Kidney Disease Research Collaborative, Translational Research Institute, The University of Queensland, Brisbane, QLD 4102, Australia.
Department of Nephrology, Princess Alexandra Hospital, Woolloongabba, Brisbane, QLD 4075, Australia.
Int J Mol Sci. 2021 Feb 10;22(4):1762. doi: 10.3390/ijms22041762.
Erroneous conclusions may result from normalization of urine cadmium and N-acetyl-β-D-glucosaminidase concentrations ([Cd] and [NAG]) to the urine creatinine concentration ([cr]). In theory, the sources of these errors are nullified by normalization of excretion rates (E and E) to creatinine clearance (C). We hypothesized that this alternate approach would clarify the contribution of Cd-induced tubular injury to nephron loss. We studied 931 Thai subjects with a wide range of environmental Cd exposure. For = Cd or NAG, E/E and E/C were calculated as []/[cr] and [][cr]/[cr], respectively. Glomerular filtration rate (GFR) was estimated according to the Chronic Kidney Disease (CKD) Epidemiology Collaboration (eGFR), and CKD was defined as eGFR < 60 mL/min/1.73m. In multivariable logistic regression analyses, prevalence odds ratios (PORs) for CKD were higher for log(E/C) and log(E/C) than for log(E/E) and log(E/E). Doubling of E/C and E/C increased POR by 132% and 168%; doubling of E/E and E/E increased POR by 64% and 54%. As log(E/C) rose, associations of eGFR with log(E/C) and log(E/C) became stronger, while associations of eGFR with log(E/E) and log(E/E) became insignificant. In univariate regressions of eGFR on each of these logarithmic variables, R was consistently higher with normalization to C. Our tabular and graphic analyses uniformly indicate that normalization to C clarified relationships of E and E to eGFR.
尿镉和 N-乙酰-β-D-氨基葡萄糖苷酶浓度 ([Cd] 和 [NAG]) 与尿肌酐浓度 ([cr]) 的归一化可能导致错误的结论。从理论上讲,通过将排泄率 (E 和 E) 标准化为肌酐清除率 (C),这些误差的来源就被消除了。我们假设这种替代方法将阐明 Cd 诱导的肾小管损伤对肾单位损失的贡献。我们研究了 931 名泰国受试者,他们的环境 Cd 暴露范围很广。对于 [Cd] 或 NAG,E/E 和 E/C 分别计算为 []/[cr] 和 [][cr]/[cr]。肾小球滤过率 (GFR) 根据慢性肾脏病 (CKD) 协作组 (eGFR) 进行估计,CKD 定义为 eGFR < 60 mL/min/1.73m。在多变量逻辑回归分析中,与 log(E/E) 和 log(E/E) 相比,log(E/C) 和 log(E/C) 的 CKD 患病率比值比 (POR) 更高。E/C 和 E/C 加倍增加 POR 分别为 132%和 168%;E/E 和 E/E 加倍增加 POR 分别为 64%和 54%。随着 log(E/C) 的升高,eGFR 与 log(E/C) 和 log(E/C) 的关联变得更强,而 eGFR 与 log(E/E) 和 log(E/E) 的关联变得不显著。在这些对数变量中,eGFR 与每个变量的单变量回归中,归一化到 C 时 R 始终更高。我们的表格和图形分析一致表明,归一化到 C 澄清了 E 和 E 与 eGFR 的关系。