Uraemic Myopathy

Uraemic myopathy is proximal muscle weakness and wasting that accompanies advanced chronic kidney disease. It is multifactorial:

• vitamin D deficiency and secondary hyperparathyroidism
• metabolic acidosis
• protein energy wasting
• chronic inflammation
• insulin resistance
• impaired mitochondrial function
• carnitine deficiency
• deconditioning
• myostatin excess
• toxic accumulation of uraemic solutes

Physical performance falls early (from stage G3), with muscle strength about 30 to 50% lower than that of healthy people in dialysis patients, and predicts hospitalisation and mortality.

Pathophysiology. Type II (fast twitch) fibre atrophy, mitochondrial dysfunction, reduced satellite cell activity, enhanced ubiquitin proteasome breakdown and impaired protein synthesis.

• Proximal weakness: difficulty rising from a chair, climbing stairs and combing hair; waddling gait; falls; reduced walking speed.
• Muscle wasting, easy fatigability, exertional dyspnoea, muscle cramps (particularly during dialysis).
• Pain and tenderness in osteomalacia related myopathy.
• Reflexes preserved; sensation normal unless neuropathy coexists.

Red flags

• Acute weakness with dark urine and creatine kinase over 5 times the upper limit: rhabdomyolysis (statins, fibrates, infection, hypokalaemia).
• Weakness with hyperkalaemia above 6.5 mmol/L or severe hypokalaemia below 2.5 mmol/L.
• Respiratory muscle weakness, dysphagia, or ptosis (myasthenia, inflammatory myositis).
• Rash with proximal weakness (dermatomyositis).

• Strength testing: handgrip strength (low if under 27 kg in men and under 16 kg in women), sit-to-stand time, gait speed (under 0.8 m/s is low), timed up and go.
• Blood tests: creatine kinase (normal or mildly raised), potassium, magnesium, calcium, phosphate (hypophosphataemia causes myopathy), parathyroid hormone, 25-hydroxyvitamin D, bicarbonate, albumin, thyroid function, cortisol if steroid excess is suspected, free and total carnitine.
• Body composition by bioimpedance or DXA (low appendicular lean mass index).
• Electromyography: myopathic pattern (short, low amplitude polyphasic potentials); MRI or biopsy rarely needed.

Differential diagnosis

• Statin and fibrate myopathy, glucocorticoid myopathy, hypothyroid or hyperthyroid myopathy, osteomalacia, hypokalaemic myopathy, inflammatory myositis, amyloid myopathy, motor neuropathy, myasthenia gravis, aluminium or colchicine toxicity.

First line: correct the metabolic drivers

• Bicarbonate at least 22 mmol/L: sodium bicarbonate 500 mg to 1 g orally two to three times daily.
• Cholecalciferol 50 000 units weekly for 6 to 8 weeks when 25-hydroxyvitamin D is under 25 nmol/L, then 800 to 2000 units daily; alfacalcidol 0.25 to 0.5 microg daily if parathyroid hormone is high and calcium is low.
• Parathyroid hormone to 2 to 9 times the upper limit in dialysis; phosphate 1.1 to 1.7 mmol/L (avoid over correction, because hypophosphataemia worsens weakness).
• Nutrition: protein 0.8 g/kg daily in non-dialysis chronic kidney disease and 1.0 to 1.2 g/kg daily on dialysis, energy 30 to 35 kcal/kg daily; oral supplements if intake is low.
• Dialysis adequacy: Kt/V of at least 1.2; control inflammation and infection.

Exercise (most effective intervention)

• Resistance training 2 to 3 sessions weekly (8 to 10 exercises, 2 to 3 sets of 8 to 12 repetitions) and aerobic exercise 30 to 45 minutes, 3 times weekly, building gradually. On haemodialysis, intradialytic cycling for 20 to 30 minutes during the first 2 hours of the session.
• Physiotherapy input for patients with falls or frailty.

Drugs

• Stop or reduce myotoxic drugs (statin dose reduction, avoid fibrate with statin, colchicine in kidney failure).
• Levocarnitine 20 mg/kg intravenously at the end of each dialysis session for 3 to 6 months in patients with documented carnitine deficiency and persistent weakness or intradialytic cramps; stop if no response after 6 months.
• Nandrolone decanoate 100 mg intramuscularly weekly for 6 months in men with protein energy wasting (50 mg in women) may improve lean mass; monitor liver tests, lipids, haematocrit and virilisation.
• Intradialytic cramps: reduce ultrafiltration rate, review dry weight, sodium profiling or higher dialysate sodium, stretching, vitamin E 400 units daily.

Monitoring. Handgrip strength and gait speed every 3 to 6 months; reassess bicarbonate, vitamin D and nutrition.

Referral and escalation. Rheumatology or neurology for suspected inflammatory myositis or progressive weakness; urgent nephrology for rhabdomyolysis; dietitian and physiotherapy for all patients with documented weakness.

Special groups

• Elderly: sarcopenia and falls; protein and resistance exercise are priority.
• Transplant recipients: steroid and calcineurin inhibitor myopathy.
• Children: growth failure and delayed motor development.