Prevalence of Self-Reported Kidney Disease in Older Adults by Sexual Orientation: Behavioral Risk Factor Surveillance System Analysis (2014-2019).

SIGNIFICANCE STATEMENT: Studies discusses CKD disparities by age, race and ethnicity, and socioeconomics. However, despite well-documented disparities in CKD risk factors in LGBT+ adults, limited literature addresses CKD prevalence in this population. This analysis uses Behavioral Risk Factor Surveillance System (2014-2019) data to compare self-reported kidney disease prevalence in LGBT+ older adults (older than 50 years) with their heterosexual peers. Our findings indicate that LGBT+ older adults have higher rates of self-reported kidney disease and a higher incidence of CKD risks including smoking, activity limitations, adverse health outcomes, and limited access to health care, housing, and employment. These results support increasing access to screening for CKD risk factors, providing culturally responsive health care, and addressing societal drivers of vulnerability in older LGBT+ adults. BACKGROUND: Existing research documents disparities in CKD by age, race and ethnicity, and access to health care. However, research on CKD in lesbian, gay, bisexual, and trans (LGBT+) older adults, despite their higher rates of diabetes, heart disease, smoking, and alcohol use, is limited. METHODS: Pooled data from the Behavioral Risk Factor Surveillance System (2014-2019) for 22,114 LGBT+ adults and 748,963 heterosexuals aged 50 and older were used to estimate the prevalence of self-reported kidney disease. Logistic regressions were used to compare older adults by sexual orientation. RESULTS: Older LGBT+ men (adjusted odds ratio=1.3; 95% confidence interval [CI], 1.09-1.54) were more likely than their heterosexual counterparts to report kidney disease, after controlling for sociodemographic factors, health behaviors, access to health care, and self-reported coronary heart disease, HIV, and diabetes; LGBT+ men and women also reported higher incidences of known risk factors for CKD. For example, both LGBT+ men (odds ratio [OR]=1.39; [95% CI], 1.26-1.54) and LGBT+ women (OR=1.39; [95% CI], 1.25-1.55) were more likely to be smokers and have a higher incidence of activity limitations, adverse health outcomes, and limited access to health care, housing, and employment. CONCLUSION: These results support increasing access to screenings for CKD risk factors, providing preventative education and culturally responsive and affirming care, and addressing other societal drivers of vulnerability in older LGBT+ adults. The findings also support the value of interventions that address the interaction between CKD risk factors and the social marginalization that older LGBT+ adults experience.

Intracellular sites of AQP2 S256 phosphorylation identified using inhibitors of the AQP2 recycling itinerary.

Vasopressin (VP)-regulated aquaporin-2 (AQP2) trafficking between cytoplasmic vesicles and the plasma membrane of kidney principal cells is essential for water homeostasis. VP affects AQP2 phosphorylation at several serine residues in the COOH-terminus; among them, serine 256 (S256) appears to be a major regulator of AQP2 trafficking. Mutation of this serine to aspartic acid, which mimics phosphorylation, induces constitutive membrane expression of AQP2. However, the intracellular location(s) at which S256 phosphorylation occurs remains elusive. Here, we used strategies to block AQP2 trafficking at different cellular locations in LLC-PK1 cells and monitored VP-stimulated phosphorylation of S256 at these sites by immunofluorescence and Western blot analysis with phospho-specific antibodies. Using methyl-ß-cyclodextrin, cold block or bafilomycin, and taxol, we blocked AQP2 at the plasma membrane, in the perinuclear trans-Golgi network, and in scattered cytoplasmic vesicles, respectively. Regardless of its cellular location, VP induced a significant increase in S256 phosphorylation, and this effect was not dependent on a functional microtubule cytoskeleton. To further investigate whether protein kinase A (PKA) was responsible for S256 phosphorylation in these cellular compartments, we created PKA-null cells and blocked AQP2 trafficking using the same procedures. We found that S256 phosphorylation was no longer increased compared with baseline, regardless of AQP2 localization. Taken together, our data indicate that AQP2 S256 phosphorylation can occur at the plasma membrane, in the trans-Golgi network, or in cytoplasmic vesicles and that this event is dependent on the expression of PKA in these cells.NEW & NOTEWORTHY Phosphorylation of aquaporin-2 by PKA at serine 256 (S256) occurs in various subcellular locations during its recycling itinerary, suggesting that the protein complex necessary for AQP2 S256 phosphorylation is present in these different recycling stations. Furthermore, we showed, using PKA-null cells, that PKA activity is required for vasopressin-induced AQP2 phosphorylation. Our data reveal a complex spatial pattern of intracellular AQP2 phosphorylation at S256, shedding new light on the role of phosphorylation in AQP2 membrane accumulation.

Noncanonical SMC protein in Mycobacterium smegmatis restricts maintenance of Mycobacterium fortuitum plasmids.

Research on tuberculosis and leprosy was revolutionized by the development of a plasmid transformation system in the fast-growing surrogate, Mycobacterium smegmatis. This transformation system was made possible by the successful isolation of a M. smegmatis mutant strain mc(2)155, whose efficient plasmid transformation (ept) phenotype supported the replication of Mycobacterium fortuitum pAL5000 plasmids. In this report, we identified the EptC gene, the loss of which confers the ept phenotype. EptC shares significant amino acid sequence homology and domain structure with the MukB protein of Escherichia coli, a structural maintenance of chromosomes (SMC) protein. Surprisingly, M. smegmatis has three paralogs of SMC proteins: EptC and MSMEG_0370 both share homology with Gram-negative bacterial MukB; and MSMEG_2423 shares homology with Gram-positive bacterial SMCs, including the single SMC protein predicted for Mycobacterium tuberculosis and Mycobacterium leprae. Purified EptC was shown to bind ssDNA and stabilize negative supercoils in plasmid DNA. Moreover, an EptC-mCherry fusion protein was constructed and shown to bind to DNA in live mycobacteria, and to prevent segregation of plasmid DNA to daughter cells. To our knowledge, this is the first report of impaired plasmid maintenance caused by a SMC homolog, which has been canonically known to assist the segregation of genetic materials.