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CARDIOVASCULAR JOURNAL OF AFRICA • Volume 31, No 4, July/August 2020
206
AFRICA
that played a part in the pathophysiology of CSA-AKI.
10
Red
blood cells were damaged by the CPB circuit, which resulted
in the release of free haemoglobin, damaging the renal tubules
by depleting plasma haptoglobin levels and promoting the
production of free oxygen radicals.
11
In sub-Saharan Africa, a 2016 systematic review by Olowu
et
al
.,
12
assessing the outcome of AKI in children and adult patients
identified 3 881 records between January 1990 and November
2014 of patients with AKI. Forty-one records met their inclusion
criteria, with 1 403 adults and 1 937 paediatric patients. The
incidence of mortality was found to be 32% in adults and
34% in the paediatric population, but had increased intensely
to 82 and 73%, respectively, when RRT was required but not
received. They concluded that the scarcity of resources in health
centres, especially RRT, stressed the need to practice preventative
approaches in the management of AKI in this continent.
12
Pathophysiology
The development of AKI following cardiac surgery is a complex
clinical phenomenon.
13
It was previously described as being
secondary only to ischaemia and reperfusion injury.
2
The
pathophysiology of CSA-AKI has however recently been seen
to be multifactorial,
2,11,14
and the causes have been classified
as pre-renal, renal and post-renal.
14
Bellomo
et al
.
13
described
the pathophysiology as involving several mechanisms of injury.
Genetic factors have also been described as contributors to
CSA-AKI.
2
Renal ischaemia and reperfusion injury
Ischaemia and reperfusion injury have been described as the most
common cause of CSA-AKI.
15
The mechanisms of injury are
related to a decrease in oxygen delivery, poor nutrient transport
and poor removal of waste products in the renal tubular cells.
15
Research has demonstrated that it is not merely the decrease in
GFR that leads to AKI, but also the regional differences in renal
blood flow.
16
These are due to the high metabolic demands of the
outer renal medulla with lower partial oxygen pressures (PaO
2
)
of 10–20 mmHg relative to other parts of the kidney, making it
susceptible to hypoxic episodes.
2,11
In the peri-operative period, renal ischaemia can be due
to low cardiac output (CO) following cardiogenic shock.
2
Activation of the sympathetic nervous system (SNS) and
the renin–angiotensin–aldosterone system (RAAS) due to a
reduction in CO will cause systemic vasoconstriction, thus
decreasing renal blood flow and leading to a low GFR.
2
The
major factors associated with AKI post cardiac surgery are a
reduced functional reserve and peri-operative renal ischaemia.
17
Inflammation and oxidative stress
Renal tissue hypoxia that results from renal hypo-perfusion due
to a decrease in CO and GFR is responsible for the inflammatory
process and oxidative stress that follows.
15
Endothelial cellular
injury as a result of ischaemia initiates tissue inflammation.
15
Selectins facilitate the adhesion of leukocytes to the injured
endothelium.
16
This promotes the cascade of an inflammatory
response.
18
Pro-inflammatory cytokines such as tumour necrosis
factor-alpha (TNF-
α
), interleukins 6 and 8 (IL-6, IL-8) and
chemotactic cytokines have been implicated in contributing to
the response of local tissue ischaemia that results in maladaptive
inflammatory tissue response.
18
Neutrophil and monocyte/
lymphocyte ischaemia-induced kidney damage has also been
described. This inflammatory cascade eventually results in
dysfunction of the renal endothelium nitric oxide system, which
is important in the renal oxygen supply.
16
Nephrotoxins
Cardiac surgical patients are exposed to a variety of nephrotoxic
agents in the peri-operative period. These may include drugs
in the form of prescription medications such as antibiotics,
antihypertensive agents, diuretics, non-steroidal anti-
inflammatory agents (NSAIDS) and radiocontrast agents used
during diagnostic medical procedures.
5,14
Aminoglycosides and beta (
β
)-lactam antibiotics are the two
groups of agents that have been implicated the most in causing
acute interstitial nephritis, leading to drug-induced AKI.
2,5
These
antibiotics can also cause direct injury to the kidneys.
2
Hypertension has been shown to be one of the pre-operative
risk factors of AKI in patients presenting for cardiac surgery.
11
Fuhrman and Kellum
2
have linked hypertension-related AKI
to the use of angiotensin-2-receptor blocking agents (ARBs),
which inhibit renal efferent arteriolar vasoconstriction in the
pre-operative period.
2
Patients on ARBs and diuretic agents
have an increased risk of hypovolaemia, which can worsen renal
failure.
14
Randomised control trials have shown the prophylactic use of
loop diuretics, such as furosemide, to be ineffective and harmful
when used in the peri-operative period in patients scheduled for
cardiac surgery.
19-21
As part of their recommendations, Kellum,
2
Lameire
5
and the KDIGO AKI guideline work group
5
advised
against the use of furosemide as a prophylactic agent in
preventing AKI, and to avoid the use of diuretic agents in
treating AKI.
NSAIDs have also been proven to worsen renal function
in susceptible groups of patients.
14
Exposure to radiocontrast
agents in the peri-operative period contribute to the risk of
contrast-induced nephropathy and should ideally be avoided.
5,14
Metabolic and neurohormonal activation
Cardiac surgery stimulates the SNS and the hypothalamic
pituitary adrenal axis.
22
This activation results in the release of
neurohormonal agents, including adrenaline and noradrenaline
from the adrenal glands.
23
Zhang
et al.
reported that during cardiac
surgery with CPB, plasma concentrations of adrenaline and
noradrenaline reach peak levels.
24
The high plasma concentrations
of these endogenous hormones give rise to erratic haemodynamic
conditions that contribute to intra-operative renal injury.
22
This
increase in sympathetic tone has led to the advocacy of the use
of alpha-2-adrenergic agonists such as dexmedetomidine and
clonidine to reduce the incidence of AKI.
22,25
Genetics
A genome-wide association study (GWAS) for AKI after CABG
surgerywas performed in 2015 by Stafford-Smith and colleagues.
26
They discovered that other than the previously reported nine