Uraemia

Uraemia is the clinical syndrome produced by retention of nitrogenous and other solutes when kidney function falls to the point at which excretion fails, usually at eGFR below 10 to 15 mL/min/1.73 m2 and a blood urea above 30 to 40 mmol/L, though the severity of symptoms correlates poorly with the urea level. The toxins responsible include guanidino compounds, middle molecules (beta-2 microglobulin), protein bound solutes (indoxyl sulphate, p-cresyl sulphate), advanced glycation end products and inflammatory mediators.

Uraemia affects virtually every organ system through toxin accumulation, volume overload, acidosis, anaemia, platelet dysfunction, secondary hyperparathyroidism and chronic inflammation. It develops over weeks in advanced chronic kidney disease and within days in acute kidney injury with catabolism.

The syndrome is relieved by dialysis or transplantation and often improves partially by correction of reversible contributors: anaemia, acidosis, fluid overload, drugs and infection.

• General: anorexia, nausea, vomiting, metallic taste, hiccups, malaise, weight loss
• Neurological: lethargy, impaired concentration, tremor, asterixis, myoclonus, seizures, coma, peripheral neuropathy, restless legs
• Cardiovascular: pericarditis with friction rub, pericardial effusion and tamponade, hypertension, fluid overload, arrhythmia
• Haematological: normochromic anaemia, platelet dysfunction with prolonged bleeding time, gastrointestinal bleeding
• Dermatological: pruritus, yellow grey pallor, uraemic frost (late)
• Respiratory: Kussmaul breathing, uraemic lung, pleuritis
• Endocrine: amenorrhoea, erectile dysfunction, growth failure

Red flags (indications for urgent dialysis): pericardial friction rub or effusion, encephalopathy, seizures, uncontrolled bleeding, refractory vomiting with nutritional failure, refractory hyperkalaemia or acidosis, pulmonary oedema.

• Urea, creatinine, eGFR, electrolytes, bicarbonate, calcium, phosphate, PTH, albumin, blood gas
• Full blood count, coagulation, bleeding time
• Chest radiograph for pulmonary oedema and effusion; ECG for hyperkalaemia and pericarditis (diffuse ST elevation, low voltage in effusion); echocardiography
• Renal ultrasound; urinalysis
• Exclude other causes of encephalopathy (hypoglycaemia, hepatic encephalopathy, sepsis, intracranial lesion)

Differentials: hepatic encephalopathy, hypercalcaemia, drug toxicity (gabapentin, opioids, baclofen accumulate in renal failure), hyponatraemia, hypothyroidism, depression.

Definitive treatment is renal replacement therapy. Start haemodialysis urgently for pericarditis, encephalopathy or bleeding; start electively for symptoms at eGFR 5 to 10 mL/min/1.73 m2. Dialyse daily for the first 2 to 3 days with short, low flux sessions (2 hours, blood flow 150 to 200 mL/min) in patients with blood urea above 40 mmol/L to avoid disequilibrium.

Symptom control

• Nausea: ondansetron 4 mg orally or intravenously (QT monitoring); metoclopramide 5 mg three times daily (half the usual dose) for gastric stasis.
• Hiccups: chlorpromazine 25 mg orally three times daily.
• Pruritus: gabapentin 100 mg orally after each dialysis session (up to 300 mg three times weekly); difelikefalin 0.5 microg/kg intravenously after dialysis three times weekly; emollients and ultraviolet B phototherapy.
• Restless legs: iron repletion, gabapentin 100 mg at night.
• Insomnia and pain: use agents safe in renal failure (paracetamol, fentanyl, hydromorphone); avoid morphine, codeine and tramadol.

Uraemic bleeding

• Desmopressin 0.3 microg/kg intravenously over 30 minutes (effect for 4 to 8 hours); repeat every 12 to 24 hours with tachyphylaxis after 2 to 3 doses.
• Cryoprecipitate 10 units if refractory.
• Conjugated oestrogens 0.6 mg/kg intravenously daily for 5 days (onset 6 hours, lasts 2 weeks) or 25 to 50 mg orally daily.
• Correct anaemia to haemoglobin 100 g/L with erythropoiesis stimulating agents and iron; transfuse only for haemoglobin below 70 g/L.

Uraemic pericarditis and tamponade

• Intensify dialysis daily for 7 to 14 days without heparin (or with minimal heparin).
• Pericardiocentesis or pericardial window for tamponade or effusion persisting beyond 7 to 14 days of intensive dialysis.
• NSAIDs and colchicine are of limited value and risk toxicity.

Seizures: lorazepam 4 mg intravenously (2 mg in older adults); treat the cause and dialyse.

Special groups. Dose adjust all drugs. Avoid magnesium containing laxatives and antacids, nitrofurantoin, and metformin. Older adults and those with limited life expectancy may choose conservative management with symptom directed palliation.