糖尿病性腎症から慢性腎臓病治療への新規治療戦略

Diabetic nephropathy（DN） has been a leading cause of the initiation of dialysis in Japan. We have concentrated on the research on the pathogenesis of DN and focused on the relevant role of proximal tubular（PT） cells based on the concept that DN is a metabolic disease on the kidney. We have identified Sirtuin molecule that was shown to be related to the lifespan of various organisms as a player in the initiation of DN in the early stage before the onset albuminuria. We have established the working hypothesis “Tubular-glomerular interaction”. Another important molecule which draws an attention in this field is sodium-coupled glucose co-transporter 2（SGLT2） which is expressed in PT and reabsorbs glucose from primary filtrate from the glomerulus. The recent clinical trials using SGLT2 inhibitor demonstrated the renoprotective effects on the DN as well as non-DN chronic kidney disease（CKD）. At present, SGLT2 inhibitor can be prescribed for the treatment to DN as well as non-DN CKD. Finally, mineralocorticoid receptor（MR） antagonist（MRA） is another reagent for the treatment of DN. Non-epithelial cells in the kidney expresses MR such as mesangial dells, podocytes, or glomerular endothelial cells. Last year it was published that MRA can retard the progression of DN and reduced the renal specific outcomes. MRA, finerenone, became available for the treatment of DN. Before that we have reported that the high serum aldosterone levels are an independent risk factors for the progression of CKD and MRA can reduce eGFR decline of CKD patients. The future picture of kidney disease will change profoundly owing to the newly developed drug, such as SGLT2 inhibitor or MRA. I have now challenged to develop new health-care system for the identification of CKD patients at the early stage.