肾小球阻力可预测无明显肾病的 2 型糖尿病患者的长期肾小球滤过率下降：来自 DEMAND 试验的纵向亚组分析。
Glomerular resistances predict long-term GFR decline in type 2 diabetic patients without overt nephropathy: a longitudinal subgroup analysis of the DEMAND trial.
机构信息
Department of Renal Medicine, Clinical Research Centre for Rare Diseases "Aldo e Cele Daccò": Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Via GB Camozzi 3, 24020, Ranica, Bergamo, Italy.
Unit of Nephrology and Dialysis, Azienda Socio-Sanitaria Territoriale Papa Giovanni XXIII, Bergamo, Italy.
出版信息
Acta Diabetol. 2022 Mar;59(3):309-317. doi: 10.1007/s00592-021-01804-9. Epub 2021 Oct 14.
AIMS
Investigating whether and to what extent changes in glomerular hemodynamic parameters, beyond glomerular hyperfiltration, could predict glomerular filtration rate (GFR) decline in hypertensive, non-proteinuric type 2 diabetic patients.
MATERIALS AND METHODS
We estimated baseline afferent (Ra) and efferent (Re) arteriolar resistances and glomerular hydrostatic pressure in 60 consecutive patients from DEMAND study, using the Gomez' equations. Baseline renal plasma flow was measured by para-aminohippurate plasma clearance, and GFR was measured by iohexol plasma clearance at baseline and every 6 months for a median of 4.0 years [IQR 3.5-4.0 years]. Patients with a GFR decline > or ≤ 3 mL/min/1.73 m/year were categorized as "Progressors" and "Non-progressors," respectively. Predictors of GFR decline were studied by univariable and multivariable logistic regression analysis.
RESULTS
•The GFR declined by a median [IQR] of 4.06 [5.46-2.00] mL/min/1.73 m/year in the study group as a whole and by 5.35 [6.60-4.48] mL/min/1.73 m/year and 1.71 [2.14-1.33] mL/min/1.73 m/year in Progressors and Non-progressors, considered separately. Progressors had a higher baseline Ra (3487.3 ± 1349.3 dyne•sec•cm vs. 2877.0 ± 668.9 dyne•sec•cm, p < 0.05) and higher Ra/Re ratio (1.4 ± 0.5 vs. 1.1 ± 0.3, p < 0.01) than Non-progressors. At multivariable logistic regression analysis, Ra/Re ratio and arterial hypertension duration were independently associated with GFR decline (odds ratio [95% CI] 8.50 [1.56-46.28] and 1.14 [1.01-1.28]), respectively.
CONCLUSIONS
Increased Ra/Re ratio and arterial hypertension duration predict early GFR decline in hypertensive non-proteinuric type 2 diabetic patients. These findings could be explained by glomerular hypoperfusion and chronic ischemic injury related to pre-glomerular arteriolar narrowing.
CLINICAL TRIAL REGISTRATION
DEMAND, NCT00157586, September 12, 2005.
目的
探讨肾小球高滤过以外的肾小球血流动力学参数的变化是否以及在何种程度上可以预测高血压、非蛋白尿 2 型糖尿病患者的肾小球滤过率（GFR）下降。
材料和方法
我们使用 Gomez 方程，在来自 DEMAND 研究的 60 名连续患者中估算了基础输入（Ra）和输出（Re）小动脉阻力以及肾小球液压。基线肾血浆流量通过对氨基马尿酸血浆清除率进行测量，而 GFR 通过 iohexol 血浆清除率在基线和每 6 个月进行测量，中位数为 4.0 年[IQR 3.5-4.0 年]。将 GFR 下降>或=3 mL/min/1.73 m/年的患者分别归类为“进展者”和“非进展者”。通过单变量和多变量逻辑回归分析研究了 GFR 下降的预测因素。
结果
在整个研究组中，GFR 中位数[IQR]下降了 4.06 [5.46-2.00] mL/min/1.73 m/年，而在进展者和非进展者中分别下降了 5.35 [6.60-4.48] mL/min/1.73 m/年和 1.71 [2.14-1.33] mL/min/1.73 m/年。进展者的基础 Ra 更高（3487.3 ± 1349.3 达因·秒·厘米比 2877.0 ± 668.9 达因·秒·厘米，p<0.05），Ra/Re 比值更高（1.4 ± 0.5 比 1.1 ± 0.3，p<0.01）。多变量逻辑回归分析显示，Ra/Re 比值和高血压持续时间与 GFR 下降独立相关（比值比[95%CI]8.50 [1.56-46.28]和 1.14 [1.01-1.28]）。
结论
升高的 Ra/Re 比值和高血压持续时间预测高血压非蛋白尿 2 型糖尿病患者的早期 GFR 下降。这些发现可以用肾小球前小动脉狭窄导致的肾小球低灌注和慢性缺血损伤来解释。
临床试验注册
DEMAND，NCT00157586，2005 年 9 月 12 日。
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