Urinary exosomes in the diagnosis of Gitelman and Bartter syndromes
| Autor: | Marina Pitto, Marie Louise Syren, Francesca Raimondo, Samuele Corbetta, Lorenza Baldi, Alberto Bettinelli, Paola Rebora, Andrea Savoia, Silvana Tedeschi |
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| Přispěvatelé: | Corbetta, S, Raimondo, F, Tedeschi, S, Syrèn, M, Rebora, P, Savoia, A, Baldi, L, Bettinelli, A, Pitto, M |
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Adult
Male medicine.medical_specialty Pathology BIO/12 - BIOCHIMICA CLINICA E BIOLOGIA MOLECOLARE CLINICA Adolescent Urinary system Blotting Western salt-losing tubulopathie Exosomes Bartter syndrome Gastroenterology NKCC2 Young Adult Internal medicine medicine Humans Solute Carrier Family 12 Member 3 Child Solute Carrier Family 12 Member 1 Transplantation Kidney NCC Receiver operating characteristic urogenital system business.industry Area under the curve Case-control study Bartter Syndrome Gitelman syndrome medicine.disease Bartter's syndrome diagnosi medicine.anatomical_structure Nephrology Case-Control Studies Child Preschool urinary exosome Female business Gitelman Syndrome urinary exosomes Biomarkers |
| Popis: | BACKGROUND Gitelman syndrome (GS) and Bartter syndrome (BS) are hereditary salt-losing tubulopathies (SLTs) resulting from defects of renal proteins involved in electrolyte reabsorption, as for sodium-chloride cotransporter (NCC) and furosemide-sensitive sodium-potassium-chloride cotransporter (NKCC2) cotransporters, affected in GS and BS Type 1 patients, respectively. Currently, definitive diagnosis is obtained through expensive and time-consuming genetic testing. Urinary exosomes (UE), nanovesicles released by every epithelial cell facing the urinary space, represent an ideal source of markers for renal dysfunction and injury, because UE molecular composition stands for the cell of origin. On these assumptions, the aim of this work is to evaluate the relevance of UE for the diagnosis of SLTs. METHODS UE were purified from second morning urines collected from 32 patients with genetically proven SLTs (GS, BS1, BS2 and BS3 patients), 4 with unclassified SLTs and 22 control subjects (age and sex matched). The levels of NCC and NKCC2 were evaluated in UE by SDS-PAGE/western blotting with specific antibodies. RESULTS Due to their location on the luminal side of tubular cells, NCC and NKCC2 are well represented in UE proteome. The NCC signal is significantly decreased/absent in UE of Gitelman patients compared with control subjects (Mann-Whitney t-test, P < 0.001) and, similarly, the NKCC2 in those of Bartter type 1 (P < 0.001). The difference in the levels of the two proteins allows recognition of Gitelman and Bartter type 1 patients from controls and, combined with clinical data, from other Bartter patients. Moreover, the receiver operating characteristic curve analysis using UE NCC densitometric values showed a good discriminating power of the test comparing GS patients versus controls and BS patients (area under the curve value = 0.92; sensitivity 84.2% and specificity 88.6%). CONCLUSIONS UE phenotyping may be useful in the diagnosis of GS and BS, thus providing an alternative/complementary, urine-based diagnostic tool for SLT patient recognition and a diagnostic guidance in complex cases. |
| Databáze: | OpenAIRE |
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