PDF(Pubmed)
Abstract：
UNASSIGNED: Tubular biomarkers may shed insight into progression of kidney tubulointerstitial pathology complementary to traditional measures of glomerular function and damage.
UNASSIGNED: We examined trajectories of tubular biomarkers in the Diabetes Control and Complications Trial and the Epidemiology of Diabetes Interventions and Complications Study (DCCT/EDIC Study) of type 1 diabetes (T1D). Biomarkers were measured in a subset of 220 participants across 7 time points over 26 years. Measurements included the following: kidney injury molecule 1 (KIM-1), soluble tumor necrosis factor 1 (sTNFR1) in serum or plasma, epidermal growth factor (EGF), monocyte chemoattractant protein-1 (MCP1) in timed urine, and a composite tubular secretion score. We described biomarker trajectories and examined how these were affected by intensive glucose-lowering therapy and glycemia.
UNASSIGNED: At baseline, participants had a mean age of 28 years, 45% were women, and 50% were assigned to intensive glucose-lowering therapy. The mean estimated glomerular filtration rate (eGFR) was 125 ml/min per 1.73 m2 and 90% of participants had a urinary albumin excretion rate (AER) <30 mg/24h. Mean changes in biomarkers over time (percent/decade) were: KIM-1: 27.3% (95% confidence interval [CI]: 21.4-33.5), sTNFR1: 16.9% (14.5-19.3), MCP1: 18.4% (8.9-28.8), EGF: -13.5% (-16.7 to -10.1), EGF-MCP1 ratio: -26.9% (-32.2 to -21.3), and tubular secretion score -0.9% (-1.8 to 0.0), versus -12.0% (CI: -12.9 to -11.1) for eGFR and 10.9% (2.5-20.1) for AER. Intensive versus conventional glucose-lowering therapy was associated with slower increase in sTNFR1 (relative difference in change: 0.94 [0.90-0.98]). Higher HbA1c was associated with faster increases in sTNFR1 (relative difference in change: 1.06 per 1% higher HbA1c [1.05-1.08]) and KIM-1 (1.09 [1.05-1.14]).
UNASSIGNED: Among participants with T1D and normal eGFR at baseline, kidney tubular biomarkers changed significantly over long-term follow-up. Hyperglycemia was associated with larger increases in serum or plasma sTNFR1 and KIM-1, when followed-up longitudinally.
UNASSIGNED: We examined trajectories of tubular biomarkers in the Diabetes Control and Complications Trial and the Epidemiology of Diabetes Interventions and Complications Study (DCCT/EDIC Study) of type 1 diabetes (T1D). Biomarkers were measured in a subset of 220 participants across 7 time points over 26 years. Measurements included the following: kidney injury molecule 1 (KIM-1), soluble tumor necrosis factor 1 (sTNFR1) in serum or plasma, epidermal growth factor (EGF), monocyte chemoattractant protein-1 (MCP1) in timed urine, and a composite tubular secretion score. We described biomarker trajectories and examined how these were affected by intensive glucose-lowering therapy and glycemia.
UNASSIGNED: At baseline, participants had a mean age of 28 years, 45% were women, and 50% were assigned to intensive glucose-lowering therapy. The mean estimated glomerular filtration rate (eGFR) was 125 ml/min per 1.73 m2 and 90% of participants had a urinary albumin excretion rate (AER) <30 mg/24h. Mean changes in biomarkers over time (percent/decade) were: KIM-1: 27.3% (95% confidence interval [CI]: 21.4-33.5), sTNFR1: 16.9% (14.5-19.3), MCP1: 18.4% (8.9-28.8), EGF: -13.5% (-16.7 to -10.1), EGF-MCP1 ratio: -26.9% (-32.2 to -21.3), and tubular secretion score -0.9% (-1.8 to 0.0), versus -12.0% (CI: -12.9 to -11.1) for eGFR and 10.9% (2.5-20.1) for AER. Intensive versus conventional glucose-lowering therapy was associated with slower increase in sTNFR1 (relative difference in change: 0.94 [0.90-0.98]). Higher HbA1c was associated with faster increases in sTNFR1 (relative difference in change: 1.06 per 1% higher HbA1c [1.05-1.08]) and KIM-1 (1.09 [1.05-1.14]).
UNASSIGNED: Among participants with T1D and normal eGFR at baseline, kidney tubular biomarkers changed significantly over long-term follow-up. Hyperglycemia was associated with larger increases in serum or plasma sTNFR1 and KIM-1, when followed-up longitudinally.
摘要：
■肾小管生物标志物可能有助于了解肾小管间质病理的进展，以补充传统的肾小球功能和损伤的测量。
■我们检查了1型糖尿病（T1D）的糖尿病控制和并发症试验以及糖尿病干预和并发症流行病学研究（DCCT/EDIC研究）中肾小管生物标志物的轨迹。在26年的7个时间点，对220名参与者的子集中的生物标志物进行了测量。测量包括：肾损伤分子1（KIM-1），血清或血浆中的可溶性肿瘤坏死因子1（sTNFR1），表皮生长因子（EGF），定时尿液中的单核细胞趋化蛋白-1（MCP1），和复合肾小管分泌评分。我们描述了生物标志物的轨迹，并检查了这些轨迹如何受到强化降糖治疗和血糖的影响。
■在基线时，参与者的平均年龄为28岁，45%是女性,50%被分配到强化降糖治疗.平均估计肾小球滤过率（eGFR）为每1.73m2125ml/min，90％的参与者尿白蛋白排泄率（AER）<30mg/24h。生物标志物随时间的平均变化（百分比/十年）为：KIM-1：27.3%（95%置信区间[CI]：21.4-33.5），sTNFR1：16.9%（14.5-19.3），MCP1：18.4%（8.9-28.8），EGF：-13.5%（-16.7至-10.1），EGF-MCP1比率：-26.9%（-32.2至-21.3），和肾小管分泌评分-0.9%（-1.8至0.0），eGFR为-12.0%（CI：-12.9至-11.1），AER为10.9%（2.5-20.1）。强化降糖治疗与常规降糖治疗相比，sTNFR1增加较慢（变化的相对差异：0.94[0.90-0.98]）。较高的HbA1c与sTNFR1的较快增加相关（变化的相对差异：HbA1c每1％升高1.06[1.05-1.08]）和KIM-1（1.09[1.05-1.14]）。
■在基线时具有T1D和正常eGFR的参与者中，肾小管生物标志物在长期随访期间发生显著变化.纵向随访时，高血糖与血清或血浆sTNFR1和KIM-1的增加有关。
■我们检查了1型糖尿病（T1D）的糖尿病控制和并发症试验以及糖尿病干预和并发症流行病学研究（DCCT/EDIC研究）中肾小管生物标志物的轨迹。在26年的7个时间点，对220名参与者的子集中的生物标志物进行了测量。测量包括：肾损伤分子1（KIM-1），血清或血浆中的可溶性肿瘤坏死因子1（sTNFR1），表皮生长因子（EGF），定时尿液中的单核细胞趋化蛋白-1（MCP1），和复合肾小管分泌评分。我们描述了生物标志物的轨迹，并检查了这些轨迹如何受到强化降糖治疗和血糖的影响。
■在基线时，参与者的平均年龄为28岁，45%是女性,50%被分配到强化降糖治疗.平均估计肾小球滤过率（eGFR）为每1.73m2125ml/min，90％的参与者尿白蛋白排泄率（AER）<30mg/24h。生物标志物随时间的平均变化（百分比/十年）为：KIM-1：27.3%（95%置信区间[CI]：21.4-33.5），sTNFR1：16.9%（14.5-19.3），MCP1：18.4%（8.9-28.8），EGF：-13.5%（-16.7至-10.1），EGF-MCP1比率：-26.9%（-32.2至-21.3），和肾小管分泌评分-0.9%（-1.8至0.0），eGFR为-12.0%（CI：-12.9至-11.1），AER为10.9%（2.5-20.1）。强化降糖治疗与常规降糖治疗相比，sTNFR1增加较慢（变化的相对差异：0.94[0.90-0.98]）。较高的HbA1c与sTNFR1的较快增加相关（变化的相对差异：HbA1c每1％升高1.06[1.05-1.08]）和KIM-1（1.09[1.05-1.14]）。
■在基线时具有T1D和正常eGFR的参与者中，肾小管生物标志物在长期随访期间发生显著变化.纵向随访时，高血糖与血清或血浆sTNFR1和KIM-1的增加有关。
