The Role of the Kidney in the Metabolism of Plasma Proteins

Strober, Warren; Waldmann, Thomas A.

doi:10.1159/000180368

Cited by 149 publications

(60 citation statements)

References 54 publications

(89 reference statements)

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“…Synthesized by the liver, a1m circulates in the blood in free and protein-bound forms, with approximately 50% of plasma a1m bound to IgA. The 26-kD free form of a1m is filtered by the glomerulus and almost entirely reabsorbed by proximal tubular epithelial cells, where it is degraded by intracellular lysosomes (29,30). Active transport of a1m from the luminal space into proximal tubular epithelial cells is mediated by the endocytic receptor megalin, which also facilitates reabsorption of other low molecular mass proteins, such as retinol-binding protein and b2-microglobulin (31).…”

Section: Discussionmentioning

confidence: 99%

Association of Urine α1-Microglobulin with Kidney Function Decline and Mortality in HIV-Infected Women

Jotwani

Scherzer

Abraham

et al. 2015

Clinical Journal of the American Society of Nephrology

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Background and objectives Despite advances in therapy, HIV-infected individuals remain at higher risk for kidney dysfunction than uninfected individuals. It was hypothesized that urine levels of a1-microglobulin, a biomarker of proximal tubular dysfunction, would predict kidney function decline and mortality risk in HIV-infected and uninfected women.Design, setting, participants, & measurements In the Women's Interagency HIV Study, urine a1-microglobulin and creatinine concentrations were measured in 903 HIV-infected and 287 uninfected women using stored urine from 1999 to 2000, when prevalence of tenofovir use was ,1%. Participants were categorized into three categories by level of a1-microglobulin-to-creatinine ratio, and associations with kidney decline and all-cause mortality over 8 years were evaluated.Results Urine a1-microglobulin was detectable in 60% of HIV-infected and 40% of uninfected women (P,0.001). Among HIV-infected women, there were 177 (22%), 61 (7%), and 128 (14%) patients with incident CKD, with 10% annual eGFR decline, and who died, respectively. Compared with HIV-infected women in the lowest a1-microglobulin category, HIV-infected women in the highest a1-microglobulin category had a 2.1-fold risk of incident CKD (95% confidence interval, 1.3 to 3.4), 2.7-fold risk of 10% annual eGFR decline (95% confidence interval, 1.2 to 5.9), and 1.6-fold mortality risk (95% confidence interval, 1.0 to 2.6) in models adjusting for kidney risk factors, baseline eGFR, and albuminuria. Among uninfected women, the highest a1-microglobulin category was associated with 3% (relative risk, 2.2; 95% confidence interval, 1.4 to 3.5) and 5% (relative risk, 2.2; 95% confidence interval, 1.1 to 4.3) annual eGFR decline relative to the lowest a1-microglobulin category.Conclusions Proximal tubular dysfunction, indicated by urine a1-microglobulin, was independently associated with kidney function decline in HIV-infected and uninfected women and mortality risk among HIV-infected women.

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Section: Discussionmentioning

confidence: 99%

Association of Urine α1-Microglobulin with Kidney Function Decline and Mortality in HIV-Infected Women

Jotwani

Scherzer

Abraham

et al. 2015

Clinical Journal of the American Society of Nephrology

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“…Owing to its small size, RBP is ®ltered at the glomerulus and both reabsorbed and metabolised in the proximal tubule (Smith & Goodman, 1979). Both reabsorption and catabolism of low molecular weight proteins are impaired in diseases in which there is nephron-loss (Strober & Waldmann, 1974). Thus, these proteins accumulate in the blood.…”

Section: Discussionmentioning

confidence: 99%

Retinol, α-tocopherol and carotenoids in diabetes

et al. 1999

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Objective: A case-control study was conducted to evaluate the effects of diabetes mellitus on serum levels of vitamin A, a-carotene, b-carotene, a-tocopherol, serum and urine RBP. Subjects: One hundred and seven patients with Type 2 diabetes mellitus (28 ± 74 y) were recruited from those attending a primary health care clinic in King Khalid University Hospital in Riyadh City (Saudi Arabia). They were matched for age and sex with 143 healthy individuals. Methods: Fasting blood samples and 10 h urine collections were obtained from all subjects. Levels of vitamins and carotenoids in serum measured by high performance liquid chromatography (HPLC), and of retinol binding protein (RBP) in serum and urine by an enzyme-linked immunosorbent assay (ELISA). Results: The mean serum concentrations of retinol, a-carotene, and a-tocopherol were similar in both groups after correction of lipid soluble vitamins for serum lipids levels. However, serum b-carotene concentration was signi®cantly higher in control subjects than diabetics (P 0.002). Serum and urine RBP concentrations were signi®cantly higher in diabetics than in controls (P 0.0001 ). In normal subjects (but not diabetics) serum concentrations of retinol and RBP were higher in men than in women (P 0.02, P 0.0001 respectively). In both normal and diabetic subjects, serum levels of a-tocopherol (P 0.007) and urine RBP (P 0.005), were higher in men than women. Urinary excretion of RBP was signi®cantly higher in diabetic patients with renal impairment than other diabetics or controls (P 0.0001). There was a negative correlation between fasting blood glucose (FBG) concentration and serum b-carotene (P 0.008) in the total combined group and a positive correlation between FBG and urinary RBPacreatinine (P 0.009) in diabetic patients. Conclusion: Serum b-carotene concentration was signi®cantly lower in diabetic patients than controls. Serum retinol concentration in patients with diabetes was normal, yet serum and urine RBP concentrations were signi®cantly higher in diabetics than in controls. Sponsorship: The research was sponsored by King Faisal Specialist Hospital and Research Center.

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“…A1M is mainly synthesized in the liver and distributed via the blood-stream to the extra-vascular compartment in all tissues [21]. Due to its small size, A1M is filtered in the renal glomeruli and partially re-absorbed in the tubuli [21,22]. Recent reports have shown that A1M is a heme-and radical-scavenger, involved in the defense against oxidative stress induced by free Hb and participating in the degradation of heme [18,19,23].…”

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confidence: 99%