Metabolic and Renal Research Group, UiT The Arctic University of Norway, Tromsø, Norway; Section of Nephrology, University Hospital of North Norway, Tromsø, Norway.
Division of Nephrology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI.
Am J Kidney Dis. 2019 Jun;73(6):777-785. doi: 10.1053/j.ajkd.2018.11.011. Epub 2019 Jan 28.
RATIONALE & OBJECTIVE: An elevated glomerular filtration rate (GFR), or renal hyperfiltration, may predispose individuals to subsequent rapid GFR decline in diabetes, obesity, and metabolic syndrome. Although this hypothesis is supported by results of experimental studies, the importance of hyperfiltration at the population level remains controversial. We investigated whether higher baseline GFR predicts a steeper decline in GFR.
Longitudinal cohort studies.
SETTING & PARTICIPANTS: 1,594 middle-aged Norwegians without diabetes (the Renal Iohexol Clearance Survey [RENIS]) and 319 Pima Indians (83% with type 2 diabetes).
Baseline measured GFR using exogenous clearance methods.
Change in measured GFR over time.
Linear mixed regression models fit to assess the correlation between the random intercept (reflecting baseline GFR) and random slope (change in GFR over time).
Mean baseline GFRs were 104.0 ± 20.1 (SD) and 149.4 ± 43.3 mL/min, and median follow-up durations were 5.6 (IQR, 5.2-6.0) and 9.1 (IQR, 4.0-15.0) years in the RENIS and Pima cohorts, respectively. Correlation between baseline GFR (random intercept) and slope of GFR decline was -0.31 (95% CI, -0.40 to -0.23) in the RENIS cohort and -0.41 (95% CI, -0.55 to -0.26) in the Pima cohort, adjusted for age, sex, height, and weight, suggesting that higher baseline GFRs were associated with steeper GFR decline rates.
Different methods for measuring GFR in the 2 cohorts. Renal hyperfiltration may not reflect higher single-nephron GFR. GFR decline is assumed to be linear, which may not match the actual pattern; observed correlations may arise from natural variation.
Higher baseline GFR is associated with faster decline in GFR over time. If this relationship were causal, elevated GFR would represent a potentially modifiable risk factor for medium- to long-term GFR decline.
肾小球滤过率(GFR)升高,即肾脏高滤过,可能使个体易发生糖尿病、肥胖和代谢综合征患者的后续快速 GFR 下降。虽然这一假说得到了实验研究结果的支持,但在人群水平上,高滤过的重要性仍存在争议。我们研究了较高的基线 GFR 是否预示着 GFR 下降更快。
纵向队列研究。
1594 名无糖尿病的挪威中年人(肾脏碘海醇清除率调查 [RENIS])和 319 名皮马印第安人(83%为 2 型糖尿病患者)。
使用外源性清除方法测量的基线 GFR。
随时间变化的 GFR 变化。
线性混合回归模型拟合,以评估随机截距(反映基线 GFR)和随机斜率(随时间的 GFR 变化)之间的相关性。
RENIS 队列和皮马队列的平均基线 GFR 分别为 104.0±20.1(SD)和 149.4±43.3mL/min,中位随访时间分别为 5.6(IQR,5.2-6.0)和 9.1(IQR,4.0-15.0)年。RENIS 队列中基线 GFR(随机截距)与 GFR 下降斜率之间的相关性为-0.31(95%CI,-0.40 至-0.23),皮马队列中为-0.41(95%CI,-0.55 至-0.26),调整年龄、性别、身高和体重后,提示较高的基线 GFR 与更陡峭的 GFR 下降率相关。
两个队列中测量 GFR 的方法不同。肾脏高滤过可能并不反映单个肾单位 GFR 升高。假设 GFR 下降呈线性,这可能与实际模式不匹配;观察到的相关性可能源于自然变异。
较高的基线 GFR 与随时间推移 GFR 的更快下降相关。如果这种关系是因果关系,那么升高的 GFR 将代表一个潜在可改变的中到长期 GFR 下降的危险因素。