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.

Improving the Dysregulation of FoxO1 Activity Is a Potential Therapy for Alleviating Diabetic Kidney Disease

“…Diabetic kidney disease (DKD), one of the common complications related to both types of diabetes, occurs in approximately 30–40% of diabetic patients and is the main cause of end-stage renal disease worldwide ( Gnudi et al, 2016 ; Bonner et al, 2020 ; Chen et al, 2020 ). Renal enlargement and increased glomerular filtration rate are the initial changes of kidneys in diabetes.…”

Current and future perspectives on functional molecular imaging in nephro-urology: theranostics on the horizon

“…Another GFR-reflecting agent, radiolabeled tilmanocept has been reported as a unique radiotracer for evaluating diabetic nephropathy. The number of diabetic patients continues to increase, with diabetic nephropathy being the leading cause of chronic renal failure and occurring in 40% 34 . In such patients, nephropathy progresses slowly over 20 to 30 years, with no symptoms or decline in kidney function in early stages.…”

Excessively Enlarged Mitochondria in the Kidneys of Diabetic Nephropathy

“…Diabetic nephropathy (DN) is the most common cause of end-stage kidney disease associated with diabetes mellitus (DM) and is one of the most serious complications of diabetes [ 1 , 2 ]. DN develops in approximately 30% of patients with type 1 DM and 40% of those with type 2 DM [ 1 ].…”

“…Podocyte loss, albuminuria, and a reduction in glomerular filtration rate are the major clinical features of DN [ 3 , 4 ]. DN also has significant long-term effects on the mortality of patients with diabetes [ 2 ]. Although several studies have been performed over a long period, the molecular mechanisms of DN pathogenesis have not been elucidated and there are no effective therapeutics for DN.…”