Department of Internal Medicine, Pusan National University Hospital, Pusan National University College of Medicine, Busan, Korea.
Biomedical Research Institute, Pusan National University Hospital, Busan, Korea.
PLoS One. 2021 Sep 10;16(9):e0257305. doi: 10.1371/journal.pone.0257305. eCollection 2021.
Anemia is a common complication of chronic kidney disease (CKD). Blood urea nitrogen (BUN) in CKD represents nitrogenous uremic toxin accumulation which could be involved in anemia of CKD. We investigated the effects of BUN independent of estimated glomerular filtration rate (eGFR) on anemia in non-dialysis CKD (NDCKD).
This prospective study included 2,196 subjects enrolled in the KoreaN Cohort Study for Outcome in Patients With Chronic Kidney Disease (KNOW-CKD) cohort with BUN and hemoglobin level data. Initially, we investigated the association between BUN and hemoglobin level. To examine the impact of baseline BUN on the incident anemia, a longitudinal study was performed on 1,169 patients without anemia at study enrollment. BUN residuals were obtained from the fitted curve between BUN and eGFR. Anemia was defined as a hemoglobin level of <13.0 g/dL for men and <12.0 g/dL for women.
BUN residuals were not related to eGFR but to daily protein intake (DPI), while BUN was related to both eGFR and DPI. BUN was inversely associated with hemoglobin level (β -0.03; 95% confidence interval [CI] -0.04, -0.03; P <0.001) in the multivariable linear regression analysis adjusted for multiple confounders including eGFR, and BUN residual used instead of BUN was also inversely associated with hemoglobin level (β -0.03; 95% CI -0.04, -0.02; P <0.001). Among the 1,169 subjects without anemia at baseline, 414 (35.4%) subjects newly developed anemia during the follow-up period of 37.5 ± 22.1 months. In the multivariable Cox regression analysis with adjustment, both high BUN level (Hazard ratio [HR] 1.02; 95% CI 1.01, 1.04; P = 0.002) and BUN residual used instead of BUN (HR 1.02; 95% CI 1.00, 1.04; P = 0.031) increased the risk of anemia development. Moreover, BUN, rather than eGFR, increased the risk of anemia development in patients with CKD stage 3 in the multivariable Cox regression.
Higher BUN levels derived from inappropriately high protein intake relative to renal function were associated with low hemoglobin levels and the increased risk of anemia independent of eGFR in NDCKD patients.
贫血是慢性肾脏病（CKD）的常见并发症。CKD 中的血尿素氮（BUN）代表含氮尿毒症毒素的积累，这可能与 CKD 贫血有关。我们研究了 BUN 对非透析 CKD（NDCKD）贫血的影响，而不考虑估计肾小球滤过率（eGFR）。
本前瞻性研究纳入了韩国慢性肾脏病患者结局研究（KNOW-CKD）队列中 2196 例有 BUN 和血红蛋白水平数据的患者。最初，我们研究了 BUN 与血红蛋白水平之间的关系。为了研究基线 BUN 对贫血发生的影响，对 1169 例入组时无贫血的患者进行了纵向研究。BUN 残差是从 BUN 与 eGFR 的拟合曲线上获得的。贫血定义为男性血红蛋白水平<13.0 g/dL，女性<12.0 g/dL。
BUN 残差与 eGFR 无关，但与每日蛋白质摄入量（DPI）有关，而 BUN 与 eGFR 和 DPI 均有关。在调整了包括 eGFR 在内的多种混杂因素的多变量线性回归分析中，BUN 与血红蛋白水平呈负相关（β -0.03；95%置信区间[CI] -0.04，-0.03；P <0.001），而使用 BUN 残差代替 BUN 也与血红蛋白水平呈负相关（β -0.03；95%CI -0.04，-0.02；P <0.001）。在基线时无贫血的 1169 例患者中，有 414 例（35.4%）在 37.5±22.1 个月的随访期间新发生贫血。在调整后的多变量 Cox 回归分析中，高 BUN 水平（危险比[HR] 1.02；95%CI 1.01，1.04；P = 0.002）和 BUN 残差（HR 1.02；95%CI 1.00，1.04；P = 0.031）均增加了贫血发生的风险。此外，在多变量 Cox 回归中，BUN 而不是 eGFR，增加了 CKD 3 期患者贫血发展的风险。
相对于肾功能，源自不适当高蛋白摄入的较高 BUN 水平与血红蛋白水平较低和 NDCKD 患者贫血风险增加有关，而与 eGFR 无关。
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