Systems biology of diuretic resistance

Abstract

Diuretics are commonly used to treat hypertension and extracellular fluid volume expansion. However, the development of compensatory responses in the kidney limits the benefit of this class of drugs. In this issue of the JCI, Grimm and colleagues use a systems biology approach in mice lacking the kinase SPAK and unravel a complex mechanism that explains thiazide diuretic resistance. The overall process involves interactions among six different cell types in the kidney.

Figure 1. Compensation for Na-Cl transport loss in the DCT involves changes in multiple renal cell types.

Using a systems biology approach, Grimm and colleagues (1) concluded that multiple renal cell types are involved in the compensatory response to thiazides. The identified cell types include DCT cells (green), α-ICs (gray), CNT cells, CCD PCs (CNT cells and CCD PCs, coral), PT cells (yellow), and β-ICs (blue). Together, adaptive responses in these cells coordinate an integrated compensatory network in the kidney. See ref. for details. ECF, extracellular fluid.