{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T07:40:00Z","timestamp":1793605200914,"version":"4.5.0"},"reference-count":58,"publisher":"American Society for Clinical Investigation","issue":"12","funder":[{"name":"Innovative Medicines Initiative","award":["115974"],"award-info":[{"award-number":["115974"]}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"crossref","award":["P30 DK081943"],"award-info":[{"award-number":["P30 DK081943"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"crossref"}]},{"name":"National Institute of Health Rare Disease Clinical Research Network","award":["U54-DK-083912"],"award-info":[{"award-number":["U54-DK-083912"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,6,20]]},"abstract":"<jats:p>\n                    An imbalance of nephroprotective factors and renal damaging molecules contributes to development and progression of chronic kidney disease (CKD). We investigated associations of renoprotective factor gene expression patterns with CKD severity and outcome. Gene expression profiles of 197 previously reported renoprotective factors were analyzed in a discovery cohort in renal biopsies of 63 CKD patients. Downregulation of dicarbonyl and L-xylulose reductase (\n                    <jats:italic>DCXR<\/jats:italic>\n                    ) showed the strongest association with disease progression. This significant association was validated in an independent set of 225 patients with nephrotic syndrome from the multicenter NEPTUNE cohort. Reduced expression of\n                    <jats:italic>DCXR<\/jats:italic>\n                    was significantly associated with degree of histological damage as well as with lower estimated glomerular filtration rate and increased urinary protein levels.\n                    <jats:italic>DCXR<\/jats:italic>\n                    downregulation in CKD was confirmed in 3 publicly available transcriptomics data sets in the context of CKD. Expression of\n                    <jats:italic>DCXR<\/jats:italic>\n                    showed positive correlations to enzymes that are involved in dicarbonyl stress detoxification based on transcriptomics profiles. The sodium glucose cotransporter-2 (SGLT2) inhibitors canagliflozin and empagliflozin showed a beneficial effect on renal proximal tubular cells under diabetic stimuli\u2013enhanced\n                    <jats:italic>DCXR<\/jats:italic>\n                    gene expression. In summary, lower expression of the renoprotective factor\n                    <jats:italic>DCXR<\/jats:italic>\n                    in renal tissue is associated with more severe disease and worse outcome in human CKD.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.128120","type":"journal-article","created":{"date-parts":[[2019,6,19]],"date-time":"2019-06-19T11:01:08Z","timestamp":1560942068000},"source":"Crossref","is-referenced-by-count":15,"title":["Identification of dicarbonyl and L-xylulose reductase as a therapeutic target in human chronic kidney disease"],"prefix":"10.1172","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2087-5691","authenticated-orcid":true,"given":"Paul","family":"Perco","sequence":"first","affiliation":[{"name":"Department of Internal Medicine IV (Nephrology and Hypertension), Medical University Innsbruck, Innsbruck, 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