AHA 2019: Expert Reviews Pathophysiology, Presentation of CKD in Diabetes
PHILADELPHIA—Diabetic kidney disease is a leading cause of chronic kidney disease (CKD) and end-stage renal disease worldwide, said Jennie Lin, MD, nephrologist and assistant professor of medicine at Northwestern University’s Feinberg School of Medicine, during her talk at the American Heart Association’s 2019 Scientific Sessions.
CKD affects approximately 25% of patients with diabetes, and renal manifestations affect approximately 75% of patients with diabetes and usually include progressive albuminuria with a steady loss of glomerular filtration rate, Dr Lin said. Managing and preventing kidney disease are key in this patient population, as CKD is associated with an increased risk of all-cause mortality, cardiovascular events, and hospitalization.
YOU MIGHT LIKE
Could Omega-3, Vitamin D Supplementation Prevent CKD in Type 2 Diabetes?
What Do You Need to Know About Type 2 Diabetes and Kidney Disease?
Dr Lin discussed the importance of the “silent phase,” or the first 5 to 10 years of having diabetes, which she called the “most critical point” in diabetic kidney disease. It is most often seen in type 1 diabetes, and although it is sometimes seen in type 2 diabetes, its presentation is often more variable in this patient population. Furthermore, patients with type 2 diabetes are often not biopsied, Dr Lin noted.
During the silent phase, patients often experience structural and functional changes, including hyperfiltration, a potential increase in kidney size, and glomerular hypertrophy, among other manifestations. Subsequently, long-term hyperglycemia often activates other mechanisms and leads to organ damage.
Genetics and epigenetics may explain why a subset of diabetes patients develop kidney issues, Dr Lin noted, referencing a 2019 genome-wide association study published in 2019 in the Journal of the American Society of Nephrology that evidenced this. Hyperglycemia is also known to alter DNA methylation patterns and downstream gene expression, she added.
Glycemic control and renin-angiotensin-aldosterone system blockade with angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers are standard-of-care for managing diabetic kidney disease, Dr Lin said.
Sodium glucose co-transporter 2 (SGLT2) inhibitors are especially promising new agents in managing diabetic kidney disease and may become a mainstay in slowing CKD progression in diabetes, she said. This drug class likely plays a key role in preventing glomerular hypertension, which often occurs in patients with diabetes. Although the exact mechanism is not known, SGLT2 inhibition is thought to decrease intra-glomerular pressure, which could explain the protective effect of this drug class in diabetic kidney disease. It is also hypothesized that SGLT2 inhibitors may serve as β blockers for the proximal tubule, Dr Lin noted.
The effects of the SGLT2 inhibitor canagliflozin were demonstrated in trials like CANVAS and CREDENCE. In the CREDENCE trial, which Dr Lin described as “one of the most exciting things since ACE inhibitors and ARBs,” canagliflozin was found to achieve the composite renal outcome compared with placebo. Although elevated amputation rates associated with canagliflozin use were observed in CANVAS, these rates were not observed in CREDENCE, potentially due to changes in monitoring protocol during CREDENCE, Dr Lin said.
—Christina Vogt
Reference:
Lin J. Diabetes and chronic kidney disease: pathophysiology and presentation. Presented at: American Heart Association 2019 Scientific Sessions; November 16-18, 2019; Philadelphia, PA.