Urea &  Creatinine




What do we learn from the urea and creatinine?

Strangely, there is very little consensus as to what exactly constitutes acute renal failure. In effect, renal function and renal physiologic reserve involves the ability to filter and clear unwanted substances, and to reabsorb essential, though filtered, material. Ideally, we would like to measure the plasma level of a substance that is neither secreted nor reabsorbed by the kidney, measure the urinary concentration and volume, and calculate the clearance of the substance and thus the glomerular filtration rate (GFR). No such substance is readily and inexpensively available. Consequently, physicians have had to “make do” with urea and creatinine.

Urea is produced as a break down product of protein. It is completely filtered by the kidney, but unfortunately is also reabsorbed. Thus urea clearance grossly underestimates GFR. In addition, the amount of urea reabsorbed increases with dehydration.

Creatinine is a metabolic by product of muscle metabolism (it is derived from creatine and phosphocreatine). For the majority of patients the muscle turnover varies little from day to day, and the serum creatinine is more or less constant. Creatinine is filtered and excreted by the kidney. Serum creatinine is probably the most widely used indirect measure of glomerular filtration rate; it is easy and inexpensive to measure. But what about accuracy? Unfortunately, serum creatinine is very insensitive to even substantial declines in glomerular filtration rate. Glomerular filtration rate may be reduced by up to 50% before serum creatinine becomes elevated. This is due to a combination of increased extrarenal metabolism and secretion of this substance by the renal tubules. Creatinine overestimates the GFR. So it is difficult to assess true renal function using serum creatinine. Conventional wisdom relates that a doubling of the serum creatinine is indicative of renal failure.

The other major problem with creatinine in the intensive care unit is that physicians often do not look at the creatinine in the clinical context: a raised serum creatinine is inevitable in any patient involved in trauma, over-exertion, heat stroke or rhabdomyolysis. Moreover, a patient who has been critically ill for some time should have a reduced serum creatinine (due to loss of muscle mass associated with catabolism), a normal looking serum level may actually be indicative of very poor renal function.

The creatinine clearance has been used as a method of overcoming these problems. The most commonly used method of calculation is that of Cockcroft and Gault:

Creatinine (Cr) Clearance ml/min = ((140 - Age) · (Wt))/(72 · Cr), multiply by 0.85 if female.

There are many reasons why this calculation may be inaccurate, including variations in creatinine production from person to person and from time to time. Further, the weight as an index of muscle mass may be inaccurate in obese or edematous (particularly in critical care) patients. A more effective method would be to compare what is in the urine to what is in the serum as a measure of clearance.

The serum creatinine is usually falsely raised by error inherent in measurement. The urinary creatinine is falsely raised by tubular secretion. These errors tend to cancel each other out, so using the following equation will give a reasonably accurate estimate of GFR:

Creatinine (Cr) Clearance = (Urinary Cr (mg/ml) x Urinary Volume) x 100 / Serum Creatinine

The major problem doing this is the 24 hour urinary collection required. A shorter two hour creatinine clearance measurement can be performed, as an alternative.

Finally, the differences in the way the kidneys handle urea and creatinine is of diagnostic value. We know that urea is reabsorbed and creatinine is not. In dehydration (pre-renal syndrome) the ratio of urea to creatinine is elevated (from a factor of 10 to a factor of 20).

In conclusion, if you suspect renal dysfunction, it is worth measuring concentrating capacity (urinary sodium and osmolality) and GFR (creatinine clearance). A consolidated figure, the renal failure index (see table above) may be used as a single score.




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