Acute kidney injury (AKI) – the basics
This article is largely written for health professionals. We will now describe the basics of AKI and its management.
Overview
Acute kidney injury (AKI) can be defined as a rapid loss of renal function over hours or days.
AKI is a very common medical condition affecting 20% of emergency hospital admissions (medical and surgical) and the mortality associated with dialysis-dependent AKI can be up to 50% and up to 80% in AKI Stage 3. Decline in renal function leads to disturbance of fluid balance, acid-base homeostasis and electrolytes.
When considering AKI, it is important to consider the whole of the urinary tract, and the heart. The kidneys receive 20% of cardiac output.
AKI has replaced the term ‘acute renal failure (ARF)’. This change in nomenclature reflects the significance that small decrements in renal function may not lead to overt renal failure but do have a clinical impact on morbidity and mortality.
Classification and diagnosis
AKI may be defined (and classified) by several systems including RIFLE, AKIN, KDIGO and NICE. There is no single agreed international definition of AKI, hence our one above and this selection of definitions.
AKI can be diagnosed if a patient has:
- An increase in serum creatinine by ≥ 26 micromol/L within 48 hours
- An increase in serum creatinine to ≥ 1.5 times baseline within 7 days
- A urine output < 0.5 mL/kg/hr for six hours.
Stages of AKI
The stages of AKI are defined by the creatinine level, the higher the creatinine, the worse the kidney function.
- Stage 1: Serum creatinine 1.5–1.9 times baseline
- Stage 2: Serum creatinine 2.0–2.9 times baseline
- Stage 3: Serum creatinine ≥ 3.0 times baseline.
Stage 1 is the mildest (best) form, and Stage 3 the most severe (worst) form.
Distinguishing AKI and CKD
Most patients with AKI look unwell, may have hyperkalaemia (potassium > 6.0 mmol/L), and are either already admitted for something else, or need admission and rapid review.
Aetiology
The causes of AKI can grouped into pre-renal (75%), renal (intrinsic; 15%) and post-renal (10%).
- Pre-renal
This is the commonest group of causes of AKI. It is usually secondary to renal hypoperfusion.
Decreased renal perfusion can be related to reduced circulating volume (e.g. hypovolaemia), reduced cardiac output (e.g. cardiac failure), systemic vasodilatation (e.g. sepsis, or vasodilatory drugs) or arteriolar changes (e.g. secondary to ACE-inhibitor or NSAID use). Often pre-renal AKI is due to two or more of these factors.
Renal hypoperfusion causes ischaemia of the renal parenchyma. Prolonged ischaemia can lead to intrinsic damage and development of acute tubular necrosis (ATN). ATN is the most common cause of renal (intrinsic) AKI.
Some important causes of AKI
- Renal (intrinsic)
The hallmark of renal (intrinsic) AKI is structural damage. It is categorised according to which part of the vasculature (pathology) is affected:
- Vascular
- Glomerular
- Tubulointerstitial.
Vascular disease – can affect the main renal arteries, branch arteries, or arterioles (depending on pathology)
Large vessel disease – can be caused by atherosclerotic disease (arterial), thromboembolic disease (venous) and dissection (e.g. aortic). An important cause in this group is renal artery stenosis (RAS) and thrombosis.
Note. If RAS is unilateral, it will not cause AKI unless the patient has a single kidney, or a background of moderate CKD.
Small vessel disease – can be secondary to vasculitides, thromboembolic disease, microangiopathic haemolytic anaemias (MAHAs, e.g. disseminated intravascular coagulation (DIC) and HUS-TTP) and accelerated hypertension.
Glomerular disease – affects the cortex, where the glomeruli are situated
Glomerular pathology can be divided into primary (not associated with systemic disease, e.g IgA nephropathy) and secondary (associated with systemic disease, e.g. SLE) causes. Glomerular pathology can lead to a number of classical acute presentations (e.g. nephritic/nephrotic syndrome). Most are associated with heavy proteinuria. They are also a major cause of chronic kidney disease (CKD).
Tubulointerstitial disease – affects the medulla, where the tubules are situated
The most common tubulointerstitial cause of AKI is ATN, which is usually secondary to prolonged pre-renal AKI, due to renal hypoperfusion. Other tubulointerstitial causes include acute interstitial nephritis. This is usually due to medication (e.g. NSAIDs, PPIs, penicillins), but is sometimes idiopathic. Tubulointerstitial pathology can lead to scarring and fibrosis in the long-term.
Note. A simple acute pyelonephritis does not cause AKI unless the patient has severe sepsis.
- Post-renal
Post-renal AKI results from obstruction (often referred to as obstructive nephropathy) to the urinary tract.
Obstruction to urinary flow can occur anywhere along the urinary tract from renal pelvis to urethra. Common causes of obstructive nephropathy include: bladder neck obstruction (e.g. benign prostatic hyperplasia) and pelvic malignancy (including intraluminal, intramural and extramural tumours). Rare causes include retroperitoneal fibrosis (RPF).
Note. Urinary stones rarely cause AKI, unless the patient has a single kidney or a background of moderate CKD.
Risk factors
There are a number of risk factors that increase the likelihood of developing an AKI during hospital admission.
- Age (> 65 years old)
- Sepsis
- History of AKI
- CKD
- Urological history (e.g. stones)
- Cardiac failure
- Liver disease
- Diabetes mellitus
- Cognitive problems
- Toxins/medications
- Other factors that predispose to acute kidney injury (AKI) – e.g. myeloma.
Pathophysiology
The pathophysiology of AKI is largely dependent on the underlying cause.
A common feature of AKI is a reduction in glomerular filtration rate (GFR), which may be secondary to hypoperfusion (pre-renal), renal parenchymal damage (renal) or obstruction to urinary flow (post-renal). We will now discuss acute tubular necrosis (ATN), a common mechanism of injury in a number of causes of AKI.
ATN can be divided into four stages:
- Initiation: acute decrease in renal perfusion causing a reduced GFR
- Maintenance: GFR remains low for days or weeks
- Recovery: GFR recovers, regeneration of tubulointerstitial cells
- Polyuric: phase may occur.
Acute tubular necrosis (ATN) has many causes. Most are ‘ischaemic’ or ‘nephrotoxic’ in origin. Ischaemic causes are those of pre-renal AKI, described above. Nephrotoxic causes include medication (aminoglycosides, chemotherapy), radiocontrast, myoglobin (in rhabdomyolysis) and multiple myeloma.
Failure of adequate renal perfusion results in ischaemia. Ongoing ischaemia causes a pro-inflammatory response with the release of cytokines, oxygen free radicals; and activation of leucocytes and coagulation pathways. At this point, if renal perfusion is not restored, the ongoing ischaemia can lead to permanent cellular damage.
Tubular cells are particularly susceptible due to their limited blood supply and high metabolic demand. Damaged tubular cells slough off into the lumen as obstructive casts that further hamper the GFR. Following restoration of a normal GFR, the kidneys usually recover and tubulointerstitial cells regenerate. A polyuric phase often occurs. This is thought to be due to failure of adequate reabsorption by the recovering tubules.
Clinical features
The clinical features associated with AKI are usually non-specific, and dominated by the underlying diagnosis.
An accurate assessment of fluid balance is key. There may be clinical features of dehydration or fluid overload, depending on the cause and duration of the AKI – i.e. the patient may be hypovolaemic, normovolaemic or hypervolaemic.
Pre-renal
Patients usually present with clinical features of hypovolaemia and dehydration:
- Reduced capillary refill time (not reliable, especially in the elderly)
- Reduced skin turgor (ditto)
- Thirst (ask the patient, ‘are you thirsty?’) (ditto)
- Dizziness (ditto)
- Reduced urine output (ditto). AKI can occur with polyuria or normal urine output
- Orthostatic hypotension.
Look for clinical features associated with fluid loss including excessive sweating, vomiting, diarrhoea and polyuria. In elderly patients, there may be evidence of confusion.
Conversely the patients may be fluid overloaded (hypervolaemic), with:
- Ankle and sacral oedema
- Orthopnoea
- Paroxysmal nocturnal dyspnoea
- Dyspnoea
- Raised JVP
- Ascites.
Renal (intrinsic)
The clinical presentation of intrinsic renal AKI is dependent on the specific aetiology.
Patients with ATN will demonstrate features consistent with the underlying aetiology. Those with intrinsic glomerular pathology may present with features of nephritic syndrome (e.g. haematuria, proteinuria, oliguria and hypertension) or nephrotic syndrome (e.g. heavy proteinuria, hypoalbuminaemia and oedema). Either may have rashes, or other signs of vasculitis (e.g. nail fold infarcts).
Patients with a tubulointerstitial disease (e.g. acute interstitial nephritis) may complain of arthralgia, rashes and fever. Eosinophilia is frequently seen.
Post-renal
The clinical features of post-renal AKI depend on the site, chronicity and laterality (unilateral or bilateral) of the obstruction.
Patients with prostatic problems may have lower urinary tract symptoms (e.g. dysuria, frequency, terminal dribbling, hesitancy). Obstruction at the bladder neck might be associated with a palpable bladder and a tender suprapubic area.
Investigation
Detailed investigation of a patient with AKI may be necessary: to determine the underlying cause, and help guide further management. But the depth of assessment required is quite variable, dependent on whether the cause is obvious, and severity of AKI. So not all patients will need all of what we are about to describe. For example, many will not need a renal screen (see below). And very few will need a renal biopsy.
Basic assessment
Assess the current fluid status of the patient, looking for signs of hypo- or hypervolaemia including checking their urine output. Do a careful examination, and look for rashes (vasculitis) and signs of obstruction (a palpable bladder). Do a PR, and PV in a woman if necessary.
Review the patient’s drug chart looking for any potential nephrotoxic drugs. After that, check the drug chart, fluid status and weight daily (are they in positive or negative fluid balance?).
Bedside tests
- Urine dipstick
- Urinary ACR (looking for the heavy proteinuria of glomerular disease)
- Urine microscopy – looking for casts (of tubules, which may be made up of blood cells)
- ECG
- Bladder scan
Bloods
Basic blood tests should include: FBC, CRP, U&E, LFT’s, glucose, bone biochemistry, blood gases (venous/arterial) and blood cultures.
This allows a quick assessment of the extent of renal injury, and the development of any potential complications like hyperkalaemia or metabolic acidosis.
Note. eGFR is not useful (and should not be measured) in AKI, partly as renal function changes so rapidly.
Other bloods can be requested depending on the severity of AKI, especially if the cause is unknown. Many of these look for intrinsic renal (intrinsic) causes of AKI.
Renal screen
- Clotting (+/- blood film) – DIC, HUS/TTP
- Creatine kinase (CK) – rhabdomyolysis
- Anti-nuclear antibody (ANA) – positive in Systemic Lupus Erythematosus (SLE, lupus)
- Anti-neutrophil cytoplasmic antibody (ANCA; with PR3 and MPO) – vasculitis
- Anti-glomerular basement membrane (anti-GBM) antibody – Goodpasture’s Disease
- Complement C3/4 – low in SLE
- Double-stranded DNA (DsDNA) – SLE
- Serum electrophoresis – looking for a paraprotein suggestive of myeloma (and other dysproteinaemias)
- Immunoglobulins (IgG, A and M) – e.g. IgA high in IgA nephropathy
- Serum free light chains (SFL) – myeloma (and dysproteinaemias)
- Hep B/C, HIV – viral associated GNs (membranous GN with Hep B, mesangiocapillary GN with Hep C, FSGS with HIV)
+/- Other blood tests:
- Eosinophilia – acute interstitial nephritis
- Antistreptolysin O (ASO) titre – post-infectious GN
- Angiotensin converting enzyme (ACE) – sarcoidosis
- Cryoglobulins – mesangiocapillary GN)
- LDH/haptoglobin – high/low; HUS/TTP
- Prostate specific antigen (PSA; in a man) – prostate cancer.
Imaging
The key radiological investigation in AKI is renal ultrasound, which looks for evidence of obstructive nephropathy (e.g. hydronephrosis) and checks there are two kidneys. If the ultrasound is equivocal, and there is a high degree of suspicion of obstruction, a non-contrast CT may be completed. If that is also unclear, it may be necessary to request nephrostomies (by a radiologist), and/or a cystoscopy with retrograde pyelograms (urology).
Other radiological investigation include:
- CXR (looking for signs of fluid overload, infection or pulmonary haemorrhage)
- +/- CT or MR angiography (renovascular assessment).
Invasive investigations
These are unusual but include a renal biopsy or renal angiogram. A nephrologist will decide if these are necessary.
Management and treatment
Principles of management
Management is guided by the underlying cause. Here we will discuss the general principles of management that can be applied to most cases of AKI.
The management of AKI involves regular assessment and monitoring, controlling volume state, and correcting electrolyte abnormalities, including metabolic acidosis.
Patients who have stage 3 AKI or no clear diagnosis may require specialist intervention (e.g. glomerulonephritis, systemic vasculitis); and should be discussed with a nephrologist within 24 hours of detection. Patients with post-renal AKI require discussion with a nephrologist and urologist.
Regular assessment and monitoring
Regular assessment of the patients’ fluid status is important, including monitoring their urine output, which may require a urinary catheter and daily weights.
FBC, Bicarbonate and U&E should be measured daily, increased to twice daily in more severe cases.
Nephrotoxic drugs should be stopped (e.g. ACE/ARBs, NSAIDs, spironolactone) and regular prescriptions may need to be altered depending on the creatinine clearance.
Volume state
If patients are hypovolaemic, then intravenous fluids should be prescribed. The amount and type of fluids will depend on the clinical status of the patient.
If the patient is hypervolaemic they may require fluid restriction +/- the use of diuretics. High dose furosemide may be required.
Electrolyte abnormalities
Severe hyperkalaemia, variably defined as >6.5 mmol/L, is a medical emergency.
The management of hyperkalaemia is critical to avoid potential life-threatening arrhythmias. It involves:
- Protection of the myocardium: 10ml of 10% calcium gluconate
- Reduce extracellular potassium: aim is to drive potassium into the intracellular compartment. Insulin (e.g 10 units ACTRAPID in 50 ml 50% dextrose, or 100ml 20% dextrose) and beta agonists (e.g. 2.5mg nebulised salbutamol) are given
- Resins (e.g. sodium zirconium) can reduce potassium absorption within a few hours.
- Also stop potassium-provoking or containing medications.
- Low potassium diet and dietetic referral
Other electrolyte problems include hypocalcaemia (or hypercalcaemia), and hyperphosphataemia.
Metabolic acidosis
Depending on the severity of acidosis and associated clinical state, choices for treatment involve oral or IV sodium bicarbonate, or dialysis.
Specific treatments
- In obstructive nephropathy, a urinary catheter +/- nephrostomies may be required.
- In unusual cases, suppression of the immune system is necessary using strong immunosuppression such as methylprednisolone, cyclophosphamide, plasma exchange and rituximab. Again a nephrologist will decide.
Indications for dialysis
If the following complications of AKI occur, and are refractory to medical therapy, urgent dialysis is warranted:
Absolute indications
- Hyperkalaemia.
- Fluid overload.
Relative indications
- Metabolic acidosis
- Uraemic complications (e.g. encephalopathy, bleeding, pericarditis).
Summary
We have explained acute kidney injury (AKI) – the basics. We hope you have found it helpful.
This article was reviewed by Rachael Lee, AKI Advanced Nurse Practitioner.
Last Reviewed on 1 November 2023