diabetes: II. Early renal structural changes in type 1 diabetes. Diabetes 51: 1580–1587, 2002 28. Osterby R, Tapia J, Nyberg G, Tencer J, Willner J, Rippe B, Torffvit O: Renal structures in type 2 diabetic patients with elevated albumin excretion rate. APMIS 109: 751–761, 2001 29. Saito Y, Kida H, Takeda S, Yoshimura M, Yokoyama H, Koshino Y, Hattori N: Mesangiolysis in diabetic glomeruli: Its role in the formation of nodular lesions. Kidney Int 34: 389–396, 1988 30. Stout LC, Kumar S, Whorton EB: Focal mesangiolysis and the pathogenesis of the Kimmelstiel-Wilson nodule. Hum Pathol 24: 77–89, 1993 31. Rossing PFP, Feldt-Rasmussen B, Parving HH: Diabetic nephropathy. In: Brenner and Rector’s The Kidney, 10th Ed., edited by Skorecki K, Chertow GM, Marsden PA, Yu ASL, Taal MW, Philadelphia, Elsevier, pp 1283–1381 32. Fioretto P, Caramori ML, Mauer M: The kidney in diabetes: Dynamic pathways of injury and repair. The Camillo Golgi Lecture 2007. Diabetologia 51: 1347–1355, 2008 33. Tervaert TWC, Mooyaart AL, Amann K, Cohen AH, Cook HT, Drachenberg CB, Ferrario F, Fogo AB, Haas M, de Heer E, Joh K, Noe¨l LH, RadhakrishnanJ, Seshan SV, BajemaIM, BruijnJA; Renal Pathology Society: Pathologic classification of diabetic nephropathy. J Am Soc Nephrol 21: 556–563, 2010 34. Mogensen CE, Christensen CK, Vittinghus E: The stages in diabetic renal disease. With emphasis on the stage of incipient diabetic nephropathy. Diabetes 32[Suppl 2]: 64–78, 1983 35. Adler AI, Stevens RJ, Manley SE, Bilous RW, Cull CA, Holman RR; UKPDS GROUP: Development and progression of nephropathy in type 2 diabetes: The United Kingdom Prospective Diabetes Study (UKPDS 64). Kidney Int 63: 225–232, 2003 36. Gaede P, Tarnow L, Vedel P, Parving H-H, Pedersen O: Remission to normoalbuminuria during multifactorial treatment preserves kidney function in patients with type 2 diabetes and microalbuminuria. Nephrol Dial Transplant 19: 2784–2788, 2004 37. Pacilli A, Viazzi F, Fioretto P, Giorda C, Ceriello A, Genovese S, Russo G, Guida P, Pontremoli R, De Cosmo S; AMD-Annals Study Group: Epidemiology of diabetic kidney disease in adult patients with type 1 diabetes in Italy: The AMD-Annals initiative [published online ahead of print December 9, 2016]. Diabetes Metab Res Rev doi:10.1002/dmrr.2873 38. Afkarian M, Zelnick LR, Hall YN, Heagerty PJ, Tuttle K, Weiss NS, de Boer IH: Clinical manifestations of kidney disease among US adults with diabetes, 1988-2014. JAMA 316: 602–610, 2016 39. Klessens CQF, Woutman TD, Veraar KAM, Zandbergen M, Valk EJJ, Rotmans JI, Wolterbeek R, Bruijn JA, Bajema IM: An autopsy study suggests that diabetic nephropathy is underdiagnosed. Kidney Int 90: 149–156, 2016 40. Thomas MC, Cooper ME, Rossing K, Parving H-H: Anaemia in diabetes: Is there a rationale to TREAT? Diabetologia 49: 1151– 1157, 2006 41. Moseley KF: Type 2 diabetes and bone fractures. Curr Opin Endocrinol Diabetes Obes 19: 128–135, 2012 42. Foley RN, Hakim RM: Why is the mortality of dialysis patients in the United States much higher than the rest of the world?J Am Soc Nephrol 20: 1432–1435, 2009 43. USRDS: United States Renal Data System Annual Data Report: Mortality, Ann Arbor, MI, USRDS, 2015 44. Tuttle KR, Bruton JL: Effect of ins Diabetic kidney disease (DKD) remains an important clinical problem with substantial medical comorbidity despite many recent medical advances (1,2). More focus on the earlier identification of patients with type 2 diabetes who are at risk for developing chronic kidney disease (CKD) is needed, especially with regard to biomarkers, genetics, and high-risk phenotypes. Another key area of opportunity is the need for better clinical care models to eliminate socioeconomic and racial disparities. Fortunately, in the past few years, new therapeutic opportunities have been discovered, and more are being considered, for possible use in improving clinical outcomes. Angiotensin receptor blockers were the last major advance for the treatment of DKD, in 2001 (3,4). The serendipitous observations of improved cardiovascular and renal outcomes with sodium–glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide 1 receptor agonists in cardiovascular outcomes trials were a major surprise (5–7). These observations were followed by the improved cardiorenal outcomes in two large renal protection trials in patients with DKD: the CREDENCE (Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation) trial (8) using the SGLT2 inhibitor canagliflozin and the FIDELIO-DKD (Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease) study (9) using the novel and not-yet-approved selective nonsteroidal mineralocorticoid receptor antagonist finerenone. As more therapeutic opportunities become established, we need an improved understanding of the mechanisms underlying the progression of diabetic vascular disease and target organ damage so that newer and traditional therapeutic options can be used together most efficiently to improve clinical outcomes. We need to consider the therapeutic index of these treatments and appreciate the massive amount of pharmacopeia that patients with diabetes and CKD consume on a daily basis. Thus, to enhance the precision of therapy, we need more knowledge of the mechanisms of kidney and cardiovascular