ESPN 54th Annual Meeting

ESPN 2022


 
Evolution of hematuria over time and correlation with different genotypes in a cohort of Alport children and young adults
LAURA LUCCHETTI 1 ALESSANDRA TERRACCIANO 2 ANNA EWA KAMINSKA 2 ALMA IAFISCO 1 ANTONIO NOVELLI 2 FRANCESCO EMMA 1 LAURA MASSELLA 1

1- DIVISION OF NEPHROLOGY, BAMBINO GESù CHILDRENS HOSPITAL IRCCS, ROME, ITALY
2- LABORATORY OF MEDICAL GENETICS, TRANSLATIONAL CYTOGENOMICS RESEARCH UNIT, BAMBINO GESù CHILDRENS HOSPITAL, IRCCS, ROME, ITALY
 
Introduction:

Hematuria is usually the earliest finding in patients with Alport Syndrome (AS). However, adults with preserved kidney function and very mild or no hematuria have also been reported. In these patients, renal biopsy usually shows focal segmental glomerulosclerosis and the diagnosis can be missed if electron microscopy is not performed.

Aim To evaluate the evolution of hematuria over time and its correlation with genotype in patients with AS.  

Material and methods:

We collected patients with X-linked, autosomal recessive or autosomal dominant AS (XL-AS, AR-AS, AD-AS) followed at our center, diagnosed before age 18 years, with eGFR ≥70 ml/min/1.73m2 at diagnosis and at least 5 years of follow-up.
Hematuria was stratified in four classes according to the number of red blood cells in the urinary sediment (1=0-15; 2=16-50; 3=51-150; 4=>150). Data were grouped according to patient age (0-11, 12-18, >18 years). Genotypes were grouped based on the theoretical impact of pathogenic variants as follows: severe genotype = AR-AS or XL-AS males with large deletions, splice-site substitutions, or frameshift variants; intermediate genotype = XL-AS males with missense variants; mild genotype = XL-AS females or AD-AS.

Results:

Eighty-nine patients (54M) were included in the study (mean age at diagnosis of 9.9 ± 5.3 years). A statistically significant decrease in the magnitude of hematuria over time was observed in all patient categories. The percentage of urine samples with highest score reduced from 33% in 0-11 years group to 11% in >18 years group (D = 22%, p<0.05). This effect was more pronounced in severe genotype group with a reduction of 34% overtime.

Conclusions:

The natural evolution of hematuria in patients with AS is to decrease overtime. In some cases, hematuria may become very mild or even absent. This may explain the unexpected findings of pathogenic variants in COLIV genes in adult patients diagnosed with FSGS.