overt proteinuria (>0.5 g/ 24 hours) ⊲ The decrease in GFR in this stage is particularly steep when comorbid hypertension is not treated. 5 (ESRD) >25 years ⊲ Global glomerular sclerosis in >50% of glomeruli ⊲ GFR 140 mmHg and/or diastolic blood pressure >90 mmHg). The target systolic and diastolic blood pressure should be 300 mg/g creatinine. Canagliflozin compared to placebo was shown to reduce the risk of a composite kidney outcome, including ESRD, doubling of serum creatinine, or death from renal or cardiovascular causes (HR 0.70, 95% CI 0.59–0.82). A recent meta-analysis of major clinical trials (159) also consolidated the above findings regarding the renoprotective effects of SGLT2 inhibitors in patients with diabetes. These findings strongly favor the idea that SGLT2 inhibitors should be routinely offered to individuals with type 2 diabetes who are at risk of progressive kidney disease. The benefit of SGLT2 inhibitors was shown in patients with kidney disease with or without diabetes in the DAPA-CKD (Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease) trial (53). Dapagliflozin was shown to improve the primary composite kidney outcome (HR 0.61, 95% CI 0.51–0.72) in patients with an eGFR ≥25 to 200 mg/g, irrespective of diabetes status. GLP-1 receptor agonists also have a renoprotective effect, albeit to a lesser extent than SGLT2 inhibitors (158). There is sufficient evidence that GLP-1 receptor agonists and DPP-4 inhibitors can be used safely in patients with impaired renal function (158). Adequate blood pressure regulation also plays a key role in the primary prevention of diabetic nephropathy. Blood pressure control in type 2 diabetes is associated with a reduction in the incidence of microalbuminuria, particularly with the use of ACE inhibitors or ARBs. Agents in these two drug classes have a renoprotective effect via both reduction in blood pressure and direct effects on the kidney (158). In the FIDELIO-DKD trial (9), treatment with finerenone resulted in lower risks of CKD progression, evaluated as a composite of kidney failure, a sustained decrease of ≥40% in eGFR from baseline, or death from renal causes. Conclusion and Future Direction CKD, HF, and type 2 diabetes are commonly associated with each other and lead to worse outcomes. Multidirectional relationships among all three comorbidities are well established. Data from trials of SGLT2 inhibitors, renin-angiotensin inhibitors, and selective MR antagonists provide support for the dual cardio- and renoprotective effects of these agents and the notion that the pathophysiologies of heart and renal disease are interconnected. Both SGLT2 inhibitors and MR antagonists have been shown to improve outcomes in patients with HFrEF who have diabetes (and in those without diabetes). The FIGARO-DKD (Efficacy and Safety of Finerenone in Subjects With Type 2 Diabetes Mellitus and the Clinical Diagnosis of Diabetic Kidney Disease; NCT02545049) will provide further evidence regarding the use of finerenone in patients with type 2 diabetes and DKD. The use of SGLT2 inhibitors in patients with HFpEF is being studied in two ongoing trials: the EMPEROR-Preserved (Empaglifozin Outcome Trial in Patients With Chronic Heart Failure With Preserved Ejection Fraction; NCT03057951) and the DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients with Preserved Ejection Fraction Heart Failure; NCT03619213) trials. Although steroidal MR antagonists did not show definitive benefit in HFpEF patients in the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist) trial (163), a re-analysis of the trial taking into account regional differences and potential of nonadherence to trial procedures found that spironolactone use was associated with benefit in HFpEF as well (164). Finerenone is being studied in the HFpEF population in the FINEARTS (Study to Evaluate the Efficacy and Safety of Finerenone on Morbidity & Mortality in Participants With Heart Failure and Left Ventricular Ejection Fraction Greater or Equal to 40%; NCT04435626) trial. Several ongoing trials are studying this issue further. See references starting on p. 34. Dr. Usman is a research associate, Dr. Khan is an assistant professor of medicine, and Dr. Butler is a professor of medicine in the Department of Medicine at the University of Mississippi in Jackson, MS CHRONIC KIDNEY DISEASE AND TYPE 2 DIABETES 19 Socioeconomic and Racial Disparities Related to Chronic Kidney Disease and Type 2 Diabetes Keith C. Norris, MD, PhD Diabetes and chronic kidney disease (CKD) are growing public health problems that have become recognized globally as important causes of premature morbidity and mortality (165). According to the Centers for Disease Control and Prevention’s National Diabetes Statistics Report, 2020, the overall estimated prevalence of diabetes (both diagnosed and undiagnosed) among U.S. adults is 13%, with higher rates noted for non-Hispanic Asian (14.7%), Hispanic (14.9%), and non-Hispanic Black Americans (16.9%) (166). Type 2 diabetes accounts for as many as 90–95% of diabetes cases, and among people with type 2 diabetes, an estimated 40% will develop microvascular evidence of diabetic kidney disease (DKD) (165). DKD is defined as urinary albumin excretion >30 mg/g creatinine and/or an