Acute kidney injury: recognise, stop nephrotoxins, act fast

What acute kidney injury actually is

Acute kidney injury (AKI) is a sudden, significant fall in kidney function. The KDIGO 2012 guideline defines it as any one of three criteria: a creatinine rise of ≥26.5 µmol/L within 48 hours; a creatinine rise of ≥1.5 times the known or presumed baseline within 7 days; or urine output below 0.5 mL/kg/h for 6 or more continuous hours. Any single criterion is sufficient — a patient can meet the AKI definition with normal urine output if the creatinine is rising fast enough.

In Australia, AKI complicates approximately 15% of all hospital admissions and up to half of intensive care admissions, according to Kidney Health Australia’s KHA-CARI guidelines. In-hospital mortality is around 25%; stage 3 AKI in the ICU carries mortality above 40%. These figures reflect why recognition matters and why delay from community to clinical response has consequences.

Community-acquired AKI — where kidney function is already falling before the patient reaches hospital — now accounts for 50–60% of cases. This is the general practice setting: the older patient on multiple medications who develops a mild viral illness and arrives in the consulting room with a creatinine that has risen significantly from the previous year’s blood test. Most of this is preventable, and the GP is the clinician best placed to act on it.

The causes of AKI divide into three groups: pre-renal (reduced blood flow to the kidneys, approximately 70% of cases), intrinsic (direct kidney damage, approximately 25%), and post-renal (obstruction, approximately 5%). The majority of general-practice-encountered AKI is pre-renal and correctable once triggering drugs are stopped and fluid status is corrected.

A. Core clinical — the AU general-practice framework

Recognising the pattern

The most common presentation in general practice is an incidental blood test in someone who has been unwell. The combination of any acute illness — gastroenteritis, respiratory tract infection, febrile illness, urinary tract infection — with existing medications that reduce kidney perfusion is the archetypal trigger.

The eTG nephrology chapter and RACGP clinical resources both highlight the ‘triple whammy’ drug combination: an ACE inhibitor or ARB (renin-angiotensin-system blocker), a diuretic, and an NSAID (including over-the-counter ibuprofen). Each drug individually reduces effective renal perfusion under physiological stress; combined, they can tip a marginally compensated kidney into outright AKI during a dehydrating illness. Any patient on this combination who presents with vomiting or diarrhoea warrants same-day creatinine checking.

SGLT2 inhibitors (dapagliflozin, empagliflozin) should also be withheld during acute illness — not because they cause AKI in the long term, but because of the risk of euglycaemic diabetic ketoacidosis during dehydration, per the TGA advisory. Metformin should be held when renal clearance is reduced due to lactic acidosis risk.

Staging severity

KDIGO stages AKI in three categories:

Stage	Serum creatinine	Urine output
1	1.5–1.9× baseline, or rise ≥26.5 µmol/L	<0.5 mL/kg/h for 6–12 h
2	2.0–2.9× baseline	<0.5 mL/kg/h for ≥12 h
3	≥3× baseline, or creatinine ≥353.6 µmol/L, or RRT started	<0.3 mL/kg/h for ≥24 h, or anuria ≥12 h

Stage 1 AKI without red flags can be managed with close GP monitoring in carefully selected patients. Stage 2–3 needs same-day hospital assessment.

History and examination

Ask specifically about: fluid intake over the last 24–48 hours; recent illness (gastroenteritis, fever, dyspnoea, dysuria); all medications including prescription, OTC, and herbal — especially any recently added antibiotics, PPIs, blood pressure agents, or NSAIDs; any history of kidney disease, diabetes, heart failure, or liver disease.

Examination: assess hydration status (postural blood pressure and heart rate, mucous membranes, skin turgor, jugular venous pressure), look for a palpable bladder (post-renal red flag indicating obstruction), and assess for signs of fluid overload (bibasal crackles, peripheral oedema, raised JVP). Patients with fluid overload need diuresis, not additional fluid.

Investigations

Same-day bloods include: UEC and creatinine compared to known baseline, full blood count, venous blood gas (pH, bicarbonate, lactate, potassium), CRP, and creatine kinase if rhabdomyolysis is suspected (trauma, extreme exercise, collapse). Urine dipstick: if protein 2+ or blood 2+ without obvious infection, add urine microscopy and culture, and urine albumin:creatinine ratio. A bedside bladder scan is essential if there is anuria or any history of prostatic disease — a retained volume above 500 mL is diagnostic and therapeutic (catheterise immediately). An ECG is necessary because hyperkalaemia can be clinically silent until potassium exceeds 6.0–6.5 mmol/L, with peaked T waves as the first change.

B. Nephrotoxins, drug interactions, and prevention

The community nephrotoxin burden

NPS MedicineWise and the Australian Medicines Handbook both highlight that a significant proportion of community-acquired AKI is medication-related and preventable. The key offenders in general practice:

NSAIDs (ibuprofen, naproxen, diclofenac, celecoxib): reduce prostaglandin-mediated afferent arteriolar dilation, impairing the kidney’s compensation for reduced perfusion. Dangerous in anyone with pre-existing CKD, diabetes, heart failure, or concurrent ACEi/ARB/diuretic use. Over-the-counter availability means many patients self-prescribe without awareness of their kidney risk.

ACE inhibitors and ARBs: reduce efferent arteriolar resistance, lowering glomerular filtration pressure during volume depletion. Renoprotective long-term but haemodynamically problematic during acute dehydration.

Diuretics: volume-depleting; safe when kidney perfusion is maintained, but accelerate AKI when combined with illness-related dehydration.

PPIs: associated with acute interstitial nephritis (AIN) in a small proportion of users — typically a temporal link of days to weeks after starting, sterile pyuria, and mild proteinuria. eTG and RACGP guidelines both note this underrecognised association.

Herbal products: TGA advisories flag aristolochic acid (found in some Chinese herbal preparations and causing progressive nephropathy), ephedra (ma huang), and Tripterygium species. Always ask specifically about supplements and traditional remedies.

The SGLT2 inhibitor nuance

The DAPA-CKD NEJM 2020 trial and the EMPA-KIDNEY trial showed that dapagliflozin and empagliflozin reduce AKI events overall in patients with CKD and albuminuria despite a small initial haemodynamic eGFR dip at commencement. The recommendation is not to permanently stop SGLT2 inhibitors because of an eGFR dip, but to withhold them during intercurrent illness, dehydration, and surgical fasting per TGA guidance and reinstate once recovered.

Contrast-associated AKI

For patients with eGFR below 45 mL/min/1.73 m² needing iodinated contrast (CT with contrast, coronary angiography), intravenous normal saline or balanced crystalloid 1 mL/kg/h for 6–12 hours before and after the procedure is the standard prevention strategy. The AMACING and PRESERVE trials demonstrated that N-acetylcysteine and sodium bicarbonate add no benefit beyond IV saline; the KDIGO 2024 update no longer recommends them. The SMART trial (Semler NEJM 2018) supports balanced crystalloid (Plasma-Lyte or Hartmann’s solution) over normal saline for most resuscitation contexts, consistent with current Australian emergency practice.

C. Diagnosing the cause — pre-renal versus intrinsic

The essential clinical question in most GP-encountered AKI is: is this pre-renal (reversible with fluid and nephrotoxin cessation) or something more serious requiring urgent nephrology?

Pre-renal AKI recovers as renal perfusion is restored. Fractional excretion of sodium (FENa) below 1% in an oliguric patient not on diuretics indicates intact tubular sodium reabsorption — consistent with pre-renal physiology. Fractional excretion of urea below 35% is more reliable when diuretics are on board. Urine in pre-renal AKI is concentrated (osmolality above 500 mOsmol/kg, specific gravity above 1.020) and sodium-avid (urine sodium below 20 mmol/L).

Acute tubular necrosis (ATN) — the commonest intrinsic cause — develops when pre-renal physiology is uncorrected for long enough to cause ischaemic or toxic tubular injury. FENa is typically above 2%. Urine microscopy shows muddy-brown or granular casts; urine is dilute and sodium-rich. ATN is the natural endpoint of untreated pre-renal AKI.

Acute interstitial nephritis (AIN) — typically drug-allergic — produces white cell casts on microscopy, sterile pyuria, and mild-to-moderate proteinuria. The classic triad of fever, rash, and eosinophilia occurs in under 30% of cases. Temporal association with a new drug (days to weeks) is the key clue. Stopping the offending agent is the primary treatment; specialist-supervised prednisolone if no recovery in 5–7 days.

Glomerulonephritis produces haematuria with dysmorphic red cells or red cell casts on microscopy, significant proteinuria (urine PCR above 100 mg/mmol), and often hypertension. This requires same-day nephrology referral.

Post-renal obstruction: the bladder scan is the fastest investigation. Hydronephrosis on renal ultrasound confirms ureteric obstruction and requires urgent urology input.

KHA-CARI guidelines recommend renal tract ultrasound within 24 hours whenever the cause is unclear, obstruction is possible, or the AKI is not recovering as expected.

D. Australian operations

Referral pathways

Immediate ED transfer is warranted for: AKI stage 2–3; potassium above 6.0 mmol/L or any ECG change of hyperkalaemia; pH below 7.20 or bicarbonate below 15; pulmonary oedema or fluid overload; uraemic symptoms (encephalopathy, pericardial rub, asterixis, bleeding); anuria beyond 12 hours; suspected obstruction in a single functioning kidney; suspected rapidly progressive glomerulonephritis; or sepsis-associated AKI with haemodynamic compromise.

Same-day nephrology phone consultation may be appropriate for community-acquired stage 1 AKI without absolute transfer indications — particularly in older patients where hospital admission itself carries risk. This is always a consultative decision, not a solo GP call.

Outpatient nephrology referral within 1–4 weeks post-recovery: to establish underlying cause if not yet determined, confirm CKD staging, optimise cardiovascular and renal risk management.

Urology for ureteric obstruction requiring stent or nephrostomy.

MBS funding for AKI care

Standard GP consultations (items 23, 36, 44) cover AKI assessment. The GP Chronic Condition Management Plan (items 965 and 967, replacing GPMP/TCA from 1 July 2025) funds dietitian and exercise physiologist input in chronic kidney disease follow-up. Aboriginal and Torres Strait Islander patients qualify for the ATSI Health Assessment (item 715) with CKD care coordination.

Pathology items: UEC (item 66536), FBC (item 66512), CRP/ESR (item 65070), creatine kinase (item 66608), urinalysis with microscopy (item 66659), urine ACR (item 66525), venous blood gas (item 73815). Renal ultrasound (items 55036, 55054). Autoimmune screen (items 71089, 71151–71161) for suspected intrinsic AKI.

Post-AKI follow-up schedule

The KHA-CARI post-AKI surveillance protocol recommends UEC + eGFR + urine ACR at 3 months, 6 months, then annually for at least 1–2 years (or lifelong if CKD evolves). Medication reconciliation after hospital discharge: restart ACEi/ARB cautiously with UEC check at 1–2 weeks; confirm metformin restart once creatinine stable; cease unnecessary NSAIDs permanently.

The Heart Foundation 2023 cardiovascular risk guideline and KDIGO 2024 both target blood pressure below 130/80 mmHg, statin therapy when 5-year CVD risk exceeds 10%, and glycaemic optimisation in diabetes. Vaccination: the Australian Immunisation Handbook recommends annual influenza vaccine, COVID-19 boosters, PCV20 pneumococcal schedule, and hepatitis B immunisation for patients with CKD (high-dose formulation if eGFR below 30).

Sick-day rules counselling

Every patient with CKD, diabetes, heart failure, or a prior AKI should receive written sick-day instructions before leaving the consulting room. Kidney Health Australia’s Kidney Smart programme provides a practical patient-facing card specifying which medications to withhold during gastroenteritis, fever, or any illness preventing normal eating and drinking. The rule: withhold ACEi, ARB, diuretic, NSAID, SGLT2 inhibitor, and metformin until well-hydrated and eating normally for 24–48 hours, then restart with GP review.

E. Special populations

Aboriginal and Torres Strait Islander Australians bear a disproportionate burden of both AKI and its progression to end-stage kidney disease, occurring at younger ages and with worse cardiovascular outcomes, as documented by AIHW Indigenous kidney disease data. Culturally safe care through Aboriginal Community Controlled Health Organisations, combined with the ATSI Health Assessment (item 715) and GP Chronic Condition Management Plan, supports better follow-up engagement. Address housing stability, food security, and social determinants alongside medication management.

Older adults frequently have reduced physiological reserve and reduced muscle mass. An eGFR of 50 mL/min/1.73 m² in a 75-year-old represents less kidney capacity than the same value in a 40-year-old because creatinine generation from muscle is lower with ageing — the absolute creatinine value is misleadingly reassuring. Polypharmacy is the rule in this group; every drug reconciliation must check renal clearance and the sick-day combination.

Patients with diabetes and CKD: SGLT2 inhibitors have demonstrated renal and cardiovascular benefit in DAPA-CKD and EMPA-KIDNEY and should not be permanently ceased after a single AKI episode without specialist discussion. The long-term benefit generally outweighs the sick-day risk when robust counselling is in place.

Pregnancy: AKI in pregnancy has specific causes — haemorrhagic shock, pre-eclampsia, HELLP syndrome, acute fatty liver of pregnancy — requiring joint obstetric and nephrology input.

When to escalate

Arrange same-day ED review for any of the following: AKI stage 2–3 confirmed or clinically suspected; potassium above 6.0 mmol/L or any ECG change of hyperkalaemia; blood pH below 7.20 or bicarbonate below 15; pulmonary oedema or severe fluid overload; uraemic symptoms (encephalopathy, pericardial rub, bleeding, asterixis); anuria beyond 12 hours; suspected obstruction in a solitary kidney; suspected rapidly progressive glomerulonephritis (haematuria + proteinuria + acute creatinine rise); or sepsis-driven AKI with haemodynamic compromise.

For stage 1 AKI in a patient who is alert, drinking fluids, producing urine, and responding to nephrotoxin removal — same-day nephrology phone consultation and next-day GP review is a reasonable alternative, but this is always a consultative decision.

What this article is and is not

This is general health information drawn from current Australian guidelines — KDIGO 2012, KHA-CARI, Therapeutic Guidelines, Australian Medicines Handbook, NPS MedicineWise, and Kidney Health Australia — and major published trials. It is not personal medical advice and does not create a doctor–patient relationship. Decisions about specific medication management, including when to withhold or restart medications, are made with your own GP and treating clinicians.

For further patient-facing information: HealthDirect — Acute kidney injury, Better Health Channel, Kidney Health Australia.

---

Sources cited

1. KDIGO 2012 Clinical Practice Guideline for Acute Kidney Injury
2. KHA-CARI Guidelines — Kidney Health Australia
3. RACGP
4. Therapeutic Guidelines (eTG) — Nephrology
5. Australian Medicines Handbook
6. NPS MedicineWise
7. Heart Foundation Australia — Cardiovascular risk guidelines 2023
8. TGA — SGLT2 inhibitor advisory
9. AIHW — Indigenous Australians and CKD
10. HealthDirect — Acute kidney injury
11. Better Health Channel
12. Semler et al. — SMART trial, NEJM 2018
13. Heerspink et al. — DAPA-CKD, NEJM 2020
14. Australian Immunisation Handbook