Glomerular NEP levels were correlated inversely with glomerulosclerosis and proteinuria measured at the time of biopsy. Tubular NEP levels were associated inversely with interstitial fibrosis. Incubation of proximal tubular cells with MPA led to a dose- and time-dependent increase of NEP gene expression. For the first time, these data suggested that MPA treatment may modulate this enzyme directly,

contributing to the slow-down of the chronic glomerular progression and tubulointerstitial damage [105]. Additionally, a few other studies using in vitro and animal models have identified, using specifically designed microarray platforms, some genes PD0325901 research buy with putative relevance to efficacy and toxicity of immunosuppressive drugs used in nephrology. However, none of the results obtained by these studies has been confirmed in a clinical setting. Interestingly, high-throughput genomic screening technologies have been used to identify biomarkers associated with immunological tolerance in renal transplant patients. It is well known that long-term allograft survival requires lifelong immunosuppression, but recipients

rarely display spontaneous ‘operational tolerance’ with stable graft function in the absence of immunosuppression [106]. The lack of biological markers of this phenomenon precludes identification Navitoclax cost of potentially tolerant patients in which immunosuppression could be tapered or interrupted early. Therefore, the objective of all these

studies was to identify markers able to identify a tolerant population clearly. Several genes have been suggested as potentially useful predictors of tolerance, including genes involved in immune quiescence, apoptosis and memory T cell response [107]. However, further validation and prospective clinical trials using these selective biological elements are needed. Microarray studies have been performed to identify specific genomic FAD fingerprints modulated during acute [108] and chronic [109,110] dialysis therapy. Interestingly, several genes were de-regulated in CKD patients undergoing these renal replacement treatments. Among the genes selected were those encoding for several chemokines with proinflammatory and chemotactic activity [e.g. interleukin (IL)-8, chemokine (C-C motif) receptor 7 (CCR7), tumour necrosis factor (TNF)-α, chemokine (C-X-C motif) receptor 4 (CXCR4)], key regulators of oxidative stress [e.g. v-rel reticuloendotheliosis viral oncogene homologue A (RELA) and glutathione synthetase (GSS)] and those implicated in the mitochondrial oxidative phosphorylation system (e.g. ATP5O, COX6C, COX7C, NDUFS5, NDUFA6, UQCRH, NDUFA1, ATP5J, UQCRB, NDUFB1 and ATP5I).