Urinary Alpha-1-Acid Glycoprotein Is a Sensitive Marker of Glomerular Protein Leakage at Altitude

Abstract

Talks, Ben J., Susie B. Bradwell, John Delamere, Will Rayner, Alex Clarke, Chris T. Lewis, Owen D. Thomas, and Arthur R. Bradwell. Urinary alpha-1-acid glycoprotein is a sensitive marker of glomerular protein leakage at altitude. High Alt Med Biol. 19:295–298, 2018.—Proteinuria is an established feature of ascent to altitude and may be caused by a loss of negative charges on glomerular capillary walls (GCWs). To test this hypothesis, we measured two similar sized but oppositely charged proteins in urine: negatively charged alpha-1-acid glycoprotein (α1-AGP, 41–43 kDa) and positively charged dimeric lambda free light chains (λ-FLCs, 50 kDa). Twenty-four-hour urinary leakage was compared with albumin, a 66 kDa negatively charged protein. We studied 23 individuals (ages 23–78 years, male = 17) at baseline (140 m) and daily during an expedition to 5035 m. The results showed a significant increase in median urinary leakage of α1-AGP (p < 0.0001; 6.85-fold) and albumin (p = 0.0006; 1.65-fold) with ascent to altitude, but no significant increase in leakage of λ-FLCs (p = 0.39; 1.14-fold). α1-AGP correlated with the daily ascent profile (p = 0.0026) and partial pressure of oxygen (p = 0.01), whereas albumin showed no correlation (p = 0.19). Urinary α1-AGP was a more sensitive marker of altitude proteinuria than urinary albumin and λ-FLCs, and supported the possibility of loss of GCW negative charges at altitude.

Diabetic Retinopathy: Changes in Levels of Orosomucoids in Patients Supplemented with Beta Glucan and Vitamin D

“…In addition, we also tried to measure ORM in urine (unpublished results). Our study showed the evaluation of ORM in urine of patients with DM and DR might be important, which agrees with results of other laboratories (Christiansen et al, 2010;KUstan et al, 2016;Talks et al, 2018). In all of our patients, we found significant increase of ORM levels when compared to normal population of the same age.…”

“…ORM is considered to be proof of association between obesity and periodontitis (Range et al, 2013). Interesting studies measuring ORM in urine of patients with DM1 might be used in induction risk evaluation with urinary tract problems concerning DR patients (Christiansen et al, 2010;Kustan et al, 2016;Talks et al, 2018). Lately, increased attention is focused on evaluation of ORM I and II subclasses.…”

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“…All samples were thawed at room temperature for 1 hour before analysis. The 24-hour urine samples were first analysed for α1-AGP using radial immunodiffusion (RID; Talks et al, 2018)7 and the results were converted to excretion rates (mg/24 hours or μg/min). A subset of samples (119 out of 201) were then analysed using a latex-enhanced immunoassay on the Optilite turbidimetric analyser (The Binding Site, Birmingham, UK; online supplementary appendix 1).…”

“…Proteinuria typically results from protein leakage from the capillary lumen through the glomerular filter,1 with some removal in the tubules, as shown by studies inhibiting renal tubular reabsorption with lysine infusions 2. Comparisons between albumin, a selectively reabsorbed,3 66 kDa, negatively charged (pI 4.7) protein that passes through the glomerular membrane via the slit diaphragm pores,4 and alpha-1 acid glycoprotein (α1-AGP),5–7 a smaller (41–43 kDa) and more negatively charged protein (pI 2.7)5 7 indicate that urinary α1-AGP is a more sensitive marker of glomerular leakage than albumin 7–9. Urinary α1-AGP excretion has implicated the glomerular origin of the proteinuria exhibited with both, altitude7 and post-exercise 5.…”

“…Comparisons between albumin, a selectively reabsorbed,3 66 kDa, negatively charged (pI 4.7) protein that passes through the glomerular membrane via the slit diaphragm pores,4 and alpha-1 acid glycoprotein (α1-AGP),5–7 a smaller (41–43 kDa) and more negatively charged protein (pI 2.7)5 7 indicate that urinary α1-AGP is a more sensitive marker of glomerular leakage than albumin 7–9. Urinary α1-AGP excretion has implicated the glomerular origin of the proteinuria exhibited with both, altitude7 and post-exercise 5. Hypothesised mechanisms for such glomerular leak have included changes in renal blood flow,5 10 increases in peritubular pressure and blood pressure2 (BP), hypoxia11 and acid–base disturbances,2 although the mechanisms remain unclear 12.…”