Creatinine: an inadequate filtration marker in glomerular diseases

The exaggerated clearance (C) of creatinine relative to inulin in patients with renal disease has been attributed to (1) increased tubular creatinine secretion (TS_creatinine) and (2) reduced inulin filtration due to restricted transglomerular inulin transport. In an attempt to gain further insight into the disparate clearances of these commonly employed markers of glomerular filtration, we performed simultaneous clearance studies of creatinine (Einstein-Stokes radius (ESR) = 3 Å, inulin ESR = 14 Å and dextran fractions with ESR = 16 ? 24 Å) in seven normal subjects, 10 patients with cardiac failure and 38 subjects with the nephrotic syndrome. Notwithstanding equivalent depression of mean C_inulin to 47 ± 6 and 42 ± 5 ml/min/1.73 m² in cardiac and nephrotic subjects, respectively, C_creatinine: C_inulin was more increased in the latter (1.70 ± 0.11 versus 1.22 ± 0.14, p < 0.01). In contrast, for dextran molecules with ESR = 16 and 18 Å, C_dextran: C_inulin was not significantly different from unity in all three experimental groups. This suggests that uncharged polysaccharides with ESR < 20Å, including inulin, are freely filtered by normal and pathologic glomeruli and that intrinsic glomerular damage is associated with relatively increased TS_creatinine, thus accounting for the increase of C_creatinine above C_inulin in patients with the nephrotic syndrome.