Metabolic Acidosis in Chronic Kidney Disease

Metabolic acidosis in chronic kidney disease is a serum bicarbonate under 22 mmol/L due to reduced renal net acid excretion. Prevalence rises from 5% at stage G3a to more than 30% at G4 to G5. The daily endogenous and dietary acid load is about 1 mmol/kg; the failing kidney cannot generate enough ammonia and excrete titratable acid, so buffers (bone, muscle) are consumed. Early disease produces a normal anion gap (hyperchloraemic) acidosis; advanced disease adds a raised anion gap from retained phosphate, sulphate and organic anions.

Consequences. Faster decline in eGFR, bone demineralisation and fracture, muscle protein catabolism and sarcopenia, insulin resistance, hyperkalaemia, impaired growth in children, worse cardiovascular outcomes, and higher mortality.

• Often silent. Fatigue, anorexia, nausea, muscle weakness, bone pain, dyspnoea on exertion.
• Kussmaul breathing in severe acidosis; confusion, hypotension and arrhythmia as pH falls.
• Children: growth failure and rickets.

Red flags

• Bicarbonate under 12 mmol/L or pH under 7.15: consider dialysis.
• Raised anion gap with high lactate (metformin, sepsis, ischaemia), ketones or osmolar gap (toxic alcohol).
• Concurrent hyperkalaemia above 6.0 mmol/L.
• Rapid fall in bicarbonate over days: look for acute kidney injury, sepsis, diarrhoea.

• Serum (venous) bicarbonate on an unhaemolysed sample; arterial or venous blood gas with pH, pCO2, base excess and lactate in unwell patients.
• Anion gap = sodium minus (chloride + bicarbonate); normal 8 to 12 mmol/L (add 2.5 mmol/L for each 10 g/L fall in albumin below 40 g/L). Raised: lactic acidosis, ketoacidosis, uraemia, toxins; normal: renal tubular acidosis, diarrhoea, early chronic kidney disease.
• Urine pH, urine anion gap (sodium + potassium minus chloride; positive suggests impaired ammonium excretion), and fractional excretion of bicarbonate if tubular acidosis is suspected.
• Lactate, ketones, osmolar gap, salicylate level in the unwell.
• Electrolytes (potassium), calcium, phosphate, parathyroid hormone, urine albumin:creatinine ratio.

Differential diagnosis

• Distal (type 1) renal tubular acidosis (urine pH above 5.5, hypokalaemia, stones), proximal (type 2), type 4 (hyperkalaemia, diabetes, obstructive uropathy, drugs).
• Diarrhoeal and ileostomy losses, pancreatic fistula, ureteric diversion, lactic acidosis, diabetic ketoacidosis, toxic alcohols, drugs (acetazolamide, topiramate, trimethoprim, amphotericin).

Chronic management (bicarbonate under 22 mmol/L on two measurements)

• Sodium bicarbonate 500 mg to 1 g orally two to three times daily, titrated every 2 to 4 weeks to serum bicarbonate at least 22 mmol/L and under 29 mmol/L. A 500 mg tablet contains about 6 mmol of sodium: counsel on oedema and hypertension, check weight and blood pressure, and tighten diuretics if overloaded.
• Check bicarbonate, potassium and calcium 2 to 4 weeks after each dose change. In hypocalcaemia, ionised calcium falls as acidosis is corrected; ensure calcium is normal before large corrections.
• Dietary: increase fruit and vegetables (acid lowering) when potassium is controlled, reduce red and processed meat, and keep protein at 0.8 g/kg daily.
• Treat hyperkalaemia with binders if it limits bicarbonate or diet.

Acute severe acidosis (pH under 7.15 or bicarbonate under 12 mmol/L)

• Treat the cause (sepsis, hypovolaemia, ketosis, toxins). If acute kidney injury is present and pH is 7.20 or lower, sodium bicarbonate 4.2% 125 to 250 mL intravenously over 30 minutes through a central line, repeated to pH above 7.30, maximum 1000 mL in 24 hours; watch sodium, calcium, potassium and fluid overload.
• Haemodialysis for refractory acidosis (pH under 7.15), hyperkalaemia, or fluid overload; continuous therapy in unstable patients.
• Metformin associated lactic acidosis with pH under 7.0 or lactate above 15 mmol/L: urgent haemodialysis.

Monitoring. Bicarbonate monthly until stable, then every 3 months; annually in stable stage G3.

Referral and escalation. Nephrology for persistent acidosis despite 1.5 g sodium bicarbonate daily, suspected tubular acidosis, or hypertension and oedema on treatment.

Special groups

• Children: sodium bicarbonate 1 to 2 mmol/kg daily in 2 to 3 doses to keep bicarbonate at least 22 mmol/L; acidosis impairs growth.
• Heart failure or severe hypertension: sodium load is limiting; use citrate preparations or loop diuretics with caution.
• Dialysis: dialysate bicarbonate 34 to 37 mmol/L; pre-dialysis bicarbonate target 22 to 26 mmol/L.