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Recent studies suggest that natriuretic peptides (NPs) are podocyte protective. The beneficial effects of NPs are inhibited by the removal of NPs from the circulation by the NP clearance receptor (NPRC). To determine if inhibiting NP clearance by NPRC ameliorated DKD, we deleted NPRC specifically in glomerular podocytes in a mouse model of type 1 diabetes (Akita mice). We found that diabetes induced a significant increase in albuminuria in WT Akita mice, which was significantly reduced by knockout (KO) of NPRC. Histologic damage was mild in both WT and KO Akita mice and limited to a modest increase in mesangial matrix in both groups. In contrast, expression of the fibrotic markers fibronectin and collagen 1 was significantly increased in isolated glomerular preparations, and expression of both fibrotic markers was significantly improved by podocyte\u2010specific KO of NPRC. Taken together, these data suggest that inhibiting NP clearance by glomerular podocytes has beneficial effects in a mouse model of early\u2010stage DKD.<\/jats:p>","DOI":"10.14814\/phy2.70899","type":"journal-article","created":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T06:36:19Z","timestamp":1778740579000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Podocyte specific knockout (\n                    <scp>KO<\/scp>\n                    ) of the natriuretic peptide clearance receptor (\n                    <scp>NPRC<\/scp>\n                    ) attenuates diabetic kidney disease (\n                    <scp>DKD<\/scp>\n                    )"],"prefix":"10.14814","volume":"14","author":[{"given":"Liming","family":"Wang","sequence":"first","affiliation":[{"name":"Division of Nephrology, Department of Medicine Duke University and Durham VA Medical Centers  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yupinp","family":"Tang","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine Duke University and Durham VA Medical Centers  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qunsheng","family":"Dai","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine Duke University and Durham VA Medical Centers  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne F.","family":"Buckley","sequence":"additional","affiliation":[{"name":"Department of Pathology Duke University Medical Center  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3858-0317","authenticated-orcid":false,"given":"Robert F.","family":"Spurney","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine Duke University and Durham VA Medical Centers  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,13]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.3780332"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.15710"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa011161"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2009070721"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-62703-068-7_2"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0033942"},{"key":"e_1_2_10_8_1","first-page":"R373","article-title":"Clearance receptors and endopeptidase 24.11: Equal role in natriuretic peptide metabolism in conscious sheep","volume":"271","author":"Charles C. 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