period. UV CP = UV and C = HISTORICAL NOTE The increased intake of meat can raise the creatinine P Renal Function Tests levels in urine and plasma during the 24-hour collection Urea Clearance period. This brief review of renal physiology shows that there are many metabolic functions and chemical interactions to be evaluated 6. Measurement of creatinine clearance is not a reliable EXAMPLE The earliest glomerular filtration tests measured urea indicator in patients suffering from muscle-wasting through laboratory tests of renal function. In Figure 4-11, the Using urine creatinine of 120 mg/dL (U), plasma creatinine of because of its presence in all urine specimens, as well as diseases or those involved in heavy exercise or athletes parts of the nephron are related to the laboratory tests used to 1.0 mg/dL (P), and urine volume of 1440 mL obtained from a the existence of routinely used methods of chemical analy- supplementing with creatine. assess their function. 24-hour specimen (V), calculate the GFR. sis. Because approximately 40% of the filtered urea is 7. Accurate results depend on the accurate completeness of Glomerular Filtration Tests reabsorbed, normal values were adjusted to reflect the a 24-hour collection. V = 1440 mL = 1 mL/min reabsorption, and patients were hydrated to produce a 60 minutes × 24 = 1440 minutes The standard tests used to measure the filtering capacity of the urine flow of 2 mL/min to ensure that no more than 40% 8. Creatinine clearance values must be corrected for body glomeruli are termed clearance tests. As its name implies, a of the urea was reabsorbed. surface area, unless normal is assumed, and must always 120 mg/dL × 1 mL/min (V) C = = 120 mL/dL clearance test measures the rate in milliliters per minute at be corrected for children. 1.0 mg/dL (P) 7582_Ch04_105-123 24/06/20 5:38 PM Page 115 7582_Ch04_105-123 24/06/20 5:38 PM Page 116 Chapter 4 | Renal Function 115 116 Part One | Basic Principles Plasma (1 mg/dL = 0.01 mg/mL creatinine) 440 420 200 The MDRD-IDMS traceable formula is: Beta2-Microglobulin 190 400 180 GFR = 175 × serum creatinine–1.154 × age–0.203 × 0.742 B2M (molecular weight 11,800) dissociates from human leuko- 380 170 360 (if patient is female) × 1.212 (if patient is black) cyte antigens at a constant rate and is removed rapidly from the Glomerulus 3.00 160 2.90 340 150 The formula is designed to essentially equal the results plasma by glomerular filtration. The B2M may be used to dis- 2.80 320 140 that compare to the reference body size of 1.73 m2. tinguish disorders of the kidney as either glomerular or tubular. 220 2.70 Plasma filtrate (120 mL/min x 0.01 mg/mL = 1.2 mg) 7' 215 2.60 300 290 Because eGFRs are calculated for an average body size, they Its excretion in urine is normally low, but when the renal tubules 130 10" 210 2.50 280 become damaged or diseased, the B2M concentration increases 8" 205 2.40 270 120 are not accurate for pediatric patients. They also have been shown 6" 200 2.30 260 to be most accurate when results are lower than 60 mL/min.4 It due to the decreased ability to reabsorb this protein. By measur- Reabsorption 195 250 (119 mL H2O) 4" 190 2.20 240 110 is recommended that results be reported with numerical values ing B2M concentrations of both blood and urine to evaluate kid- 2" 230