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.
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 CKDpatients 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 CKDpatients 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.
Authors: A F Subar; F E Thompson; V Kipnis; D Midthune; P Hurwitz; S McNutt; A McIntosh; S Rosenfeld Journal: Am J Epidemiol Date: 2001-12-15 Impact factor: 4.897
Authors: Emil Hagström; Per Hellman; Tobias E Larsson; Erik Ingelsson; Lars Berglund; Johan Sundström; Håkan Melhus; Claes Held; Lars Lind; Karl Michaëlsson; Johan Arnlöv Journal: Circulation Date: 2009-05-18 Impact factor: 29.690
Authors: Ming Teng; Myles Wolf; Edmund Lowrie; Norma Ofsthun; J Michael Lazarus; Ravi Thadhani Journal: N Engl J Med Date: 2003-07-31 Impact factor: 91.245
Authors: L Rejnmark; P Vestergaard; A R Pedersen; L Heickendorff; F Andreasen; L Mosekilde Journal: Eur J Clin Invest Date: 2003-01 Impact factor: 4.686
Authors: Mariette W C J Schoofs; Marjolein van der Klift; Albert Hofman; Chris E D H de Laet; Ron M C Herings; Theo Stijnen; Huibert A P Pols; Bruno H Ch Stricker Journal: Ann Intern Med Date: 2003-09-16 Impact factor: 25.391
Authors: Harold I Feldman; Lawrence J Appel; Glenn M Chertow; Denise Cifelli; Borut Cizman; John Daugirdas; Jeffrey C Fink; Eunice D Franklin-Becker; Alan S Go; L Lee Hamm; Jiang He; Tom Hostetter; Chi-Yuan Hsu; Kenneth Jamerson; Marshall Joffe; John W Kusek; J Richard Landis; James P Lash; Edgar R Miller; Emile R Mohler; Paul Muntner; Akinlolu O Ojo; Mahboob Rahman; Raymond R Townsend; Jackson T Wright Journal: J Am Soc Nephrol Date: 2003-07 Impact factor: 10.121
Authors: Scott Sibbel; Adam G Walker; Carey Colson; Francesca Tentori; Steven M Brunelli; Jennifer Flythe Journal: Clin J Am Soc Nephrol Date: 2018-12-19 Impact factor: 8.237
Authors: Rosilene Motta Elias; Maria Aparecida Dalboni; Ana Carolina E Coelho; Rosa M A Moysés Journal: Curr Osteoporos Rep Date: 2018-12 Impact factor: 5.096
Authors: Sushrut S Waikar; Anand Srivastava; Ragnar Palsson; Tariq Shafi; Chi-Yuan Hsu; Kumar Sharma; James P Lash; Jing Chen; Jiang He; John Lieske; Dawei Xie; Xiaoming Zhang; Harold I Feldman; Gary C Curhan Journal: JAMA Intern Med Date: 2019-04-01 Impact factor: 21.873
Authors: David J Margolis; Jayanta Gupta; Stephen R Thom; Raymond R Townsend; Peter A Kanetsky; Ole Hoffstad; Maryte Papdopoulos; Michael Fischer; Jeffrey R Schelling; Nandita Mitra Journal: Wound Repair Regen Date: 2012-12-10 Impact factor: 3.617