Diabetes is the most common etiology in patients with chronic kidney disease (CKD). Patients with both type 1 and 2 diabetes are at increased risk of developing diabetic kidney disease (DKD), characterized by an accelerated deterioration of kidney function and albuminuria (due to endothelial dysfunction). The management of blood pressure (e.g. renin-angiotensin-aldosterone-system (RAAS)-blockers and diuretics) in addition to lifestyle management, has substantially delayed progression of renal and cardiovascular complications in diabetic patients. However, despite the standard of care, diabetic patients are still at higher risk of developing DKD, cardiovascular events and mortality than the general population.
During disease progression, DKD patients present with mesangial expansion and thickening of the glomerular basement membrane (GBM). It has been shown that the extracellular matrix (ECM) composition in the kidney changes during disease progression. Type IV collagen in the basement membrane, for example, is partially replaced by type VI collagen, which acts as a scaffold for initiation of wound healing thanks to its von Willebrand factor domains. Although changes to the glomerulus are the main histological signature of DKD, tubulointerstitial fibrosis is largely present in the kidneys of DKD patients.
Tubulointerstitial fibrosis is caused by an abnormal shift in the turnover of components of the renal ECM, with a prevalence of collagen and other ECM proteins formation over degradation. Assessment of collagen formation may identify patients with active fibrosis at higher risk for rapid deterioration of kidney function and adverse events, such as cardiovascular events and mortality.
Currently, no anti-fibrotic drugs are available, and the treatment of patients with advanced DKD relies on dialysis and ultimately transplantation. Biomarkers, which adds useful information to the currently available risk factors, are required to promote the development of such compounds. Biomarkers of ECM turnover may be used to reflect the effect of antifibrotic compounds on the state of the tissue.
How many have DKD?
Diabetes is the major cause of CKD and end-stage renal disease in the western world. Approximately 40% of patients with CKD have diabetes as their primary causal diagnosis. In the US, more than 8.4 million adults have diabetes and CKD.
How is DKD treated?
The first step in treating diabetic nephropathy is to treat and control diabetes and, if needed, high blood pressure (hypertension). With good management of blood sugar and hypertension, kidney dysfunction and other complications can be prevented or delayed. Due to the reservoir of nephrons, patients are usually diagnosed when CKD is already advanced. Patients that reach end-stage kidney disease require dialysis or kidney transplantation. The main classes of treatments for CKD are drugs regulating blood-pressure or treating the underlying disease drivers (e.g. GLP-1 agonists and SGLT2 inhibitors in diabetes, which have a positive effect on kidney health).
How is DKD diagnosed?
DKD is defined as CKD with diabetes as the main causal driver. Patients are diagnosed with CKD if the concentration of creatinine in blood and/or proteins or albumin in urine is above a certain threshold. Since serum creatinine only rises after the loss of many nephrons and not all patients present with proteinuria or albuminuria, better diagnostic tools are needed to identify patients at risk of developing CKD.