A decreased pore size is not the only possible mechanism leading to SPS and/or reduced estimated GFR from cystatin C versus creatinine, but could potentially result also from a thicker glomerular barrier leading to an increased diffusion length for middle molecules like cystatin C. One of the earliest structural alterations in DKD, preceding microproteinuria, is thickening of the glomerular basal membrane (GBM) (Marshall, 2016), whereas this condition is absent in minimal change disease (MCD). This evidence concerns the gene CST3 and diabetic kidney disease.