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Limitations of creatinine as a filtration marker in glomerulopathic patients
Insights
Creatinine overestimates kidney function in glomerular disease because remnant tubules secrete more of it as the disease progresses. True filtration markers are more reliable for assessing glomerular filtration rate (GFR).
Area of Science:
- Nephrology
- Renal Physiology
- Diagnostic Markers
Background:
- Creatinine is a commonly used marker for estimating glomerular filtration rate (GFR).
- However, its accuracy in patients with glomerular diseases is questionable due to potential tubular secretion.
- Reliable GFR assessment is crucial for managing kidney diseases.
Purpose of the Study:
- To evaluate the reliability of creatinine as a GFR marker in patients with various glomerular diseases.
- To compare creatinine clearance with the clearance of true filtration markers of different sizes.
- To investigate the impact of tubular secretion on creatinine's GFR estimation.
Main Methods:
- Simultaneous clearance measurements of creatinine, inulin, 99mTc-DTPA, and dextran in 171 patients.
- Assessment of fractional clearance relative to inulin.
- Administration of cimetidine to block tubular creatinine secretion.
- Longitudinal study of patients with deteriorating or remitting glomerular disease.
Main Results:
- Fractional clearance of true filtration markers (99mTc-DTPA, dextran) relative to inulin did not differ from unity.
- Fractional clearance of creatinine significantly exceeded unity (1.64 +/- 0.05), indicating hypersecretion.
- Tubular secretion of creatinine was reduced by cimetidine, bringing its clearance closer to unity.
- Fractional creatinine secretion varied inversely with GFR, worsening as the disease progressed.
- Changes in creatinine clearance relative to inulin were blunted or imperceptible in longitudinal studies.
Conclusions:
- True filtration markers (inulin, DTPA, dextran) with radii < 20 A are reliable in glomerular disease.
- Creatinine is progressively hypersecreted by remnant renal tubules as glomerular disease worsens.
- Using creatinine to evaluate or monitor glomerulopathic patients leads to significant and unpredictable overestimations of GFR.
Abstract:
To determine the reliability of creatinine as a measure of the glomerular filtration rate (GFR), we compared the simultaneous clearance of creatinine to that of three true filtration markers of graded size in 171 patients with various glomerular diseases. Using inulin (radius [rs] = 15 A) as a reference marker, we found that the fractional clearance of 99mTc-DTPA (rs = 4 A) was 1.02 +/- 0.14, while that of a 19 A rs dextran was 0.98 +/- 0.13, with neither value differing from unity. In contrast, the fractional clearance (relative to inulin) of creatinine (rs = 3 A) exceeded unity, averaging 1.64 +/- 0.05 (P less than 0.001), but could be lowered towards unity by acute blockade of tubular creatinine secretion by IV cimetidine. Cross-sectional analysis of all 171 patients revealed fractional creatinine secretion to vary inversely with GFR. This inverse relationship was confirmed also among individual patients with either deteriorating (N = 28) or remitting (N = 26) glomerular disease, who were studied longitudinally. As a result, changes in creatinine relative to inulin clearance were blunted considerably or even imperceptible. We conclude that true filtration markers with rs less than 20 A, including inulin, are unrestricted in glomerular disease, and that creatinine is hypersecreted progressively by remnant renal tubules as the disease worsens. Accordingly, attempts to use creatinine as a marker with which to evaluate or monitor glomerulopathic patients will result in gross and unpredictable overestimates of the GFR.