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Urine protein profile of IgA nephropathy patients may predict the response to ACE‐inhibitor therapy
Author(s) -
Rocchetti Maria Teresa,
Centra Marta,
Papale Massimo,
Bortone Grazia,
Palermo Carmen,
Centonze Diego,
Ranieri Elena,
Di Paolo Salvatore,
Gesualdo Loreto
Publication year - 2007
Publication title -
proteomics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.26
H-Index - 167
eISSN - 1615-9861
pISSN - 1615-9853
DOI - 10.1002/pmic.200700492
Subject(s) - proteinuria , medicine , nephropathy , urine , renal function , urinary system , gastroenterology , proteome , angiotensin converting enzyme , urinalysis , excretion , endocrinology , bioinformatics , kidney , biology , blood pressure , diabetes mellitus
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‐α‐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).