Introduction

A 24-hour urinalysis is a timed urine collection used in the metabolic evaluation of urinary stone disease, proteinuria evaluation, and renal function via creatinine clearance, estimating residual renal function in end-stage renal disease with urea and creatinine clearance. The testing is usually performed in an outpatient setting while the patient consumes their usual diet. Results are combined with detailed medical and dietary history, serum chemistry, and stone composition to guide prophylactic stone-reducing treatment. A 24-hour urine study can also be used in the pediatric population when inherited conditions such as primary hyperoxaluria and cystinuria are involved.[1][2]

Specimen Requirements and Procedure

Instructions for collecting a 24-hour urine sample vary by the laboratory. Typically, the patient's first voided morning urine is discarded. Subsequent urine produced for the next 24 hours, including the next morning's first voided specimen, is collected in containers that the laboratory provides. A preservative solution is added to the urine collection to stabilize the sample for later analysis. The total volume is recorded after a full 24 hours of urine collection. A representative sample from the total collection is then submitted to the laboratory for analysis. Serum samples, usually calcium, potassium, uric acid, and phosphorus, are sometimes also included in the study. Patients need to adhere to their normal diet and activities during the collection.[3][4]

When the analysis is complete, a detailed report of the results is provided to the ordering clinician. These results are used to direct prophylactic medical management. Collecting a sample for 24 hours can be difficult and inconvenient for some patients. However, it is necessary to accurately and reliably identify urinary chemistry risk factors for calculus formation, as spot urine chemistry is inadequate. A chemical composition analysis of any stone material is beneficial if available.

Diagnostic Tests

Various labs offer 24-hour urine testing, providing clinicians with a detailed laboratory report stratifying stone risk based on the laboratory data points. Typically, 24-hour urine tests for nephrolithiasis prophylaxis will include urinary volume, pH, calcium, citrate, magnesium, phosphate, sulfate, oxalate, and uric acid. Supersaturation ratios for various stone types can then be calculated. In patients with a history of cystine stones or a positive cystine cyanide test, 24-hour cystine levels can also be measured.[5][6]

Finding or selecting a laboratory for processing 24-hour urine chemistries can sometimes be challenging. Optimally, all the testing is completed in a single laboratory, and the results are presented clearly on just 1 or 2 pages. The 24-hour totals and the relative concentrations should both be given. Normal values are not necessarily "optimal" for urinary chemical constituents. Optimal urinary chemistry reference values are not reported, making interpretation a little more complicated. Try to use a laboratory that performs a lot of 24-hour urine testing and reports all the results together. When multiple reports from several laboratories must be combined to retrieve all the data, it is far more difficult to correlate and analyze.

Results, Reporting, and Critical Findings

Components of 24-hour urine exams vary by laboratory. Most standard 24-hour analyses include urine volume, calcium concentration, oxalate, citrate, uric acid concentration, urine pH level, and supersaturation values. Supersaturation of calcium oxalate, calcium phosphate, and uric acid are commonly reported. Other analytes include urine potassium, magnesium, phosphorus, ammonium, chloride, sulfate, and nitrogen in the form of urea. Reports typically include reference range values that help stratify the risk of stone formation. Specialized testing is also available for pediatric patients and patients with cystinuria. These tests include cysteine excretion, supersaturation, and urine pH. The interpretation of urine chemistry requires reference ranges. Urine chemistry is a continuous variable, making the strict cut-off points and abnormal values somewhat arbitrary. As urinary constituents reach outside of normal or optimal ranges, the lithogenic risk increases.[7]

Below is a summary of the key components of the 24-hour urinalysis and their importance.

Urine Volume and Creatinine

Decreased urine volume is a major risk factor for stone disease, as concentrated urine increases the supersaturation of all stone-forming salts. A prospective trial by Borghi et al in 1999 helped define a goal urinary volume level of 2500 mL per day to reduce stone risk. Furthermore, urine volumes over this amount can decrease stone risk even further.

Urine creatinine excretion is used to determine the accuracy of a timed urine collection. As a byproduct of muscle metabolism, creatinine excretion is relatively stable based on muscle mass. The average daily creatinine excretion for males is 18 to 24 mg/kg and 15 to 20 mg/kg for females. Thus, a lower-than-expected creatinine excretion suggests an incomplete collection.

pH

Human urine has a pH typically between 4.5 and 8.0. Urine pH is a critical data point, as changes in urine pH can drive the crystallization of certain salts. Crystallization of calcium phosphate, calcium oxalate, uric acid, cystine, and struvite are all pH-dependent. Calcium oxalate precipitation is typically not as pH-dependent as the others. Uric acid stone risk is most significant in the acidic range below 5.5. Calcium phosphate crystals form in an alkaline environment of 6.5 and above. Average urine pH over 24 hours should fall between 5.7 and 6.3, which limits pH-dependent stone formation.

Sodium and Potassium

Urinary sodium excretion roughly equates to dietary sodium intake. As urinary sodium increases, urinary calcium excretion increases. Because of this relationship, control of dietary sodium is key to controlling hypercalciuria. Lower sodium diets typically allow up to 1500 mg of dietary sodium daily. Urinary potassium concentration is most useful in monitoring compliance with treatments such as potassium citrate. Potassium citrate supplements should result in marked increases in urinary potassium secretion.

Magnesium

Magnesium inhibits urinary crystallization, decreasing the risk of stones. Roughly half of dietary magnesium is excreted in the urine; low urine magnesium is typically dietary in origin.

Calcium

Elevated urinary calcium concentration can be found in nearly half of patients forming calcium stones. Urine calcium concentration depends on dietary calcium, sodium, and protein intake. Moderate calcium intake is recommended to limit urinary excretion while maintaining bone health. Diets low in calcium can be lithogenic due to increased oxalate absorption in a low-calcium diet. Modulation of urine calcium is often accomplished with diet changes or medications depending on etiology.

Citrate

Citrate is a potent inhibitor of calcium salt crystallization. Hypocitraturia is a common risk factor for stone disease found in up to a third of calcium stone formers. Low urinary citrate can be due to diet, metabolic acidosis, or hypokalemia. Hypocitraturia can also be idiopathic. Citrate can be found in foods such as citrus juice. Most patients with low urinary citrate require supplementation as dietary means alone are insufficient.

Concentrated citrate supplements such as potassium citrate are commonly available. Optimal urinary citrate levels are roughly 300 mg per 1000 mL of urine. Low urinary citrate levels in the setting of thiazide therapy may correlate with hypokalemia. A 24-hour urine study monitors urinary citrate concentration and resultant urinary pH level. Over-alkalinizing the urine can predispose it to calcium phosphate stones if the pH consistently exceeds 7.0.

Oxalate

High urine oxalate is another common abnormality in the urine of calcium stone formers. Roughly a third of calcium stone formers will have elevated urine oxalate. Oxalate is both endogenous and dietary. Dietary oxalate is absorbed in the colon and distal portions of the ileum. Normal oxalate excretion ranges from around 40 to 50 mg per day. Reductions in excretion can have goals as low as 25 mg per day. Dietary sources of oxalate include black tea, nuts, chocolate, and green leafy vegetables like spinach. Excessive vitamin C supplements are also metabolized to oxalate in the urine. For this reason, vitamin C supplements should be limited to 1000 mg or less daily. Enteric hyperoxaluria can be a significant risk factor for patients with inflammatory bowel disease, cystic fibrosis, pancreatic insufficiency, or previous bariatric bowel surgery.

Our companion review article, 24-Hour Urine Testing for Nephrolithiasis: Guide to Interpretation, by Leslie and Bashir, provides a more detailed review of 24-hour urine chemistry interpretation and a treatment guide for kidney stone prevention.

Clinical Significance

The 24-hour urinalysis is a key component of the metabolic workup for recurrent stone formers. Accurate collections can detect treatable abnormalities predisposing to nephrolithiasis and monitor treatment progress. Urinary constituents are highly variable based on diet and lifestyle factors. Interpretation is complex and often subjective due to this variability. Commercially available tests make analysis easily accessible. Metabolic evaluation utilizing 24-hour analysis is recommended for recurrent stone formers based on current guidelines.

Over 90% of kidney stone patients tested will demonstrate at least one sub-optimal chemical disorder. The fact that patients typically feel no better on treatment makes it far more challenging to keep patients on therapy long-term. Patients who are highly motivated to minimize their long-term kidney stone risk and continue treatment will benefit the most from this testing. Twenty-four-hour urine testing is not curative, but it does direct effective prophylactic treatment for those who are willing to follow therapeutic guidelines on a long-term basis.

Enhancing Healthcare Team Outcomes

A 24-hour urinalysis is a timed urine collection used in the metabolic evaluation of several types of kidney disorders. The nurse most often does the urine collection for in-patients. The nurse should be familiar with the urine collection and the need to keep it free of contaminants. When the testing is done in an outpatient setting, the patient must be educated on collecting the urine. Accurate collections can detect treatable abnormalities predisposing to nephrolithiasis, glomerulonephritis, or nephrotic syndrome and help monitor treatment progress.[8][9]