Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Jul;44(4):566-575.
doi: 10.23876/j.krcp.24.065. Epub 2024 Sep 26.

A comprehensive review of Alport syndrome: definition, pathophysiology, clinical manifestations, and diagnostic considerations

Eunjeong Kang  1   2 , Byung Hwa Park  3   4 , Hajeong Lee  2 , Hee Gyung Kang  5 , Ji Hyun Kim  6 , Ye Na Kim  3   4 , Yeonsoon Jung  3   4 , Hark Rim  3   4 , Ho Sik Shin  3   4
Affiliations

A comprehensive review of Alport syndrome: definition, pathophysiology, clinical manifestations, and diagnostic considerations

Eunjeong Kang et al. Kidney Res Clin Pract. 2025 Jul.

Abstract

Alport syndrome, a rare genetic disorder affecting around 1 in 50,000 individuals, primarily presents as microscopic hematuria and chronic kidney disease (CKD) with associated extrarenal complications. The Alport syndrome results from mutations in COL4A3, COL4A4, and COL4A5 genes, disrupting the formation of the α3-α4-α5 chain in the collagen IV network. The etiology involves X chromosome- related, autosomal dominant, autosomal recessive, and digenic inheritance patterns. The disease primarily manifests as kidney involvement, featuring persistent hematuria, proteinuria, and a progressive decline in renal function. Hearing loss, ocular abnormalities, and extrarenal manifestations further contribute to its complexity. Genotype-phenotype correlations are relatively evident, with distinct presentations in X-linked, autosomal recessive, and autosomal dominant cases. Diagnosis relies on urinalysis, histologic examination, and genetic testing with advancements in next-generation sequencing aiding identification. Although no specific treatment exists, early diagnosis improves outcomes, emphasizing the importance of genetic testing for prognosis and familial screening. The purpose of this review is to advance knowledge and enhance understanding of Alport syndrome.

Keywords: Alport syndrome; Diagnosis; Genetic kidney disease; Genetic testing; Pathophysiology.

PubMed Disclaimer

Conflict of interest statement

Conflicts of interest

Hee Gyung Kang is an Associate Editor of Kidney Research and Clinical Practice and was not involved in the review process of this article. The author has no other conflicts of interest to declare.

Figures

Figure 1.
Figure 1.. Representative signs and symptoms of Alport syndrome.
Figure 2.
Figure 2.. Types and composition of type IV collagen genes present on various chromosomes.
Figure 3.
Figure 3.. Type IV collagen from gene to protein trimerization to disease.
ADAS, autosomal dominant Alport syndrome; AS, Alport syndrome; ARAS, autosomal recessive Alport syndrome; CAKUT, congenital anomalies of the kidney and urinary tract; XLAS, X-linked Alport syndrome.
Figure 4.
Figure 4.. Factors that affect disease severity in AS.
ADAS, autosomal dominant Alport syndrome; AS, Alport syndrome; ARAS, autosomal recessive Alport syndrome; XLAS, X-linked Alport syndrome.
Figure 5.
Figure 5.. Diagnostic approach for AS.
AS, Alport syndrome; RAAS, renin-angiotensin-aldosterone system; VUS, variant of uncertain significance.
See this image and copyright information in PMC

References

    1. Kashtan CE, Ding J, Garosi G, et al. Alport syndrome: a unified classification of genetic disorders of collagen IV α345: a position paper of the Alport Syndrome Classification Working Group. Kidney Int. 2018;93:1045–1051. doi: 10.1016/j.kint.2017.12.018. - DOI - PubMed
    1. Hudson BG. The molecular basis of Goodpasture and Alport syndromes: beacons for the discovery of the collagen IV family. J Am Soc Nephrol. 2004;15:2514–2527. doi: 10.1097/01.asn.0000141462.00630.76. - DOI - PubMed
    1. Kashtan CE, Michael AF. Alport syndrome. Kidney Int. 1996;50:1445–1463. doi: 10.1038/ki.1996.459. - DOI - PubMed
    1. Kobayashi T, Uchiyama M. Characterization of assembly of recombinant type IV collagen alpha3, alpha4, and alpha5 chains in transfected cell strains. Kidney Int. 2003;64:1986–1996. doi: 10.1046/j.1523-1755.2003.00323.x. - DOI - PubMed
    1. Yoshioka K, Hino S, Takemura T, et al. Type IV collagen alpha 5 chain: normal distribution and abnormalities in X-linked Alport syndrome revealed by monoclonal antibody. Am J Pathol. 1994;144:986–996. doi: 10.1038/ki.1994.196. - DOI - PMC - PubMed

LinkOut - more resources