RESUMO
BACKGROUND: Early detection of pre-eclampsia remains one of the major focuses of antenatal obstetric care. There is often a delay in the diagnosis, mainly due to the non-specific nature of the condition. Podocytes which play a pivotal role in glomerular function become injured in pre-eclampsia leading to subsequent proteinuria. Our aim was to review available studies to determine the clinical utility of biomarkers of podocyte injury in pre-eclampsia. METHODS: We used QUADAS (Quality Assessment of Diagnostic Accuracy Studies) criteria to perform a systematic review of the literature to determine the clinical utility of podocyte injury biomarkers in predicting pre-eclampsia. RESULTS: This study identified five potential renal biomarkers including podocytes, nephrin, synaptopodin, podocin and podocalyxin. The pooled sensitivity of all biomarkers was 0.78 (95% CI 0.74-0.82) with a specificity of 0.82 (95% CI 0.79-0.85). The area under the Summary of Receiver Operating Characteristics Curve (SROC) was 0.926 (SE 0.30). Urinary nephrin achieved the highest diagnostic values with a sensitivity of 0.81 (95% CI 0.72-0.88) and specificity of 0.84 (95% CI 0.79-0.84). CONCLUSION: Biomarkers of glomerular injury show promise as diagnostic aids in pre-eclampsia. A large-scale prospective cohort study is warranted before these biomarkers can be recommended for routine clinical care.
Assuntos
Glomérulos Renais/lesões , Podócitos/metabolismo , Pré-Eclâmpsia/urina , Biomarcadores/urina , Estudos de Casos e Controles , Feminino , Barreira de Filtração Glomerular/lesões , Humanos , Proteínas de Membrana/urina , Podócitos/patologia , Pré-Eclâmpsia/diagnóstico , Gravidez , Proteinúria/urina , Curva ROC , Sensibilidade e Especificidade , Sialoglicoproteínas/urinaRESUMO
OBJECTIVE: Obesity-related glomerulopathy is characterized initially by glomerular hyperfiltration with hypertrophy and then development of proteinuria. Putative mechanisms include endothelial dysfunction and filtration barrier injury due to oxidant stress and immune activation. There has been recent interest in targeting dipeptidyl peptidase 4 (DPP4) enzyme due to increasing role in non-enzymatic cellular processes. METHODS: The Zucker obese (ZO) rat (aged 8 weeks) fed a normal chow or diet containing the DPP4 inhibitor linagliptin for 8 weeks (83 mg/kg rat chow) was utilized. RESULTS: Compared to lean controls, there were increases in plasma DPP4 activity along with proteinuria in ZO rats. ZO rats further displayed increases in glomerular size and podocyte foot process effacement. These findings occurred in parallel with decreased endothelial stromal-derived factor-1α (SDF-1α), increased oxidant markers, and tyrosine phosphorylation of nephrin and serine phosphorylation of the mammalian target of rapamycin (mTOR). DPP4 inhibition improved proteinuria along with filtration barrier remodeling, circulating and kidney tissue DPP4 activity, increased active glucagon like peptide-1 (GLP-1) as well as SDF-1α, and improved oxidant markers and the podocyte-specific protein nephrin. CONCLUSIONS: These data support a role for DPP4 in glomerular filtration function and targeting DPP4 with inhibition improves oxidant stress-related glomerulopathy and associated proteinuria.