ABSTRACT
RATIONALE & OBJECTIVE: Alport syndrome is a common genetic kidney disease accounting for approximately 2% of patients receiving kidney replacement therapy (KRT). It is caused by pathogenic variants in the gene COL4A3, COL4A4, or COL4A5. The aim of this study was to evaluate the clinical and genetic spectrum of patients with autosomal dominant Alport syndrome (ADAS). STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: 82 families (252 patients) with ADAS were studied. Clinical, genetic, laboratory, and pathology data were collected. OBSERVATIONS: A pathogenic DNA variant in COL4A3 was identified in 107 patients (35 families), whereas 133 harbored a pathogenic variant in COL4A4 (43 families). Digenic/complex inheritance was observed in 12 patients. Overall, the median kidney survival was 67 (95% CI, 58-73) years, without significant differences across sex (P=0.8), causative genes (P=0.6), or type of variant (P=0.9). Microhematuria was the most common kidney manifestation (92.1%), and extrarenal features were rare. Findings on kidney biopsies ranged from normal to focal segmental glomerulosclerosis. The slope of estimated glomerular filtration rate change was-1.46 (-1.66 to-1.26) mL/min/1.73m2 per year for the overall group, with no significant differences between ADAS genes (P=0.2). LIMITATIONS: The relatively small size of this series from a single country, potentially limiting generalizability. CONCLUSIONS: Patients with ADAS have a wide spectrum of clinical presentations, ranging from asymptomatic to kidney failure, a pattern not clearly related to the causative gene or type of variant. The diversity of ADAS phenotypes contributes to its underdiagnosis in clinical practice.
Subject(s)
Autoantigens/genetics , Collagen Type IV/genetics , Genetic Testing/methods , Genetic Variation/genetics , Nephritis, Hereditary/diagnosis , Nephritis, Hereditary/genetics , Adolescent , Adult , Aged , Aged, 80 and over , Cohort Studies , Female , Humans , Male , Middle Aged , Nephritis, Hereditary/epidemiology , Renal Insufficiency/diagnosis , Renal Insufficiency/epidemiology , Renal Insufficiency/genetics , Retrospective Studies , Young AdultABSTRACT
Methylobacterium sp. is isolated from water distribution systems and has been linked in the biofilms of the systems with a lower presence of Mycobacterium avium. In this study we aimed to determine the in vitro activity of Methylobacterium sp. in the development of rapidly growing mycobacteria (RGM) biofilms. Methylobacterium sp. CECT 7805 was added as a suspension of living bacteria (LB), an autoclaved suspension (AS), and an extract obtained after sonication (ES) at different times (24, 48, and 72 h), to preformed biofilms of Mycobacterium abscessus DSM 44196, Mycobacterium chelonae ATCC 19235, and Mycobacterium fortuitum ATCC 6841, using a 96 h control of each species. The biofilms were analyzed by confocal laser scanning microscopy and by the Calgary biofilm device using the plates MBECTM Biofilm Inoculator. A statistically significant reduction in the thickness and covered surface was observed in all mycobacterial biofilms with all forms of Methylobacterium sp. A statistically significant increase in the autofluorescence was observed in M. abscessus biofilms but not in other biofilms. The increased percentage of dead mycobacteria was statistically significant in all cases. The reduced log CFU (colony-forming units)/peg recount was statistically significant in M. chelonae biofilms after treatment with AS and ES, but in M. fortuitum biofilms the recount decreased only with AS. M. abscessus biofilms were always significantly reduced with AS at 72 h and with ES. Methylobacterium sp. could inhibit RGM biofilm formation. Living cells of Methylobacterium sp. were not necessary to inhibit the growth of a preformed biofilm. M. chelonae biofilms were the most greatly reduced.
