Can glomerular mRNAs in human type 1 diabetes be used to predict transition from normoalbuminuria to microalbuminuria?
BACKGROUND
mRNAs of pathogenetic importance in the development of diabetic nephropathy were measured in subjects with type 1 diabetes to determine whether these might be used to predict progression from normoalbuminuria to microalbuminuria. We proposed that conversion from normoalbuminuria to microalbuminuria would be most likely in subjects whose connective tissue growth factor (CTGF) and collagen mRNAs were above the 95% confidence interval (CI) for live renal donors and within the 95% CI for subjects with abnormal albuminuria.


METHODS
Glomerular CTGF, collagen alpha2(IV), and control glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNAs were measured in microdissected glomeruli from living renal donors (n = 10), and subjects with normoalbuminuria (n = 12), microalbuminuria (n = 5), and overt proteinuria (n = 6).


RESULTS
After 44 +/- 2 months of follow-up, one subject converted from normoalbuminuria to microalbuminuria. Although the data are limited, progression from normoalbuminuria to microalbuminuria occurred in the only normoalbuminuric subject whose mRNA levels were above the live renal donors' 95% CI for CTGF and collagen alpha2(IV) and within the 95% CI of subjects with abnormal albuminuria. No clinical or histopathologic finding distinguished the progressor from the nonprogressors at the time of biopsy.


CONCLUSIONS
This case report provides proof-of-principle that a panel of glomerular mRNA markers chosen because of their pathogenetic relevance may be useful adjuncts to albuminuria and histology in predicting clinical stability or clinical progression in diabetic nephropathy.
Adler
Sharon G
SG
Division of Nephrology and Hypertension, Harbor-UCLA Research and Education Institute Torrance, CA 90502, USA. sadler@rei.edu
Kang
Shin-Wook
SW
Feld
Stella
S
Cha
Dae Ryong
DR
Barba
Lilly
L
Striker
Liliane
L
Striker
Gary
G
Riser
Bruce L
BL
LaPage
Janine
J
Nast
Cynthia C
CC
D000328:Adult; D000419:Albuminuria / Q000209:etiology / Q000235:genetics* / Q000503:physiopathology; D024141:Collagen Type IV / Q000032:analysis; D055513:Connective Tissue Growth Factor; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000235:genetics* / Q000473:pathology; D003928:Diabetic Nephropathies / Q000209:etiology / Q000235:genetics* / Q000503:physiopathology; D018450:Disease Progression; D006133:Growth Substances / Q000032:analysis; D006801:Humans; D017874:Immediate-Early Proteins / Q000032:analysis; D036341:Intercellular Signaling Peptides and Proteins; D007678:Kidney Glomerulus / Q000378:metabolism* / Q000502:physiology / Q000503:physiopathology; D019520:Living Donors; D008297:Male; D025202:Molecular Diagnostic Techniques / Q000379:methods; D011237:Predictive Value of Tests; D012333:RNA, Messenger / Q000032:analysis*
C526317:CCN2 protein, human; D024141:Collagen Type IV; D006133:Growth Substances; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D055513:Connective Tissue Growth Factor