Early Blocking of RAAS Seen to Treat Alport Syndrome Progression in Child

Blocking the renin-angiotensin-aldosterone system (RAAS) before kidney function is impaired is critical, and was seen in a case study to delay progression in a boy with Alport syndrome (AS), according to a study in the Tohoku Journal of Experimental Medicine.

“We hope that the initiation of RAAS blockade with no delay would improve the prognosis of AS by early diagnosis and careful monitoring in entire pediatric population with AS,” wrote the authors of the study, “Early RAAS Blockade Exerts Renoprotective Effects in Autosomal Recessive Alport Syndrome.”

Researchers led by Dr. Shigeo Kure, with the Department of Pediatrics at Tohoku University School of Medicine in Japan, reported the case of three siblings and their father. All four were diagnosed with the autosomal recessive form of AS, where two copies of a faulty gene must be present for the disease to develop.

All three children had hematuria, or blood in the urine since infancy. Genetic analysis found they all had the same mutations in the COL4A3 gene. This gene encodes for collagen type IV alpha 3, which is part of the collagen chain, a structural material that is needed for different parts of the body, including the kidneys, to work normally.

The children received RAAS blockade therapy, which has recently been shown to effectively slow disease progression in AS. However, by the time the treatment was initiated, the kidneys of the older sister and brother were already damaged and the disease continued to progress. The siblings experienced renal failure.

In the youngest brother, born 10 years after the others, RAAS treatment was started while kidney function was still normal, and function was maintained with very mild proteinuria, or protein in the urine, a sign of kidney impairment. The researchers reported that, now at age 17, this brother still has normal kidney function.

“We propose that in Alport syndrome, RAAS blockade should be initiated earlier than renal function is impaired,” the researchers concluded.

RAAS is a hormone system that is involved in the regulation of arterial blood pressure. Blocking RAAS with angiotensin converting enzyme (ACE) inhibitors, such as Capoten (captopril), has been shown to slow the deterioration of kidney function and delay the need for dialysis and kidney transplants in AS.