Chapter 1 8 Proteinuria and chronic kidney disease Proteinuria is an independent predictor of the progression of kidney injury, cardiovascular morbidity, and overall mortality (1). Under physiological circumstances, no sustained proteinuria is present. Proteinuria only occurs when serum proteins are able to pass the glomerular filtration barrier and when tubular reabsorption mechanisms are saturated or fail. Damage to any of these components can result in proteinuria. Moreover, although the mechanisms of damage and disease vary across the different types of renal diseases, many still lead to proteinuria and can result in chronic kidney disease (CKD). CKD is classified according to the remaining glomerular filtration rate and the amount of proteinuria in the Kidney Disease Improving Global Outcomes (KDIGO) guidelines (2). The prevalence of CKD is expected to rise further due to an aging population. The 2019 ‘Global burden of disease study’ reports that chronic kidney disease rose from rank 29 to 18 between 1990 and 2019 as a cause for disease-adjusted life years (3). In the Netherlands, an estimated 12% of the population suffers from chronic kidney disease (CBS/nierstichting). Treatment of underlying disease and general cardiovascular risk management such as treating hypertension and dyslipidaemia are still the cornerstone of management of chronic kidney disease (CKD) and attenuating proteinuria. A specific treatment for proteinuria might become feasible when the pathways leading to proteinuria are elucidated further. For this, a closer investigation of the structures and mechanisms that normally prevent proteinuria from occurring is required. The glomerular filtration barrier Figure 1 shows an overview of human renal anatomy with each image going into more detail. Most humans have two kidneys as seen in the top left image. They are located in the retroperitoneal space. The parenchyma of the kidney is usually divided in the outer cortex and inner medulla. Each human kidney contains around one million functional units called nephrons. Each nephron consists of a glomerulus and a tubular apparatus, shown in the detail of the sagittal image of the human kidney. The glomerulus, seen in the top right, is a specialized capillary bed that starts with the afferent arteriole which comes from the renal artery, which in turn directly sprouts from the abdominal aorta. 20 to 25% of cardiac output is routed to the kidneys, where it first passes the glomerulus. There, around 20% of passing serum is filtered by passing the glomerular filtration barrier, and the other 80% continues through the efferent arteriole to the peritubular capillaries where both active and passive secretion and reabsorption take place. The entire glomerular capillary bed is lined by the glomerular filtration barrier, shown in the middle image. Below, the detail shows a schematic overview of the distinct structures
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