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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 -
Clinical Rheumatology May 2019Podocytic infolding glomerulopathy (PIG) is a newly proposed disease entity, and only 29 cases have been reported worldwide so far, characterized by microspheres or...
Podocytic infolding glomerulopathy (PIG) is a newly proposed disease entity, and only 29 cases have been reported worldwide so far, characterized by microspheres or microtubular structures or both associated with podocytic infolding into the glomerular basement membrane (GBM) on electron microscopy. We present two new cases of PIG with connective tissue disease (CTD), one with primary Sjögren's syndrome and the other with systemic lupus erythematosus (SLE), and make a systemic review of the literature. In the entire 31 patients of PIG, 24 (77.42%) were women and seven (22.58%) were men, with an average age of 41.2 ± 15.2 (ranging from 14 to 79) years old. Almost two-thirds of patients (67.74%) were diagnosed with CTD, in which 76.19% were SLE. All patients presented with proteinuria and six (19.35%) patients were accompanied with hematuria. Serum creatinine was elevated in six (19.35%) patients. Pathological findings of all patients were consistent with PIG characteristics, and four patients with repeated renal biopsies further provided profound insights.
Topics: Adult; Creatinine; Female; Glomerular Basement Membrane; Hematuria; Humans; Kidney Diseases; Lupus Erythematosus, Systemic; Podocytes; Proteinuria; Sjogren's Syndrome; Young Adult
PubMed: 30879204
DOI: 10.1007/s10067-019-04504-6 -
Molecular Genetics and Metabolism Mar 2019Fabry disease is caused by a deficiency of the lysosomal enzyme α-galactosidase, resulting in progressive accumulation of globotriaosylceramide (GL-3). The disease can...
BACKGROUND
Fabry disease is caused by a deficiency of the lysosomal enzyme α-galactosidase, resulting in progressive accumulation of globotriaosylceramide (GL-3). The disease can manifest early during childhood and adolescence. Enzyme replacement therapy (ERT) with recombinant human α-galactosidase is the first specific treatment for Fabry disease and has been available in Europe since 2001. This paper presents the findings of a systematic literature review of clinical outcomes with ERT in paediatric patients with Fabry disease.
METHODS
A comprehensive systematic review of published literature on ERT in Fabry disease was conducted in January 2017. The literature analysis included all original articles reporting outcomes of ERT in paediatric patients.
RESULTS
Treatment-related outcomes in the paediatric population were reported in six publications derived from open-label clinical trials and in 10 publications derived from observational or registry-based studies. ERT was shown to significantly reduce plasma and urine GL-3 levels in paediatric patients with Fabry disease. The effect of ERT on GL-3 clearance from renal podocytes appeared to be agalsidase dose-dependent. ERT relieved pain and improved gastrointestinal symptoms and quality of life.
CONCLUSIONS
Based on the published literature, the use of ERT in paediatric patients can significantly clear GL-3 accumulation, ameliorate the early symptoms of Fabry disease, and improve quality of life. Treatment with ERT in paediatric patients with Fabry disease may be important to prevent further disease progression and overt organ damage.
Topics: Child; Enzyme Replacement Therapy; Europe; Fabry Disease; Female; Humans; Isoenzymes; Male; Observational Studies as Topic; Pain; Quality of Life; Randomized Controlled Trials as Topic; Recombinant Proteins; Treatment Outcome; Trihexosylceramides; alpha-Galactosidase
PubMed: 29785937
DOI: 10.1016/j.ymgme.2018.04.007