Identification of Diabetic Nephropathy in Patients Undergoing Kidney Biopsy through Blood and Urinary Profiles of D-Serine
Identification of Diabetic Nephropathy in Patients Undergoing Kidney Biopsy through Blood and Urinary Profiles of D-Serine
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DOI：
10.34067/kid.0004282021
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发表时间：
2021-11-25
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影响因子：
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通讯作者：
Kimura, Tomonori
中科院分区：
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作者：
Iwata, Yukimasa;Okushima, Hiroki;Kimura, Tomonori
糖尿病肾病（diabetic nephropathy，DN）是ESKD的主要病因，诊断DN需要肾活检. D-丝氨酸在人体中仅以微量存在，是肾脏疾病的生物标志物，并显示出区分肾脏疾病起源的潜力，肾脏疾病的诊断通常需要肾脏活检。我们扩展了这一概念，并研究了D-丝氨酸在DN诊断中的潜力。方法我们招募了活检样本证实的DN和原发性GN（微小病变和伊加肾病）患者和无肾脏疾病的参与者。本研究共纳入388名受试者，采用二维高效液相色谱法测定血液和尿液中D-丝氨酸水平，并计算D-丝氨酸的尿排泄分数（FE）。使用来自259名参与者的数据，我们通过逻辑回归分析开发了检测DN的预测模型，并在129名参与者中验证了该模型。结果D-丝氨酸血液水平> 2.34 mM表明排除无肾脏疾病参与者的特异性为83%（95%CI，70%至93%）。在D-丝氨酸血液水平> 2.34 mM的参与者中，D-丝氨酸FE中47%的阈值为检测DN提供了最佳阈值（AUC，0.85 [95% CI，0.76至0.95];灵敏度，79% [95% CI，61%至91%];特异性，83% [95% CI，67%至94%]）。D-丝氨酸的这种血浆高和FE高特征与临床因素（年龄、性别、eGFR和白蛋白尿）组合正确预测DN，灵敏度为91%（95% CI，72%至99%），特异性为79%（95% CI，63%至80%），并且在验证数据集中优于仅基于临床因素的模型（P，0.02）。结论血、尿D-丝氨酸检测对肾活检患者DN的诊断有重要意义。分析肾脏疾病患者的D-丝氨酸支持通过肾脏疾病起源的辅助诊断进行适当的治疗。
Background The diagnosis of diabetic nephropathy (DN), the major cause of ESKD, requires kidney biopsy. D-Serine, present only in trace amounts in humans, is a biomarker for kidney diseases and shows potential to distinguish the origin of kidney diseases, whose diagnoses usually require kidney biopsy. We extended this concept and examined the potential of D-serine in the diagnosis of DN. Methods We enrolled patients with biopsy sample-proven DN and primary GN (minimal change disease and IgA nephropathy) and participants without kidney disease. A total of 388 participants were included in this study, and D-serine levels in blood and urine were measured using two-dimensional high-performance liquid chromatography, and urinary fractional excretion (FE) of D-serine was calculated. Using data from 259 participants, we developed prediction models for detecting DN by logistic regression analyses, and the models were validated in 129 participants. Results A D-serine blood level of > 2.34 mM demonstrated a high specificity of 83% (95% CI, 70% to 93%) for excluding participants without kidney diseases. In participants with a D-serine blood level > 2.34 mM, the threshold of 47% in FE of D-serine provided an optimal threshold for the detection of DN (AUC, 0.85 [95% CI, 0.76 to 0.95]; sensitivity, 79% [95% CI, 61% to 91%]; specificity, 83% [95% CI, 67% to 94%]). This plasma-high and FE-high profile of D-serine in combination with clinical factors (age, sex, eGFR, and albuminuria) correctly predicted DN with a sensitivity of 91% (95% CI, 72% to 99%) and a specificity of 79% (95% CI, 63% to 80%), and outperformed the model based on clinical factors alone in the validation dataset (P,0.02). Conclusions Analysis of D-serine in blood and urinary excretion is useful in identifying DN in patients undergoing kidney biopsy. Profiling of D-serine in patients with kidney diseases supports the suitable treatment through the auxial diagnosis of the origins of kidney diseases.