Diabetic Nephropathy: A Chronic, Life-Threatening Complication of Diabetes

It is estimated that out of the 22 million people in the U.S. diagnosed with diabetes, about 40% exhibit kidney disease. Of these, approximately 1.4 million people are at high risk of developing kidney damage, approximately 6 million people have damage that cause them to leak a small amount of albumin into their urine and approximately 2 million people have advanced damage to the kidneys and leak a significant amount of protein into their urine.

The causative and promoting factors in diabetic nephropathy are complex and not completely understood. Long-standing diabetes and hypertension have been implicated in the development of diabetic nephropathy. Additionally, epidemiological and familial studies have demonstrated that genetic susceptibility contributes to the development of the disease in diabetic patients. The most vulnerable populations are African Americans, Hispanic Americans, Asians, Pacific Islanders, and American Indians.

Chronically elevated glucose in the bloodstream that is characteristic of diabetes, is believed to be one of the major underlying pathophysiological causes of kidney damage. Hyperglycemia results in both short-term changes in the body such as excessive urination, and long-term changes that lead to damage to vital organs such as the kidneys and the eyes.

Within the bloodstream, the excessively high glucose reacts with proteins to form unstable compounds known as Schiff bases which are rapidly converted to more stable compounds known as Amadori products. These Amadori products are in-turn converted to advanced glycation end products (AGEs) that cause the damage that results in diabetic nephropathy.

Diabetic nephropathy can eventually lead to end stage renal disease

The two main stages of diabetic nephropathy are:
• Microalbuminuria (also referred to as incipient nephropathy), which is defined as a urinary albumin excretion ranging from 30 to 300 mg in a 24-hour urine collection;
• Macroalbuminuria (also referred to as overt nephropathy), which is defined as a urinary albumin excretion of ≥300 mg in a 24-hour urine collection.

Microalbuminuria generally precedes overt nephropathy by 5 to 10 years. With the onset of macroalbuminuria, renal function gradually deteriorates over the next 10 to 15 years.

Many patients with diabetic nephropathy progress to end stage renal disease (ESRD), a condition in which the kidney is functioning at an extremely weak level, if at all. At this point, a patient would require dialysis or a kidney transplant. End stage renal disease is considered life-threatening, and has a 20% annual mortality rate in the U.S.