Amiloride Reduces Urokinase/Plasminogen-Driven Intratubular Complement Activation in Glomerular Proteinuria

What is it about?

Kidney disease is often accompanied by defect filtration barrier such that proteins from blood plasma passes through and are excreted in urine. This leads to an accelerated decline in kidney function, but the mechanisms are unknown. We show that a protein from the coagulation system, plasmin, at early stages of urine formation activates components from the immune system, complement. This generates molecules that promote inflammation and injury from inside the tubular system. We demonstrate that this can be mitigated by an old drug, the diuretic amiloride. Together the study shows a new mechanism for kidney injury and how it can be treated by repurposing a known drug.

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