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Journal of Ophthalmology 2022Alport syndrome (AS) is a severe, rare hereditary disorder that can lead to end-stage renal disease, auditory degeneration, and ocular abnormalities. Despite extensive... (Review)
Review
OBJECTIVES
Alport syndrome (AS) is a severe, rare hereditary disorder that can lead to end-stage renal disease, auditory degeneration, and ocular abnormalities. Despite extensive research on AS in relation to auditory and renal disorders, more research is needed on the ocular presentations of AS. This systematic review aims to summarize the common ocular abnormalities in patients with AS and to explore the potential treatment options for these irregularities.
METHODS
The PubMed, MEDLINE, and EMBASE databases were systematically searched from January 1977 to April 2022. Only papers that were published in the English language and explored the ocular abnormalities in AS patients were selected. We manually searched reference lists of included papers for additional studies.
RESULTS
A total of 23 articles involving 195 patients were included in this review. The common ocular manifestations in AS patients are lenticonus, macular holes, fleck retinopathy, and thinning of the macula. Although published literature has described the use of cataract surgeries and vitrectomies as standard surgical techniques to alleviate ocular abnormalities in non-AS patients, it must be noted that surgical techniques have not been evaluated in a large research study as a solution for AS abnormalities. Another prospective treatment for AS is gene therapy through the reversion of causative variants to wild type or exon-skipping therapy for -linked AS with truncating mutations. Gene therapy, however, remains unable to treat alterations that occur in the fetal and early development phase of the disease.
CONCLUSIONS
The review found no definitive conclusions regarding the efficacy and safety of surgical techniques and gene therapy in AS patients. Recognition of ocular abnormalities through an ophthalmic examination with an optical coherence tomography (OCT) and slit-lamp examination is critical to the medical field, as ophthalmologists can aid nephrologists and other physicians in diagnosing AS. Early diagnosis and care can minimize the risk of detrimental ocular outcomes, such as blindness and retinal detachment.
PubMed: 36119140
DOI: 10.1155/2022/9250367 -
Kidney International Reports Nov 2022Women and girls with X-linked Alport syndrome have a risk of disease progression that is difficult to predict. This systematic review examined whether proteinuria...
INTRODUCTION
Women and girls with X-linked Alport syndrome have a risk of disease progression that is difficult to predict. This systematic review examined whether proteinuria correlated with genotype and disease severity in this population.
METHODS
PubMed and Scopus were searched for manuscripts from the past 20 years with "," "female," "proteinuria" and related terms. Genotypes and clinical data for women and girls with pathogenic heterozygous variants were extracted. Features were then compared between females with proteinuria or without proteinuria; and genotype-phenotype correlations for age at proteinuria and kidney failure determined.
RESULTS
Three-hundred sixty-six women and girls with variants and a median age of 29 years (interquartile range 15-46) were identified. Eighty-eight (24%) had large rearrangements or truncating variants, 63 (17%) had splicing variants, and 215 (59%) had missense changes. In all, 236 (64%) had proteinuria, 56 (16%) had kidney failure, 40 (16%) had a hearing loss, and 15 (7%) had ocular abnormalities. Women and girls with proteinuria were more likely to have large rearrangements or truncating variants ( = 0.005), and less likely to have missense changes ( = 0.0002). Those with proteinuria were also more likely to develop kidney failure ( < 0.0001). Women and girls with truncating, large or splicing variants developed proteinuria earlier than those with missense changes ( = 0.001, < 0.0001 respectively). Those whose proteinuria was detected before the age of 15 progressed to kidney failure sooner ( < 0.0001).
CONCLUSION
Proteinuria correlates with a more severe genotype in women and girls with X-linked Alport syndrome and is an indicator of disease severity and likely progression.
PubMed: 36531881
DOI: 10.1016/j.ekir.2022.08.021 -
International Journal of Molecular... Jun 2022Alport syndrome (AS) is the second most common cause of inherited chronic kidney disease. This disorder is caused by genetic variants on , and genes. These genes... (Review)
Review
Alport syndrome (AS) is the second most common cause of inherited chronic kidney disease. This disorder is caused by genetic variants on , and genes. These genes encode the proteins that constitute collagen type IV of the glomerular basement membrane (GBM). The heterodimer COL4A3A4A5 constitutes the majority of the GBM, and it is essential for the normal function of the glomerular filtration barrier (GFB). Alterations in any of collagen type IV constituents cause disruption of the GMB structure, allowing leakage of red blood cells and albumin into the urine, and compromise the architecture of the GFB, inducing inflammation and fibrosis, thus resulting in kidney damage and loss of renal function. The advances in DNA sequencing technologies, such as next-generation sequencing, allow an accurate diagnose of AS. Due to the important risk of the development of progressive kidney disease in AS patients, which can be delayed or possibly prevented by timely initiation of therapy, an early diagnosis of this condition is mandatory. Conventional biomarkers such as albuminuria and serum creatinine increase relatively late in AS. A panel of biomarkers that might detect early renal damage, monitor therapy, and reflect the prognosis would have special interest in clinical practice. The aim of this systematic review is to summarize the biomarkers of renal damage in AS as described in the literature. We found that urinary Podocin and Vascular Endothelial Growth Factor A are important markers of podocyte injury. Urinary Epidermal Growth Factor has been related to tubular damage, interstitial fibrosis and rapid progression of the disease. Inflammatory markers such as Transforming Growth Factor Beta 1, High Motility Group Box 1 and Urinary Monocyte Chemoattractant Protein- 1 are also increased in AS and indicate a higher risk of kidney disease progression. Studies suggest that miRNA-21 is elevated when renal damage occurs. Novel techniques, such as proteomics and microRNAs, are promising.
Topics: Biomarkers; Collagen Type IV; Fibrosis; Humans; Kidney; Nephritis, Hereditary; Vascular Endothelial Growth Factor A
PubMed: 35806283
DOI: 10.3390/ijms23137276 -
Journal of Clinical Medicine Feb 2019Alport syndrome (AS) is one of the most frequent hereditary nephritis leading to end-stage renal disease (ESRD). Although X-linked (XLAS) inheritance is the most common...
Alport syndrome (AS) is one of the most frequent hereditary nephritis leading to end-stage renal disease (ESRD). Although X-linked (XLAS) inheritance is the most common form, cases with autosomal recessive inheritance with mutations in or are being increasingly recognized. A systematic review was conducted on autosomal recessive Alport syndrome (ARAS). Electronic databases were searched using related terms (until Oct 10th, 2018). From 1601 articles searched, there were 26 eligible studies with 148 patients. Female and male patients were equally affected. About 62% of patients had ESRD, 64% had sensorineural hearing loss (SNHL) and 17% had ocular manifestation. The median at onset was 2.5 years for hematuria (HU), 21 years for ESRD, and 13 years for SNHL. Patients without missense mutations had more severe outcomes at earlier ages, while those who had one or two missense mutations had delayed onset and lower prevalence of extrarenal manifestations. Of 49 patients with kidney biopsy available for electron microscopy (EM) pathology, 42 (86%) had typical glomerular basement membrane (GBM) changes, while 5 (10%) patients showed GBM thinning only. SNHL developed earlier than previously reported. There was a genotype phenotype correlation according to the number of missense mutations. Patients with missense mutations had delayed onset of hematuria, ESRD, and SNHL and lower prevalence of extrarenal manifestations.
PubMed: 30717457
DOI: 10.3390/jcm8020178 -
Clinical Kidney Journal Dec 2020Patients heterozygous for or mutations show a wide spectrum of disease, extending from familial isolated microscopic haematuria, as a result of thin basement membranes...
BACKGROUND
Patients heterozygous for or mutations show a wide spectrum of disease, extending from familial isolated microscopic haematuria, as a result of thin basement membranes (TBMs), to autosomal dominant Alport syndrome (ADAS) and end-stage renal disease (ESRD). Many patients are mentioned in the literature under the descriptive diagnosis of TBM nephropathy (TBMN), in which case it actually describes a histological finding that represents the carriers of autosomal recessive Alport syndrome (ARAS), a severe glomerulopathy, as most patients reach ESRD at a mean age of 25 years.
METHODS
We performed a systematic literature review for patients with heterozygous / mutations with the aim of recording the spectrum and frequency of pathological features. We searched three databases (PubMed, Embase and Scopus) using the keywords 'Autosomal Dominant Alport Syndrome' OR 'Thin Basement Membrane Disease' OR 'Thin Basement Membrane Nephropathy'. We identified 48 publications reporting on 777 patients from 258 families.
RESULTS
In total, 29% of the patients developed chronic kidney disease (CKD) and 15.1% reached ESRD at a mean age of 52.8 years. Extrarenal features and typical Alport syndrome (AS) findings had a low prevalence in patients as follows: hearing loss, 16%; ocular lesions, 3%; basement membrane thickening, 18.4%; and podocyte foot process effacement, 6.9%. Data for 76 patients from 54 families emphasize extensive inter- and intrafamilial heterogeneity, with age at onset of ESRD ranging between 21 and 84 years (mean 52.8).
CONCLUSIONS
The analysis enabled a comparison of the clinical course of patients with typical ARAS or X-linked AS with those with heterozygous mutations diagnosed with TBMN or ADAS. Despite the consequence of a potential ascertainment bias, an important outcome is that TBM poses a global high risk of developing severe CKD, over a long follow-up, with a variable spectrum of other findings. The results are useful to practicing nephrologists for better evaluation of patients.
PubMed: 33391746
DOI: 10.1093/ckj/sfz176 -
Cureus Jan 2024Dialysis in pediatric groups is complicated by a wide range of factors that can affect long-term prognosis. The purpose of this meta-analysis and systematic review is to... (Review)
Review
Dialysis in pediatric groups is complicated by a wide range of factors that can affect long-term prognosis. The purpose of this meta-analysis and systematic review is to better understand the demographic and clinical factors that affect dialysis success in children. We searched a variety of databases for relevant articles and included 14 reports that dealt with the case studies of pediatric patients undergoing dialysis for a wide range of renal diseases. Patients' demographics, clinical presentations, laboratory findings, and treatment outcomes were the primary areas of data collection. To get a better sense of the overall prevalence of certain outcomes and to spot noteworthy trends or patterns in the disease process, we conducted a meta-analysis. Variations in dialysis efficacy and outcomes are highlighted throughout a wide range of ages in the pediatric dialysis cohort, from neonates to teenagers. Acute kidney injuries (AKI) tended to impact more boys, but chronic kidney diseases (CKD), such as lupus nephritis, disproportionately afflicted girls. Many different ethnic groups were represented, and there was evidence that some diseases having a hereditary component were more common in some areas than others. However, the potential for long-term consequences remained a concern. Hemodialysis was found to be effective in controlling end-stage renal disease (ESRD) and AKI, with some patients going on to have a kidney transplant. At the same time, peritoneal dialysis was associated with an increased risk of infection. This comprehensive analysis highlights the importance of demographic and clinical parameters in determining pediatric dialysis outcomes. A 14.47% mortality rate and gender disparities are revealed by this meta-analysis of pediatric renal diseases, which included a cohort of 235 patients with conditions like lupus nephritis and hepatitis C infection. The findings stress the necessity for individualized treatment techniques and suggest that demographic characteristics should be addressed in prognostic models. For better patient outcomes, the study also suggests standardized reporting in pediatric dialysis studies.
PubMed: 38344624
DOI: 10.7759/cureus.51978