Kidney calling lung and call back: how organs talk to each other.

Midkine (MK) is a retinoic acid-inducible heparin-binding growth factor involved in developmental and regeneration processes (e.g. vasculogenesis, proliferation, neurite outgrowth), but apparently also in inflammation (e.g. fibrinolysis, chemokine production, leucocyte migration) [1]. In [2] Hobo et al. show that hypertension and kidney injury that follow 5/6 nephrectomy are mediated by midkine through the activation of the renin–angiotensin system (RAS). Intriguingly, the only organ in which 5/6 nephrectomy caused upregulation of angiotensin-converting enzyme (ACE) gene and protein expression as well as enzyme activity was the lung. Midkine-deficient mice showed no upregulation of pulmonary ACE and were largely protected from hypertension and severe renal damage. Chronic administration of recombinant midkine to the MK−/− mice restored hypertension and the increased pulmonary ACE expression seen after 5/6 nephrectomy. The authors provide evidence for a chain of events: the kidney communicates with the lungs via midkine; expression of ACE in lung microvascular endothelial cells is enhanced; this in turn promotes angiotensin-II-mediated hypertension and renal damage independent of the hypertension (Figure 1). These data identify midkine as a novel regulator of the RAS (at least in mice) and provide evidence for an interorgan crosstalk in the pathogenesis of angiotensin-II-mediated renal damage.