Changes

June to July 2023 — reviewed. A literature search was conducted in June 2023 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomized controlled trials published since the last revision of this topic. The recommendations have been updated in line with the current literature including updates to various Think Kidneys publications. There have been no major changes to recommendations.

Update

Goals

To support primary healthcare professionals to:

• Make a diagnosis of acute kidney injury (AKI).
• Offer appropriate initial and ongoing management in primary care.
• Arrange emergency hospital admission or specialist referral for people with AKI, depending on clinical judgement.
• Arrange appropriate follow-up in primary care after an episode of AKI.
• Advise on measures to prevent the development of AKI in people with risk factors.
• Provide advice on sources of information and support.

Outcome measures

No outcome measures were found during the review of this topic.

Audit criteria

No audit criteria were found during review of this topic.

QOF indicators

QIPP - Options for local implementation

NICE quality standards

NICE quality standards relating to people with acute kidney injury which may be relevant to this CKS topic include:

• Children, young people, and adults who are at risk of acute kidney injury are given advice on maintaining kidney health.
• Children, young people, and adults admitted to hospital who are at risk of acute kidney injury have their serum creatinine level monitored.
• Adults with an acute kidney injury warning stage 2 test result have a clinical review within 6 hours if they are acutely ill or admitted to hospital, or within 24 hours if they are clinically stable.
• Adults with an acute kidney injury warning stage 3 test result have a clinical review within 6 hours or, if they are acutely ill in the community, an immediate review to consider admission to hospital.
• Children, young people, and adults with acute kidney injury who meet the criteria for renal replacement therapy are referred immediately to a nephrologist or, if appropriate, a critical care specialist.
• Adults discharged from hospital after acute kidney injury have a clinical review within 3 months, or sooner if they are at higher risk of poor outcomes.

[NICE, 2023]

What is it?

• Acute kidney injury (AKI) is a term covering a spectrum of injury to the kidneys that can result from a number of causes which may co-exist. It is a clinical syndrome rather than a biochemical diagnosis [Think Kidneys, 2018a; NICE, 2021a].
  • It is characterized by a sudden decline in renal excretory function over hours or days that can result in failure to maintain fluid, electrolyte, and acid-base balance [Makris, 2016; Think Kidneys, 2018a]. The 2012 KDIGO guideline defined AKI as an abrupt decrease in kidney function occurring over 7 days or fewer [KDIGO, 2012].
  • The diagnosis of AKI and its staging is based on acute changes in serum creatinine and/or a reduction in urine output (oliguria) [Think Kidneys, 2018a].
  • The term 'acute kidney injury' has replaced the concept of 'acute renal failure', as it more accurately describes a wide range of injury (structural damage) and impairment (loss of function) causing earlier stages of kidney damage, not just kidney failure [Makris, 2016; Think Kidneys, 2018a; NICE, 2021a].
• AKI may be considered to be part of a continuum of 'acute kidney diseases and disorders' (AKD), which describes 'abnormalities in kidney structure or function that have existed for fewer than 90 days (the point at which chronic kidney disease [CKD] is defined)' [Ronco, 2019]. 

What causes it?

• There are multiple possible causes of acute kidney injury (AKI) which may co-exist, which have traditionally been divided into:
  • Pre-renal (most common) — due to reduced perfusion of the kidneys and/or hypotension leading to a decreased glomerular filtration rate (GFR). It is usually reversible with appropriate early treatment [Makris, 2016; Think Kidneys, 2018b; NICE, 2019].
  • Intra-renal — a consequence of structural damage to the kidney, for example, tubules, glomeruli, interstitium, and intrarenal blood vessels. It may result from persistent pre-renal or post-renal causes damaging renal cells [Makris, 2016; Think Kidneys, 2018b].
  • Post-renal (least common, accounting for around 10% of AKI) — due to acute obstruction of urine flow within the renal tract resulting in increased intratubular pressure and decreased GFR [Makris, 2016; Think Kidneys, 2018a; NICE, 2019].
• More than one contributing cause is often present [KDIGO, 2012]. See Table 1 for more detailed information on possible causes.

Table 1. Possible causes of acute kidney injury (AKI).

How common is it?

The reported incidence of acute kidney injury (AKI) in epidemiological studies varies depending on the definition used, patient population, clinical setting, and geographical area [Makris, 2016].

• It is estimated that one in five emergency hospital admissions is associated with AKI in the UK, prolonging inpatient care and contributing to 100,000 deaths in secondary care [NHSE, 2014].
  • The 2009 National Confidential Enquiry into Patient Outcome and Death (NCEPOD) report estimated that one-fifth of post-admission AKI was both predictable and avoidable [NCEPOD, 2009].
• Expert opinion in a review article cites study evidence that community-acquired AKI is 2-3 times more prevalent than hospital-acquired cases [Mesropian, 2016].
• A Welsh prospective cohort study analyzing electronic AKI alert data over 6 months identified 17,689 incident episodes of AKI which equated to an AKI incidence of 577 per 100,000 population [Holmes, 2016].
  • 49.3% of episodes were community-acquired.
  • 42% of people had pre-existing chronic kidney disease (CKD).
  • The 90-day mortality rate was 25.6%.
• The incidence of AKI is increasing, possibly as a result of the number of people in the population who are elderly or at-risk with multiple comorbidities. Improved detection of AKI is also likely to have contributed to this documented rise in the literature [Larmour, 2015; Thornburg, 2016].  
• The estimated cost of AKI-related inpatient care to the NHS in England over a 1 year period is estimated to be £1.2 billion, and the ongoing cost for subsequent CKD and end-stage kidney disease care is estimated to be £179 million [Kerr, 2014].  

What are the risk factors?

• The risk of acute kidney injury (AKI) depends on a person's susceptibility and the type and extent of exposure to a potential insult [KDIGO, 2012]. Those at increased risk of AKI include people [Think Kidneys, 2018a] [Think Kidneys, 2018b] [Think Kidneys, 2020a] [NICE, 2021a]:
  • Aged 65 years or over.
  • With a history of AKI.
  • With Chronic kidney disease (people with an estimated glomerular filtration rate [eGFR] less than 60 mL/min/1.73m² are at particular risk). See the CKS topic on Chronic kidney disease for more information.
  • With symptoms or history of urological obstruction or conditions which may lead to obstruction. See the CKS topics on LUTS in men and Prostatitis - chronic for more information.
  • With chronic conditions such as heart failure, liver disease, and diabetes mellitus (particularly if proteinuria). See the CKS topics on Diabetes - type 1, Diabetes - type 2, and Heart failure - chronic for more information.
  • With neurological or cognitive impairment or disability (may be reliant on others for fluid intake and at risk of reduced intake).
  • With Sepsis. See the CKS topics on Sepsis and Neutropenic sepsis for more information.
  • With hypovolaemia; hypotension; dehydration; or reduced fluid intake.
  • With oliguria (urine output less than 0.5 mL/kg/hour).
  • Who have used specific medication within the last week (especially if hypovolaemic) — such as nonsteroidal anti-inflammatory drugs (NSAIDs), angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor antagonists (ARBs), diuretics including mineralocorticoid receptor antagonists, and antibiotics including aminoglycosides.
  • Exposured to iodine-based contrast agents within the past week.
  • With cancer and or undergoing cancer therapy (risk will depend on the type of cancer, proposed treatment, and premorbid risk factors).
  • Who are immunocompromised (such as untreated HIV infection or malnourishment) or immunosuppressed. See the CKS topic on HIV infection and AIDS for more information.
  • Exposured to toxins (for example some herbal remedies and poisonous plants and animals).

What are the complications?

• Complications from acute kidney injury (AKI) occur as a result of impairment of the kidney's excretory, endocrine, and metabolic actions. The risk of complications is related to the severity and duration of AKI, the clinical context, and the person's comorbidities, and can involve multiple organ systems, including [Ostermann, 2016] [Levey, 2017]: 
  
  • Hyperkalaemia [KDIGO, 2012; NICE, 2021a].
    • This is usually asymptomatic until severe, and may cause muscle weakness, paralysis, cardiac arrhythmias, or in extreme cases cardiac arrest.
  • Other electrolyte imbalances, for example, hyperphosphataemia, hyponatraemia, hypermagnesaemia, and hypocalcaemia [Levey, 2017]. 
  • Metabolic acidosis [KDIGO, 2012; Jacob, 2020; NICE, 2021a]. 
    • Can present with altered level of consciousness, circulatory collapse, and hyperventilation.
  • Fluid overload (peripheral and pulmonary oedema); heart failure; lung injury; and liver injury [Jacob, 2020]  [Kellum, 2021; NICE, 2021a].
    • Signs include tachypnoea, tachycardia, cyanosis, and lung crepitations.
  • Uraemia [Mercado, 2019; Jacob, 2020; Kellum, 2021; NICE, 2021a]. 
    • Occurs in severe AKI, and may be associated with pericarditis, neuropathy, or encephalopathy requiring renal replacement therapy.
    • Symptoms include confusion, lethargy, and altered level of consciousness.
  • Chronic kidney disease (CKD), progressive loss of renal function over time, and end-stage kidney disease [Think Kidneys, 2018b; Think Kidneys, 2018a].
    • People who have had AKI have an increased risk of hypertension and CKD, which can be end-stage. Predictors for CKD after AKI include older age, lower baseline estimated glomerular filtration rate (eGFR), higher baseline albuminuria, and higher stages of AKI [Levey, 2017; NICE, 2019]. See the CKS topics on Chronic kidney disease and Hypertension for more information.
    • A meta-analysis of cohort studies of hospitalized adults found the additional risk of end-stage kidney disease after AKI is an estimated additional 0.4 extra cases per 100 person-years, and the additional risk of new or progressive CKD after AKI is an estimated extra 10 cases per 100 person-years [See, 2019].

What is the prognosis?

Evidence from epidemiological studies suggests that acute kidney injury (AKI) has important clinical consequences, even in mild, reversible cases. It has potentially variable outcomes, with increasing severity of AKI correlating with a higher risk of a worse prognosis [Think Kidneys, 2018a].

• AKI can contribute to increased length of hospital stay, together with higher in-hospital and longer-term mortality rates [Think Kidneys, 2018a; Semogas, 2019].
• A large Scottish population-based cohort study (n = 50,835) identified and followed up with people with hospital-acquired, community-acquired AKI admitted to hospital within 7 days, and community-acquired AKI not admitted within 7 days. Outcomes included 30-day, 1- and 5-year mortality, 90-day renal recovery, and the need for chronic renal replacement therapy (RRT) [Sawhney, 2016].
  • Of 4550 participants diagnosed with AKI, 61.1% were hospital-acquired, 22.9% were community-acquired and admitted, and 16.0% were community-acquired and not admitted.
  • 30-day mortality was similar for the hospital-acquired and community-acquired but admitted groups, and significantly lower for the community-acquired not admitted group (24.2%, 20.2%, and 2.6% respectively).
  • 5-year mortality was high in all groups, but lower for the community-acquired not admitted group compared with the other two cohorts (67.1, 64.7 and 46.2%).
  • People in the community-acquired not admitted group had greater non-recovery at 90 days.
  • 30% of people with community-acquired AKI who were admitted had developed chronic kidney disease (CKD) at 90 days.
• Another Scottish population-based cohort study of adults with at least one episode of AKI (n = 56,906) found [Wang, 2022]:
  • 33% of participants had an acute kidney disease or disorder (AKD) persisting between 7–90 days. Of these, 27% had non-recovery at 90 days post-AKI diagnosis.
  • Compared with early AKI recovery, progression to AKD was associated with an increased risk of 1-year mortality and developing de novo CKD.
• Mortality increases with increasing stage of AKI [Think Kidneys, 2018b]. A UK hospital-based prospective study with 9 months follow-up reported [Selby, 2012]:
  • A diagnosis of AKI in 5.4% of admissions.
  • An overall mortality rate of 23.8% (16.1% for stage 1 AKI, 36.1% for stage 3 AKI).
  • Renal recovery was dependent on the severity of AKI, with an 80% recovery seen in people with stage 1 AKI, and a 59% recovery in people with stage 3 AKI.
• A UK retrospective analysis of patients admitted to hospital with hospital-acquired (n = 334) and community-acquired (n = 686) AKI over a 14-month follow-up period since their initial AKI episode found [Wonnacott, 2014]:
  • Overall, there was a 6.4% incidence of AKI among all hospital admissions, with approximately two-thirds of cases developing in the community before hospitalization.
  • There was a 45% mortality rate in people with community-acquired AKI who were admitted to hospital, of which 44% occurred in hospital. This compared with a 63% mortality rate for the hospital-acquired AKI group, of which 68% of deaths occurred in hospital.
  • 39.4% and 33.6% of people in the community- and hospital-acquired groups, respectively, developed de novo CKD or progression of pre-existing CKD within the follow-up period.
• A hospital-based study of critically ill patients (n = 16,968) with AKI stage 2 or 3 assessed rates of AKI reversal (patient no longer meeting criteria for even stage 1 AKI) and recovery (reversal of AKI at hospital discharge) over the first week following AKI detection in hospital, and found [Kellum, 2017]:
  • Nearly two-thirds of patients showed 'early reversal' of AKI within the 7-day study period.
  • The age-adjusted 1-year survival varied from more than 90% for early AKI reversal to less than 40% for patients who had no AKI reversal.
  • Relapses were common affecting about one-third of patients, especially in the first 72 hours after AKI reversal, and were associated with a five-fold increased risk for death by 1 year compared with patients showing early sustained AKI reversal.
• A systematic review of 30 observational studies assessing long-term prognosis after AKI found that people with pre-existing CKD had a four- to five-fold increased risk of end-stage kidney disease, and mortality rates were doubled compared with people with a diagnosis of AKI alone. It noted, however, significant variation in the risk of poor outcomes between studies [Sawhney, 2015].
• A meta-analysis of 25 cohort studies (n = 254,408) found that AKI was associated with an 86% and 38% elevated risk of cardiovascular mortality and major cardiovascular events respectively, particularly heart failure, acute myocardial infarction, and stroke [Odutayo, 2017].

When should I suspect acute kidney injury?

Acute kidney injury (AKI) is often asymptomatic, especially in the early stages.

• Suspect a diagnosis of AKI in a person with:
  • Symptoms and signs such as:
    • Nausea and vomiting, diarrhoea, or suspected dehydration.
    • Reduced urine output or changes to urine colour.
    • Confusion, fatigue, or drowsiness. 
  • An acute illness and any risk factors for AKI.
  • An illness with no clear acute component and any of the following:
    • Chronic kidney disease (CKD, especially stage 3B, 4, or 5), or urological disease. See the CKS topic on Chronic kidney disease for more information.
    • New-onset or significant worsening of urological symptoms. See the CKS topics on LUTS in men and Prostatitis - chronic for more information.
    • Symptoms suggesting a complication of AKI.
    • Symptoms or signs of a multisystem disease affecting the kidneys and other organ systems (for example thrombotic thrombocytopenic purpura).
  • An AKI warning stage test result generated from electronic detection systems in a biochemistry laboratory. This flags up changes in creatinine levels suggestive of AKI in primary care.
    • See the sections on Responding to AKI warning stage test results and Diagnosis of AKI for more information.

How should I respond to AKI warning stage test results?

An acute kidney injury (AKI) warning stage test result may be generated from electronic detection systems in a biochemistry laboratory. This flags up changes in creatinine levels suggestive of AKI in primary care.

• Respond to AKI warning stage test results within an appropriate timescale using clinical judgement, as suggested below. Consider arranging an urgent review and clinical assessment if there are:
  • Poor fluid intake or urine output.
  • Evidence of hyperkalaemia (especially if moderate with potassium 6–6.4 mmol/L or severe with potassium 6.5 mmol/L or more).
  • Previous AKI.
  • Known chronic kidney disease (CKD) stage 4 or 5 or history of renal transplant — urgent liaison with a nephrologist may be needed. See the CKS topic on Chronic kidney disease for more information.
  • A history of frailty and/or chronic disease such as diabetes, liver disease, or heart failure. See the CKS topics on Diabetes - type 1, Diabetes - type 2, and Heart failure - chronic for more information.
  • Suspected intrinsic kidney disease or urinary tract obstruction. See the CKS topics on LUTS in men and Chronic prostatitis for more information.
• If there is a creatinine change suggesting a potential AKI, take into account the clinical context (for example assessment of acute illness, chronic disease monitoring, or drug monitoring).
  • If AKI warning stage 1 (current creatinine 1.5 or more times the baseline level, or creatinine rise more than 26 micromol/L or greater within 48 hours) and there is a:
    • Low pre-test probability of AKI (stable clinical context), consider clinical review within 72 hours of the result.
    • High pre-test probability of AKI (in the context of acute illness), consider clinical review within 24 hours of the result.
  • If AKI warning stage 2 (current creatinine two or more times the baseline level) and there is a:
    • Low pre-test probability of AKI (stable clinical context), consider clinical review within 24 hours of the result.
    • High pre-test probability of AKI (in the context of acute illness), consider clinical review within 6 hours of the result.
  • If AKI warning stage 3 (current creatinine three or more times the baseline level, or creatinine 1.5 times the baseline and more than 354 micromol/L) and there is a:
    • Low pre-test probability of AKI (stable clinical context), consider clinical review within 6 hours of the result.
    • High pre-test probability of AKI (in the context of acute illness), consider immediate hospital admission. See the section on Management in the Scenario on Management of acute kidney injury for more information.
  • Note: for more information on calculating a baseline creatinine value, see the section on Diagnosis. If the clinical context is unknown, assume a high pre-test probability of AKI until proven otherwise.

How should I diagnose acute kidney injury?

• In people with suspected acute kidney injury (AKI) who do not require urgent admission to hospital, measure or review the serum creatinine level and, taking into account the clinical context, compare with baseline.
  • To obtain a baseline value for the initial detection of AKI:
    • Use the lowest creatinine value within 7 days of the current value, or, if not available,
    • Review older results and use the lowest or mean creatinine value from between 7 days and 1 year before the current value. 
  • If no baseline creatinine value is available, consider repeating the serum creatinine measurement after 48–72 hours, depending on clinical judgement.
    • Monitor the person closely and do not let waiting for a second creatinine result delay treatment or referral if AKI is possible, particularly if the person is acutely unwell or the serum creatinine level is high.
    • Be aware that serum creatinine is a slow-changing surrogate for decreased glomerular filtration rate (GFR) and may take 24–72 hours to reach a new steady state following AKI.
  • Take into consideration if the person has:
    • Chronic kidney disease (CKD) — an increase in serum creatinine may be due to progression of CKD rather than AKI. Assess the pattern of serum creatinine values over a longer period of time, and consider arranging a repeat serum creatinine measurement to see if changes are sudden or stable, depending on clinical judgement. See the CKS topic on Chronic kidney disease for more information.
    • Recently been treated with trimethoprim — this can cause a false positive result, as trimethoprim may increase serum creatinine, but not affect the GFR.
    • Recently completed a pregnancy — this can cause a false positive result due to an apparent rise in creatinine compared with naturally reduced creatinine values in pregnancy.
• Detect AKI by using any of the following criteria:
  • A rise in serum creatinine of 26 micromol/L or greater within 48 hours.
    • Be aware that in the absence of a baseline creatinine value, a high serum creatinine level may indicate AKI, even if the rise in creatinine over 48 hours is less than 26 micromol/L (particularly if the person has been acutely unwell for a few days).
  • A 50% or greater rise in serum creatinine (more than 1.5 times the baseline) which is known or presumed to have occurred within the past 7 days.
  • A fall in urine output to less than 0.5 mL/kg/hour for more than 6 hours, if measurable (for example, if there is a catheter in situ).
    • Be aware that if a person has acute interstitial nephritis, polyuria can occur as a result of defects in tubular urine concentration ability.
• If there is ongoing uncertainty as to whether a person with CKD has worsening of their condition or acute-on-chronic kidney disease, assume the results represent AKI and manage accordingly.
  • See the Scenario on Management of acute kidney injury for more information.

How should I assess a person with acute kidney injury?

• If a person has confirmed acute kidney injury (AKI), assess:
  • Volume status and possible underlying cause(s) by checking:
    • Fluid intake and losses.
    • Pulse/blood pressure (including any postural changes) and jugular venous pressure — particularly for signs of hypotension and hypovolaemia.
    • Peripheral perfusion (capillary refill time); moistness of mucous membranes; and skin turgor — for signs of dehydration.
    • Changes in urinary output and when last passed urine.
    • For peripheral oedema and crackles on lung auscultation — for signs of fluid overload.
    • For a palpable bladder, abdominal or pelvic mass, or enlarged prostate (if clinically appropriate) — for signs of urinary tract obstruction.
  • Renal function and serum potassium level — to assess for hyperkalaemia.
  • For possible underlying cause(s) and the likelihood of AKI, by asking about:
    • Current symptoms, including acute intercurrent illness (such as diarrhoea and vomiting, urinary or renal tract infection, and sepsis) and symptoms suggesting urinary tract obstruction (for example lower urinary tract symptoms, bloating from a pelvic mass, and renal colic). See the CKS topics on LUTS in men, Prostatitis - chronic, and Renal or ureteric colic - acute for more information.
    • Fluid intake and any reduction in urine output (oliguria or anuria).
    • Any co-morbidities or risk factors for AKI.
    • Any systemic symptoms associated with intrinsic renal disease (for example vasculitic rash, arthralgia, uveitis, epistaxis, or haemoptysis).
    • Drug history — any medication that can cause or exacerbate AKI, or that may accumulate and cause harm during AKI; and any recent dose increases, including over-the-counter preparations, herbal remedies, and recreational drugs such as ketamine, synthetic cannabinoids, and 'legal highs'.
    • Risk factors for rhabdomyolysis, such as skeletal muscle injury, muscle overexertion, crush injury, or prolonged immobility.
    • Social situation and need for a carer to support fluid intake.
  • For renal disease by urine dipstick analysis for blood, protein, leucocytes, nitrites, and glucose.
    • AKI with negative urinalysis usually indicates a pre-renal or drug cause.
    • Positive protein and blood may suggest glomerular disease (particularly if 2+ blood, 2+ protein) if there is no evidence of urinary tract infection or trauma due to catheterisation.
    • Increased white cells are non-specific but may suggest infection (most common) or interstitial nephritis. See the CKS topics on Pyelonephritis - acute, Urinary tract infection (lower) - men, and Urinary tract infection (lower) - women for more information.
    • Note: be aware that urine dipstick analysis in a person with a catheter in situ should be interpreted with caution as there may be false-positive results (such as haematuria due to simple trauma).
  • The stage of AKI.
    • Assess the stage of AKI according to the criterion which gives the highest (worst) stage. See Table 2 for more detailed information.
    • In a primary care setting, the creatinine level will usually be the most readily available result, but if urine output is also being monitored, base staging on whichever shows the highest (worst) stage if creatinine and urine output correspond with different stages.

Table 2. Summarized staging system for AKI in adults (based on the KDIGO^§ classification).

Scenario: Management of acute kidney injury

From age 18 years onwards.

Scenario: Prevention of acute kidney injury

From age 18 years onwards.

Search strategy

Scope of search

A full literature search was not required as this CKS topic is primarily based on the National Institute for Health and Care Excellence (NICE) guideline Acute kidney injury: prevention, detection and management of acute kidney injury up to the point of renal replacement therapy.

The search excluded children, pregnant women, and people with a renal transplant.

Search dates

March 2018 - June 2023

Key search terms

Various combinations of searches were carried out. The terms listed below are the core search terms that were used for Medline.

• exp Acute Kidney Injury/, ((acute or early) adj (kidney or renal) adj (failure$ or injur$ or insufficien$ or dysfunction$ or impair$)).tw.

Sources of guidelines

• National Institute for Health and Care Excellence (NICE)
• Scottish Intercollegiate Guidelines Network (SIGN)
• Royal College of Physicians
• Royal College of General Practitioners
• Royal College of Nursing
• NICE Evidence
• World Health Organization
• Guidelines International Network
• TRIP database
• Agency for Healthcare Research and Quality
• Institute for Clinical Systems Improvement
• National Health and Medical Research Council (Australia)
• Royal Australian College of General Practitioners
• British Columbia Medical Association
• Canadian Medical Association
• Alberta Medical Association
• Michigan Quality Improvement Consortium
• Singapore Ministry of Health
• National Resource for Infection Control
• RefHELP NHS Lothian Referral Guidelines
• Medline (with guideline filter)
• Driver and Vehicle Licensing Agency
• NHS Health at Work (occupational health practice)

Sources of systematic reviews and meta-analyses

• The Cochrane Library:
  • Systematic reviews
  • Protocols
  • Database of Abstracts of Reviews of Effects
• Medline (with systematic review filter)
• EMBASE (with systematic review filter)

Sources of health technology assessments and economic appraisals

• NIHR Health Technology Assessment programme
• The Cochrane Library:
  • NHS Economic Evaluations
  • Health Technology Assessments
• Canadian Agency for Drugs and Technologies in Health
• International Network of Agencies for Health Technology Assessment

Sources of randomized controlled trials

• The Cochrane Library:
  • Central Register of Controlled Trials
• Medline (with randomized controlled trial filter)
• EMBASE (with randomized controlled trial filter)

Sources of evidence based reviews and evidence summaries

• Bandolier
• Drug and Therapeutics Bulletin
• TRIP database
• Central Services Agency COMPASS Therapeutic Notes

Sources of national policy

• Department of Health
• Health Management Information Consortium (HMIC)

Patient experiences

• Healthtalk
• BMJ - Patient Journeys

Sources of medicines information

The following sources are used by CKS pharmacists and are not necessarily searched by CKS information specialists for all topics. Some of these resources are not freely available and require subscriptions to access content.

• British National Formulary (BNF)
• electronic Medicines Compendium (eMC)
• European Medicines Agency (EMEA)
• LactMed
• Medicines and Healthcare products Regulatory Agency (MHRA)
• REPROTOX
• Scottish Medicines Consortium
• Stockley's Drug Interactions
• TERIS
• TOXBASE
• Micromedex
• UK Medicines Information

Stakeholder engagement

Our policy

The external review process is an essential part of CKS topic development. Consultation with a wide range of stakeholders provides quality assurance of the topic in terms of:

• Clinical accuracy.
• Consistency with other providers of clinical knowledge for primary care.
• Accuracy of implementation of national guidance (in particular NICE guidelines).
• Usability.

Principles of the consultation process

• The process is inclusive and any individual may participate.
• To participate, an individual must declare whether they have any competing interests or not. If they do not declare whether or not they have competing interests, their comments will not be considered.
• Comments received after the deadline will be considered, but they may not be acted upon before the clinical topic is issued onto the website.
• Comments are accepted in any format that is convenient to the reviewer, although an electronic format is encouraged.
• External reviewers are not paid for commenting on the draft topics.
• Discussion with an individual or an organization about the CKS response to their comments is only undertaken in exceptional circumstances (at the discretion of the Clinical Editor or Editorial Steering Group).
• All reviewers are thanked and offered a letter acknowledging their contribution for the purposes of appraisal/revalidation.
• All reviewers are invited to be acknowledged on the website. All reviewers are given the opportunity to feedback about the external review process, enabling improvements to be made where appropriate.

Stakeholders

• Key stakeholders identified by the CKS team are invited to comment on draft CKS topics. Individuals and organizations can also register an interest to feedback on a specific topic, or topics in a particular clinical area, through the Getting involved section of the Clarity Informatics website.
• Stakeholders identified from the following groups are invited to review draft topics:
  • Experts in the topic area.
  • Professional organizations and societies (for example, Royal Colleges).
  • Patient organizations, Clarity has established close links with groups such as Age UK and the Alzheimer’s Society specifically for their input into new topic development, review of current topic content and advice on relevant areas of expert knowledge.
  • Guideline development groups where the topic is an implementation of a guideline.
  • The British National Formulary team.
  • The editorial team that develop MeReC Publications.
• Reviewers are provided with clear instructions about what to review, what comments are particularly helpful, how to submit comments, and declaring interests.

Patient engagement

Clarity Informatics has enlisted the support and involvement of patients and lay persons at all stages in the process of creating the content which include:

• Topic selection
• Scoping of topic
• Selection of clinical scenarios
• First draft internal review
• Second draft internal review
• External review
• Final draft and pre-publication

Our lay and patient involvement includes membership on the editorial steering group, contacting expert patient groups, organizations and individuals.

Evidence exclusion criteria

Our policy

Scoping a literature search, and reviewing the evidence for CKS is a methodical and systematic process that is carried out by the lead clinical author for each topic. Relevant evidence is gathered in order that the clinical author can make fully informed decisions and recommendations. It is important to note that some evidence may be excluded for a variety of reasons. These reasons may be applied across all CKS topics or may be specific to a given topic.

Studies identified during literature searches are reviewed to identify the most appropriate information to author a CKS topic, ensuring any recommendations are based on the best evidence. We use the principles of the GRADE and PICOT approaches to assess the quality of published research. We use the principles of AGREE II to assess the quality of published guidelines.

Standard exclusions for scoping literature:

• Animal studies
• Original research is not written in English

Possible exclusions for reviewed literature:

• Sample size too small or study underpowered
• Bias evident or promotional literature
• Population not relevant
• Intervention/treatment not relevant
• Outcomes not relevant
• Outcomes have no clear evidence of clinical effectiveness
• Setting not relevant
• Not relevant to UK
• Incorrect study type
• Review article
• Duplicate reference

Organizational, behavioural and financial barriers

Our policy

The CKS literature searches take into consideration the following concepts, which are discussed at the initial scoping of the topic.

• Feasibility
  • Studies are selected depending on whether the intervention under investigation is available in the NHS and can be practically and safely undertaken in primary care.
• Organizational and Financial Impact Analysis
• Studies are selected and evaluated on whether the intervention under investigations may have an impact on local clinical service provision or national impact on cost for the NHS. The principles of clinical budget impact analysis are adhered to, evaluated and recorded by the author. The following factors are considered when making this assessment and analysis.
  • Eligible population
  • Current interventions
  • Likely uptake of new intervention or recommendation
  • Cost of the current or new intervention mix
  • Impact on other costs
  • Condition-related costs
  • In-direct costs and service impacts
  • Time dependencies
• Cost-effectiveness or cost-benefit analysis studies are identified where available. 

We also evaluate and include evidence from NICE accredited sources which provide economic evaluations of recommendations, such as NICE guidelines. When a recommended action may not be possible because of resource constraints, this is explicitly indicated to healthcare professionals by the wording of the CKS recommendation.

Declarations of interest

Our policy

Clarity Informatics requests that all those involved in the writing and reviewing of topics, and those involved in the external review process to declare any competing interests. Signed copies are securely held by Clarity Informatics and are available on request with the permission of the individual. A copy of the declaration of interest form which participants are asked to complete annually is also available on request. A brief outline of the declarations of interest policy is described here and full details of the policy is available on the Clarity Informatics website. Declarations of interests of the authors are not routinely published, however competing interests of all those involved in the topic update or development are listed below. Competing interests include:

• Personal financial interests
• Personal family interest
• Personal non-financial interest
• Non-personal financial gain or benefit

Although particular attention is given to interests that could result in financial gains or losses for the individual, competing interests may also arise from academic competition or for political, personal, religious, and reputational reasons. An individual is not obliged to seek out knowledge of work done for, or on behalf of, the healthcare industry within the departments for which they are responsible if they would not normally expect to be informed.

Who should declare competing interests?

Any individual (or organization) involved in developing, reviewing, or commenting on clinical content, particularly the recommendations should declare competing interests. This includes the authoring team members, expert advisers, external reviewers of draft topics, individuals providing feedback on published topics, and Editorial Steering Group members. Declarations of interest are completed annually for authoring team and editorial steering group members, and are completed at the start of the topic update and development process for external stakeholders.

Competing interests declared for this topic:

None.