#4879 PREDICTORS OF KIDNEY DISEASE PROGRESSION IN MALES WITH X-LINKED ALPORT SYNDROME

Abstract

Abstract Background and Aims Alport's syndrome is the second most common monogenic cause of end-stage renal disease (ESRD). Males with X-linked Alport's syndrome (XLAS) have a high risk of early ESRD development. The aim of study was to determine the predictors of unfavorable renal prognosis in boys with XLAS. Method The children with genetically confirmed XLAS (n = 84, age 8.7±4.3 yrs, eGFR 102±16.2 ml/min/1.73 m2, 59 pts with missense COL4A5 mutations) were included in observation single center study (FU 6.9±2.4 yrs). Seventy three pts (q = 0.87) were treated with ACEi (age of start 7.6±3.3 yrs, dose for Ramipril 2.7±0.8 mg/m2/day). Arterial blood pressure (BP), proteinuria (Pr, mg/m2/day), eGFR (Schwartz equation, ml/min/1,73m2), gene mutation type and ACEi-treatment data (age of pts and disease stage at the therapy start, ACEi dosage, dynamics of Pr and eGFR) were obtained and updated for each patients. BP >90 perc for gender, age and height was defined as uncontrolled (uBP); Pr was categorised according to its level as a low (100-<250 mg/m2/day), moderate (≥250-500 mg/m2/day), high (≥500-1000 mg/m2/day) and nephrotic (≥1000 mg/m2/day). Gene mutations were divided into severe (nonsense, deletion, splicing) and less severe (missense) mutations. The eGFR<60 ml/min/1,73m2 was defined as primary outcome. Results Twenty pts (q = 0.24, age 13.5±2.96 yrs) reached the end point during observation period. Non-missense COL4A5 mutations (HR = 4.28, 95% CI 1.47-12.4, p = 0.007), uBP (HR = 20, 95% CI 4.68-29.6, p<0.001), persistent Pr >250 mg/m2/day (HR = 20, 95% CI 3.36-21, p<0.001), absence of ACEi treatment (HR = 10.7, 95% CI 2.45-14.7, p = 0.02) or start therapy at proteinuric stage of disease (HR = 20, 95% CI 2.2-13.8, p<0.001) were the risk factors of disease progression. Multiple regression analysis adjusted for age, initial eGFR revealed that late start of ACEi treatment (β = 0.23, p = 0.036), persistence of uBP (β = 0.26, p = 0.008) and Pr >250 mg/m2/day (β = 0.17, p = 0.04) had independent significance and predict unfavorable renal prognosis (R = 0.76, R2 = 0.57, p<0.000). Conclusion Persistent proteinuria and uncontrolled blood pressure, initiation of ACEi treatment at the proteinuric stage of glomerulopathy are the factors of unfavorable prognosis in male with XLAS.