Chronic kidney disease (CKD) is defined as the long term, progressive decline in kidney function due to accumulated renal damage. As renal injury accrues, CKD can eventually transition to its final stage, a devastating and costly complication, referred to as end-stage renal disease (ESRD). At ESRD, one of two permanent measures must be implemented to replace the failing kidneys. Patients will either need a renal transplant or an initiation of life-long hemodialysis therapy.

Future projections anticipate a significant increase in diabetes cases, with close to 700 million diabetes patients internationally by the year 2045 [1]. According to the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), there are several risk factors which can contribute to CKD development. These include drug-induced or infection-induced kidney injury, systemic autoimmune diseases, such as lupus and Goodpasture’s syndrome, or genetic conditions, like polycystic kidney disease [2]. However, the two most common causes for renal injury leading to CKD are hypertension and diabetes, with the latter being the leading cause of CKD ^[2][3][2,3]. Globally, diabetic nephropathy (DN), commonly referred to as diabetic kidney disease (DKD), contributes to over two-thirds of all CKD cases [4].

Diabetic kidney disease (DKD) is defined by both physiological and structural pathologic alterations. Three classic maladaptive renal changes are seen on histologic examination: nodular glomerulosclerosis, mesangial cell expansion, and fibrosis of the glomerular and tubular basement membranes ^[5][6][5,6]. The progressive parenchymal injury interferes with the vital metabolic and homeostatic functions of the kidney. As a result, the objective evidence used for DKD diagnosis involves a gradual decrease in the estimated glomerular filtration rate (eGFR) and progressive micro- to macro-albuminuria [7]. GFR and urinary albumin levels are categorized and correlated with the sequential CKD stages (1 through 4) and ESRD (stage 5). Among those with type 1 diabetes, up to 40% of patients are diagnosed with DKD within 15–20 years of diabetes onset [8]. For type 2 diabetes patients, the UK Prospective Diabetes Study (UKPDS) reported that more than 50% of patients develop DKD after an average of 15 years post-diabetes diagnosis [9]. As many as 20% of newly diagnosed type 2 diabetes patients already have signs of renal disease at the time of their diabetes diagnosis [10]. There also exists a prolonged asymptomatic phase of DKD, where renal injury is occurring but at a level undetectable by serum and urinary screening tests [11].

DKD is unfortunately a very prevalent consequence of long-term inadequate disease control in both type 1 and type 2 diabetes populations. The 2017 National Diabetes Statistics Report released by the Center for Disease Control (CDC), estimated that in 2015 diabetes affected approximately 30.3 million people of all ages (9.4% of the U.S. population). Among all individuals with diabetes, type 2 diabetes accounted for about 95% of the cases [12]. There is a similar concerning upward trend in diabetes worldwide, especially with type 2 diabetes in low- and middle-income countries largely due to the ongoing obesity pandemic ^[12][13][12,13]. The International Diabetes Federation (IDF) recently published the 2019 results on current global diabetes rates, including future disease projections. The report identified that 436 million adults, ages 20–79, are currently living with diabetes. Furthermore, the IDF report estimated that by the year 2045, there will be near 700 million people worldwide with diabetes [13].

Even more troubling is the simultaneous rise in the diabetes-associated mortality rate, which in 2019, accounted for 4.2 million deaths globally [13]. Diabetes is known to significantly reduce total life expectancy compared to non-diabetic populations. In fact, current statistics suggests a 6-year decrease in total life expectancy in those with a diabetes diagnosis [14]. Within the diabetes population, cardiovascular (CV) disease (coronary heart disease, stroke, heart failure) remains a prevalent cause of death. Although the majority of diabetes deaths are the result of CVD, recent reports have highlighted the steady incline in DKD-attributed mortality. A risk analysis study published by the American Diabetes Association (ADA) found an increase in all-cause mortality rates in diabetes cohorts compared to non-diabetes cohorts, even after adjusting for age, BMI, systolic blood pressure, and total and HDL cholesterol [15]. Specifically, there was a strong positive correlation between chronic diabetes and death from associated complications, including renal nephropathy and fatty liver disease.

In an effort to reduce the global burden of DKD, as well as DKD-associated mortality, it is critically important to address the risk factors for DKD in diabetes populations. The primary modifiable risk factors for DKD include uncontrolled glycemic index, hypertension and hyperlipidemia co-morbidities, and lifestyle factors (smoking, poor nutrition, and minimal exercise) ^[5][16][17][5,16,17]. Since the incidence of diabetes is expected to significantly rise over the next couple of decades, it is equally necessary to inform and educate at-risk diabetes patients on the potential end-organ complications resulting from inadequate diabetes management. This entry will review the current preventative approach for DKD, including strict glycemic control, treatment of hypertension and hyperlipidemia, promotion of patient-driven lifestyle modifications, and incorporation of point-of care patient education.