RISK FACTORS FOR POOR NEPHROLOGICAL PROGNOSIS IN BOYS WITH X-LINKED ALPORT SYNDROME: A SINGLE CENTER COHORT STUDY
Authors:   Research and Clinical Institute of Pediatrics and Pediatric Surgery named after Academician Yuri Veltischev with the Pirogov Russian National Research Medical University, Moscow, Russia, Aksenova M.E. , Konkova N.E. ,   Research and Clinical Institute of Pediatrics and Pediatric Surgery named after Academician Yuri Veltischev with the Pirogov Russian National Research Medical University, Moscow, Russia, Piruzeeva O.R. ,   Research and Clinical Institute of Pediatrics and Pediatric Surgery named after Academician Yuri Veltischev with the Pirogov Russian National Research Medical University, Moscow, Russia, Zaikova N.M. ,   Research and Clinical Institute of Pediatrics and Pediatric Surgery named after Academician Yuri Veltischev with the Pirogov Russian National Research Medical University, Moscow, Russia, Lepaeva T.V. ,   Research and Clinical Institute of Pediatrics and Pediatric Surgery named after Academician Yuri Veltischev with the Pirogov Russian National Research Medical University, Moscow, Russia, Nikishina T.A. ,   Research and Clinical Institute of Pediatrics and Pediatric Surgery named after Academician Yuri Veltischev with the Pirogov Russian National Research Medical University, Moscow, Russia, Obukhova V.A. ,   Research and Clinical Institute of Pediatrics and Pediatric Surgery named after Academician Yuri Veltischev with the Pirogov Russian National Research Medical University, Moscow, Russia, Dlin V.V. ,   Research and Clinical Institute of Pediatrics and Pediatric Surgery named after Academician Yuri Veltischev with the Pirogov Russian National Research Medical University, Moscow, Russia
Published: July 2023

Males with X-linked Alport syndrome (XLAS) have a poor prognosis with a risk of developing kidney failure at a young age. Renal survival in glomerulopathies is determined by genetic and non-genetic risk factors with the role of the latter in Alport syndrome not being studied enough as yet. The purpose of this research was to determine the risk factors for poor nephrological prognosis in boys with XLAS. Materials and methods used: 89 boys aged 3 to 14 y/o with XLAS were included in a single-center cohort retrospective study. Blood pressure (BP), proteinuria (Pr, mg/m2/day), estimated glomerular filtration rate according to Bedside Schwartz Formula (eGFR, ml/min/1.73 m2 with norm≥90 ml/min/1.73 m2) and the data on therapy with angiotensin-converting enzyme inhibitors (ACEI) were monitored one time per 6 to 12 months for 4 [3; 6] years. BP≥90% was defined as uncontrolled (UHBP); proteinuria criterion Pr>100 mg/m2/day; the research endpoint was the time to reach eGFR<60 ml/min/1.73 m2. Results: 69 children had eGFR≥60 ml/min/1.73 m2 in dynamics (Group 1), 20 had reached the endpoint (Group 2). Age at inclusion, incidence of non-missense COL4A5 variants, birth weight, incidence of low body weight for gestational age, gross hematuria and age at onset of hematuria were not statistically significantly different between groups; UHBP (0.2 for G1 vs. 0.65 for G2; p<0.001), Pr (0.61 vs. 0.95, respectively; p=0.004), decrease in eGFR (0.06 vs. 0.45; p<0.001) were statistically significantly more common in G2. Boys from G2 were less likely to receive ACEI therapy (0.97 vs. 0.65; p=0.012); age of onset and doses of ACEI for ramipril were not statistically significantly different between the groups. Non-missense variants of COL4A5 (p=0.007), NBP (p<0.001), persistence of Pr>250 mg/m2/day (p<0.001), no ACEI therapy (p<0.001) and its onset at the stage of proteinuria (p<0.001) were the risk factors for reaching the endpoint. Persistence of Pr, UHBP, initiation of ACEI therapy at the proteinuria stage independently affected the progression of the disease. Conclusion: UHBP, proteinuria, lack of therapy/appointment of ACEI at the proteinuria stage of the disease are the risk factors for further poor nephrological prognosis in boys with XLAS.