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Albumin is recycled from the primary urine by tubular transcytosis.

ABSTRACT: Under physiologic conditions, significant amounts of plasma protein pass the renal filter and are reabsorbed by proximal tubular cells, but it is not clear whether the endocytosed protein, particularly albumin, is degraded in lysosomes or returned to the circulatory system intact. To resolve this question, a transgenic mouse with podocyte-specific expression of doxycycline-inducible tagged murine albumin was developed. To assess potential glomerular backfiltration, two types of albumin with different charges were expressed. On administration of doxycycline, podocytes expressed either of the two types of transgenic albumin, which were secreted into the primary filtrate and reabsorbed by proximal tubular cells, resulting in serum accumulation. Renal transplantation experiments confirmed that extrarenal transcription of transgenic albumin was unlikely to account for these results. Genetic deletion of the neonatal Fc receptor (FcRn), which rescues albumin and IgG from lysosomal degradation, abolished transcytosis of both types of transgenic albumin and IgG in proximal tubular cells. In summary, we provide evidence of a transcytosis within the kidney tubular system that protects albumin and IgG from lysosomal degradation, allowing these proteins to be recycled intact.

SUBMITTER: Tenten V

PROVIDER: S-EPMC3839546 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature

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Albumin is recycled from the primary urine by tubular transcytosis.

Tenten Verena V Menzel Sylvia S Kunter Uta U Sicking Eva-Maria EM van Roeyen Claudia R C CR Sanden Silja K SK Kaldenbach Michaela M Boor Peter P Fuss Astrid A Uhlig Sandra S Lanzmich Regina R Willemsen Brigith B Dijkman Henry H Grepl Martin M Wild Klemens K Kriz Wilhelm W Smeets Bart B Floege Jürgen J Moeller Marcus J MJ

Journal of the American Society of Nephrology : JASN 20130822 12

Under physiologic conditions, significant amounts of plasma protein pass the renal filter and are reabsorbed by proximal tubular cells, but it is not clear whether the endocytosed protein, particularly albumin, is degraded in lysosomes or returned to the circulatory system intact. To resolve this question, a transgenic mouse with podocyte-specific expression of doxycycline-inducible tagged murine albumin was developed. To assess potential glomerular backfiltration, two types of albumin with diff ...[more]

PMID: 23970123

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Project description:BackgroundThe prevalence of chronic kidney disease (CKD) is predicted to rise over the next few decades. In resource-limited settings access to central laboratory services is limited. Point-of-care (POC) urine dipstick testing offers the potential to detect markers of kidney damage (albuminuria) as well as markers of other disease processes. We evaluated the diagnostic accuracy of the semi-quantitative albumin-creatinine ratio (ACR) Sysmex UC-1000 POC urine dipstick system as well as the extent of other abnormal dipstick findings in urine.Methods700 participants from a rural area in South Africa were screened for albuminuria. A spot urine sample was used to measure POC and central laboratory ACR. We determined the sensitivity, specificity, positive predictive value and negative predictive value of the POC ACR, and recorded dipstick parameters.ResultsThe prevalence of albuminuria was 11.6% (95%CI; 9.3-14.2). Those with albuminuria had higher mean diastolic (82 vs 79 mmHg, p = 0.019) and systolic (133 vs 128 mmHg, p = 0.002) blood pressures and a higher proportion of diabetes mellitus (17.6 vs 4.9%, p < 0.001). The sensitivity of the POC ACR system was 0.79, specificity 0.84, positive predictive value 0.39 and negative predictive value 0.97. The sensitivity improved to 0.80, 0.85, 0.85 and 0.89 in those with elevated blood pressure, diabetes mellitus, HIV positive status, and those 65 years and older, respectively. Abnormalities other than albuminuria were detected in 240 (34.3%) of the samples; 88 (12.6%) were positive for haematuria, 113 (16.1%) for leucocytes, 66 (9.4%) for nitrites and 27 (3.9%) for glycosuria.ConclusionOur study shows that POC ACR has good negative predictive value and could be used to rule out albuminuria when screening for CKD. Additionally, a high proportion of participants had other urine abnormalities detected with dipsticks which may reflect kidney disease or co-morbid untreated genitourinary pathology such as urinary tract infections or endemic schistosomiasis with important implications for CKD.

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Albumin is recycled from the primary urine by tubular transcytosis.

Publications

Albumin is recycled from the primary urine by tubular transcytosis.

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