New strategies to improve clinical outcomes for diabetic kidney disease

Abstract

Background: Diabetic kidney disease (DKD), the most common cause of kidney failure and end-stage kidney disease worldwide, will develop in almost half of all people with type 2 diabetes. With the incidence of type 2 diabetes continuing to increase, early detection and management of DKD is of great clinical importance.

Main body: This review provides a comprehensive clinical update for DKD in people with type 2 diabetes, with a special focus on new treatment modalities. The traditional strategies for prevention and treatment of DKD, i.e., glycemic control and blood pressure management, have only modest effects on minimizing glomerular filtration rate decline or progression to end-stage kidney disease. While cardiovascular outcome trials of SGLT-2i show a positive effect of SGLT-2i on several kidney disease-related endpoints, the effect of GLP-1 RA on kidney-disease endpoints other than reduced albuminuria remain to be established. Non-steroidal mineralocorticoid receptor antagonists also evoke cardiovascular and kidney protective effects.

Conclusion: With these new agents and the promise of additional agents under clinical development, clinicians will be more able to personalize treatment of DKD in patients with type 2 diabetes.

Keywords: Diabetic kidney disease; Kidney protective agents; Type 2 diabetes.

Fig. 1

Histology images showing structural changes related to diabetic glomerulopathy. A Normal glomerulus. B Diffuse mesangial expansion with mesangial cell proliferation. C Prominent mesangial expansion with early nodularity and mesangiolysis. D Accumulation of mesangial matrix forming Kimmelstiel-Wilson nodules. E Dilation of capillaries forming microaneurysms, with subintimal hyaline (plasmatic insudation). F Obsolescent glomerulus. A–D and F were stained with period acid-Schiff stain. E was stained with Jones stain. Original magnification ×400. Reprinted with permission from American Society of Nephrology (Alicic et al., Diabetic Kidney Disease: Challenges, Progress, and Possibilities; CJASN 2017; 12; (2032-45) [11]

Fig. 2

Histology images showing tubulointerstitial changes seen in diabetic kidney disease. A Normal kidney cortex. B Thickened tubular basement membrane and interstitial widening. C Arteriole with an intimal accumulation of hyaline material with significant luminal compromise. D Renal tubules and interstitium in advancing diabetic kidney disease, with thickening and wrinkled tubular basement membranes (solid arrows), atrophic tubules (dashed arrow), some containing casts, and interstitial widening with fibrosis and inflammatory cells (dotted arrow). All sections stained with period acid-Schiff stain, original magnification ×200. Reprinted with permission from American Society of Nephrology (Alicic et al. [11])

Fig. 3

Prognosis of chronic kidney disease by GFR and albuminuria category. This figure was developed by Kidney Disease Improving Global Outcomes (KDIGO) [22] and reproduced with permission from KDIGO

Fig. 4

Clinical strategies to prevent development/progression of chronic kidney disease in people with diabetes. This figure was developed by Kidney Disease Improving Global Outcomes (KDIGO) [27] and reproduced with permission from KDIGO. Abbreviations: SGLT2, sodium glucose transport protein 2; RAS, renin-angiotensin system; CKD, chronic kidney disease