Identification of Diabetic Nephropathy Biomarkers Through Transcriptomics

Type 2 diabetes (T2D) is defined as a group of metabolic diseases characterized by chronic hyperglycemia, resulting from defects in insulin secretion, insulin action or both. According to the National Health Survey 2012, in Mexico, approximately 1 out of 10 persons is affected with T2D, though is important to mention that these data only reflect subjects previously diagnosed with the disease, but we expect a two fold increase in this number when including newly diagnosed T2D patients. In addition, the prevalence of T2D in younger age groups has increased (25% of diabetes cases in Mexico occurs in young adults <43 years of age), which implies >20 years living with the disease. In consequence, T2D is found among the leading causes of death, which represents a health burden for the country.

It has been estimated that more than 40% of people with diabetes will develop chronic kidney disease (CKD), accounting for about 40% of all patients beginning renal replacement therapy. In the Instituto Mexicano del Seguro Social, nephropathy is among the five leading causes of medical care in general hospitals in the area and in high-specialty hospitals. A study in Tuxtla Gutiérrez, Chiapas, informed a 35% incidence of nephropathy was observed in diabetic patients. Cueto-Manzano et al., reported a 40% incidence of early nephropathy and 29% of established nephropathy in 756 diabetic patients from Jalisco. Other study in Mexico that included 3,609 diabetic patients in Guanajuato, reported a 23.8% of diabetic nephropathy. A recent study conducted in the State of Mexico, which included 44 458 subjects diagnosed with T2D, registered the presence of diabetic nephropathy in 9.1% .

Diabetic kidney disease is uncommon if diabetes is less than one decade duration. The highest incidence rates of 3% per year are on average seen 10 to 20 years after diabetes onset, after which the rate of nephropathy tapers off. It is important to say that a diabetic patient for 20 to 25 years without clinical signs of diabetic nephropathy has low chance to develop such complication. The progression of T2D to diabetic nephropathy has become a health problem, not only for the costs to health sector, but to the worsening of life quality of the patient and the outcomes.

The main risk factors of progression to diabetic nephropathy includes: hyperglycemia, response to drugs, and long duration of diabetes, high blood pressure, obesity and dyslipidemia. Most of these factors are modifiable by drugs or changes in life style. Therefore, the management of the modifiable risk factors is a key for preventing and delaying the decline in renal function. Early diagnosis of diabetic nephropathy is another essential component in the management of diabetes and its complications such as nephropathy. The American Diabetes Association (ADA) recommends the routine screening to diabetic subjects with progressive diabetic nephropathy and CKD. The most widely accepted guidelines of National Kidney Foundation were implicating in measuring glomerular filtration rate (GFR) and stages of CKD using serum creatinine in patients. However, due to creatinine undergo tubular secretion in addition to glomerular filtration and its extrarenal elimination via the gastrointestinal tract, particularly in advanced renal failure, the GFR could be overestimated. In case of GFR, the techniques are overwhelming due to invasive methods and some markers are difficult to handle. Another marker used in the clinic is microalbuminuria, in most patients, the first sign of diabetic nephropathy is the moderate increase of urinary albumin excretion, i.e. 30-300 mg/g creatinine in a urine sample (also termed microalbuminuria). Patients who develop macroalbuminuria (>30-300 mg/g creatinine) are at high risk for developing diabetic nephropathy. Nonetheless, approximately up to 40% of patients with moderate albuminuria returns to normoalbuminuria. Moreover, up to 50% of patients with type 1 diabetes or T2D experience a decline in eGFR, despite the presence of only moderate albuminuria or even normoalbuminuria. Consequently, the actual markers available in the clinic are inaccurate, so it is necessary the identification of new markers that can recognize those patients at high risk for developing diabetic nephropathy to delay the progress of the complications taking the adequate measures.

The transcriptomics