Acute kidney injury (AKI) is defined as an acute decline in kidney function leading to a rise in serum creatinine and/or fall in urine output. Before we discuss AKI further, let’s recap our normal physiology of the kidneys as well as creatinine excretion:
🦴 Anatomy and physiology
The kidney is the body’s natural filtration system but also helps to regulate fluid, blood volume, blood pressure, pH and electrolytes.
The functional unit is the nephron which extends from the cortex into the medulla and can be divided into 5 components:
- Renal corpuscle - made up of the glomerular capillaries enclosed within Bowman’s capsule. This is the site of ultrafiltration. This occurs through blood arriving through afferent arteriole being squeezed out due to higher resistance in the efferent arteriole. This filtrate passes through the glomerular basement membrane and podocytes which filters ions and small molecules out while large molecules such as proteins, immunoglobulins, RBCs, WBCs remain in the blood.
- Proximal convoluted tubule (PCT) - this is the sight of water, HCO3-, Na+ and K+ reabsorption, as well as 100% of glucose and amino acid reabsorption.
- Loop of Henle - this is where an osmotic gradient is setup to allow for further reabsorption of water. The descending limb is permeable to water but not ions while the ascending limb actively pumps out ions to set up a gradient through which water will then diffuse out of the descending limb and be reabsorbed into the blood via the vasa recta.
- Distal convoluted tubule - once again water is reabsorbed here, but importantly there is also the macula densa sensor of Na+ (forming a part of the juxtaglomerular apparatus along with the juxtaglomerular cells of the afferent arteriole) which helps control the release of renin.
- Collecting duct - here we find principal cells which are the site of aldosterone receptors which allow for the reabsorption of sodium and water and excretion of potassium. ADH also acts on principal cells to activate aquaporins for water reabsorption as well. Another type of cell here is the intercalated cell which help with HCO3- reabsorption and H+ excretion to maintain acid-base balance.
The kidneys receive blood directly from the renal artery (directly branching off of the abdominal aorta). It enters the hilum of the kidney before branching into segmental arteries → interlobar arteries → arcuate arteries → cortical radiate/interlobular arteries → afferent arterioles.
Creatinine is a byproduct of creatine phosphate used in skeletal muscle. It is released by the body at a constant rate. It is of particular importance as it is filtered through the glomerulus and excreted freely without reabsorption or secretion. Therefore it is a good indicator of GFR.
High serum creatinine levels indicate poor clearance and impaired kidney function.
Reference ranges:
- Male serum creatinine: 60-110umol/L
- Female serum creatinine: 45-90umol/L (due to their lower muscle mass)
Urine output is also a good marker for cardiovascular and renal function. Normal urine output is 0.5-1.5mL/kg/hour. Oliguria is defined as <0.5mL/kg/hour.
Pathophysiology
We can divide the causes of AKI based on its pathophysiology:
- Pre-renal AKI - due to impaired perfusion into the kidneys. The kidney responds to lower perfusion by increasing sodium and water reabsorption. The glomerular efferent arteriole constricts while the afferent arteriole dilates to increase perfusion and maintain GFR. The RAAS also activated to increase blood pressure and increase water reabsorption. It makes up 55% of cases.
- Renal/intrinsic AKI - damage to the glomeruli, renal tubules or interstitial of the kidneys due to toxins or autoimmune attacks. 35% of cases.
- Post-renal AKI - due to obstruction of urine flow (obstructive uropathy) after the kidneys (ureter, bladder, urethra). 20% of cases.
Let’s look at some of the causes of these 3 types of AKI:
Pre-renal AKI
- Hypovolaemia due to diarrhoea or vomiting.
- Shock (hypovolaemic, cardiogenic, distributive)
- Renal artery stenosis
- Hepatorenal syndrome
Renal/intrinsic AKI
- Acute tubular necrosis
- Glomerulonephritis
- Acute interstitial nephritis
- Rhabdomyolysis
- Haemolytic uraemic syndrome
Post-renal AKI
- Kidney/ureteric stone
- BPH
- Tumour of the urinary tract
- External compression
⚠️ Risk factors
- Chronic kidney disease
- Heart failure
- Liver disease
- Diabetes mellitus
- History of AKI
- Nephrotoxic drugs - see below
- Nephrotoxic contrast mediums within 1 week - such as those used for CT scans (iodinated contrast agents)
- >65 years old
- Emergency surgery
- Aminoglycosides
- Vancomycin
- NSAIDs
- ACEIs
- ARBs
- Diuretics
- Cyclosporin
- Cisplatin
- Amphotericin
😷 Presentation
Early on, AKI may be asypmtomatic. It may present with symptoms suggestive of the cause for AKI such as LUTS (suggesting obstruction) or signs of sepsis.
AKI is a silent disease and so it is important to be suspicious in patients who are acutely ill.
As the renal failure progresses, we may see:
- Oliguria - below <0.5ml/kg/hour for at least 6 consecutive hours.
- Pulmonary and peripheral oedema - due to fluid congestion and increased capillary hydrostatic pressure.
- Arrhythmias - due to elevated potassium levels and acid-base disturbances which predispose to arrhythmias (we can use calcium gluconate for cardiac protection in these instances).
- Uraemia features - due to build up of urea in the blood:
- Pericarditis
- Encephalopathy
- Muscle cramps and twitching
- Nausea and vomiting
- Asterixis
🔍 Investigations
U&E’s are needed to assess their baseline levels and also to assess if they meet NICE criteria for AKI using their creatinine levels (this will be discussed below).
We need to look at:
- Potassium → hyperkalaemia is a big concern. If elevated >6.0mmol/L and/or ECG changes are seen we need urgent treatment.
- Bicarbonate → if reduced, may suggest acidosis.
- Urea
Other tests to order include:
- FBC - assessing for anaemia (suggestive of HUS), leukocytosis/leukopenia (sepsis), thrombocytopenia (HUS).
- CRP
- Blood cultures
- VBG
- Urinalysis
- Glucose → suggests diabetes
- Leukocytes and nitrites → suggests infection
- Protein and blood → suggests infection or acute nephritis
- Urine culture
- Urine output monitoring
- ECG
If no identifiable cause is present or they are at risk of obstruction, we should do a renal ultrasound within 24 hours (not necessary if alternative cause is present).
💯 Criteria and staging
NICE states that AKI can be diagnosed according to the RIFLE, AKIN and KDIGO criteria with any of the following criteria:
- Raised serum creatinine >26umol/L within 48 hours
- >50% rise in serum creatinine within the past 7 days
- Urine output <0.5ml/kg/hour for 6 hours or more (8 hours in children)
- >25% fall in eGFR in children/adults in 7 days
The Kidney Disease: Improving Global Outcomes (KDIGO) criteria are used to stage AKI from 1-3:
Stage 1 | Increase in creatinine 1.5-1.9 times baseline
Increase in creatinine >26.5umol/L
Reduction in urine output <0.5mL/kg/hour for >6 hours |
Stage 2 | Increase in creatinine 2.0-2.9 times baseline
Reduction in urine output <0.5mL/kg/hour for >12 hours |
Stage 3 | Increase in creatinine >3.0 times baseline
Increase in creatinine >353.6umol/L
Reduction in urine output <0.3mL/kg/hour for >24 hours
Initiation of kidney replacement therapyy
Decrease in eGFR <35mL/min/1.73m2 in patients <18 years old. |
🧰 Management
As it is an acute presentation, an A-E approach should be followed initially. A medication review should also be conducted and nephrotoxic drugs should be stopped as well as renally excreted drugs.
- Pre-renal AKI: rehydrate with IV fluids if due to dehydration (but be careful not to overload the patient).
- If a patient has a urine output of < 0.5ml/kg/hr post-operatively, the firs thing to consider is a 500 ml 0.9% sodium chloride over 15 minutes fluid challenge, if there are no contraindications or signs of haemorrhage.
- Renal AKI: stop nephrotoxic drugs.
- Post-renal AKI: relieve obstruction by catheterisation.
The hyperkalaemia also needs management to avoid arrhythmias. This can be done by:
- 🥇 Cardioprotection - calcium gluconate
- 🥇 Shifting potassium into intracellular space - insulin (actrapid).
- 🥈 Salbutamol may also be used as a second-line option.
- 🥈 Sodium bicarbonate infusion can also be used as a second-line option to correct any hyperkalaemic acidosis.
- Excretion of potassium - calcium resonium or non-potassium sparing loop diuretics such as (bumetanide/furosemide/thiazides).
Peripheral or pulmonary oedema can be treated with furosemide. However, we should not give them routinely to fix the AKI as this does not resolve the issue Drugs in AKI that are safe to continue/may need to be stopped/should be stopped:
Safe to continue | May need to be stopped (renally excreted) | Need to be stopped |
Paracetamol | Metformin | NSAIDS - except 75mg OD aspirin |
Warfarin | Lithium | Aminoglycosides (such as gentamicin) |
Statins | Digoxin | ACEIs |
Aspirin (75mg OD) | ARBs | |
Clopidogrel | Diuretics | |
B-blockers |
For example haemodialysis if the patient is refractory to medical treatment for complications.
Indications for dialysis can be remembered through the mnemonic AEIOU:
- A - Acidosis with a pH <7.2
- E - Electrolyte imbalance persistent hyperkalaemia >7mmol/L
- I - Intoxication
- O - Oedema that is refractory to diuretic therapy.
- U - Uraemia presenting with encephalopathy or pericarditis.
- Renal transplant
- Vasculitis/glomerulonephritis/tubulointerstitial nephritis/myeloma
- AKI of unknown cause
- Inadequate response to treatment
- Complicated AKI
- Stage 3 AKI
- CKD stage 4 or 5
AKI vs CKD
CKD is often detected on ultrasound with bilateral small kidneys. However, this is not always true. Some exceptions include:
- Autosomal dominant polycystic kidney disease (ADPKD)
- Diabetic nephropathy
- Amyloidosis
- HIV-associated nephropathy
Hypocalcaemia is also seen in CKD due to a lack of activation of vitamin D (needed for calcium absorption) through hydroxylation of 25-OH-D → 1,25-(OH)2-D.