Prevention and treatment has been focused on ensuring patients were hemodynamically optimised and stable.
Recent studies have identified that not all patients with SAKI have evidence of hypo perfusion. A complex pathophysiological cascade of events and changes are now beginning to be researched further to gain better understanding of the underlying mechanisms at play
Sepsis (bacteraemia) occurs in response to an infection. Chemicals are released in the body to fight the infection. This triggers a cascade of inflammatory changes which can lead to multi organ damage and failure. Sepsis is potentially life threatening.
Acute Kidney Injury (AKI)
AKI is a syndrome and not a disease – a sudden occurrence of damage to the kidney or kidney failure. The ability of the kidney to filtrate out waste products from the circulatory system is effected causing a build-up of these waste products.
Patients who experience AKI have an increased risk for other health problems ie kidney disease, stroke, heart disease and of further episodes of AKI. Each additional episode of AKI increases the chances of developing Kidney Failure and Kidney Disease.
Until recently it was believed that a major characteristic of SAKI was kidney hypo perfusion.
Studies are now finding that AKI does occur in septic patients without kidney hypo perfusion or haemodynamic deterioration suggesting other mechanisms are at work.
Pathophysiological mechanisms underlying the development and progression of SAKI are quite complex and still not completely understood. Recent studies suggest
“key pathophysiological processes include renal macro circulatory and micro circulatory disturbance, glycocalyx disruption, surge of inflammatory markers and oxidative stress, coagulation cascade activation, imbalanced energy metabolism with release of ATP from damaged cells, bioenergetics adaptive response with controlled cell-cycle arrest, renalvenous congestion, and maladaptive TGF mechanism”
Damage to kidney tissue activates a repair process following the common ischemic reperfusion pathway.
Possibly due to a maladaptive response during this repair process AKI survivors are at a higher risk of Chronic Kidney Disease (CKD) and cardiovascular morbidities and mortality. Each subsequent episode of AKI further increases these risks.
Current treatments for SAKI are supportive therapies by nature
- Fluid Therapy – use of isotonic crystalloids as initial management for expansion of intravascular volume.
- Haemodynamic Optimisation – use of fluids and vasopressors help minimise further extension of kidney injury and facilitates renal recovery.
- Diuretics – with AKI there is an increased risk for fluid overload and therefore use of diuretics is necessary to help rid the body of excess fluid and salt through urine.
- Renal Replacement Therapy (RRT) – haemodialysis is this use of a dialyser which aides in removing waste from blood, restores electrolyte balance and removes extra fluid from the body.
There are now new and proposed treatments available which target the underlying complex pathophysiological changes of SAKI which are just starting to be used with some confidence.
- Alkaline Phosphatase (AP) – an endogenous enzyme which has detoxification capacity
- a-Melanocyte-Stimulating Hormone (a-MSH) – a strong anti-inflammatory cytokine which decreases inflammatory cytokines.
- Toll-like Receptor 4 Inhibitor (TLR4) – Lipopolysaccharide binds to TLR4 on antigen-presenting cells to inhibit an inflammatory response
- Heparin – suppresses the activation of inflammatory cells by binding and neutralising inflammatory mediators/enzymes released during the inflammatory phase.
- Mesenchymal Stem Cells – have a renoprotective effect derived from the paracrine/endocrine secretion of bioactive factors and exosomes.
SAKI is on the rise in many counties possibly due to various factors associated with microorganism resistance to antibiotics, increased use of cytotoxic drugs leading to large numbers of individuals in communities who are immune compromised and an aging population.
Further research and better understanding of the pathophysiology underlying SAKI will provide an opportunity for a more robust and vigorous response by health clinicians to this scenario.