An elevation in the serum creatinine concentration (SCr) usually reflects a reduction in the glomerular filtration rate and is associated with a concomitant rise in the blood urea nitrogen (BUN). (See "Assessment of kidney function".)
There are, however, a variety of settings in which the SCr can increase acutely independent of the GFR, and therefore, in which there is no true change in overall kidney function. This may be due to one of three factors: decreased creatinine secretion; interference with the serum assay; or enhanced creatinine production.
In normal subjects, approximately 15 percent of the urinary creatinine is derived from secretion in the proximal tubule. This value can rise to as high as 50 percent in patients with advanced kidney disease and accounts for the overestimation of the true GFR by the creatinine clearance . (See "Calculation of the creatinine clearance".)
Creatinine is an organic cation in the physiologic pH range and is secreted by the organic cation secretory pump that can be inhibited by other organic cations. Commonly used drugs that can interfere with creatinine secretion and, therefore, result in a self-limited and reversible rise in the SCr by as much as 0.4 to 0.5 mg/dL (35 to 44 micromol/L) without changing the true GFR include:
- The antimicrobial trimethoprim (which is most often given in combination with sulfamethoxazole) .
- The antiarrhythmic drug dronedarone (which is used in some patients with atrial fibrillation) .
- The H2-blocker cimetidine [4,5]. Ranitidine and famotidine, which are other commonly used H2-blockers, have a much less prominent effect on creatinine handling .
The effect of cimetidine has been used clinically to improve the accuracy of the creatinine clearance [4,6,7]. By competitively inhibiting creatinine secretion, the creatinine clearance becomes a more accurate measure of the true glomerular filtration rate. (See "Calculation of the creatinine clearance".)
- Tenofovir disoproxil fumarate (TDF), a drug used to treat chronic hepatitis B infection and HIV infection, has been reported to acutely increase the serum creatinine, thereby decreasing the estimated GFR. It is not clear whether this is due to an effect on creatinine secretion or on filtration [8-11]. There is no direct evidence that TDF inhibits creatinine secretion.