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The Role of Mesencephalic Astrocyte-Derived Neurotrophic Factor (MANF) in Biomarkers of Diabetic Nephropathy

Yıl 2025, Cilt: 11 Sayı: 2, 65 - 69, 27.05.2025
https://doi.org/10.30934/kusbed.1653929

Öz

Objective: This study investigates the potential role of Mesencephalic Astrocyte-Derived Neurotrophic Factor (MANF) as a novel biomarker, evaluating its associations with established urinary biomarkers and glycemic control indicators in diabetes mellitus and diabetic nephropathy (DN).
Methods: A cross-sectional study was conducted involving 84 participants stratified by albuminuria levels into normoalbuminuria, microalbuminuria, and macroalbuminuria groups. MANF levels were quantified using enzyme-linked immunosorbent assays (ELISA), while urinary biomarkers and HbA1C were measured using standard clinical methods. Correlation analyses and multivariate regression models were employed to assess relationships between MANF and biomarkers.
Results: MANF levels demonstrated a significant upward trend across albuminuria categories, with the highest levels observed in the macroalbuminuria group (514.5±112.3 pg/mL, p<0.01). MANF positively correlated with HbA1C (R=0.78, p<0.001) and negatively with estimated glomerular filtration rate (eGFR) (R=0.72, p<0.001). These associations remained significant after adjusting for confounders such as age, sex, and body mass index (BMI).
Conclusion: MANF is a promising biomarker that reflects glycemic dysregulation and renal dysfunction, offering potential advantages over traditional markers. Its integration into clinical practice could enhance the early detection and personalized management of chronic kidney disease (CKD) and diabetes. Future longitudinal studies are warranted to validate its predictive value.

Kaynakça

  • Fassett RG, Venuthurupalli SK, Gobe GC, Coombes JS, Cooper MA, Hoy WE. Biomarkers in chronic kidney disease: a review. Kidney Int. 2011;80(8):806-821. doi:10.1038/ki.2011.198
  • Zhao YY. Metabolomics in chronic kidney disease. Clin Chim Acta. 2013;422:59-69. doi:10.1016/j.cca.2013.03.033
  • Wasung ME, Chawla LS, Madero M. Biomarkers of renal function, which and when? Clin Chim Acta. 2015;438:350-357. doi:10.1016/j.cca.2014.08.039
  • Julkunen H. Metabolic blood biomarker profiling for chronic kidney disease prediction. Nephrol Dial Transplant. 2023;38. doi:10.1093/ndt/gfad063c_5650
  • Tesch GH. Review: Serum and urine biomarkers of kidney disease: a pathophysiological perspective. Nephrology (Carlton). 2010;15(6):609-616. doi:10.1111/j.1440- 1797.2010.01361.x
  • Zhang ZH, Chen H, Vaziri ND, et al. Metabolomic signatures of chronic kidney disease of diverse etiologies in the rats and humans. J Proteome Res. 2016;15(10):3802-3812. doi:10.1021/acs.jproteome.6b00583
  • Breit M, Weinberger KM. Metabolic biomarkers for chronic kidney disease. Arch Biochem Biophys. 2016;589:62-80. doi:10.1016/j.abb.2015.07.018
  • Kim Y, Lee H, Manson SR, et al. Mesencephalic astrocytederived neurotrophic factor as a urine biomarker for endoplasmic reticulum stress-related kidney diseases. J Am Soc Nephrol. 2016;27(10):2974-2982. doi:10.1681/ASN.2014100986
  • Liu H, Tang X, Gong L. Mesencephalic astrocyte-derived neurotrophic factor and cerebral dopamine neurotrophic factor: new endoplasmic reticulum stress response proteins. Eur J Pharmacol. 2015;750:118-122. doi:10.1016/j.ejphar.2015.01.016
  • Lindahl M, Danilova T, Palm E, et al. MANF is indispensable for the proliferation and survival of pancreatic β cells. Cell Rep. 2014;7(2):366-375. doi:10.1016/j.celrep.2014.03.023
  • Kim WJ, Park CY, Lee KB, et al. Serum 1,5-anhydroglucitol concentrations are a reliable index of glycemic control in type 2 diabetes with mild or moderate renal dysfunction. Diabetes Care. 2012;35(2):281-286. doi:10.2337/dc11-1462
  • Zhang H, Zuo JJ, Dong SS, et al. Identification of potential serum metabolic biomarkers of diabetic kidney disease: a widely targeted metabolomics study. J Diabetes Res. 2020;2020:3049098. doi:10.1155/2020/3049098
  • Inaba M, Okuno S, Kumeda Y, et al. Glycated albumin is a better glycemic indicator than glycated hemoglobin values in hemodialysis patients with diabetes: effect of anemia and erythropoietin injection. J Am Soc Nephrol. 2007;18(3):896- 903. doi:10.1681/ASN.2006070772
  • Dozio E, Corradi V, Proglio M, et al. Usefulness of glycated albumin as a biomarker for glucose control and prognostic factor in chronic kidney disease patients on dialysis (CKDG5D). Diabetes Res Clin Pract. 2018;140:9-17. doi:10.1016/j.diabres.2018.03.017
  • Looker HC, Colombo M, Hess S, et al. Biomarkers of rapid chronic kidney disease progression in type 2 diabetes. Kidney Int. 2015;88(4):888-896. doi:10.1038/ki.2015.199
  • Zelnick LR, Batacchi ZO, Ahmad I, et al. Continuous glucose monitoring and use of alternative markers to assess glycemia in chronic kidney disease. Diabetes Care. 2020;43(10):2379- 2387. doi:10.2337/dc20-0915
  • Mizdrak M, Kumrić M, Kurir TT, Božić J. Emerging biomarkers for early detection of chronic kidney disease. J Pers Med. 2022;12(4):548. doi:10.3390/jpm12040548
  • Speeckaert M, Van Biesen W, Delanghe J, et al. Are there better alternatives than haemoglobin A1c to estimate glycaemic control in the chronic kidney disease population? Nephrol Dial Transplant. 2014;29(12):2167-2177. doi:10.1093/ndt/gfu006
  • Chaudhary K, Phadke G, Nistala R, Weidmeyer CE, McFarlane SI, Whaley-Connell A. The emerging role of biomarkers in diabetic and hypertensive chronic kidney disease. Curr Diab Rep. 2010;10(1):37-42. doi:10.1007/s11892-009-0080-z
  • Lousa I, Reis F, Beirão I, Alves R, Belo L, Santos-Silva A. New potential biomarkers for chronic kidney disease management— a review of the literature. Int J Mol Sci. 2020;22(1):43. doi:10.3390/ijms22010043
  • Galindo RJ, Beck RW, Scioscia MF, Umpierrez GE, Tuttle KR. Glycemic monitoring and management in advanced chronic kidney disease. Endocr Rev. 2020;41(5):756-774. doi:10.1210/endrev/bnaa017
  • Cardenas-Gonzalez M, Srivastava A, Pavkovic M, et al. Identification, confirmation, and replication of novel urinary microRNA biomarkers in lupus nephritis and diabetic nephropathy. Clin Chem. 2017;63(9):1515-1526. doi:10.1373/clinchem.2017.274175
  • Lecamwasam A, Ekinci EI, Saffery R, Dwyer KM. Potential for novel biomarkers in diabetes-associated chronic kidney disease: epigenome, metabolome, and gut microbiome. Biomedicines. 2020;8(9):341. doi:10.3390/biomedicines8090341

The Role of Mesencephalic Astrocyte-Derived Neurotrophic Factor (MANF) in Biomarkers of Diabetic Nephropathy

Yıl 2025, Cilt: 11 Sayı: 2, 65 - 69, 27.05.2025
https://doi.org/10.30934/kusbed.1653929

Öz

Objective: This study investigates the potential role of Mesencephalic Astrocyte-Derived Neurotrophic Factor (MANF) as a novel biomarker, evaluating its associations with established urinary biomarkers and glycemic control indicators in diabetes mellitus and diabetic nephropathy (DN).
Methods: A cross-sectional study was conducted involving 84 participants stratified by albuminuria levels into normoalbuminuria, microalbuminuria, and macroalbuminuria groups. MANF levels were quantified using enzyme-linked immunosorbent assays (ELISA), while urinary biomarkers and HbA1C were measured using standard clinical methods. Correlation analyses and multivariate regression models were employed to assess relationships between MANF and biomarkers.
Results: MANF levels demonstrated a significant upward trend across albuminuria categories, with the highest levels observed in the macroalbuminuria group (514.5±112.3 pg/mL, p<0.01). MANF positively correlated with HbA1C (R=0.78, p<0.001) and negatively with estimated glomerular filtration rate (eGFR) (R=0.72, p<0.001). These associations remained significant after adjusting for confounders such as age, sex, and body mass index (BMI).
Conclusion: MANF is a promising biomarker that reflects glycemic dysregulation and renal dysfunction, offering potential advantages over traditional markers. Its integration into clinical practice could enhance the early detection and personalized management of chronic kidney disease (CKD) and diabetes. Future longitudinal studies are warranted to validate its predictive value.

Kaynakça

  • Fassett RG, Venuthurupalli SK, Gobe GC, Coombes JS, Cooper MA, Hoy WE. Biomarkers in chronic kidney disease: a review. Kidney Int. 2011;80(8):806-821. doi:10.1038/ki.2011.198
  • Zhao YY. Metabolomics in chronic kidney disease. Clin Chim Acta. 2013;422:59-69. doi:10.1016/j.cca.2013.03.033
  • Wasung ME, Chawla LS, Madero M. Biomarkers of renal function, which and when? Clin Chim Acta. 2015;438:350-357. doi:10.1016/j.cca.2014.08.039
  • Julkunen H. Metabolic blood biomarker profiling for chronic kidney disease prediction. Nephrol Dial Transplant. 2023;38. doi:10.1093/ndt/gfad063c_5650
  • Tesch GH. Review: Serum and urine biomarkers of kidney disease: a pathophysiological perspective. Nephrology (Carlton). 2010;15(6):609-616. doi:10.1111/j.1440- 1797.2010.01361.x
  • Zhang ZH, Chen H, Vaziri ND, et al. Metabolomic signatures of chronic kidney disease of diverse etiologies in the rats and humans. J Proteome Res. 2016;15(10):3802-3812. doi:10.1021/acs.jproteome.6b00583
  • Breit M, Weinberger KM. Metabolic biomarkers for chronic kidney disease. Arch Biochem Biophys. 2016;589:62-80. doi:10.1016/j.abb.2015.07.018
  • Kim Y, Lee H, Manson SR, et al. Mesencephalic astrocytederived neurotrophic factor as a urine biomarker for endoplasmic reticulum stress-related kidney diseases. J Am Soc Nephrol. 2016;27(10):2974-2982. doi:10.1681/ASN.2014100986
  • Liu H, Tang X, Gong L. Mesencephalic astrocyte-derived neurotrophic factor and cerebral dopamine neurotrophic factor: new endoplasmic reticulum stress response proteins. Eur J Pharmacol. 2015;750:118-122. doi:10.1016/j.ejphar.2015.01.016
  • Lindahl M, Danilova T, Palm E, et al. MANF is indispensable for the proliferation and survival of pancreatic β cells. Cell Rep. 2014;7(2):366-375. doi:10.1016/j.celrep.2014.03.023
  • Kim WJ, Park CY, Lee KB, et al. Serum 1,5-anhydroglucitol concentrations are a reliable index of glycemic control in type 2 diabetes with mild or moderate renal dysfunction. Diabetes Care. 2012;35(2):281-286. doi:10.2337/dc11-1462
  • Zhang H, Zuo JJ, Dong SS, et al. Identification of potential serum metabolic biomarkers of diabetic kidney disease: a widely targeted metabolomics study. J Diabetes Res. 2020;2020:3049098. doi:10.1155/2020/3049098
  • Inaba M, Okuno S, Kumeda Y, et al. Glycated albumin is a better glycemic indicator than glycated hemoglobin values in hemodialysis patients with diabetes: effect of anemia and erythropoietin injection. J Am Soc Nephrol. 2007;18(3):896- 903. doi:10.1681/ASN.2006070772
  • Dozio E, Corradi V, Proglio M, et al. Usefulness of glycated albumin as a biomarker for glucose control and prognostic factor in chronic kidney disease patients on dialysis (CKDG5D). Diabetes Res Clin Pract. 2018;140:9-17. doi:10.1016/j.diabres.2018.03.017
  • Looker HC, Colombo M, Hess S, et al. Biomarkers of rapid chronic kidney disease progression in type 2 diabetes. Kidney Int. 2015;88(4):888-896. doi:10.1038/ki.2015.199
  • Zelnick LR, Batacchi ZO, Ahmad I, et al. Continuous glucose monitoring and use of alternative markers to assess glycemia in chronic kidney disease. Diabetes Care. 2020;43(10):2379- 2387. doi:10.2337/dc20-0915
  • Mizdrak M, Kumrić M, Kurir TT, Božić J. Emerging biomarkers for early detection of chronic kidney disease. J Pers Med. 2022;12(4):548. doi:10.3390/jpm12040548
  • Speeckaert M, Van Biesen W, Delanghe J, et al. Are there better alternatives than haemoglobin A1c to estimate glycaemic control in the chronic kidney disease population? Nephrol Dial Transplant. 2014;29(12):2167-2177. doi:10.1093/ndt/gfu006
  • Chaudhary K, Phadke G, Nistala R, Weidmeyer CE, McFarlane SI, Whaley-Connell A. The emerging role of biomarkers in diabetic and hypertensive chronic kidney disease. Curr Diab Rep. 2010;10(1):37-42. doi:10.1007/s11892-009-0080-z
  • Lousa I, Reis F, Beirão I, Alves R, Belo L, Santos-Silva A. New potential biomarkers for chronic kidney disease management— a review of the literature. Int J Mol Sci. 2020;22(1):43. doi:10.3390/ijms22010043
  • Galindo RJ, Beck RW, Scioscia MF, Umpierrez GE, Tuttle KR. Glycemic monitoring and management in advanced chronic kidney disease. Endocr Rev. 2020;41(5):756-774. doi:10.1210/endrev/bnaa017
  • Cardenas-Gonzalez M, Srivastava A, Pavkovic M, et al. Identification, confirmation, and replication of novel urinary microRNA biomarkers in lupus nephritis and diabetic nephropathy. Clin Chem. 2017;63(9):1515-1526. doi:10.1373/clinchem.2017.274175
  • Lecamwasam A, Ekinci EI, Saffery R, Dwyer KM. Potential for novel biomarkers in diabetes-associated chronic kidney disease: epigenome, metabolome, and gut microbiome. Biomedicines. 2020;8(9):341. doi:10.3390/biomedicines8090341
Toplam 23 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular İç Hastalıkları
Bölüm Özgün Araştırma
Yazarlar

Kağan Tur 0000-0001-5989-2099

Kenan Güçlü 0000-0002-0092-652X

Yayımlanma Tarihi 27 Mayıs 2025
Gönderilme Tarihi 8 Mart 2025
Kabul Tarihi 28 Nisan 2025
Yayımlandığı Sayı Yıl 2025 Cilt: 11 Sayı: 2

Kaynak Göster

APA Tur, K., & Güçlü, K. (2025). The Role of Mesencephalic Astrocyte-Derived Neurotrophic Factor (MANF) in Biomarkers of Diabetic Nephropathy. Kocaeli Üniversitesi Sağlık Bilimleri Dergisi, 11(2), 65-69. https://doi.org/10.30934/kusbed.1653929
AMA Tur K, Güçlü K. The Role of Mesencephalic Astrocyte-Derived Neurotrophic Factor (MANF) in Biomarkers of Diabetic Nephropathy. KOU Sag Bil Derg. Mayıs 2025;11(2):65-69. doi:10.30934/kusbed.1653929
Chicago Tur, Kağan, ve Kenan Güçlü. “The Role of Mesencephalic Astrocyte-Derived Neurotrophic Factor (MANF) in Biomarkers of Diabetic Nephropathy”. Kocaeli Üniversitesi Sağlık Bilimleri Dergisi 11, sy. 2 (Mayıs 2025): 65-69. https://doi.org/10.30934/kusbed.1653929.
EndNote Tur K, Güçlü K (01 Mayıs 2025) The Role of Mesencephalic Astrocyte-Derived Neurotrophic Factor (MANF) in Biomarkers of Diabetic Nephropathy. Kocaeli Üniversitesi Sağlık Bilimleri Dergisi 11 2 65–69.
IEEE K. Tur ve K. Güçlü, “The Role of Mesencephalic Astrocyte-Derived Neurotrophic Factor (MANF) in Biomarkers of Diabetic Nephropathy”, KOU Sag Bil Derg, c. 11, sy. 2, ss. 65–69, 2025, doi: 10.30934/kusbed.1653929.
ISNAD Tur, Kağan - Güçlü, Kenan. “The Role of Mesencephalic Astrocyte-Derived Neurotrophic Factor (MANF) in Biomarkers of Diabetic Nephropathy”. Kocaeli Üniversitesi Sağlık Bilimleri Dergisi 11/2 (Mayıs2025), 65-69. https://doi.org/10.30934/kusbed.1653929.
JAMA Tur K, Güçlü K. The Role of Mesencephalic Astrocyte-Derived Neurotrophic Factor (MANF) in Biomarkers of Diabetic Nephropathy. KOU Sag Bil Derg. 2025;11:65–69.
MLA Tur, Kağan ve Kenan Güçlü. “The Role of Mesencephalic Astrocyte-Derived Neurotrophic Factor (MANF) in Biomarkers of Diabetic Nephropathy”. Kocaeli Üniversitesi Sağlık Bilimleri Dergisi, c. 11, sy. 2, 2025, ss. 65-69, doi:10.30934/kusbed.1653929.
Vancouver Tur K, Güçlü K. The Role of Mesencephalic Astrocyte-Derived Neurotrophic Factor (MANF) in Biomarkers of Diabetic Nephropathy. KOU Sag Bil Derg. 2025;11(2):65-9.