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UPJ INSIGHT Class-Specific Side Effects Across Preventative Pharmacologic Therapies for Kidney Stone Disease

By: Ryan S. Hsi, MD, Vanderbilt University Medical Center, Nashville, Tennessee; Joseph J. Crivelli, MD, University of Alabama at Birmingham School of Medicine and Birmingham Veterans Affairs Medical Center; Phyllis L. Yan, MS, University of Michigan, Ann Arbor; Vahakn Shahinian, MD, MS, University of Michigan, Ann Arbor; John M. Hollingsworth, MD, MS, NorthShore University Health System, Chicago, Illinois | Posted on: 19 Jan 2024

Hsi RS, Crivelli JJ, Yan PL, Shahinian V, Hollingsworth JM. Comparison of class-specific side effects across preventative pharmacologic therapies for kidney stone disease. Urol Pract. 2024;11(1):171-178.

Study Need and Importance

Preventative pharmacologic therapy (PPT) is an important treatment strategy for reducing kidney stone recurrence events. Among the different medication classes of PPT—specifically alkali citrate, thiazide diuretics, and allopurinol—improving the knowledge base on the side effects from PPT might inform patients and providers choosing among PPT classes. Within this context, we performed an observational study using medical claims data to understand the occurrence of side effects within 2 years following the initiation of PPT for kidney stone prevention.

What We Found

Our cohort consisted of 1776 (34%), 2767 (53%), and 677 (13%) patients prescribed alkali citrate, thiazides, or allopurinol, respectively. Comparing unadjusted rates of incident diagnoses, thiazides compared to alkali citrate and allopurinol were associated with the highest rates of hypercalcemia (2.3% vs 1.5% and 1.0%, respectively, P = .04), hypokalemia (6% vs 3% and 2%, respectively, P < .01), and hyperglycemia/diabetes (17% vs 11% and 16%, respectively, P < .01). In adjusted analyses, compared to alkali citrate, thiazides were associated with a higher odds of hypokalemia (OR = 2.01, 95% CI 1.44-2.81) and hyperglycemia/diabetes (OR = 1.52, 95% CI 1.26-1.83), while allopurinol was associated with a higher odds of hyperglycemia/diabetes (OR = 1.34, 95% CI 1.02-1.75; Figure).

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Figure. Adjusted rates of side effects over 2 years comparing preventative pharmacologic therapy medication classes among patients with kidney stone disease. * indicates adjusted for age, sex, race/ethnicity, education, region of residence, Charlson Index, high-risk status for stone recurrence, and preventative pharmacologic therapy adherence; CI, confidence interval; ref, reference.

Limitations

We acknowledge the possibility of missing data, miscoding, and unmeasured differences between the PPT groups. The administrative data set lacks detail beyond kidney stone diagnosis and procedure codes. Claims-based diagnoses of side effects likely underestimate the true incidence of side effects; however, since these are captured during the course of care, they should represent more serious clinical presentations.

Interpretation for Patient Care

We confirm known relationships between thiazides with hypokalemia, hyperglycemia/diabetes, and less commonly, hypercalcemia. These data provide evidence to support clinical guidelines that recommend periodic serum testing to assess for adverse effects from PPT.

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