Research into biomarkers for early detection of Autosomal Dominant Polycystic Kidney Disease

The kidneys, two bean shaped organs located on either side of the spine in the back of the abdomen, are important excretory organs of the human body. Apart from the removal of waste, kidneys have other important functions such as maintaining the blood pressure and the activation of vitamin D. Since these tasks are essential for a healthy life, we can say that a good renal function is vital. Nevertheless, today exist a variety of kidney diseases, each with their own symptoms and treatments. In this project, we will mainly work on the autosomal dominant polycystic kidney disease (ADPKD). ADPKD is, despite the general rarity of kidney diseases, the most common hereditary renal disease with an incidence between 1:400 and 1:1000 of all life births. This disease is caused by mutations in either the polycystic kidney disease 1 gene (PKD1) (chromosome 16, 85% of cases) or the PKD2 gene (chromosome 4, 15% of cases). Since ADPKD is dominant, each child of a sick parent has a 50% chance of developing the same disease. Despite the heritability, there is a high inter- and intra-familiar variability. As a result, the prediction for the progression of the disease is hampered. ADPKD is characterized by the continuous growth of innumerable cysts in both kidneys. This leads to an enlargement of the kidneys themselves and a loss in the normal architecture of the kidney. During the years, the amount of cysts increases and eventually, the normal kidney tissue is displaced by cyst tissue. Although the continuous growth of those cysts starts early in childhood, most of the patients develop symptoms like artificial hypertension and a decline in glomerular filtration rate starting from the third decade of life. Eventually, the latter leads to an end-stage renal disease (ESRD). Kidney dialysis and kidney transplantation are the only two treatments for ESRD. The average age of developing ESRD is 55 years for the PKD1 mutation and 75 years for the PKD2 mutation. So far, the diagnosis of ADPKD is based on the observation of cysts by imaging techniques like MRI, ultrasonography and CT. Despite the reliability of these techniques, they have a limited sensitivity in children and young adults, particularly those with a PKD2 mutation. As a conclusion, ADPKD can't be reliably excluded by these different imaging techniques before the age of 30 years. Like previously mentioned, the cyst formation starts early in childhood, therefore there is a need for a technique that can give an early diagnosis to ADPKD. Via metabolic analysis we will investigate possible early biomarkers for ADPKD. The aim of the project is the early characterization of the disease in young children and, consequently, that the found biomarkers can characterize the beginning of the pathology. We apply these techniques on urine, since this body fluid is abundant, can be obtained noninvasively and does not undergo degradation by endogenous proteases. All these things lead to the minimalisation of the pre-analytical steps.

Jaar van publicatie:2021

Toegankelijkheid:Embargoed