Sodium Glucose Transport 2 (SGLT2) Inhibition Decreases Glomerular Hyperfiltration

Abstract

Chronic kidney disease (CKD) is a growing major worldwide health problem.1 In the United States, ≈14% of the population has CKD defined as an estimated glomerular filtration of <60 mL/min or an increased urine albumin/creatinine ratio of >30 mg/g.1 Decreasing estimated glomerular filtration or increasing urine albumin level is associated with development of many comorbid conditions, including highly significant increases in cardiovascular disease2 and a significant increase in mortality rates as compared with age-matched controls without CKD.3 A recent analysis led to the conclusion that possibly all of the excess mortality in people with type 2 diabetes mellitus (DM) as compared with the nondiabetic population is attributable to the development of CKD.4 Perhaps the impact of CKD is best illustrated by the epidemic rise in the end-stage renal disease (ESRD) population. In 1978, there were 41 421 people with ESRD (these numbers include all people on hemodialysis, on peritoneal dialysis, and who have received a transplant). In 2011, 612 966 people in the United States had ESRD (an ≈15-fold increase in prevalence in 35 years).1 Considering that death rates for people on dialysis are ≈20% per year1 and that there is a much better chance a CKD patient will die from cardiovascular disease than reach dialysis,5 there must be a very large number of people with CKD to produce the continued increase in prevalence in the ESRD population. There is also an enormous societal financial burden in that the cost of care for ESRD patients was nearly 30 billion dollars (≈6% of the Medicare budget for ≈0.2% of the population). And because this dollar amount does not take into account care the CKD (pre-ESRD) population, the financial costs are actually much higher for the care of all people with kidney disease. In …