Abstract
An accurate assessment of which patient with glomerular disease will progress to end-stage renal failure would be an important addition to establishing prognosis and evaluating therapeutic strategies. We previously found the development of glomerular scarring in animal models was preceded by an increase in glomerular type IV collagen mRNAs and that the level of scarring predicted the rate of progression. The purpose of this study was to determine whether these findings apply to human glomerular diseases using microdissected glomeruli and assessment of mRNA by competitive PCR. After showing that the levels of type IV collagen mRNAs were elevated in sclerotic glomeruli isolated from nephrectomies, we undertook this preliminary cross-sectional study of type IV collagen subchain mRNAs in renal biopsies in two of the leading causes of glomerulosclerosis, diabetic nephropathy, and membranous glomerulopathy. We found that glomerular type IV collagen mRNA levels were altered in disease-specific ways. The relative levels of the individual alpha-chains of type IV collagen depended on the anatomic site of the glomerular lesions. The alpha 2 type IV/alpha 3 type IV collagen mRNA ratio was high in diabetes mellitus, but not in membranous glomerulopathy. These data, coupled with those obtained from experimental animals, suggest that a dysregulation of basement collagen synthesis underlies progressive glomerular scarring. If these conclusions are verified in prospective studies it will be feasible to assess the risk of developing progressive glomerulosclerosis in the individual patient and to quantitatively assess therapeutic responses in a timely manner.
| Original language | English |
|---|---|
| Pages (from-to) | 209-217 |
| Number of pages | 9 |
| Journal | Proceedings of the Association of American Physicians |
| Volume | 108 |
| Issue number | 3 |
| Publication status | Published - May 1996 |
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Cite this
Molecular analysis of glomerular diseases in renal biopsies : initial results of a collaborative international study. The International Study Group for Molecular Study of Kidney Biopsies. / Esposito, C.; Striker, L. J.; Patel, A.; Peten, E.; Liu, Z. H.; Sakai, H.; Striker, G. E.
In: Proceedings of the Association of American Physicians, Vol. 108, No. 3, 05.1996, p. 209-217.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Molecular analysis of glomerular diseases in renal biopsies
T2 - initial results of a collaborative international study. The International Study Group for Molecular Study of Kidney Biopsies.
AU - Esposito, C.
AU - Striker, L. J.
AU - Patel, A.
AU - Peten, E.
AU - Liu, Z. H.
AU - Sakai, H.
AU - Striker, G. E.
PY - 1996/5
Y1 - 1996/5
N2 - An accurate assessment of which patient with glomerular disease will progress to end-stage renal failure would be an important addition to establishing prognosis and evaluating therapeutic strategies. We previously found the development of glomerular scarring in animal models was preceded by an increase in glomerular type IV collagen mRNAs and that the level of scarring predicted the rate of progression. The purpose of this study was to determine whether these findings apply to human glomerular diseases using microdissected glomeruli and assessment of mRNA by competitive PCR. After showing that the levels of type IV collagen mRNAs were elevated in sclerotic glomeruli isolated from nephrectomies, we undertook this preliminary cross-sectional study of type IV collagen subchain mRNAs in renal biopsies in two of the leading causes of glomerulosclerosis, diabetic nephropathy, and membranous glomerulopathy. We found that glomerular type IV collagen mRNA levels were altered in disease-specific ways. The relative levels of the individual alpha-chains of type IV collagen depended on the anatomic site of the glomerular lesions. The alpha 2 type IV/alpha 3 type IV collagen mRNA ratio was high in diabetes mellitus, but not in membranous glomerulopathy. These data, coupled with those obtained from experimental animals, suggest that a dysregulation of basement collagen synthesis underlies progressive glomerular scarring. If these conclusions are verified in prospective studies it will be feasible to assess the risk of developing progressive glomerulosclerosis in the individual patient and to quantitatively assess therapeutic responses in a timely manner.
AB - An accurate assessment of which patient with glomerular disease will progress to end-stage renal failure would be an important addition to establishing prognosis and evaluating therapeutic strategies. We previously found the development of glomerular scarring in animal models was preceded by an increase in glomerular type IV collagen mRNAs and that the level of scarring predicted the rate of progression. The purpose of this study was to determine whether these findings apply to human glomerular diseases using microdissected glomeruli and assessment of mRNA by competitive PCR. After showing that the levels of type IV collagen mRNAs were elevated in sclerotic glomeruli isolated from nephrectomies, we undertook this preliminary cross-sectional study of type IV collagen subchain mRNAs in renal biopsies in two of the leading causes of glomerulosclerosis, diabetic nephropathy, and membranous glomerulopathy. We found that glomerular type IV collagen mRNA levels were altered in disease-specific ways. The relative levels of the individual alpha-chains of type IV collagen depended on the anatomic site of the glomerular lesions. The alpha 2 type IV/alpha 3 type IV collagen mRNA ratio was high in diabetes mellitus, but not in membranous glomerulopathy. These data, coupled with those obtained from experimental animals, suggest that a dysregulation of basement collagen synthesis underlies progressive glomerular scarring. If these conclusions are verified in prospective studies it will be feasible to assess the risk of developing progressive glomerulosclerosis in the individual patient and to quantitatively assess therapeutic responses in a timely manner.
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UR - http://www.scopus.com/inward/citedby.url?scp=0030139670&partnerID=8YFLogxK
M3 - Article
C2 - 8774054
AN - SCOPUS:0030139670
VL - 108
SP - 209
EP - 217
JO - Proceedings of the Association of American Physicians
JF - Proceedings of the Association of American Physicians
SN - 1081-650X
IS - 3
ER -