The pathophysiology underlying chronic kidney disease

Abstract

1 mL/min/year after the age of 40 in otherwise healthy individuals. Figure 1 shows how this age-related decline leads the ‘normal’ GFR (accurately measured by isotopic means) for individuals over 70 years to fall into the range where the equivalent estimated GFR (eGFR, which is calculated from serum creatinine, using a formula) would be compatible with a diagnosis of chronic kidney disease (CKD). This is why there is still debate about the implications of a low eGFR in the elderly. In certain individuals, however, glomerulosclerosis occurs either prematurely or more rapidly than expected as a consequence of systemic vascular disease. These individuals are then identified as having CKD. Glomerulosclerosis T he glomerulus is essentially a knot of blood vessels and there are about a million of them in each kidney. Appreciating that the kidneys are highly vascular organs is the key to understanding why their function is affected by systemic vascular damage, such as that due to hypertension, atheroma or diabetes. It also explains why they are a good place to look for evidence of early disease when assessing the overall health of a patient’s vasculature and their risk of future cardiovascular events. Glomeruli lose their function as part of the normal ageing process and healthy tissue is replaced by scar tissue. This process, known as glomerulosclerosis, causes the glomerular filtration rate (GFR) to fall by approximately Once started, CKD becomes a selfperpetuating condition (Figure 2). Initial reduction in the number of nephrons by whatever mechanism (for the purposes of this discussion, glomerulosclerosis caused by systemic vascular disease) leads to structural and functional changes in surviving nephrons. These changes are mediated by vasoactive molecules, notably the renin-angiotensin system (RAS), cytokines, and growth factors. Initially, the kidneys increase capillary flow to non-sclerosed glomeruli in an effort to maintain GFR. But this state of ‘hyperfiltration’ eventually causes intraglomerular hypertension and accelerated sclerosis of remaining nephrons. As the nephrons sclerose, the demands placed on surviving nephrons increase, accelerating their sclerosis in turn. DISEASE REVIEW