Protein Energy Wasting

Protein energy wasting is the state of decreased body stores of protein and energy fuels (muscle and fat) in chronic kidney disease, unrelated to dietary intake alone. It affects 30 to 60% of dialysis patients and many with stage G4 to G5 disease. It is among the strongest predictors of mortality.

Diagnosis needs at least three of four categories:

• Low serum albumin (under 38 g/L), prealbumin (under 300 mg/L) or cholesterol (under 2.6 mmol/L)
• Reduced body mass: BMI under 23 kg/m², unintentional weight loss of 5% over 3 months or 10% over 6 months, or body fat under 10%
• Reduced muscle mass: loss of muscle mass of 5% over 3 months or 10% over 6 months, or reduced mid-arm muscle circumference
• Low dietary intake: protein under 0.8 g/kg daily for 2 months in dialysis, under 0.6 g/kg daily in non-dialysis disease, or energy under 25 kcal/kg daily

Causes

• Reduced intake: anorexia (uraemic toxins, cytokines, leptin), dietary restrictions, dental problems, gastroparesis, depression, poverty, hospitalisation, fluid restriction.
• Increased losses and catabolism: metabolic acidosis, inflammation (interleukin-6, tumour necrosis factor alpha), insulin and growth hormone resistance, dialysis losses (amino acids 10 to 12 g in each haemodialysis session; peritoneal protein losses 5 to 15 g daily), comorbid illness, frequent infections.
• Medications and hormonal disturbance: hyperparathyroidism, glucocorticoids, hypogonadism.

• Weight loss, muscle wasting (temporal, interosseous), loss of subcutaneous fat, weakness, fatigue, poor appetite, early satiety, nausea.
• Oedema masking weight loss (assess dry weight), pressure ulcers, poor wound healing, recurrent infection.
• Reduced albumin, anaemia, ESA hyporesponsiveness, depression.

Red flags

• Weight loss over 5% in 3 months, BMI under 20 kg/m² or albumin under 30 g/L.
• Refusal to eat, dysphagia, persistent vomiting, or abdominal pain.
• Infection, unexplained fever, night sweats or malignancy symptoms.
• Pressure ulcers or non-healing fistula site.

• Subjective global assessment or malnutrition inflammation score; three day food diary or dietitian assessment of protein and energy intake; normalised protein catabolic rate (under 0.8 g/kg daily suggests low intake in stable haemodialysis).
• Anthropometry (weight, BMI, mid-arm muscle circumference, skinfolds), handgrip strength, bioimpedance or DXA.
• Biochemistry: albumin, prealbumin, cholesterol, creatinine (low pre-dialysis creatinine may reflect low muscle mass), bicarbonate, CRP, full blood count, ferritin, urea, Kt/V, glucose, thyroid function, vitamin D.
• Exclude other causes: malignancy, tuberculosis, HIV, depression, gastrointestinal disease, diabetic gastroparesis, hyperthyroidism, adrenal insufficiency, chronic infection.

Differential diagnosis

• Simple undernutrition, cachexia of malignancy, hypermetabolic state of sepsis, malabsorption, endocrine disease, advanced heart failure cachexia.

First line: diet and dialysis

• Dietitian review. Protein 0.8 g/kg daily in non-dialysis disease (do not restrict protein further once wasting is present), 1.0 to 1.2 g/kg daily on haemodialysis and 1.2 to 1.3 g/kg daily on peritoneal dialysis, with at least 50% high biological value protein.
• Energy 30 to 35 kcal/kg daily (adjust for age and activity); liberalise dietary restrictions (potassium and phosphate) when controlled with binders, dialysis and drugs, and avoid long fasting.
• Dialysis: Kt/V of at least 1.2, treat acidosis (bicarbonate at least 22 mmol/L), correct anaemia, vitamin D deficiency and hyperparathyroidism, treat infections and dental problems, and provide a meal during dialysis.

Nutritional support

• Oral nutritional supplements, 1 to 2 portions daily (250 to 500 kcal and 10 to 20 g protein), preferably renal specific, between meals or during dialysis.
• If oral intake stays under 70% of requirement after 2 to 4 weeks of supplements, enteral tube feeding (nasogastric or gastrostomy).
• Intradialytic parenteral nutrition or total parenteral nutrition for patients who cannot tolerate enteral feeding, under specialist supervision.
• Peritoneal dialysis: use amino acid dialysate for one exchange daily if oral intake is poor; control glucose load.

Anabolic and appetite measures

• Exercise: resistance and aerobic training 2 to 3 times weekly.
• Mirtazapine 7.5 to 15 mg at night for anorexia or depression (low dose in kidney failure); megestrol acetate 400 mg daily is used for refractory anorexia but increases thrombosis risk.
• Nandrolone decanoate 100 mg intramuscularly weekly for 6 months (50 mg in women) in selected dialysis patients; monitor liver tests, lipids, haematocrit and virilisation.
• Treat depression, review polypharmacy and dental or swallowing difficulty.

Monitoring. Weight and BMI monthly; albumin, prealbumin and nPCR monthly; handgrip strength every 3 months. Failure to gain weight, or to raise albumin to at least 38 g/L, within 3 months warrants escalation.

Referral and escalation. Renal dietitian for all dialysis patients; gastroenterology for persistent vomiting or malabsorption; palliative care discussion when wasting is advanced and reversible causes are excluded.

Special groups

• Children: energy 100 to 120% of requirement for age, early tube feeding, growth hormone (somatropin 0.045 to 0.05 mg/kg daily subcutaneously) after nutrition is optimised.
• Elderly and frail: balance restrictions against intake; conservative kidney management may be appropriate.
• Diabetes: control glucose carefully with enteral feeding; consider gastroparesis.