ACUTE KIDNEY INJURY

Acute kidney injury (AKI), also referred to as acute renal failure, describes the situation
where there is a sudden and often reversible loss of renal function, which develops
over days or weeks and is usually accompanied by a reduction in urine volume.

Approximately 7% of all hospitalised patients and 20% of acutely ill patients develop signs of AKI.
In uncomplicated AKI, such as that due to haemorrhage or drugs, mortality is low, even when renal replacement
therapy is required.
In AKI associated with serious infection and multiple organ failure, mortality is 50–70% and the outcome is
usually determined by the severity of the underlying disorder and other complications, rather than by renal failure
itself.

Causes :
Prerenal causes of acute renal failure Renal causes of acute renal failure Obstructive causes of acute renal
include include: failure include:
: • drugs; • calculi;
• hypovolaemia; • poisons; • pelvic malignancy;
• blood loss; • contrast media; • surgery;
• sepsis; • eclampsia; • retroperitoneal fibrosis;
• cardiogenic shock; • myoglobinuria; • bilharzia;
• anaesthesia; • incompatible blood transfusion; • crystalluria
• hypoxia. • disseminated intravascular
coagulation

Pathophysiology
There are many causes of AKI and it is frequently multifactorial.
It is often classified into three subtypes:
 ‘prerenal’, when perfusion to the kidney is reduced;
 ‘renal’, when the primary insult affects the kidney itself; a
 ‘post-renal’, when there is obstruction to urine flow at any point from the tubule to the urethra

pre-renal AKI, . Renal AKI Post-renal AKI

the kidney becomes damaged as the may be caused by nephrotoxic drugs occurs as the result of obstruction
result of hypoperfusion, leading to which can cause acute tubular to the renal tract, with kidney
acute tubular necrosis. necrosis and a similar histological damage arising as the result of back
Histologically, the kidney shows picture to pre-renal AKI or pressure.
inflammatory changes, focal breaks interstitial nephritis.
in the tubular basement membrane
and interstitial oedema. The other common cause is
glomerulonephritis, in which there
Dead tubular cells may also be is direct inflammatory damage to
shed into the tubular lumen, leading the glomeruli
to tubular obstruction.
Although tubular cell damage is the
dominant feature under the
microscope, there may also be
profound alterations in the renal
microcirculation
Anaemia is common in AKI and may occur as the result of :
 blood loss,
 haemolysis or
 decreased erythropoiesis.

In established AKI, there is an increased risk of bleeding and spontaneous gastrointestinal haemorrhage due to the
uraemia.

Prerenal
Hypovolaemi This may result from inadequate fluid intake or from excessiveloss of body water. Dehydration,
a prolonged vomiting, diarrhoeaand other abnormal gastrointestinal fluid losses, burns andexcessive
sweating are all common causes of hypovolaemia.
Blood loss This is usually caused by trauma or surgery, but acute bloodloss from the gastrointestinal tract or
haemorrhage associatedwith childbirth may be sufficient to cause hypovolaemic renalimpairment.
Sepsis Gram-negative septicaemia from a urinary tract source is aparticularly potent cause of bacteraemic
shock. Sepsis fromthe biliary tract and overwhelming infection from other sites,especially in the
immunocompromised individual, are alsoassociated with acute renal failure.blood.
Cardiogenic Acute dysrhythmia secondary to myocardial infarction, cardiactamponade and pulmonary embolus
shock may all result in reducedcardiac output of often poorly oxygenated

Anaesthesia Hypotension is a hazard of epidural and spinal anaesthesia.

Hypoxia Prolonged hypoxia from any cause may occasionally be responsible

Renal
Drugs Aminoglycosides, cephalosporins and diuretics can be nephrotoxic,particularly if used in
combination. They are quitecommonly used in patients whose renal function is alreadycompromised
by sepsis or circulatory abnormalities. Prolongeduse of non-steroidal anti-inflammatory drugs
(NSAIDs) cancause a chronic interstitial nephritis and papillary necrosis; theyalso reduce renal
plasma flow and therefore have nephrotoxicproperties. Angiotensin-converting enzyme inhibitors
used forthe control of hypertension can cause a rapid reduction in the glomerular filtration rate; this
is particularly liable to occur inpatients who have a reduced renal blood flow..
Poisons Some of these are nephrotoxic.

Contrast Even modern contrast media may cause renal failure wheninjected into a dehydrated patient with
media compromised renalfunction

Eclampsia The early recognition of pre-eclampsia is vital to avoid thenephrotoxic consequences of toxaemia
and uncontrolled hypertension.
Myoglobinu The presence of myoglobin in the urine is associated with the‘crush’ syndrome after major trauma.
ria Less severe injuries canalso cause the syndrome, especially if a compartment syndromeis
unrecognised or pressure areas break down.
Incompatibl This may lead to renal failure with myoglobinuria.
e blood
transfusion

Disseminate Disseminated intravascular coagulation usually follows majorsepsis or massive blood transfusion
d and may occur post-partum.
intravascula
r
coagulation

Post renal
Calculi Renal calculus disease is probably the most common cause ofacute obstruction leading to
anuria. The patient is likely tohave unilateral renal colic against a background of non-
functionof the contralateral kidney, often due to previous surgery orpre-existing obstruction
by calculus.
Pelvic malignancy Carcinomas arising from the bladder, prostate, cervix, ovaryor rectum can all lead to
obstruction of one or both ureters. Ahistory of haematuria and vaginal or rectal bleeding
signpostthe diagnosis. A large pelvic mass is commonly palpable onbimanual examination.
Surgery The ureters are vulnerable to damage during pelvic and retroperitonealsurgery, but injury
should be avoided if proper care istaken. It is unusual, but not impossible, to damage both
ureters.,.
Retroperitoneal
fibrosis

Bilharzia Schistosomiasis may lead to ureteric fibrosis and stenosis, andmay be responsible for the
development of squamous cell carcinomaof the bladder.
Crystalluria Uric acid crystalluria can develop in patients receiving chemotherapyfor leukaemia or
lymphoma unless they are givenprophylactic treatment with allopurinol

Clinical features
Answers to the following questions should indicate the probablecause of reduced urine output.
• Is urine being produced?
Bladder catheterisation is essentialif a voided sample cannot be obtained. If urine is
 available,check the specific gravity, look for the presence of casts(implying a renal
cause), test for myoglobinuria and send asample for culture and microscopy
.• Is there an obvious This can usually beanswered by clinical examination, assessment of the
prerenal cause? patient’svital signs, examination of the fluid balance chart andmeasurement of the
arterial oxygen concentration
Is there ureteric Hydronephrosis may not bemarked in acute obstruction, but ultrasonography will
obstruction? usuallyshow some degree of ureteric dilatation. A plain abdominalx-ray should be
checked for calculi
What drugs have been If a drug is thoughtto be responsible for renal impairment, it should obviously
given recently? bewithdrawn unless its use is vital
Is this a progression to The presenceof shrunken kidneys on ultrasound, normochromic anaemiaand
chronic renal failure? hypertension suggest progression to a chronic state evenif a previous history of renal
failure is not available.
Early recognition and intervention is important in AKI; all emergency admissions to hospital should have renal
function, blood pressure, temperature and pulse checked on arrival and should undergo a risk assessment for the
likelihood of developing AKI.

 This includes looking at coexisting diseases such as :

o diabetes,
o vascular disease
o and liver disease, which make AKI more likely,

 gathering information on drug treatments such as ACE inhibitors and NSAIDs, which may be associated
with renal dysfunction.

If a patient is found to have a high serum creatinine, it is important to establish whether this is an acute or acute-
on-chronic phenomenon, or a sign of chronic kidney disease.

Previous measurements of renal function can be of great value in differentiating these possibilities.
Patients with AKI need to be assessed quickly to determine the likely underlying cause.

Investigations that are required in all cases are

.

Additional investigations that are required in some cases, depending on the clinical picture are
The diagnosis of pre-renal AKI is usually obvious clinically
Various criteria have been proposed to classify AKI and to help identify high-risk patients, guide treatment and
provide information regarding prognosis.
The most commonly used are the KDIGO and RIFLE criteria which use serum creatinine and urine output as
biomarkers of kidney function.

c/p

pre-renal AKI Renal AKI Post-renal AKI

typically hypotensive and
tachycardic with signs of poor
peripheral perfusion, such as
delayed capillary return.
Tachycardia and postural
hypotension (a fall in blood pressure
of > 20/10 mmHg from lying to
standing) are valuable
signs of early hypovolaemia.
Many patients with sepsis initially
present with poor peripheral
perfusion, as mentioned above, but
then show evidence of peripheral
vasodilatation once they have
Factors that can help differentiate
the various causesnof renal and post-
renal AKI are
Patients with glomerulonephritis
usually demonstrate significant
haematuria and proteinuria and
may have clinical manifestations of
an underlying disease, such as SLE
or systemic vasculitis.
Drug-induced acute interstitial
nephritis is harder to spot but
should be suspected in a previously
well patient if there is an acute
Patients should be examined
clinically to look for evidence of
bladder enlargement and should
also undergo
imaging with ultrasound to detect
evidence of obstruction above the
level of the bladder.
Post-renal AKI is usually
accompanied by hydronephrosis,
but this can be
absent if the ureters are affected by
fibrosis or malignancy, or if
obstruction of the renal tract occurs
in combination with a renal disorder
such as acute tubular necrosis that
undergone initial resuscitation with
intravenous fluids.
However, this is accompanied by
relative underfilling of the arterial
tree and the kidney responds as it
would to absolute hypovolaemia,
with renal vasoconstriction leading
to AKI with acute tubular necrosis.
deterioration of renal function causes reduced urinary flow.
coinciding with introduction
of a new drug treatment.
Drugs that are commonly implicated
include gentamicin, omeprazole,
cisplatin and amphotericin B.

It is important to note that

pre-renal AKI may also occur
without systemic hypotension,
particularly in patients taking
NSAIDs or ACE inhibitors.
The cause of the hypotension is
usually
obvious clinically, but concealed
blood loss can occur into the
gastrointestinal tract, following
trauma (particularly
where there are fractures of the
pelvis or femur), and into the
pregnant uterus.

Large volumes of intravascular

fluid may also be lost into tissues
after crush injuries or burns, and
in severe inflammatory skin
diseases
or sepsis.

Biochemical assessment in prerenal Although blood tests, including an

AKI usually reveals evidence of a immunological screen, should be
metabolic acidosis performed to clarify the diagnosis in
and hyperkalaemia. glomerulonephritis, a renal biopsy is
usually required.

AKI in non-septic patient / unstable

Urinary tract • Suggested by a history of loin pain, haematuria, renal colic or difficulty in micturition
obstruction but often clinically silent
• Can usually be excluded by renal ultrasound: essential in any patient with unexplained
AKI
• Prompt relief of the obstruction restores renal function
Drugs and toxins • Poisoning, paraphenylenediamine hair dye, snake bite, paraquat, paracetamol, herbal
medicines, Cortinarius mushrooms
• Therapeutic agents: direct toxicity (aminoglycosides, amphotericin, tenofovir); or
haemodynamic effects (NSAIDs, ACE inhibitors), often with other factors. Phosphate
crystallisation after IV administration or from bowel preparation
• Sometimes associated with systemic vasculitis, systemic lupus erythematosus (SLE)
and Goodpasture’s (anti-GBM) disease
• Useful blood tests include: antineutrophil cytoplasmic antibodies (ANCA), antinuclear
antibodies (ANA), anti-GBM antibodies, complement, immunoglobulins
• Renal biopsy shows aggressive glomerular inflammation, usually with crescent
formation
Acute interstitial • Usually caused by an adverse drug reaction
nephritis • Characterised by small amounts of blood and protein in urine, often with leucocyturia
• Kidneys are normal size
• Requires cessation of drug and often prednisolone treatm

Management
Management options common to all forms of AKI are:
• Correct hypovolaemia and optimise systemic haemodynamic status with inotropic drugs if necessary
• Administer glucose and insulin to correct hyperkalaemia if K+ > 6.5 mmol/L
• Consider administering sodium bicarbonate (100 mmol) to correct acidosis if pH < 7.0 (> 100 nmol/L)
• Discontinue potentially nephrotoxic drugs and reduce doses of therapeutic drugs according to level of renal
function
• Match fluid intake to urine output plus an additional 500 mL to cover insensible losses once patient is euvolaemic
• Measure body weight on a regular basis as a guide to fluid requirements
• Ensure adequate nutritional support
• Administer proton pump antagonists to reduce the risk of upper gastrointestinal bleeding
• Screen for intercurrent infections and treat promptly if present

Item Measurement
Haemodynamic If hypovolaemia is present, it should be corrected by replacement of intravenous fluid or blood;
status excessive
administration of fluid should be avoided, since this can worsen outcome in AKI due to the
development of pulmonary oedema.
Monitoring of the central venous pressure may be of value in determining the rate of
administration of fluid in these circumstances.
Balanced salt solutions, such as Hartmann’s or Ringer’s lactate, may be preferable to isotonic
(0.9%) saline when large volumes of fluid resuscitation are required, in order to avoid
hyperchloraemic acidosis, but whether this substantially influences outcome remains unclear.
Administration of hydroxyethyl starch solutions should be avoided, since they have been
associated with higher rates of established AKI
Critically ill patients may require inotropic drugs to restore an effective blood pressure but
clinical trials do not support a specific role for low-dose dopamine.

Hyperkalaemia Hyperkalaemia is common, particularly in patients with sepsis, burns, haemolysis or metabolic
and acidosis acidosis

If serum K+ concentration is > 6.5 mmol/L, this should be treated immediately, to prevent
life-threatening cardiac arrhythmias.
Metabolic acidosis develops unless prevented by loss of hydrogen ions through vomiting or
aspiration of gastric contents.
Severe acidosis can be ameliorated with sodium bicarbonate if volume status allows.
Restoration of blood volume will correct acidosis by restoring kidney function. Infusions of
sodium bicarbonate (50 mL of 8.4%) may also be used, if acidosis is severe, to reduce life-
threatening hyperkalaemia
Cardiopulmonar Pulmonary oedema may result from the administration of excessive amounts of fluids relative
y complications to
urine output and because of increased pulmonary capillary permeability.

If pulmonary oedema is present and urine output cannot be rapidly restored, treatment with
dialysis may be required to remove excess fluid.
Temporary respiratory support may also be necessary with continuous positive airways
pressure (CPAP) or intermittent positive pressure ventilation (IPPV).
Once initial resuscitation has been performed, fluid intake should be matched to urine output
plus 500 mL to cover insensible losses, unless diarrhoea is present, in which case additional
fluids might be required.

Electrolyte Electrolyte disturbances, such as dilutional hyponatraemia, may occur if the patient has
disturbances continued to drink
freely despite oliguria or has received inappropriate amounts of intravenous dextrose.

They can be avoided by paying careful attention to fluid balance and by giving intravenous
fluids slowly.

Modest hypocalcaemia is common but rarely requires treatment.

Serum phosphate levels are usually high but may fall to dangerously low levels in patients on
daily or continuous dialysis or haemofiltration, necessitating phosphate replacement.

Dietary Adequate nutritional support should be ensured and it is important to give sufficient
measures amounts of energy and adequate amounts of protein; high protein intake should be avoided.

This is particularly important in patients with sepsis and burns who are hypercatabolic.
Enteral or parenteral nutrition may be required
Infection Patients with AKI are at substantial risk of intercurrent infection because humoral and
cellular immune mechanisms are depressed.

Regular clinical examination, supplemented by microbiological investigation where

appropriate, is required to diagnose infection.
If infection is discovered, it should be treated promptly according to standard principles

Medications Patients with drug-induced acute tubular necrosis or drug-induced acute interstitial nephritis
should have the offending drug withdrawn.
Additionally, vasoactive drugs, such as : NSAIDs and ACE inhibitors, should be discontinued,
as they may prolong AKI.

H2-receptor antagonists should be given to prevent gastrointestinal bleeding.

Other drug treatments should be reviewed and the doses adjusted if necessary, to take account
of renal function.
Nonessential drug treatments should be stopped.

Immunosuppress Patients with glomerulonephritis may require immunosuppressive drugs , plasma infusion and
ion plasma
exchange
Renal tract In post-renal AKI, the obstruction should be relieved as soon as possible.
obstruction This may involve catheterisation in urethral obstruction, or correction of ureteric
obstruction
with a ureteric stent or percutaneous nephrostomy.

Renal Conservative management can be successful in AKI with meticulous attention to fluid
replacement balance, electrolytes and nutrition, but renal replacement therapy (RRT) may be required in
therapy patients who are not showing signs of recovery with these measures.

Typically, the decision to start RRT is driven by hyperkalaemia, fluid overload or acidosis.
Severe uraemia with pericarditis and neurological signs (uraemic encephalopathy) is uncommon
in
AKI but, when present, is a strong indication for RRT.

No specific cut-off values for serum urea or creatinine have been identified at which RRT
should be commenced, and clinical trials of earlier versus later RRT in unselected patients with
AKI have not shown differences in outcome.

Furthermore, RRT can be a risky intervention in patients with comorbidity, since it requires
the placement of large intravenous catheters that may become infected and can also represent a
major haemodynamic challenge in unstable patients.

Accordingly, the decision to institute RRT should be made on an individual basis, taking
account of the potential risks and benefits, comorbidity and other aspects of the patient’s care,
including an assessment of whether early or delayed recovery is likely.

The two main options for RRT in AKI are haemodialysis and high-volume haemofiltration, or
the hybrid approach of haemodiafiltration.
Peritoneal dialysis is also an option if haemodialysis is not available

.
Recovery from AKI
o This is usually heralded by a gradual return of urine output and a steady improvement in plasma
biochemistry.
o During recovery, there is often a diuretic phase in which urine output increases rapidly and remains
excessive for several days before returning to normal.

o This may be due in part to tubular damage and to temporary loss of the medullary concentration gradient.
o This gradient plays a key role in concentrating urine in the collecting duct, and depends on continued
delivery of filtrate to the ascending limb of the loop of Henle and active tubular transport.
 o After a few days, urine volume falls to normal as the concentrating mechanism and tubular reabsorption
are restored.
o During the recovery phase of AKI, it may be necessary to provide supplements of sodium chloride,
sodium bicarbonate, potassium chloride and sometimes phosphate temporarily, to compensate for increased
urinary losses.

Obstructive renal failure

When the patient is too ill for surgery to remove the cause ofobstruction to the upper urinary tract, the treatment of
obstructiverenal impairment is drainage, either externally using anephrostomy or internally using an indwelling stent
1. Percutaneous nephrostomy
2. Insertion of a J-stent
3. Open surgery
AKI IN ELDERLY :
• Physiological change: nephrons decline in number with age and average GFR falls progressively.
• Creatinine: as muscle mass falls with age, less creatinine is produced each day. Serum creatinine can be
misleading as a guide to renal function.
• Renal tubular function: declines with age, leading to loss of urinary concentrating ability.
• Drugs: increased drug prescription in older people (diuretics, ACE inhibitors and NSAIDs) may contribute to risk
of AKI.
• Causes: infection, renal vascular disease, prostatic obstruction, hypovolaemia and severe cardiac dysfunction are
common.
• Mortality: rises with age, primarily because of comorbid conditions.