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Abstract：
BACKGROUND: Tubular biomarkers, which reflect tubular dysfunction or injury, are associated with incident chronic kidney disease and kidney function decline. Several tubular biomarkers have also been implicated in the progression of autosomal dominant polycystic kidney disease (ADPKD). We evaluated changes in multiple tubular biomarkers in four groups of patients with ADPKD who participated in one of two clinical trials (metformin therapy and diet-induced weight loss), based on evidence suggesting that such interventions could reduce tubule injury.
METHODS: 66 participants (26 M/40 F) with ADPKD and an estimated glomerular filtration rate (eGFR) ≥ 30 ml/min/1.73m2 who participated in either a metformin clinical trial (n = 22 metformin; n = 23 placebo) or dietary weight loss study (n = 10 daily caloric restriction [DCR]; n = 11 intermittent fasting [IMF]) were included in assessments of urinary tubular biomarkers (kidney injury molecule-1 [KIM-1], fatty-acid binding protein [FABP], interleukin-18 [IL-18], monocyte chemoattractant protein-1 [MCP-1], neutrophil gelatinase-associated lipocalin [NGAL], clusterin, and human cartilage glycoprotein-40 [YKL-40]; normalized to urine creatinine), at baseline and 12 months. The association of baseline tubular biomarkers with both baseline and change in height-adjusted total kidney volume (HtTKV; percent change from baseline to 12 months) and estimated glomerular filtration rate (eGFR; absolute change at 12 months vs. baseline), with covariate adjustment, was also assessed using multiple linear regression.
RESULTS: Mean ± s.d. age was 48 ± 8 years, eGFR was 71 ± 16 ml/min/1.73m2, and baseline BMI was 30.5 ± 5.9 kg/m2. None of the tubular biomarkers changed with any intervention as compared to placebo. Additionally, baseline tubular biomarkers were not associated with either baseline or change in eGFR or HtTKV over 12 months, after adjustments for demographics, group assignment, and clinical characteristics.
CONCLUSIONS: Tubular biomarkers did not change with dietary-induced weight loss or metformin, nor did they associate with kidney disease progression, in this cohort of patients with ADPKD.
METHODS: 66 participants (26 M/40 F) with ADPKD and an estimated glomerular filtration rate (eGFR) ≥ 30 ml/min/1.73m2 who participated in either a metformin clinical trial (n = 22 metformin; n = 23 placebo) or dietary weight loss study (n = 10 daily caloric restriction [DCR]; n = 11 intermittent fasting [IMF]) were included in assessments of urinary tubular biomarkers (kidney injury molecule-1 [KIM-1], fatty-acid binding protein [FABP], interleukin-18 [IL-18], monocyte chemoattractant protein-1 [MCP-1], neutrophil gelatinase-associated lipocalin [NGAL], clusterin, and human cartilage glycoprotein-40 [YKL-40]; normalized to urine creatinine), at baseline and 12 months. The association of baseline tubular biomarkers with both baseline and change in height-adjusted total kidney volume (HtTKV; percent change from baseline to 12 months) and estimated glomerular filtration rate (eGFR; absolute change at 12 months vs. baseline), with covariate adjustment, was also assessed using multiple linear regression.
RESULTS: Mean ± s.d. age was 48 ± 8 years, eGFR was 71 ± 16 ml/min/1.73m2, and baseline BMI was 30.5 ± 5.9 kg/m2. None of the tubular biomarkers changed with any intervention as compared to placebo. Additionally, baseline tubular biomarkers were not associated with either baseline or change in eGFR or HtTKV over 12 months, after adjustments for demographics, group assignment, and clinical characteristics.
CONCLUSIONS: Tubular biomarkers did not change with dietary-induced weight loss or metformin, nor did they associate with kidney disease progression, in this cohort of patients with ADPKD.
摘要：
背景：管状生物标志物，反映了肾小管功能障碍或损伤，与慢性肾脏病和肾功能下降有关。几种肾小管生物标志物也与常染色体显性多囊肾病(ADPKD)的进展有关。我们评估了参与两项临床试验（二甲双胍治疗和饮食诱导的体重减轻）之一的四组ADPKD患者中多种肾小管生物标志物的变化，基于证据表明这种干预措施可以减少小管损伤。
方法：66名患有ADPKD且估计肾小球滤过率（eGFR）≥30ml/min/1.73m2的参与者（26M/40F）参加了二甲双胍临床试验（n=22二甲双胍；n=23安慰剂）或饮食体重减轻研究（n=10每日热量限制[DCR]；n=11个间歇性肾KIM-1分子评估中包括[空腹]脂肪酸结合蛋白[FABP]，白细胞介素-18[IL-18]，单核细胞趋化蛋白-1[MCP-1]，中性粒细胞明胶酶相关脂质运载蛋白[NGAL]，clusterin,和人软骨糖蛋白-40[YKL-40]；归一化为尿肌酐），在基线和12个月。基线肾小管生物标志物与基线和高度调整后的总肾脏体积（HtTKV；从基线到12个月的百分比变化）和估计的肾小球滤过率（eGFR；12个月时的绝对变化与基线)，用协变量调整，还使用多元线性回归进行了评估。
结果：平均±s.d.年龄为48±8岁，eGFR为71±16ml/min/1.73m2,基线BMI为30.5±5.9kg/m2。与安慰剂相比，任何干预都没有改变肾小管生物标志物。此外,基线肾小管生物标志物与基线或eGFR或HtTKV在12个月内的变化无关，在人口统计调整后，组分配,和临床特征。
结论：肾小管生物标志物不会随着饮食诱导的体重减轻或二甲双胍而改变，它们也不与肾脏疾病进展有关，在这一ADPKD患者队列中。
方法：66名患有ADPKD且估计肾小球滤过率（eGFR）≥30ml/min/1.73m2的参与者（26M/40F）参加了二甲双胍临床试验（n=22二甲双胍；n=23安慰剂）或饮食体重减轻研究（n=10每日热量限制[DCR]；n=11个间歇性肾KIM-1分子评估中包括[空腹]脂肪酸结合蛋白[FABP]，白细胞介素-18[IL-18]，单核细胞趋化蛋白-1[MCP-1]，中性粒细胞明胶酶相关脂质运载蛋白[NGAL]，clusterin,和人软骨糖蛋白-40[YKL-40]；归一化为尿肌酐），在基线和12个月。基线肾小管生物标志物与基线和高度调整后的总肾脏体积（HtTKV；从基线到12个月的百分比变化）和估计的肾小球滤过率（eGFR；12个月时的绝对变化与基线)，用协变量调整，还使用多元线性回归进行了评估。
结果：平均±s.d.年龄为48±8岁，eGFR为71±16ml/min/1.73m2,基线BMI为30.5±5.9kg/m2。与安慰剂相比，任何干预都没有改变肾小管生物标志物。此外,基线肾小管生物标志物与基线或eGFR或HtTKV在12个月内的变化无关，在人口统计调整后，组分配,和临床特征。
结论：肾小管生物标志物不会随着饮食诱导的体重减轻或二甲双胍而改变，它们也不与肾脏疾病进展有关，在这一ADPKD患者队列中。
