Vol 71, No 6 (2020)
Review paper
Published online: 2020-12-29
What do we know about biomarkers in diabetic kidney disease?
Abstract
Diabetic kidney disease (DKD) remains the leading cause of the end-stage renal disease (ESRD) and the most common reason for renal replacement therapy. Research has been carried out for years to find a marker that would enable early identification of people at risk of DKD occurrence, as well as people who will progress from DKD to ESRD. With regard to daily medical practice, the only existing prognostic biomarkers in DKD remain urine albumin-creatinine ratio based on the urinary assessment of albumin and creatinine, and estimated glomerular filtration rate — on the basis of serum creatinine concentration. The development of other biomarkers that would enable the identification of patients at risk of DKD, the stratification of the risk of progression to ESRD, as well as the creation of personalised therapy is currently of great interest. This article discusses selected studies in this field, which have been published in recent years.
Keywords: diabetic kidney diseasebiomarkerUACReGFR
References
- Livingstone SJ, Levin D, Looker HC, et al. Scottish Diabetes Research Network epidemiology group, Scottish Renal Registry. Estimated life expectancy in a Scottish cohort with type 1 diabetes, 2008-2010. JAMA. 2015; 313(1): 37–44.
- Livingstone SJ, Looker HC, Hothersall EJ, et al. Risk of cardiovascular disease and total mortality in adults with type 1 diabetes: Scottish registry linkage study. PLoS Med. 2012; 9(10): e1001321.
- Sharma P, McCullough K, Scotland G, et al. Does stage-3 chronic kidney disease matter?: A systematic literature review. Br J Gen Pract. 2010; 60(575): e266–e276.
- Cypryk K, Małecki P. A review of cardiovascular outcome trials in type 2 diabetes. Endokrynol Pol. 2018; 69(4).
- Szczech LA, Stewart RC, Su HL, et al. Primary care detection of chronic kidney disease in adults with type-2 diabetes: the ADD-CKD Study (awareness, detection and drug therapy in type 2 diabetes and chronic kidney disease). PLoS One. 2014; 9(11): e110535.
- FDA-NIH Biomarker Working Group. BEST (Biomarkers, EndpointS, and other Tools) Resource [Internet]. Silver Spring (MD): Food and Drug Administration (US); 2016. Co-published by National Institutes of Health (US), Bethesda (MD). https://www.ncbi.nlm.nih.gov/books/NBK326791/ (13.08.2020).
- Mogensen CE. Microalbuminuria as a predictor of clinical diabetic nephropathy. Kidney Int. 1987; 31(2): 673–689.
- Jones RH, Hayakawa H, Mackay JD, et al. Progression of diabetic nephropathy. Lancet. 1979; 1(8126): 1105–1106.
- Araszkiewicz A, Bandurska-Stankiewicz E, Budzyński A, et al. 2020 Guidelines on the management of diabetic patients. A position of Diabetes Poland. Clin Diab. 2020; 9(1): 1–101.
- American Diabetes Association. 11. Microvascular Complications and Foot Care. Standards of Medical Care in Diabetes — 2020. Diabetes Care. 2020; 43(Suppl 1): S135–S151.
- Viberti GC, Jarrett RJ, Keen H. Microalbuminuria as prediction of nephropathy in diabetics. Lancet. 1982; 2(8298): 611.
- Skupien J, Warram JH, Smiles AM, et al. Patterns of Estimated Glomerular Filtration Rate Decline Leading to End-Stage Renal Disease in Type 1 Diabetes. Diabetes Care. 2016; 39(12): 2262–2269.
- Oshima M, Toyama T, Haneda M, et al. Research Group of Diabetic Nephropathy, Ministry of Health, Labour, and Welfare of Japan. Estimated glomerular filtration rate decline and risk of end-stage renal disease in type 2 diabetes. PLoS One. 2018; 13(8): e0201535.
- Skupien J, Warram JH, Smiles AM, et al. The early decline in renal function in patients with type 1 diabetes and proteinuria predicts the risk of end-stage renal disease. Kidney Int. 2012; 82(5): 589–597.
- Krolewski AS, Warram JH, Forsblom C, et al. Serum concentration of cystatin C and risk of end-stage renal disease in diabetes. Diabetes Care. 2012; 35(11): 2311–2316.
- Colhoun HM, Marcovecchio ML. Biomarkers of diabetic kidney disease. Diabetologia. 2018; 61(5): 996–1011.
- Jendrzejewski JP, Sworczak K, Comiskey DF, et al. Clinical implications of GWAS variants associated with differentiated thyroid cancer. Endokrynol Pol. 2019; 70(5): 423–429.
- Kwiendacz H, Nabrdalik K, Adamczyk P, et al. Association of single nucleotide polymorphism (rs741301) of the ELMO1 gene with diabetic kidney disease in Polish patients with type 2 diabetes: a pilot study. Endokrynol Pol. 2020; 71(1): 66–72.
- Pavkov ME, Weil EJ, Fufaa GD, et al. Tumor necrosis factor receptors 1 and 2 are associated with early glomerular lesions in type 2 diabetes. Kidney Int. 2016;89:226-234. Kidney Int. 2016; 90(3): 709.
- Niewczas MA, Gohda T, Skupien J, et al. Circulating TNF receptors 1 and 2 predict ESRD in type 2 diabetes. J Am Soc Nephrol. 2012; 23(3): 507–515.
- Jian WX, Peng WH, Jin J, et al. Association between serum fibroblast growth factor 21 and diabetic nephropathy. Metabolism. 2012; 61(6): 853–859.
- Bidadkosh A, Lambooy SPH, Heerspink HJ, et al. Predictive Properties of Biomarkers GDF-15, NTproBNP, and hs-TnT for Morbidity and Mortality in Patients With Type 2 Diabetes With Nephropathy. Diabetes Care. 2017; 40(6): 784–792.
- Boertien WE, Riphagen IJ, Drion I, et al. Copeptin, a surrogate marker for arginine vasopressin, is associated with declining glomerular filtration in patients with diabetes mellitus (ZODIAC-33). Diabetologia. 2013; 56(8): 1680–1688.
- Nielsen SE, Reinhard H, Zdunek D, et al. Tubular markers are associated with decline in kidney function in proteinuric type 2 diabetic patients. Diabetes Res Clin Pract. 2012; 97(1): 71–76.
- Wu L, Li XQ, Chang DY, et al. Associations of urinary epidermal growth factor and monocyte chemotactic protein-1 with kidney involvement in patients with diabetic kidney disease. Nephrol Dial Transplant. 2020; 35(2): 291–297.
- Li B, Zhang Y, Wang F, et al. Urinary epidermal growth factor as a prognostic marker for the progression of Alport syndrome in children. Pediatr Nephrol. 2018; 33(10): 1731–1739.
- Isaka Y. Epidermal growth factor as a prognostic biomarker in chronic kidney diseases. Ann Transl Med. 2016; 4(Suppl 1): S62.
- Kurosu H, Yamamoto M, Clark JD, et al. Suppression of aging in mice by the hormone Klotho. Science. 2005; 309(5742): 1829–1833.
- Flotyńska J, Uruska A, Araszkiewicz A, et al. Klotho protein function among patients with type 1 diabetes. Endokrynol Pol. 2018; 69(6): 696–704.
- Wong MG, Perkovic V, Woodward M, et al. Circulating bone morphogenetic protein-7 and transforming growth factor-β1 are better predictors of renal end points in patients with type 2 diabetes mellitus. Kidney Int. 2013; 83(2): 278–284.
- Nowak N, Skupien J, Smiles AM, et al. Markers of early progressive renal decline in type 2 diabetes suggest different implications for etiological studies and prognostic tests development. Kidney Int. 2018; 93(5): 1198–1206.
- Drew DA, Katz R, Kritchevsky S, et al. Association between Soluble Klotho and Change in Kidney Function: The Health Aging and Body Composition Study. J Am Soc Nephrol. 2017; 28(6): 1859–1866.
- Liu QF, Yu LX, Feng JH, et al. The Prognostic Role of Klotho in Patients with Chronic Kidney Disease: A Systematic Review and Meta-analysis. Dis Markers. 2019; 2019: 6468729.
- Kim SS, Song SH, Kim InJ, et al. Decreased plasma α-Klotho predict progression of nephropathy with type 2 diabetic patients. J Diabetes Complications. 2016; 30(5): 887–892.
- Fountoulakis N, Maltese G, Gnudi L, et al. Reduced Levels of Anti-Ageing Hormone Klotho Predict Renal Function Decline in Type 2 Diabetes. J Clin Endocrinol Metab. 2018; 103(5): 2026–2032.
- Salem RM, Todd JN, Sandholm N, et al. SUMMIT Consortium, DCCT/EDIC Research Group, GENIE Consortium. Genome-Wide Association Study of Diabetic Kidney Disease Highlights Biology Involved in Glomerular Basement Membrane Collagen. J Am Soc Nephrol. 2019; 30(10): 2000–2016.
- Tebani A, Afonso C, Marret S, et al. Omics-Based Strategies in Precision Medicine: Toward a Paradigm Shift in Inborn Errors of Metabolism Investigations. Int J Mol Sci. 2016; 17(9).
- Mayer G, Heerspink HJL, Aschauer C, et al. SYSKID Consortium. Systems Biology-Derived Biomarkers to Predict Progression of Renal Function Decline in Type 2 Diabetes. Diabetes Care. 2017; 40(3): 391–397.
- Ahlqvist E, Storm P, Käräjämäki A, et al. Novel subgroups of adult-onset diabetes and their association with outcomes: a data-driven cluster analysis of six variables. Lancet Diabetes Endocrinol. 2018; 6(5): 361–369.
- van Zuydam NR, Ahlqvist E, Sandholm N, et al. Finnish Diabetic Nephropathy Study (FinnDiane), Hong Kong Diabetes Registry Theme-based Research Scheme Project Group, Warren 3 and Genetics of Kidneys in Diabetes (GoKinD) Study Group, GENIE (GEnetics of Nephropathy an International Effort) Consortium, Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) Research Group, SUrrogate markers for Micro- and Macrovascular hard endpoints for Innovative diabetes Tools (SUMMIT) Consortium. A Genome-Wide Association Study of Diabetic Kidney Disease in Subjects With Type 2 Diabetes. Diabetes. 2018; 67(7): 1414–1427.
- Colombo M, Looker HC, Farran B, et al. SUMMIT Investigators. Serum kidney injury molecule 1 and β-microglobulin perform as well as larger biomarker panels for prediction of rapid decline in renal function in type 2 diabetes. Diabetologia. 2019; 62(1): 156–168.
- Mayer P, Mayer B, Mayer G. Systems biology: building a useful model from multiple markers and profiles. Nephrol Dial Transplant. 2012; 27(11): 3995–4002.
- Afshinnia F, Rajendiran TM, Wernisch S, et al. Lipidomic Signature of Progression of Chronic Kidney Disease in the Chronic Renal Insufficiency Cohort. Kidney Int Rep. 2016; 1(4): 256–268.
- Kammer M, Heinzel A, Willency JA, et al. BEAt-DKD Consortium. Integrative analysis of prognostic biomarkers derived from multiomics panels helps discrimination of chronic kidney disease trajectories in people with type 2 diabetes. Kidney Int. 2019; 96(6): 1381–1388.
- Tofte N, Lindhardt M, Adamova K, et al. PRIORITY investigators. Early detection of diabetic kidney disease by urinary proteomics and subsequent intervention with spironolactone to delay progression (PRIORITY): a prospective observational study and embedded randomised placebo-controlled trial. Lancet Diabetes Endocrinol. 2020; 8(4): 301–312.
- Heerspink HJL, Stefansson BV, Chertow GM, et al. DAPA-CKD Investigators. Rationale and protocol of the Dapagliflozin And Prevention of Adverse outcomes in Chronic Kidney Disease (DAPA-CKD) randomized controlled trial. Nephrol Dial Transplant. 2020; 35(2): 274–282.
- Sinha N, Kumar V, Puri V, et al. Urinary exosomes: Potential biomarkers for diabetic nephropathy. Nephrology (Carlton). 2020 [Epub ahead of print].
- Lu Y, Liu D, Feng Qi, et al. Diabetic Nephropathy: Perspective on Extracellular Vesicles. Front Immunol. 2020; 11: 943.
- Tonneijck L, Muskiet MHA, Blijdorp CJ, et al. Renal tubular effects of prolonged therapy with the GLP-1 receptor agonist lixisenatide in patients with type 2 diabetes mellitus. Am J Physiol Renal Physiol. 2019; 316(2): F231–F240.
- Ninčević V, Omanović Kolarić T, Roguljić H, et al. Renal Benefits of SGLT 2 Inhibitors and GLP-1 Receptor Agonists: Evidence Supporting a Paradigm Shift in the Medical Management of Type 2 Diabetes. Int J Mol Sci. 2019; 20(23).
- Scheen AJ. Effects of glucose-lowering agents on surrogate endpoints and hard clinical renal outcomes in patients with type 2 diabetes. Diabetes Metab. 2019; 45(2): 110–121.
