From the Guidelines
SGLT2 inhibitors reduce the odds of chronic kidney disease progression by approximately 30-40%. These medications, including empagliflozin, canagliflozin, dapagliflozin, and ertugliflozin, were originally developed for type 2 diabetes but have shown significant renal protective effects 1. The typical dosing ranges from 5-25mg once daily depending on the specific medication. SGLT2 inhibitors work by blocking glucose reabsorption in the proximal tubule of the kidney, which reduces glomerular hyperfiltration and decreases albuminuria. This mechanism helps preserve kidney function over time by reducing intraglomerular pressure and oxidative stress.
Some of the key benefits of SGLT2 inhibitors include:
- Reduction in the risk of incident or worsening nephropathy by 39% with empagliflozin 1
- Reduction in the risk of progression of albuminuria by 27% with canagliflozin 1
- Reduction in the risk of reduction in eGFR, ESKD, or death from ESKD by 40% with canagliflozin 1
- Reduction in the risk of new or worsening nephropathy by 22% with liraglutide and 36% with semaglutide 1
The most recent and highest quality study, EMPA-KIDNEY, showed a 24% lower hazard ratio for major kidney disease events with empagliflozin compared to placebo 1. Common side effects include genital mycotic infections and volume depletion, so adequate hydration and monitoring are important when initiating therapy. The renal protective effects typically begin within months of starting treatment and continue with ongoing use.
It's worth noting that SGLT2 inhibitors have been shown to have benefits in both diabetic and non-diabetic kidney disease patients, and their effects appear to occur independently of glycemic control 1. Overall, the evidence suggests that SGLT2 inhibitors are a valuable treatment option for patients with chronic kidney disease, and can help reduce the risk of disease progression and improve outcomes.
From the Research
SGLT2 Inhibitors and Chronic Kidney Disease Progression
- SGLT2 inhibitors have been shown to lower the odds of chronic kidney disease (CKD) progression in patients with and without type 2 diabetes 2, 3, 4, 5.
- The exact percentage by which SGLT2 inhibitors lower the odds of CKD progression is not specified in the provided studies, but they have been found to reduce the risk of CKD progression and slow disease progression 2, 3, 5.
- SGLT2 inhibitors have been found to have renoprotective effects, including reducing the risk of development or worsening of albuminuria, a marker of renal damage 4.
- The use of SGLT2 inhibitors in patients with CKD has been associated with improved cardiovascular outcomes, including reduced risk of major adverse cardiovascular events, death, and hospitalizations for heart failure 3, 5.
Mechanisms of SGLT2 Inhibitors in CKD
- SGLT2 inhibitors affect the kidneys through changes in sodium transport and metabolic factors that interfere with the primary pathological mechanisms shared by most kidney diseases 3.
- SGLT2 inhibitors have been found to exert renal protection by suppressing inflammation and fibrosis, in addition to modulating hemodynamic and metabolic activities 5.
- The glucose-lowering efficacy of SGLT2 inhibitors is dependent on renal function, but the cardiovascular and renal benefits of SGLT2 inhibition appear to be maintained to estimated glomerular filtration levels as low as 30 mL/min/1.73 m2 4, 6.
Clinical Use of SGLT2 Inhibitors in CKD
- SGLT2 inhibitors are proposed as a novel approach for the management of type 2 diabetes mellitus and CKD 6.
- The pharmacokinetic parameters of SGLT2 inhibitors are slightly altered in the case of CKD, and dose adjustments may be required in patients with moderate CKD 6.
- The clinical impact of SGLT2 inhibitors on renal function and their potential to influence the course of diabetic nephropathy deserve attention due to preliminary favorable results in animal models 6.