Buku Medicine

Introduction

Overview

Quick tip: Stage 3 AKI occurs when creatinine has increased 3 fold. AKI 3 with either unclear cause, suspected intrinsic renal disease or those with complications (anuria/acidosis/hyperkalaemia) or those not responding to initial treatment as expected, should be referred.

Acute kidney injury (AKI) refers to a sudden deterioration in kidney function from a person’s baseline, which is known or presumed to have occurred within the previous 7 days. The e-alert systems used in some hospitals which send the notices can be ‘fooled' in a number of ways so it is important to pay reference to the patient’s ‘baseline’ kidney function where previous records exist.

AKI can be grouped into 3 stages:

Stage 1: 1.5 x increase in serum creatinine from baseline
Stage 2: 2 x increase in serum creatinine from baseline
Stage 3: 3 x increase in serum creatinine from baseline

AKI can also be staged by urine output, however this is often less helpful upon initial presentation.

AKI is a heterogeneous syndrome - it is NOT a diagnosis on its own.
When faced with a patient with AKI, document the STAGE and CAUSE of the AKI (see causes module)
E.g. AKI stage 2 secondary to volume depletion (vomiting), hypotension, sepsis and contributing medications (NSAIDs, gentamicin)
E.g. AKI stage 3 with unclear precipitant - ?vasculitis

Outpatient workup

For patients with AKI in the community, follow these steps to provide a thorough workup to help with diagnosis, management and referral:

History
- Volume loss or intercurrent illness?
- Any new medications? E.g ACEi, PPI, NSAIDs, SGLT2 inhibitor
- Lower urinary tract symptoms in men
- Already known to the renal team?
Examination
- Are they hypotensive?
- Absolute hypotension; < 100mmHg systolic
- Relative hypotension; 40mmHg below their usual systolic BP in the community when well
- Assess fluid status – volume deplete or overloaded?
- Is bladder palpable?
Bloods
- U&Es, FBC, Calcium, bicarbonate, CRP
Urine dip
- Blood and protein? (see causes of AKI module for tips for interpreting urine dip)
Urine protein:creatinine ratio
- Send for uPCR (or urine protein:creatinine ratio) (see nephrotic syndrome module for tips on interpreting uPCR)
Review medications
- Medications that can cause/contribute to AKI? (See causes of AKI module)
- Medications that need dose adjusted in AKI? E.g. opioids, gabapentin, antibiotics, metformin

Do they need admission?

Judgement based on the severity of AKI, potassium and the presence of reversible causes.
If managed in the community, repeat bloods should be arranged to ensure resolution.
E.g. patient with stage 2 AKI who is otherwise well but has recently started trimethoprim and has just had 24 hours vomiting can often be safely managed in the community if they are able to increase oral intake, stop trimethoprim and have bloods repeated within 7 days.
If stage 3 AKI, or stage 2 AKI without easily reversible causes, then the patient is likely to require admission. Most patients with AKI are admitted to general medical receiving. If the patient is known to renal, has severe AKI, has a renal transplant, or you are considering an intrinsic renal cause (usually because of blood or protein in their urine), then discussion with the local renal team is welcome.

If you are referring someone to outpatient renal clinic because of an AKI incidentally found on blood tests it is useful to;

Include the reason why the blood tests were done (e.g. patient feeling unwell versus routine check as on methotrexate)
Include any new medications started (including any recent course of antibiotics)
Ensure blood tests are repeated at a sensible interval if the patient is not for urgent referral

See the excellent https://www.rcgp.org.uk/aki AKI in primary care toolkit for more information.

Inpatient workup

Quick tip: Always dipstick urine (and make sure the result is documented) when AKI is identified.

History
- Volume loss or intercurrent illness?
- Any new medications? E.g ACEi, PPI, NSAIDs, SGLT2 inhibitor
- Lower urinary tract symptoms in men
Examination
- Are they hypotensive?
  - Absolute hypotension; < 100mmHg systolic
  - Relative hypotension; 40mmHg below their usual systolic BP in the community when well
- Assess fluid status – volume deplete or overloaded?
- Is bladder palpable?
- Consider use of point of care ultrasound as an examination adjunct
Bloods
- U&Es, FBC, Calcium, bicarbonate, CRP
Urine dip
- Blood and protein? (click here for tips for interpreting urine dip)
- Sadly it is often easier for a renal physician to find the results of the PR3 antibody than the urine dip when a patient is referred, despite the fact that the clue to the diagnosis is usually offered by this inexpensive and rapid test. If you require a renal opinion, please perform and document urine dip yourself.
Urine protein:creatinine ratio
- Send for uPCR (or urine protein:creatinine ratio) (click here for tips on interpreting uPCR)
Review medications
- Medications that can cause/contribute to AKI? (see here)
- Medications that need dose adjusted in AKI? E.g. opioids, gabapentin, antibiotics, metformin
Renal tract imaging – usually ultrasound
- Consider in all patients with AKI in first 24 hours of admission, unless clear alternative cause or spontaneous improvement.
- Reason for imaging:
  - Exclude hydronephrosis
  - Check kidney number and size
  - Get clues on chronicity of renal disease (e.g small renal size with thinned cortices suggests longstanding CKD)
  - Certain malformations/ stones can predispose to recurrent infections which may provoke AKI
  - If you suspect an infected and obstructed renal tract then imaging should be performed within 6 hours (CTKUB if ultrasound unavailable out of hours)
Monitor urine output
- All patients with AKI requiring hospital admission should have careful documentation of urine output.
- Expected urine output is typically calculated using the following formula = (0.5 x body weight in kilograms) mls/ hour.
- For ease of reference, < 30 ml/hour is oliguria and is abnormal.

Do patients with AKI need a urinary catheter?

Yes if;
- Concern over bladder outlet obstruction (e.g. men over 65; palpable bladder)
- Haemodynamic compromise
No if;
- They are able to pass sufficient volumes of urine into bottles without concern of post-renal causes (i.e. normal USS or no risk factors)

When to send a glomerulonephritis (GN) or ‘renal’ screen?

Send a GN screen in patients who have unexplained AKI with blood and/or protein on urine dipstick.
Also consider sending a myeloma screen (i.e. serum protein electrophoresis, with either serum free light chains (SFLC) or urine bence jones proteins (use SFLC over BJP if available as it is a much more sensitive and specific test).
A paired urine sample for microalbuminuria and proteinuria can be valuable in investigating suspected light chain disease (paired uACR and uPCR).
Click here to see section on GN screen

Use of eGFR in AKI

It is generally better to discuss creatinine changes and urine output trends, rather than eGFR, in patients with AKI.
This is because eGFR is used only in conditions of steady state, and will not reflect true GFR when renal function is rapidly changing.
Nevertheless, as creatinine rises the eGFR will fall, so only the most pedantic of renal doctors will take issue with this.

Causes

Quick tip: in most patients the cause of AKI is pre-renal and multifactorial. If it’s not and there’s no hydronephrosis on imaging, consider rare causes.

When approaching AKI it is helpful to consider pre-renal, renal and post-renal causes.

Pre-renal AKI accounts for >80% of AKI.
Post-renal AKI accounts for >10% of AKI.
Renal causes of AKI are relatively rare but are the ones that you don’t want to miss. Rapidly progressive glomerulonephritis requires urgent, specific treatment that can save a patient’s long-term kidney function and reduce their risk of dying.

Pre-renal causes (>80% of cases)

Quick-tip: Pre-renal AKI is usually multifactorial. Don’t stop at 1 cause – there are usually at least 3 contributing factors to find. If not, consider less common causes.

Shock/Hypotension
- The kidneys need blood to make urine. If blood pressure is low, then this IS the cause of the AKI until proven otherwise. Hypotension can be absolute hypotension (e.g. systolic <90 mmHg) or relative hypotension (decrease of 40 mmHg from baseline BP). Identifying relative hypotension can be difficult. Remember baseline BP is not the admission BP but the last documented BP when the patient was well (e.g. clinic letter; GP records).
- Remember that it takes time for creatinine to rise after an insult, and the rise lags behind the drop in eGFR. Commonly a patient has a prolonged hypotensive episode (e.g. intra-operative blood loss; sepsis on admission) but their AKI is only apparent 2-3 days later. It can be helpful to think of the kidneys having been “stunned” and taking time to recover.
- Even once normal circulation is restored, the creatinine may continue to rise. In this situation an increase in urine output from oliguria to polyuria is a reassuring sign that heralds the onset of recovery.
Intravascular volume depletion (without hypotension)
- More common in patients with AKI risk factors (e.g. vascular disease, heart failure, liver disease, baseline CKD).
- Clinical history of volume loss (e.g. reported vomiting/poor intake) is often a more reliable indicator than examination findings (e.g. dry mucous membranes).
- Fluid status assessment may be challenging and typical examination findings may be unhelpful (e.g. peripheral oedema is less reliable as a marker of intravascular status in a patient with chronic lymphoedema). The best strategy is repeated volume status assessments over a period of days in combination with a trend in observations, daily weights and point of care ultrasound assessment (if possible).
Sepsis (without shock)
- Even in the absence of shock, co-existent infection is a common cause of AKI.
Medications
- Cardiovascular drugs - ACE inhibitors e.g. ramipril, angiotensin receptor blockers e.g. losartan, mineralocorticoid receptor antagonists e.g. spironolactone, neprilysin-inhibtors e.g. sacubitril-valsartan– these medications are widely accepted to be contributory causes in pre-renal AKI, beyond just their blood pressure lowering effects. HOWEVER, these drugs have proven symptomatic and survival benefits in many settings (e.g. heart failure with reduced ejection fraction) and stopping these drugs is associated with increased risk of re-admission after AKI. So, while it is often appropriate to suspend these drugs in patients with AKI, it is vital that there is a clear plan regarding if and when these drugs should restart.
- Other antihypertensives – if absolute or relative hypotension all antihypertensive drugs should be suspended.
- Diuretics (e.g. furosemide; indapamide) – diuretics only contribute towards AKI if the patient is volume deplete - either in the setting of another contributing factor such as shock, or if the diuretic dose is too high (often referred to as ‘over-diuresed’). If a patient with AKI has fluid overload then continuing (or more likely increasing) their diuretics is appropriate.
- Aminoglycoside antibiotics (e.g. gentamicin; amikacin).
- Non-steroidal anti-inflammatories (e.g. ibuprofen; naproxen) – these medications contribute to pre-renal AKI, independent from their association with acute interstitial nephritis (see renal causes below).
- Iodinated contrast (e.g. for CT or angiograms)– We are now confident that the risk of AKI due to venous iodinated contrast alone is small and may not exist at all, especially when given intravenously. Nevertheless, most nephrologists would accept that CT contrast as a possible contributing factor in patients with multi-factorial pre-renal AKI.

Intrinsic renal causes (<5% of cases)

Quick tip: always get the urine dipstick and document it

Rapidly progressive glomerulonephritis (‘RPGN’)

An umbrella term that refers to the clinical phenotype of a rapid fall in renal function over days to months almost always in the presence of an active urinary sediment (otherwise referred to as haematoproteinuria or ‘blood and protein’ on dipstick urinalysis).
May be associated with haemoptysis and systemic features e.g. malaise, purpuric rash, generalised arthralgia, fever, raised inflammatory markers +/- episcleritis, epistaxis.
The key challenge is identifying the possibility of a primary renal cause to allow appropriate immunological investigations to be sent and early discussion with renal to consider renal biopsy and empirical treatment.
Given features often present which could be infective (cough, fever, high CRP) and treatment is with immunosuppression, perform a full infection screen including multiple blood cultures (NB, serum procalcitonin cannot reliably be used to differentiate active vasculitis from infection).

RPGN causes are autoimmune and include:

Vasculitis e.g. ANCA-associated vasculitis, anti-GBM disease, cryoglobulinaemia
Glomerulonephritis e.g. crescentic IgA nephropathy, post-infectious GN
Lupus nephritis

What is the difference between glomerulonephritis and vasculitis?

Glomerulonephritis refers to inflammation within the glomeruli, which is seen on histology. Vasculitis is a systemic process that can cause glomerulonephritis, or can affect other organs without renal involvement.

Acute interstitial nephritis

An “allergic” reaction within the kidney
Can occur over days, weeks, months or years after the initial insult
Consider AIN in any patient with unexplained AKI
80% are due to drug causes, of which proton-pump inhibitors, NSAIDs and antibiotics account for the majority of cases
Other causes include infection (incl TB) and immune causes (Sjogrens, sarcoidosis)
The “classic” features of fever, rash, arthralgia and peripheral eosinophilia are RARE
Urinalysis may have ‘+’ blood and/or protein
Diagnosed on renal biopsy (or clinically if AKI improves with cessation of offending drug)

Interpreting urine dipstick in setting of ‘?glomerulonephritis’:

Blood and protein (everything else negative) – is it a catheter sample? If so it could be from trauma. Otherwise consider glomerulonephritis/vasculitis if clinically relevant. Haematoproteinuria is possible solely due to diabetic nephropathy, but most patients will require a renal biopsy to exclude other causes of intrinsic renal disease.
Protein only – could be glomerulonephritis but if longstanding diabetes this might represent chronic diabetic nephropathy (check previous uPCR).
Blood only – could be glomerulonephritis but consider surgical causes first (e.g. stones, tumour). Depending on age, patient may require urological work up prior to renal referral (see referral criteria).
Blood, protein, leucocytes +/- nitrites – either UTI (if symptoms) or chronic bacterial colonization. Unhelpful in differentiating likelihood of glomerulonephritis if clinically suspected.
Negative or ‘bland’ urinalysis – essentially excludes possibility of rapidly progressive glomerulonephritis. Consider pre-renal causes. Could still be interstitial nephritis, thrombotic microangiopathy or myeloma.

Other causes of intrinsic ‘renal’ AKI:

Rhabdomyolysis – check Creatine Kinase (CK); CK usually >10,000 for it to be the cause of AKI. May have history of ‘long-lie’, recreational drug use, or statin treatment. Also note that CK can be released during cardiac events so always review the clinical history and ECG.
Myeloma – can present as AKI, with or without proteinuria, due to a variety of mechanisms. Anaemia and hypercalcaemia are suggestive. Send myeloma screen (see here for interpretation) in unexplained AKI especially if they are over 50.
Thrombotic Microangiopathy – umbrella term that includes diagnoses such as: haemolytic urameic syndrome (HUS), atypical hameolytic uraemic syndrome (aHUS), thrombotic thrombocytopaenic purpura (TTP), scleroderma crisis and hypertensive emergency. Consider if low platelets, +/- low haemoglobin. Request urgent blood film (?fragments). Many of these conditions have disease-specific therapies so early discussion with renal and haematology is appropriate, which may include the national specialist aHUS referral team in Newcastle: http://www.atypicalhus.co.uk/contact-us/.
Tumour lysis syndrome – recent chemo with hypocalcaemia, hyperphosphataemia and hyperkalaemia. Hyperkalaemia often disproportionate to degree of AKI. See for more.
Hepato-renal syndrome – the vast majority (70%) of AKI in patients with decompensated liver disease is due to the ‘usual’ pre-renal causes. Where HRS is considered, discussion with both gastroenterology and renal is appropriate.
Cholesterol-emboli syndrome – AKI, eosinophilia +/- typical rash. Often with history of vascular disease or recent vascular intervention.
Bacterial endocarditis – can cause rapidly progressive glomerulonephritis and urine dip positive for blood and protein. Look for signs of endocarditis and discuss with cardiology.
Drug toxicity - numerous drugs can cause AKI in overdose including paracetamol, NSAIDs, lithium, toxic alcohols.

Post-renal causes (~10%)

Quick tip: patients with AKI due to obstruction usually still pass urine! Anuria is an extremely late sign of obstruction.

Quick tip: 1/1000 people are born with a solitary kidney

Renal imaging should be considered in every patient with AKI in the first 24 hours (unless clear alternative cause or spontaneous improvement), or within 6 hours if an obstructed and infected renal tract is suspected.

Bladder outlet obstruction

Most common cause of post-renal AKI. Early bladder scan is useful
Can be acute or chronic
Usually diagnosed with the insertion urethral catheter and documentation of a residual volume >400mls
Results in bilateral hydronephrosis, which resolves in hours-days after urethral catheter placement
Hydronephrosis chronicity can to some extent be determined by the appearance of the renal cortex. If echogenic and thin this raises the likelihood that obstruction is longstanding and renal recovery is less likely.
Causes: prostatic enlargement (cancer or BPH), bladder cancer, neurogenic bladder, urethral stricture, urinary catheter malposition

Ureteric obstruction

Diagnosed as hydronephrosis on imaging (ultrasound or CT) with an empty bladder.
In order for ureteric obstruction to cause AKI it must be bilateral, occur in presence of pre-existing CKD or occur in the presence of a single functioning kidney (e.g. small kidney on imaging from previous obstruction of vascular disease, previous nephrectomy, congenital single kidney).
Causes include; bladder cancer, stones, lymphadenopathy (usually malignant and may be first presentation), retroperitoneal fibrosis.

Management

Quick tip: IV fluids are the cornerstone of AKI management in inpatients with volume depletion. However, overuse of IV fluids is a significant cause of iatrogenic morbidity in patients with AKI. Aim for euvolaemia.

General principles:

Correct volume status
- If volume deplete – IV fluids
- If fluid overloaded – diuretics +/- dialysis
- In AKI patients require larger doses of diuretics as less of the drug reaches the tubules
Correct hypotension/shock
- Fluids +/- vasopressors
- Suspend antihypertensives
Manage hyperkalaemia – see here
Suspend offending/contributing drugs – see here
Adjust medication doses e.g. antibiotics, LMWH, opioids, gabapentin, insulin/gliclazide (and increase frequency of blood glucose monitoring)
Manage obstruction if present
- Urethral catheter +/- stent +/- nephrostomy
If stage 3 AKI or oliguria – discuss with renal

When to give IV sodium bicarbonate?

1.26% sodium bicarbonate is appropriate to give in the setting of AKI if:
- Volume deplete
- Metabolic acidosis (serum bicarb <18) not driven by lactic acid or ketones
- Avoid if hypocalcaemia or hypokalaemia

The main evidence for IV sodium bicarbonate in AKI is reducing the need for dialysis due to hyperkalaemia and severe acidaemia, but remember that reversing the underlying pathology and alternative strategies to manage hyperkalaemia (calcium gluconate, insulin, salbutamol) are more important.

Indications for dialysis

The 2 main indications for emergency dialysis in AKI are:

Refractory hyperkalaemia
Refractory pulmonary oedema

The presence of oliguria is crucial when considering starting dialysis, as if passing good quantities of urine it is rare to require emergency dialysis. On the other hand if the patient is oliguric, then dialysis is much more likely to be required. Documentation of urine output is of vital importance in making this decision and should be stressed to all team members caring for the patient.

The timing of dialysis in AKI is a balance. Emergency dialysis should be initiated BEFORE the onset of life-threatening complications but given the invasiveness of line/ peritoneal dialysis catheter insertion, potential haemodynamic instability caused by dialysis and the delay to renal recovery once starting dialysis there is also harm from starting too early, when dialysis could have been potentially avoided.

Other indications for dialysis include:

Refractory acidosis; (difficult to say if this is cause or consequence of acute illness).
Symptomatic uraemia; uncommon in isolation and mainly refers to uraemic pericarditis. Difficult to distinguish uraemic encephalopathy from general metabolic encephalopathy in acute illness.
Toxins; toxic alcohols, lithium toxicity, aspirin overdoses.

TIP: A useful mnemonic for acute dialysis indications is AEIOU

Acidosis
Electrolytes (hyperkalaemia)
Ingestions (e.g. aspirin, ethylene glycol)
Oedema (pulmonary)
Uraemia (pericarditis, encephalopathy)

IV fluids in AKI

IV fluids are the cornerstone of AKI management in inpatients with volume depletion. However, overuse of IV fluids is a significant cause of iatrogenic morbidity in patients with AKI. Aim for euvolaemia and do not reflexively prescribe IV fluid in AKI.

Pitfalls to watch

The anuric patient. Patients with anuria can quickly tip into fluid overload (that is then very difficult to treat without emergency dialysis). If oliguria/anuria, IV fluids need to be regularly re-assessed. Once euvolaemia is achieved, IV fluids should be stopped.
The patient who is now euvolaemic. If a patient is volume deplete at presentation, their AKI (in terms of serum creatinine) will often continue to get worse even once euvolaemia has been restored. The answer here is time, not ongoing IV fluids.
Shock. If a patient’s hypotension is not fluid responsive they require consideration of vasopressors, not ongoing excessive IV fluids.

When to refer patients with AKI to renal?

All patients with stage 3 AKI
All patients with prolonged oliguria
Patients with unexplained AKI
Patients who have, or are at risk of developing, indications for emergency dialysis

Pitfalls to watch when referring patients to renal:

Do they actually need ITU rather than renal?
Are they safe to transfer (if renal off-site)?

Referral checklist (try to have a many of these as possible to hand)

Cause of their AKI (or at least what your team think is most likely)
Urine dip result
Baseline renal function, current creatinine and creatinine trends
BP – most recent reading, lowest reading, baseline (GP/clinic) reading
Urine output with trend
Results of any immunology (see link to renal immunology)
Medications – current and recent changes
What is their pre-morbid functional status?
Current potassium
Current EWS and oxygen requirements
Infection status (bay versus sideroom)
COVID19 status

Recovery

The return of urine output is often the first sign of recovery in AKI. As urine output improves the creatinine usually continues to rise for several days before plateauing and eventually falling. Urine volume is not helpful if the patient has non-oliguric AKI.

Renal recovery can still occur months after AKI onset.
In most AKI, the likelihood of recovery is dictated by their baseline renal function and the duration of their insult.

Polyuria during recovery from AKI

Polyuria is common after pre-renal and post-renal AKI
During recovery, the kidneys produce copious volumes of dilute ‘poor quality’ urine
Many patients need IV fluids in the early stage of post-AKI polyuria to prevent volume depletion hindering their recovery
In patients who can reliably drink, it may be appropriate to let them guide their own fluid replacement according to thirst (as long as AKI continues to improve at same rate)
Often patients have accumulated excess total body water and so it is appropriate to aim for a neutral or slightly negative (e.g 500-1000ml) fluid balance
In general do not discharge people until urine output <3 litres as patients will struggle to drink more than this if needed.

Discharge summary following admission with AKI should include;

Maximum stage of AKI
Aetiology
Treatment, including if they needed dialysis
Degree of recovery at time of discharge
Post-discharge monitoring e.g. do they need bloods repeated? Do they need medications restarted or avoided?
When is clinic follow-up? This will be guided by renal team and will vary with degree of renal recovery prior to discharge

References

References for AKI content

https://renal.org/wp-content/uploads/2017/07/FINAL-AKI-Guideline.pdf

https://www.thinkkidneys.nhs.uk/aki/wp-content/uploads/sites/2/2018/11/Nov-18-TK-AKI-Primary-Care-Slides-FINAL.pdf

https://www.rcgp.org.uk/clinical-and-research/resources/toolkits/acute-kidney-injury-toolkit.aspx

https://cks.nice.org.uk/acute-kidney-injury#!scenario

McDonald J, McDonald R, Lieske J, et al. Risk of Acute Kidney Injury, Dialysis, and Mortality in Patients With Chronic Kidney Disease After Intravenous Contrast Material Exposure. Mayo Clin Proc. 2015;90(8):1046-1053. https://www.ncbi.nlm.nih.gov/pubmed/26250726.