Increase of Total Nephron Albumin Filtration and Reabsorption in Diabetic Nephropathy

HANDLE Open Access

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

Journal

Details 詳細情報について

  • CRID
    1050282810812405376
  • NII Article ID
    120005820888
  • ISSN
    10466673
  • HANDLE
    2433/216097
  • Text Lang
    en
  • Article Type
    journal article
  • Data Source
    • IRDB
    • CiNii Articles

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