Section 2: Scientific Principles
Part D: Physiology and Anesthesia
Chapter 18: Renal Physiology

Tubular Function Tests

Tests of renal tubular function can define states of diuresis and antidiuresis and natriuresis and antinatriuresis. Under certain circumstances the tests can distinguish oliguria due to prerenal azotemia, which is reversed by restoration of hemodynamic status to normal, from that due to established acute renal failure, which persists despite restoration of normal renal blood flow. In the former, tubular conservation mechanisms are enhanced, and in the latter they are lost. However, in nonoliguric renal dysfunction, which accounts for more than 50 percent of cases encountered clinically, the differences in tubular function are less distinct from prerenal azotemia. Diuretic therapy overcomes tubular conserving function. Thus, treatment with loop diuretics, osmotic diuretics, saline loading, or natriuretic vasodilators (low-dose dopamine, fenoldopam, prostaglandin E1, or ANP) may render tubular function tests uninterpretable.

Urinary Concentrating Ability

Concentrating ability is a very sensitive index of tubular function. In prerenal states, urinary osmolar concentration is markedly increased. In acute tubular necrosis, the ability to concentrate urine may be lost 24 to 48 hours before serum creatinine or blood urea nitrogen (BUN) starts to increase.

Urine-to-Plasma Osmolar Ratio

The normal tubular response to dehydration or hypovolemia is to generate a urine-to-plasma osmolar ratio (U:POSM) of 1.5 or greater. Isosthenuria (U:POSM = 1.0) in the presence of oliguria implies loss of tubular function and established acute renal failure. However, isosthenuria can occur in a prerenal state following diuretic administration.

Free Water Clearance

Free water clearance (CH2O) attempts to represent the degree of urinary concentration or dilution by distinguishing the clearance of solute from that of free water. The solute or osmolar clearance (COSM) is calculated by standard methods, using urine osmolality in mOs/kg (UOSM), plasma osmolality in mOs/kg (POSM), and urine flow in mL/min (V):

Then, the osmolar clearance is subtracted from the urine flow rate to give free water clearance:

If the urine is isosmotic with plasma, the osmolar clearance equals the urine flow rate so that CH2O is zero. If the urine is dilute (hypo-osmotic), the urine flow rate exceeds osmolar clearance, and the difference is the free water clearance. If the kidney is able to concentrate urine normally (hyperosmotic urine), urine flow rate is less than osmolar clearance, which results in a negative free water clearance (i.e., free water retention), also known as tubular conservation of water (TCH2O). Conceptually, TCH2O represents the volume of fluid that would have to be added to the urine to make its osmolality equivalent to that of plasma. 24 

With the onset of acute tubular necrosis and loss of concentrating ability, the urine becomes isosmotic, and CH2O approaches zero (±0.25 mL/min). However, in distinguishing between prerenal and intrarenal oliguria, CH2O does not really provide any more information about concentrating ability than U:POSM, and in addition it requires a timed urine collection.

The concept of free water excretion emphasizes that renal regulation of solute and of water balance are independent of each other. The kidney has an enormous range in its ability to handle water. The maximum excretion of water, or positive free water clearance, is 18 L/d, about 10 percent of the GFR. The maximum conservation of water, or negative free water clearance, is 8 L/d. 24 

Water Conservation

Urine-to-Plasma Creatinine Ratio

The urine-to-plasma creatinine ratio (U:PCR) represents the proportion of water filtered by the glomerulus that is abstracted by the distal tubule. Normally, about 98 percent of water is abstracted, and urine creatinine is much greater than plasma creatinine. The ratio can increase a hundred-fold in severe prerenal states. When tubular function is lost, the ratio declines to less than 20:1. For example, two patients have a serum creatinine of 2.0 mg/dL. In one, urine creatinine is 100 mg/dL, which implies a prerenal state (U:PCR 50:1). In the other, urine creatinine is 20 mg/dL, which suggests acute tubular necrosis (U:PCR only 10:1). Similar information may be obtained during the performance of an inulin clearance test by calculating the urine-to-plasma inulin ratio.

Sodium Conservation

Urine Sodium

During dehydration or hypovolemia, the tubules intensely reabsorb sodium so that urine sodium (UNa) declines to less than 20 mEq/L. In established acute renal failure, the ability to conserve sodium and protect the intravascular volume is lost, and UNa exceeds 60 to 80 mEq/L. Diuretic therapy overcomes tubular sodium conservation so that a high UNa does not necessarily imply loss of tubular function. However, if UNa remains low in the face of diuretic therapy, an intense prerenal state exists.

Fractional Excretion of Sodium

Fractional excretion of sodium (FENa) expresses sodium clearance as a percentage of creatinine clearance:

Based on the relationship expressed in Equation 5:

Urine flow rate (V) is identical in the numerator and denominator and it cancels out:

Thus, FENa may be calculated from a spot sample of blood and urine without requiring a timed urine collection.

During dehydration or hypovolemia, sodium clearance and FENa are decreased to less than 1 percent of creatinine clearance. When tubular ability to conserve sodium is lost in acute renal failure, FENa increases to more than 3 percent. However, FENa increases with normal tubular function after diuretic therapy and during postoperative sodium mobilization. Sequential increases in FENa associated with declining creatinine clearance indicate more reliably deteriorating renal function than an isolated high FENa.