The strength and consistency of relationships between spe- cific isosmolar or low-osmolar agents and contrast-induced nephropathy or renal failure are insufficient for selection of low-osmolar and isosmolar media. Limitation of the risk of contrast-induced nephropathy is based on reduced contrast and adequate hydration.661 A recent meta-analysis of 5 RCTs evaluated 1453 patients with NSTE-ACS and CKD, all with GFR <60 mL per min- Patients were analyzed according to baseline renal function: stage 3a, 3b, and 4 to 5. An invasive strategy was associated with a nonsignificant reduction in all-cause mortality and the composite of death or nonfatal MI. An early invasive strategy in patients with CKD and ACS reduced rehospitalization and resulted in a trend toward lower mortal- ity and nonfatal reinfarction. The increased risk of mortality associated with mild, moderate, and severe CKD is evident across studies, and risks are increased as the gradient of renal See Online Data Supplement 29 for additional information on CKD. 7.6.1. Antiplatelet Therapy Patients with CKD with ACS are at increased risk for isch- emic complications, including stent thrombosis and post PCI ischemic events.663 They are also predisposed to higher bleeding complications, which, in addition to the lack of clinical trial data, result in their undertreatment with anti- platelet therapy. Patients with advanced CKD exhibit high residual platelet reactivity despite treatment with clopi- dogrel independent of the presence of diabetes mellitus.664 Hyporesponsiveness to thienopyridines is associated with increased adverse cardiovascular outcomes, including car- and higher dosing regimens of clopidogrel do not appear to further suppress adenosine diphosphate-induced platelet aggregation.664,666 Although prasugrel may be more efficient than doubling the dose of clopidogrel in achieving adequate platelet inhi- no clinical studies have demonstrated its efficacy in patients with CKD with ACS. 