estimated glomerular filtration rate (eGFR) 300 mg/24 hours, historically called macroalbuminuria) and decline in GFR in the ensuing several years (218,219). Because of challenges in obtaining adequate 24-hour urine collections from patients, the albumin-to-creatinine ratio (ACR) in random spot urine samples has been validated as a convenient and reliable alternative approach (168,220). The simple measurement of a spot urine albumin level alone by dipstick or other methods is inadequate for assessing renal TABLE 1 Screening for CKD in Patients with Diabetes Test Frequency Values Albuminuria test in spot urine specimen, mg/g creatinine ⊲ Type 1 diabetes: annually from 5 years after diagnosis ⊲ Type 2 diabetes: annually from time of diagnosis ⊲ More frequently in patients with values >300 mg/g to assess progression and response to treatment ⊲ Normal: 300 eGFR, mL/min/1.73 m2 ⊲ Type 1 diabetes: annually from 5 years after diagnosis ⊲ Type 2 diabetes: annually from time of diagnosis ⊲ More frequently in patients with eGFR 300 mg/g and/or an eGFR in the range of 30–60 mL/min/1.73 m2 should be monitored more frequently to gauge the adequacy of treatment interventions (168). Approach to Prevention and Treatment of CKD in People with Diabetes Lifestyle Modification Adoption of healthy lifestyle habits should be promoted in people with diabetes and CKD. In particular, smoking cessation should be encouraged and supported with proven medical interventions such as prescription of bupropion or varenicline and/or cognitive behavioral counseling (168,216,217,222). Current dietary recommendations for adjunctive CKD management have become less stringent than in the past. The dietary protein intake recommended for people with CKD not yet requiring dialysis treatment is ~0.8 g/kg body weight/day, similar to the daily allowance for healthy people. Dietary protein intake at this level has been shown to delay eGFR decline compared with higher levels of intake (168). Indeed, dietary protein intake >1.3 g/kg/day has been associated with worsening albuminuria and accelerated loss of kidney function (168,223). However, reducing dietary protein intake to 300 mg/day). Combined data from the DCCT and its follow-up Epidemiology of Diabetes Interventions and Complications (EDIC) cohort (median follow-up 22 years) showed that intensive glycemic control during the DCCT was associated with a 50% risk reduction in the incidence of CKD (GFR 300 mg/day may continue.) Limited glycemic benefit but no dose adjustment needed to decrease the risk of cardiovascular death or hospitalization for heart failure in patients with diabetes down to an eGFR of 30 ⊲ Do not initiate ⊲ Discontinue if GFR falls into this range. ⊲ Do not use in patients with an eGFR 300 mg/24 hours) or both, diabetic kidney disease (DKD) is a progressive disease that affects one in seven individuals worldwide eventuating renal replacement therapy (RRT) and premature death secondary to cardiovascular causes (2,270). In 2010, the number of RRT recipients worldwide was 2.618 million, 78% of whom were on dialysis. This figure is expected to burgeon by more than twofold by 2030, reaching 5.435 million, based on demographic projections of “unhealthy” aging populations (271). Although lifesaving, RRT expansion is not economically sustainable for health care systems in developed nations and remains largely inaccessible to many low- to middle-income countries. Thus, several organizations launched by a U.S. government executive order have called for the development of novel approaches to identify therapeutic options to prevent or slow DKD progression, with the overarching goal of reducing the incidence of end-stage renal disease (ESRD) by 25% by 2030 (272). This article aims to provide an overview of the major clinical trials conducted within the past 20 years, addressing this critical clinical need. Specifically, we will review several therapeutic drug classes that have demonstrated renoprotective potential by halting the progression of DKD. Angiotensin II Receptor Blockers Albuminuria levels >30 mg/day are an established continuous variable associated with adverse cardiovascular outcomes, while levels >300 mg/day indicate established kidney disease associated with faster DKD progression (273,274). Two early randomized trials—RENAAL (Reduction of End Points in Non-insulin Dependent Diabetes With the Angiotensin II Antagonist Losartan) (3) and IDNT (Irbesartan Diabetic Nephropathy Trial) (4)—support the renoprotective effects of the angiotensin receptor blockers (ARBs) losartan and irbesartan in people with type 2 diabetes who have albuminuria >300 mg/day. In comparison to placebo, losartan achieved a 25% relative risk reduction in time to doubling of serum creatinine, a 28% risk reduction in time to ESRD, and a 35% decline in proteinuria. In a trial using the same endpoints, irbesartan showed a similar benefit pattern, with a 33% lower risk of doubling of creatinine and a 23% lower relative risk of glomerulopathy progression relative to the comparator groups. Notably, the renoprotective effects conferred by both ARBs in these separate trials were not attributable to any blood pressure differences observed between the active and control arms. This conclusion was confirmed by statistically correcting for any small blood