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Title: Increase of Total Nephron Albumin Filtration and Reabsorption in Diabetic Nephropathy
Authors: Mori, Keita P.
Yokoi, Hideki  kyouindb  KAKEN_id
Kasahara, Masato
Imamaki, Hirotaka
Ishii, Akira  kyouindb  KAKEN_id
Kuwabara, Takashige
Koga, Kenichi
Kato, Yukiko
Toda, Naohiro
Ohno, Shoko
Kuwahara, Koichiro
Endo, Tomomi
Nakao, Kazuwa
Yanagita, Motoko  kyouindb  KAKEN_id
Mukoyama, Masashi
Mori, Kiyoshi
Author's alias: 森, 慶太
森, 潔
Issue Date: 6-Jul-2016
Publisher: American Society of Nephrology (ASN)
Journal title: Journal of the American Society of Nephrology
Abstract: There is a hot debate concerning actual amount of albumin filtered through glomeruli and reabsorbed at proximal tubules in normal kidneys and diabetic conditions. To overcome current technical problems, we generated a drug-inducible megalin knockout mouse line, megalin(lox/lox);Ndrg1-CreER[T2] (or iMegKO), whose protein reabsorption can be shut off anytime by tamoxifen (Tam). After Tam administration, renal megalin protein expression was reduced by 92% compared to wild-type C57BL/6J mice, and renal reabsorption of intravenously-injected retinol binding protein was almost completely abrogated. Urinary albumin excretion increased to 175 μg/day (0.460 mg/mg-creatinine), suggesting that this was the amount of total nephron albumin filtration. Glomerular sieving coefficient of albumin was 1.7 x 10[-5]. By comparing streptozotocin-induced, Tam-treated, diabetic STZ;iMegKO mice with non-STZ;iMegKO mice, we estimated that daily albumin filtration was increased by 1.9-fold, reabsorption was increased by 1.8-fold, and reabsorption efficiency was reduced to 86% by development of diabetes (versus 96% in control). Such abnormalities were well normalized after insulin treatment. Another type 1 diabetic model of Akita;iMegKO mice showed equivalent results. This study reveals actual values and changes of albumin filtration and reabsorption in early diabetic nephropathy, bringing new insights into our understanding of renal albumin dynamics in hyperfiltration status of diabetic nephropathy
Rights: This is the accepted version of the article, which has been published in final form at http://jasn.asnjournals.org/content/early/2016/07/05/ASN.2015101168.
この論文は出版社版でありません。引用の際には出版社版をご確認ご利用ください。This is not the published version. Please cite only the published version.
URI: http://hdl.handle.net/2433/216097
DOI(Published Version): 10.1681/ASN.2015101168
PubMed ID: 27382987
Appears in Collections:Journal Articles

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