Blood urea nitrogen is independently associated with renal outcomes in Japanese patients with stage 3-5 chronic kidney disease: A prospective observational study

Background: Blood urea nitrogen (BUN) is one of the substances that affects the calculated serum osmolality (cSosm). A previous study demonstrated that BUN and cSosm were independently associated with the development of chronic kidney disease (CKD) in patients with preserved kidney function. In advanced CKD stages, there is a concomitant increase in cSosm and BUN levels. However, it remains unclear whether BUN or cSosm levels are related to renal outcomes in patients with moderate to severe kidney dysfunction. The aim of this study was to clarify whether the BUN or cSosm level is associated with kidney disease progression in patients with advanced CKD. Methods: In this prospective study, we enrolled 459 patients with CKD (stages 3-5). The composite renal endpoint was end-stage renal disease (ESRD) or death, and ESRD alone was added as an alternative outcome. A Cox proportional hazards model was utilized to determine the risk factors for a poor renal outcome. We adjusted for covariates including estimated glomerular filtration rate (eGFR). The cSosm (mOsm/kg) was calculated using the following formula: (2 × sodium) + (BUN/2.8) + (glucose/18). Results: During a median follow-up of 25.8 months, the renal endpoint was observed in 210 patients. Multivariable Cox analysis determined the hazard ratio (HR) [95% confidence interval (CI)] for the composite renal outcome in the second, third, and fourth BUN quartiles were 1.36 (0.72-2.58), 1.87 (0.95-3.66), and 2.66 (1.23-5.76) (P for trend < 0.01), respectively compared with the first BUN quartile. Conversely, by multivariable Cox analysis, the HRs (95% CIs) for poor outcomes in the second, third, and fourth cSosm quartiles, compared with the first cSosm quartile, were 1.13 (0.69-1.87), 0.95 (0.58-1.55), and 1.26 (0.78-2.03), respectively (P for trend = 0.39). In addition, with regard to the renal outcome of ESRD alone, higher BUN quartiles had a significantly increased risk for the outcome, but cSosm levels were not associated with the outcome. Conclusions: Higher BUN levels, but not cSosm levels, were associated with adverse renal outcomes independent of the eGFR, suggesting that BUN may be a useful marker for predicting kidney disease progression.