ANGIOTENSIN-CONVERTING ENZYME INHIBITORS IN PREVENTING PROTEINURIA IN BOYS WITH X-LINKED ALPORT SYNDROME: A SINGLE-CENTER COHORT NON-RANDOMIZED STUDY

Patients with a hemizygous mutation in the COL4A5 gene have a high risk of developing renal failure at a young age. Proteinuria reflects the progression of glomerulopathy in Alport syndrome (AS). In order to improve renal survival in AS patients with proteinuria are prescribed with angiotensin system inhibitors. There is a limited, insufficient number of studies demonstrating the effectiveness of angiotensin-converting enzyme inhibitors (ACEI) in children with AS; the therapeutic effect initiated prior to the development of proteinuria has not been studied as yet. The purpose of the research was to determine the effectiveness of ACEI therapy in the form of enalapril in the prevention of proteinuria in boys with X-linked AS (XLAS). Materials and methods used: boys aged 2 to 15 y/o with genetically confirmed XLAS were included in a single-center prospective cohort study. Enalapril was prescribed at doses of 1 to 3 mg/m2/day. Urinary protein excretion (Pr) and estimated glomerular filtration rate (eGFR) were studied at the time of inclusion and with a frequency of one time per six months for the three-year period or longer. The primary endpoint was the time of onset of proteinuria. Results: 72 boys in total, incl. 29 without proteinuria, who received enalapril therapy (Group 1, age 6.2±1.9 y/o, Pr 67±20 mg/m2/day, eGFR 118±15.2 ml /min/1.73 m2) and 43 children without therapy (Group 2, age 6.8±1.9 y/o, Pr 87±23 mg/m2/day, eGFR 119±17.3 ml/min/1.73 m2). The incidence of proteinuria (0.45 in G1 vs. 0.98 in G2, p<0.001), incl. up to the age of 10 y/o (0.42 vs 0.91, respectively, p<0.001) was statistically significantly lower in G1. Proteinuria developed later in the treatment group (10.2±2.9 vs. 4.9±1.4 years, p=0.300). Non-missense mutations in the COL4A5 gene, episodes of macrohematuria in records and lack of therapy were the risk factors for proteinuria; the lack of enalapril therapy was a predictor for proteinuria. The risk of proteinuria during therapy was reduced by 50% (RR=0.46 (95% CI 0.31; 0.68); ARR=0.53; NNT=1.9). Conclusion: initiation of enalapril therapy at the pre-proteinuria stage of nephropathy in boys with XLAS reduces the risk of proteinuria preventing its occurrence in every 50$ of cases when receiving treatment. Early initiation of therapy may be effective in preventing the progression of kidney disease in boys with XLAS.