CKDdb-logoCKDdb - Study ID Exp18095357

PubMed ID18095357
AuthorsRocchetti MT, Centra M, Papale M, Bortone G, Palermo C, Centonze D, Ranieri E, Di Paolo S, Gesualdo L.
TitleUrine protein profile of IgA nephropathy patients may predict the response to ACE-inhibitor therapy.
JournalProteomics. 2008 Jan;8(1):206-16.
AbstractThis 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).

Sample characteristics

SpeciesTissue / SourceCompartmentDiseaseNDetection method
Homo sapiensurinewholeGlomerulonephritis38nano-HPLC-ESI-MS/MS

Sample description and preparation

N (case)18
N (control)20
Disease (case)IgA nephropathy
Disease (control)healthy
Digestin-gel, trypsin
Separation2-DE

Molecule list

Molecule IDextExternal IDGeneNameSource accRegulation (case/control)Scores
A8369XA1AT_HUMANA1A, SERPINA1, AATAlpha-1-antitrypsin precursorP01009ratio: 8.33
A1539XKNG1_HUMANKNG1, BDK, KNGKininogen-1P01042ratio: 0.05
A8383XAMBP_HUMANAMBP, ITIL, HCPAMBP protein precursorP02760ratio: 0.24
A648CXTTHY_HUMANTTR, PALB, TBPATransthyretin precursorP02766ratio: 3.8
A1581XALBU_HUMANALB, GIG20, GIG42Serum albumin precursorP02768ratio: 11.46
A1630 CD59_HUMANCD59, MIC11, MIN1CD59 glycoprotein precursorP13987ratio: 0
A1555XPGBM_HUMANHSPG2Basement membrane-specific heparan sulfate proteoglycan core proteinP98160ratio: 0.2
A8434XITIH4_HUMANITIH4, IHRP, ITIHL1Inter-alpha-trypsin inhibitor heavy chain H4 precursorQ14624ratio: 0.3

Compile date 08-10-2018© iMODE-CKD consortium