Renal diseases: Proteomics and genomics analysis
Kidney disease is common. In 2000, the estimated prevalence of earlier stages of chronic kidney disease (CKD) in US adults was 20 millions (11.7%), and approximately 398,000 people (0.2%) were treated by dialysis or transplantation. By 2030, this number is expected to rise to more than 2 million people. Kidney disease is due to glomerular, tubular or vascular lesions. Until yet, diagnosis of kidney diseases and follow-up of the pathological process activity are made respectively with renal biopsy and laboratory data (serum creatinine, proteinuria and urinary sediment). The renal biopsy allows appreciating the state of the lesions at a precise time point of the disease. However, it is not rare that clinicians choose not to perform a renal biopsy because of the high risks of bleeding, a unique kidney, etc. Moreover, it is not common to do a second biopsy in order to follow the morphological evolution of the lesions. Usual laboratory data, such as serum creatinine and urinary albumin levels, allow appreciating the severity of renal impairment. Unfortunately, they are neither specific for each type of lesions nor sensitive enough to reflect the activity of the disease. Therefore, noninvasive procedures with improved diagnostic value are extremely desirable.
We believe that urinary specific and sensitive markers could be one of these tools. One of the difficulties in the identification of urinary proteins as specific biological biomarkers of the kidney disease comes from the fact that urine proteins arise from various sources. These sources include (1) filtration of plasma proteins; (2) impaired tubular reabsorptionof filtered proteins and (3) appearance of proteins that originatefrom injured glomeruli, tubules, infiltrating inflammatory cells,or connective tissue as well as those that enter the urine inthe urinary tract below the kidney. During the past few years, proteomic techniques have been applied to healthy and pathological urine samples for the discovery of protein biomarkers of renal diseases. However, most proteomic studies were performed on unfractionated normal and pathological human and obtained global “patterns” of the renal disease, but did not identify specific urinary biomarker(s). Therefore, we choose to apply is a proteomic analysis of a urinary fraction enriched with the vesicles sheded by podocytes. Indeed, podocytes, or glomerular visceral epithelial cells, which are in direct contact with urinary space in the glomerulus, release small vesicles into urine. This vesiculation process was demonstrated to be increased in urines of patients with nephrotic and nephritic syndromes. Moreover, recent studies suggest that podocyte dysfunction is the starting point of segmental glomerulosclerosis, launching the podocyte into the center stage of CKD.
The aim of our study is to identify new urinary biomarkers that could improve diagnosis, follow-up and therapy of renal diseases. In addition, analysis of the identified proteins in the human kidney will help to better understand the pathophysiological processes of renal diseases.