Renal Pathophysiology




The urine albumin concentration is proportional to the urine volume as well as the quantity of albumin present. For example, drinking a large volume of fluid will dilute the urinary protein concentration and reduce the intensity of the finding on the urine dipstick. Likewise, the urinary creatinine excretion will be reduced to a similar degree, allowing variability in urine volume to be ignored in the estimation of daily protein excretion when both the urine protein and creatinine are measured on the same sample and expressed as the urine protein/creatinine ratio. This patient has severe AKI (presuming a normal baseline creatinine), and the differential diagnosis is very broad and includes prerenal, intrarenal pro cesses. The normal renal ultrasound effectively excludes postrenal processes. The clue to the diagnosis of rhabdomyolysis is in the urine findings; the dipstick will detect filtered hemoglobin and myoglobin, so a strongly positive finding on the dipstick in the absence of significant numbers of red blood cells suggests intravas cular hemolysis with free heme or myoglobin in the circulation, which are filtered into the urine and cause tubular injury. The urine sodium concentration is affected by the rate of water excretion as well as by the rate of sodium excretion. For example, the urine sodium concentration will be 60 mEq/L in a patient ingesting 60 mEq of sodium and 1 L of water. If, however, water intake and excretion were increased to 2.5 L, the urine so dium concentration would fall to 24 mEq/L even though there had been no change in sodium excretion. The FENa is 0.5% [(35 × 3.2 × 100) ÷ (140 × 160)], suggesting that the patient has a prerenal disease with intact tubular function. The FENa is 0.83% [(67 × 1.0 × 100) ÷ (120 × 67)]. Although this might suggest volume depletion, note that the patient is excreting a total of 100 mEq of so dium per day (67 mEq/L × 1.5 L/day) and is therefore likely to be normovolemic. The apparent discrepancy relates to the effect of the filtered sodium load (determined pri marily by the GFR) on the level of FENa, which is indicative of volume depletion. A value < 1% applies to renal failure when the filtered sodium load is relatively low. If, for exam ple, the GFR is markedly reduced at 20 L/day (14 mL/min) and the plasma water sodium concentration is 150 mEq/L, then the filtered sodium load is 3,000 mEq/day. Reducing sodium excretion to < 20 mEq/day with volume depletion requires a FENa < 1%. The results are quite different when the GFR is relatively normal. At a GFR of 180 L/day (125 mL/min) and a plasma water sodium concentration of 150 mEq/L, the filtered sodium load is much greater at 27,000 mEq/day. A FENa of 1% in this setting represents the excretion of 270 mEq/day, which is greater than the average sodium intake of 80 to 250 mEq/day. Thus, almost all normal subjects have a FENa < 1% as in the patient described. Reducing sodium excretion to < 20 mEq/day requires a FENa < 0.1%. As the GFR falls in patients with renal disease, the FENa indicative of volume depletion (ie, the FENa associated with sodium excretion < 20 mEq/day) gradually rises from 0.1% to, as noted earlier, almost 1% in near end-stage renal disease. These examples illustrate that the difficulty is using the FENa in settings other than advanced renal failure. Unless the FENa is very low ( < 0.1% to 0.2%), the approx imate GFR must be known to determine if sodium is being appropriately conserved. 1 2 3 4 5

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