Diabetic Kidney Disease: Challenges, Advances, and Opportunities

Abstract

Background: Diabetic kidney disease (DKD) is the most common cause of the end-stage renal disease (ESRD). Regardless of intensive treatments with hyperglycemic control, blood pressure control, and the use of renin-angiotensin system blockades, the prevalence of DKD remains high. Recent studies suggest that the spectrum of DKD has been changed and many progresses have been made to develop new treatments for DKD. Therefore, it is time to perform a systemic review on the new developments in the field of DKD.

Summary: Although the classic clinical presentation of DKD is characterized by a slow progression from microalbuminuria to macroalbuminuria and by a hyperfiltration at the early stage and progressive decline of renal function at the late stage, recent epidemiological studies suggest that DKD patients have a variety of clinical presentations and progression rates to ESRD. Some DKD patients have a decline in renal function without albuminuria but display prominent vascular and interstitial fibrosis on renal histology. DKD patients are more susceptible to acute kidney injury, which might contribute to the interstitial fibrosis. A large portion of type 2 diabetic patients with albuminuria could have overlapping nondiabetic glomerular disease, and therefore, kidney biopsy is required for differential diagnosis for these patients. Only a small portion of DKD patients eventually progress to end-stage renal failure. However, we do not have sensitive and specific biomarkers to identify these high-risk patients. Genetic factors that have a strong association with DKD progression have not been identified yet. A combination of circulating tumor necrosis factor receptor (TNFR)1, TNFR2, and kidney injury molecular 1 provides predictive value for DKD progression. Artificial intelligence could enhance the predictive values for DKD progression by combining the clinical parameters and biological markers. Sodium-glucose co-transporter-2 inhibitors should be added to the new standard care of DKD patients. Several promising new drugs are in clinical trials.

Key messages: Over last years, our understanding of DKD has been much improved and new treatments to halt the progression of DKD are coming. However, better diagnostic tools, predictive markers, and treatment options are still urgently needed to help us to better manage these patients with this detrimental disease.

Keywords: Diabetic kidney disease; Inflammation; Nonproteinuric pathway; Progression; Treatment.

Fig. 1

Overview of DKD. DKD, diabetic kidney disease, ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin II receptor blocker; SGLT2, sodium-glucose cotransporter 2; eGFR, estimated glomerular filtration rate; BP, blood pressure.

Fig. 2

Progression and biomarkers of DKD. KIM-1, kidney injury molecular 1; TNFR, tumor necrosis factor receptor; GBM, glomerular basement membrane; eGFR, estimated glomerular filtration rate; KW, Kimmelstiel-Wilson; ESRD, end-stage renal disease; MA, microalbuminuria.