|Values are valid only on day of printing.|
Diagnosis and management of patients with renal lithiasis:
-In patients who have a radiopaque stone, for whom stone analysis is not available, the supersaturation data can be used to predict the likely composition of the stone. This may help in designing a treatment program.
-Individual components of the supersaturation profile can identify specific risk factors for stones.
-During follow-up, changes in the urine supersaturation can be used to monitor the effectiveness of therapy by confirming that the crystallization potential has indeed decreased.
Urine is often supersaturated, which favors precipitation of several crystalline phases such as calcium oxalate, calcium phosphate, and uric acid. However, crystals do not always form in supersaturated urine because supersaturation is balanced by crystallization inhibitors that are also present in urine. Urinary inhibitors include ions (eg, citrate) and macromolecules but remain poorly understood.
Urine supersaturation is calculated by measuring the concentration of all the ions that can interact (potassium, calcium, phosphorus, oxalate, uric acid, citrate, magnesium, sodium, chloride, sulfate, and pH). Once the concentrations of all the relevant urinary ions are known, a computer program can calculate the theoretical supersaturation with respect to the important crystalline phases, eg, calcium oxalate.(1)
Since the supersaturation of urine has been shown to correlate with stone type(2), therapy is often targeted towards decreasing those urinary supersaturations that are identified. Treatment strategies include alterations in diet and fluid intake as well as drug therapy, all designed to decrease the urine supersaturation.
SUPERSATURATION REFERENCE MEANS (DG)
Calcium oxalate: 1.77
Uric acid: 1.04
Sodium urate: 1.76
INDIVIDUAL URINE ANALYTES
0-11 months: 50-750 mOsm/kg
> or =12 months: 150-1,150 mOsm/kg
ALL REFERENCE RANGES BELOW ARE BASED ON 24-HOUR COLLECTIONS.
41-227 mmol/24 hours
17-77 mmol/24 hours
Males: 25-300 mg/specimen*
Females: 20-275 mg/specimen*
Hypercalciuria: >350 mg/specimen
*Values are for persons with average calcium intake (ie, 600-800 mg/day).
0-15 years: not established
> or =16 years: 75-150 mg/specimen
40-224 mmol/24 hours
0-19 years: not established
20 years: 150-1,191 mg/specimen
21 years: 157-1,191 mg/specimen
22 years: 164-1,191 mg/specimen
23 years: 171-1,191 mg/specimen
24 years: 178-1,191 mg/specimen
25 years: 186-1,191 mg/specimen
26 years: 193-1,191 mg/specimen
27 years: 200-1,191 mg/specimen
28 years: 207-1,191 mg/specimen
29 years: 214-1,191 mg/specimen
30 years: 221-1,191 mg/specimen
31 years: 228-1,191 mg/specimen
32 years: 235-1,191 mg/specimen
33 years: 242-1,191 mg/specimen
34 years: 250-1,191 mg/specimen
35 years: 257-1,191 mg/specimen
36 years: 264-1,191 mg/specimen
37 years: 271-1,191 mg/specimen
38 years: 278-1,191 mg/specimen
39 years: 285-1,191 mg/specimen
40 years: 292-1,191 mg/specimen
41 years: 299-1,191 mg/specimen
42 years: 306-1,191 mg/specimen
43 years: 314-1,191 mg/specimen
44 years: 321-1,191 mg/specimen
45 years: 328-1,191 mg/specimen
46 years: 335-1,191 mg/specimen
47 years: 342-1,191 mg/specimen
48 years: 349-1,191 mg/specimen
49 years: 356-1,191 mg/specimen
50 years: 363-1,191 mg/specimen
51 years: 370-1,191 mg/specimen
52 years: 378-1,191 mg/specimen
53 years: 385-1,191 mg/specimen
54 years: 392-1,191 mg/specimen
55 years: 399-1,191 mg/specimen
56 years: 406-1,191 mg/specimen
57 years: 413-1,191 mg/specimen
58 years: 420-1,191 mg/specimen
59 years: 427-1,191 mg/specimen
60 years: 434-1,191 mg/specimen
>60 years: not established
Diet-dependent: <750 mg/specimen
15-25 mg/kg of body weight/24 hours
Reported in unit of mg/specimen
Delta G (DG), the Gibbs free energy of transfer from a supersaturated to a saturated solution is negative for undersaturated solutions and positive for supersaturated solutions. In most cases the supersaturation levels are slightly positive even in normal individuals but are balanced by an inhibitor activity.
While the DG of urine is often positive, even in the urine of nonstone formers, on average, the DG is even more positive in those individuals who do form kidney stones. The "normal" values are simply derived by comparing urinary DG values for the important stone-forming crystalline phases between a population of stone formers and a population of nonstone formers. Those DG values that are outside the expected range in a population of nonstone formers are marked "abnormal."
A normal or increased citrate value suggests that potassium citrate may be a less effective choice for treatment of a patient with calcium oxalate or calcium phosphate stones.
If the urine citrate is low, secondary causes should be excluded including hypokalemia, renal tubular acidosis, gastrointestinal bicarbonate losses (eg, diarrhea or malabsorption), or an exogenous acid load (eg, excessive consumption of meat protein).
An increased urinary oxalate value may prompt a search for genetic abnormalities of oxalate production (ie, primary hyperoxaluria). Secondary hyperoxaluria can result from diverse gastrointestinal disorders that result in malabsorption. Milder hyperoxaluria could result from excess dietary oxalate consumption, or reduced calcium (dairy) intake, perhaps even in the absence of gastrointestinal disease.
The results can be used to determine the likely effect of a therapeutic intervention on stone-forming risk. For example, taking oral potassium citrate will raise the urinary citrate excretion, which should reduce calcium phosphate supersaturation (by reducing free ionic calcium), but citrate administration also increases urinary pH (because it represents an alkali load) and a higher urine pH promotes calcium phosphate crystallization. The net result of this or any therapeutic manipulation could be assessed by collecting a 24-hour urine and comparing the supersaturation calculation for calcium phosphate before and after therapy.
Important stone-specific factors:
-Calcium oxalate stones: urine volume, calcium, oxalate, citrate, and uric acid excretion are all risk factors that are possible targets for therapeutic intervention.
-Calcium phosphate stones (apatite or brushite): urinary volume, calcium, pH, and citrate significantly influence the supersaturation for calcium phosphate. Of note, a urine pH <6 may help reduce the tendency for these stones to form.
-Uric acid stones: urine pH, volume, and uric acid excretion levels influence the supersaturation. Urine pH is especially critical, in that uric acid is unlikely to crystallize if the pH is >6.
-Sodium urate stones: alkaline pH and high uric acid excretion promote stone formation.
A low urine volume is a universal risk factor for all types of kidney stones.
The urine is often supersaturated with respect to the common crystalline constituents of stones, even in nonstone formers.
Individual interpretation of the supersaturation values in light of the clinical situation is critical. In particular, treatment may reduce the supersaturation with respect to 1 crystal type, but increase the supersaturation with respect to another. Therefore, the specific goals of treatment must be considered when interpreting the test results.
1. Werness PG, Brown CM, Smith LH, Finlayson B: EQUIL2: a BASIC computer program for the calculation of urinary saturation. J Urol 1985;134:1242-1244
2. Parks JH, Coward M, Coe FL: Correspondence between stone composition and urine supersaturation in nephrolithiasis. Kidney Int 1997;51:894-900
3. Finlayson B: Calcium stones: Some physical and clinical aspects. In Calcium in Renal Failure and Nephrolithiasis. Edited by DS David. New York, John Wiley and Sons, 1977, pp 337-382