IgA-nephropathy in children with alport syndrome

Autor: M. E. Aksenova, E. S. Stolyarevich, P. E. Povilaitite
Rok vydání: 2022
Předmět:
Zdroj: Nephrology (Saint-Petersburg). 26:74-79
ISSN: 2541-9439
1561-6274
Popis: BACKGROUND. The widespread use of genetic methods in clinical practice has shown that pathogenic variants in COL4A3, COL4A4, COL4A5 genes associated with Alport syndrome (AS) are detected in 10 % of sporadic and in 20 % of familial cases of IgA nephropathy (IgAN), which suggested a relationship between the two diseases. THE AIM was to determine the frequency and characteristics of the course of IgAN in children with AS. PATIENTS AND METHODS. A single-centre retrospective pilot study included 102 patients with AS. The inclusion criteria were: age 2-18 years, genetic and/or morphological confirmation of AS, availability of morphological data of pts. The comparison group included children and adolescents 2-18 years with morphologically confirmed primary IgAN; the exclusion criterion was the presence of AS-specific glomerular basement membrane changes. IgAN was classified according to the MESTC scale. Demographic (gender, age), clinical (arterial hypertension, AH) and laboratory data (proteinuria (Pr, mg/m2/day), (Schwartz eGFR, ml/min/1.73m2) at the time of the biopsy and at the last examination of patients were assessed. Arterial pressure ≥95‰ for sex, age, height was defined as AH. Pr >100 mg/m2/day, Pr≥500 mg/m2/day and Pr>1000 mg/m2/day were defined as proteinuria, high-level proteinuria and nephrotic level proteinuria, respectively. The statistic parametric and nonparametric methods were used ("Statistica 10", StatSoft Russia). RESULTS. IgAN was detected in 3 of 102 children with AS (q=0.03): 2 girls had heterozygous variants in COL4A3 and COL4A4, a boy had X-linked AS. Two patients had nephrotic proteinuria, 1 had SRNS at onset of IgAN. The comparison group included 25 children with IgAN (17M). Baseline patients age (9±4.2 vs 13±2.7 years), frequency of AH (q1=0.66 vs q2=0.28), eGFR decrease (q1=0.33 vs q2=0.44), eGFR level (91±24 vs 90.8±24 ml/ min/1.73 m2), morphological characteristics of IgAN did not differ significantly by groups; patients with AS were more likely to have nephrotic proteinuria (q1=1 vs q2=0.32, p=0.023). At follow-up (3.8±1.4 years), the groups were comparable in age (12.3±5.2 vs 15±1.8 years), AH frequency (q1=0.66 vs q2=0.5), eGFR level (87±16 vs 91±13 ml/min/1.73m2); children with AS had higher grade Pr (800[0;1150] vs 30[10;100] mg/m2/day, p=0.048) and more often had high-level Pr (q1=0.66 vs q2=0.06, p=0.006) at follow-up observation. The AS was associated with the development of nephrotic-level Pr at onset (r=0.41, p=0.008) and with high-level Pr (r=0.38, p=0.012) during follow-up. CONCLUSION. IgAN was detected in 3 % of children with AS. The presence of COL4A3, COL4A4, COL4A5 genes variants is associated with more pronounced proteinuria at the onset of IgAN and its preservation in the follow-up, and may be a risk factor for more severe course glomerulonephritis. The main limitations of the study: small sample size and duration of follow-up.
Databáze: OpenAIRE
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