Role of mass-spectrometry in diagnostics of chronic glomerulonephritis

Abstract

Objective: Early diagnostics and prognosis of the risk of renal pathology allow modulating of approaches of prophylaxis and treatment that, in turn, affects both life expectancy and standards of living. The goal of this study was to reveal the markers of pathological process in patients with renal pathology using noninvasive techniques. Methods: The study involved 13 patients: 6 males and 7 females (average age 37 years) with different morphological variants of chronic glomerulonephritis. The remote molecular diagnostic pattern was obtained for each biological sample using Ultraflex II TOF/TOF device (Bruker, United States) on the basis of MALDI-TOF-МС. Also, the «Expect» analysis was carried out for each protein. Identification of peptides and proteins in urine was performed in on-line regime followed by analysis of their primary structure and 3D structure. Results: It was found out that four patients with IgA-nephropathy possessed receptors VI of renal blood vessels to Tolloid-like-2 protein (TILL2) that is considered to be a risk factor of arterial hypertension. TILL2 protein was identified in biological samples obtained from patients with membranoproliferative glomerulonephritis (MPGN) and membranous glomerulopathy (MGP). Prostacyclin stimulating factor was identified in four patients (two MPGN patients and two patients with lipoid nephrosis). Mass-spectrogram revealed TACC1 (Transforming, acidic coiled-coil containing protein 2) antioncogene in five patients (three patients with lipoid nephrosis and two MPGN patients). The presence of Integrin alpha-7 indicated high risk of cancer and its relapse. Profilin II protein, which is involved into the actin cytoskeleton remodelling and reparation processes, was found in spectrogram of MGP patients. Filamin A, which is involved in cytoskeleton formation, vascularization and thrombus formation, was found in two out of four MPGN patients. Conclusions: Proteins responsible for inflammation and immune response typical for different stages of pathogenesis are revealed. Each form of chronic glomerulonephritis is characterised by a specific proteomic mirror. This study is noninvasive and perspective for early diagnostics of both inner pathology and particularly renal disorders. The assessed markers are the risk factors present in urine. They allow predicting of therapy efficacy, clinical outcome, chronic renal insufficiency progression rate, and as well as revealing of hidden pathology at early stages.