Child Kidney Dis.  2022 Jun;26(1):31-39. 10.3339/ckd.22.022.

Alport syndrome: new advances in the last decade

• Kim JH

• KMID: 2531932
• DOI: http://doi.org/10.3339/ckd.22.022

Abstract

Alport syndrome (AS) is a progressive hereditary nephritis that is often accompanied by sensorineural hearing loss and ocular abnormalities. It is inherited in three modes of X-linked (XLAS), autosomal recessive (ARAS), and autosomal dominant (ADAS). XLAS is caused by pathogenic variants in COL4A5, while ARAS and ADAS are caused by those in COL4A3 or COL4A4. There is currently no curative treatment for AS; however, angiotensin-converting enzyme inhibitors (ACEi) can improve the outcome of AS. In the past decade, multiple studies have shown that early intervention with ACEi upon isolated microscopic hematuria or microalbuminuria could delay disease progression, and early diagnosis is crucial for early treatment. Therefore, a new classification of AS based on molecular diagnoses has been proposed, including the paradigm shift of re-classifying female “carriers” to “patients” and “thin basement membrane nephropathy” to “ADAS.” In addition, with the detection of COL4A mutations in some patients with biopsy-confirmed IgA nephropathy, focal segmental glomerulosclerosis, and chronic kidney disease of unknown origin, it is suggested that the phenotype of AS should be expanded. In this review, we highlight the landmark studies and guidelines published over the past decade and introduce strategies for early diagnosis and treatment to improve the outcomes of AS.

Keyword

Alport syndrome; Thin basement membrane nephropathy; Angiotensin-converting enzyme inhibitor; Early medical intervention; Early diagnosis

Figure

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  Fig. 1. Electron microscopy findings: the glomerular basement membrane (GBM) abnormalities caused by COL4A mutations. The GBM in Alport syndrome (AS) patients demonstrates irregular thickening with abnormal splitting and lamination. In patients with a thin basement membrane lesion, which is currently proposed to be regarded as AS, the GBM shows abnormally diffuse thinning. Reused from Warady et al. [20]. Images were used with permission from J. Charles Jennette. www.unckidneycenter.org. Accessed March 9, 2022.

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  Fig. 2. Immunofluorescence staining of type IV collagen in glomerulus. (A) Normal control exhibits full expression in both the glomerular basement membrane (GBM) and Bowman capsule (BC). (B) An X-linked Alport syndrome (XLAS) male patient shows entirely negative expression in both GBM and BC. (C) An XLAS female patient displays a mosaic pattern of expression in both GBM and BC. Green and red colors indicate α5 and α2 chains of type IV collagen, respectively. (D) An autosomal recessive AS patient presents negative expression only on GBM, but positivity on BC. Reused from Nozu et al. [1].

Reference

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