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In many diabetics, the kidneys slowly thicken and become progressively scarred over time. The nephrons, possible side effects of lisinopril which are the basic functional and structural units of the kidneys, become leaky and allow albumin, a protein made by the liver, to pass freely into the urine. The damage to the kidney may be ongoing for many years before a patient becomes symptomatic and loses the ability to filter the blood, control the fluid balance of the body, and remove waste products.

By definition, diabetic nephropathy (DN) is typically macroalbuminuria and abnormal kidney function. Macroalbuminuria is regarded as an excretion of albumin in the urine in excess of 300 mg over a 24-hour period. Kidney function is taken as abnormal in cases where there are abnormalities in serum creatinine, the calculated clearance of serum creatinine or glomerular filtration rate (GFR).

DN is considered the case when there is macroalbuminuria alone or macroalbuminuria together with abnormal renal function. Clinical signs of DN include increasing amounts of albumin in the urine with reduced GFR and high blood pressure with increased risk of cardiovascular morbidity and mortality.

Etiology of Diabetic Nephropathy

While the exact cause of DN remains unknown, several mechanisms have been postulated. These include, hyperglycemia, glycation products, and the activation of pro-inflammatory cytokines. Some studies believe that poor glycemic control and hyperglycemia causes hyper-filtration and kidney injury. Moreover, genetic and/ or familial factors may also play a role. African Americans, Hispanics, and native American Indians have been observed as being at a higher risk of developing DN. Kidney damage is also more likely to occur in those who smoke, have high blood pressure, and have had type 1 diabetes before the second decade of life.

Pathophysiology

In the early stages of diabetes, there is glomerular hyper-inflation and a resultant increase in GFR, which is believed to be mediated by hyperglycemia. This may be related to the mesangial expansion of the kidney and an increase in the growth of renal cells with the help of cytokines, such as transforming growth factor B (TGF-B). TGF-B is especially important in expansion and subsequently fibrosis. Additionally, glucose binds reversibly and irreversibly to some proteins in both the kidneys and the circulation to form what are called advanced glycosylation end products (AGEs). These AGEs contribute to kidney damage when they form complexes that can stimulate growth and fibrosis.

Hypertension is believed to play a role in DN, because controlling this parameter has shown to decrease the progression of diabetics to DN. Studies on animals highlighted the importance of this factor, where the degree of DN was strongly correlated to the animals’ systemic blood pressures. High blood pressure known to cause endothelial injury and dysregulation of the blood pressure at the level of the kidney is a contributing factor.

In persons with type 1 diabetes, there is first microalbuminuria by the age of 5, which is followed by DN and macroalbuminuria about a decade later. Half of these patients develop end-stage renal disease (ESRD) within the 10- to 15-year period after the onset of microalbuminuria.

In contrast, about 3 in every 10 type 2 diabetics, without intervention, may progress to DN. After about 2 decades of kidney disease, about 20% of them may develop ESRD. While a lesser percentage of type 2 diabetics progress to ESRD in comparison to type 1 diabetics, those with type 2 diabetes comprise a greater percentage of the population requiring dialysis treatment, because type 2 diabetes is more common than type 1.

Further Reading

• All Diabetic Nephropathy Content
• What is Diabetic Nephropathy?
• Diabetic Nephropathy Treatment
• Diabetic Nephropathy Symptoms

Written by

Dr. Damien Jonas Wilson

Dr. Damien Jonas Wilson is a medical doctor from St. Martin in the Carribean. He was awarded his Medical Degree (MD) from the University of Zagreb Teaching Hospital. His training in general medicine and surgery compliments his degree in biomolecular engineering (BASc.Eng.) from Utrecht, the Netherlands. During this degree, he completed a dissertation in the field of oncology at the Harvard Medical School/ Massachusetts General Hospital. Dr. Wilson currently works in the UK as a medical practitioner.