Diuretics, Calciuria and Secondary Hyperparathyroidism in the Chronic Renal Insufficiency Cohort
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Nephrology
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Background: Secondary hyperparathyroidism is a common complication of chronic kidney disease (CKD) that is associated with bone disease, cardiovascular disease and death. Pathophysiological factors that maintain secondary hyperparathyroidism in advanced CKD are well-known, but early mechanisms of the disease that can be targeted for its primary prevention are poorly understood. Diuretics are widely used to control volume status and blood pressure in CKD patients but are also known to have important effects on renal calcium handling, which we hypothesized could alter the risk of secondary hyperparathyroidism.
Methods: We examined the relationship of diuretic treatment with urinary calcium excretion, parathyroid hormone (PTH) levels and prevalence of secondary hyperparathyroidism (PTH ≥ 65 pg/mL) in a cross-sectional study of 3616 CKD patients in the Chronic Renal Insufficiency Cohort.
Results: Compared with no diuretics, treatment with loop diuretics was independently associated with higher adjusted urinary calcium (55.0 versus 39.6 mg/day; P < 0.001), higher adjusted PTH [67.9, 95% confidence interval (CI) 65.2-70.7 pg/mL, versus 52.8, 95% CI 51.1-54.6 pg/mL, P < 0.001] and greater odds of secondary hyperparathyroidism (odds ratio 2.1; 95% CI 1.7-2.6). Thiazide monotherapy was associated with lower calciuria (25.5 versus 39.6 mg/day; P < 0.001) but only modestly lower PTH levels (50.0, 95% CI 47.8-52.3, versus 520.8, 95% CI 51.1-54.6 pg/mL, P = 0.04) compared with no diuretics. However, coadministration of thiazide and loop diuretics was associated with blunted urinary calcium (30.3 versus 55.0 mg/day; P <0.001) and odds of hyperparathyroidism (odds ratio 1.3 versus 2.1; P for interaction = 0.05) compared with loop diuretics alone.
Conclusions: Loop diuretic use was associated with greater calciuria, PTH levels and odds of secondary hyperparathyroidism compared to no treatment. These associations were attenuated in patients who were coadministered thiazides. Diuretic choice is a potentially modifiable determinant of secondary hyperparathyroidism in CKD.
Hirai T, Mori Y, Ogura T, Kondo Y, Sakazaki Y, Ishitsuka Y J Pharm Health Care Sci. 2024; 10(1):60.
PMID: 39334301 PMC: 11437979. DOI: 10.1186/s40780-024-00380-8.
Heitman K, Alexander M, Faul C Int J Mol Sci. 2024; 25(10).
PMID: 38791164 PMC: 11121428. DOI: 10.3390/ijms25105117.
Phelps K, Gemoets D, May P PLoS One. 2022; 17(8):e0272380.
PMID: 35913960 PMC: 9342777. DOI: 10.1371/journal.pone.0272380.
Determinants and Outcomes Associated With Urinary Calcium Excretion in Chronic Kidney Disease.
Liu J, Tio M, Verma A, Schmidt I, Ilori T, Knauf F J Clin Endocrinol Metab. 2021; 107(1):e281-e292.
PMID: 34390334 PMC: 8684460. DOI: 10.1210/clinem/dgab574.
Effects of diuretics furosemide and hydrochlorothiazide on CKD-MBD: A prospective randomized study.
Vasco R, Takayama L, Pereira R, Moyses R, Elias R Bone Rep. 2021; 14:100746.
PMID: 33490315 PMC: 7811042. DOI: 10.1016/j.bonr.2021.100746.