Contrast nephropathy, rhabdomyolysis and acute tubular

• Acute tubular injury (ATI) is damage to the kidney's urine-forming tubules from reduced blood flow, toxins (drugs, contrast, heavy metals) or pigments (myoglobin and haemoglobin). It is one of the main forms of intrinsic acute kidney injury.
• Contrast-associated acute kidney injury (CA-AKI) is any rise in creatinine within 48 hours of iodinated contrast; the smaller subset that is truly caused by the contrast (contrast-induced AKI, CI-AKI) is much rarer than the coincidence rate suggests.
• Rhabdomyolysis releases myoglobin and other muscle contents; if it is recognised early and the patient is rehydrated vigorously, much of the resulting kidney injury can be prevented.
• Drug-induced tubular injury is prevented best by recognising the responsible drug classes and by dosing, monitoring and hydration.
• Whatever the cause, daily management follows the same sequence as in the acute kidney injury topic (plain name, no link): remove or blunt the insult, restore renal perfusion, manage potassium, acidosis and volume, and use dialysis when those measures fail.

By the end of this page you should be able to:

1. Define acute tubular injury and explain how contrast, drugs, myoglobin and haemoglobin each damage tubules, and distinguish contrast-associated from contrast-induced AKI.
2. Stratify a patient's risk of contrast-associated and contrast-induced AKI from eGFR and clinical state, and translate that into a prevention plan including hydration volumes.
3. Explain the causes, clinical picture and biochemical findings of rhabdomyolysis, including the role of myoglobin and Tamm-Horsfall protein, and why CK is the most useful marker.
4. Manage rhabdomyolysis with fluid targets, electrolyte monitoring and a clear position on bicarbonate, mannitol and diuretics.
5. List the main nephrotoxic drugs and toxins, their typical tubular mechanism, and the practical safeguards for each.
6. Distinguish contrast nephropathy from atheroembolism by timing and clinical findings, and state when renal replacement therapy is needed.

The term acute kidney injury (AKI) names the syndrome (a rapid fall in kidney function over days to weeks, defined by KDIGO), while acute tubular injury names one of the mechanisms that can produce it. ATI sits in the intrinsic renal group of causes. Several distinct mechanisms fall within it in this page:

• Contrast nephropathy / contrast-induced AKI (CI-AKI). Tubular damage attributed to iodinated contrast media.
• Drug-induced (toxic) ATI. Direct tubular toxicity or intratubular precipitation from a drug or toxin.
• Pigment (myoglobin or haemoglobin) nephropathy. Tubular obstruction and oxidative injury from free muscle or red cell pigment, classically from rhabdomyolysis or haemolysis.
• Ischaemic ATI. Prolonged or severe underperfusion (the extreme of a prerenal state), particularly in sepsis, shock, burns, cardiac surgery or dehydration.
• Crystal and light-chain injury. Uric acid, calcium oxalate, or myeloma light chains precipitating in tubules, which can coexist with the other forms.

This distinction is central to modern teaching. Three terms are now used:

• Contrast-associated acute kidney injury (CA-AKI): any AKI (by KDIGO creatinine criteria) that appears within 48 hours of contrast administration. It is a correlation, not a diagnosis of cause. ^[2]
• Post-contrast acute kidney injury (PC-AKI): an alternative name for CA-AKI used in radiology guidelines. ^[3]
• Contrast-induced AKI (CI-AKI): the subset that can genuinely be causally linked to the contrast. The historic name "contrast nephropathy" is interchangeable with CI-AKI in everyday practice. ^[1][3]

Because many patients who need contrast are unwell, dehydrated or septic at the same time, a large fraction of post-contrast creatinine rises are coincidental AKI from another cause. Recognising this matters, because over-inclusive diagnosis has in the past driven withholding of needed imaging. ^[2]

The older diagnostic definitions are still worth knowing:

• ESUR 2002 definition: a rise in serum creatinine of 25% or 44.2 micromol/L above baseline within 72 hours of contrast, after excluding surgery, nephrotoxic drugs and other factors. ^[3]
• KDIGO 2012 / CI-AKI: an absolute rise of at least 26.5 micromol/L within 48 hours, or a relative rise of more than 50% within 7 days. ^[3]

In practice the KDIGO-style definition is now the one to use, and many radiology units define the event as a creatinine rise within 48 hours of contrast.

All iodinated contrast agents are nephrotoxic to some degree. The mechanism is a combination of medullary vasoconstriction (a shift in vasoactive mediators towards vasoconstriction, reducing renal blood flow and glomerular filtration, especially in the outer medulla), medullary hypoxia, direct tubular cytotoxicity, reactive oxygen species, and increased tubular viscosity. Newer agents are nonionic with lower osmolality, and the risk is lower with them than with older high-osmolal agents. ^[1][3]

Renal function usually returns to baseline. Acute tubular necrosis from contrast must also be distinguished from cholesterol (athero)embolism, in which creatinine rises more than 48 hours after catheterisation and may be accompanied by livedo reticularis or brittle purple toes. ^[1]

Contrast-associated injury. In cohorts undergoing contrast-enhanced computed tomography, using stage I KDIGO serum creatinine criteria, the risk of CA-AKI is approximately 5% with an eGFR equal to or above 60, 10% at 45 to 59, 15% at 30 to 44, and 30% at under 30 mL/min/1.73 m2. ^[2] These figures describe coincident AKI and overstate the true contrast effect. For CI-AKI specifically, well-controlled studies describe a risk near 0% with eGFR equal to or above 45, 0 to 2% at 30 to 44, and 0 to 17% under 30 mL/min/1.73 m2; these studies are underpowered in severe kidney disease, and no randomised trial separates CA-AKI from CI-AKI with eGFR under 30. ^[2]

All iodinated agents are nephrotoxic, but newer nonionic low-osmolal agents carry less risk than older high-osmolal agents, whose osmolality is about 1400 to 1800 mOsm/kg. Exposure to more than 100 mL of a high-osmolal agent is a particular risk factor. ^[1]

Rhabdomyolysis. About 10% to 50% of patients with rhabdomyolysis develop acute kidney injury. ^[4] Rhabdomyolysis with statins is rare: the overall reported incidence of fatal rhabdomyolysis is 0.15 deaths per million statin prescriptions. ^[4]

Other toxic injury. Drug-induced tubular injury cannot be summarised by a single global rate, because it varies with the drug, dose, duration, baseline kidney function and monitoring. It is a standard differential diagnosis in hospital-acquired AKI, and the risk is greatest when several insults coincide (hypoperfusion, dehydration and a nephrotoxin together).

Risk rises as baseline filtration falls. Non-contrast factors that add risk include volume depletion, recent AKI, obstruction, and simultaneous exposure to multiple nephrotoxins. ^[2] Active risk factors from the Merck Manual review are:

• older age, chronic kidney disease, diabetes mellitus, heart failure;
• volume depletion or effective arterial hypovolaemia;
• multiple myeloma;
• high doses of a high-osmolal agent (more than 100 mL);
• concomitant nephrotoxic medications. ^[1]

Medication and comorbidity interactions differ by route. The 2018 ESUR guideline proposed eGFR under 45 mL/min/1.73 m2 for arterial injection of contrast, or under 30 mL/min/1.73 m2 for intravenous injection, as independent CI-AKI risk thresholds based on route. ^[3] In this page the simpler universal thresholds of the ACR/NKF consensus (under 30 for prophylaxis, with case-by-case consideration at 30 to 44) drive the prevention plan. ^[2]

The same tubules that are blocked by contrast are damaged by many common drugs. The pattern is usually proximal tubular injury (direct cytotoxicity or mitochondrial damage) or intratubular precipitation of an insoluble drug or metabolite, often in a dehydrated or hypoperfused patient. Major classes include: ^[6][2]

In the ACR/NKF framework, non-essential potentially nephrotoxic medications (NSAIDs, diuretics, aminoglycosides, amphotericin, platins, zoledronate, methotrexate) should be withheld 24 to 48 hours before and 48 hours after contrast exposure when clinically feasible. ^[2]

Rhabdomyolysis is the rapid breakdown of skeletal muscle, releasing myoglobin, potassium, phosphate, urate and creatine kinase into the blood. ^[4] Causes include:

• Trauma and crush injury (including prolonged immobilisation, building collapse, earthquakes);
• Severe exertion (marathon running, military training, prolonged seizures);
• Drugs and toxins (statins and fibrates, especially in combination; antipsychotics; intravenous drug use; alcohol; cocaine; snake or insect venom);
• Metabolic and inherited muscle defects (hypokalaemia, hypophosphataemia, mitochondrial defects, malignant hyperthermia);
• Infections (influenza, COVID-19, sepsis);
• Thermal injury and heat stroke;
• Prolonged surgical or tourniquet positions.

Haemolysis produces a similar pigment nephropathy from haemoglobin. Myoglobin and haemoglobin are small enough to pass freely into the glomerular filtrate; when the renal tubule is acidic and flow is low, they precipitate with Tamm-Horsfall protein into casts, obstruct the lumen, and release iron-derived free radicals that injure the tubular epithelium. ^[4][5]

Iodinated contrast produces a characteristic sequence. First there is an initial transient vasodilation with a brief rise in renal blood flow, then sustained vasoconstriction with increased afferent resistance and reduced medullary oxygen delivery. Medullary hypoperfusion is amplified by contrast-induced release of adenosine and endothelin, and by reduced nitric oxide and prostaglandin effect. Hypoxia increases production of reactive oxygen species, which overwhelm local antioxidant defences and cause mitochondrial damage, ATP depletion and tubular cell injury. Contrast is also directly cytotoxic to tubular epithelium, producing characteristic vacuolation of cells, and its high viscosity slows tubular flow. The combination of hypoxic, oxidative and direct injury produces the acute tubular damage that may lead to a rise in creatinine. These changes are most marked in the outer medulla, where oxygen tension is normally low. ^[3]

Different toxins use different routes but converge on the same end-points (cell energy failure, membrane damage, cell death and intratubular obstruction):

• Proximal tubular uptake and accumulation, as with aminoglycosides (concentrated in lysosomes of proximal cells) and tenofovir, produces swelling, rupture of lysosomes and mitochondrial injury.
• Vasoconstriction, as with NSAIDs and calcineurin inhibitors, reduces renal blood flow and behaves largely like a prerenal injury at first; in a dehydrated patient this can tip into ATN.
• Direct cytotoxicity and DNA cross-linking, as with cisplatin and other platinums, produce necrosis of proximal cells, often dose-dependent and cumulative.
• Intratubular crystal precipitation, as with high-dose methotrexate, acyclovir and sulphadiazine in concentrated or acidic urine, causes obstruction and local inflammation.
• Amphotericin B forms pores in membranes and produces vasoconstriction and magnesium and potassium wasting.
• Heme proteins (myoglobin, haemoglobin) are filtered in large amounts, precipitate with Tamm-Horsfall protein in acidic urine and release free radicals that injure tubular cells. ^[4][6]

The common theme is demand versus reserve. A healthy, well-hydrated kidney with abundant perfusion clears contrast, drugs and pigment easily. Injury becomes likely when baseline filtration is already reduced, volume is depleted, the medulla is hypoxic, several toxins arrive together, or the kidney is subjected to an extra haemodynamic challenge. This is also why stopping non-essential toxins before contrast or surgery matters: the kidney's reserve is an organ-level balance, not a fixed threshold. ^[2][6]

CK is the most sensitive and useful marker of muscle injury: in the absence of myocardial or brain infarction, CK above 5000 U/L indicates serious muscle injury. ^[4] Serum myoglobin rises and falls quickly (half-life of a few hours), so CK is the more useful retrospective and prognostic marker; urine myoglobin testing is not necessary when CK is clearly elevated. A dipstick test for haemoglobin is usually positive in rhabdomyolysis because myoglobin cross-reacts, but microscopy shows no red blood cells (or only a few), separating pigmenturia from glomerular bleeding. ^[4]

Two factors are repeatedly emphasised in myoglobinuric AKI: hypovolaemia (dehydration) and aciduria. A volume-depleted patient has maximal reabsorption of sodium and water, so tubule flow is slow, urine is concentrated and acidic, and filtered myoglobin has time to precipitate with Tamm-Horsfall protein. Bicarbonate has therefore been proposed to alkalinise both the urine and the serum, preventing cast formation and reducing free-radical generation. ^[4][5] Whether this works in practice is discussed below; current evidence is weak.

Most drug- and contrast-induced tubular injury is silent: there are no specific symptoms, and the injury is detected on routine creatinine testing. When symptoms occur they reflect the underlying cause or complications rather than the kidney injury itself.

Suspect contrast nephropathy if serum creatinine rises 24 to 48 hours after a contrast study. ^[1] Most patients remain asymptomatic. The differential importance is distinguishing it from atheroembolism, whose creatinine rise usually begins more than 48 hours after femoral catheterisation and may be accompanied by livedo reticularis, digital infarcts or eosinophilia. ^[1] Other causes of a post-contrast creatinine rise (sepsis, dehydration, heart failure, obstruction) are usually separable by clinical assessment. ^[2]

The classic triad is muscle pain, muscle weakness and dark brown urine, but all three need not be present and older patients are often weak rather than painful. Other clues include:

• swollen, tense or tender muscle compartments;
• fever, nausea or tachycardia;
• tea-coloured or cola-coloured urine;
• hyperkalaemia, hyperphosphataemia, hypocalcaemia and metabolic acidosis;
• arrhythmias or oliguria as kidney injury develops. ^[4][6]

Drug-induced injury is usually discovered with a drug history and routine monitoring. Take the full prescription, over-the-counter, herbal and recreational drug history, because many patients do not volunteer NSAIDs, diuretics or proton pump inhibitors. The first suspicion point is a creatinine rise after starting, escalating or combining a known nephrotoxin. ^[6]

Drug- and pigment-induced ATI must be separated from other causes of AKI, including prerenal hypoperfusion and obstruction, and from glomerular and interstitial disease. The table focuses on the common confusion points within tubular and toxin-related disease.

In any patient with known or suspected toxin-related AKI:

• creatinine and eGFR (or creatinine clearance discussion as in the AKI topic), urea, electrolytes including potassium, calcium and phosphate, full blood count, glucose and acid-base status;
• urine dipstick for blood, protein, leucocytes, nitrites and glucose, with microscopy for casts and cells; ^[6]
• volume status assessment by examination, weight trend and fluid balance;
• drug and contrast exposure history with dates;
• renal ultrasound when obstruction is possible, or when the cause is unclear, with timing according to the acute kidney injury topic. ^[6]

Before elective contrast in at-risk patients, use a properly calibrated serum creatinine and calculate eGFR (CKD-EPI or MDRD) rather than relying on creatinine alone. ^[2] Screen on eGFR rather than creatinine, and prefer eGFR-based risk stratification. For patients who already have AKI or an eGFR below 30 mL/min/1.73 m2, non-essential nephrotoxic medications should be withheld. ^[2]

• creatine kinase (most sensitive marker; CK above 5000 U/L indicates serious muscle injury);
• baseline and serial renal function;
• potassium, phosphate, calcium (initially hypocalcaemia with hyperphosphataemia; hypercalcaemia can occur during recovery);
• urate and blood-gas acid-base status;
• liver function (especially if heat stroke or drugs are involved);
• compartment (pressure) measurement when a limb is swollen and tense. ^[4][6]

In patients with rhabdomyolysis, reported CK values do not correlate tightly with whether AKI develops; urine myoglobin is not required for diagnosis.

Drug-level monitoring (gentamicin trough or AUC, vancomycin trough or AUC, methotrexate levels, calcineurin inhibitor troughs), renal function trends, electrolytes (potassium, magnesium for amphotericin and calcineurin inhibitors, phosphate for tenofovir and foscarnet), and urine pH for methotrexate. For cisplatin, baseline and serial kidney function between cycles.

Renal biopsy is reserved for cases where diagnosis remains unclear after assessment, imaging and blood tests, or where histology would change treatment. It is not needed when a drug or contrast temporal relationship is convincing and the patient is improving. ^[6]

There is no separate staging system for ATI; stage the underlying AKI using KDIGO (creatinine and urine output) as described in the acute kidney injury topic. A practical risk stratification for contrast nephropathy uses eGFR and the CA-AKI versus CI-AKI distinction. ^[2]

• Prophylaxis threshold: patients not on dialysis who have AKI or an eGFR under 30 mL/min/1.73 m2. ^[2]
• Borderline range 30 to 44: in individual high-risk circumstances (recent AKI, many risk factors, borderline eGFR) prophylaxis may be considered at the ordering clinician's discretion. ^[2]
• Stable eGFR 30 or above: prophylaxis not indicated; give usual care. ^[2]

The risk stratification for contrast should not be raised on the basis of diabetes alone: in a propensity-matched study of stable eGFR 30 to 44, diabetes did not independently increase CI-AKI risk after contrast-enhanced CT. ^[2]

For rhabdomyolysis, there is no single diagnostic creatine kinase threshold for kidney injury, but CK above 5000 U/L indicates serious muscle injury and was associated with an increased risk of renal failure in a cohort of trauma patients (peak CK above 5000 U/L). ^[4] A renal failure incidence of about 12% in injured patients with a raised CK has been reported in that cohort, with nearly half of those with creatinine rise requiring dialysis. ^[4]

1. Remove the insult (stop the offending drug, avoid further contrast, unblock any compartment).
2. Restore renal perfusion (correct hypovolaemia, treat sepsis, heart failure or tamponade, support blood pressure).
3. Relieve obstruction if present (bladder scan, catheter, nephrostomy, stent).
4. Manage complications of established AKI (hyperkalaemia, acidosis, pulmonary oedema, urea) as set out in the acute kidney injury topic.
5. Dialyse when medical therapy fails (uncontrolled potassium, acidosis, pulmonary oedema, fluid overload, or uraemic symptoms).

Supportive measures include adjusting doses of renally cleared drugs and maintaining nutrition and water balance; the role of diuretics in AKI is detailed in the acute kidney injury topic.

The best treatment is to avoid the injury. Approach:

• Avoid contrast when it will not change management (for example, choosing ultrasound or non-contrast imaging when either answers the question). ^[1]
• Use the safest agent: a nonionic agent with the lowest available osmolality at the lowest effective dose. ^[1]
• Stratify by eGFR: screen all patients with a calibrated eGFR. Prophylaxis is indicated for those with AKI or eGFR under 30 who are not on dialysis; consider it at 30 to 44 in high-risk circumstances. Prophylaxis is not indicated for stable eGFR 30 or above, for patients on chronic dialysis, or for patients at high risk of heart failure. ^[2]
• Volume expansion with isotonic saline when prophylaxis is indicated. Typical regimens begin 1 hour before and continue 3 to 12 hours after contrast administration. Doses range from fixed (500 mL before and after) to weight-based (1 to 3 mL/kg per hour). Longer regimens (approximately 12 hours) lower CA-AKI compared with shorter ones, but longer protocols are often impractical in outpatients. Oral hydration is not well studied in eGFR under 30 or in AKI, so intravenous saline is preferred for high-risk patients. ^[2] Saline amounts in this range are compatible with a daily target of several litres in at-risk hospital inpatients. ^[5]
• Do not use sodium bicarbonate as first-line for intravenous contrast prophylaxis: it is probably similar to saline but requires pharmacist compounding and is not preferred. ^[2]
• N-acetylcysteine has no proven benefit versus placebo in modern trials; it is sometimes still offered in very high risk cases, but should not be depended on. ^[1][2]
• Withhold non-essential nephrotoxic medications (NSAIDs, diuretics, aminoglycosides, amphotericin, platins, zoledronate, methotrexate) 24 to 48 hours before and 48 hours after contrast when clinically feasible. ^[2]
• RAAS inhibitors: evidence is conflicting; in patients at risk, consider withholding them for at least 48 hours before elective contrast-enhanced imaging, and restart if no CA-AKI occurs or once kidney function returns to baseline. ^[2]
• Metformin: withhold in AKI or eGFR under 30; if eGFR is 30 to 59, decision-making should be individualised because the risk of CI-AKI is sufficiently low. ^[2]
• Continuous venovenous haemofiltration has no proven benefit over less invasive strategies and is not used for prevention. ^[1]
• Dialysis after contrast is not preventive and is not routinely required in chronic dialysis patients.

Treatment priorities:

1. Address the cause (remove crush, terminate seizures, stop the offending drug, treat heat stroke or compartment syndrome urgently).
2. Support ABCs and correct hypovolaemia early. Fluid resuscitation is the most effective intervention to prevent myoglobinuric AKI. ^[4][5]
3. Aggressive but monitored volume expansion with crystalloids (lactated Ringer's or normal saline), with regimens reported in studies from 6 to 24 litres per day. ^[5] Targets include correcting hypovolaemia and maintaining a high urine flow. Urine output is a good sign of recovery, targeted at 1 to 3 mL/kg per hour, up to 300 mL per hour. ^[5]
4. Avoid both extremes of fluid administration. High-volume therapy of 3 mL/kg per hour or more was associated with worse renal outcomes and lower survival than lower volume therapy in a propensity-matched cohort; Iraj and colleagues suggest at least 3 litres per day for mild and at least 6 litres per day for severe rhabdomyolysis (CK at least 15000 U/L). ^[5]
5. Electrolyte management: treat hyperkalaemia promptly (calcium, insulin with glucose, dialysis when needed), monitor phosphate and calcium, and replete as required; avoid premature calcium replacement except for ECG changes.
6. Bicarbonate: controversial. Alkalinising urine is theoretically attractive but unsupported by robust clinical evidence; combined bicarbonate and mannitol showed no benefit over saline in prevention of renal failure, dialysis or mortality. Sodium bicarbonate can worsen hypocalcaemia and should be avoided if hypocalcaemia, alkalaemia or metabolic alkalosis is already present. Its role should be decided by the treating clinician. ^[4][5]
7. Mannitol: considered (especially in neurosurgical or compartment settings) but unproven; avoid in established early AKI because it can reduce renal cortical ATP and worsen function. ^[4][5]
8. Loop diuretics: not routinely beneficial; only for volume overload; evidence is weak. ^[5]
9. Dialysis for AKI complications as in the acute kidney injury topic (uncontrolled potassium, acidosis below pH 7.2, pulmonary oedema, fluid overload or uraemic symptoms).

A flowchart summarises the practical approach.

• Aminoglycosides: choose a non-nephrotoxic alternative if clinically equivalent; use extended interval dosing; check trough or AUC, kidney function and urine output; avoid volume depletion and concurrent contrast.
• Vancomycin: dose to trough or AUC targets; check kidney function during therapy; avoid combining with aminoglycosides or high-risk contrast.
• Amphotericin B: prefer lipid formulations in at-risk patients; saline prehydration; monitor potassium, magnesium and kidney function.
• Cisplatin: vigorous hydration before, during and after dosing; magnesium supplementation; dose adjust by kidney function and avoid early repeat courses.
• Methotrexate: alkalinise urine and maintain high urine flow; give leucovorin rescue per local protocol; monitor methotrexate and creatinine levels.
• Calcineurin inhibitors: trough-level monitoring with dose reduction as needed; avoid NSAIDs and unnecessary contrast.
• Antivirals and antiretrovirals: slow intravenous infusion with hydration, alkalinise where appropriate, and check kidney function and phosphate.
• NSAIDs and RAAS inhibitors: avoid in at-risk patients and pause during intercurrent illnesses; consider withholding ACE inhibitors or ARBs before elective contrast in at-risk patients.
• Contrast itself is managed by the prevention protocol above; if a contrast study is unavoidable in high-risk renal patients, the case should be discussed between the requesting clinician and radiology, and the lowest effective dose used.

Dialysis should be started on the patient's clinical condition, not on a single creatinine or urea number. The indications are: potassium that will not stay under control (severe, rising or with ECG changes); fluid in the lungs or fluid overload not controllable with diuretics; acidosis that does not respond to treatment (pH below 7.20); and symptoms or complications of uraemia (persistent vomiting thought to be due to uraemia, confusion or encephalopathy, pericarditis, seizures). Consult nephrology or critical care when any of these appear. ^[6]

• Hyperkalaemia, the most dangerous acute complication of rhabdomyolysis and established ATI, especially with oliguria.
• Hypocalcaemia and hyperphosphataemia in rhabdomyolysis (with possible hypercalcaemia during recovery).
• Metabolic acidosis, usually moderate (bicarbonate 15 to 20 mmol/L in ATN, worse with sepsis or ischaemia). ^[6]
• Fluid overload and pulmonary oedema when fluids are given without urine output.
• Uraemic complications (pericarditis, encephalopathy) in prolonged severe injury.
• Compartment syndrome in rhabdomyolysis (a surgical emergency).
• CKD after the acute event: even mild or reversed AKI increases the long-term risk of chronic kidney disease. ^[6]

• Contrast nephropathy (CI-AKI): usually reversible, with renal function returning towards baseline; a rise more than 48 hours after catheterisation suggests atheroembolism instead.
• Drug-induced ATI: generally reversible if the offending agent is stopped early; delayed recognition (aminoglycosides), high-dose cisplatin or repeated methotrexate courses can cause incomplete recovery.
• Rhabdomyolysis: if recognised and rehydrated early, kidney injury is often prevented; once established oliguric AKI develops, recovery depends on the underlying muscle injury, sepsis and comorbidities.
• Ischaemic ATI: prognosis follows the trigger (sepsis, shock, surgery); non-oliguric injury carries a better outlook than oliguric or anuric disease.

• Protect perfusion and avoid prolonged underperfusion in sepsis, shock, burns, trauma and major surgery. ^[6]
• Avoid nephrotoxins (NSAIDs especially) in hypovolaemic, older or CKD patients, and pause them during intercurrent illness.
• Use the contrast prevention protocol whenever kidney function is at risk (eGFR thresholds above).
• Monitor high-risk inpatients with daily creatinine and urine output after exposures. ^[6]
• Prevent rhabdomyolysis in at-risk settings (heat illness, exertion, seizure management) by early cooling and fluids; the value of prophylactic aggressive hydration before extreme exertion is not established beyond general measures.
• Review all medicines after any AKI episode and advise patients about the risks of dehydration and over-the-counter NSAIDs.

• Children: eGFR is best estimated with the Bedside Schwartz equation rather than adult equations. The ACR/NKF thresholds and principles should not be changed, only the estimation method. Diagnostic thresholds and fluid management in children should follow paediatric nephrology guidance and local practice. ^[2][6]
• Older adults: the largest group with AKI, through impaired thirst, dependence on carers and limited renal reserve; hypernatraemia and AKI often coexist.
• Pregnancy: imaging decisions involving contrast are made case by case with obstetric and nephrology teams; drug choices are selected for pregnancy safety.
• Patients with chronic kidney disease: already at higher risk; monitor more closely for several days after contrast and avoid further renal insults during that window.

• Clinical assessment carries the diagnosis: pulse, postural blood pressure, jugular venous pressure, skin turgor, mucous membranes and urine output. Repeated weight and a simple fluid balance chart are the cheapest monitors available.
• Measure creatinine where possible; where unavailable, trends in urine output and signs of obstruction carry the diagnosis.
• Urine dipstick and a plain ultrasound (including a bedside bladder scan or even a catheter) detect obstruction. A post-void residual above 100 mL is a prompt to relieve it. ^[6]
• Urine microscopy by sediment, where available, separates brown granular casts of tubular injury from red cell casts of glomerulonephritis. In rhabdomyolysis, a brown dipstick positive for haemoglobin with few red blood cells supports pigmenturia.
• Fluids: oral and enteral hydration are adequate for many prerenal cases; intravenous normal saline restores perfusion in shock, then hypotonic fluids replace the free water deficit. Where only normal saline exists, restore volume first and add water by mouth.
• Drug access: use what is available on the essential list; avoid aminoglycosides if any alternative exists; monitor hydration rather than drug levels when laboratory support is limited.
• Contrast studies: prefer a single, well-planned low-dose study; oral or simple intravenous hydration may be the only available prophylaxis; discuss with radiology how much volume can realistically be given.
• Rhabdomyolysis: early oral hydration may suffice for mild cases; severe cases need large intravenous volumes (6 litres or more per day) and close electrolyte monitoring; where these cannot be provided, early referral is essential.
• Dialysis: temporary catheter dialysis or peritoneal dialysis may be the available modality; refer early for anuria, no response to fluids, suspected intrinsic disease, severe hyperkalaemia, or acidosis.

• Acute tubular injury is tubular epithelial damage from ischaemia, toxins or pigments and is a major intrinsic cause of AKI.
• Contrast-associated AKI (any AKI within 48 hours of contrast) is far more common than true contrast-induced AKI, which is rare with eGFR above 45.
• Risk of CA-AKI rises with eGFR: about 5%, 10%, 15% and 30% for eGFR equal or above 60, 45 to 59, 30 to 44 and under 30 mL/min/1.73 m2 respectively; CI-AKI risk is near 0% above 45, 0 to 2% at 30 to 44 and 0 to 17% under 30. ^[2]
• Newer contrast agents are nonionic with lower osmolality (about 1400 to 1800 mOsm/kg for older high-osmolal agents); all are nephrotoxic, and doses above 100 mL of high-osmolal agent add risk. ^[1]
• Contrast nephropathy is diagnosed by a creatinine rise 24 to 48 hours after contrast and must be separated from atheroembolism, whose rise begins later.
• Prophylaxis is indicated for AKI or eGFR under 30 (not on dialysis): volume expansion with isotonic saline (1 to 3 mL/kg per hour, or 500 mL before and after), 1 hour before to 3 to 12 hours after; longer (approximately 12 hours) is better. N-acetylcysteine has no proven benefit, and sodium bicarbonate is not preferred. ^[2]
• Withhold non-essential nephrotoxins 24 to 48 hours before and 48 hours after contrast; decide ACE inhibitors or ARBs and metformin case by case.
• Rhabdomyolysis affects about 10% to 50% of patients' kidneys; CK above 5000 U/L indicates serious muscle injury; myoglobin precipitates with Tamm-Horsfall protein in acid, low-flow urine and generates free radicals.
• Early vigorous crystalloid (lactated Ringer's or saline) is the treatment of choice for rhabdomyolysis; target urine output 1 to 3 mL/kg per hour up to 300 mL per hour; avoid excessive volumes above about 3 mL/kg per hour. ^[5]
• Bicarbonate and mannitol are unproven and controversial; bicarbonate should not be given with hypocalcaemia, alkalaemia or metabolic alkalosis; loop diuretics are not routine.
• Common nephrotoxic drugs (aminoglycosides, vancomycin, amphotericin, cisplatin, high-dose methotrexate, calcineurin inhibitors, antivirals, NSAIDs) injure tubules through uptake, vasoconstriction, crystal precipitation or direct toxicity; dosing, monitoring and hydration reduce risk.
• Management of established AKI is the same as in the acute kidney injury topic: remove the insult, restore perfusion, relieve obstruction, control complications and dialyse when medical therapy fails.
• Kidney function should be rechecked after recovery, because even mild AKI increases long-term chronic kidney disease risk.

Acute kidney injury (the general syndrome, staging, hyperkalaemia and dialysis indications, referenced throughout this page); drug-induced acute interstitial nephritis; glomerulonephritis and vasculitis; cholesterol atheroembolism; myeloma cast nephropathy; compartment syndrome and crush injury; heat illness.