Blood Urea Nitrogen and Serum Creatinine
Not Married in Heart Failure
Klein and colleagues1 have retrospectively analyzed results derived from the prospective, randomized Outcomes of a Prospective Trial of Intravenous Milrinone for Exacerbations of Chronic Heart Failure (OPTIME-CHF) study and contribute an interesting article to this inaugural issue of Circulation: Heart Failure. Their analysis provides further evidence that the level of renal function in patients with worsening heart failure and impaired systolic function is an important predictor of rehospitalization for cardiovascular events and death within 60 days of discharge. Renal function was assessed at admission. Change during hospitalization was recorded for blood urea nitrogen (BUN) and estimated glomerular filtration rate (GFR). Estimated GFR was calculated with the 4-variable equation of the Modification of Diet in Renal Disease study, which depends on serum creatinine, age, and sex.2 Of interest, the BUN on admission and change in BUN during the hospital stay (independent of the admission value) was a statistically better predictor of the 60-day death rate and days of rehospitalization than was estimated GFR. Because BUN is affected by protein intake, catabolism, and tubular reabsorption of urea, it is not as reliable an index of renal function as GFR. Thus, this observation by Klein et al1 is of particular interest and deserves explanation.
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Serum creatinine is freely filtered at the glomerulus, not reabsorbed, but undergoes tubular secretion. Thus, creatinine clearance exceeds inulin clearance, the gold standard for GFR. In contrast, urea is freely filtered, not secreted, but is reabsorbed by the renal tubules. This reabsorption of urea is flow dependent so that more urea is reabsorbed at lower urine flow rates (Figure 1).3 Most importantly, the reabsorption of urea in the collecting duct is mediated by the effect of arginine vasopressin (AVP) on the urea transporter in the collecting …