Worsening Renal Function Defined as an Absolute Increase in Serum Creatinine Is a Biased Metric for the Study of Cardio-Renal Interactions

Abstract

Objectives: Worsening renal function (WRF) during the treatment of decompensated heart failure, frequently defined as an absolute increase in serum creatinine ≧0.3 mg/dl, has been reported as a strong adverse prognostic factor in several studies. We hypothesized that this definition of WRF is biased by baseline renal function secondary to the exponential relationship between creatinine and renal function. Methods: We reviewed consecutive admissions with a discharge diagnosis of heart failure. An increase in creatinine ≧0.3 mg/dl (WRF_CREAT) was compared to a decrease in GFR ≧20% (WRF_GFR). Results: Overall, 993 admissions met eligibility. WRF_CREAT occurred in 31.5% and WRF_GFR in 32.7%. WRF_CREAT and WRF_GFR had opposing relationships with baseline renal function (OR = 1.9 vs. OR = 0.51, respectively, p < 0.001). Both definitions had similar unadjusted associations with death at 30 days [WRF_GFR OR = 2.3 (95% CI 1.1–4.8), p = 0.026; WRF_CREAT OR = 2.1 (95% CI 1.0–4.4), p = 0.047]. Controlling for baseline renal insufficiency, WRF_GFR added incrementally in the prediction of mortality (p = 0.009); however, WRF_CREAT did not (p = 0.11). Conclusions: WRF, defined as an absolute change in serum creatinine, is heavily biased by baseline renal function. An alternative definition of WRF should be considered for future studies of cardio-renal interactions.