Saitama Medical University, Japan
Title: Recent Progress for the Treatment of Diabetic Nephropathy
Biography: Shigehiro Katayama
In Japan, diabetic nephropathy is the leading cause requiring dialysis since 1998. The number of patients under dialysis is about 320,000, 40% of which are diabetics. Since dialysis costs expensive, prevention of the progression of diabetic nephropathy is an urgent target. We evaluated the incidence of diabetic nephropathy (macroalbuminuria of more than 300 mg/g・Cre) from normo- and low-microalbuminuria (<150 mg/g・Cre) in 1550 type 2 diabetics during 8 years (JDCS; Japan Diabetes Complications Study). The onset of macroalbuminuria was observed in 0.67% of the patients, which was one third of the incidence reported in UKPDS. Moreover, 30% of patients with low-microalbunminuria returned to normoalbuminuria (remission/regression). The higher the initial albuminuria, HbA1c, or systolic blood pressure was, the progression risk to macroalbuminuria was higher. Smoking was also the risk for diabetic nephropathy.
There were many trials which elucidated the effectiveness of ACE inhibitors or ARBs (angiotensin II receptor antagonists) including ours such as Japan IDDM, INNOVATION, ORIENT and ROADMAP study. However, relative risk reduction with these RAS inhibitors was about 20 - 30% in patients with macroalbuminuria and 60% in patients with microalbuminuria. We need more vigorous strategy to prevent the new onset and/or progression of diabetic nephropathy. Recent trials using SGLT2 inhibitors such as empagliflozin or canagliflozin decreased not only cardiovascular outcomes by 14% but also renal outcomes by 30 – 40%. SGLT2 inhibitors may increase sodium delivery to the macula densa and then improve tubuloglomerular (TG) feedback, which may result in constriction of afferent arteriole and hence amelioration of hyperfiltration. DPP-4 inhibitors and GLP-1 receptor antagonists may have such an action as well. These new hypoglycemic agents may have a great potential to protect renal functions, especially diabetics with hyperfiltration. Furthermore, we are waiting new renoprotective drugs such as anti-oxidant Nrf2 stimulator, bardoxolone methyl, or non-steroidal mineralocorticoid receptor antagonist (MRA), finerenone.