Creatinine
Creatinine is generated by muscle metabolism and derived from the cyclic use of phosphocreatine—the muscle energy store—resulting in the production of inorganic phosphate and creatine that degrades into creatinine.
In the resting animal, this process occurs at a relatively constant rate. The absolute muscle mass and level of physical activity may influence the rate of creatinine production and thus the serum concentration. Starvation, with loss of muscle mass, may result in a slightly reduced serum creatinine level, whereas serum creatinine may be slightly higher in muscular, athletic individuals compared with sedentary animals. Creatinine is distributed throughout the body water and is not reused. Creatinine is normally excreted by the kidneys, primarily by glomerular filtration, and is not normally reabsorbed in the tubules. In azotemic patients a substantial part of creatinine is metabolized and excreted by nonrenal routes. Serum or urine creatinine concentrations determined by the standard alkaline picrate reaction may be falsely elevated by the presence of noncreatinine chromogenic compounds in the serum. These chromogens include glucose, fructose, ascorbic acid, hippuric acid, urea, ketones, cephalosporins, amino acids, and several other compounds. The contribution of these compounds can be reduced or eliminated, and most automated chemical laboratories use such methodology. However, if inappropriately high creatinine is reported in patients without other evidence of renal failure, the method of creatinine measurement should be ascertained.The serum creatinine concentration provides a crude measure of the glomerular filtration rate. However, serum creatinine, like BUN, is not a sensitive or early indicator of changes in renal function. Alterations in renal blood flow caused by decreases in effective circulating fluid volume (hypovolemia) produce an elevation in serum creatinine and BUN; this can be considered a prerenal azotemia (Box 22.21).
It occurs with some frequency in animals with acute enteritis, peritonitis, acute heart failure, massive blood loss, and some forms of colic and in horses with exhaustive disease syndrome. An important point is that many of these disorders initiate the release of inflammatory mediators, which may cause renal damage and impaired renal function above and beyond that associated with impaired renal blood flow and hypovolemia. Prerenal azotemia is usually seen in animals that are dehydrated and volume depleted and that have a history of loss or compartmentalization of sodium-containing fluid. Prerenal azotemia often can be marked (creatinine level above 6 mg/dL; 530 μmol/L), but if uncomplicated, it generally responds rapidly to fluid replacement therapy. Urine production, the urine sodium concentration, and the fractional excretion of■ BOX 22.21
■ BOX 22.22
Causes of Elevated Creatinine
Common Causes
Prerenal azotemia
Reduced renal perfusion
Hypovolemia
Congestive heart failure
Dehydration after endurance exercise
Renal azotemia
Acute renal failure
Chronic renal failure
Postrenal azotemia
Urolithiasis
Renal calculi
Ureteral calculi
Urethral calculi
Ruptured bladder
Uncommon Causes
False azotemia
Noncreatinine chromogens in serum or plasma Perirenal abscess
Renal carcinoma
Renal dysgenesis
Carcinoma of the bladder
Postexhaustion multisystemic syndrome in horses Severe exertional rhabdomyolysis with myoglobinuria Severe intravascular hemolysis with hemoglobinuria Intoxication or poisoning
Heavy metal poisoning
Nonsteroidal antiinflammatory drug intoxication Aminoglycoside intoxication
sodium are usually low, and the urine specific gravity is usually elevated. The ratio of urine to plasma urea or creatinine, as well as the urine-to-plasma ratio of osmolality, is reported to be higher in horses with prerenal azotemia compared with renal azotemia.31 In ruminants, creatinine is a more reliable indicator of renal failure than is BUN.
Urea nitrogen can be secreted in saliva and metabolized by the ruminal microflora; this frequently results in a disparity between BUN and creatinine levels in ruminants with renal failure.Although small increases in creatinine may be seen with progressively compromised renal function, nearly two thirds to three fourths of the nephrons must be nonfunctional before the serum creatinine level clearly exceeds the normal range. Both ARF and CRF are usually associated with elevated creatinine. ARF, especially in animals with anuria or oliguria, is usually associated with progressive daily changes in blood parameters. In contrast, blood parameters of animals with CRF tend to remain relatively constant. A transient but markedly elevated serum creatinine has been observed in some newborn foals that have no other evidence of compromised renal function. Many of these foals are born to mares that had medical problems before parturition. Alterations in placental function may allow the accumulation of creatinine in the foal's circulation. This is called spurious hypercreatinemia in foals, and the exact mechanism for this to date is not elucidated. In most of these otherwise normal foals, this marked elevation in serum creatinine resolves within the first few days of life; but usually fluid therapy has been used to help resolve it. There is no clinical significance to decreased serum creatinine levels.