尿视黄醇结合蛋白作为糖尿病肾病肾脏结局的独立预测因子。
Urinary RBP as an Independent Predictor of Renal Outcome in Diabetic Nephropathy.
机构信息
Kidney Disease Center, The First Affiliated Hospital, Zhejiang University School of Medicine; Institute of Nephrology, Zhejiang University; Key Laboratory of Kidney Disease Prevention and Control Technology, Zhejiang Province; Zhejiang Clinical Research Center of Kidney and Urinary System Disease, Hangzhou, China.
Sanmen People's Hospital, Ningbo, China.
出版信息
Dis Markers. 2022 Oct 17;2022:9687868. doi: 10.1155/2022/9687868. eCollection 2022.
BACKGROUND
Renal tubular impairment is prevalent in diabetic nephropathy (DN) and the histological severity predicted renal outcome. Biomarkers of tubular injury also increased in the urine of DN patients. The retrospective study aimed to assess the prognostic value of clinically widely applied urinary tubular injury markers, retinol-binding protein (RBP), 2-microglobulin (2-MG) and N-acetyl--D-glucosaminidase (NAG) in DN.
METHOD
A total of 305 patients with biopsy-proven DN were enrolled. The baseline urine total protein and components including albumin, IgG, RBP, 2-MG and NAG were retrieved from medical records. The primary outcome was end stage renal disease (ESRD). Cox proportional hazard analysis and restricted cubic splines were performed to evaluate the association of parameters with ESRD. Nomograms were constructed and concordance index (C-index) was used to measure the prediction ability.
RESULT
The levels of urinary RBP, 2-MG and NAG were positively correlated with the severity of interstitial fibrosis and tubular atrophy (IFTA). Positive correlations were also observed among 2-MG, NAG and mesangial expansion. Urinary RBP was not correlated with any glomerular lesions. Urinary RBP, 2-MG and NAG were risk factors for ESRD in hazard analysis with adjustment for age, gender and body mass index (BMI). The hazard ratios increased with the increment of baseline levels. In the multivariate Cox model including serum creatinine (SCr), total urinary protein, urinary albumin, urinary IgG and the tubular injury biomarkers, urinary RBP (with every g/mol.Cr increase: HR 1.06, 95% CI 1.03-1.10, =0.001) remained as an independent risk factor for ESRD in DN patients. Patients were divided by the medium value of urinary RBP into the low RBP and high RBP groups. Survival analysis showed that significantly more patients in the high RBP progressed to ESRD compared to those in the low RBP group ( =0.02) when urinary total protein was less than 3.5 g/g. The C-index of the nomogram incorporating age, gender, BMI, SCr and total urine protein was 0.757. The value increased to 0.777 after adding urinary RBP to the model.
CONCLUSIONS
Urinary RBP excretion was only correlated with the severity of IFTA and independently predicted ESRD in DN patients.
背景
肾小管损伤在糖尿病肾病（DN）中很常见，其组织学严重程度可预测肾脏结局。DN 患者的尿液中也会增加肾小管损伤的生物标志物。这项回顾性研究旨在评估临床上广泛应用的尿肾小管损伤标志物视黄醇结合蛋白（RBP）、2-微球蛋白（2-MG）和 N-乙酰-β-D-氨基葡萄糖苷酶（NAG）在 DN 中的预后价值。
方法
共纳入 305 例经活检证实的 DN 患者。从病历中检索基线尿总蛋白及其成分，包括白蛋白、IgG、RBP、2-MG 和 NAG。主要结局是终末期肾病（ESRD）。采用 Cox 比例风险分析和限制立方样条进行评估，以观察参数与 ESRD 的相关性。构建列线图并使用一致性指数（C 指数）衡量预测能力。
结果
尿 RBP、2-MG 和 NAG 水平与间质纤维化和肾小管萎缩（IFTA）的严重程度呈正相关。2-MG、NAG 和系膜扩张之间也存在正相关。尿 RBP 与任何肾小球病变均无相关性。在调整年龄、性别和体重指数（BMI）后，尿 RBP、2-MG 和 NAG 在危险分析中是 ESRD 的危险因素。随着基线水平的升高，危险比也随之增加。在包括血清肌酐（SCr）、总尿蛋白、尿白蛋白、尿 IgG 和肾小管损伤生物标志物的多变量 Cox 模型中，尿 RBP（每 g/mol.Cr 增加：HR 1.06，95%CI 1.03-1.10，=0.001）仍然是 DN 患者 ESRD 的独立危险因素。根据尿 RBP 的中位数将患者分为低 RBP 和高 RBP 组。生存分析表明，当尿总蛋白小于 3.5 g/g 时，与低 RBP 组相比，高 RBP 组中更多的患者进展为 ESRD（=0.02）。纳入年龄、性别、BMI、SCr 和总尿蛋白的列线图的 C 指数为 0.757。将尿 RBP 加入模型后，该值增加至 0.777。
结论
尿 RBP 排泄仅与 IFTA 的严重程度相关，可独立预测 DN 患者的 ESRD。
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