Disease: Improving Global Outcomes) 2012 clinical practice guideline (109). The GFR and albuminuria grid depicts the risk of progression, morbidity, and mortality by color, from best to worst. Green indicates low risk (if no other markers of kidney disease and no CKD), yellow indicates moderately increased risk, orange indicates high risk, and red indicates very high risk. Reprinted with permission from Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. Kidney Int Suppl 2013;3:1–150. Persistent Albuminuria Categories, Description and Range A1 A2 A3 Normal to mildly increased Moderately increased Severely increased 300 mg/g GFR Categories (mL/min/1.73 m2 ), Description and Range G1 Normal or high >90 G2 Mildly decreased 60–89 G3a Mildly to moderately decreased 45–59 G3b Moderately to severely decreased 30–44 G4 Severely decreased 15–29 G5 Kidney failure 30 mg/24 hour or a urinary ACR >30 mg/g creatinine, confirmed in at least two out of three samples (132). As such, its diagnosis is clinical, requiring little more than basic clinical and laboratory evaluations. The normal range for albuminuria is 15,000 people with type 2 diabetes suggested that patients with elevated albuminuria display the typical microvascular phenotype, whereas nonalbuminuric subjects with impaired kidney function had a more cardiovascular or macrovascular phenotype. FIGURE 3 Pathways and biomarkers of CKD. BNP, brain natriuretic peptide; KRIS, kidney risk inflammatory signature; U-CAD238, urinary proteome-based classifer for coronary artery disease 238 ; U-CKD273, urinary proteome-based classifer for chronic kidney disease 273. Adapted from Rossing P, Persson F, Frimodt-Moller M, Hansen TW. Diabetes 2021;70:39–50. ⊲ Hyperglycemia ⊲ Obesity ⊲ Hypertension ⊲ Metabolic ⊲ Hemodynamic ⊲ Inflammation ⊲ Fibrosis ⊲ Oxidative stress ⊲ Blood glucose ⊲ Blood pressure, BNP ⊲ KRIS ⊲ U-CKD273, U-CAD238, PRO-C6 ⊲ 8-oxoGuo Risk factors Pathway to damage Related biomarkers 12 CHRONIC KIDNEY DISEASE AND TYPE 2 DIABETES For CKD in general, including in people with diabetes, it has been recommended to stage the severity using a combination of etiology (if known), level of urinary albumin excretion, and eGFR (Figure 2) (109). Conclusion Advances in diagnosis and treatment have provided new options and potential for better outcomes for CKD in diabetes. As treatment opportunities continue to expand, biomarkers and, most likely, combinations of biomarkers will help us select the optimal treatment or combination of treatments for each patient. This ability will ensure better outcomes and reduce adverse events and unnecessary polypharmacy. A more detailed approach applying multiple biomarkers to select the right treatment for the right person may seem complicated and costly initially but has the potential to save both patients and the health care system considerable costs (137). Integrating multiple “-omics” platforms may lead to a much deeper understanding of the disease. Hopefully, such an approach will help to prevent CKD in diabetes and improve kidney outcomes in the future. For now, much can already be achieved if we ensure full integration of the use of simple biomarkers such as albuminuria and eGFR (138). See references starting on p. 34. Dr. Rossing is a professor of endocrinology and head of complications research at the Steno Diabetes Center Copenhagen and Department of Clinical Medicine at the University of Copenhagen in Denmark. CHRONIC KIDNEY DISEASE AND TYPE 2 DIABETES 13 The Interplay Between Diabetes, Cardiovascular Disease, and Kidney Disease Muhammad Shariq Usman, MD, Muhammad Shahzeb Khan, MD, MSc, and Javed Butler, MD, MPH, MBA Burden of Diabetes and Associated Cardiorenal Disorders The Global Burden of Disease Study estimates that there are currently 476 million patients with diabetes worldwide, the large majority of whom suffer from type 2 diabetes. In the United States, the prevalence of type 2 diabetes is 32.6 million, or ~1 in 10 people. These numbers are expected to continue to rise (139). The metabolic system is closely interrelated with the cardiac and renal systems, and these three systems share a symbiotic relationship that helps maintain homeostasis. The heart is one of the most metabolically demanding organs and is sensitive to changes in energy and volume status. Thus, it relies on the liver, pancreas, and fat for optimal energy metabolism and on the kidneys for volume maintenance. Similarly, the kidneys rely on the heart for adequate perfusion and on the metabolic system for the appropriate hormonal milieu, both of which are necessary to maintain their function. The metabolic system depends on functioning heart and kidneys to prevent neurohormonal activation, which keeps metabolic derangements such as insulin resistance, glucose dysregulation, and dyslipidemias at bay (140). Given the close-knit physiology of the metabolic, cardiac, and renal systems, it is not surprising that type 2 diabetes frequently coexists with cardiovascular disease (CVD) and chronic kidney disease (CKD). A 2018 study of >500,000 adults living with type 2 diabetes in the United States demonstrated that 25 years ⊲ Mesangial nodules (Kimmelstiel-Wilson lesions) and tubulointerstitial fibrosis ⊲ Progressively declining GFR and