Alport syndrome

Alport syndrome is one of the most common inherited kidney diseases caused by mutations in the type Ⅳ collagen genes. It has a complex pattern of inheritance and diverse clinical manifestations, and severe cases will rapidly progress to end-stage kidney disease. With the rapid development of genetic testing technology, there is a deeper understanding of the genetic spectrum of Alport syndrome, the effectiveness of clinical therapies, and the prediction of disease prognosis. Therefore, the purpose of the article is to introduce the advances in the diagnosis and treatment of Alport syndrome, aiming to improve the early diagnosis and standardized treatment of this disease...

RATIONALE: Alport Syndrome (AS) is a progressive genetic condition characterized by chronic kidney disease (CKD), hearing loss, and eye abnormalities. It is caused by mutations in the genes COL4A3, COL4A4 , and COL4A5 . Heterozygous mutations in COL4A4 and COL4A3 cause autosomal dominant Alport Syndrome (ADAS), and a spectrum of phenotypes ranging from asymptomatic hematuria to CKD, with variable extra-renal features. In the past, heterozygous mutations in these genes were thought to be benign, however recent studies show that about 30% of patients can progress to CKD, and 15% can progress to end stage kidney disease (ESKD)...

PURPOSE: To evaluate the corneal endothelial cell morphology in children with autosomal recessive Alport syndrome (ARAS). METHODS: This is a longitudinal, prospective cohort study that evaluated pediatric patients with genetically diagnosed ARAS. Fifty-eight eyes of 29 pediatric patients (12 patients, 17 controls) underwent a full ophthalmic examination. Corneal endothelial cell density (ECD) (cells/mm²), coefficient variation (CV) of cell area (polymegathism), the percentage of hexagonal cells (HEX) (pleomorphism), and central corneal thickness (CCT) were analyzed automatically using a noncontact specular microscopy...

Inherited diseases are a frequent cause of end-stage kidney disease and often seen in the kidney clinic. Clinical genomic testing is increasingly available in the UK and eligible patients in England can be referred through the NHS Genomic Medicine Service. Testing is useful for diagnosis, prognostication and management of conditions such as autosomal dominant polycystic kidney disease (ADPKD), Alport syndrome, autosomal dominant tubulointerstitial kidney disease (ADTKD) and focal segmental glomerulosclerosis (FSGS)...

Here we present a case of complement-mediated thrombotic microangiopathy (TMA) in a patient who has a background of Stage 5 chronic kidney disease secondary to Alport syndrome. We explain our approach to the diagnosis of TMA, especially the reliance on non-renal manifestations of TMA and the role of kidney biopsy given there was a background of advanced kidney impairment at baseline.

Glomerular filtration relies on the type IV collagen (ColIV) network of the glomerular basement membrane, namely, in the triple helical molecules containing the α3, α4, and α5 chains of ColIV. Loss of function mutations in the genes encoding these chains ( Col4a3 , Col4a4 , and Col4a5 ) is associated with the loss of renal function observed in Alport syndrome (AS). Precise understanding of the cellular basis for the patho-mechanism remains unknown and a specific therapy for this disease does not currently exist...

UNLABELLED: Alport syndrome is a hereditary chronic kidney disease, attributed to rare pathogenic variants in either of three collagen genes ( COL4A3/4/5 ) with most localized in COL4A5 . Trimeric type IV Collagen α3α4α5 is essential for the glomerular basement membrane that forms the kidney filtration barrier. A means to functionally assess the many candidate variants and determine pathogenicity is urgently needed. We used Drosophila , an established model for kidney disease, and identify Col4a1 as the functional homolog of human COL4A5 in the fly nephrocyte (equivalent of human podocyte)...

Alport syndrome (AS) is a hereditary kidney disorder of type IV collagen caused by pathogenic variants in the COL4A3, COL4A4 and COL4A5 genes. Previously several cases of digenic AS, caused by two pathogenic variants in two of the three COL4A genes, have been reported. Patients with digenic AS may present with a more severe phenotype compared to patients with single variants, depending on the percentage affected type IV trimeric collagen chain. We report a newly discovered case of trigenic AS. A 52-year-old female presented with hematuria at the age of 24 years and developed hypertension by the age of 30...

No abstract text is available yet for this article.

BACKGROUND: Relapses or new-onset IgA nephropathy (IgAN) have been documented in patients after vaccination against SARS-CoV-2; however, only one adult patient has been reported in whom pre-existing IgAN worsened during coronavirus disease 2019 (COVID-19). CASE: We present the first pediatric case with biopsy-proven IgAN and genetically confirmed Alport syndrome, who developed end-stage kidney disease after an exacerbation of IgAN associated with COVID-19. The patient`s basal serum creatinine was 0...

Here, we used digital spatial profiling (DSP) to describe the glomerular transcriptomic signatures that may characterize the complex molecular mechanisms underlying progressive kidney disease in Alport syndrome, focal segmental glomerulosclerosis, and membranous nephropathy. Our results revealed significant transcriptional heterogeneity among diseased glomeruli, and this analysis showed that histologically similar glomeruli manifested different transcriptional profiles. Using glomerular pathology scores to establish an axis of progression, we identified molecular pathways with progressively decreased expression in response to increasing pathology scores, including signal recognition particle-dependent cotranslational protein targeting to membrane and selenocysteine synthesis pathways...

RATIONALE & OBJECTIVE: Alport Syndrome (AS) is the most common genetic glomerular disease caused by mutations that affect Type IV collagen. However, the clinical characteristics and significance of AS with kidney cysts are not well defined. This study investigated the prevalence and clinical significance of cystic kidney phenotype in AS. STUDY DESIGN: Retrospective cohort study. SETTING: & Participants: One hundred-eight patients with AS and a comparison cohort of 79 patients with IgA Nephropathy (IgAN)...

INTRODUCTION: Alport syndrome (AS) is one of the most common fatal hereditary renal diseases in human, with a high risk of progressing to end-stage renal disease without effective treatments. Mesenchymal stem cells (MSCs) have recently emerged as a promising therapeutic strategy for chronic kidney disease. However, the safety and therapeutic potential of MSC transfusion for patients with AS are still need to be confirmed. Therefore, we have designed a clinical trial to evaluate the hypothesis that intravenous infusion of human umbilical cord-derived MSC (hUC-MSC) is safe, feasible, and well-tolerated in children with AS...

No abstract text is available yet for this article.

PURPOSE OF REVIEW: With the latest classification, variants in three collagen IV genes, COL4A3, COL4A4, and COL4A5, represent the most prevalent genetic kidney disease in humans, exhibiting diverse, complex, and inconsistent clinical manifestations. This review breaks down the disease spectrum and genotype-phenotype correlations of kidney diseases linked to genetic variants in these genes and distinguishes "classic" Alport syndrome (AS) from the less severe nonsyndromic genetically related nephropathies that we suggest be called "Alport kidney diseases"...

PURPOSE: To describe a patient with a rare co-occurrence of Usher syndrome type 1C (USH1C) and renal disease, suspected to be secondary to Alport syndrome. METHOD: Case report and literature review of cases with Usher syndrome and renal failure. Clinical examination, color fundus photography, visual field tests, electroretinography and whole exome sequencing were used to diagnose and document the patient's clinical presentation. RESULTS: An 18-year-old female with known history of congenital hearing loss and chronic renal failure, presents with progressive night and peripheral visual impairment suspicious for an inherited retinal disease...

Mainzer-Saldino syndrome (MSS) or conorenal syndrome (CRS) is a rare autosomal recessive ciliopathy characterized by multiorgan affection, typically presents with a triad of nephronophthisis (NPHP), retinitis pigmentosa (RP), and cone-shaped epiphysis (CSE) with varying degrees of severity. A 20-month-old male is experiencing recurrent pneumonia attacks, an elevated serum creatinine level, proteinuria, and high anion gap partially compensated metabolic acidosis were incidentally discovered during one of his hospitalizations...

Chronic kidney disease (CKD) is associated with renal metabolic disturbances, including impaired fatty acid oxidation (FAO). Nicotinamide adenine dinucleotide (NAD + ) is a small molecule that participates in hundreds of metabolism-related reactions. NAD + levels are decreased in CKD, and NAD + supplementation is protective. However, both the mechanism of how NAD + supplementation protects from CKD, as well as the cell types most responsible, are poorly understood. Using a mouse model of Alport syndrome, we show that nicotinamide riboside (NR), an NAD + precursor, stimulates renal peroxisome proliferator-activated receptor α signaling and restores FAO in the proximal tubules, thereby protecting from CKD in both sexes...

BACKGROUND: Personalized disease models are crucial for assessing the specific response of diseased cells to drugs, particularly novel biological therapeutics. Extracellular vesicles (EVs), nanosized vesicles released by cells for intercellular communication, have gained therapeutic interest due to their ability to reprogram target cells. We here utilized urinary podocytes obtained from children affected by steroid-resistant nephrotic syndrome with characterized genetic mutations as a model to test the therapeutic potential of EVs derived from kidney progenitor cells...

No abstract text is available yet for this article.