Evidence for shrunken pore syndrome in children.

The link between cystatin C and mortality independent of glomerular filtration rate (GFR) in adults has prompted the "Shrunken Pore Syndrome" (SPS) hypothesis, where high serum cystatin C with normal creatinine is explained by smaller glomerular pores, through which creatinine can pass freely, while the larger cystatin C, beta-trace protein (BTP) and pro-inflammatory molecules are retained. This study set out to apply the definition of SPS to children. In 294 children who underwent inulin clearance (Cin) test, serum creatinine, cystatin C and BTP were measured. For all three markers eGFR_x was calculated using the full age spectrum equations. The ratio eGFR_cys/eGFR_crea was plotted against the error of eGFR_BTP(%) (i.e. eGFR_BTP-Cin)/Cin*100%). Patients with and without SPS according to different cut-off points of eGFRcys/eGFRcrea and eGFR_cys/Cin (i.e. ≤0.6,0.7,0.8) were compared in terms of eGFR_x, Cin, error of eGFRx(%) and eGFR_BTP/eGFR_crea-ratio. The ratio eGFR_cys/eGFR_crea and error of eGFR_BTP(%) were positively correlated. The prevalence of SPS by eGFR_cys/eGFR_crea with a cut-off of 0.6 was 4.8%. Patients with SPS had a more negative error of eGFR_cys(%) and eGFR_BTP(%) and higher Cin regardless of the definition. Overestimation of eGFR_crea in patients with SPS was only present when using the eGFR_cys/eGFR_crea rather than the eGFR_cys/Cin definition. Cystatin C and BTP are related independent of creatinine, suggesting glomerular pore size as a common denominator. The prevalence of SPS in children is comparable to adults. For research in SPS, a definition based on eGFR_cys/exogenous clearance study may be useful to study the effect of SPS on creatinine metabolism.

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