International Diabetes Federation. IDF Diabetes Atlas, 11th edn. Brussels, Belgium: 2025. Available at: https://www.diabetesatlas.org.
Hill CJ, Cardwell CR, Patterson CC, et al. Chronic kidney disease and diabetes in the national health service: a cross-sectional survey of the U.K. national diabetes audit. Diabet Med. 2014;31(4):448–54. https://doi.org/10.1111/dme.12312.
Google Scholar
Low Wang CC, Hess CN, Hiatt WR, Goldfine AB. Clinical update: cardiovascular disease in diabetes mellitus: atherosclerotic cardiovascular disease and heart failure in type 2 diabetes mellitus-mechanisms, management, and clinical considerations. Circulation. 2016;133(24):2459–502. https://doi.org/10.1161/CIRCULATIONAHA.116.022194.
Google Scholar
Lawson CA, Seidu S, Zaccardi F, et al. Outcome trends in people with heart failure, type 2 diabetes mellitus and chronic kidney disease in the UK over twenty years. EClinicalMedicine. 2021;32:100739. https://doi.org/10.1016/j.eclinm.2021.100739.
Google Scholar
Renard CB, Kramer F, Johansson F, et al. Diabetes and diabetes-associated lipid abnormalities have distinct effects on initiation and progression of atherosclerotic lesions. J Clin Invest. 2004;114(5):659–68. https://doi.org/10.1172/JCI17867.
Google Scholar
Ndumele CE, Neeland IJ, Tuttle KR, et al. A synopsis of the evidence for the science and clinical management of cardiovascular-kidney-metabolic (CKM) syndrome: a scientific statement from the American Heart Association. Circulation. 2023;148(20):1636–64. https://doi.org/10.1161/CIR.0000000000001186.
Google Scholar
Eeg-Olofsson K, Cederholm J, Nilsson PM, et al. Risk of cardiovascular disease and mortality in overweight and obese patients with type 2 diabetes: an observational study in 13,087 patients. Diabetologia. 2009;52(1):65–73. https://doi.org/10.1007/s00125-008-1190-x.
Google Scholar
Mogensen CE, Christensen CK, Vittinghus E. The stages in diabetic renal disease. With emphasis on the stage of incipient diabetic nephropathy. Diabetes. 1983;32(Suppl 2):64–78. https://doi.org/10.2337/diab.32.2.s64.
Google Scholar
Thomas MC, Macisaac RJ, Jerums G, et al. Nonalbuminuric renal impairment in type 2 diabetic patients and in the general population (national evaluation of the frequency of renal impairment cO-existing with NIDDM [NEFRON] 11). Diabetes Care. 2009;32(8):1497–502. https://doi.org/10.2337/dc08-2186.
Google Scholar
Vistisen D, Andersen GS, Hulman A, Persson F, Rossing P, Jørgensen ME. Progressive decline in estimated glomerular filtration rate in patients with diabetes after moderate loss in kidney function-even without albuminuria. Diabetes Care. 2019;42(10):1886–94. https://doi.org/10.2337/dc19-0349.
Google Scholar
Krolewski AS, Niewczas MA, Skupien J, et al. Early progressive renal decline precedes the onset of microalbuminuria and its progression to macroalbuminuria. Diabetes Care. 2014;37(1):226–34. https://doi.org/10.2337/dc13-0985.
Google Scholar
Penno G, Russo E, Garofolo M, et al. Evidence for two distinct phenotypes of chronic kidney disease in individuals with type 1 diabetes mellitus. Diabetologia. 2017;60(6):1102–13. https://doi.org/10.1007/s00125-017-4251-1.
Google Scholar
Scirica BM, Mosenzon O, Bhatt DL, et al. Cardiovascular outcomes according to urinary albumin and kidney disease in patients with type 2 diabetes at high cardiovascular risk: observations from the SAVOR-TIMI 53 trial. JAMA Cardiol. 2018;3(2):155–63. https://doi.org/10.1001/jamacardio.2017.4228.
Google Scholar
Sheng CS, Wang D, Yuan J, et al. CVD risk in non-albuminuric chronic kidney disease in hypertensive, non-diabetic subjects: a post-hoc analysis from SPRINT. Front Cardiovasc Med. 2022;9:977938. https://doi.org/10.3389/fcvm.2022.977938.
Google Scholar
Kim YJ, Hwang SW, Lee T, Lee JY, Uh Y. Association between urinary albumin creatinine ratio and cardiovascular disease. PLoS ONE. 2023;18(3):e0283083. https://doi.org/10.1371/journal.pone.0283083.
Google Scholar
Choi Y, Jacobs DR Jr, Shroff GR, Kramer H, Chang AR, Duprez DA. Progression of chronic kidney disease risk categories and risk of cardiovascular disease and total mortality: coronary artery risk development in young adults cohort. J Am Heart Assoc. 2022;11(21):e026685. https://doi.org/10.1161/JAHA.122.026685.
Google Scholar
Yokoyama H, Araki SI, Kawai K, et al. The prognosis of patients with type 2 diabetes and nonalbuminuric diabetic kidney disease is not always poor: implication of the effects of coexisting macrovascular complications (JDDM 54). Diabetes Care. 2020;43(5):1102–10. https://doi.org/10.2337/dc19-2049.
Google Scholar
Nabrdalik K, Kwiendacz H, Drożdż K, et al. Machine learning predicts cardiovascular events in patients with diabetes: the Silesia Diabetes-Heart project. Curr Probl Cardiol. 2023;48(7):101694. https://doi.org/10.1016/j.cpcardiol.2023.101694.
Google Scholar
KDIGO 2024 Clinical practice guideline for the evaluation and management of chronic kidney disease [Internet]. Available from: www.kidney-international.org
Kofod DH, Carlson N, Ballegaard EF, et al. Cardiovascular mortality in patients with advanced chronic kidney disease with and without diabetes: a nationwide cohort study. Cardiovasc Diabetol. 2023;22(1):140. https://doi.org/10.1186/s12933-023-01867-8.
Google Scholar
Chao CT, Lee SY, Wang J, Chien KL, Hung KY. The risk trajectory of different cardiovascular morbidities associated with chronic kidney disease among patients with newly diagnosed diabetes mellitus: a propensity score-matched cohort analysis. Cardiovasc Diabetol. 2021;20(1):86. https://doi.org/10.1186/s12933-021-01279-6.
Google Scholar
Liu WC, Tomino Y, Lu KC. Impacts of indoxyl sulfate and p-cresol sulfate on chronic kidney disease and mitigating effects of AST-120. Toxins (Basel). 2018;10(9):367. https://doi.org/10.3390/toxins10090367.
Google Scholar
Harlacher E, Wollenhaupt J, Baaten CCFMJ, Noels H. Impact of uremic toxins on endothelial dysfunction in chronic kidney disease: a systematic review. Int J Mol Sci. 2022;23(1):531. https://doi.org/10.3390/ijms23010531.
Google Scholar
Cook S, Schmedt N, Broughton J, Kalra PA, Tomlinson LA, Quint JK. Characterising the burden of chronic kidney disease among people with type 2 diabetes in England: a cohort study using the clinical practice research datalink. BMJ Open. 2023;13(3):e065927. https://doi.org/10.1136/bmjopen-2022-065927.
Google Scholar
Afkarian M, Katz R, Bansal N, et al. Diabetes, kidney disease, and cardiovascular outcomes in the Jackson Heart Study. Clin J Am Soc Nephrol. 2016;11(8):1384–91. https://doi.org/10.2215/CJN.13111215.
Google Scholar
Scilletta S, Di Marco M, Miano N, et al. Update on diabetic kidney disease (DKD): focus on non-albuminuric DKD and cardiovascular risk. Biomolecules. 2023;13(5):752. https://doi.org/10.3390/biom13050752.
Google Scholar
Ninomiya T, Perkovic V, de Galan BE, et al. Albuminuria and kidney function independently predict cardiovascular and renal outcomes in diabetes. J Am Soc Nephrol. 2009;20(8):1813–21. https://doi.org/10.1681/ASN.2008121270.
Google Scholar
Svensson MK, Cederholm J, Eliasson B, Zethelius B, Gudbjörnsdottir S; Swedish National Diabetes Register. Albuminuria and renal function as predictors of cardiovascular events and mortality in a general population of patients with type 2 diabetes: a nationwide observational study from the Swedish National Diabetes Register. Diab Vasc Dis Res. 2013;10(6):520–9. https://doi.org/10.1177/14791641135007
Drury PL, Ting R, Zannino D, et al. Estimated glomerular filtration rate and albuminuria are independent predictors of cardiovascular events and death in type 2 diabetes mellitus: the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study. Diabetologia. 2011;54(1):32–43. https://doi.org/10.1007/s00125-010-1854-1.
Google Scholar
Penno G, Solini A, Orsi E, et al. Non-albuminuric renal impairment is a strong predictor of mortality in individuals with type 2 diabetes: the Renal Insufficiency and Cardiovascular Events (RIACE) Italian multicentre study. Diabetologia. 2018;61(11):2277–89. https://doi.org/10.1007/s00125-018-4691-2.
Google Scholar
Di Marco M, Scilletta S, Miano N, et al. Cardiovascular risk and renal injury profile in subjects with type 2 diabetes and non-albuminuric diabetic kidney disease. Cardiovasc Diabetol. 2023;22(1):344. https://doi.org/10.1186/s12933-023-02065-2.
Google Scholar
Kramer HJ, Nguyen QD, Curhan G, Hsu CY. Renal insufficiency in the absence of albuminuria and retinopathy among adults with type 2 diabetes mellitus. JAMA. 2003;289(24):3273–7. https://doi.org/10.1001/jama.289.24.3273.
Google Scholar
Shi S, Ni L, Gao L, Wu X. Comparison of nonalbuminuric and albuminuric diabetic kidney disease among patients with type 2 diabetes: a systematic review and meta-analysis. Front Endocrinol (Lausanne). 2022;13:871272. https://doi.org/10.3389/fendo.2022.871272.
Google Scholar
Gaede P, Tarnow L, Vedel P, Parving HH, Pedersen O. Remission to normoalbuminuria during multifactorial treatment preserves kidney function in patients with type 2 diabetes and microalbuminuria. Nephrol Dial Transpl. 2004;19(11):2784–8. https://doi.org/10.1093/ndt/gfh470.
Google Scholar
de Zeeuw D, Remuzzi G, Parving HH, et al. Proteinuria, a target for renoprotection in patients with type 2 diabetic nephropathy: lessons from RENAAL. Kidney Int. 2004;65(6):2309–20. https://doi.org/10.1111/j.1523-1755.2004.00653.x.
Google Scholar
Jin Q, Luk AO, Lau ESH, et al. Nonalbuminuric diabetic kidney disease and risk of all-cause mortality and cardiovascular and kidney outcomes in type 2 diabetes: findings from the Hong Kong Diabetes Biobank. Am J Kidney Dis. 2022;80(2):196-206.e1. https://doi.org/10.1053/j.ajkd.2021.11.011.
Google Scholar
de Boer IH, Khunti K, Sadusky T, et al. Diabetes management in chronic kidney disease: a consensus report by the American Diabetes Association (ADA) and kidney disease: improving global outcomes (KDIGO). Diabetes Care. 2022;45(12):3075–90. https://doi.org/10.2337/dci22-0027.
Google Scholar
Gæde P, Oellgaard J, Carstensen B, et al. Years of life gained by multifactorial intervention in patients with type 2 diabetes mellitus and microalbuminuria: 21 years follow-up on the Steno-2 randomised trial. Diabetologia. 2016;59(11):2298–307. https://doi.org/10.1007/s00125-016-4065-6.
Google Scholar
Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373(22):2117–28. https://doi.org/10.1056/NEJMoa1504720.
Google Scholar
The EMPA-KIDNEY Collaborative Group, Herrington WG, Staplin N, et al. Empagliflozin in patients with chronic kidney disease. N Engl J Med. 2023;388(2):117–27. https://doi.org/10.1056/NEJMoa2204233.
Google Scholar
Wiviott SD, Raz I, Bonaca MP, et al. Dapagliflozin and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2019;380(4):347–57. https://doi.org/10.1056/NEJMoa1812389.
Google Scholar
Heerspink HJL, Stefánsson BV, Correa-Rotter R, et al. Dapagliflozin in patients with chronic kidney disease. N Engl J Med. 2020;383(15):1436–46. https://doi.org/10.1056/NEJMoa2024816.
Google Scholar
KDIGO 2020 Clinical practice guideline for the evaluation and management of chronic kidney disease [Internet]. Available from: www.kidney-international.org.
KDIGO 2022 Clinical practice guideline for the evaluation and management of chronic kidney disease [Internet]. Available from: www.kidney-international.org.
Summary of Product Characteristics FARXIGA® (dapagliflozin) tablets, for oral use Initial U.S. Approval: 2014 [Internet]. Available from: https://www.fda.gov/drugsatfda.
Summary of Product Characteristics JARDIANCE® (empagliflozin) tablets, for oral use Initial U.S. Approval: 2014 [Internet]. Available from: https://www.fda.gov/drugsatfda.
Bhandari S, Mehta S, Khwaja A, et al. Renin-angiotensin system inhibition in advanced chronic kidney disease. N Engl J Med. 2022;387(22):2021–32. https://doi.org/10.1056/NEJMoa2210639.
Google Scholar