Renal Function and Assessment

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Renal Function and Assessment

Learning Objectives

After studying this chapter, the student should be able to:

  1. 1. Discuss renal tubular mechanisms that alter solute concentration and urine volume; use terms to describe volume variations.
  2. 2. State the solute composition of normal urine.
  3. 3. Differentiate between solute number and solute mass, and describe their effect on osmolality and specific gravity measurements.
  4. 4. Discuss the effects that diet, disease, and some exogenous substances (e.g., x-ray contrast media) have on measurements of urine concentration.
  5. 5. State the principle of the following osmometry methods:

  6. 6. Describe a protocol and one purpose for each of the following procedures:

  7. 7. Calculate osmolar clearance and free-water clearance results using data provided.
  8. 8. Compare and contrast the creatinine clearance test and the inulin clearance test for assessment of glomerular filtration.
  9. 9. Describe a protocol for a creatinine clearance test and discuss factors that can influence the results obtained.
  10. 10. Calculate creatinine clearance and estimated glomerular filtration rate (eGFR) results using data provided.
  11. 11. Describe the p-aminohippurate clearance test for assessment of renal plasma flow.
  12. 12. Discuss briefly the relationship of renal tubular secretory function to the urinary excretion of acids.
  13. 13. Describe the oral ammonium chloride test for the assessment of tubular function.

Key Terms1

Urine Composition

The volume and solute composition of urine can vary greatly depending on an individual’s diet, physical activity, and health. Because of these variables, normal (i.e., reference) urine values for each organic and inorganic component are difficult to establish. Urine is an ultrafiltrate of plasma with selected solutes reabsorbed, other solutes secreted, and the final water volume determined by the body’s state of hydration. When an individual is healthy, the final urine contains the solutes the body does not need, diluted in the amount of water the body does not need. Excreted urine is normally 94% water and 6% solutes. The ability of the kidneys to alter the excretion of water and solutes (as discussed in Chapter 3) makes it the principal organ for regulating body fluids and their composition.

Urine Volume

The total daily volume of urine excreted reflects the quantity of solutes ingested, the amount of fluid intake, and the activity of antidiuretic hormone (ADH) on urine excretion, as discussed in Chapter 3. However, when renal and metabolic diseases are present, urine volume can decrease to zero output or can increase to as much as 15 times normal. Typically, urine volume varies from 600 to 1800 mL/day, with less than 400 mL excreted at night. When an individual excretes more than 500 mL of urine at night, the condition is termed nocturia. Although nocturia is a classic feature of renal disease, it also occurs with conditions characterized by reduced bladder capacity (e.g., pregnancy, bladder stones, prostate enlargement) or simply from excessive fluid intake at night.

A person’s diet, health, and exercise directly affect daily urine volume. An average daily load of solutes is 600 to 700 mOsm, which requires the kidneys to produce at least 500 mL of urine to eliminate them. The kidneys maintain a balance between fluid intake and urine excretion, but the control is one-sided. Any excess fluid ingested but not needed will be excreted as urine; however, the kidneys have a limited ability to compensate for lack of adequate fluid intake. As the quantity of metabolic solutes that need elimination from the body increases, so does the volume of water required to excrete them. If the body lacks adequate hydration, these solutes accumulate in the body despite the best efforts of the kidneys to eliminate them.

Any increase in urine excretion (>1800 mL/day) is termed diuresis. However, when excretion is excessive and the volume exceeds 3 L in a day (>3 L/day), it is called polyuria. The causes of polyuria can be divided diagnostically into two types: (1) conditions with water diuresis (urine osmolality <200 mOsm/kg) and (2) conditions with solute diuresis (urine osmolality ≥300 mOsm/kg).1 Fig. 4.1 provides a flowchart for evaluating polyuria. Conditions characterized by water diuresis have a common link—ADH. With these disorders, ADH secretion is inadequate, or its action on the renal receptors is ineffective or inhibited. In contrast, conditions characterized by solute diuresis have no common feature but most often involve the solutes: glucose, urea, or sodium.

Diabetes mellitus and diabetes insipidus derive the name diabetes from the Greek word diabainein, which means “to pass through or siphon” and refers to the copious amount of urine produced by individuals with these disorders. Despite being entirely different conditions, both are characterized by intense thirst (polydipsia) and the excretion of large volumes of urine (polyuria). Diabetes mellitus, a disorder of carbohydrate metabolism, results from inadequate secretion or utilization of insulin, resulting in the excretion of glucose in urine (i.e., solute diuresis). Diabetes insipidus is a disorder characterized by decreased production or function of ADH, which results in an inability to control the excretion of water in urine (i.e., water diuresis). Table 4.1 summarizes conditions of water and solute diuresis that can result in polyuria.

Table 4.1

Urine Volume, Terms, and Clinical Correlations
Urine Volume and Associated Terms Clinical Correlation
600–1800 mL/day (normal) Urine osmolality: 275–900 mOsm/kg; varies with diet, hydration, and exercise

Solute diuresis: urine osmolality 300 ± 50 mOsm/kg

Water diuresis: urine osmolality ≤200 mOsm/kg

<400 mL/day (oliguria) Decreased renal blood flow

Renal disease

No urine excreted (anuria) Acute renal failure

Urinary tract obstruction
Hemolytic transfusion reactions


ADH, Antidiuretic hormone.

Oliguria is a decrease in urine excretion (<400 mL/day) that can be caused by simple water deprivation or from dehydration due to excessive sweating, diarrhea, or vomiting. Essentially, any condition that decreases the blood supply to the kidneys can cause oliguria and eventually anuria if not corrected. Oliguric urines have an elevated specific gravity (SG; ≈1.030) because the kidneys maximally excrete solutes into the decreased water available, forming a concentrated urine. Oliguria can occur in conditions characterized by edema or conditions where plasma protein is lost and water shifts from the intravascular (bloodstream) to the extravascular (tissue) compartment. Oliguria also develops with various renal diseases, ranging from urinary tract obstruction to end-stage renal disease. Note that the decreased urine volume excreted does not allow the elimination of a normal daily solute load and, if prolonged, death can occur.

Anuria is the complete lack of urine excretion. It is fatal if not immediately addressed because of the accumulation of toxic metabolic byproducts in the body. Anuria usually develops gradually after an initial presentation of oliguria but can occur suddenly (e.g., acute decrease in renal perfusion). Basically, any condition or disease—chronic or acute—that destroys functioning renal tissue can result in anuria. Principal among these are conditions that decrease the blood supply to renal tissue causing ischemia, such as hypotension, hemorrhage, shock, and heart failure. Toxic chemicals and nephrotoxic antibiotics can induce acute tubular necrosis, leading to loss of functional renal tissue and anuria (or oliguria). In addition, hemolytic transfusion reactions as well as urinary tract obstructions can result in anuria.

In conclusion, urine volume measurements are not performed routinely. Although this information can serve as a valuable diagnostic aid, urine volume is usually determined with timed urine collections (e.g., every 24 h, 12 h) that are subsequently used to calculate the concentration of specific urine solutes or assess renal function (e.g., the glomerular filtration rate, GFR). The terms polyuria, oliguria, and anuria are usually assigned on the basis of a patient’s health history and clinical observation, and are not based on timed urine collections. Table 4.1 lists urine volume terms, definitions, and possible causes.

Solute Elimination

Besides its role in selectively conserving electrolytes and water, renal excretion is the primary mode for elimination of soluble metabolic waste (e.g., organic acids and bases) and exogenous substances (e.g., radiographic contrast media and drugs). Carbon dioxide and water, the normal byproducts of carbohydrate and triglyceride metabolism, do not require renal excretion. In contrast, the metabolism of proteins and nucleic acids yields soluble substances such as urea, creatinine, uric acid, and other inorganic solutes that can only be eliminated from the body in the urine. Of these substances exclusively excreted by the kidneys, urea and creatinine in particular provide a means of monitoring and evaluating renal function, specifically glomerular filtration. In addition, because of their characteristically high concentrations in urine, creatinine and urea provide a means of positively distinguishing urine from other body fluids.

Table 4.2 compares the amounts and masses of the principal urine components. Note that the amount of a component in millimoles relates to the number of particles present, whereas the mass indicates the “weight” of the component. For example, the number of inorganic phosphate molecules present is less than that of potassium molecules; however, the mass of inorganic phosphate present is actually greater than that of potassium. The importance of making this distinction between the number of solute particles present and the mass of particles present relates directly to osmolality and SG measurements, respectively. These measurements are used to assess the quantity of solutes present in urine, which reflects the ability of the kidneys to produce a concentrated urine.

Table 4.2

Composition of Selected Components in an Average 24-Hour Urine Collection
Component Average Amount, mmol Average Mass, mg
Water (1.2 La) 67,000.00 1,200,000.0
Urea 400.00 24,000.0
Chloride 185.00 6570.0
Sodium 130.00 2990.0
Potassium 70.00 2730.0
NH4 40.00 720.0
Inorganic PO4 30.00 2850.0
Inorganic SO4 20.00 1920.0
Creatinine 11.80 1335.0
Uric acid 3.00 505.0
Glucose 0.72 130.0
Albumin 0.001 90.0

aAverage 24-hour urine volume with a glomerular filtration rate of 125 mL/min.

Urine Concentration and Measurement

Urine concentration is an expression of the amount of solutes (i.e., molecules in solution) relative to the volume of water they reside in. The concentration of urine will vary with an individual’s diet, exercise, and health as the amount and type of solutes as well as the volume of water available for their excretion will differ. Concentration is a physical characteristic of urine that can be measured and expressed by parameters such as osmolality and SG.


Osmolality is the concentration of a solution expressed in osmoles of solute particles per kilogram of solvent. An osmole (Osm) is defined as the amount of a substance that dissociates to produce 1 mole of particles (6.023 × 1023 particles, Avogadro’s number) in a solution. Because the osmolality of biological fluids (urine, serum) is very low, the term milliosmole (mOsm) is the unit of choice. A mOsm is 1 millimole (mmol) of particles “in solution.” Because osmolality is directly related to particle number, a solute that dissociates in solution will produce a higher osmolality than a solute that does not dissociate. For example, glucose (MW 180) in solution does not dissociate; hence 1 mmol of glucose (180 mg) produces 1 mmol of particles, or 1 mOsm. In contrast, sodium chloride (NaCl) in solution dissociates into two particles: Na+ ions and Cl ions; hence 1 mmol (58 mg) of NaCl produces 2 mmol of particles in solution, or 2 mOsm. Note that the molecular weight of the solute does not play a role in osmolality. Despite the larger molecular weight of glucose (MW 180), the osmolality of a molar-equivalent sodium chloride (MW 58) solution will be approximately double that of the glucose solution. In urine, the solvent is water and the solute particles are those molecules that remain in the final ultrafiltrate after passage through the nephrons.

The initial ultrafiltrate in Bowman’s space has almost the same solute composition as the plasma. It only lacks albumin and other high-molecular-weight solutes in the bloodstream that could not pass through the glomerular filtration barrier. Note that the amount of these large solutes in the ultrafiltrate are very small in number compared with the total number of solutes that freely pass the barrier (see Table 4.2). Therefore, in Bowman’s space, the osmolality of the initial filtrate is the same as that of the plasma (≈300 mOsm) and is termed isosmotic. As discussed in Chapter 3, the solute composition (concentration and type) in the filtrate changes continuously throughout its passage through the tubules of the nephron. In contrast, the osmolality remains unchanged (isosmotic at ≈300 mOsm) until the filtrate reaches the thin descending limb of the loop of Henle (Fig. 4.2). Here, the countercurrent multiplier mechanism causes the filtrate in the loops of Henle to become progressively hyperosmotic in the descending limb and then hypo-osmotic in the ascending limb. When the filtrate enters the distal tubules, it is slightly hypo-osmotic (≈100 mOsm).

The final osmolality of urine is determined in the distal tubules and collecting ducts. The surrounding medullary interstitium has a hypertonic concentration gradient that facilitates the reabsorption of water when ADH is present. In the distal tubules with ADH present, the filtrate again becomes isosmotic (≈300 mOsm), matching the hypertonicity of the cortical interstitium (see Fig. 4.2). As the filtrate passes through the collecting tubules, the osmolality of the filtrate can continue to increase (as water is absorbed) until it matches that of the surrounding hypertonic medullary interstitium, provided ADH is present. Note that the maximum urine osmolality possible—1200 to 1400 mOsm/kg—is determined by the osmolality of the medullary interstitium. The collecting tubules do not exchange solutes but can passively reabsorb water until an osmotic equilibrium is attained.

The osmolality of a random urine specimen can be as low as 50 mOsm/kg or as high as 1400 mOsm/kg. Under normal circumstances, urine osmolality ranges from one to three times (275–900 mOsm/kg) that of serum (275–300 mOsm/kg). The urine-to-serum osmolality (U/S) ratio is a good indicator of the ability of the kidneys to concentrate the urine. In normal individuals with an average fluid intake, the U/S ratio is between 1.0 and 3.0.

It is important to note that in the bloodstream, the plasma osmolality remains relatively constant. In contrast, urine osmolality can vary greatly as the kidneys excrete unwanted solutes in the volume of water that the body does not need. With a typical American diet, 100 to 1200 mOsm of solutes require elimination each day. Other diets higher in salt and protein require a larger volume of water to excrete the increased solute load. Some disorders (e.g., diabetes mellitus) can produce as much as 5000 mOsm/day of solutes for elimination. Consequently, a large volume of water is required to excrete them in the urine. Because the kidneys have no direct means of replacing excessive water loss, adequate fluid intake is mandatory. These individuals experience intense thirst, known as polydipsia. It is only with an increased water intake that these individuals are able to excrete the excessive load of solutes.

Osmolality Methods

Osmolality is determined by measuring a colligative property of the sample. Colligative properties of a solution depend only on the number of solute particles present. Particle size and ionic charge have no effect; only the number of particles present as ions or as undissociated molecules in the solution affects colligative properties. The four colligative properties are (1) depression of freezing point, (2) depression of vapor pressure, (3) elevation in osmotic pressure, and (4) elevation of boiling point. These properties are interrelated, and the value of one can be used to calculate each of the others. In the clinical laboratory, freezing point depression osmometry predominates for several reasons. This method can be used to detect the presence of volatile solutes (e.g., ethanol, methanol, ethylene glycol) and results are accurate even with lipemic serum samples.2 Table 4.3 summarizes osmolality methods and their limitations.

Table 4.3

Osmolality Methods and Limitations
Method Limitations
Freezing point depression No limitations; all solutes contribute equally to result obtained; time-consuming compared with SG methods
Vapor pressure depression Does not detect volatile solutes (e.g., ethanol, methanol, ethylene glycol); time-consuming compared with SG methods

SG, Specific gravity.

Freezing Point Osmometry

A contemporary freezing point osmometer consists of four principal components: (1) a mechanism to supercool the sample slowly to about −7°C, (2) a thermistor to monitor the temperature of the sample, (3) a means to initiate freezing (or “seeding”) of the sample, and (4) a direct readout display.

The specimen, urine or serum, in a sample chamber is placed into the osmometer. The instrument begins the cooling sequence depicted in Fig. 4.3. The initial supercooling process (segment AB, Fig. 4.3) proceeds slowly to prevent premature freezing of the sample. As the sample temperature approaches −7°C, freezing of the sample is induced (seeded) by the instrument (point B). As ice crystals form, the heat of fusion released to the sample (segment BC) is detected by a thermistor. The sample temperature increases until an equilibrium between the solid (ice) and liquid phases is reached, which by definition is the freezing point (segment CD). This temperature plateau is maintained for approximately 1 minute or longer before it again decreases (segment DE). Using the freezing point obtained, the instrument calculates and then displays the osmolality of the sample using the proportionality formula given in Equation 4.1.

1000 mOsm  particles1.86°C=χ mOsm  particlesmeasured  freezing  point  of sample Equation 4.1

image Equation 4.1

Measurement of freezing point depression is based on the fact that pure water freezes at 0°C, and that adding 1 mole (1000 mOsm) of solute particles to 1 kg pure water causes the freezing point to decrease by 1.86°C. This relationship is constant and enables the use of a simple proportionality formula. For example, assume that the thermistor probe measures the freezing point of a urine specimen as −1.20°C. By inserting this value into the equation and solving for x, the osmolality of the urine sample is found to be 645.2 mOsm/kg. To achieve the precision of ±2 mOsm/kg, as is seen with freezing point osmometers, accurate temperature measurements are crucial. The thermistor obtains these temperature measurements accurately and rapidly.

For osmolality results to be read directly from the instrument readout, the microprocessor of the osmometer must be calibrated using sodium chloride standard solutions of known osmolality. These sodium chloride solutions are available commercially in concentrations ranging from 50 to 2000 mOsm or are prepared by the laboratory. After calibration, the osmometer measures the freezing point, converts it to the corresponding osmolality value, and displays it on the direct readout.

The sample size necessary for osmolality determinations varies from 20 μL to 2.0 mL, depending on the osmometer used. A problem occasionally encountered with freezing point osmometry is premature freezing, which can be caused by particulate matter in the sample that prevents proper supercooling. This is usually overcome by simply repeating the determination.

Vapor Pressure Osmometry

Another instrument that can be used to determine osmolality is the vapor pressure osmometer. This instrument indirectly measures the decrease in vapor pressure caused by solutes in a sample. The smaller sample size (7 μL) is advantageous; however, because of its inability to detect volatile solutes, vapor pressure osmometers are usually not used in clinical laboratories. See Table 4.3 for a summary of osmolality methods and their limitations.

In conclusion, osmolality and SG are expressions of urine concentration. Heavy molecules such as glucose, protein, and radiographic media significantly affect SG measurements but do not affect osmolality measurements because the amount of these substances is insignificant compared with the total number of other solutes present. Because all solutes contribute equally to osmolality regardless of their molecular size, osmolality is considered a better and more accurate assessment of solute concentration in serum and urine.

Specific Gravity

Specific gravity (SG) is another expression of solute concentration. It relates the density of urine to the density of an equal volume of pure water. Because SG is a ratio comparing the mass of the solutes present in urine to pure water, urine SG measurements are always greater than 1.000.

The initial ultrafiltrate (i.e., protein-free plasma) that forms in Bowman’s space has an SG of 1.010. As the filtrate passes through the tubules, the SG changes as solute exchange and water absorption occur. Urine SG values indicate whether the plasma ultrafiltrate was concentrated (SG > 1.010) or diluted (SG < 1.010) during its passage through the nephrons. Normally, urine SG values range from 1.002 to 1.035. Urine specimens with an SG less than 1.010 are termed hyposthenuric, whereas those with an SG greater than 1.010 are termed hypersthenuric. Note that these are simply descriptive terms regarding urine solute concentration.

Occasionally, urine specimens will have an extremely high SG value (≥1.050) by refractometry that appears to exceed values that are physiologically possible (≈1.040). This can occur when a high-molecular-weight substance, such as radiopaque contrast media (x-ray dye) or mannitol is present in the urine specimen. These exogenous substances are infused into patients and excreted in the urine. The high SG values obtained do not suggest a disorder or disease process; rather they indicate interference with the refractometry SG method. If the reagent strip SG method is used, the SG will reside within the physiologic range. Similarly, if the osmolality is determined on these urine specimens, the results will not be abnormal because osmolality values are affected only by the “number” of solutes present. In these specimens, the number of high-molecular-weight solutes is too few compared with the total number of other solutes in the urine (e.g., sodium, urea). In other words, the mass of these solutes present is significant and affects the urine SG by refractometry, but their number is too small to significantly affect the urine osmolality. These urine specimens are considered contaminated and unacceptable for analysis. A new specimen should be collected after a suitable time has passed (~8 hours for imaging agents) to allow for complete elimination of the imaging agent or other exogenous substance.

Osmolality Versus Specific Gravity

Because density depends on two variables—the number of solutes present and their relative mass—the relationship of SG to osmolality is close but not linear (see Fig. 4.4). This relationship is relatively constant in health. However, with some conditions this relationship is nonexistent, as high-molecular-weight solutes such as glucose, urea, or proteins are being excreted in the urine. Table 4.4 shows SG values of water with NaCl, urea, and glucose added. Each solute addition represents essentially the same number of particles added to the solution—approximately 5.2 × 1023 particles. In each solution, despite the presence of the same number of particles, the values for “true” density and SG by refractive index differ, demonstrating the effect of solute mass. In other words, the presence of large-molecular-weight solutes (e.g., glucose, protein, radiographic media) will dramatically increase urine density more so than an equivalent number of small-molecular-weight solutes such as sodium or chloride ions. Note that this effect is not observed with the reagent strip SG method, which detects only ionized solutes.

Table 4.4

Comparison of Specific Gravities of Different Solutions
Solute Characteristic Specific Gravity
Solution Number of Solute Particles Added Amount of Solute, mol/L “True” Density Refractive Index Ionic (Reagent Strip)
Water 0.0 0.0 1.000 1.000 1.000
Water and NaCl 5.2 × 1023 0.43 1.017 1.012 1.005
Water and urea 5.2 × 1023 0.86 1.021 1.020 1.000
Water and glucose 5.2 × 1023 0.86 1.056 >1.050 1.000


In summary, osmolality and SG are physical properties used to assess urine concentration. Osmolality measurements detect only the number of solutes present, regardless of solute type or mass. In contrast, SG determined by refractometry reflects the collective number and mass of solutes in the urine, whereas the reagent strip SG method detects only ionic solutes. See Chapter 5 for a detailed discussion of the SG methods most commonly used when performing a routine urinalysis.

Assessment of Renal Concentrating Ability/Tubular Reabsorptive Function

Osmolality and Specific Gravity

Osmolality or SG measurements can be used to demonstrate that the renal tubules are able to conserve water—a tubular reabsorptive function—and produce concentrated urine. A urine specimen is considered “concentrated” when the osmolality is greater than 800 mOsm/kg or the SG is greater than 1.025.

Although SG determinations are easier and require less time to perform, osmolality determinations are preferred when evaluating renal concentrating ability. Osmolality measurements are considered a more accurate assessment because, as previously discussed, each solute particle contributes equally to the osmolality value. In contrast, SG measurements are a density comparison that is affected more by some solutes than others. Recall from Table 4.2 that the three most prevalent urine solutes are urea, chloride, and sodium. Chloride and sodium are reabsorbed selectively throughout the nephrons by active and passive tubular transport mechanisms. Therefore, monitoring the concentration of chloride and sodium in urine reveals the kidney’s ability to process and concentrate the ultrafiltrate. In contrast, urea is not an accurate indicator of the kidney’s ability to concentrate urine because it is only passively processed in the nephrons (i.e., urea cycle), and the magnitude of this exchange varies owing to several factors (e.g., tubular flow rate).

Another reason that osmolality determinations are better than SG determinations for assessing the concentrating ability of the kidneys is that small quantities of high-molecular-weight solutes (e.g., glucose, protein) will affect SG measurements but do not affect osmolality measurements. Glucose and protein are solutes that are actively and essentially completely reabsorbed in the proximal tubules. It is important to note that their presence in urine indicates a disease process, not a change in kidney function (i.e., concentrating ability). In contrast to SG measurements, the osmolality value of urine is not affected by the presence of glucose and protein. In such urine, the density (SG) is significantly increased because of the high mass of glucose and protein molecules, but the actual increase in particle numbers is small compared with the total solutes present (Fig. 4.4). Another advantage of osmolality measurements is that results increase or decrease in direct proportion to the solute number, regardless of the solute type.

With some chronic renal diseases, the renal tubules are no longer able to selectively reabsorb and secrete solutes and water from the ultrafiltrate as it passes through the nephron, and the solute concentration remains unchanged. Consequently, regardless of the patient’s hydration status, the urine osmolality and SG are the same as that of the initial ultrafiltrate in Bowman’s space—namely, the urine has a fixed SG of 1.010 and an osmolality of approximately 300 mOsm/kg (i.e., the same as protein-free plasma). Isosthenuria is the term used to describe an unchanging SG (or osmolality) regardless of hydration. It implies significant renal tubular dysfunction, is a feature of end-stage renal disease, and is also associated with polyuria and nocturia—excessive urination at night.

In summary, SG and osmolality are nonspecific tests used to determine the concentration of urine. They can only suggest or support a suspected decrease in renal function. The underlying problem—whether it is renal disease, diabetes insipidus, overhydration, or the effect of diuretic therapy—cannot be discerned using these tests.

Fluid Deprivation Tests

Polyuria due to water diuresis can result from excessive water intake or from disorders involving ADH (vasopressin) see Table 4.1. When ADH production or secretion is defective, this indicates neurogenic diabetes insipidus. When the problem is lack of renal response to ADH, it is called nephrogenic diabetes insipidus. To differentiate the cause of water diuresis, a fluid deprivation test can be performed.

A fluid deprivation test evaluates the ability of renal tubular cells to selectively absorb and secrete solutes. In other words, it assesses the renal concentrating ability of the kidneys. During this test, water consumption by the patient is restricted and the concentration of the urine is evaluated at timed intervals. In a typical protocol, the patient eats a normal evening meal, and then from 6 PM until 8 AM the next day he or she drinks no water or other fluids. At 8 AM, a urine specimen is collected and the osmolality determined. If the urine osmolality is greater than 800 mOsm/kg, the renal concentrating ability of the kidneys is considered normal and the test is ended.

If the osmolality is less than 800 mOsm/kg, fluid deprivation continues. At 10 AM, both serum and urine specimens are collected for osmolality determinations. If the urine osmolality is greater than 800 mOsm/kg or the U/S ratio is greater than 3.0, normal renal concentrating ability is demonstrated and the test is ended. If neither condition is met, ADH (vasopressin) is administered subcutaneously, and at 2 PM and 6 PM serum and urine specimens are collected for osmolality testing. Note that regardless of a patient’s response, the test is terminated at 6 PM (i.e., after 24 hours). A positive response to ADH administration is a urine osmolality greater than 800 mOsm/kg or a U/S ratio of 3.0 or greater. These results indicate that the patient’s kidneys can respond to ADH but that inadequate ADH is produced by the patient (i.e., a neurogenic problem). In contrast, a negative response to ADH indicates a nephrogenic problem—the renal receptors for ADH are dysfunctional (see Fig. 4.1).

Other tests that assess renal concentrating ability use urine SG measurements. In the Fishberg concentration test, the patient undergoes the same fluid deprivation regimen as previously described. At each timed interval, a urine specimen is collected and the SG determined. If the urine SG becomes 1.025 or greater, renal concentrating ability is normal and the test ends.

Differing from the tests already discussed, Mosenthal’s test allows patients to maintain their normal diet and fluid intake and requires a special 24-hour urine collection. The 24-hour collection is unique in that it is collected as two separate 12-hour urine collections—a 12-hour day portion and a 12-hour night portion. The volume and SG of each 12-hour urine collection are determined. A normal Mosenthal’s test is indicated by a daytime urine volume that exceeds the nighttime volume and by a nighttime urine SG that is 1.020 or greater.

Osmolar and Free-Water Clearance

Just as simultaneous measurement of serum and urine osmolality can aid a clinician in the differential diagnoses of disease (e.g., neurogenic diabetes insipidus versus nephrogenic diabetes insipidus), determining the quantity of water and solutes not reabsorbed by the kidneys has diagnostic value. This is done by measuring the renal clearance of “solutes” and comparing it with the renal clearance of “solute-free” water. To do so requires the osmolality from a timed urine collection and a corresponding serum specimen. The ratio of urine osmolality to serum osmolality multiplied by the timed urine volume gives the osmolar clearance, designated COsm:

COsm(mL  plasma  per  minute)=UOsm(mOsm/kg)SOsm(mOsm/kg)×V (mL/min) Equation 4.2

image Equation 4.2

Oct 18, 2022 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Renal Function and Assessment
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