Tissue and plasma aldosterone levels in CKD. Besides multiple factors stimulating aldosterone synthesis and release, novel mechanisms contribute to the elevated aldosterone levels in CKD. Impaired renal function is associated with reduced aldosterone excretion  and acid retention, the latter causing enhanced aldosterone production [27, 28]. Furthermore, the expression of CYP11B2, an aldosterone-producing enzyme, in the adipose tissue of 5/6-nephrectomized rats is upregulated, resulting in increased tissue aldosterone content . Finally, the continued use of ACE inhibitors or ARB may cause paradoxical increases in plasma aldosterone concentrations through aldosterone breakthrough phenomenon [32, 33]. These mechanisms would act in concert to elevate plasma aldosterone concentrations as renal function declines. The schematic bar graphs and line graphs depicted therein are constructed de novo from Hosoya et al.