Department of Nephropathy, the First Affiliated Hospital of Anhui Medical University, Hefei, 230022, Anhui, People's Republic of China.
Department of Endocrinology, the First Affiliated Hospital of Anhui Medical University, Hefei, 230022, Anhui, People's Republic of China.
Amino Acids. 2021 May;53(5):687-700. doi: 10.1007/s00726-021-02975-z. Epub 2021 Apr 3.
Diabetic nephropathy (DN) is one of the major complications of diabetes and contributes significantly towards end-stage renal disease. Previous studies have identified the gene encoding carnosinase (CN-1) as a predisposing factor for DN. Despite this fact, the relationship of the level of serum CN-1 and the progression of DN remains uninvestigated. Thus, the proposed study focused on clarifying the relationship among serum CN-1, indicators of renal function and tissue injury, and the progression of DN. A total of 14 patients with minimal changes disease (MCD) and 37 patients with DN were enrolled in the study. Additionally, 20 healthy volunteers were recruited as control. Further, DN patients were classified according to urinary albumin excretion rate into two groups: DN with microalbuminuria (n = 11) and DN with macroalbuminuria (n = 26). Clinical indicators including urinary protein components, serum carnosine concentration, serum CN-1 concentration and activity, and renal biopsy tissue injury indexes were included for analyzation. The serum CN-1 concentration and activity were observed to be the highest, but the serum carnosine concentration was the lowest in DN macroalbuminuria group. Moreover, within DN group, the concentration of serum CN-1 was positively correlated with uric acid (UA, r = 0.376, p = 0.026) and serum creatinine (SCr, r = 0.399, p = 0.018) and negatively correlated with serum albumin (Alb, r = - 0.348, p = 0.041) and estimated glomerular filtration rate (eGRF, r = - 0.432, p = 0.010). Furthermore, the concentration of serum CN-1 was discovered to be positively correlated with indicators including 24-h urinary protein-creatinine ratio (24 h-U-PRO/CRE, r = 0.528, p = 0.001), urinary albumin-to-creatinine ratio (Alb/CRE, r = 0.671, p = 0.000), urinary transferrin (TRF, r = 0.658, p = 0.000), retinol-binding protein (RBP, r = 0.523, p = 0.001), N-acetyl-glycosaminidase (NAG, r = 0.381, p = 0.024), immunoglobulin G (IgG, r = 0.522, p = 0.001), cystatin C (Cys-C, r = 0.539, p = 0.001), beta-2-microglobulin (β2-MG, r = 0.437, p = 0.009), and alpha-1-macroglobulin (α1-MG, r = 0.480, p = 0.004). Besides, in DN with macroalbuminuria group, serum CN-1 also showed a positive correlation with indicators of fibrosis, oxidative stress, and renal tubular injury. Taken together, our data suggested that the level of CN-1 was increased as clinical DN progressed. Thus, the level of serum CN-1 might be an important character during the occurrence and progression of DN. Our study will contribute significantly to future studies focused on dissecting the underlying mechanism of DN.
糖尿病肾病（DN）是糖尿病的主要并发症之一，也是导致终末期肾病的主要原因之一。先前的研究已经确定了编码肌肽酶（CN-1）的基因是 DN 的易患因素。尽管如此，血清 CN-1 水平与 DN 进展之间的关系仍未得到研究。因此，本研究旨在阐明血清 CN-1 与肾功能和组织损伤指标以及 DN 进展之间的关系。本研究共纳入 14 例微小病变性肾病（MCD）患者和 37 例 DN 患者，另外招募 20 名健康志愿者作为对照。此外，DN 患者根据尿白蛋白排泄率分为两组：DN 伴微量白蛋白尿（n=11）和 DN 伴大量白蛋白尿（n=26）。分析了包括尿蛋白成分、血清肌肽浓度、血清 CN-1 浓度和活性以及肾活检组织损伤指标在内的临床指标。DN 大量白蛋白尿组血清 CN-1 浓度和活性最高，血清肌肽浓度最低。此外，在 DN 组中，血清 CN-1 浓度与尿酸（UA，r=0.376，p=0.026）和血清肌酐（SCr，r=0.399，p=0.018）呈正相关，与血清白蛋白（Alb，r=-0.348，p=0.041）和估算肾小球滤过率（eGRF，r=-0.432，p=0.010）呈负相关。此外，血清 CN-1 浓度与 24 小时尿蛋白-肌酐比（24 h-U-PRO/CRE，r=0.528，p=0.001）、尿白蛋白与肌酐比（Alb/CRE，r=0.671，p=0.000）、尿转铁蛋白（TRF，r=0.658，p=0.000）、视黄醇结合蛋白（RBP，r=0.523，p=0.001）、N-乙酰-β-D-氨基葡萄糖苷酶（NAG，r=0.381，p=0.024）、免疫球蛋白 G（IgG，r=0.522，p=0.001）、半胱氨酸蛋白酶抑制剂 C（Cys-C，r=0.539，p=0.001）、β2-微球蛋白（β2-MG，r=0.437，p=0.009）和α1-巨球蛋白（α1-MG，r=0.480，p=0.004）呈正相关。此外，在 DN 大量白蛋白尿组中，血清 CN-1 也与纤维化、氧化应激和肾小管损伤的指标呈正相关。综上所述，我们的数据表明，随着临床 DN 的进展，CN-1 的水平增加。因此，血清 CN-1 水平可能是 DN 发生和发展过程中的一个重要特征。我们的研究将为未来研究 DN 的潜在机制做出重要贡献。
