Twenty-Four Hour Urine Testing and Prescriptions for Urinary Stone Disease–Related Medications in Veterans

Discussion

In this study we used a large national cohort of Veterans to specifically test whether clinicians initiate or continue medications for prevention of urinary stone disease in response to 24-hour urine testing. We found that clinicians are more likely to prescribe thiazides, alkali therapy, or allopurinol for stone formers who complete 24-hour urine testing. Moreover, clinicians are more likely to prescribe these medications if a 24-hour urine test detects an elevated metabolic risk parameter for urinary stone disease. These findings suggest that clinicians do respond to results obtained from 24-hour urine testing and adjust their prescription patterns for the prevention of urinary stone disease.

However, we also show that clinicians could be more cognizant of initiating or continuing medications that decrease urolithiasis risk in patients with abnormal 24-hour urine tests. For example, only 38% of patients with severe hypercalciuria (urine calcium excretion >400 mg/d) were prescribed thiazides—drugs that are well known to decrease urinary calcium excretion. Similarly, only 44% of patients with severe hypocitraturia (urine citrate excretion ≤200 mg/d) were prescribed alkali therapy. Reasons for the lower-than-expected use of these medications are unclear. Patient factors such as unwillingness to initiate new medications, inability to tolerate side effects of medications (e.g., hypotension and/or hyperuricemia with thiazides or gastrointestinal discomfort with potassium citrate), or contraindications (e.g., hyponatremia with thiazides or hyperkalemia with potassium citrate) may play a role. Some patients may have opted for dietary and lifestyle modifications only. For example, some providers may have recommended a reduction in dietary sodium rather than a prescription with a thiazide as a strategy to reduce urine calcium excretion. In support of this possibility, we found that patients who completed 24-hour urine testing were more likely to visit a nutritionist or dietitian compared with those who did not. Although we are unable to determine the exact reason(s) for these visits, we can assume that at least a proportion of these were related to dietary counseling for stone prevention.

We considered possible geographic or provider factors underlying the lower-than-expected use of medications which are believed to decrease risk for urolithiasis. However, we found no clinically meaningful regional differences that could explain the limited use of these medications (in other words, there appears to be underutilization of potentially effective medications for stone prevention across the VHA system). We also found that prescriptions of stone-related medications differed significantly depending on whether patients visited a specialist after a 24-hour urine collection. Approximately one in five patients who completed 24-hour urine testing did not visit a urologist or nephrologist within 6 months of a 24-hour urine test; these stone formers had the lowest utilization of stone-related medications. These findings could reflect the relative lack of patient follow-up visits, denying stone specialists the opportunity to respond. Alternatively, patients who completed 24-hour urine testing could have returned to see primary care physicians or nonphysician providers who might be less inclined to respond to 24-hour urine testing. In contrast, patients who visited both a urologist and nephrologist within 6 months of 24-hour urine collection were the group most likely to be prescribed stone-related medications, suggesting that multidisciplinary care with urologists and nephrologists for high-risk stone formers could represent an approach toward improving medical (and ultimately surgical) management of urinary stone disease.

This study has several strengths. The VHA is well suited for evaluating the practice of 24-hour urine testing in prevention of urolithiasis. The VHA is an integrated health care system, which enabled us to link prescription patterns across this nationwide stone cohort with a broad and diverse array of patients. Veterans receiving care in the VHA are older, more likely to be men, and have higher rates of comorbid illnesses compared with the general patient population, all attributes that place them at higher risk for urinary stone disease (1). The VHA also provides full access to laboratory results, allowing us to compare use of stone prevention medications stratified by 24-hour urine results—a feature not possible in other large data sets devoid of laboratory and prescription data, where claims are used exclusively. Finally, clinicians in the VHA do not require prior authorization from insurance companies to order 24-hour urine collections, which could reduce detection bias that may be present in civilian health care systems.

This study has several limitations. First, because the majority of the VHA study population consists of men, we may not be able to fully generalize these results to populations with higher proportions of women. Second, we defined a 24-hour urine collection for the purpose of determining risk for urinary stone disease to be any one of four urinary parameters (calcium, oxalate, citrate, or sulfate). Whereas the objective of this approach was to maximize specificity for evaluation and/or prevention of urinary stone disease, it is possible that some of these tests, particularly 24-hour urine calcium, were ordered for other indications. It is also possible that we did not capture data from all VHA facilities that send 24-hour urine samples to an outside laboratory for processing. To address this concern, we queried 24-hour urine data from our local VHA facility, which sends out 24-hour urine samples to an outside laboratory. We confirmed that 24-hour urine calcium, oxalate, citrate, and sulfate were recorded in the VHA, but we acknowledge that we do not know if this would be the case for all VHA facilities. Third, the use of ICD-9 codes to capture patients with urinary stone disease may overestimate prevalence of symptomatic stone disease because some patients may be asymptomatic stone formers. Fourth, we did not capture medical care for patients stone formers who received care outside the VHA. Fifth, we were unable to abstract information on stone composition. Finally, we were not able to determine from VHA data the specific reasons why clinicians prescribed or discontinued stone-related medications. Although we suggest that clinicians respond to 24-hour urine testing by initiating or continuing medications that reduce stone risk, we cannot exclude the possibility that clinicians happen to order 24-hour urine testing in Veterans with more severe stone disease and who happen to be on medical therapy. We also cannot exclude the possibility that a clinician may have considered a previous 24-hour urine test, outside our observation period, in his or her decision to prescribe a stone-related medication. Alternatively, we were limited by the difficulty in surmising from aggregate data what were the individual reasons that led to discontinuation, or lack of initiation, of medications for stone prevention.

In conclusion, our study suggests that clinicians use information from 24-hour urine testing and adjust their practice patterns by increasing prescriptions of medications believed to reduce risk in stone formers. In spite of our observations that relevant clinical data changes provider practice patterns in patients with urinary stone disease, the fact remains that the majority of stone formers with urine abnormalities predisposing them to a high risk of stone recurrence are not prescribed stone-related medications that could reduce that risk. Acquisition of additional observational or interventional evidence evaluating the use of stone-related medications to prevent stone recurrence, implementation of multidisciplinary care with urologists and nephrologists for patients who are high-risk stone formers, and determination of the optimal use of urine testing for diagnosis of metabolic abnormalities could improve the care of Veterans and non-Veterans with urinary stone disease.