Elsevier

Seminars in Nephrology

Volume 31, Issue 6, November 2011, Pages 535-541
Seminars in Nephrology

Diuretics and Disorders of Calcium Homeostasis

https://doi.org/10.1016/j.semnephrol.2011.09.008Get rights and content

Summary

Diuretics commonly are administered in disorders of sodium balance. Loop diuretics inhibit the Na-K-2Cl transporter and also increase calcium excretion. They are often used in the treatment of hypercalcemia. Thiazide diuretics block the thiazide-sensitive NaCl transporter in the distal convoluted tubule, and can decrease calcium excretion. They are often used in the treatment of nephrolithiasis. Carbonic anhydrase inhibitors decrease bicarbonate absorption and the resultant metabolic acidosis can increase calcium excretion. Their use can promote nephrocalcinosis and nephrolithiasis. This review will address the use of diuretics on disorders of calcium homeostasis.

Section snippets

Use of Diuretics in Nephrolithiasis

Nephrolithiasis is a common disorder, affecting as many as 12% of men living in industrialized nations.1, 2 Approximately 70% to 80% of all kidney stones contain calcium, usually in the form of calcium oxalate or calcium phosphate, and hypercalciuria is found in 40% to 50% of these calcium stone formers. The precise etiology of hypercalciuria in these stone formers is generally not known and is termed idiopathic hypercalciuria. Without treatment, 40% to 50% of stone formers will pass a second

Association of Thiazides With Bone Health

Osteoporosis is the most prevalent metabolic bone disorder in developed countries. It is characterized by low bone mass and abnormal bone architecture, which predisposes to fractures. Risk factors for osteoporosis include age; genetic factors including sex, ethnicity, and family history; as well as environmental characteristics including nutrition and calcium intake. Many hypercalciuric patients have decreased bone density whether or not they form stones.22 Thiazides reduce urine calcium

Thiazide-Induced Hypercalcemia

Thiazide diuretics are associated with and presumably cause hypercalcemia in some patients. The hypercalcemia is typically mild and in the absence of other causes of hypercalcemia is promptly reversible on discontinuation of the thiazide. Wermers et al30 investigated the incidence of thiazide-associated hypercalcemia in Olmsted County, Minnesota. They found that the incidence was 7.7 per 100,000, with the highest rate of 55.3 per 100,000 in women aged 70 to 79 years. The average of the highest

Use of Loop Diuretics in the Treatment of Hypercalcemia

The serum calcium level represents a balance between gastrointestinal absorption of calcium, calcium flux into and out of the skeleton, as well as urinary excretion of calcium. The most common causes of hypercalcemia include primary hyperparathyroidism and malignant disease. In primary hyperparathyroidism, parathyroid hormone (PTH) will increase the serum 1,25-dihydroxycholecalciferol, resulting in increased intestinal calcium absorption. In addition, both parathyroid hormone and

Loop Diuretics and Osteoporosis

Loop diuretics increase renal calcium excretion. Treatment with loop diuretics is associated with a decrease in bone mineral density. In one cohort study including 348 postmenopausal women, use of a loop diuretic was associated with an increased risk of osteoporotic fractures.44 Rejnmark et al,45 in a randomized controlled study with bumetanide in postmenopausal women, showed that treatment with this loop diuretic for 1 year resulted in a decrease in bone mineral density measured from: the

Loop Diuretics, Nephrolithiasis, and Nephrocalcinosis

Furosemide-related nephrocalcinosis was first reported by Hufnagle et al47 in low-birth-weight premature infants in 1982. These calcifications generally resolve on discontinuation of the diuretic. The nephrocalcinosis caused by furosemide appears related to hypercalciuria, but has been reported even in infants who are not hypercalciuric.48 Resolution of the nephrocalcinosis occurs more often if the hypercalciuria resolves after stopping furosemide.

In adults, Kim et al49 reported medullary

Carbonic Anhydrase Inhibitors and Nephrocalcinosis

Carbonic anhydrase inhibitors act in the proximal tubule to inhibit bicarbonate reabsorption and can cause metabolic acidosis. Hypocitraturia, hypercalciuria, nephrocalcinosis, and nephrolithiasis have been reported with acetazolamide.50, 51 It is likely that both hypocitraturia and hypercalciuria lead to nephrocalcinosis and nephrolithiasis owing to the carbonic anhydrase inhibitors. Metabolic acidosis will decrease urinary citrate, which is an important inhibitor of nephrolithiasis because it

Conclusions

Although diuretics commonly are administered to increase sodium excretion, they do have significant effects on calcium balance. The effects often can be explained physiologically by the site of action of these diuretics in the nephron. Thiazides can be used therapeutically in nephrolithiasis whereas loop diuretics can be used as an adjunct to the treatment of hypercalcemia. Both thiazides and loop diuretics appear to have effects on bone. In the case of acetazolamide, secondary metabolic

References (55)

  • S.E. Leibman et al.

    Idiopathic hypercalciuria

    Curr Rheumatol Rep

    (2006)
  • E.M. Worcester et al.

    Calcium kidney stones

    N Engl J Med

    (2010)
  • R.A. Sutton

    Diuretics and calcium metabolism

    Am J Kidney Dis

    (1985)
  • T. Nijenhuis et al.

    Enhanced passive Ca2+ reabsorption and reduce Mg2+ channel abundance explains thiazide-induced hypocalciuria and hypomagnesemia

    J Clin Invest

    (2005)
  • D.A. Bushinsky et al.

    Thiazides reduce brushite, but not calcium oxalate, supersaturation, and stone formation in genetic hypercalciuric stone-forming rats

    J Am Soc Nephrol

    (2005)
  • Bushinsky DA, Willett T, Asplin JR, Grynpas MD. Chlorthalidone improves bone quality in genetic hypercalciuric...
  • R.F. Reilly et al.

    The evidence-based use of thiazide diuretics in hypertension and nephrolithiasis

    Clin J Am Soc Nephrol

    (2010)
  • M.S. Pearle

    Prevention of nephrolithiasis

    Curr Opin Nephrol Hypertens

    (2001)
  • M.S. Pearle et al.

    Meta-analysis of randomized trials for medical prevention of calcium oxalate nephrolithiasis

    J Endourol

    (1999)
  • D.C. Brater

    Diuretic therapy

    N Engl J Med

    (1998)
  • L. Borghi et al.

    Randomized prospective study of a nonthiazide diuretic, indapamide, in preventing stone recurrences

    J Cardiovasc Pharmacol

    (1993)
  • E. Laerum et al.

    Thiazide prophylaxis of urolithiasis

    Acta Med Scand

    (1984)
  • L. Borghi et al.

    Comparison of two diets for the prevention of recurrent stones in idiopathic hypercalciuria

    N Engl J Med

    (2002)
  • A.S. Brickman et al.

    Changes in serum and urinary calcium during treatment with hydrochlorothiazide: studies on mechanisms

    J Clin Invest

    (1972)
  • L.A. Frasetto et al.

    Comparative effects of potassium chloride and bicarbonate on thiazide-induced reduction in urinary calcium excretion

    Kidney Int

    (2000)
  • D. Leppla et al.

    Effect of amiloride with or without hydrochlorothiazide on urinary calcium and saturation of calcium salts

    J Clin Endocrinol Metab

    (1983)
  • I.P. Heilberg et al.

    Bone disease in idiopathic hypercalciuria

    Curr Opin Nephrol Hypertens

    (2006)
  • Cited by (33)

    • Parathyroid hormone independent hypercalcemia in adults

      2018, Best Practice and Research: Clinical Endocrinology and Metabolism
      Citation Excerpt :

      PTH-secretion is not believed to be directly stimulated, but PTH is often inappropriately high and this makes differentiation towards primary hyperparathyroidism challenging [122,123]. Thiazide induced hypercalcemia is normally mild and non-progressive (equilibrium) [124,125]. Hypercalcemia normally resolves within months after discontinuation of medication.

    • The evidence and rationale for the perioperative use of loop diuretics during kidney transplantation: A comprehensive review

      2018, Transplantation Reviews
      Citation Excerpt :

      This causes inactivation of calcium dependent proteases and mitochondrial dysfunction [72,86–88]. LD increase calcium excretion via multiple mechanisms [89]. In rat hearts, LD use significantly improved the mechanical recovery and the coronary flow of the hearts preserved for 8 h [88].

    • Primary Hyperparathyroidism and the Kidney

      2015, The Parathyroids: Basic and Clinical Concepts: Third Edition
    • Nutritional Prevention and Treatment of Kidney Stones

      2013, Nutritional Management of Renal Disease
    View all citing articles on Scopus
    View full text