Alport

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.

BACKGROUND: Alport syndrome (AS) is a genetically heterogeneous disorder resulting from mutations in the collagen IV genes COL4A3, COL4A4, and COL4A5. The genetic diagnosis of AS is very important to make precise diagnosis and achieve optimal outcomes. METHODS: In this study, 16 Chinese families with suspected AS were recruited after pedigree analysis, and the clinical presentations were analyzed by a nephrologist. The genetic diagnosis was performed by whole-exome sequencing (WES) and the disease-causing variants were confirmed by Sanger sequencing...

BACKGROUND: Hereditary nephritis (HN), including Alport syndrome (AS) and thin basement membrane nephropathy (TBMN), is a rare genetic cause of hematuria. A definitive diagnosis requires electron microscopy (EM). Therefore, the clinical characteristics of these conditions are less known. This study aimed to determine the percentage and clinicopathological features of HN in patients from a referral center in Iran. METHODS: We checked kidney biopsy reports from 2007 to 2021 and extracted cases with HN...

The role of NRF2 in kidney biology has received considerable interest over the past decade. NRF2 transcriptionally controls genes responsible for cellular protection against oxidative and electrophilic stress and has anti-inflammatory functions. NRF2 is expressed throughout the kidney and plays a role in salt and water handling. In disease, animal studies show that NRF2 protects against tubulointerstitial damage and reduces interstitial fibrosis and tubular atrophy, and may slow progression of polycystic kidney disease...

BACKGROUND AND OBJECTIVE: Hereditary kidney diseases (HKD) are a frequent cause of chronic kidney disease, and their diagnosis has increased since the introduction of next generation sequencing (NGS). In 2018, the Multidisciplinary Unit for Hereditary Kidney Diseases of the Region of Murcia (UMERH-RM) was founded based on the genetic study of HKD. The objective of this study is to analyze the results obtained in the first 3 years of operation, and to analyze the clinical factors associated to a final genetic diagnosis...

Alport syndrome is characterized by type IV collagen network disruptions leading to renal, auditory, and ocular manifestations. This case report details a 24-year-old man with Alport syndrome who developed a rhegmatogenous retinal detachment following macular hole repair. The patient underwent a successful vitrectomy and internal limiting membrane peel for macular hole repair but returned with vision loss due to retinal detachment five weeks later, which necessitated a combined scleral buckle and vitrectomy...

Focal segmental glomerulosclerosis (FSGS) lesions have been linked to variants in COL4A3/A4/A5 genes, which are also mutated in Alport syndrome. Although it could be useful for diagnosis, quantitative evaluation of glomerular basement membrane (GBM) type IV collagen (colIV) networks is not widely used to assess these patients. To do so, we developed immunofluorescence imaging for collagen α5(IV) and α1/2(IV) on kidney paraffin sections with Airyscan confocal microscopy that clearly distinguishes GBM collagen α 3 α 4 α5(IV) and α 1 α 1 α2(IV) as two distinct layers, allowing quantitative assessment of both colIV networks...

BACKGROUND: X-linked Alport syndrome (XLAS) is an inherited renal disease caused by rare variants of COL4A5 on chromosome Xq22. Many studies have indicated that single nucleotide variants (SNVs) in exons can disrupt normal splicing process of the pre-mRNA by altering various splicing regulatory signals. The male patients with XLAS have a strong genotype-phenotype correlation. Confirming the effect of variants on splicing can help to predict kidney prognosis. This study aimed to investigate whether single nucleotide substitutions, located within three bases at the 5' end of the exons or internal position of the exons in COL4A5 gene, cause aberrant splicing process...

Alport syndrome, a rare genetic condition, can manifest various ocular abnormalities. This case report presents a unique instance of Alport syndrome where bilateral reduced visual acuity led to cataract surgery and subsequent central serous chorioretinopathy due to steroid treatment. By utilizing multiple imaging modalities, we aim to illustrate classical and atypical findings, addressing a literature gap and sharing our experience for educational purposes.

Conduit arterial disease in CKD is an important cause of cardiac complications. Cardiac function in CKD has not been studied in the absence of arterial disease. In an Alport syndrome model bred not to have conduit arterial disease, mice at 225 days of life (dol) had CKD equivalent to human stage 4-5 CKD. PTH and FGF23 levels were one log order elevated, circulating sclerostin was elevated, and renal activin A was strongly induced. Aortic Ca levels were not increased and VSMC transdifferentiation was absent...

A 13-year-old boy presented with hypoxia, microscopic hematuria, and elevated blood pressures. Persistent microscopic hematuria and hypertension led to investigation of glomerular and non-glomerular causes of hematuria. After reviewing his clinical course, family history, and laboratory testing, an additional test was sent, revealing the diagnosis.

Individualized pre-pregnancy counseling and antenatal care for women with chronic kidney disease (CKD) require disease-specific data. Here, we investigated pregnancy outcomes and long-term kidney function in women with COL4A3-5 related disease (Alport Syndrome, (AS)) in a large multicenter cohort. The ALPART-network (mAternaL and fetal PregnAncy outcomes of women with AlpoRT syndrome), an international collaboration of 17 centers, retrospectively investigated COL4A3-5 related disease pregnancies after the 20th week...

No abstract text is available yet for this article.

No abstract text is available yet for this article.

INTRODUCTION: Alport syndrome (AS) is an inherited, rare, progressive kidney disease that affects the eye and ear physiology. Pathogenic variants of COL4A5 account for 85% of all cases, while COL4A3 and COL4A4 account for the remaining 15%. METHODS: Targeted next-generation sequencing of the COL4A3 , COL4A4 , and COL4A5 genes was performed in 125 Turkish patients with AS. The patients were compared to 45 controls and open-access population data. RESULTS: The incidence of AS variants in patients was found as 21...

Data about the prevalence of biopsy-proven kidney diseases in Iran are rare, and none of the previous studies used electron microscopy for diagnosis. This study aimed to analyze the prevalence of biopsy-proven kidney diseases in Iran's primary referral center. To the best of our knowledge, this is the most extensive study carried out in Iran. Reports of kidney biopsy samples from patients referred to our center in 2007-2018 were reviewed for demographic data, clinical presentation, and final diagnosis. Statistical analyses were performed...

Between 15-20% of patients with end stage renal disease (ESRD) do not know the cause of the primary kidney disease and can develop complications after kidney transplantation. We performed a genetic screening in 300 patients with kidney transplantation, or undiagnosed primary renal disease, in order to identify the primary disease cause and discriminate between overlapping phenotypes. We used a custom-made panel for next-generation sequencing (Agilent technology, Santa Clara, CA, USA), including genes associated with Fabry disease, podocytopaties, complement-mediated nephropathies and Alport syndrome-related diseases...