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Impaired kidney function is also associated with increased IGFBP levels (e.g., IGFBP-1, -2, -3, -4, and -6) (75, 77) and IGFBP-3 protease activity, which subsequently increases low-molecular-weight IGFBP-3 fragments (78), most likely due to a compromised renal IGFBP-clearance ( Figure 4 )