Urine protein profile of IgA nephropathy patients may predict the response to ACE-inhibitor therapy.
This study was aimed at the search of urinary biomarkers which might help to predict the clinical response of IgA nephropathy (IgAN) patients to angiotensin converting enzyme inhibitors (ACEi). First, we studied the urinary proteome of 18 IgAN patients (toward 20 healthy controls) who had been chronically treated with ACEi by using 2-D PAGE coupled to nano-HPLC-ESI-MS/MS analysis. We identified 3 proteins, kininogen (p = 0.02), inter-alpha-trypsin-inhibitor heavy chain 4 (35 kDa fragment) (p = 0.02) and transthyretin (p<0.0001), whose urinary excretion was different in IgAN patients' responders when compared to those who had not responded to ACEi. A reduction of daily proteinuria >50% and a stable renal function over time were used to classify patients as responders. Then, we adopted immunoblotting to confirm the predictive power of one of the above proteins, kininogen, in 20 patients with biopsy-proven IgAN, before starting any therapy. Thus, we confirmed that very low levels of kininogen urine excretion were indeed predictive of an inadequate or absent clinical response to ACEi therapy of IgAN patients, after 6-month follow-up. Concluding, the analysis of urine proteome of IgAN patients generated a set of proteins which distinguished subjects responsive to ACEi from those unresponsive to the inhibition of renin-angiotensin system (RAS).
Rocchetti
Maria Teresa
MT
Molecular Medicine Center, Section of Nephrology, Department of Biomedical Sciences and Bioagromed, Faculty of Medicine, University of Foggia, Viale Pinto 1, Foggia, Italy.
Centra
Marta
M
Papale
Massimo
M
Bortone
Grazia
G
Palermo
Carmen
C
Centonze
Diego
D
Ranieri
Elena
E
Di Paolo
Salvatore
S
Gesualdo
Loreto
L
D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D002851:Chromatography, High Pressure Liquid; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D005922:Glomerulonephritis, IGA / Q000188:drug therapy* / Q000652:urine*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D040081:Protein Array Analysis; D011507:Proteinuria / Q000188:drug therapy* / Q000652:urine; D020543:Proteome / Q000737:chemistry / Q000145:classification / Q000378:metabolism; D021241:Spectrometry, Mass, Electrospray Ionization; D053719:Tandem Mass Spectrometry
D000806:Angiotensin-Converting Enzyme Inhibitors; D020543:Proteome