Umapathy Dhamodharan, Dornadula Sireesh, Krishnamoorthy Ezhilarasi, Mariappanadar Vairamani, Viswanathan Vijay, Ramkumar Kunka Mohanram
Life Science Division, SRM Research Institute, SRM University, Kattankulathur, Chennai-603 203, Tamilnadu, India.
Department of Biochemistry and Molecular Genetics, Prof. M. Viswanathan Diabetes Research Centre and M.V. Hospital for Diabetes (A WHO Collaborating Centre for Research, Education & Training in Diabetes), International Diabetes Federation, Centre of Education and Centre of Excellence in Diabetes Care, Royapuram, Chennai-600 013, Tamilnadu, India.
Immunobiology. 2018 Nov;223(11):718-727. doi: 10.1016/j.imbio.2018.07.020. Epub 2018 Jul 20.
Diabetic Nephropathy (DN) is an important cause of morbidity and death amongst diabetes. Persistent micro and macroalbuminuria are well known predictors of DN leading to progressive end-stage renal disease. However, albuminuria has several limitations. Increasing evidences show that YKL-40 is highly expressed in variety of inflammatory diseases and also recognized as a non-invasive prognostic biomarker for inflammation. In the present study, we measured plasma YKL-40 levels in different stages of albuminuria and assessed its diagnostic accuracy as a biomarker for DN and correlated with different families of circulatory cytokines. A total of 306 subjects were recruited and divided into three groups [Group-I, control (n = 83), Group-II, Normoalbuminuria (n = 81), Group-III, DN (n = 142)]. Group-III is further subdivided into: Group-IIIa, microalbuminuria (n = 73), Group-IIIb, macroalbuminuria (n = 69). The median levels of YKL-40 (p = 0.001) showed a marked stepwise increase from normo to macroalbuminuria and positively correlated with eGFR. The AUC for YKL-40 was found to be high [0.95; (95% CI: 0.88-1.0)], when compared to other acute phase markers. Plasma YKL-40 showed a positive correlation with LIGHT/TNFSF14, sIL-6Ra, gp130/sIL-6Rβ, IFN-β, IL-8, TNFSF14, sCD-30 and eGFR meanwhile a negative correlation with TWEAK/TNFSF12, IL-7 like cytokine and IFN-λ2. Plasma YKL-40 could be a potential biomarker for early diagnosis of incipient DN among South Indian population.
糖尿病肾病（DN）是糖尿病患者发病和死亡的重要原因。持续性微量和大量白蛋白尿是导致进行性终末期肾病的DN的众所周知的预测指标。然而，白蛋白尿有几个局限性。越来越多的证据表明，YKL-40在多种炎症性疾病中高表达，也被认为是炎症的一种非侵入性预后生物标志物。在本研究中，我们测量了不同白蛋白尿阶段的血浆YKL-40水平，并评估了其作为DN生物标志物的诊断准确性，以及与不同循环细胞因子家族的相关性。总共招募了306名受试者，并将其分为三组[第一组，对照组（n = 83），第二组，正常白蛋白尿组（n = 81），第三组，糖尿病肾病组（n = 142）]。第三组进一步细分为：第三a组，微量白蛋白尿组（n = 73），第三b组，大量白蛋白尿组（n = 69）。YKL-40的中位数水平（p = 0.001）显示从正常白蛋白尿到大量白蛋白尿有明显的逐步升高，并且与估算肾小球滤过率（eGFR）呈正相关。与其他急性期标志物相比，发现YKL-40的曲线下面积（AUC）较高[0.95；（95%可信区间：0.88 - 1.0）]。血浆YKL-40与LIGHT/TNFSF14、可溶性白细胞介素-6受体α（sIL-6Ra）、糖蛋白130/可溶性白细胞介素-6受体β（gp130/sIL-6Rβ）、干扰素-β（IFN-β）、白细胞介素-8（IL-8）、TNFSF14、可溶性CD30（sCD-30）和eGFR呈正相关，而与肿瘤坏死因子相关弱凋亡诱导因子/TNFSF12（TWEAK/TNFSF12）、白细胞介素-7样细胞因子和干扰素-λ2呈负相关。血浆YKL-40可能是南印度人群早期诊断初期糖尿病肾病的潜在生物标志物。
