Can We Rely on Blood Urea Nitrogen as a Biomarker to Determine When to Initiate Dialysis?

Abstract

The article by Liu et al. in this issue of CJASN is a product of the very productive five-center collaborative effort to study acute kidney injury: The Program to Improve Care in Acute Kidney Disease (PICARD) (1). The authors conclude that “initiation of dialysis at higher BUN [blood urea nitrogen] concentrations was associated with an increased risk for death.” The question of when to initiate dialysis in patients with acute kidney injury (AKI) has been debated for nearly 50 years. Teschan et al. (2), in a landmark paper published in 1960, introduced the concept of “prophylactic hemodialysis.” The rationale and hypothesis that were put forth by these authors were straightforward: Sepsis is a common complication of uremia and often is fatal. If one postulates that uremia contributes to the propensity to develop sepsis, then prophylactic dialysis, by preventing the uremic syndrome, may prevent many of its lethal sequelae. It is interesting to note, however, that prophylactic treatment in this study was defined prospectively as treatment of patients before the nonprotein nitrogen reached 200% (BUN reached 160 mg/dl). In the Teschan study, dialysis was initiated 2 to 3 d after onset of diagnosis of renal failure. Since that time, a number of reports, many retrospective, have addressed this issue of “early versus late” initiation of dialysis, although, as in the Teschan study, many used higher levels of BUN as cutoff levels to define “early” than we would use today. In the studies of Liu et al. and others that address the timing of initiation of dialysis, BUN has been used as the biomarker to define the treatment groups. Urea, discovered in human urine by H.M. Rouelle in 1773, is one of the oldest biomarkers in nephrology. For estimation of renal function, however, urea is suboptimal. The blood urea concentration is affected …