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- Tencer, Jan
(författare)
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Endogenous proteins as markers of glomerular function and dysfunction
- 1997
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Plasma and urine concentrations of endogenous proteins are frequently used in the diagnosis of kidney diseases and in studies of glomerular filter function. The main issues addressed in these studies were: storage of urine samples for subsequent protein analysis, use of protein concentrations in urine and in plasma in health and as markers of glomerular diseases, and the application of renal plasma-to-urine clearance of endogenous proteins in estimating the size-selectivity properties of the glomerular capillary wall. Studies of the stability of endogenous proteins in urine stored under different conditions showed certain proteins (immunoglobulin G, protein HC, and a1-antitrypsin) to deteriorate in native urine stored at -20°C, and a1-antitrypsin to be also unstable in native urine kept at room temperature or at 4°C. The addition of the preservative solution employed in these studies was shown to allow reliable measurements to be made of all the proteins investigated, and under all conditions tested, with the exception of a1-antitrypsin in frozen urine. Measurements of urine concentrations of endogenous proteins in healthy adults, using rapid, generally available methods, showed that the same upper reference limits for urinary protein excretion may be used for both genders and regardless of age or the type of urine collection. Moreover, the protein content in normal urine does not correlate to the presence of haematuria or granular casts in urinary sediment. Increased plasma concentrations of acute phase proteins, a1-antitrypsin, haptoglobin and orosomucoid, but not C-reactive protein, were detected in patients with primary chronic glomerulonephritides. The findings imply that, despite the indolent clinical picture, persistent inflammatory processes occur in chronic glomerulonephritides and that, the three first-mentioned acute phase proteins may be used as markers of these diseases. Moreover, the C-reactive protein level may be used to diagnose infections or other inflammatory conditions affecting patients with chronic glomerulonephritides. Urine excretion of glycosaminoglycans was decreased in patients with primary glomerulonephritis or renal amyloidosis. Significant differences in this variable were also observed between various kinds of glomerular diseases, urine concentrations being lower in acute glomerulonephritis compared to the chronic forms of the disease, and in amyloidosis compared to other glomerular diseases. These findings indicate that urinary glycosaminoglycans excretion can not only be used as a marker of glomerulonephritis or renal amyloidosis, but it can also be used in the differential diagnosis of the acute and chronic forms of the former disease, and in screening for amyloidosis in patients with glomerular diseases or with chronic inflammatory diseases, with or without clinical signs of renal involvement. Finally, based on findings in the study of fractional protein clearance in rats with inhibited tubular protein reabsorption, the large pore radius of the glomerular basement mem-brane could be estimated to be 110-115 Å. Thus, the existence of ‘shunt pathways’ in the glomerular basal membrane is open to question.
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| 2. |
- Tencer, Jan, et al.
(författare)
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Long-term Stability of Albumin, Protein HC, Immunoglobulin G, κ- and λ-chain-immunoreactivity, Orosomucoid and α1-antitrypsin in Urine Stored at -20°C
- 1997
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Ingår i: Scandinavian Journal of Urology and Nephrology. - : Informa UK Limited. - 0036-5599 .- 1651-2065. ; 31:1, s. 67-71
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Tidskriftsartikel (refereegranskat)abstract
- The stability of albumin, protein HC, immunoglobulin G, κ- and λ-chain immunoreactivity, orosomucoid and α1 -antitrypsin in urine stored at -20°C for up to 24 months was investigated. Significant decreases of the median concentration values for protein HC, IgG and α1-antitrypsin were observed for native urine. Addition to urine of a preservative solution containing benzamidinium chloride, EDTA, tris(hydroxymethyl)-aminomethane and azide prevented the decreases of the concentration values for protein HC and IgG but not for α1-antitrypsin. The median concentration values for albumin, orosomucoid and κ-and λ-chain immunoreactivity did not change significantly upon storage of native urine, nor for urine with the preservative solution.
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| 3. |
- Tencer, Jan, et al.
(författare)
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Size-selectivity of the glomerular barrier to high molecular weight proteins: upper size limitations of shunt pathways
- 1998
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Ingår i: Kidney International. - : Elsevier BV. - 1523-1755 .- 0085-2538. ; 53:3, s. 709-715
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Tidskriftsartikel (refereegranskat)abstract
- To evaluate the large pore radius of the glomerular capillary filter, plasma-to-urine fractional clearances of a number of endogenous proteins were assessed in normal and in nephrotic Wistar rats in which proximal tubular reabsorption had been inhibited using lysine. The proteins studied varied in radius from 16.2 A (Beta 2-microglobulin) to 90 A (alpha 2-macroglobulin). The nephrotic syndrome was induced by puromycin aminonucleoside (PAN). A marked restriction of the transport of large proteins across the glomerular capillary wall was found, indicating that there are no non-discriminatory 'shunt pathways' in the glomerular barrier. Rather, there seems to be large pores of radius 110 to 115 A accounting for the clearance of large proteins into the primary urine. This protein excretion pattern was almost the same for control and nephrotic rats, except that in the latter, the number of large pores was increased 170 times. The ratio between the number of large and small pores was calculated to be approximately equal to 7 x 10(-7) in normal rats and to 1.2 x 10(-4) in PAN nephrotic rats, assuming no classic shunt pathways. If classic shunt pathways had still existed, they would normally contribute to no more than approximately equal to 10(-5) of the total glomerular filtration rate. We postulate that very large macromolecules like IgM will not pass the glomerular filter at all under normal conditions, whereas the urine concentration of alpha2-macroglobulin will normally be extremely low.
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