Pathophysiology of AKI
Kidney function can be considered as the rate of passage of solute across the specialised walls of the capillaries within the glomerulus. In the normal glomerulus the pressure within the glomerular capillaries determines the rate of filtration (Glomerular filtration rate: GFR).
The majority of cases of AKI are due to vascular insults to the kidney that affect this perfusion pressure. Understanding the pathophysiology underlying these cases is particularly rewarding as it makes sense of why many patients are at risk of AKI. This understanding also rationalises interventions to prevent progression and facilitate recovery. The dos and don’ts of AKI are no longer meaningless lists but become rational diagnostic and management decisions.
Importance of blood supply to kidney function
Historically, ATN and ARF have been considered to be due to pre-renal (i.e. vascular) insults, intrinsic renal disease (including glomerulonephritis, interstitial nephritis and toxic insults) or obstruction. Studies in secondary care established vascular insults as the commonest cause of ATN/ARF with both the overall blood flow to the kidneys and intrarenal vascular ‘reflexes’ both being important. These haemodynamic factors determine the pressure within the blood vessels that form the ‘glomerular tuft’, which in turn determines the level of kidney function: exactly as in any filter system. Changes in this intraglomerular pressure will always be reflected in changes in the rate of filtration and therefore kidney function.
Considering renal blood flow and the intrarenal vascular reflexes in turn:
- The factors determining overall renal blood flow are self-evident: intravascular volume, cardiac output and the health of the arterial tree supplying the kidneys. In turn, acute and chronic conditions that will be associated with reduced overall renal blood flow, and that may therefore confer risk of AKI, become obvious.
- The pressure within the glomerular capillaries is ‘fine tuned’ by reflexes that alter the tone in the blood vessels supplying blood to (afferent arteriole) and draining blood from (efferent arteriole) the glomerulus. These reflexes buffer the glomerular pressure against changes in incoming flow in order to maintain the perfusion pressure, critical to kidney function, within the required range. This process is termed autoregulation and is discussed further below.
Much acute kidney injury may be thought of as angina or a TIA of the kidneys, with the aim being to prevent progression to an MI or CVA. Conditions that may reduce overall renal blood flow, acutely or chronically, are mostly self-evident: hypovolaemia, left ventricular failure and atherosclerosis being the most common. It is important to add that renal artery stenosis is a relatively infrequent cause, more wide spread ‘small vessel disease’, as seen in many patients with T2DM, being much more common. The glomerulus will often be able to protect itself in the face of such insults, but if the function of the autoregulatory reflexes is compromised, the impact of any reductions in renal blood flow will be more significant.
Acute kidney injury may be thought of, in many instances, as akin to angina or a TIA affecting the kidneys. Early intervention prevents progression to more serious kidney injury.