Rhabdomyolysis and pigment nephropathy

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

Pigment nephropathy is most likely when a high myoglobin burden is combined with aciduria, volume depletion and reduced renal perfusion. Myoglobin disappears from plasma and urine more rapidly than CK, so a patient can have a diagnostic CK rise after dark urine has resolved. CK magnitude helps stratify risk but cannot replace the clinical picture: even a lower value can be important in CKD, sepsis or ongoing muscle ischaemia, while a high value with prompt treatment may not lead to AKI.

The first management priority is the cause. Release a crush only within an organised rescue plan, terminate seizures, cool heat illness, stop a toxic exposure, treat infection and obtain urgent surgical assessment for compartment syndrome or threatened limb. Simultaneously check an ECG and potassium because intracellular potassium release can cause fatal arrhythmia before creatinine rises. Fluids should restore perfusion and dilute tubular pigment, but aggressive administration becomes dangerous once oliguria or lung congestion prevents excretion.

This topic crosses emergency medicine, surgery, toxicology, critical care and nephrology. Fluid composition, electrolyte protocols and any alkalinisation strategy vary locally; use the current UKKA hyperkalaemia and institutional rhabdomyolysis guidance. Drug doses here are framed as supervised pathways rather than invented precision.

Key points

Rhabdomyolysis releases myoglobin, potassium, phosphate, urate and enzymes from injured skeletal muscle; kidney injury reflects pigment toxicity, tubular obstruction and the accompanying hypovolaemia or shock.
Common settings include crush or prolonged immobilisation, seizures, extreme exertion, hyperthermia, limb ischaemia, infection, metabolic disturbance, toxins and drug interactions involving statins.
Muscle pain, weakness and dark urine form a memorable triad but are often incomplete. Examine for swollen tender muscle, reduced limb perfusion, pressure injury and the precipitating neurological or thermal illness.
Urine dipstick detects haem pigment and may be strongly positive despite few or no red cells on microscopy, supporting myoglobinuria rather than urinary bleeding.
Creatine kinase confirms and tracks muscle injury but may rise and peak after presentation. The clinical cause, potassium, renal function, acid–base state and urine output determine immediate risk more directly than one CK number.
Early isotonic crystalloid is important when the patient is depleted and not congested, with repeated reassessment and an individual urine-output strategy; there is no universally safe fixed volume target.
Routine urinary alkalinisation with bicarbonate and routine mannitol are not established standard prophylaxis. Consider any exceptional use only with renal or critical-care oversight and a defined physiological indication.
Early hypocalcaemia often reflects calcium deposition in damaged muscle and should not be corrected solely by a laboratory value; give calcium for symptoms or a separate emergency indication, and anticipate rebound hypercalcaemia during recovery.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

Compression and ischaemia

Crush injury, prolonged immobilisation, limb ischaemia and compartment pressure disrupt muscle perfusion and cell membranes, often with concurrent hypovolaemia.

Exertional, seizure and thermal injury

Extreme exertion, prolonged seizures, hyperthermia and electrical injury create intense energy failure and direct myocyte damage.

Infective and metabolic injury

Severe infection, electrolyte disturbance and inherited metabolic susceptibility can precipitate muscle breakdown, sometimes without trauma or the classic symptom triad.

Medicine and toxin exposure

Statins, particularly with interacting medicines, recreational substances and other toxins can injure muscle; timing, overall exposure and competing causes determine attribution.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Myocyte membrane failure
Energy depletion, mechanical disruption or toxin effects allow intracellular calcium accumulation and destructive enzyme activation within skeletal muscle.
2
Intracellular-content release
Damaged cells release myoglobin, potassium, phosphate, urate and enzymes into the circulation, while fluid shifts into injured muscle.
3
Pigment tubular injury
Filtered myoglobin causes oxidative epithelial toxicity and combines with cellular debris to obstruct tubules, especially during hypovolaemia and acidic conditions.
4
Self-amplifying renal dysfunction
Falling filtration reduces potassium and acid clearance, while shock and ongoing muscle necrosis continue generating the same dangerous solutes.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

Traumatic or compression injuryRed flag

Crush injury, entrapment, prolonged unconsciousness or pressure necrosis causes swollen tender muscle and systemic pigment release. Limb neurovascular compromise or pain out of proportion raises compartment syndrome and demands urgent surgical review.

Exertional or heat-related syndromeRed flag

Severe exercise, heat exposure, hyperthermia, collapse or altered cognition can precede rhabdomyolysis. Heat stroke is a critical illness requiring immediate cooling and multi-organ support, not merely intravenous fluid for a high CK.

Drug and toxin associationRed flag

A statin interaction, stimulant, antipsychotic-associated hyperthermic syndrome, serotonin toxicity, alcohol or illicit drug exposure may be causal. Look for rigidity, autonomic features and co-ingestants rather than attributing all cases to the prescribed statin.

Pigment urine pattern

Dark brown urine and a strongly haem-positive dipstick with few erythrocytes support myoglobin. The pattern is time-dependent and its absence does not exclude muscle breakdown once pigment has cleared.

Electrolyte toxicityRed flag

Rapid potassium and phosphate release, metabolic acidosis and early hypocalcaemia can occur before kidney injury is fully visible. ECG change, weakness or arrhythmia determines emergency treatment, while later rebound hypercalcaemia can complicate recovery.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
Serial creatine kinaseFirst step
Why
Confirm significant skeletal-muscle injury and determine whether release is continuing or resolving.
Interpretation and limitations
Interpret CK against timing, cause, muscle mass and trajectory rather than a universal dialysis threshold. A rising value prompts renewed search for ongoing seizure, compression, heat, ischaemia or drug effect.
02
Urine dipstick and microscopy
Why
Identify a haem-pigment pattern and distinguish myoglobin from intact urinary red cells.
Interpretation and limitations
Haem positivity with few red cells supports myoglobinuria; visible haematuria with many erythrocytes points to urinary bleeding. A negative result later in the course cannot exclude earlier pigment exposure.
03
Potassium, phosphate, calcium, bicarbonate, creatinine and urate
Why
Detect life-threatening release products, acid–base disturbance and pigment-associated AKI.
Interpretation and limitations
Treat severe hyperkalaemia from the whole result and ECG. Early low calcium is often redistributed and may reverse; rising creatinine, phosphate and persistent oliguria indicate escalating renal risk.
04
Twelve-lead ECG and continuous rhythm monitoring
Why
Find conduction toxicity from hyperkalaemia before cardiac arrest occurs.
Interpretation and limitations
Peaked T waves, PR prolongation, P-wave loss and QRS widening are dangerous, but a normal ECG does not neutralise a markedly high or rapidly rising potassium. Repeat after emergency treatment.
05
Focused limb and compartment assessment
Why
Detect ongoing ischaemic muscle necrosis requiring urgent decompression rather than supportive renal care alone.
Interpretation and limitations
Pain out of proportion, pain on passive stretch, tense swelling, sensory or motor change and perfusion abnormality demand immediate surgical evaluation. A palpable pulse does not exclude compartment syndrome.
06
Cause-directed toxicology, cultures and endocrine studies
Why
Find the driver when trauma is absent or the CK continues to rise unexpectedly.
Interpretation and limitations
Select tests from the presentation: drug concentrations or toxicology, cultures, thyroid studies, glucose and ketones, or viral assessment. A broad unstructured panel delays rather than replaces causal history.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

True haematuria

Urinary erythrocytes on microscopy support bleeding, whereas strongly positive dipstick blood with few cells and muscle injury suggests myoglobinuria.

Intravascular haemolysis

Anaemia, low haptoglobin, indirect hyperbilirubinaemia and plasma haemoglobin support haemoglobinuria rather than muscle-derived pigment in urine.

Inflammatory myopathy

Subacute symmetrical weakness, autoimmune features and persistent muscle inflammation suggest immune myositis, though severe cases can themselves cause rhabdomyolysis.

Hepatic enzyme elevation

AST may originate from damaged muscle; creatine kinase trajectory, other liver tests and the clinical context prevent mislabelling isolated rhabdomyolysis as primary hepatitis.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01ImmediateStabilise pigment and electrolyte threatFirst stepRhabdomyolysis is suspected from the setting, symptoms, pigment urine or elevated CK.

11. Perform ABCDE, obtain ECG, potassium, gas, renal profile, calcium, phosphate and CK, and begin continuous monitoring when hyperkalaemia or severe systemic illness is possible.
2Definitive2. Treat hyperkalaemic membrane toxicity and redistribute potassium through the current UKKA emergency protocol while arranging definitive removal if refractory.
33. Restore circulating volume with isotonic crystalloid when examination supports depletion, reassessing pressure, lungs, urine output and cumulative balance after each phase.
44. Involve nephrology early for oliguria, rising potassium, acidosis or overload, because continued large-volume fluid may be unsafe and dialysis decisions are complication-based.

02CauseStop continuing muscle destructionInitial assessment identifies trauma, compression, seizure, heat, ischaemia, drug effect or infection.

11. Release pressure and obtain urgent surgical assessment for threatened limb or compartment syndrome; do not wait for CK to peak before source control.
22. Terminate seizures, initiate active cooling for heat stroke and treat sepsis through the relevant emergency protocol.
33. Stop suspected myotoxic drugs and check interactions, but investigate endocrine, metabolic, inflammatory and toxic causes when the explanation is incomplete.
44. Repeat CK and physiological assessment to confirm that injury is resolving; a continuing rise requires a new search for hidden muscle damage or ongoing exposure.

03RecoveryPrevent late renal and calcium complicationsCK is falling and the acute trigger has been controlled.

11. Reduce fluid as perfusion is restored and pigment release settles, particularly if urine output is poor or weight and respiratory findings show accumulation.
22. Continue potassium, phosphate, calcium and renal monitoring; treat symptomatic calcium disturbance rather than normalising every early low result.
33. Watch for rebound hypercalcaemia, polyuria and delayed compartment or pressure-wound complications during the recovery phase.
4Alternative4. Document the cause and future prevention, including a structured specialist decision about statin rechallenge or alternative lipid therapy if a medicine was implicated.

Key medicines and prescribing safety3 treatments · regimens, roles and cautions

Corrects extracellular depletion, supports renal blood flow and reduces intratubular pigment concentration while muscle release is controlled.

Intravenous isotonic crystalloid

Start promptly when hypovolaemia or major pigment burden is present, using locally approved boluses and ongoing rates titrated to perfusion, urine output, weight and respiratory reassessment.

No fixed multi-litre target is safe for every patient. Slow or stop when oliguria, heart failure or pulmonary congestion emerges; fluid cannot clear potassium or pigment when filtration has failed.

Stabilises the myocardium during dangerous hyperkalaemia while insulin–glucose, other redistribution measures and potassium removal are arranged.

Intravenous calcium salt for hyperkalaemic cardiac toxicity

Give the calcium preparation and repeat strategy specified in the current UKKA or local resuscitation protocol when ECG toxicity is present, with immediate rhythm reassessment.

It does not lower serum potassium. Do not give solely for an asymptomatic early low calcium in rhabdomyolysis, and verify the local choice of calcium chloride versus gluconate and access requirements.

Temporarily shifts potassium into cells while the muscle source is controlled and renal, gastrointestinal or dialysis removal is secured.

Insulin with glucose for severe hyperkalaemia

Use the current UKKA emergency regimen and local glucose adaptation, with scheduled capillary glucose monitoring for several hours after administration.

Hypoglycaemia is common and can be delayed, especially in renal failure. This is a temporising measure, so repeat potassium and do not allow a transient fall to delay dialysis when release continues.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Hyperkalaemic cardiac arrest

Rapid potassium release from muscle, compounded by renal failure and acidosis, can cause malignant arrhythmia before creatinine peaks.

Pigment-associated AKI

Tubular toxicity, obstruction and hypoperfusion can produce severe oliguric AKI and a temporary need for renal replacement therapy.

Compartment syndrome

Muscle swelling within a closed fascial space impairs perfusion and nerves, creating a limb-threatening process that further accelerates necrosis.

Calcium disturbance

Calcium initially enters damaged muscle, causing hypocalcaemia, then may return during recovery and produce rebound hypercalcaemia.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

Repeat potassium and ECG after emergency treatment at the intervals required by the UKKA pathway, anticipating rebound while damaged muscle continues releasing intracellular contents.
Trend CK until a clear peak and sustained fall are established, and pair it with limb, seizure, temperature and exposure reassessment rather than treating the number alone.
Measure urine output, weight, lung findings and cumulative balance closely during crystalloid therapy so pigment prevention does not become iatrogenic pulmonary oedema.
Check creatinine, bicarbonate, phosphate, calcium and magnesium serially, including for rebound hypercalcaemia during renal and muscle recovery.
After statin-associated injury, record interacting medicines and arrange a deliberate cardiovascular-risk and lipid-treatment review instead of unplanned permanent cessation.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

Myoglobin outruns creatine kinase

Myoglobin is cleared quickly, whereas CK often peaks later. Dark urine can disappear before presentation, so a negative pigment dip does not invalidate a strongly compatible history and rising CK.

Potassium may be the first catastrophe

Massive muscle disruption releases potassium immediately, and arrhythmia can precede the creatinine rise used to label AKI. ECG and electrolyte testing belong at the front of the pathway.

Calcium changes direction

Calcium can fall early through deposition in injured tissue and rise later as it remobilises during recovery. Treat the patient and emergency indication, not an isolated asymptomatic early value.

A pulse does not clear the compartment

Compartment pressure can compromise muscle and nerves while large arteries still transmit a palpable pulse. Pain pattern, tense swelling and neurological change require surgical judgement.

Statin attribution needs an interaction review

A new CYP-interacting medicine, dose change, frailty, hypothyroidism or acute illness may convert tolerated therapy into toxicity. Recording the context informs safer future lipid management.

11Common pitfallsFrequent interpretation and management errors.

01
Waiting for muscle pain, weakness and dark urine together misses many cases in unconscious, elderly or critically ill patients.
02
Using CK alone to determine dialysis ignores the actual indications: refractory potassium, acidosis, overload, uraemic complications and overall physiology.
03
Driving a universal high urine-output target with fluid despite anuria or lung congestion can produce severe respiratory failure without clearing pigment.
04
Giving routine calcium for asymptomatic early hypocalcaemia may increase tissue calcium deposition and does not address the underlying muscle injury.
05
Restarting a suspected statin without reviewing interactions and the cardiovascular indication risks recurrence, while permanent unreviewed cessation loses preventable cardiovascular benefit.