#2327 Extent of proteinuria in autosomal dominant Alport syndrome compared to X linked Alport syndrome

Abstract

Abstract Background and Aims Alport syndrome (AS), as first described by Arthur Cecil Alport in late XIX century, encompasses a clinical picture of neurosensorial hypoacusia, ocular abnormalities, hematuria and proteinuric kidney disease progressing to end-stage kidney disease in the young adulthood. Differently from X-linked and autosomal recessive AS, autosomal dominant AS (ADAS), a more recently recognized entity, whose prevalence based on populational studies may be near to 1%, generally presents with a milder kidney involvement and with negligible extrarenal features. Nevertheless, some of these patients progress to chronic kidney disease (CKD) category G5, with marked intra and interfamilial variability. Although hematuria is almost universally present all three inheritance patterns, the magnitude of proteinuria, a reliable prognostic marker of the X-linked form has not been thoroughly studied in ADAS. We aimed to compare the extent of proteinuria between patients with X-Linked and autosomal dominant AS. Method Retrospective registry data on type of Alport hereditary pattern and spot urine protein to creatinine ratio per CKD category were collected. The 2021 CKD-EPI formula for calculation of glomerular filtration rate (eGFR) was used. Non-parametric test was used to analyze variables that did not follow normal distribution. Results We analyzed proteinuria and eGFR of 127 patients with Alport Syndrome. Information on patient gender, hereditary pattern and gene involved is illustrated it Table 1. Increased proteinuria was observed with CKD progression in all categories (p < 0.05). Within each CKD category, X-linked males had greater median proteinuria followed by, X-linked females and autosomal dominant patients (Table 2 and Fig. 1). No difference in median proteinuria was observed between X-linked females and those with autosomal dominant inheritance throughout CKD categories G1, G2, G4 and G5 (p = 0.142, 0.878, 0.327, 0.909 respectively). Difference in median proteinuria between X-linked females and autosomal dominant inheritance revealed statistical significance in CKD category G3 (p = 0.034), however the small sample size in this group must be taken into account. Conclusion Pathogenic variants in COL4A3, COL4A4, and COL4A5 are all causes of CKD, and proteinuria serves as a hallmark of disease progression. However, the extent of proteinuria in ADAS is significantly lower than that observed in XLAS. Additionally, some ADAS patients develop CKD with only albuminuria. While there is still much to be understood about this common condition, the renal mechanism of damage in ADAS appears to differ definitively from that in XLAS or ARAS.