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Endogenous proteins as markers of glomerular function and dysfunction

Tencer, Jan LU (1997)
Abstract (Swedish)
Popular Abstract in Swedish

Koncentrationer av proteiner i plasma och urin används i ökande utsträckning i diagnostik av njursjukdomar och i studier av den glomerulära barriärens funktion. De viktigaste frågor som behandlats i denna avhandling var: förvaring av urinprover inför efterföljande proteinanalyser, tillämpningar av proteinkoncentrationer i urin och plasma vid hälsa och vid glomerulära (njurcystanets) sjukdomar, samt mätningar av endogena proteiners transport från plasma till urin för beräkningar av den glomerulära kapillärväggens storleksselektiva egenskaper. Studier av endogena proteiners stabilitet i urin förvarad under varierande betingelser visade att proteinerna immunoglobulin G, protein HC och a1-antitrypsin... (More)
Popular Abstract in Swedish

Koncentrationer av proteiner i plasma och urin används i ökande utsträckning i diagnostik av njursjukdomar och i studier av den glomerulära barriärens funktion. De viktigaste frågor som behandlats i denna avhandling var: förvaring av urinprover inför efterföljande proteinanalyser, tillämpningar av proteinkoncentrationer i urin och plasma vid hälsa och vid glomerulära (njurcystanets) sjukdomar, samt mätningar av endogena proteiners transport från plasma till urin för beräkningar av den glomerulära kapillärväggens storleksselektiva egenskaper. Studier av endogena proteiners stabilitet i urin förvarad under varierande betingelser visade att proteinerna immunoglobulin G, protein HC och a1-antitrypsin är instabila i obehandlad urin förvarad vid -20°C, och att a1-antitrypsin inte heller är stabil i obehandlad urin förvarad i rumstemperatur eller i 4°C. Tillsats av en i dessa studier beskriven konserverande lösning möjliggör tillförlitliga koncentrationsbestämningar av alla proteiner och under alla förvaringsbetingelser med undantag för a1-antitrypsin i frusen urin. Mätningar av endogena proteiners urinkoncentrationer i en vuxen, frisk population med hjälp av snabba och generellt tillgängliga analysmetoder visade att identiska övre referensgränser kan användas för båda könen och oberoende av ålder och typ av urinsamling. Dessutom fann man ingen korreleration mellan urinutsöndringen av dessa proteiner och hematuri eller förekomsten av korniga cylindrar i urinsedimentet. Förhöjda plasmakoncentrationer av de akut-fas proteinerna a1-antitrypsin, haptoglobin och orosomucoid, men inte av C-reaktivt protein, påträffades hos patienter med primära kroniska glomerulonefriter. Dessa fynd indikerar en pågående inflammatorisk process i dessa kliniskt indolenta tillstånd. Plasmakoncentrationer av de tre förstnämnda akut-fas proteinerna kan därför användas i den icke-invasiva diagnostiken av kroniska glomerulonefriter, medan plasmanivåer av C-reaktivt protein kan bli användbara i diagnostiken av infektioner eller andra inflammatoriska tillstånd hos denna patientgrupp. Urinutsöndring av glykosaminoglykaner befanns vara minskad hos patienter med primära glomerulonefriter och med njuramyloidos. Skillnader observerades också mellan olika former av glomerulära sjukdomar, med signifikant lägre utsöndring i akuta glomerulonefriter jämfört med kroniska former av denna sjukdom, och i amyloidos jämfört med andra glomerulära sjukdomar. Dessa fynd indikerar att urinutsöndring av glykosaminoglykaner - förutom som markör av glomerulonefriter och njuramyloidos - kan också användas i differentialdiagnostiken av akuta och kroniska glomerulonefriter. Därutöver torde urinutsöndring av dessa proteiner kunna användas i screeningen av njuramyloidos hos patienter med kroniska inflammatoriska sjukdomar, med och utan tecken på njurengagemang. Slutligen, genom beräkningar av endogena proteiners fraktionella clearance hos råttor med hämmad tubulär återresorption av proteiner har den funktionella storporsradien i det glomerulära basalmembranet beräknats till 110-115 Å. Dessa fynd resulterade i att existensen av "shunt pathways" kunde ifrågasättas. (Less)
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... (More)
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. (Less)
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author
opponent
  • Doc. Pettersson, Erna, Huddinge
organization
publishing date
type
Thesis
publication status
published
subject
keywords
glomerular filter, amyloidosis, glomerulonephritis, glomerular disease, proteins, proteinuria, Urology, nephrology, Urologi, nefrologi
pages
144 pages
publisher
Department of Nephrology, Lund University
defense location
N/A
defense date
1997-04-25 10:15
external identifiers
  • Other:ISRN: LUMEDW / (MENM-1016)-SE
ISBN
91-628-2401-5
language
English
LU publication?
yes
id
2f011314-a8f6-46a8-b424-59c4b6c3737f (old id 29070)
date added to LUP
2007-06-12 11:48:21
date last changed
2016-09-19 08:45:14
@misc{2f011314-a8f6-46a8-b424-59c4b6c3737f,
  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.},
  author       = {Tencer, Jan},
  isbn         = {91-628-2401-5},
  keyword      = {glomerular filter,amyloidosis,glomerulonephritis,glomerular disease,proteins,proteinuria,Urology,nephrology,Urologi,nefrologi},
  language     = {eng},
  pages        = {144},
  publisher    = {ARRAY(0xb8433d0)},
  title        = {Endogenous proteins as markers of glomerular function and dysfunction},
  year         = {1997},
}