1 Department of Internal Medicine 2 Laboratory of Biochemistry, University Hospital, University of Ioannina, Medical School Ioannina, Greece
Sir,
We read with great interest the recently published letter by Lipscombe and Bargman [1] concerning the impact of various fibric acid derivatives on renal function. In a previous comment [2], we reported an increase in serum urea and creatinine levels induced by fenofibrate and ciprofibrate administration. On the contrary, no significant changes were observed in a gemfibrozil group but the sample size was not large enough to draw firm conclusions. To extend these observations, we prospectively evaluated the effect of gemfibrozil (600 mg bid for 8 weeks) on serum urea and creatinine levels in 30 hyperlipidemic patients attending the Outpatient Lipid Clinic of the University Hospital of Ioannina. In agreement with previously published results [2,3], no significant changes were observed in either serum urea (from 35.2±10.5 to 37.5±17.2 mg/dl) or creatinine levels (from 1.13±0.42 to 1.17±0.47 mg/dl) after gemfibrozil administration.
In their letter [1], Lipscombe and Bargman reported on the development of renal dysfunction in patients treated with fibric acid derivatives. However, an important point is how renal dysfunction was defined. According to some investigators, the increase in serum creatinine levels induced by fibrates does not represent a real deterioration in renal function since other more precise estimators of GFR (as PAH and inulin clearances) remain unaffected [4]. On the other hand, it should be mentioned that fibrates may increase both serum creatinine and homocysteine levels [5]. It has been speculated that the fibrate-induced deterioration in renal function could be responsible for the observed increase in homocysteine values. We believe that further studies are needed to determine whether this increase in creatinine levels induced by fibrates is a class effect or a characteristic of some particular members of this class. More importantly, the reliability of serum creatinine as a marker of renal function in patients receiving fibric acid derivatives should be established.
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Toronto General Hospital, Toronto, Canada
Sir,
We would like to thank Dr Tsimihodimos and colleagues for their comments. Within our cohort of patients published in the original article [1], three of our patients had an increase in serum creatinine on gemfibrozil therapy. Two of these three patients were also challenged with fenofibrate and had a similar increase in their serum creatinine. Therefore, we suspect that gemfibrozil can produce a transient increase in serum creatinine similar to that reported for other fibrates. Furthermore, since the fibrate effect on renal function appears to be uncommon and idiosyncratic, it is not surprising that there was no change in mean serum creatinine averaged over 30 hyperlipidemic patients with near-normal renal function attending Dr Tsimihodimos and colleagues' outpatient lipid clinic.
With respect to whether the increase in serum creatinine really does reflect a decrement in glomerular filtration rate, as stated in our paper, we do not have PAH or inulin clearances. Certainly, in the patients for whom urinalysis was performed, there was nothing to suggest the development of acute tubular necrosis or interstitial nephritis. The urinalyses were routinely bland. However, a subset of patients also had serum urea measurements performed and these showed a similar elevation and a return to baseline after the drug was discontinued. Therefore, if this is simply a laboratory effect, it must be affecting both creatinine and urea concentrations. Otherwise, one has to postulate that the rising creatinine and urea truly reflects a fall in glomerular filtration rate. The potential mechanisms have been discussed in our paper [1].
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