Tsuda Akihiro, Mori Katsuhito, Uedono Hideki, Nakatani Shinya, Nagata Yuki, Kurajoh Masafumi, Yamada Shinsuke, Morioka Tomoaki, Ishimura Eiji, Uchida Junji, Emoto Masanori
Department of Metabolism, Endocrinology and Molecular Medicine, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan.
Department of Nephrology, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan.
Hypertens Res. 2025 Mar;48(3):1115-1124. doi: 10.1038/s41440-024-02020-y. Epub 2024 Dec 12.
The definition of hyperfiltration, the main pathogenesis in renal impairment in obesity and diabetes mellitus, is uncertain. Glomerular filtration rate (GFR) declines physiologically with aging, and there is inaccuracy in GFR in obesity due to body surface area (BSA) correction. Here, we defined hyperfiltration using GFR without BSA correction, but with inclusion of aging, and investigated hyperfiltration using this definition and absolute GFR > 125 mL/min. The subjects were 180 kidney donor candidates (56.4 ± 11.3 years old, 79 males). GFR was evaluated using inulin clearance. A two-hour 75-g oral glucose tolerance test was also performed. The subjects were divided into four groups with and without a combination of glucose tolerance disorder and BMI. Normal glucose tolerance (NGT) and BMI < 25 kg/m were defined as normal, and hyperfiltration was defined as the upper 95% confidence interval of the relationship of aging and GFR in normal cases, and compared with GFR > 125 mL/min. RESULTS: GFR without BSA correction and UAE in non-NGT subjects with obesity were higher than in other groups, but GFR with BSA correction did not show this relationship. In multiple regression analysis, BMI was independently associated with GFR without BSA correction, but not with BSA correction. Aging was consistently associated with GFR. The prevalence of hyperfiltration by our definition (GFR = -0.883 × Age + 167.398) was significantly higher than that using GFR > 125 mL/min (P < 0.0001). Hyperfiltration in obesity and/or glucose tolerance disorder should be evaluated using GFR without BSA correction and including the decline of GFR due to aging.
高滤过是肥胖和糖尿病患者肾功能损害的主要发病机制，但其定义尚不明确。肾小球滤过率（GFR）会随着年龄增长而生理性下降，而且肥胖患者由于体表面积（BSA）校正，其GFR存在不准确之处。在此，我们使用未经BSA校正但纳入了年龄因素的GFR来定义高滤过，并使用该定义以及绝对GFR > 125 mL/min来研究高滤过情况。研究对象为180名肾脏供体候选者（年龄56.4 ± 11.3岁，男性79名）。使用菊粉清除率评估GFR。还进行了两小时的75克口服葡萄糖耐量试验。根据是否合并葡萄糖耐量异常和BMI将研究对象分为四组。正常糖耐量（NGT）且BMI < 25 kg/m被定义为正常，高滤过被定义为正常情况下年龄与GFR关系的上95%置信区间，并与GFR > 125 mL/min进行比较。结果：肥胖且非NGT的受试者未经BSA校正的GFR和尿白蛋白排泄率（UAE）高于其他组，但经BSA校正的GFR未显示出这种关系。在多元回归分析中，BMI与未经BSA校正的GFR独立相关，但与经BSA校正的GFR无关。年龄始终与GFR相关。根据我们的定义（GFR = -0.883×年龄 + 167.398），高滤过的患病率显著高于使用GFR > 125 mL/min时的患病率（P < 0.0001）。肥胖和/或葡萄糖耐量异常患者的高滤过应使用未经BSA校正且包括因年龄导致的GFR下降的GFR来评估。
