Uraemic Syndrome

Uraemic syndrome is the multisystem clinical state caused by retention of uraemic toxins when kidney function falls to the point of failure, generally eGFR under 10 to 15 mL/min/1.73 m² or acute kidney injury with sustained oliguria.

Urea itself is only a marker; the toxicity is mediated by protein bound solutes (indoxyl sulphate, p-cresyl sulphate), guanidino compounds, middle molecules (beta-2 microglobulin, parathyroid hormone, cytokines), advanced glycation end products, and disturbed fluid, electrolyte, acid base and endocrine homeostasis. Symptoms improve after renal replacement therapy, but many patients present only when disease is advanced.

Pathophysiology. Impaired clearance of toxins combined with loss of tubular secretion, metabolic and endocrine functions of the kidney (erythropoietin, calcitriol, renin), and a pro inflammatory milieu. Gut microbial metabolism contributes through production of precursors of protein bound toxins.

• General: fatigue, malaise, weakness, pallor with a sallow tint, weight loss, sleep disturbance, loss of libido.
• Gastrointestinal: anorexia, nausea and vomiting, metallic taste, hiccups, uraemic breath odour, gastritis, peptic ulcer, gastrointestinal bleeding, diarrhoea.
• Neurological: impaired concentration, irritability, drowsiness, asterixis, myoclonus, seizures, coma; peripheral neuropathy with restless legs and burning feet; autonomic neuropathy.
• Cardiovascular and respiratory: hypertension, fluid overload with oedema and pulmonary oedema, pericarditis with pericardial rub, accelerated atherosclerosis, uraemic lung.
• Haematological: anaemia, platelet dysfunction with bruising and bleeding, immune suppression.
• Skin: pruritus, dry skin, uraemic frost (late, rare), nail changes (half-and-half nails), ecchymoses.
• Endocrine and musculoskeletal: hyperparathyroidism, bone pain, myopathy, amenorrhoea and erectile dysfunction, glucose intolerance, malnutrition.

Red flags (urgent dialysis considerations)

• Pericardial friction rub or effusion; encephalopathy, seizures or asterixis; uncontrolled bleeding.
• Refractory hyperkalaemia above 6.5 mmol/L, pH under 7.15, or fluid overload unresponsive to diuretics.
• Persistent vomiting preventing nutrition or medication; weight loss with hypoalbuminaemia.

• Urea, creatinine and eGFR; electrolytes, bicarbonate, calcium, phosphate, magnesium; blood gas; full blood count; parathyroid hormone; albumin; CRP; liver tests; glucose.
• Urea above 40 mmol/L (blood urea nitrogen above 110 mg/dL) often accompanies symptoms, but severity does not correlate with a single value.
• ECG, echocardiography (pericardial effusion), chest radiograph (pulmonary oedema, effusions), renal ultrasound (small echogenic kidneys in chronic disease, obstruction).
• Look for reversible factors: obstruction, volume depletion, nephrotoxins, infection, hypercalcaemia, heart failure.

Differential diagnosis

• Hepatic encephalopathy, hypercalcaemia, hyponatraemia, hypothyroidism, Wernicke encephalopathy, drug toxicity (gabapentin, baclofen, lithium, opioids), depression, sepsis, malignancy related cachexia, gastrointestinal disease unrelated to kidney failure.

Decision to start dialysis

• Start when symptoms attributable to uraemia, volume overload, hyperkalaemia, acidosis or nutritional decline persist despite maximal medical care, usually at eGFR 5 to 10 mL/min/1.73 m², and at any eGFR if complications develop. Early asymptomatic start at higher eGFR gives no benefit.
• Emergency indications: potassium above 6.5 mmol/L refractory to treatment, pH under 7.15, fluid overload with pulmonary oedema unresponsive to diuretics, and uraemic complications (pericarditis, encephalopathy, bleeding).
• Prepare ahead: vascular access creation 3 to 6 months before expected start, education on modalities, hepatitis B vaccination (40 microg at 0, 1, 2 and 6 months), pre-emptive transplant listing at eGFR under 20 mL/min/1.73 m².

First dialysis

• When urea is very high (above 50 mmol/L), limit the first sessions to 2 hours at blood flow 150 to 200 mL/min to prevent disequilibrium syndrome, then build up to 4 hours.
• Give mannitol 100 mL of 20% or use higher dialysate sodium if headache or confusion develops.
• Aim for Kt/V of at least 1.2 on thrice weekly treatment.

Medical care before dialysis and conservative management

• Protein 0.8 g/kg daily (0.6 g/kg daily with keto analogue supplementation under dietitian supervision), sodium under 2 g daily, adequate energy (30 to 35 kcal/kg daily).
• Nausea: ondansetron 4 mg orally or intravenously every 8 hours (maximum 16 mg daily), metoclopramide 5 mg three times daily (reduced dose). Hiccups: chlorpromazine 25 mg orally three times daily; avoid baclofen because of neurotoxicity in kidney failure.
• Pruritus, restless legs, anaemia, bone disease, acidosis and hypertension treated as separate problems at the usual thresholds.
• Adjust doses of renally cleared drugs; stop NSAIDs, metformin when eGFR is under 30, and magnesium containing laxatives.
• Conservative kidney management without dialysis for patients who choose it or have limited prognosis: symptom control, advance care planning, palliative care referral.

Referral and escalation. Refer to nephrology at eGFR under 30 mL/min/1.73 m² and urgently for any red flag; the uraemic emergency needs same day dialysis.

Special groups

• Elderly and frail: weigh dialysis benefit against comorbidity; offer a time limited course of dialysis or conservative care.
• Children: growth failure and neurocognitive effects dominate; early peritoneal dialysis and transplantation.
• Pregnancy: intensive dialysis (more than 20 hours weekly) improves foetal outcomes.