Differing sensitivities to angiotensin converting enzyme inhibition of kidney disease mediated by APOL1 high-risk variants G1 and G2.

Apolipoprotein L1 (APOL1) variants G1 and G2 contribute to the excess risk of kidney disease in individuals of recent African ancestry. Since disease mechanisms and optimal treatments remain controversial, we study the effect of current standard-of-care drugs in mouse models of APOL1 kidney disease. Experiments were performed in APOL1 BAC-transgenic mice, which develop proteinuria and glomerulosclerosis following injection with a pCpG-free IFNɤ plasmid. Proteinuric, plasmid injected G1/G1 and G2/G2 mice were randomized to drug treatment or no treatment. Lisinopril, dapagliflozin, and hydralazine were administered in drinking water starting day seven. The urine albumin/creatinine ratio was measured twice weekly, and the kidneys examined histologically with the focal segmental glomerulosclerosis score computed from periodic acid-Shiff-stained sections. The angiotensin converting enzyme inhibitor lisinopril, at standard dose, reduced proteinuria by approximately 90-fold and reduced glomerulosclerosis in the APOL1 G1/G1 BAC-transgenic mice. These effects were independent of blood pressure. Dapagliflozin did not alter disease progression in either G1/G1 or G2/G2 mice. Proteinuria reduction and glomerulosclerosis in G2/G2 BAC-transgenic mice required lisinopril doses two times higher than were effective in G1/G1 mice but achieved a much smaller benefit. Therefore, in these BAC-transgenic mouse models of APOL1 disease, the anti-proteinuric and anti-glomerulosclerotic effects of standard dose lisinopril were markedly effective in G1/G1 compared with G2/G2 APOL1 mice. Comparable reduction in blood pressure by hydralazine treatment provided no such protection. Neither G1/G1 or G2/G2 mice showed improvement with the sodium-glucose cotransporter-2 inhibition dapagliflozin. Thus, it remains to be determined if similar differences in ACE inhibitor responsiveness are observed in patients.

Convivial Quarantines: Cultivating Co-presence at a Distance.

Sociology's focus on sociality and co-presence has long oriented studies of commensality-the social dimension of eating together. This literature commonly prioritizes face-to-face interactions and takes physical proximity for granted. The onset of the COVID-19 pandemic in March 2020 largely halted in-person gatherings and altered everyday foodways. Consequently, many people turned to digital commensality, cooking and eating together through video-call technology such as Zoom and FaceTime. We explore the implications of these new foodways and ask: has digital commensality helped cultivate co-presence amidst pandemic-induced physical separation? If so, how? To address these questions, we analyze two forms of qualitative data collected by the first author: interviews with individuals who cooked and ate together at a distance since March 2020 and digital ethnography during different groups' online food events (e.g., happy hours, dinners, holiday gatherings, and birthday celebrations). Digital commensality helps foster a sense of co-presence and social connectedness at a distance. Specifically, participants use three temporally oriented strategies to create or maintain co-presence: they draw on pre-pandemic pasts and reinvent culinary traditions to meet new circumstances; they creatively adapt novel digital foodways through online dining; and they actively imagine post-pandemic futures where physically proximate commensality is again possible.