Recent advances in diabetic kidney disease

Diabetes mellitus is the leading cause of chronic kidney disease (CKD) in the USA and worldwide. An estimated 422 million adults are living with diabetes globally, and up to 40% of them may develop CKD during their lifetime [1]. Diabetic kidney disease (DKD) does not reflect a specific pathological phenotype. In fact, it can be diagnosed clinically based on the presence of persistent albuminuria, sustained reduction in the estimated glomerular filtration rate (eGFR), or both in patients with diabetes [2]. DKD is usually identified after five years of the diagnosis of type 1 diabetes, while it can be recognized at the time of diagnosis of type 2 diabetes. The presence of proliferative diabetic retinopathy typically correlates with ongoing DKD in patients with albuminuria. Even though a kidney biopsy can confirm the diagnosis of DKD, this procedure is usually considered when an alternative diagnosis suspected.

Albuminuria has more recently been classified into moderate (30 to 300 mg/g) or severe (> 300 mg/g). Nonetheless, any degree of albuminuria has been associated with an increased risk for CKD progression, end-stage kidney disease (ESKD), adverse cardiovascular disease outcomes, and mortality in patients with diabetes [3]. A reduced eGFR in diabetic patients has been observed in the absence of albuminuria; however, the progression of DKD appears to be slower in these individuals [3]. Furthermore, the combined presence of albuminuria and lower eGFR independently increases the risks for cardiovascular events and mortality in individuals with diabetes [3]. The Kidney Disease: Improving Global Outcomes (KDIGO) and the American Diabetes Association (ADA) guidelines recommend that all diabetic patients undergo annual screening by checking serum creatinine-based eGFR and urine tests to evaluate for albuminuria [2].

What is unique about the challenges with DKD compared with other types of kidney disease?
Individuals with type 2 diabetes may develop DKD before a clear diagnosis of diabetes is established. This has the consequence of delaying the diagnosis and appropriate treatment of DKD. More recently, we have witnessed significant progress in the treatment options for slowing DKD, but no real advance in reversing DKD. To date, available therapies are targeting DKD progression. Furthermore, not all DKD patients are eligible for these therapies because of variable side effects such as hyperkalemia, acute kidney injury (AKI), and extent of the DKD. Indeed, because of safety concerns, many of these newer medications are not approved for patients with eGFR below 30 mL/min/1.73 m2.