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Diabetes:中国2型糖尿病患者急性肾损伤对糖尿病肾病进展的远期影响及临床预测因素

2022-03-18 Naomi MedSci原创

近日,研究人员评估了急性肾损伤(AKI)对糖尿病肾病(DKD)进展和全因死亡率的长期影响,并调查中国2型糖尿病(T2D)患者AKI的决定因素。研究发现,尿酸是可改变的危险因素,PRS则为不可控因素。

      糖尿病肾病(DKD),尤其是2型糖尿病(T2D)终末期肾病(ESRD)的最常见原因,并与心血管疾病和过早死亡的风险增加相关。在亚洲,据估计,超过60%的糖尿病患者会出现肾脏并发症,而欧洲人的这一比例为30%-40%,尽管他们的糖尿病病程相似,这给卫生保健系统带来了巨大的经济负担。鉴于糖尿病患者数量的持续增加,确定那些进展为DKD的高风险患者并制定有效的策略来预防和治疗这种疾病尤为重要。然而,由于DKD是一种复杂的多因素疾病,其发病机制尚不清楚,因此对DKD进展的决定因素的调查是一个关键的研究重点。

      急性肾损伤(AKI)是世界范围内的一个普遍问题,尤其是在住院患者中,影响到13%-18%的住院患者和高达40%的危重患者。许多研究强调AKI是选定人群中肾功能衰竭事件的决定因素。例如,在亚洲的一项前瞻性队列研究中,AKI与心脏手术后ESRD风险增加五倍以上相关。虽然糖尿病是终末期肾病最常见的原因,但AKI与糖尿病患者长期肾脏并发症的关系尚未得到很好的研究。最近,Monseu 等在1,371名T2D患者队列中,发现AKI是主要不良心血管事件心肌梗死和其他不良后果的有力预测因子。然而,关于AKI及其危险因素对T2D患者长期肾脏并发症的影响的数据很少。

      已知不同的临床因素与AKI相关,包括低血容量、利尿剂的使用和CKD。血清尿酸(SUA)已被确定为AKI的潜在可控危险因素,并与T2D的DKD有关。在最近的全基因组关联研究中,许多与血尿酸浓度相关的遗传变异已被识别,强调了可以改变血尿酸浓度的遗传因素的存在。

        近日,有研究人员试图评估急性肾损伤(AKI)对糖尿病肾病(DKD)进展和全因死亡率的长期影响,并调查中国2型糖尿病(T2D)患者AKI的决定因素。

      研究者假设AKI可能对T2D患者进展为慢性肾脏疾病(CKD)和终末期肾病(ESRD)有重要影响,进一步试图确定AKI的临床预测因子及其生物学意义。在队列中确定SUA是AKI的重要决定因素后,进一步探讨了SUA在AKI和DKD中的作用,在T2D中国前瞻性队列中,检查了SUA的多基因风险评分(PRS)与AKI风险以及不同的DKD结果之间的关联。更好地了解AKI的主要预测因素将使医生能够识别高危患者,进行早期强化和个体化治疗,以预防AKI及其对长期肾脏并发症的潜在影响。

      对9,096例来自香港糖尿病登记处的中国T2D患者的连续队列进行了跟踪调查,研究对象为12岁以下患者(m e a n±S D a g e 57±1 3)。2是a r s;4.。糖尿病病程中位数为5年)。AKI是根据肾脏疾病:改善全球预后(KDIGO)标准使用血清肌酐定义的。估计的肾小球滤过率测量被用来确定首发的慢性肾脏疾病(CKD)和终末期肾脏疾病(ESRD)。采用由27个单核苷酸多态(SNPs)组成的多基因风险评分(PRS)来研究SUA在AKI、CKD和ESRD发病机制中的作用。

  • 在包括6007名患者的独立队列中寻求验证(年龄61.2±10.9岁;59.5%的男性;糖尿病病程的中位数为10年)。
  • 与非AKI患者相比,AKI患者发生CKD(危险比14.3[95%可信区间12.69~16.11])、发生ESRD(12.1[10.74~13.62])和全因死亡(7.99[7.31~8.74])的风险较高。
  • 在没有AKI发作和1次、2次和3次或更多AKI发作的患者中,ESRD的发病率分别为7.1、24.4、32.4和37.3/1000人年。
  • 基线血尿酸是AKI的一个强有力的独立预测因子。
  • 在发现和复制队列中,由27个SUA相关SNPs组成的PRS与AKI和CKD相关,但与ESRD无关。
  • 血尿酸升高可能通过增加AKI增加DKD的风险。

       将血尿酸确定为可改变的危险因素,将PRS确定为不可改变的危险因素,可有助于识别高危个体以预防急性肾功能衰竭及其对T2D的长期影响。

文献来源:Jiang G, Luk AO, Tam CHT, et al. Clinical Predictors and Long-term Impact of Acute Kidney Injury on Progression of Diabetic Kidney Disease in Chinese Patients With Type 2 Diabetes. Diabetes. 2022;71(3):520-529. doi:10.2337/db21-0694

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