Mitochondrial Dysfunction in Individuals with Diabetic Kidney Disease: A Systematic Review

Area of Science:

• Nephrology
• Mitochondrial Biology
• Diabetology

Background:

• Mitochondrial dysfunction is a known factor in diabetic kidney disease (DKD) pathogenesis.
• Preclinical evidence is abundant, but human studies on mitochondrial dysfunction in DKD are limited.
• This review synthesizes current human research on mitochondrial dysfunction in DKD.

Purpose of the Study:

• To comprehensively review and synthesize human evidence linking mitochondrial dysfunction to diabetic kidney disease.
• To identify specific markers and patterns of mitochondrial dysfunction in individuals with DKD.

Main Methods:

• A systematic literature search was conducted across PubMed, Embase, and Scopus in March 2022.
• A total of 1339 articles were identified, with 22 meeting the inclusion criteria for analysis.
• Findings were compared between individuals with DKD, non-diabetic controls (NDC), and diabetes without kidney disease (DC).

Main Results:

• Individuals with DKD exhibited significant evidence of mitochondrial dysfunction compared to NDC and/or DC.
• Key findings included disrupted mitochondrial dynamics, uncoupling, oxidative damage, decreased respiratory capacity, reduced mtDNA content, and lower antioxidant capacity.
• The presence and severity of DKD, rather than diabetes duration or glycemic control, appeared to correlate with the degree of mitochondrial dysfunction.

Conclusions:

• Human studies confirm mitochondrial dysfunction as a significant feature in diabetic kidney disease.
• The severity of DKD is closely associated with the extent of mitochondrial dysfunction.
• Future research should investigate mitochondrial dysfunction earlier in diabetes to understand its role in DKD development versus consequence.