SP067NEW INSIGHTS ON THE PATHOGENESIS OF EARLY STAGES OF OBESITY RELATED GLOMERULOPATHY

Abstract

Introduction and Aims: Kidney disease is an important cause of obesity-related comorbidity. A study carried out by our group first showed the presence of early histological lesions (mostly podocyte alterations) in obese patients lacking overt clinical renal symptoms. Several factors seem to be related to obesity-related glomerulopathy (ORG), although the pathogenic mechanisms are still unknown. Genes related to inflammatory cytokines and lipid metabolism have been found to be expressed in patients with ORG. Additionally, it is unknown whether these genes are expressed in the early stages of ORG. The major aim of our study is to investigate glomerular injury mechanisms in ORG by real time PCR assessment of the expression of several genes (interleukine-6, vascular endothelial growth factor, insulin-like growth factor-1, TNF-alpha, leptine receptor, glucose transporter-1, heart-type fatty acid binding protein, CD44 and spleen-derived interleukine-10) in renal biopsies of patients with early stages of ORG and renal biopsies of healthy non-obese patients. The comparison of the gene expression profiles found in the two renal biopsy groups will detect differences allowing the establishment of a cause-effect relationship in ORG. Methods: Fifty morbidly obese patients (BMI≥ 40 Kg/m2) without history of diabetes, without proteinuria and with normal renal function were selected. These patients underwent a renal biopsy during bariatric surgery. The hystologic study showed the presence of early stages of ORG ( matrix mesangial incresase, mesangial cell proliferation, podocyt hypertrophy, glomerulomegaly and focal and segmental glomerulosclerosis). We selected as the control group patients with normal weight and renal function. They were non-diabetic, non-hypertensive, and they were undergoing nephrectomy or donating a kidney. After real time PCR assessment, we have used the Livak Method to calculate the expression ratio or fold difference of our target genes. We have used Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as the housekeeping gene. Results: We show our preliminary results. Comparison between morbid obese (MO) group and nephrectomy control group. We observed that glucose transporter-1 gene and IL-6 gene are more expressed in MO group Glut-1: LnΔΔCt =3,93; IL6: LnΔΔCt =7,51) than in control group (Glut-1: LnΔΔCt =2,13; IL-6: LnΔΔCt =2,09) with p values 0,025 and <0,0001 respectively. However, IGF-1 gene (an anti-inflammatory gene) is more expressed in the control group (IGF-1: LnΔΔCt =6,83) than in MO group (IGF-1: LnΔΔCt = 4,99) with a p value of 0,046. The Livak method analyses are showed figure 1. Conclusions: Although these are preliminary results, this study shows that inflammatory cytokines and insulin resistance (dysmetabolism caused by obesity) are involved in the development of ORG. (Figure Presented).