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Tests of renal tubular function essentially measure urinary concentrating ability and sodium handling. As such, they can distinguish oliguria caused by dehydration (prerenal syndrome) from that attributable to tubular injury (acute tubular necrosis). In prerenal oliguria, tubular function is preserved, in fact "switched on" to concentrate urine and conserve sodium. It is reset by restoration of hemodynamic status to normal. In established acute tubular necrosis, concentrating ability and sodium conservation are lost and are not reestablished by restoration of normal RBF. However, in nonoliguric renal failure, which accounts for as much as 75% of cases of acute tubular necrosis encountered clinically, the changes in tubular function are less distinct from those of prerenal syndrome. In addition, any potent diuretic may override the tubular conserving function and generate a diuresis and natriuresis despite intravascular hypovolemia. These agents include loop diuretics, osmotic diuretics, and natriuretic vasodilators such as low-dose dopamine, fenoldopam, prostaglandin E1 (PGE1 ), and ANP.
Concentrating ability is a very sensitive index of tubular function. In prerenal states, the 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.
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 when it is induced by diuretic administration (see earlier).
Free water clearance (CH2
O)
attempts to represent the degree of urinary concentration or dilution in the tubules
by distinguishing the renal clearance of solute from that of free water. Solute
or osmolar clearance (COsm
) is calculated by standard methods that entail
the use of urine osmolality in mOsm/kg (UOsm
), plasma osmolality in mOsm/kg
(POsm
), and urine flow in mL/min (V):
COsm
= (UOsm
× V)/POsm
(mL/min) (15)
Then, osmolar clearance is subtracted from the urine flow rate to give free water
clearance:
CH2
O
= V − COsm
(mL/min) (16)
When the urine is isosmotic with plasma (i.e., UOsm = POsm ), osmolar clearance equals the urine flow rate (i.e., COsm = V) and CH2 O is zero. Dilute urine reflects a hypo-osmotic state in which the urine flow rate exceeds osmolar clearance, and free water clearance has a positive value. Concentrated urine reflects a hyperosmotic state in which the urine flow rate is less than osmolar clearance. This situation results in negative free water clearance (i.e., free water retention), also known as tubular conservation of water (TCH2 O). Conceptually, TCH2 O represents the volume of fluid that would have to be added to urine to make its osmolality equivalent to that of plasma.[22]
With the onset of acute tubular necrosis and loss of concentrating ability, the urine becomes isosmotic, and CH2 O approaches zero (±0.25 mL/min). However, in distinguishing between prerenal and intrarenal oliguria, CH2 O does not really provide any more information about concentrating ability than U:POsm does, and in addition, it requires a timed urine collection.
The concept of free water excretion emphasizes that renal regulation of solute and water balance occur independently of each other. The kidney has an enormous range in its ability to handle water. The maximal excretion of water, or positive free water clearance, is 18 L/day, about 10% of the GFR. The maximal conservation of water, or negative free water clearance, is 8 L/day.[22]
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% 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.
During dehydration or hypovolemia, the tubules intensely reabsorb sodium so that the urinary sodium
Fractional excretion of sodium (FENa
) expresses sodium
clearance as a percentage of creatinine clearance:
FENa
= (Sodium clearance/Creatinine clearance)
× 100%
Based on the relationship expressed in Equation 5,
FENa
= [(UNa
× V)/PNa
]/[(UCr
× V)/PCr
] × 100%
The urine flow rate (V) is identical in the numerator and denominator and thus cancels
out:
FENa
= (UNa
/PNa
)/(UCr
/PCr
)
× 100% (17)
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% of creatinine clearance. When tubular ability to conserve sodium is lost in acute renal failure, FENa increases to more than 3%. However, FENa increases with normal tubular function after diuretic therapy and during postoperative sodium mobilization. Sequential increases in FENa associated with a declining creatinine clearance provide a more reliable indicator of deteriorating renal function than an isolated high FENa value does.
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