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Diabetic Nephropathy (DN)

About DN

DN is a complex and heterogeneous disease with numerous overlapping disease-causing pathways including changes in glomerular hemodynamics, oxidative stress, inflammation, interstitial fibrosis and tubular atrophy.

It is a common, serious complication of type 1 and type 2 diabetes mellitus, or T2DM, and is characterized by extreme urinary albumin excretion, glomerular lesions, hypertension and progressive loss of kidney function. Diagnosis of DN is based on increased UACR and/or reduced eGFR in people with diabetes. DN is the most common cause of kidney failure and is a major risk factor for cardiovascular disease, a primary driver of excess cardiovascular mortality and the single strongest predictor of death. DN is progressive, and people that progress to end-stage kidney disease require chronic dialysis treatment and/or kidney transplant.

What are the symptoms of DN?

In the early stages of DN, the person with DN may not exhibit any symptoms. However, as the disease progresses, symptoms and complications arise. Those with DN may experience fatigue, swelling in the feet, ankles, hands, or eyes, increased need to urinate, cognitive difficulties, trouble with breathing and erectile dysfunction.

People with DN are at higher risk for cardiovascular disease and may have other lab abnormalities such as a rise in potassium, worsening blood pressure, increase in proteinuria, and may also become anemic due to a reduced number of healthy red blood cells.

What causes DN?

DN is a common microvascular complication of type 1 and type 2 diabetes occurring in as many as 40% of people with diabetes. Over time, poorly controlled diabetes can cause damage to blood vessel clusters in your kidneys that filter waste from your blood and manage fluid levels in your body. The combination of diabetes and kidney disease often go hand in hand, creating a dangerous combination, increasing the risk of mortality.

A subset of people with DN have their disease due to severe insulin resistant diabetes (SIRD). SIRD is characterized by high BMI and greater insulin resistance compared with other clusters of diabetes.

 

People with SIRD are at higher risk of progression to CKD and macroalbuminuria and have a 5X higher risk of ESKD progression compared to other clusters.

How is DN Diagnosed?

Key stats about DN

2.9M

people have DN due to SIRD in U.S., E.U., and U.K., collectively.

#1

leading cause of CKD and ESKD.

$43K

estimated average annual per patient healthcare cost.

How is DN treated?

Current first-line therapy for DN includes glycemic and blood pressure control and treatment with renin-angiotensin-aldosterone system inhibitors; either an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker. An emergence of data from various trials on sodium glucose cotransporter-2 inhibitors have demonstrated a reduced risk of kidney failure and prolonged survival compared to placebo, however, patients continue to progress to end-stage kidney disease, necessitating additional treatments that target the underlying cause of kidney disease.