Measurement of urinary chemokine and growth factor messenger RNAs: a noninvasive monitoring in lupus nephritis.
Noninvasive molecular tests of urine cells have been developed to monitor the activity of kidney diseases. We evaluate whether measurement of urinary messenger RNA (mRNA) levels of chemokine and growth factor genes could distinguish between diffuse proliferative lupus nephritis (class IV LN) and others and whether it is able to predict the response to therapy. Prebiopsy urine samples were collected from 26 LN patients. Urine specimens were serially collected over a period of 6 months from class IV LN patients who were receiving standard immunosuppressive treatments. Urinary interferon-producing protein 10 and its CXC chemokine receptor (CXCR)3, transforming growth factor-beta (TGF-beta), and vascular endothelial growth factor (VEGF) mRNA levels were analyzed by quantitative real-time polymerase chain reactions. Levels of chemokine or growth factor mRNAs in urine could distinguish class IV LN from others, with a sensitivity of 85% and a specificity of 94%. The receiver-operative characteristic curve demonstrated that urine mRNA levels of these genes could identify active class IV LN with an accuracy greater than the current available clinical markers, namely systemic lupus erythematosus (SLE) disease activity index, proteinuria, renal function, or urinalysis. A significant reduction of interferon-producing protein 10 (IP-10), CXCR3, TGF-beta, and VEGF mRNA levels from baselines was observed in patients who responded to therapy, whereas the levels tended to increase in those who resisted to treatment. Measurement of urinary chemokine and growth factor mRNAs can precisely distinguish class IV LN from others. Temporal association between these markers and therapeutic response is demonstrated. This noninvasive approach serves as a practical tool in diagnosis and management of LN.
Avihingsanon
Y
Y
Lupus Research Unit, Division of Nephrology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. fmedyah@md.chula.ac.th
Phumesin
P
P
Benjachat
T
T
Akkasilpa
S
S
Kittikowit
V
V
Praditpornsilpa
K
K
Wongpiyabavorn
J
J
Eiam-Ong
S
S
Hemachudha
T
T
Tungsanga
K
K
Hirankarn
N
N
D000328:Adult; D015415:Biomarkers / Q000652:urine; D054357:Chemokine CXCL10; D018925:Chemokines / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D005786:Gene Expression Regulation; D006133:Growth Substances / Q000235:genetics*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008137:Longitudinal Studies; D008181:Lupus Nephritis / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics / Q000652:urine*; D008297:Male; D012333:RNA, Messenger / Q000652:urine*; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D016212:Transforming Growth Factor beta / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
D015415:Biomarkers; C114753:CXCL10 protein, human; C515187:CXCR3 protein, human; D054357:Chemokine CXCL10; D018925:Chemokines; D006133:Growth Substances; D007166:Immunosuppressive Agents; D012333:RNA, Messenger; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine; D016212:Transforming Growth Factor beta; D042461:Vascular Endothelial Growth Factor A