Clinical therapeutic strategies for early stage of diabetic kidney disease

Abstract

Diabetic kidney disease (DKD) is the most common cause of chronic kidney disease, leading to end-stage renal disease and cardiovascular disease. The overall number of patients with DKD will continue to increase in parallel with the increasing global pandemic of type 2 diabetes. Based on landmark clinical trials, DKD has become preventable by controlling conventional factors, including hyperglycemia and hypertension, with multifactorial therapy; however, the remaining risk of DKD progression is still high. In this review, we show the importance of targeting remission/regression of microalbuminuria in type 2 diabetic patients, which may protect against the progression of DKD and cardiovascular events. To achieve remission/regression of microalbuminuria, several steps are important, including the early detection of microalbuminuria with continuous screening, targeting HbA1c < 7.0% for glucose control, the use of renin angiotensin system inhibitors to control blood pressure, the use of statins or fibrates to control dyslipidemia, and multifactorial treatment. Reducing microalbuminuria is therefore an important therapeutic goal, and the absence of microalbuminuria could be a pivotal biomarker of therapeutic success in diabetic patients. Other therapies, including vitamin D receptor activation, uric acid-lowering drugs, and incretin-related drugs, may also be promising for the prevention of DKD progression.

The Association of Vitamin D Status and Vitamin D Replacement Therapy with Glycemic Control, Serum Uric Acid Levels, and Microalbuminuria in Patients with Type 2 Diabetes and Chronic Kidney Disease

“…This seems to support the linear relation between vitamin D deficiency and progression of MAU reported in T2DM patients [13,27] , while also emphasizing the potential benefit of the normalization of vitamin D levels in the reduction of renal and cardiovascular risks associated with MAU in these patients [12,13] .…”

“…This seems notable, since MAU is considered to be a biomarker for diagnosing diabetic kidney disease, and is a predictive factor for the progression to end-stage renal disease (ESRD) and increased cardiovascular risk among diabetic patients [12,13] .…”

A very-low-protein diet ameliorates advanced diabetic nephropathy through autophagy induction by suppression of the mTORC1 pathway in Wistar fatty rats, an animal model of type 2 diabetes and obesity

“…Multifactorial management, including diet therapy and glycaemic, BP and lipid control, is recommended for diabetic nephropathy. Regarding diet therapy, the efficacy of a low-protein diet (LPD) for advanced diabetic nephropathy remains controversial [2]. Previous clinical studies have not consistently shown beneficial effects of an LPD for the preservation of renal function in diabetic nephropathy [3][4][5][6][7][8].…”

Rodent models of diabetic nephropathy: their utility and limitations

“…1 Multifactorial management, including diet therapy and glycemic, blood pressure (BP), and lipid control, is recommended for diabetic nephropathy. 2 Some patients with advanced diabetic nephropathy rapidly progress to ESRD, despite having received adequate multifactorial treatment. Therefore, a novel and more beneficial treatment to suppress diabetic nephropathy has to be developed.…”

“…2 Clinically, albuminuria is the hallmark biomarker for the diagnosis of diabetic nephropathy, and it is also used to stage diabetic nephropathy. The histopathological features of diabetic nephropathy in humans include glomerular hypertrophy, a thickening of the glomerular basement membrane, and mesangial matrix expansion, including the formation of glomerular nodular lesions known as Kimmelstiel-Wilson nodules.…”