The kidneys are of fundamental importance in the regulation of fluid and electrolytes, maintaining permissive extracellular fluid composition (salts and water), pH, and volume, while also mediating the removal of waste products. Based on the anatomy of the nephron, three main processes occur in order to deliver this balance: glomerular filtration, tubular secretion, and tubular resorption. Drugs can act at different sites within this system, so that functional equilibrium can be restored in various disease states (e.g. hypertension, heart failure, liver failure, nephrotic syndrome). CKD is a long- term condition that lasts more than 3 months and affects the function of both kidneys. It results from any pathology that reduces renal functional capacity and produces a decrease in GFR to less than 60 mL/ min/ 1.73 m<sup>2</sup>. Prevalence within the UK is high, particularly in the elderly and affects 6– 8% of the population. The most common cause of CKD is idiopathic (unknown, usually with small kidneys), then diabetes mellitus. In both, glomerular damage and mesangial injury (causing metabolic and haemodynamic effects) occur. Mild- moderate essential hypertension does not cause CKD. Knowledge of the functional anatomy of the proximal tubule and loop of Henle is essential in understanding therapeutic targets and treatment of pathologies, as each region and transporter system has a key role. In brief, the journey of solutes from the blood to the production of urine occurs at five main anatomical sites— the glomerulus, the proximal tubule, the loop of Henle, the distal tubule (proximal part and distal part), and the collecting ducts (Figures 5.1 and 5.2). The glomerulus is a network of capillaries (like a ball of string), which merge with the nephron via Bowman’s capsule. It is the first site of filtration and the place where solutes, toxins, and small proteins are removed from the wider circulatory system, after delivery by the renal arteries (via an afferent arteriole). Blood and larger proteins remain in the arteriole and leave via an efferent branch, while the filtrate enters the proximal convoluted tubule. The afferent:efferent system ensures that a constant filtration pressure is maintained irrespective of variations in arterial pressure. The capillary bed is very large, so that permeability and filtration rates are high. A normal glomerular filtration rate (GFR) i.e. 90– 120 mL/ min/ 1.73 m<sup>2</sup>, depends on hydrostatic pressure, the colloid osmotic pressure and hydraulic per¬meability.
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