Can dipsticks be used for specific gravity in urine samples from chemotherapy?

The dipstick method is a fast and easy way to assess urinalysis; however, the technology is prone to many interferences that can disrupt the chemical reaction or interfere with the color developing/reading (1). Recently, we have learned a discordance in specific gravity between the Clinitek Status Analyzer (Siemens Healthcare Diagnostics, Tarrytown, NY), a semi-automated urinalysis analyzer reading dipsticks, and refractometer in patients receiving chemotherapy. Chemotherapy agents, such as methotrexate and cisplatin, require a hydration protocol based on urine specific gravity and pH before and during the course of treatment to minimize renal toxicity (2). We observed that the dipstick method (manual or Clinitek) produced a higher specific gravity than the refractometer. The discrepancy can sometimes be greater than 0.01 and either delayed the chemotherapy by unnecessary hydration or misled the treatment course.

The solute concentration of urine, which reflects the concentrating ability of kidneys, can be quantitated by measuring either specific gravity or osmolality. The specific gravity is the ratio of the mass of a solution compared with the mass of an equal volume of water. This is actually a comparison of weights; it does not measure the exact number of dissolved particles like does osmolality. Nevertheless, specific gravity is preferred due to a number of rapid techniques available, including the dipstick method. The pad reagent contains an electrolyte-dye mixture that elicits a pH change based on the ionic concentration (pKa) of the urine and prompts a color change of the dye. The refractometer is another method, which is used by most fully automated urine chemistry analyzers. It measures refractive index, which is the ability to bend light, and is proportional to the amount of total solids dissolved in a liquid.

There are a couple of possible mechanisms why chemotherapy agents could affect the dipstick method. Urine produced by patients receiving methotrexate presents with fluorescent yellow color, which might interfere with the color-reading of the dipstick. Another possible cause could be that methotrexate is highly ionized at physiological pH and affects the dipstick method more than the refractometer method, which represents the weight of total dissolved solids in urine.

Studies have also shown discrepant results in pH or specific gravity produced by the dipsticks and a pH meter or a refractometer in patients receiving chemotherapy (3,4), which are consistent with our observations. Moreover, the manufacturer of the Multistix Reagent Strips (Siemens Healthcare Diagnostics, Tarrytown, NY) issued a customer bulletin stating that the specific gravity reagent test in Multistix products should not be used to make a medical decision regarding chemotherapy treatment in patients. Limitations given for the reagents include specific substances and conditions that may affect the test results (5).

REFERENCES

1. Siemens Healthcare Diagnostics. Multistix 10 SG package insert; 2010 [Rev 06/10 USA].
2. Meredith S, Hilliard J, Vaillancourt R. Evaluation of a rapid hydration protocol: safety and effectiveness. J Oncol Pharm Pract. 2017 Jun;23(4):249-254.
3. Wockenfus AM, Koch CD, Conlon PM, Sorensen LD, Cambern KL, Chihak AJ, Zmolek JA, Petersen AE, Burns BE, Lieske JC, Karon BS. Discordance of urine pH measured by dipstick and pH meter: implications for methotrexate administration protocols. Clin Biochem. 2013 Jan;46(1-2):152-154.
4. Kalbfeld K,  Parkosewich J, Teng W, Funk M. Comparison of Point-of-Care Testing Methods and Laboratory Analysis for Assessing Urine Specific Gravity and pH of Children Undergoing Chemotherapy. J Pediatr Oncol Nurs. 2021;38(1):6-15.
5. Siemens Healthcare Diagnostics. Customer Bulletin: Use of Multistix Specific Gravity Reagent for Chemotherapy Decisions; 11/2016.