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Letters |
1
Dept. of Physiol.,
2
Cardiovasc. Res. Inst. (CARIM),
3
Dept. of Nephrol., Med. School of Bialystok, 15–230 Bialystok, Poland, Univ. of Limburg, P.O. Box 616, 6200 MD Maastricht, The Netherlands
a Author for correspondence.
To the Editor:
The soluble cytoplasm of most cells contains low-molecular-mass (14–15 kDa) proteins able to bind long-chain unesterified fatty acids. Of these so-called fatty acid-binding proteins (FABP), nine different types have been identified (1)(2). Heart and skeletal muscles contain the same type of FABP [referred to as heart-type (H)-FABP] (1)(2), but its concentration in the heart is severalfold higher than that in the skeletal muscles (3). The concentration of FABP in the plasma of healthy persons is relatively low (2–6 µg · L-1) (4). FABP is released from the heart early after the onset of infarction, whereafter its plasma concentration increases manyfold (3)(4)(5)(6). Increased excretion of FABP in urine also occurs after infarction (5)(7). Several recent studies indicate the usefulness of the plasma FABP concentration as an early biochemical marker for myocardial infarction diagnosis (3)(5)(7). However, to interpret properly the values of plasma FABP concentration, one has to take into account not only its source and rate of release into plasma but also its elimination from plasma. It is obvious that any change in the clearance rate of FABP would affect its plasma concentration, and thus may lead to erroneous interpretation. Kleine et al. (8) reported a patient with acute myocardial infarction and severe renal insufficiency in whom the plasma FABP concentration remained increased for the whole course of blood sampling (25 h after the infarction), whereas in patients with normal kidney function it normalized in ~10 h after the infarction. Unfortunately, preinfarction data on plasma FABP in this patient were not available. Low-molecular-mass proteins such as FABP and myoglobin are cleared mostly by the kidney (9)(10). As it remains an open question whether, and, if so, to what extent an insufficiency of the kidneys affects the plasma FABP concentration in patients with heart and skeletal muscles intact, we studied plasma FABP and myoglobin in patients with chronic renal failure.
Blood samples were obtained from 15 blood donors (males) and 27 chronically hemodialyzed patients with renal failure (18 males, 9 females, ages 17–66 years; period of dialysis 2–70 months). Their primary renal diseases were: chronic glomerulonephritis (n = 14), interstitial nephritis (n = 2), acute renal failure (n = 3), adult dominant polycystic kidney disease (n = 3), hypertensive nephropathy (n = 3), diabetes mellitus (n = 1), and amyloidosis (n = 1). The patients were clinically stable and free of any severe intercurrent illnesses. They had no clinical evidence of severe secondary hyperparathyroidism. Hemodialysis was performed three times a week with the double needle technique, with cuprophane capillary dialyzers, and with bicarbonate as buffer in the dialysate. The membrane allows the passage of low-molecular-mass solutes up to ~2 kDa. Vascular access was in all cases a Cimino-Brescia arteriovenous fistula. Blood samples were obtained immediately before and after dialysis.
Plasma FABP concentration was measured by a sensitive noncompetitive sandwich ELISA (4). Plasma concentration of myoglobin was measured with a turbidimetric immunoassay (Unimate 3 MYO; Roche Diagnostic Systems, Basel, Switzerland) on a Cobas Mira Plus analyzer (Roche). The concentrations of urea and creatinine in plasma were measured by the urease method and Jaffe reaction, respectively.
The significance of the differences between the means was evaluated statistically by unpaired and paired Student t-tests, where appropriate. Correlations between plasma FABP and (or) myoglobin concentrations and the period of dialysis, and plasma urea and creatinine concentrations were determined by Pearson product–moment correlation, and the level of significance was taken at P <0.05.
Plasma creatinine and urea concentrations were high before dialysis and
dropped markedly after dialysis (Table 1
). The mean plasma concentration of FABP in the uremic patients
before and after dialysis was 21 and 25 times higher, respectively,
than that in the blood donors. The mean plasma myoglobin concentration
in the uremic patients before and after dialysis was 3.7 and 4.0 times
higher, respectively, than that in the blood donors. The insignificant
increase in plasma concentrations of FABP and myoglobin after dialysis
may reflect removal of blood water during dialysis. In the patients,
before dialysis the mean myoglobin/FABP ratio was five times lower than
in the donors, and after dialysis six times lower (Table 1
). Neither
plasma FABP nor plasma myoglobin concentrations showed a correlation
with the period of dialysis or urea or creatinine concentration in
plasma.
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The present data are the first to show that plasma FABP concentration is markedly increased in patients with chronic renal failure and normal heart function, similar to that found for myoglobin (11). It is clear that a certain amount of each protein must be constantly removed either by the kidney or by other tissues, thus preventing progressive increase in the concentration with time of renal failure. Interestingly, the plasma FABP concentration is much higher (20–25 fold) than that of myoglobin (fourfold) despite the fact that these proteins have similar molecular masses (15 and 18 kDa, respectively) and show a similar plasma release curve in patients with acute myocardial infarction and normal renal function (3). These findings suggest that the kidneys play a more dominant role in the clearance of plasma FABP than of myoglobin.
The ratio of the concentrations of myoglobin over that of FABP is lower in the heart (ratio ~5) than in skeletal muscles (20–70, depending on muscle type) (3). The use of the ratio of the plasma concentrations of myoglobin over that of FABP to discriminate between heart and skeletal muscle tissue injury has been suggested (3). Because of the relatively longer increase in plasma FABP compared with myoglobin, the ratio calculated for uremic patients (~3) is similar to that found in patients after heart infarction. Thus, with respect to the discrimination of myocardial from skeletal muscle injury, the decrease of the ratio in chronic renal failure indicates the limitation of the use of this ratio for this purpose.
Serial monitoring of the plasma FABP concentration can also be used to estimate infarct size (6). However, our results indicate that if the myocardial infarction occurred in a patient with chronic renal failure, the plasma FABP concentration would be relatively higher than in a patient with intact kidneys, thus leading to overestimation of infarct size. Since preinfarct values differ widely among patients, a judgment about infarct size cannot be made.
In conclusion, our data indicate that in patients with chronic renal failure the plasma concentrations of the biochemical markers FABP and myoglobin each are markedly increased. Thus, caution must be taken when using these marker proteins for early diagnosis of myocardial infarction, in case of renal insufficiency, as the preinfarct plasma concentration is very likely to be already high.
Acknowledgments
We thank M. Pelsers for expert technical assistance. This work was supported by the Polish State Research Committee, project number 6 P20705607 and the European Community, grant CIPD CT. 940273.
References
The following articles in journals at HighWire Press have cited this article:
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  C. J. McCann, B. M. Glover, I. B.A. Menown, M. J. Moore, J. McEneny, C. G. Owens, B. Smith, P. C. Sharpe, I. S. Young, and J. A. Adgey Novel biomarkers in early diagnosis of acute myocardial infarction compared with cardiac troponin T Eur. Heart J., December 1, 2008; 29(23): 2843 - 2850. [Abstract] [Full Text] [PDF]
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