PT  - JOURNAL ARTICLE
AU  - Kristan H Cleveland
AU  - Rick G. Schnellmann
TI  - Pharmacological Targeting of Mitochondria in Diabetic Kidney Disease
AID  - 10.1124/pharmrev.122.000560
DP  - 2022 Jan 01
TA  - Pharmacological Reviews
PG  - PHARMREV-AR-2021-000560
4099  - http://pharmrev.aspetjournals.org/content/early/2022/12/12/pharmrev.122.000560.short
4100  - http://pharmrev.aspetjournals.org/content/early/2022/12/12/pharmrev.122.000560.full
AB  - Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease (ESRD) in the United States and many other countries. DKD occurs through a variety of pathogenic processes that are in part driven by hyperglycemia and glomerular hypertension, leading to gradual loss of kidney function and eventually progressing to ESRD. In type 2 diabetes, chronic hyperglycemia and glomerular hyperfiltration leads to glomerular and proximal tubular dysfunction. Simultaneously, mitochondrial dysfunction occurs in the early stages of hyperglycemia and has been identified as a key event in the development of DKD. Clinical management for DKD relies primarily on blood pressure and glycemic control through the use of numerous therapeutics that slow disease progression. Because mitochondrial function is key for renal health over time, therapeutics that improve mitochondrial function could be of value in different renal diseases. Increasing evidence supports the idea that targeting aspects of mitochondrial dysfunction, such as mitochondrial biogenesis and dynamics, restores mitochondrial function and improves renal function in DKD. We will review mitochondrial function in DKD and the effects of current and experimental therapeutics on mitochondrial biogenesis and homeostasis in DKD over time. Significance Statement Diabetic kidney disease (DKD) affects 20% to 40% of patients with diabetes and has limited treatment options. Mitochondrial dysfunction has been identified as a key event in the progression of DKD, and pharmacologically restoring mitochondrial function in the early stages of DKD may be a potential therapeutic strategy in preventing disease progression.