Glycemic Variability and KIM-1-Induced Inflammation in the Diabetic Kidney.

Abstract

Diabetes, the “other pandemic,” has progressively increased in magnitude despite advances in knowledge about diabetes prevention over the last two decades (1). Therefore, diabetes will remain a major public health problem for the foreseeable future. More patients with diabetic complications inevitably accompany more people living with diabetes. Diabetic kidney disease (DKD) is one of the most serious, risky, and common, occurring in ∼30% of patients with type 1 diabetes and ∼40% of those with type 2 diabetes (2). Progressive DKD is now the foremost cause of kidney failure worldwide, accounting for half of all cases (3). However, in many regions, treatment for kidney failure by dialysis or transplantation is inaccessible and DKD becomes an unescapable death sentence. Indeed, DKD is now the most common cause of death in Mexico City (4). However, even such sobering observations fail to capture the true magnitude of the impact, as DKD independently increases risks of all-cause and cardiovascular mortality by more than fivefold even before patients develop kidney failure (5). Indeed, the mortality rate outpaces the rate of progression to kidney failure by more than 2:1 once macroalbuminuria develops (6). The need to find better ways to identify and treat DKD has never been more urgent. Recent therapeutic advances with the sodium–glucose cotransporter 2 inhibitors demonstrate clear benefits on top of the standard of care, yet substantial residual risk of kidney failure and death remains (7,8). Uncovering the biological basis of disease is essential to further therapeutic advancement. While hyperglycemia is a well-recognized DKD risk factor, the traditional biomarker of glycated hemoglobin is an average …