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Interpretation of urea and electrolytes

Urea and creatinine



  • Creatine is a substance produced primarily by the liver 
  • Creatine is phosphorylated to creatine phosphate, which is used as an energy store for muscles
  • To produce energy, creatine phosphate is broken down to creatine and phosphate, which allows ADP to be converted to ATP 
  • Creatine is metabolised to the waste product creatinine, which passes to the kidneys where it is excreted
  • Changes in creatinine concentration are fairly specific for determining kidney injury, but baseline level depends on muscle mass


  • Ammonia is a toxic waste product produced during amino acid catabolism
  • Ammonia is converted to urea in the liver by the ‘urea cycle’
  • Urea then passes to the kidneys where it is excreted
  • Serum urea concentration also rises in kidney injury but it is not specific for this. Other causes of high/low urea include:
    • ↑urea = dehydration, GI bleeding, increased protein breakdown (trauma, infection, malignancy), high protein intake
    • ↓urea = malnutrition, liver disease, pregnancy

Acute kidney injury

Acute kidney injury (AKI) = rise in serum creatinine >50% from baseline, or urine output <0.5ml/kg/hour for 6 hours.

Determine if AKI is pre-renal, renal, or post-renal.

ALL patients need:

  • Urine dipstick (interpreted in context of history)
  • Bloods: FBC ± haematinics, U&Es, CRP, Ca2+, PO43-, PTH
  • VBG: check for: metabolic acidosis/low bicarbonate (may need weak bicarbonate infusion); and hyperkalaemia
  • Accurate fluid balance chart (requires catheterisation)
  • Stop nephrotoxic drugs and stop/dose-reduce renal excreted drugs

Pre-renal AKI (70%) – caused by renal hypoperfusion

  • Causes: hypovolaemia/sepsis (most common AKI cause), renovascular disease, cardiorenal failure (increased venous pressure reduces renal perfusion pressure)
  • Suggested by: history, dehydration, hypotension, rise in urea greater than rise in creatinine
  • Investigation:
    • Renal artery Doppler (if suspect renovascular disease)
  • Treatment: treat cause (IV fluids in hypovolaemia) 
  • Complications: acute tubular necrosis 

Intrinsic AKI (20%) – caused by renal damage

  • Causes
    • Acute tubular necrosis (ischaemic or nephrotoxic): suggested by renal hypoperfusion or tubular nephrotoxin
    • Acute interstitial nephritis: suggested by causative drugs, sometimes with eosinophillia or rash 
    • Glomerulonephritis: suggested by haematuria/proteinuria on dip and other glomerulonephritis/vasculitic symptoms
    • Thrombotic microangiopathy (e.g. microangiopathic haemolytic anaemia, malignant hypertension, scleroderma renal crisis): suggested by anaemia, thrombocytopaenia ± haemolysis evidence (e.g. hyperbilirubinaemia, fragments on film)
  • Investigation: 
    • Urine dipstick: blood +++ protein +++ in glomerulonephritis; in acute tubular necrosis, urine is usually bland
    • Urine protein:creatinine ratio (to quantify and monitor proteinuria if dipstick is positive for protein; <15mg/mmol = normal; >300mg/mmol = nephrotic)

NB: urine protein:creatinine ratio (mg/mmol) X 10 ≈ 24 hour protein loss (mg)

  • Possible further tests
    • Nephritic screen (if suspect glomerulonephritis): antinuclear antibodies, anti-neutrophil cytoplasmic antibodies, anti-glomerular basement membrane antibody, complement, rheumatoid factor, anti-streptolysin O titre, anti-DNase B, hepatitis B/C serology, HIV serology, antiphospholipid antibodies
    • Myeloma screen: immunoglobulins/protein electrophoresis and serum free light chains
    • If thrombocytopenia/suspicion of haemolysis: blood film, lactate dehydrogenase, haptoglobin, bilirubin
    • Creatinine kinase (if rhabdomyolysis suspected)
    • Renal biopsy indications: unexplained AKI, suspected glomerulonephritis, positive nephritic screen, persistent acute tubular necrosis, or suspected interstitial nephritis
      • Urgent renal biopsy if rapidly progressive glomerulonephritis suspected (suggested by rapid loss of kidney function, worsening severe proteinuria/haematuria, and nephritic syndrome)
  • Treat cause, for example:
    • Stop causative agent for acute interstitial nephritis
    • Corticosteroids, diuretics and ACE inhibitor may be required for glomerulonephritis

Post-renal AKI (10%) – caused by obstruction of the urinary tract

  • Cause: urinary tract obstruction 
    • Ureters: ureteric calculi, vesico-ureteric reflux, ureteric stricture, tumour (e.g. transitional cell carcinoma), extrinsic compression
    • Bladder: neurogenic bladder, bladder calculi, tumour (e.g. bladder carcinoma)
    • Urethra: benign prostatic hypertrophy, prostate cancer, stricture, blocked catheter
  • Suggested by: history, urea and creatinine raised in equal proportion
  • Investigation: 
    • Bladder scan
    • Renal tract USS
  • Treatment: relieve obstruction (catheter if urethral; nephrostomy/ureteric stent if ureteric) and treat cause

Complications: hydronephrosis (can progress to irreversible renal damage)

Indications for renal replacement therapy in acute kidney injury


  • Acidosis – pH<7.2
  • Electrolyte abnormalities (hyperkalaemia, hyponatraemia, hypercalcaemia) – K+>6.5 or ECG changes
  • Intoxicants (methanol, lithium, salicylates)            
  • Overload – acute pulmonary oedema
  • Uraemia – urea >60, uraemic pericarditis or encephalopathy

NB: in chronic kidney disease, regular dialysis is required when the GFR is <15ml/minute, and there are symptoms or complications of kidney disease.

Chronic kidney disease

Chronic kidney disease = presence of marker of kidney damage (e.g. proteinuria) or decreased GFR for > 3 months

Commonest causes

  1. Diabetes (secondary glomerular disease)
  2. Chronic hypertension
  3. Chronic glomerulonephritis
  4. Polycystic kidney disease

Determining cause

  • History
  • Urine dipstick
  • Renal USS
  • Renal biopsy if required


  • Manage cause, e.g. diabetic control, antihypertensives, cardiovascular risk factor modification
  • General measures: fluid restriction, dietary protein restriction, ACE inhibitor
  • Treat complications: 
    • Hypertension → antihypertensives
    • Oedema → fluid restriction ± furosemide
    • Anaemia → iron supplementation ± erythropoietin
    • Secondary hyperparathyroidism →
      • Active vitamin D therapy, e.g. alfacalcidol, calcitriol 
      • Dietary phosphate restriction ± phosphate binders, e.g. calcium edetate/sevelamer
      • PTH-control with parathyroidectomy or cinacalcet
    • Acidosis → sodium bicarbonate
    • Hyperlipidaemia → statin
    • Hyperkalaemia → dietary potassium restriction
    • Acidosis → sodium bicarbonate
  • Dialysis (when GFR is <15ml/minute, and there are symptoms or complications of kidney disease)



  • Na+ is an extracellular ion
  • H2O follows solutes due to osmosis (e.g. Na+, albumin)
  • Aldosterone increases Na+ reabsorption (in exchange for K+) from the distal convoluted tubule
  • Antidiuretic hormone causes reabsorption of H2O (alone) from the collecting duct


→ nausea/vomiting, headache, confusion, seizures, reduced consciousness


Hyponatraemia causes


  • Plasma osmolality (to confirm if true hyponatraemia) + glucose
    • Low = true hyponatraemia 
    • Normal = false hyponatraemia (‘pseudohyponatraemia’ due to hyperlipidaemia or hyperproteinemia)
    • High = dilutional (due to hyperglycaemia, e.g. in hyperosmolar hyperglycaemic state/DKA; alcohols; or mannitol)
  • Urinary sodium and osmolality (to determine whether the problem is occurring in the kidneys or elsewhere)
  • Specific tests to investigate for specific causes, for example:
    • SIADH: low plasma osmolality (<275) with high urine osmolality (>100) and high urine sodium (>30); investigate cause
    • Adrenal insufficiency: 9am cortisol screening test, Synacthen (synthetic ACTH) test 
    • Hypothyroidism: TFTs
Check TFTs and 9am cortisol in all euvolaemic patients 


  • Treat cause
  • Sodium correction
    • Severe symptoms (e.g. vomiting, seizures, low GCS), regardless of cause: consider 3% hypertonic saline (e.g. 150ml over 20 minutes, repeated if necessary), usually in ICU with close monitoring 
    • Hypovolaemic: replace lost fluid with 0.9% saline/Hartmann’s solution – slowly if chronic, e.g. 1L over 12 hours
    • Euvolaemic: treat cause 
    • If SIADH or oedematous: fluid restrict to 1 litre/day (excess H2O causes dilutional hyponatraemia); consider demeclocycline (± tolvaptan) for fluid restriction-resistant SIADH; diuretics for heart failure

NB: chronic hyponatraemia (onset over 48 hours) must be corrected slowly, i.e. maximum 10mmol/L change in 24 hours (risk of osmotic change causing osmotic demyelination syndrome).


→ thirst, confusion, muscle twitching/spasms


  • Euvolaemic = iatrogenic (e.g. excess IV sodium-containing fluids, sodium-containing drugs)
  • Hypovolaemic
    • Producing small volumes of concentrated urine (normal response to hypovolaemia) = dehydration
    • Not producing small volumes of concentrated urine (abnormal response to hypovolaemia)
      • Diabetes insipidus = urine osmolality <750 + serum osmolality >300 (kidneys not reabsorbing sufficient H2O)
      • Osmotic diuresis, e.g. due to hyperglycaemia or osmotic diuretics (kidneys losing H20 and solutes)


  • Urine and serum osmolality 
  • Fluid deprivation test to confirm diabetes insipidus


  • Treat cause
  • Sodium correction
    • Hypovolaemic (signs include hypotension, tachycardia, orthostatic hypotension): replace deficit with 0.9% saline/Hartmann’s solution
    • Euvolaemic: 5% dextrose – slowly if chronic, e.g. 1L over 12 hours

NB: chronic hypernatraemia (onset over 48 hours) must be corrected slowly, i.e. maximum 10mmol/L change in 24 hours (risk of osmotic change causing osmotic demyelination syndrome).



  • K+ is 90% intracellular
  • Multiple pumps affect serum K+:


→ arrhythmias, tremor, muscle weakness/cramps, constipation 


  • Increased renal loss
    • Diuretics (except potassium-sparing diuretics) 
    • Endocrinological (steroids, Cushing’s syndrome, hyperaldosteronism)
    • Renal tubular acidosis
    • Hypomagnesaemia
    • Systemic alkalosis
  • Intestinal loss
    • Intestinal fluid loss (vomiting/diarrhoea)
  • Increased cellular uptake
    • Salbutamol
    • Insulin
    • Systemic alkalosis


  • >2.5mmol/L: potassium supplements (e.g. Sando-K 2 tablets TDS x 3/7), or 20-40mmol potassium chloride in each litre IV fluids
  • <2.5mmol/L: 40mmol/L potassium chloride in 1L 0.9% saline over 4-6 hours (NEVER give >10mmol/hour K+ outside ICU)
  • Treat cause 


→ arrhythmias, lethargy, muscle weakness 


  • Reduced renal excretion
    • Acute/chronic kidney injury
    • Drugs (potassium-sparing diuretics, ACE inhibitors, NSAIDs)
    • Aldosterone deficiency (Addison’s disease/adrenal insufficiency) – ↓Na+ ↑K+
    • Systemic acidosis
  • Excess K+ load
    • Iatrogenic
    • Massive blood transfusion
  • Release from intracellular fluid
    • Systemic acidosis
    • Tissue breakdown, e.g. rhabdomyolysis, haemolysis, tumour lysis syndrome, burns, crush injury

NB: may be due to pseudohyperkalaemia (haemolysis/EDTA-contaminated sample).


  • Acute management
  • ECG and 3-lead cardiac monitoring
    • Changes: flat wide P waves, wide bizarre QRS, tall tented T waves
  • Calcium gluconate: 30ml 10% IV over 15 minutes
    • Protects myocytes (required if there are ECG changes; also consider if severe, i.e. ≥6.5mmol/L, without ECG changes)
    • Works in minutes – check ECG changes resolved; repeat dose if no effect within 10 minutes
    • Lasts 30-60 minutes
  • Actrapid insulin: 10 units in 125ml 20% dextrose IV over 30 minutes + 10mg salbutamol neb
    • Temporarily shifts potassium into cells
    • There is a risk of hypoglycaemia: monitor capillary glucose before, during and regularly after. Consider giving 10% glucose infusion at 50ml/h for 5 hours after, if the pre-treatment capillary glucose is <7mmol/L.
    • Gradually decreases potassium and lasts 1-2 hours, after which there is usually a slow rebound
    • Check K+ has normalised after 2 hours (dose can be repeated if not) and check again a few hours later
    • Nebulised salbutamol may be used in addition for similar but lesser effect – lasts 2 hours
  • Sodium zirconium cyclosilicate 10g PO TDS for up to 72 hours
    • Works slowly 
    • Only treatment that actually removes potassium from body
    • May start with this if only moderate hyperkalaemia, i.e. K+ ≤ 5.9mmol/L
  • Consider renal replacement therapy if above fails (also consider sodium bicarbonate in severe acidosis)
  • Treat cause



  • Arrows indicate movement of calcium under influence of vitamin D and PTH:
  • PTH should increase in response to hypocalcaemia due to hormonal feedback
  • Always look at the corrected calcium value, which is adjusted for albumin


→ CATs go numb: Convulsions, Arrhythmias, Tetany, numbness (periorbital, hands, feet)


  • PTH deficiency (↑PO43-, ↓PTH)
    • Hypoparathyroidism
    • Hypomagnesaemia (magnesium is required for PTH secretion)
    • imageCinacalcet
  • Vitamin D deficiency (↓PO43-, ↑PTH)
  • Increased deposition in bones          
    • Bisphosphonates
  • Other causes (↑PO43-, ↑PTH)
    • Chronic kidney disease (inability to hydroxylate 25-OH vitamin D and calcium binding to retained phosphate)
    • Pseudohypoparathyroidism (resistance to PTH)
    • Rhabdomyolysis/tumour lysis syndrome (calcium binds to high phosphate)


  • Initial tests
    • Renal function
    • PTH
    • Phosphate, magnesium


  • Severe (<1.9mmol/L or symptomatic): calcium gluconate 10ml 10% IV over 10 minutes – may be repeated until asymptomatic and can be followed by an infusion if required (50ml 10% calcium gluconate in 500ml 0.9% saline over 12 hours)
  • Mild (>1.9mmol/L and asymptomatic): calcium supplements (e.g. Sandocal or Calcichew 1000mg BD)
  • Treat cause: in severe vitamin D deficiency, load with 50,000 units colecalciferol once weekly for 6 weeks; in mild vitamin D deficiency, give 800 units once daily long-term; or, if calcium and vitamin D deficient, give Adcal-D3 long-term; in end-stage CKD-associated vitamin D deficiency, use alfacalcidol (1-α hydroxycholecalciferol) instead because the kidney disease impairs the terminal hydroxylation required for vitamin D synthesis.


→ ‘painful bones, renal stones, abdominal groans, and psychic moans’


  • PTH excess
    • Primary hyperparathyroidism (↑PTH) or tertiary hyperparathyroidism (↑↑↑PTH)
    • Ectopic PTH/PTH-related peptide secretion (e.g. squamous cell lung cancer)
  • Vitamin D excess
    • Excessive vitamin D intake
    • Granulomatous diseases (e.g. sarcoidosis)
  • Increased release from bones
    • Bony metastasis (↑ALP)
    • Myeloma (normal ALP)
    • Thyrotoxicosis (mechanism unknown)
  • Other causes 
    • Drugs that decrease renal excretion (e.g. thiazide diuretics)

NB: dehydration is also a common cause. (Urea and albumin also likely raised.)


Investigate for cause if not clear:

  • Initial tests: renal function, ALP, PTH, phosphate
  • Myeloma screen (if myeloma suspected)
  • Serum ACE (if sarcoidosis suspected)
  • Isotope bone scan (if bony metastasis suspected)


  • IV fluids: replace fluid deficit and keep patient well hydrated (e.g. continuous 0.9% saline at 1L over 4-6 hours)
  • IV bisphosphonate (e.g. zoledronic acid 4mg IV): may be used in severe hypercalcaemia (>3.5mmol/L or symptomatic) if calcium stops falling with IV fluids alone. One-off dose; generally takes a few days to work. Dose may be reduced for poor renal function. 
  • Treat cause



→ lethargy, muscle weakness/cramps, tremors, arrhythmias, seizures


  • Reduced intake
    • Poor nutritional intake 
    • Malabsorption
    • Alcoholism 
  • Excess loss
    • GI loss, e.g. severe diarrhoea, vomiting, NG losses, proton pump inhibitors
    • Renal loss, e.g. ketoacidosis, renal tubular diseases, hyperaldosteronism, diuretics, aminoglycosides

         NB: hypomagnesaemia can cause hypokalaemia (magnesium normally inhibits renal potassium excretion) and hypocalcaemia 

         (magnesium is required for PTH secretion and sensitivity)


  • PO: magnesium aspartate 1 sachet (10mmol) BD x 3/7
  • IV: 5grams (20mmol) magnesium in 500ml 0.9% saline over 5 hours
  • Correct hypomagnesaemia before concurrent hypokalaemia and hypocalcaemia if possible 



→ lethargy, muscle weakness (skeletal, cardiac and diaphragmatic), change in mental state


  • Reduced intake/absorption
    • Vitamin D deficiency
    • Poor nutrition
    • Malabsorption (including due to alcoholism and drugs, e.g. antacids) 
  • Increased use (phosphate shifts into cells to produce ATP from ADP for energy stores)
    • Refeeding syndrome
    • Insulin therapy
    • Alkalosis
  • Excess renal loss
    • Primary hyperparathyroidism
    • Renal tubular diseases 


  • PO: Phosphate-Sandoz 2 tablets TDS x 3/7
  • IV: Phosphate Polyfusor (50mmol in 500ml), 100-300ml over 12-24 hours depending on severity and patient weight or sodium glycerophosphate 10mmol in 500ml 0.9% saline over 12 hours
  • Do not give if hypercalcaemic or oliguric