Acute kidney injury: causes, diagnosis and management

Introduction

Acute kidney injury (AKI) is a serious, broad clinical syndrome associated with increased short-term mortality and long-term morbidity. AKI is defined as an abrupt decrease in kidney function leading to an increase in serum creatinine and/or a decrease in urine output. The condition is often multi-factorial in origin^​1​. While the origin of an AKI is with the kidneys, the implications can be system-wide and can affect anyone^​1​. Without prompt treatment, AKI can cause further complications, multi-system organ failure and, ultimately, death. However, AKI may be reversible if treated promptly^​2​.

A 2014 study assessed the economic impact of AKI in England and found that it costs the NHS in England more than £1bn per year, more than breast, lung and skin cancer combined. The study results also revealed that AKI could be responsible for at least 40,000 deaths annually. However, recent estimates suggest this may be higher than 80,000^​3,4​. Despite two national patient safety alerts in 2014^​5​ and 2016^​6​, and the Think Kidneys campaign^​7​, UK Renal Registry data and the 2021 Renal Medicine Getting It Right First Time (GIRFT) report highlights little improvement in AKI outcomes since 2018, underlining the need for immediate action to improve system-wide AKI care^​4,8,9​.

The 2024 UK Renal Registry AKI report found:

• 16.6% of people with an AKI episode died within 30 days of the first alert, compared with 17.6% in 2023 and 18.8% in 2022. Mortality reduced to 7.9% in those who were not hospitalised.
• Mortality within 30 days increased with peak AKI stage — 11.5% for AKI stage 1, 26.3% for AKI stage 2 and 33.2% for AKI stage 3, compared with 12.3%, 27.6% and 34.3%, respectively, in 2023 (see below for more information on staging)^​4​.

Pharmacy professionals play a vital role in recognising and reducing the risk of AKI. Prompt intervention can reduce the severity of the AKI, as well as mortality and morbidity^​2​. Pharmacy professionals are essential members of the multiprofessional team and are involved in stopping, adjusting and restarting medicines for patients with AKI. This is especially important as the AKI evolves and resolves, and the patient transitions between healthcare settings to ensure medicine changes are followed through and optimised.

Risk factors

Anyone can develop AKI, but risk factors increase the risk of AKI. Patients with an AKI are at greater risk of acute deterioration in their clinical condition (see Figure 1)^​8,10​. Anyone can develop AKI, but risk factors increase the risk of AKI. Patients with an AKI are at greater risk of acute deterioration in their clinical condition (see Figure 1)^​8,10​.

Figure 1: Acute kidney injury risk factors

Causes and symptoms

AKI is an abrupt (i.e. within 48 hours) reduction in kidney function. Identifying the causes, which can be multi-factorial, will direct appropriate management. The causes can be grouped into three categories, with medicines potentially being implicated in all three^​1​.

Pre-renal

Pre-renal AKIs are caused by anything that affects the blood flow to the kidneys, resulting in reduced renal perfusion. The causes of pre-renal AKIs include dehydration, sepsis, hypotension — including iatrogenic hypotension owing to antihypertensive drugs — blood loss through bleeding or injury, and heart failure. Pre-renal is the most common category of AKI — estimates vary, but some studies put it as high as 70–80% of all AKI^{​11–13​}. If pre-renal causes are not appropriately treated, then ischaemic injury to the kidney can occur (namely, acute tubular necrosis or acute tubular necrosis). Symptoms are generally reflective of the cause — for example, symptoms of low blood pressure (e.g. dizziness, syncope), of sepsis (e.g. fevers and localising symptoms), or the cause of hypovolaemia (e.g. diarrhoea and vomiting, bleeding)^{​11–13​}.

Post-renal

Post-renal AKIs are caused by urinary tract obstruction. Causes include any conditions that may block or impair outflow of urine anywhere between the kidneys, ureters, bladder and urethra (e.g., kidney or bladder stones, malignancies, retroperitoneal fibrosis, enlarged prostate, tumours of the bladder, a blocked catheter or nephrostomy)^​1,13​.

Renal/intrinsic AKI

Intrinsic AKI is caused by damage to the cells — typically the glomerulus or tubules — that form part of the filtration unit of the kidney, which are the nephrons. It is managed by specialist renal clinicians. Causes include:

• Acute tubulointerstitial nephritis (TIN) caused by a hypersensitivity reaction and often drug-induced — symptoms can include haematuria, fever, rash and arthralgia, but patients can present without these classic symptoms;
• Myeloma — symptoms include bone pain and fatigue;
• Immunological renal disease, including vasculitis and other forms of glomerulonephritis — symptoms can include fever/malaise, weight loss, non-blanching rashes and frothy urine;
• Rhabdomyolysis — myoglobin from muscle breakdown is toxic to renal tubule cells and symptoms include myalgia and dark-coloured urine^​1,13​.

Once AKI has developed, signs and symptoms will depend on the cause but may include the examples shown in Figure 2^​14​.

Figure 2: Acute kidney injury signs and symptoms

AKI may be asymptomatic and frequently is in the early stages^​14​.

Complications

Acute complications from AKI arise because of impairment of the kidney’s excretory, endocrine and metabolic processes. The risk of complications increases with the stage of AKI and can include:

• Hyperkalaemia;
• Metabolic acidosis;
• Uraemia;
• Volume overload (i.e. peripheral and pulmonary oedema);
• Acute or chronic need for renal replacement therapy (e.g. dialysis);
• Other electrolyte imbalances^​1,14​.

Chronic complications include hypertension, chronic kidney disease (CKD) and end-stage kidney disease, including the need for kidney replacement therapy. Prompt recognition and action can prevent these complications^​15​.

Diagnosis and assessment

AKI often forms part of a wider picture of clinical deterioration in a multi-morbid patient, and early recognition of AKI with timely intervention can significantly reduce harm and improve outcomes^​16​.

AKI is diagnosed based on blood tests or urine output. Medical history and physical examination are an important part of the diagnostic assessment of a patient with or suspected of having AKI. Patients should be asked about recent illnesses, fluid intake and output, as well as symptoms^​1,16​.

A thorough medication history is essential and should include questions about over-the-counter medicines, herbal remedies, teas or drinks, alternative therapies, recreational drugs and prescription medicines obtained from disreputable sources (e.g. unregulated websites)^​1,16​. Additional information on history taking can be found in ‘Principles of effective history taking when prescribing‘.

A patient’s vital signs should be assessed, including temperature, blood pressure, pulse, urine output and respiratory rate. Clinical signs of sepsis (e.g. fever, tachycardia) should be considered^​1,16​.

Serum creatinine is a measurement of renal function as it is solely excreted by the kidneys. Acute changes in serum creatinine levels can indicate changes in kidney function. The lowest available serum creatinine measurement in the past three months should be used to identify AKI. This is known as the baseline creatinine (i.e. the creatinine that is normal for the patient). The difference from baseline to current creatinine can determine the stage of acute kidney injury. The higher the stage of AKI, the worse the prognosis^​1,16​.

Globally, the Kidney Disease: Improving Global Outcomes (KDIGO) guidance is used to define and stage AKI. AKI is defined as any of the following:

• Increase in serum creatinine by ≥26 micromol/l) within 48 hours;
• Increase in serum creatinine to ≥1.5 times baseline, which is known or presumed to have occurred within the prior seven days;
• Urine volume <0.5 ml/kg/hr for six hours^​16​.

AKI is staged for severity on a 1 to 3 scale according to the criteria shown in Table 1^​1,16​.

Table 1: Acute kidney injury staging, according to KDIGO guidance

A 2025 GIRFT report highlighted that there continues to be unwarranted variation in the laboratory analysis of estimated glomerular filtration rate (eGFR), laboratory AKI algorithms, and prompt local processes to alert the responsible clinical team for all blood samples that trigger a new stage 2 or 3 AKI warning alert^​17​.

The stage of AKI can be determined using the times increase in creatinine over baseline. This is calculated as shown in Box^​16​. 

Other laboratory tests that are important in diagnosing and assessing the cause of AKI are:

• Serum urea — elevated levels can indicate impaired kidney function;
• Electrolytes — hyperkalaemia, acidosis (i.e. bicarbonate), hypo- or hypernatraemia and hypo- or hypercalcaemia;
• Urinalysis — presence of protein, blood, leucocytes aid the diagnosis of the type of AKI (e.g. urinary tract infection, glomerulonephritis). Blood and protein on dipstick can point to a glomerulonephritis, while leucocytes point to infection or an interstitial nephritis. Protein picked up on a dipstick can be quantified with a spot protein:creatinine ratio;
• Full blood count, C-reactive protein (CRP) and creatinine kinase (CK);
• More specific tests, such as immunology screens (e.g. anti-neutrophil cytoplasmic antibodies, anti-glomerular basement membrane disease, anti-nuclear antibodies), tests for myeloma and consideration of a kidney biopsy, are guided by nephrology specialists to identity intrinsic renal cases once pre- and post-renal causes have been ruled out^​1,16​.

Imaging tests

An ultrasound scan of the kidneys, ureters and bladder allows clinicians to check for obstructive causes, the size of the kidneys and/or structural abnormalities. UK guidance suggests this should be performed within 24 hours of identifying the AKI and within six hours if there is a suspicion of an infected obstructed system^​10​.

Management of AKI

The National AKI summit in 2023 aimed to improve care of people with an episode of AKI by bringing together healthcare professionals who care for patients with AKI. Recommendations from this summit were published in 2024^​8​. Important recommendations were:

• Not calling renin angiotensin aldosterone inhibitors (RAASi) nephrotoxic;
• Recognising AKI promptly as a marker of acute deterioration;
• Optimising all medications^​8,18​.

Once an AKI has been diagnosed, it is important that the appropriate management is implemented to minimise complications and disease progression. Any patient identified with an AKI, even stage 1, should be flagged to the responsible clinician. While AKI stage 1 can often be managed in primary care, higher stages of AKI — particularly when in the context of acute illness — often require hospital admission^​1​.

Management of AKI focuses on treating the potential causes, supporting the kidney function, medicines optimisation and prevention of disease progression and complications (see Figure 3)^{​1,10,16,19,20​}.

Figure 3: Initial management, daily steps and indications for kidney replacement therapy

Medicines optimisation

Pharmacy professionals are essential members of the multiprofessional team in stopping, adjusting and restarting medicines for people with AKI. Continual medicines optimisation is required as AKI evolves and resolves, and good communication is needed on transition between care settings^​21​.

Patients with AKI should have all their medicines reviewed. The review should focus on the following aspects:

• Stop/temporarily stop any potentially harmful or unhelpful medications, such as non-steroidal anti-inflammatory drugs, antihypertensives (especially if hypotensive), aminoglycosides, proton pump inhibitors (PPIs) (see below for more detail on potentially harmful or unhelpful medications);
• Caution is needed when stopping/temporarily stopping heart failure medicine to avoid worsening heart failure (e.g. seek specialist heart failure advice if it is not immediately clear whether to hold heart failure medication or not, as inappropriately withholding these could worsen the clinical picture if the patient has decompensated heart failure);
• All renally cleared medications should be reviewed in patients with AKI and, if necessary, dose-adjusted or temporarily stopped (e.g. opiates, gabapentin, digoxin);
• Antimicrobial frequency and/or dose should be optimised daily;
• As AKI resolves, it is important to review medications again with a plan to restart medications or readjust doses where appropriate;
• Ensure information on medicines optimisation is communicated between care settings.

A Medicines and Healthcare products Regulatory Agency (MHRA) Yellow Card report should be completed where a medicine is suspected to have contributed to AKI^​10​.

Few medications are truly “nephrotoxic” (i.e. commonly cause AKI in people who are otherwise well in the absence of any other AKI risk factors). Medicines with nephrotoxic potential should generally be avoided in patients with AKI. Where high-risk prescribing is indicated after an evaluation of risk versus clinical benefit, it should be accompanied by enhanced monitoring of kidney function. For example, there are rare situations where aminoglycosides or amphotericin are the only suitable antimicrobial agents in which case their use can potentially be justified in the balance of risks versus benefit but with careful dose titration and monitoring^​1,21​.

Antihypertensive medications, including diuretics, may risk worsening AKI severity or duration by reducing kidney blood perfusion if used in specific clinical circumstances, such as hypovolaemia, relative hypotension or severe sepsis. These medications are not nephrotoxic, which is a common misconception, and labelling them as such can be damaging when considering whether to restart them following an AKI^​18​. In the setting of hypotension/hypovolaemia/sepsis, all antihypertensive medication, not just RAASi, should be reduced or temporarily stopped. Beta-blockers should not be stopped abruptly and should usually be continued in patients with a history of ischaemic heart disease, atrial fibrillation or heart failure. Diuretics should be stopped in the setting of volume depletion but may need to be increased in decompensated heart failure, highlighting the importance of careful fluid balance assessment and regular clinical review^​21,22​. 

Outcome-modifying medications for cardiovascular disease, CKD and diabetes, such as angiotensin-converting enzyme inhibitors/ angiotensin II receptor blockers and sodium-glucose cotransporter 2 inhibitors (SGLT2i), are not directly nephrotoxic. While these drugs can cause a temporary increase in serum creatinine, this effect reflects appropriate haemodynamic changes rather than kidney damage^​18​.

Medication reviews should be repeated as the AKI evolves and begins to resolve, because some medications, such as antibiotics, may require dose or frequency changes as kidney function changes. If drugs are adjusted or suspended at the time of AKI, it is important that criteria for restarting these medications are documented, and clearly communicated to patients and onward healthcare professionals, especially during transitions of care. Providing such advice to patients aligns with the National Institute for Health and Care Excellence’s quality standard for AKI^​23​. It is imperative that medications with clear prognostic benefit — such as RAASi, SGLT2i, for patients with cardiovascular disease, CKD and diabetes — are restarted or followed up with a view to restart as early as possible after safe resolution of the AKI. This may be in a post-AKI follow-up clinic, by GP services, or in a virtual “NHS at home” ward. Local specialists — including heart-failure teams, nephrologists and diabetologists — should be contacted for expert guidance where there is uncertainty about restarting medications^​1,21​.

Useful resources relating to medicines optimisation and AKIs:

• The UK Renal Pharmacy Group (UKRPG) has a valuable AKI medicines optimisation information sheet and medication table, detailing effects on renal/fluid/electrolyte physiology, changes in the side-effect profile when renal function is reduced and action in the presence of AKI for key drug classes;
• The British National Formulary;
• Medicine-specific summaries of product characteristics, Electronic Medicines Compendium;
• Renal Drug Database;
• Medicines Complete.

Recovery of renal function

Prolonged pre-renal causes (e.g. hypotension or hypovolaemia) may result in damage to the nephrons. After an episode of AKI, creatinine may not return to baseline, or it may take time to recover. Baseline or a new baseline kidney function is typically obtained no later than 90 days after an AKI^​16,24​.

There is not a universally accepted definition of AKI recovery. Evidence of recovery should be sought no later than 90 days after the AKI and based on blood tests (i.e. creatinine), a urine dipstick/protein:creatinine ratio for evidence of proteinuria as a marker of chronic damage or a marker of an ongoing intrinsic renal process, and blood pressure to look for new hypertension. Even if creatinine has returned to within 25% of the previous baseline and there is no new proteinuria or hypertension (apparent full resolution), the patient should always be considered to be at an increased risk of further AKI. Steps should be taken to mitigate this risk; for example, with patient education (see below), regular monitoring and medicines optimisation^​16,24​.

In primary care and community settings, formal coding of AKI in the electronic health record can prompt a further medicines review post-AKI. For example, when a patient is discharged from hospital post-AKI, it is important to record that the patient has had an AKI and follow up on medicines changes. Pharmacy teams can record interventions directly in the electronic record, and use inbuilt messaging or task functions to liaise with prescribers and the wider multidisciplinary team. For audit and quality improvement, pharmacy teams can use e-alert data to monitor the frequency of alerts and associated pharmacy interventions.

Patient counselling and support

RAASi medication (e.g. angiotensin converting enzyme inhibitors, angiotensin receptor blockers and mineralocorticoid aldosterone antagonists) should not be termed “nephrotoxic”, as this risks patients and healthcare professionals misunderstanding their overall long-term benefit of slowing disease progression^​8​. RAASi are known to reduce cardiovascular mortality, reduce hospital admissions owing to heart failure and reduce progression of kidney disease. People with long-term health conditions are at increased risk of developing AKI, especially if they develop acute illness. However, it is pathology associated with these long-term health conditions that most often underlies their high risk of AKI, rather than RAASi medication^​8​.

Patients should be informed about which medicines have been temporarily stopped and why, what follow-up to expect — including blood tests — why medicines need to be restarted, and what this looks like in terms of medicines names, doses, frequency and timeline, and if further titration post-AKI is required^​21​. Patients can be signposted to Kidney Care UK and NHS websites.

While sick-day advice is commonly used to try to mitigate AKI during acute-illness episodes, there is no evidence that this is beneficial for RAASi medications, and it may risk overall harm if applied inappropriately^​8​. Sick day medication guidance typically includes recommendations to withhold specific medications for the duration of an acute illness when symptoms lead to reduced oral intake, such as fevers, sweats, vomiting and diarrhoea unless minor^​7​. There is no robust evidence to support widespread, routine implementation of generic sick-day advice to prevent AKI — this should be tailored to the patient in front of you^​25​.

Using technology for AKI detection and management

In the simplest form, AKI e-alerts reported in the patient’s laboratory results list can flag a patient with AKI when blood results are reviewed. Automatic integration of AKI e-alerting into patients’ electronic health records, or electronic prescribing and medicines administration systems (EPMA), can prompt a review of the patient and their medicines in real-time. Where auto-integration into other digital systems does not yet exist, the AKI e-alerts can often be pulled from laboratory management systems as a daily report, or integrated into prescribing dashboards or clinical prioritisation tools. Pharmacy professionals in all care settings can be proactive with reviewing AKI e-alerts and finding actionable ways of integrating them into real-time clinical practice. These urgent prompts can then lead to timely advice and interventions for medicines optimisation^​26,27​. The pharmacy team at Wrexham Maelor Emergency Department showed that during a 90-day pilot reviewing 50 patients with AKI, 74% of the patients required pharmacy intervention for AKI medicines optimisation^​28​. In the United States, a tool applied to the electronic prescribing system in a paediatric inpatient setting led to more rapid recognition of AKI, prompting increased monitoring and earlier AKI medicines optimisation, with this resulting in a reduced incidence of AKI^​29,30​.

The increasing use and promise of technology for improving AKI detection and management at population level, in combination with pro-active pharmacy interventions, could have an impact on how AKI is prevented, managed and followed up. This would support the Renal Medicine GIRFT in responding to the overdue and much-needed improvements in system-wide AKI care^​9​.

Summary

• Acute kidney injury — a sudden decline in kidney function that affects fluid, electrolyte and acid-base homeostasis, which is detected by elevated creatinine levels or reduced urine output. Early identification of AKI and its causes, to enable effective treatment, can decrease or prevent long-term damage to the kidneys;

• Risk factors — being aged over 65 years, heart failure, liver failure, diabetes, neurological or cognitive impairment, CKD, previous AKI, hypotension and medications;

• Causes:
  • Pre-renal — about 70–80% of cases. Inadequate blood flow to the kidneys (e.g. hypotension, dehydration, heart failure);
  • Intrinsic/renal — damage to kidney tissue (e.g. drugs, toxins, glomerulonephritis);
  • Post-renal — urinary tract obstruction (e.g. stones, enlarged prostate, tumours).

• Identification and staging — AKI stages are based on the rise in creatinine levels and reduced urine output. Anyone with an AKI, even stage 1, should be flagged to the responsible clinician. Higher stages of AKI, particularly when in the context of acute illness, often require hospital admission.

Management

• Sepsis/urinary obstruction — treat promptly if present;
• Optimise blood pressure/volume status;
• Prescribing — review and adjust medications:
  • Review medication daily — medications affecting renal blood flow, renally excreted drugs, or those potentially damaging to the kidneys should be stopped, held, or adjusted;
  • Review fluid prescription;
  • Treat complications such as hyperkalaemia/acidaemia. Antimicrobial frequency and/or dose should be optimised daily.
• Patient safety post-AKI — ensure medication follow-up to restart stopped, temporarily stopped or adjusted medications as kidney function recovers.