{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T22:57:57Z","timestamp":1766012277605,"version":"3.37.3"},"reference-count":27,"publisher":"American Physiological Society","issue":"3","funder":[{"DOI":"10.13039\/100000062","name":"HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)","doi-asserted-by":"publisher","award":["P50 DK 096418"],"award-info":[{"award-number":["P50 DK 096418"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Renal Physiology"],"published-print":{"date-parts":[[2017,9,1]]},"abstract":"<jats:p> The early events that signal renal dysfunction in presymptomatic heart failure are unclear. We tested the hypothesis that functional and mechanistic changes occur in the kidney that precede the development of symptomatic heart failure. We employed a transgenic mouse model with cardiomyocyte-specific overexpression of mutant \u03b1-B-crystallin that develops slowly progressive cardiomyopathy. Presymptomatic transgenic mice displayed an increase in serum creatinine (1.17\u2009\u00b1\u20090.34 vs. wild type 0.65\u2009\u00b1\u20090.16 mg\/dl, P &lt; 0.05) and in urinary neutrophil gelatinase-associated lipocalin (NGAL; 278.92\u2009\u00b1\u2009176.24 vs. wild type 49.11\u2009\u00b1\u200922.79 ng\/ml, P &lt; 0.05) but no renal fibrosis. Presymptomatic transgenic mouse kidneys exhibited a twofold upregulation of the Ren1 gene, marked overexpression of renin protein in the tubules, and a worsened response to ischemia-reperfusion injury based on serum creatinine (2.77\u2009\u00b1\u20090.66 in transgenic mice vs. 2.01 \u00b1 0.58 mg\/dl in wild type, P &lt; 0.05), urine NGAL (9,198.79 \u00b1 3,799.52 in transgenic mice vs. 3,252.94 \u00b1 2,420.36 ng\/ml in wild type, P &lt; 0.05), tubule dilation score (3.4 \u00b1 0.5 in transgenic mice vs. 2.6 \u00b1 0.5 in wild type, P &lt; 0.05), tubule cast score (3.2 \u00b1 0.4 in transgenic mice vs. 2.5 \u00b1 0.5 in wild type, P &lt; 0.05), and TdT-mediated dUTP nick-end labeling (TUNEL)-positive nuclei (10.1 \u00b1 2.1 in the transgenic group vs. 5.7 \u00b1 1.6 per 100 cells counted in wild type, P &lt; 0.01). Our findings indicate functional renal impairment, urinary biomarker elevations, and induction of renin gene and protein expression in the kidney that occur in early presymptomatic heart failure, which increase the susceptibility to subsequent acute kidney injury. <\/jats:p>","DOI":"10.1152\/ajprenal.00505.2016","type":"journal-article","created":{"date-parts":[[2017,7,5]],"date-time":"2017-07-05T20:20:15Z","timestamp":1499286015000},"page":"F699-F705","source":"Crossref","is-referenced-by-count":4,"title":["Increased susceptibility to structural acute kidney injury in a mouse model of presymptomatic cardiomyopathy"],"prefix":"10.1152","volume":"313","author":[{"given":"LaTawnya","family":"Pleasant","sequence":"first","affiliation":[{"name":"Nephrology and Hypertension, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, Ohio; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qing","family":"Ma","sequence":"additional","affiliation":[{"name":"Nephrology and Hypertension, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, Ohio; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mahima","family":"Devarajan","sequence":"additional","affiliation":[{"name":"Nephrology and Hypertension, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, Ohio; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Priyanka","family":"Parameswaran","sequence":"additional","affiliation":[{"name":"Nephrology and Hypertension, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, Ohio; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keri","family":"Drake","sequence":"additional","affiliation":[{"name":"Nephrology and Hypertension, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, Ohio; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian","family":"Siroky","sequence":"additional","affiliation":[{"name":"Nephrology and Hypertension, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, Ohio; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kritton","family":"Shay-Winkler","sequence":"additional","affiliation":[{"name":"Molecular Cardiovascular Biology, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey","family":"Robbins","sequence":"additional","affiliation":[{"name":"Molecular Cardiovascular Biology, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Prasad","family":"Devarajan","sequence":"additional","affiliation":[{"name":"Nephrology and Hypertension, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, Ohio; 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