24-Hour Urine Collection

The 24-hour urine collection measures the total amount of an analyte excreted over a full day. It is used when a timed total is needed that a spot sample cannot give: protein quantification when the spot ratio is unreliable, creatinine clearance, sodium excretion, and the metabolic assessment of kidney stones (calcium, oxalate, citrate, urate, volume and pH). The same collection is used for urinary free cortisol, catecholamines and metanephrines.

Spot urine ratios and eGFR have replaced it for most routine uses, because incomplete collection is common and the burden on the patient is high. It remains valuable in stone formers, for estimating sodium intake, and for quantifying proteinuria when the ratio and the clinical picture disagree.

Indications. Recurrent or multiple kidney stones, suspected hypercalciuria or hyperoxaluria, proteinuria that cannot be quantified reliably by a spot ratio (extremes of muscle mass, unsteady state), GFR estimation with unusual diet or body composition when cystatin C is unavailable, assessment of sodium intake and diuretic response in ascites and heart failure, evaluation of polyuria, and workup of unexplained hypokalaemia or hypercalcaemia.

Method.

• Start at a stated time. The bladder is emptied and that urine is discarded.
• Every later void is collected into the container supplied, including a final void at the same clock time the next day.
• The container is kept cool and away from light. Start and finish times and any missed void are recorded. A missed void invalidates the collection, and it is restarted.
• Usual diet and fluid intake are kept, and unusual exercise is avoided. Collection is avoided during menstruation, urinary infection and in the days after contrast.
• Preservative depends on the analyte. Hydrochloric acid is used for calcium, oxalate and catecholamines, boric acid for some other analytes, and none for protein, sodium, potassium and creatinine. The laboratory states the container to use. Acid containers are hazardous and are handled with care, particularly with children.
• For creatinine clearance, a blood sample for plasma creatinine is taken at the midpoint or end of the collection.

Validity check. Total volume is measured and recorded. Creatinine excretion is used to judge completeness, and is about 15 to 25 mg/kg of body weight over 24 hours in men and about 10 to 20 mg/kg in women. A value clearly under this range suggests under collection, and a value over it suggests over collection or high muscle mass or meat intake. Day-to-day variation in the same person is about 10 to 15%.

Volume. Usual output is 800 to 2000 mL over 24 hours. Under 400 mL is oliguria, and over 3000 mL is polyuria.

Adult values on an unrestricted diet are given. Local ranges take precedence.

Protein. Total protein excreted, mostly albumin with smaller amounts of Tamm-Horsfall protein and low molecular weight proteins. Range: under 150 mg/24 h, with albumin under 30 mg/24 h. Raised: glomerular disease, tubular disease, overflow from light chains, fever, exercise, heart failure, urinary infection, pregnancy. Lowered: not applicable.

Nephrotic range proteinuria is over 3.5 g/24 h (in children over 40 mg/m²/h). In pregnancy, 300 mg/24 h or more with hypertension after 20 weeks supports pre-eclampsia. Orthostatic proteinuria is shown by a split collection, with daytime protein raised and overnight protein under about 50 mg over 8 hours.

Creatinine clearance. Urine creatinine multiplied by urine volume, divided by plasma creatinine and by the collection time in minutes, then adjusted to a body surface area of 1.73 m². Range: about 90 to 130 mL/min/1.73 m² in young adults, falling with age. Raised: pregnancy, high protein intake, early diabetic hyperfiltration, large muscle mass. Lowered: reduced GFR, incomplete collection.

Tubular secretion of creatinine makes clearance overestimate true GFR by 10 to 20%, and by more when GFR is low. Equations using creatinine, cystatin C or measured clearance with iohexol or an isotope are more accurate, so a timed collection seldom adds information.

Sodium. Reflects intake in the steady state. Range: about 40 to 220 mmol/24 h, depending on diet. An excretion of 100 mmol/24 h corresponds to about 2.3 g of sodium or 5.8 g of salt. Raised: high intake, diuretics, adrenal insufficiency, salt wasting nephropathy, cerebral salt wasting, osmotic diuresis, acute tubular necrosis. Lowered: low intake, volume depletion, hepatorenal syndrome, nephrotic syndrome, heart failure, cirrhosis with ascites.

In SIADH, sodium excretion matches intake and is typically over 40 mmol/L in a spot sample. In cirrhosis with ascites on a controlled sodium diet, excretion under about 78 mmol/24 h while on diuretics suggests an inadequate diuretic response or dietary non-adherence.

Potassium. Range: about 25 to 125 mmol/24 h, depending on intake. Raised: diuretics, primary hyperaldosteronism, Cushing syndrome, magnesium deficiency, renal tubular acidosis, vomiting with alkalosis, high intake. Lowered: low intake, gastrointestinal loss, advanced kidney disease.

In hypokalaemia, excretion over 20 mmol/24 h indicates renal loss, and under 20 mmol/24 h indicates gastrointestinal loss, poor intake or cellular shift.

Calcium. Range: up to about 7.5 mmol/24 h (300 mg) in men and 6.25 mmol/24 h (250 mg) in women, or under 0.1 mmol/kg (4 mg/kg). Raised: idiopathic hypercalciuria, primary hyperparathyroidism, vitamin D excess, sarcoidosis, immobilisation, distal renal tubular acidosis, loop diuretics, high sodium or protein intake, malignancy, hyperthyroidism. Lowered: familial hypocalciuric hypercalcaemia, thiazide diuretics, vitamin D deficiency, hypoparathyroidism, malabsorption, advanced chronic kidney disease, low intake.

In hypercalcaemia, a calcium clearance to creatinine clearance ratio under 0.01 supports familial hypocalciuric hypercalcaemia, and a ratio over 0.02 supports primary hyperparathyroidism. Values between 0.01 and 0.02 are indeterminate. The test is unreliable with vitamin D deficiency, thiazide use or an eGFR under 30.

Oxalate. Range: under 0.5 mmol/24 h (about 45 mg). Raised: enteric hyperoxaluria (fat malabsorption, ileal disease or resection, bariatric surgery, short bowel), high dietary oxalate, low dietary calcium, high vitamin C intake, primary hyperoxaluria (often over 1 mmol/24 h/1.73 m²), ethylene glycol poisoning. Lowered: no clinical significance.

Enteric hyperoxaluria typically occurs with low citrate and low volume, and carries a high risk of calcium oxalate stones and oxalate nephropathy.

Citrate. A urinary inhibitor of stone formation that binds calcium. Range: about 1.7 to 6.0 mmol/24 h. Raised: alkali therapy, which is the usual target of treatment. Lowered: distal renal tubular acidosis, chronic diarrhoea, thiazide related hypokalaemia, high animal protein intake, acetazolamide, topiramate, urinary tract infection, hypomagnesaemia.

A value under 1.7 mmol/24 h (about 320 mg) is hypocitraturia, a frequent and treatable stone risk.

Urate. Range: up to about 4.8 mmol/24 h (800 mg) in men and 4.5 mmol/24 h (750 mg) in women on an unrestricted diet. Raised: high purine intake, overproduction states, myeloproliferative disease, tumour lysis, uricosuric drugs. Lowered: reduced GFR, drugs that reduce production.

Hyperuricosuria promotes uric acid stones and also calcium oxalate stones.

Urine volume and pH. The volume is a stone risk and a polyuria marker. A urine volume under about 2 L increases stone risk, and the usual target in stone formers is over 2.5 L. Mean urine pH is about 5.5 to 6.5. A persistent pH under 5.5 favours uric acid stones, and a persistent pH over 7.0 suggests distal renal tubular acidosis (calcium phosphate stones) or urease producing infection (struvite stones).

Interferences and pitfalls.

• Incomplete collection is the commonest error, and is found by checking total creatinine excretion against body weight.
• Contamination with menstrual blood, semen or faeces, and urinary infection, raise protein and alter other results.
• Contrast media and some drugs interfere with protein assays for 24 to 48 hours.
• Collection during acute illness or unusual diet does not reflect baseline.
• Drugs that block tubular creatinine secretion (trimethoprim, cimetidine, dolutegravir) lower clearance without lowering GFR.
• Creatinine clearance is invalid in acute kidney injury and unsteady state.
• Warm storage allows bacterial overgrowth and urate or calcium oxalate precipitation. Acidification dissolves these but alters pH measurement, which is therefore taken from a separate fresh sample.
• Reference ranges for stone risk are population based, and the usual practice is to repeat the collection once.

Special groups.

• Children: collection is difficult and often incomplete. Spot ratios are used when possible. Protein is expressed for each square metre of body surface area, and the normal upper limit is about 4 mg/m²/h.
• Pregnancy: creatinine clearance is raised, protein excretion rises modestly, and a 300 mg/24 h threshold applies.
• Older adults: incontinence and low creatinine excretion reduce validity.
• Catheterised patients and those with spinal cord injury: collection is practical but infection alters results.

Follow up tests. Urine albumin-to-creatinine ratio, urine protein-to-creatinine ratio, urinalysis with microscopy, cystatin C and eGFR, measured GFR, serum calcium, phosphate, PTH and vitamin D, stone composition analysis, renal tract ultrasound or non-contrast CT, urine culture, urinary free cortisol and metanephrines when endocrine causes are suspected.