The Promise of next generation sequencing micro RNA for the discovery of new targets in contrast induced acute kidney injury

Ayman Haq, Peter A. McCullough


Contrast induced acute kidney injury (CI-AKI) is defined by KDIGO as an increase in serum creatinine by 1.5 times within 7 days of exposure to contrast, a serum creatinine increase of 0.3 mg/dL or a urine output less than 0.5 mL/kg of body weight for at least 6 h following iodinated contrast exposure (1). Patients with pre-existing renal disease are at greatest risk for developing CI-AKI. Its pathogenesis is thought to be multifactorial. Contrast initially causes nitric oxide mediated vasodilation of renal vasculature. This is followed by intrarenal vasoconstriction that persists for several hours causing ischemia, particularly in the outer medulla where the oxygen tension is lower than that of many tissues (2). As it is water soluble, contrast is freely filtered by the glomerulus with little alteration of podocyte or filtration barrier function. However, it is taken up by proximal tubular cells and results in cellular dysfunction and apoptosis. The contrast also permeates into the tubulointerstitial space leading to the loss of cellular architecture. Tubular epithelial cells slough off into the tubular space, thus reducing the clearance of contrast and promoting its deleterious effects. The cellular damage also results in the formation of reactive oxygen species which perpetuate cellular injury. Since the glomerulus is relatively unaffected, the reduction in glomerular filtration and rise in serum creatinine associated with CI-AKI is mediated by tubuloglomerular feedback and occurs well after the renal parenchyma has been injured (3). However, the exact mechanism of CI-AKI remains unclear and no definitive therapy has been established.