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Science Papers Examine Chronic Kidney Disease GWAS, Pneumonia Microbiome

By analyzing data from existing genome-wide association studies of chronic kidney disease, a University of Pennsylvania-led team uncovers new insights into the link between mutations in a single gene and kidney disease. Previous GWAS have implicated genetic variants on chromosome 4 in kidney disease, but details about this association have been lacking. To investigate, the researchers examined GWAS data on more than 40,000 subjects and individuals at high risk for chronic kidney disease. As reported in Science Translational Medicine, they find that those at higher risk harbored rare loss-of-function mutations in MANBA, a lysosomal gene highly expressed in kidney tubule cells, and had abnormally low levels of an enzyme encoded by the gene. Further analysis revealed structural and functional lysosomal alterations in human subjects with chronic kidney disease risk alleles, as well as mice engineered to lack MANBA. Notably, these mice were more vulnerable to induced kidney fibrosis. "Our studies highlight the critical role of lysosomal integrity in protecting from kidney disease development … [and] could open new avenues for therapeutic targeting of the autolysosomal pathways in kidney disease development," the study's authors write.

The role of the microbiomes of the upper respiratory tract and gut in pneumonia is discussed by a trio of Charité-Universitätsmedizin Berlin scientists in Science Translational Medicine this week. In the review, the researchers discuss how these microbes help prevent pneumonia by blocking colonization by potentially dangerous bacteria and controlling immune responses and highlight how certain treatments and medical interventions can alter these microbiomes and disrupt their protective functions. They also touch on ways to potentially boost microbiota-dependent defense mechanisms and call for additional research that leverages advances in genome sequencing to characterize microbiota at the level of microbial species and their genetic repertoire. "A better understanding will help to refine our current clinical approaches for preventing microbiota perturbations and will foster the development of intervention strategies to preserve microbiota-dependent defense mechanisms and to protect patients against pneumonia," they write.