An initial challenge for determining the effect of renal insufficiency on heart failure therapy is the inconsistent definitions of renal insufficiency. Measuring GFR is expensive, time-consuming, and cumbersome and requires a radiolabeled isotope. Serum creatinine levels have been commonly used in research studies and clinical practice; however, they are insensitive markers for renal insufficiency, and they have a nonlinear association with GFR that varies by age, sex, race, and lean body mass. Rather than rely on the serum creatinine levels, clinicians should estimate renal function by using either the Cockcroft–Gault equation [(140 − age) × body weight (kg) × 0.85 if female]/[72 × serum creatinine level (mg/dL)] or the Modification of Diet in Renal Disease formula (6 - 7). A panel convened by the National Kidney Foundation defined moderate renal insufficiency as a GFR of 30 to 60 mL/min per 1.73 m2, severe renal insufficiency as a GFR of 15 to 30 mL/min per 1.73 m2, and kidney failure as a GFR less than 15 mL/min per 1.73 m2(8). I use these definitions through the remainder of this paper.