Clinical Note

Creatinine Balance and the Plasma Creatinine Concentration

Consider the following hypothetical and idealized example to understand why a patient with reduced renal function remains in creatinine balance, but with a higher plasma creatinine concentration.

An 80-kg patient has a normal metabolism and diet and produces 1.8 g of creatinine per day. He then undergoes a uninephrectomy to remove a renal carcinoma. Presume that after the uninephrectomy the function of his remaining kidney is unchanged with one half of his normal total (two-kidney) GFR, and that his metabolism and diet also remain unchanged.

• How is body creatinine balance normally maintained so that the total body creatinine and plasma creatinine concentration remain unchanged from day to day?

• If, before the uninephrectomy, the patient had a plasma creatinine concentration of 1.0 mg/ dL, what was his GFR?

• What is the patient's rate of creatinine excretion immediately after removal of the other kidney and why?

• What happens to the plasma creatinine concentration in the hours immediately after surgery?

• When is a new steady state of creatinine balance achieved, and what are the plasma creatinine concentration and the daily rate of creatinine excretion at this new steady state? These questions relate to the normal renal handling of creatinine, the necessary equality of production and excretion in the steady state, and the effect of the GFR on the plasma creatinine concentration. Because creatinine is assumed to be neither reabsorbed nor secreted, creatinine excretion is equal to the rate of filtration. The rate of creatinine production depends on the rate of turnover of endogenous muscle and that in the diet, and is relatively constant on a fixed diet unless the individual is in a markedly anabolic or catabolic state.

If the excretion of creatinine is decreased by a fall in GFR, the plasma creatinine concentration will rise rapidly. This can be appreciated semi-quantitatively by considering that retention of one day's production of creatinine (1.8 g), which would distribute primarily in the extracellular volume compartment (~15 L in this person), would raise the plasma creatinine concentration by about 12 mg/dL. In other words, even if the GFR decreases abruptly, there is only a short transient period during which the rate of production exceeds the rate of excretion. The resulting rise in plasma creatinine concentration causes a proportional increase in filtration and thus in excretion until a new steady state is achieved with an elevated plasma creatinine concentration.

It is important to understand that partial renal failure does not mean that the rate of excretion of solutes is chronically less than the rate of ingestion or production. Rather, the patient reaches a new steady state but one that is not normal or optimal. Only when the renal disease reaches end stage is it no longer possible to achieve a steady state, leading to death in the absence of intervention.

Here are the answers to the questions:

• The rate of filtration of creatinine (= GFR • Pcr) is equal to the rate of excretion of creatinine (= UF • Ucr), which is equal to the rate of production = ~1.8 g/day; thus, the GFR can be calculated to be ~180 L/day.

• Immediately after uninephrectomy, the rate of excretion is one-half normal, or ~0.9 g/day.

• Because the rate of filtration and thus the rate of excretion is less than the rate of production initially, the Pcr rises.

• A new steady state is achieved when the rate of filtration of creatinine again becomes equal to the rate of production of creatinine, that is, when:

determination. A higher-than-normal plasma creatinine concentration can be due to abnormal rates of production (e.g., catabolic processes associated with an underlying disease or excessive meat intake) or even to lab error. Similarly, a low plasma creatinine concentration can sometimes be observed in the severely ill or fasting patient (e.g., a patient who has been unable to eat or retain food because of gastrointestinal problems). For these reasons, the plasma creatinine concentration or BUN must be regarded with thoughtful interpretation in trying to estimate renal function and the patient's GFR. Although an elevated plasma creatinine concentration and BUN in a routine blood sample are indicators of deficient renal function that should be followed up immediately, these parameters are best used to follow the progress of renal disease in the relatively stable patient, rather than as quantitative estimates of GFR in an acute illness.

Suggested Reading

Levinsky NG, Lieberthal W. Clearance techniques. In Windhager EE, ed. Handbook of Physiology, Section 8: Renal Physiology, Vol I. New York: Oxford, 1992, pp 226-247. Rose BD Rennke HG. Renal pathophysiology—the essentials.

Baltimore: Williams & Wilkins, 1994. Schuster VL, Seldin DW. Renal clearance. In Seldin DW, Giebisch G, eds. The kidney: Physiology and pathophysiology, Vol 1, 2nd ed. New York: Raven Press, 1992, pp 943-997.

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