Azotaemia

Azotaemia is an elevated concentration of urea (blood urea nitrogen) and creatinine in the blood because of a decrease in glomerular filtration, without necessarily producing the clinical syndrome of uraemia. It is classified by site:

• Prerenal azotaemia: reduced renal perfusion with intact tubular function (hypovolaemia, low cardiac output, hepatorenal states, renal artery stenosis, drugs that reduce glomerular pressure such as NSAIDs, ACE inhibitors and angiotensin receptor blockers)
• Intrinsic renal azotaemia: acute tubular injury, interstitial nephritis, glomerulonephritis, vascular disease and tubular obstruction
• Postrenal azotaemia: obstruction anywhere from the renal pelvis to the urethral meatus

Prerenal azotaemia is the most common and reversible form. It becomes tubular injury if hypoperfusion continues beyond about 24 to 72 hours.

Urea rises disproportionately to creatinine (ratio of BUN to creatinine above 20:1 in conventional units, which is a urea (mmol/L) to creatinine (micromol/L) ratio above 0.08) in prerenal states because of increased proximal reabsorption of urea, and also with gastrointestinal bleeding, high protein intake, catabolic states, corticosteroids and tetracyclines. A low ratio occurs in liver disease, malnutrition and rhabdomyolysis.

Features are those of the cause rather than azotaemia itself.

• Prerenal: thirst, postural hypotension, tachycardia, dry mucous membranes, reduced skin turgor, low JVP, diuretics or vomiting or diarrhoea; or oedema and elevated JVP in heart failure or cirrhosis (effective hypovolaemia)
• Intrinsic: nephrotoxin exposure, sepsis, haematuria, rash, fever
• Postrenal: lower urinary tract symptoms, palpable bladder, suprapubic pain, anuria or fluctuating output

Red flags: anuria, oliguria below 0.3 mL/kg/h for 24 hours, potassium above 6.0 mmol/L, bicarbonate below 15 mmol/L, hypotension with lactate above 2 mmol/L, palpable bladder or hydronephrosis.

• Confirm with repeat urea and creatinine; compare with baseline to stage acute kidney injury (creatinine rise of 26.5 micromol/L in 48 hours, or 1.5 times baseline within 7 days)
• Urinalysis: bland in prerenal disease; muddy brown casts in tubular injury; red cell casts in glomerulonephritis
• Urine indices: fractional excretion of sodium below 1% and urine sodium below 20 mmol/L, urine osmolality above 500 mOsm/kg, fractional excretion of urea below 35% in prerenal states; fractional excretion of sodium above 2% and urine osmolality below 350 mOsm/kg in tubular injury. Use fractional excretion of urea if diuretics have been given.
• Bladder scan: residual volume above 200 mL
• Renal ultrasound for hydronephrosis, size and asymmetry
• Response to a fluid challenge (250 to 500 mL crystalloid over 30 minutes): urine output above 0.5 mL/kg/h and creatinine falling over 24 to 48 hours supports prerenal azotaemia
• Echocardiography and assessment of cardiac output in suspected cardiorenal state

Differentials: pseudo azotaemia (creatinine assay interference from ketones, cefoxitin), creatinine rise from trimethoprim, cimetidine or fenofibrate (blocked tubular secretion with unchanged GFR), and high urea from catabolism or bleeding with normal GFR.

First line

• Identify and treat the cause.
• Hypovolaemia: balanced crystalloid 250 to 500 mL over 15 to 30 minutes, reassessing perfusion after each aliquot; stop at haemodynamic restoration or signs of overload. Replace blood in haemorrhage.
• Stop NSAIDs, ACE inhibitors, angiotensin receptor blockers, SGLT2 inhibitors, diuretics and other nephrotoxins temporarily; resume once creatinine returns to baseline.
• Maintain mean arterial pressure at least 65 mmHg; noradrenaline 0.05 to 0.5 microg/kg/min if vasopressors are required after volume restoration.

Postrenal

• Urethral or suprapubic catheter for outlet obstruction; nephrostomy or ureteric stent for upper tract obstruction. Monitor for post-obstructive diuresis (output above 200 mL/h for 2 hours): replace with 0.45% sodium chloride at 50% to 75% of the previous hour's output.

Cardiorenal or hepatorenal

• Heart failure: loop diuretic, vasodilators if blood pressure allows, inotropes if low output.
• Cirrhosis with hypovolaemia: albumin 20% 1 g/kg (maximum 100 g) daily for 2 days, withdraw diuretics; terlipressin if hepatorenal syndrome.

Monitoring. Fluid balance, urine output (catheter if necessary), creatinine and electrolytes every 12 to 24 hours until trending to baseline.

Escalation. Renal replacement therapy for refractory hyperkalaemia, acidosis (pH below 7.15), overload or uraemic complications; nephrology referral if no improvement within 48 to 72 hours of volume restoration.