Association of serum levels of secreted frizzled-related protein 5 and Wnt member 5a with glomerular filtration rate in patients with type 2 diabetes mellitus and chronic renal disease
a cross-sectional study
Keywords:
Sfrp5 protein, human [supplementary concept], Wnt5a protein, human [supplementary concept], Diabetes mellitus, type 2, Renal insufficiency, chronic, Diabetes mellitusAbstract
BACKGROUND: Diabetic nephropathy is a common complication of chronic kidney disease (CKD). Inflammation in the kidneys is crucial for promoting development and progression of this complication. Wnt member 5a (Wnt5a) and secreted frizzled-related protein 5 (Sfrp5) are proinflammatory proteins associated with insulin resistance and chronic low-grade adipose tissue inflammation. OBJECTIVE: To determine the correlation between serum Sfrp5 and Wnt5a concentrations and glomerular filtration rate in patients with type 2 diabetes mellitus and CKD. DESIGN AND SETTING: Cross-sectional, comparative and observational study in the Department of Endocrinology, Civil Hospital, Culiacán, Sinaloa, Mexico. METHODS: Eighty individuals with chronic kidney disease were recruited. Their serum Sfrp5 and Wnt5a concentrations were quantified using the enzyme-linked immunosorbent assay (ELISA) test. The statistical analysis consisted of the Mann-Whitney U test for independent samples and Spearman correlation, with statistical significance of P < 0.05. RESULTS: Serum Sfrp5 concentration continually increased through the stages of CKD progression, whereas serum Wnt5a concentration presented its highest levels in stage 3 CKD. Negative correlations be- tween estimated glomerular filtration rate (eGFR) and serum concentrations of Sfrp5 (r = -0434, P = 0.001) and Wnt5a (r = -0481, P = 0.001) were found. CONCLUSIONS: There were negative correlations between serum Sfrp5 and Wnt5a concentrations and eGFR at each stage of CKD, with higher levels in female patients. This phenomenon suggests that Sfrp5 and Wnt5a might be involved in development and evolution towards end-stage renal disease.
Downloads
References
Hernández-Ávila M, Gutiérrez JP, Reynoso-Noverón N. Diabetes mellitus en México. El estado de la epidemia [Diabetes mellitus in Mexico. Status of the epidemic]. Salud Pública Mex. 2013;55(S2):S129-36. PMID: 24626688.
Abascal REC, Febles OF, Simón OG, Padrón GR, Moya OA. Nefropatía diabética en pacientes diabéticos tipo 2 [Diabetic nephropathy in type 2 diabetes patients]. Rev Cubana Med. 2011;50(1):29-39. Available from: Available from: http://scielo.sld.cu/scielo.php?script=sci_arttext&pid=S0034-75232011000100003&lng=es Accessed in 2019 (Dec 10).
Sacks DB, Arnold M, Bakris GL, et al. Guidelines and recommendations for laboratory analysis in the diagnosis and management of diabetes mellitus. Clin Chem. 2011;34(6):e1-e47. PMID: 21617152; doi: 10.1373/clinchem.2010.161596.
Martín-López A, Soto-Montenegro M, Jara-Albarrán A. Nefropatía diabética. Medicina Clínica. 2002;118(8):312-7. doi: 10.1016/S0025-7753(02)72368-3.
Zenteno-Castillo P, Muñoz-López DB, Merino-Reyes B, et al. Prevalence of diabetic nephropathy in type 2 Diabetes Mellitus in rural communities of Guanajuato, Mexico. Effect after 6 months of Telmisartan treatment. J Clin Transl Endocrinol. 2015; 2(4):125-128. PMID: 29159116; doi: 10.1016/j.jcte.2015.08.001.
Lim AK, Tesch GH. Inflammation in diabetic nephropathy. Mediators Inflamm. 2012;2012:146154. PMID: 22969168; doi: 10.1155/2012/146154.
Bilkovski R, Schulte DM, Oberhauser F, et al. Adipose tissue macrophages inhibit adipogenesis of mesenchymal precursor cells via Wnt-5a in humans. Int J Obes (Lond). 2011;35(11):1450-4. PMID: 21285942; doi: 10.1038/ijo.2011.6.
Toan NL, Van Hoan N, Cuong DV, et al. Adipose tissue-derived cytokines and their correlations with clinical characteristics in Vietnamese patients with type 2 diabetes mellitus. Diabetol Metab Syndr. 2018;10:41. PMID: 29785210; doi: 10.1186/s13098-018-0343-4.
Liu LB, Chen XD, Zhou XY, Zhu Q. The Wnt antagonist and secreted frizzled-related protein 5: implications on lipid metabolism, inflammation, and type 2 diabetes mellitus. Biosci Rep. 2018;38(4). Pii BSR20180011. PMID: 29789397; doi: 10.1042/BSR20180011.
Wang CP, Yu TH, Wu CC, et al. Circulating secreted frizzled-related protein 5 and chronic kidney disease in patients with acute ST-segment elevation myocardial infarction. Cytokine. 2018;110:367-73. PMID: 29807686; doi: 10.1016/j.cyto.2018.04.009.
Treviño BA, Baca ER, Meza CC, Chávez ZMI, Gamboa MVE. Medición de la filtración glomerular comparativa por cistatina C y métodos convencionales basados en la depuración de creatinina. Rev Hosp Jua Mex. 2010;77(1):22-7. Available from: Available from: https://www.medigraphic.com/pdfs/juarez/ju-2010/ju101e.pdf Accessed in 2019 (Aug 20).
Nirwan DS, Vyas RK, Jain S. Comparative study of serum urea, creatinine and C-reactive protein level in chronic kidney disease patients with healthy subjects. Int J Res Med Sci. 2017;5(4):1480-3. doi: 10.18203/2320-6012.ijrms20171250.
Tong S, Ji Q, Du Y, et al. Sfrp5/Wnt pathway: a protective regulatory system in atherosclerotic cardiovascular disease. J Interferon Cytokine Res. 2019;39(8):472-82. PMID: 3199714; doi: 10.1089/jir.2018.0154.
Liu LB, Chen XD, Zhou XY, Zhu Q. The Wnt antagonist and secreted frizzled-related protein 5: implications on lipid metabolism, inflammation, and type 2 diabetes mellitus. Biosci Rep. 2018;38(4):BSR20180011. PMID: 29789397; doi: 10.1042/BSR20180011.
Ehrlund A, Mejhert N, Lorente-Cebrián S, et al. Characterization of the Wnt inhibitors secreted frizzled-related proteins (SFRPs) in human adipose tissue. J Clin Endocrinol Metab. 2013;98(3):E503-8. PMID: 23393180; doi: 10.1210/jc.2012-3416.
Carstensen M, Herder C, Kempf K, et al. Sfrp5 correlates with insulin resistance and oxidative stress. Eur J Clin Invest. 2013;43(4):350-7. PMID: 23398169; doi: 10.1111/eci.12052.
Kawano Y, Kypta R. Secreted antagonists of the Wnt signalling pathway. J Cell Sci. 2013;116(Pt 13):2627-34. PMID: 12775774; doi: 10.1242/jcs.00623.
Almario RU, Karakas SE. Roles of circulating WNT-signaling proteins and WNT-inhibitors in human adiposity, insulin resistance, insulin secretion, and inflammation. Horm Metab Res. 2015;47(2):152-7. PMID: 25089371; doi: 10.1055/s-0034-1384521.
Bretón-Romero R, Feng B, Holbrook M, et al. Endothelial dysfunction in human diabetes is mediated by Wnt5a-JNK signaling. Arterioscler Thromb Vasc Biol. 2016;36(3):561-9. PMID: 26800561; doi: 10.1161/ATVBAHA.115.306578.
Viloria AT, Castillo ZR. Nefropatía diabética. Rev Hosp Gral Dr. M Gea Gonzaléz. 2002;5(1-2):24-32. Available from Available from http://medicinadeurgencias.tripod.com/sitebuildercontent/sitebuilderfiles/nefropatiadiabetica.pdf Accessed in 2019 (Aug 20).
Navarro JF, Mora C, Muros M, García J. Urinary tumor necrosis factor-alpha excretion independently correlates with clinical markers of glomerular and tubulointerstitial injury in type 2 diabetic patients. Nephrol Dial Transplant. 2006;21(12):3428-34. PMID: 16935891; doi: 10.1093/ndt/gfl469.
Munarriz CL, Zevallos JC, Barahona CN, Benites KB. ¿Llegan oportunamente los pacientes con nefropatía diabética al servicio de Nefrología del Hospital Nacional Cayetano Heredia durante el periodo enero 2011-enero 2012? [Do patients with diabetic nephropathy arrive on time to the Nephrology Service in Cayetano Heredia Hospital? A one-year assessment: January 2011-January 2012]. Acta Med Per. 2013;30(2):57-62. Available from: Available from: http://www.scielo.org.pe/scielo.php?script=sci_arttext&pid=S1728-59172013000200002&lng=es Accessed in 2019 (Dec 10).
Tsou PL, Jiang YD, Chang CC, et al. Sex-related differences between adiponectin and insulin resistance in schoolchildren. Diabetes Care. 2004;27(2):308-13. PMID: 14747205; doi: 10.2337/diacare.27.2.308.
Pichler R, Afkarian M, Dieter BP, Tuttle KR. Immunity and inflammation in diabetic kidney disease: translating mechanisms to biomarkers and treatment targets. Am J Physiol Renal Physiol. 2017;312(4):F716-31. PMID: 27558558; doi: 10.1152/ajprenal.00314.2016.
Matsuoka A, Kizuka F, Lee L, et al. Progesterone increases manganese superoxide dismutase expression via a cAMP-dependent signaling mediated by noncanonical Wnt5a pathway in human endometrial stromal cells. J Clin Endocrinol Metab. 2010;95(11):E291-9. PMID: 20685861; doi: 10.1210/jc.2010-0619.
Navarro JF, Mora C, Muros M, García J. Urinary tumour necrosis factor-alpha excretion independently correlates with clinical markers of glomerular and tubulointerstitial injury in type 2 diabetic patients. Nephrol Dial Transplant. 2006;21(12):3428-34. PMID: 16935891; doi: 10.1093/ndt/gfl469.
Flores-Ramírez J, Aguilar-Rebolledo F. Diabetes mellitus y sus complicaciones. La epidemiología, las manifestaciones clínicas de la diabetes tipo 1 y 2. Diabetes gestacional. Parte 1. Plast & Rest Neurol. 2006;5(2):139-51. Available from: Available from: https://pdfs.semanticscholar.org/ba79/4b9de3cf0a2ab6286e0389e39871f356830f.pdf Accessed in 2019 (Aug 20).
