Utilidad clínica de biomarcadores en el diagnóstico y tratamiento de la enfermedad glomerular del adulto

Abstract

In this thesis project, by developing observational studies including groups of patients with primary and secondary forms of glomerulopathies causing nephrotic syndrome, specifically focal segmental glomerulosclerosis (FSG), and membranous nephropathy (MN), where serum and urinary measurements of specific molecules (soluble urokinase receptor and antibodies against M-type phospholipase A2 receptor) are practice to determine and validate the usefulness of these biomarkers in the diagnosis, prognosis and treatment of these glomerular diseases._x000D_ As a result of these investigations, five publications have been produced. Two related to the titles of soluble urokinase receptor and focal segmental glomerulosclerosis, and three regarding the relationship between the presence of antibodies against phospholipase A2 receptor and membranous nephropathy. The aforementioned studies have allowed to validate and demonstrate the importance of measuring biomarkers not only from a diagnostic point of view, but also in the prognostic and therapeutic aspects, in patients affected by these glomerulopathies. These are the final conclusions of the studies mentioned above:_x000D_ A) The serum levels of soluble urokinase receptor (suPAR) appear to be related to the glomerular injury pattern corresponding to focal segmental glomerulosclerosis, specifically its primary forms. However, the strength of this relationship is not strong enough. In our case, a marked overlap in the serum values was found, between patients with idiopathic FSG and MN, as well as those with idiopathic and secondary FSG. The diagnostic performance of this test to diagnose primary FSG is insufficient, lacking adequate sensitivity and specificity. Other published studies, question the etiologically association of suPAR with idiopathic FSG._x000D_ B) The presence of antibodies against the receptor type M of phospholipase A2, either as circulating antibodies or immune deposits in the GBM, are associated with a high specifity with idiopathic membranous nephropathy. Our results, in agreement with studies carried out in European and North American populations show that there are such antibodies in 70% of patients with idiopathic MN. Among the tests available to determine the presence of such circulating antibodies in serum, the results are comparable, however, the ELISA method is relatively simple, inexpensive and allows to accurately quantify the level of circulating antibodies, which in turn enables its monitoring. In our experience, the presence of these antibodies and their magnitude at the time of diagnosis, is unrelated to the severity of proteinuria, glomerular filtration or initial treatment response. However, the dynamics of their titles is influenced by immunosuppressive therapy and is correlated with the clinical status of the disease and therapeutic response. The relative fluctuations of the securities at 3 and 6 months after starting treatment, and depending on its nature, can predict response with acceptable sensitivity and specificity at 9 and 12 months after initiating treatment. The information provided by these measurements facilitates decision making regarding the duration, continuation or change in immunosuppressive therapy, while it could avoid unnecessary and relatively prolonged exposures to potentially toxic agents, such as alkylating agents. An important element to consider, that was not possible to cover methodologically, is whether there is a degree of anti-PLA2R antibodies to be associated with the probability of spontaneous remission or relapse once treatment ends.

Date of Award	28 Jul 2015
Original language	Spanish
Supervisor	Vicente Fonollosa Pla (Director) & Alfonso Segarra Medrano (Director)