Gene Linked to Severe Diabetic Retinopathy and Renal Disease

Researchers have identified a gene called erythropoietin (EPO) that is linked to higher risk of severe retinopathy and nephropathy, eye and kidney diseases that often affect diabetic patients.

Diabetic retinopathy (PDR) is the most common cause of legal blindness in working-aged adults in the United States, accounting for 10% of new cases of blindness. Diabetes is also the leading cause of kidney disease, called end-stage renal disease (ESRD), in the U.S. and the Western world.

While researchers have known that these conditions in diabetic patients can be hereditary, the actual genese involved have been relatively unknown until now.

Researchers discovered the involvement of the EPO gene in a study of 1,618 people with diabetic retinopathy and end-stage renal disease, and 954 diabetes patients without any eye or kidney disease in three separate populations. Their studies demonstrate that if a person has a copy of the mutant EPO gene, they have an increased risk of developing PDR and ESRD during their lifetime.

According to Dr. Dean Li from the Program in Human Molecular Biology and Genetics at the University of Utah, while there is no proven pharmacologic treatment for diabetic vascular eye diseases, "inhibiting the growth of unwanted blood vessel growth using antibodies directed against vascular endothelial growth factor (anti-VEGF therapy) has been advocated. This genetic study suggests that future therapeutic strategies need to consider blunting the effects of erythropoietin in addition or as an alternative to an anti-VEGF strategy."

The study was led by Kang Zhang M.D., Ph.D., Director of the Division of Ophthalmic Genetics at the Moran Eye Center and Associate Professor of Ophthalmology and Visual Sciences at the University of Utah, and was published in the journal Proceedings of National Academy of Sciences.

Low Level Lead Exposure Leads to Chronic Renal Disease in Animal Study

While lead exposure has long been associated with hypertension, arteriolosclerosis and kidney disease, a new animal study from the University of Florida, Gainesville indicates that even low level exposure to lead accelerates chronic renal disease–primarily by raising blood pressure and accelerating injury to kidney tissues and blood vessels.

The study used male rats which were fed a standard diet. In addition, 16 of the rats were given water with lead acetate at a dosage resulting in similar or slightly lower than the levels observed in subjects with occupational lead exposure. Thereafter they underwent remnant kidney (RK) surgery and afterwards continued on the lead acetate for 12 more weeks.

A control group also underwent RK surgery but without lead acetate. At eight and 12 weeks after surgery, the body weight of all the rats was measured and systolic blood pressure was assessed. Twelve weeks after RK surgery, kidney tissue was collected for histologic and molecular biologic studies from both groups.

Study Results
Lead treatment was well tolerated and resulted in modest elevations in whole blood lead levels. However, the lead exposure reduced body weight, increased blood pressure and worsened renal dysfunction.

Specifically, lead exposure:

  • was associated with higher systolic blood pressure and worse renal function, and with a tendency for greater urinary protein; and
  • while scarring in the renal capillary system tended to be worse in lead treated rats, the most striking finding was that kidney tissue disease (arteriolar disease, peritubular capillary loss, tubulointerstitial damage and macrophage infiltration) worsened with lead exposure. These developments were associated with the significantly increased renal expression of monocyte chemoattractant protein-1 mRNA.

According to Dr. Richard J. Johnson, the seior researcher, "This study examined the effect of mild, chronic lead intoxication in an experimental model of chronic renal disease. The dose of lead administered resulted in mild toxicity. This degree of lead poisoning was sufficient to cause higher blood pressures and accelerate the progression of renal failure."

Source: American Journal of Physiology—Renal Physiology (Online Edition)