Idiopathic hypercalciuria: diagnosis, classification, and treatment
Keywords:
idiopathic hypercalciuria, therapy, diagnosis, classification, calcium, calciuria, nephrolithiasis
Abstract
Introduction: Idiopathic hypercalciuria is defined as urine calcium excretion greater than 220 mg/day in women and 300 mg/day in men, or greater than 4 mg/kg under regular dietary conditions. Objective: The aim of this study is to review the diagnosis, classification, and treatment of hypercalciuric patients with renal lithiasis. Methods: We enrolled 250 patients suffering from renal lithiasis and idiopathic hypercalciuria and 80 healthy subjects as control group. Lab tests were performed to diagnose renal lithiasis. Results: Although the 24-hour urine test is the gold standard to determine calciuria, in this study we propose considering the Ca/Kg >4 mg/Kg ratio or an index of >140 mg of Ca per gram urine creatinine. Regarding the different types of hypercalciuria, after following a strict diet, subjects were divided into two groups: diet-dependent and diet-independent hypercalciuria. Concerning the treatment, we suggest diuretic therapy to achieve a urine output of 2-2.5 liters per day. In the case of subjects with diet-dependent hypercalciuria, we advise an intake of 600-800 mg of calcium and a moderate reduction in animal protein and salt intake. In cases of non-response to treatment in subjects with diet-dependent hypercalciuria, thiazides, chlorthalidone, indapamide and, in some cases, bisphosphonates may help control hypercalciuria with a lower risk of lithiasis recurrence and healthier bones. Conclusions: We believe it is important to consider not only the methods to diagnose hypercalciuria but also its classification to provide a better treatment.
References
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7) Giannini S, Nobile M, Dalle Carbonare L, Lodetti MG, Sella S, Vittadello G, et al. Hypercalciuria is a common and important finding in postmenopausal women with osteoporosis. Eur J Endocrinol. 2003;149(3):209-13. doi: 10.1530/eje.0.1490209.
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23) Bihl G, Meyers A. Recurrent renal stone disease-advances in pathogenesis and clinical management. Lancet. 2001;358(9282):651-6. doi: 10.1016/S0140-6736(01)05782-8.
24) Weisinger JR, Alonzo E, Machado C, Carlini R, Martinis R, Paz-Martinez V, et al. Papel del hueso en la fisiopatología de la hipercalciuria idiopática. Medicina (B. Aires). 1997;57(supl. 1):45-8.
25) Coe FL, Parks JH. New insights into the pathophysiology and treatment of nephrolithiasis: new research venues. J Bone Miner Res. 1997;12(4):522-33. doi: 10.1359/jbmr.1997.12.4.522.
26) Weisinger JR, Alonzo E, Bellorín-Font E, Blasini AM, Rodríguez MA, Paz-Martínez V, et al. Possible role of cytokines on the bone mineral loss in idiopathic hypercalciuria. Kidney Int. 1996;49(1):244-50. doi: 10.1038/ki.1996.34.
27) Farías ML, Delgado AG, Rosenthal D, Vieira JG, Kasamatsu T, Lazarevitch MJ, et al. The cause of maintained hypercalciuria after the surgical cure of primary hyperparathyroidism is a defect in renal calcium reabsorption. J Endocrinol Invest. 1996;19(1):12-20. doi: 10.1007/BF03347852.
28) Breslau NA. Pathogenesis and management of hypercalciuric nephrolithiasis. Miner Electrolyte Metab. 1994;20(6):328-39.
29) Pacifici R. Idiopathic hypercalciuria and osteoporosis: distinct clinical manifestations of increased cytokine-induced bone resorption? J Clin Endocrinol Metab. 1997;82(1):29-31. doi: 10.1210/jcem.82.1.3706.
30) Ishimi Y, Miyaura C, Jin CH, Akatsu T, Abe E, Nakamura Y, et al. IL-6 is produced by osteoblasts and induces bone resorption. J Immunol. 1990;145(10):3297-303.
31) Passeri G, Girasole G, Jilka RL, Manolagas SC. Increased interleukin-6 production by murine bone marrow and bone cells after estrogen withdrawal. Endocrinology. 1993;133(2):822-8. doi: 10.1210/endo.133.2.8393776.
32) Costanzo LS, Weiner IM. On the hypocalciuric action of chlorothiazide. J Clin Invest. 1974;54(3):628-37. doi: 10.1172/JCI107800.
33) Jang HR, Kim S, Heo NJ, Lee JH, Kim HS, Nielsen S, et al. Effects of thiazide on the expression of TRPV5, calbindin-D28K, and sodium transporters in hypercalciuric rats. J Korean Med Sci. 2009;24 Suppl(Suppl 1):S161-9. doi: 10.3346/jkms.2009.24.S1.S161.
34) Spivacow FR, Negri AL, del Valle E. Efecto a largo plazo de tiazidas sobre la masa ósea en mujeres con nefrolitiasis hipercalciúrica. Rev Nefrol Dial Traspl. 2013;33(4):180-7.
35) Zanchetta JR, Rodríguez G, Negri AL, del Valle E, Spivacow FR. Bone mineral density in patients with hypercalciuric nephrolithiasis. Nephron. 1996;73(4):557-60. doi: 10.1159/000189140.
36) Ceylan K, Topal C, Erkoc R, Sayarlioglu H, Can S, Yilmaz Y, et al. Effect of indapamide on urinary calcium excretion in patients with and without urinary stone disease. Ann Pharmacother. 2005;39(6):1034-8. doi: 10.1345/aph.1E544.
2) del Valle EE, Spivacow FR, Zanchetta JR. Alteraciones metabólicas en 2612 pacientes con litiasis renal. Medicina (B Aires). 1999;59(5/1):417-22.
3) Coe FL, Evan A, Worcester E. Kidney stone disease. J Clin Invest. 2005;115(10):2598-608. doi: 10.1172/JCI26662.
4) Lauderdale DS, Thisted RA, Wen M, Favus MJ. Bone mineral density and fracture among prevalent kidney stone cases in the Third National Health and Nutrition Examination Survey. J Bone Miner Res. 2001;16(10):1893-8. doi: 10.1359/jbmr.2001.16.10.1893.
5) Melton LJ 3rd, Crowson CS, Khosla S, Wilson DM, O'Fallon WM. Fracture risk among patients with urolithiasis: a population-based cohort study. Kidney Int. 1998;53(2):459-64. doi: 10.1046/j.1523-1755.1998.00779.x.
6) Vezzoli G, Soldati L, Gambaro G. Hypercalciuria revisited: one or many conditions? Pediatr Nephrol. 2008;23(4):503-6. doi: 10.1007/s00467-007-0574-3.
7) Giannini S, Nobile M, Dalle Carbonare L, Lodetti MG, Sella S, Vittadello G, et al. Hypercalciuria is a common and important finding in postmenopausal women with osteoporosis. Eur J Endocrinol. 2003;149(3):209-13. doi: 10.1530/eje.0.1490209.
8) Coe FL, Parks JH, Asplin JR. The pathogenesis and treatment of kidney stones. N Engl J Med. 1992;327(16):1141-52. doi: 10.1056/NEJM199210153271607.
9) Manz F, Kehrt R, Lausen B, Merkel A. Urinary calcium excretion in healthy children and adolescents. Pediatr Nephrol. 1999;13(9):894-9. doi: 10.1007/s004670050723.
10) Hodgkinson A, Pyrah LN. The urinary excretion of calcium and inorganic phosphate in 344 patients with calcium stone of renal origin. Br J Surg. 1958;46(195):10-8. doi: 10.1002/bjs.18004619504.
11) Worcester EM, Coe FL. Evidence for altered renal tubule function in idiopathic calcium stone formers. Urol Res. 2010;38(4):263-9. doi: 10.1007/s00240-010-0299-9.
12) Coe FL, Parks JH. Nephrolithiasis: Pathogenesis and treatment. 2nd ed. Chicago: Year Book Medical Publishers,1998, pp. 109-10.
13) Spivacow FR, Pailler M, Martínez P. Hipercalciuria Idiopática: ¿se pueden evitar los diuréticos? Medicina (B Aires). 2019;79(6):477-82.
14) Pak CY. Medical stone management: 35 years of advances. J Urol. 2008;180(3):813-9. doi: 10.1016/j.juro.2008.05.048.
15) Bataille P, Fardellone P, Ghazali A, Cayrolle G, Hottelart C, Achard JM, et al. Pathophysiology and treatment of idiopathic hypercalciuria. Curr Opin Rheumatol. 1998;10(4):373-88. doi: 10.1097/00002281-199807000-00017.
16) McDonald MW, Stoller ML. Urinary stone disease: a practical guide to metabolic evaluation. Geriatrics. 1997;52(5):38-40, 49-52, 55-6.
17) Ghazali S, Barratt TM. Urinary excretion of calcium and magnesium in children. Arch Dis Child. 1974;49(2):97-101. doi: 10.1136/adc.49.2.97.
18) Tekin A, Tekgul S, Atsu N, Sahin A, Ozen H, Bakkaloglu M. A study of the etiology of idiopathic calcium urolithiasis in children: hypocitruria is the most important risk factor. J Urol. 2000;164(1):162-5.
19) Nordin BE. Assessment of calcium excretion from the urinary calcium/creatinine ratio. Lancet. 1959;2(7099):368-71. doi: 10.1016/s0140-6736(59)91635-6.
20) Coe FL, Favus MJ, Crockett T, Strauss AL, Parks JH, Porat A, et al. Effects of low-calcium diet on urine calcium excretion, parathyroid function, and serum 1,25(OH)2D3 levels in patients with idiopathic hypercalciuria and in normal subjects. Am J Med. 1982;72(1):25-32. doi: 10.1016/0002-9343(82)90567-8.
21) Giusti A, Barone A, Pioli G, Girasole G, Siccardi V, Palummeri E, et al. Alendronate and indapamide alone or in combination in the management of hypercalciuria associated with osteoporosis: a randomized controlled trial of two drugs and three treatments. Nephrol Dial Transplant. 2009;24(5):1472-7. doi: 10.1093/ndt/gfn690.
22) Lerolle N, Lantz B, Paillard F, Gattegno B, Flahault A, Ronco P, et al. Risk factors for nephrolithiasis in patients with familial idiopathic hypercalciuria. Am J Med. 2002;113(2):99-103. doi: 10.1016/s0002-9343(02)01152-x.
23) Bihl G, Meyers A. Recurrent renal stone disease-advances in pathogenesis and clinical management. Lancet. 2001;358(9282):651-6. doi: 10.1016/S0140-6736(01)05782-8.
24) Weisinger JR, Alonzo E, Machado C, Carlini R, Martinis R, Paz-Martinez V, et al. Papel del hueso en la fisiopatología de la hipercalciuria idiopática. Medicina (B. Aires). 1997;57(supl. 1):45-8.
25) Coe FL, Parks JH. New insights into the pathophysiology and treatment of nephrolithiasis: new research venues. J Bone Miner Res. 1997;12(4):522-33. doi: 10.1359/jbmr.1997.12.4.522.
26) Weisinger JR, Alonzo E, Bellorín-Font E, Blasini AM, Rodríguez MA, Paz-Martínez V, et al. Possible role of cytokines on the bone mineral loss in idiopathic hypercalciuria. Kidney Int. 1996;49(1):244-50. doi: 10.1038/ki.1996.34.
27) Farías ML, Delgado AG, Rosenthal D, Vieira JG, Kasamatsu T, Lazarevitch MJ, et al. The cause of maintained hypercalciuria after the surgical cure of primary hyperparathyroidism is a defect in renal calcium reabsorption. J Endocrinol Invest. 1996;19(1):12-20. doi: 10.1007/BF03347852.
28) Breslau NA. Pathogenesis and management of hypercalciuric nephrolithiasis. Miner Electrolyte Metab. 1994;20(6):328-39.
29) Pacifici R. Idiopathic hypercalciuria and osteoporosis: distinct clinical manifestations of increased cytokine-induced bone resorption? J Clin Endocrinol Metab. 1997;82(1):29-31. doi: 10.1210/jcem.82.1.3706.
30) Ishimi Y, Miyaura C, Jin CH, Akatsu T, Abe E, Nakamura Y, et al. IL-6 is produced by osteoblasts and induces bone resorption. J Immunol. 1990;145(10):3297-303.
31) Passeri G, Girasole G, Jilka RL, Manolagas SC. Increased interleukin-6 production by murine bone marrow and bone cells after estrogen withdrawal. Endocrinology. 1993;133(2):822-8. doi: 10.1210/endo.133.2.8393776.
32) Costanzo LS, Weiner IM. On the hypocalciuric action of chlorothiazide. J Clin Invest. 1974;54(3):628-37. doi: 10.1172/JCI107800.
33) Jang HR, Kim S, Heo NJ, Lee JH, Kim HS, Nielsen S, et al. Effects of thiazide on the expression of TRPV5, calbindin-D28K, and sodium transporters in hypercalciuric rats. J Korean Med Sci. 2009;24 Suppl(Suppl 1):S161-9. doi: 10.3346/jkms.2009.24.S1.S161.
34) Spivacow FR, Negri AL, del Valle E. Efecto a largo plazo de tiazidas sobre la masa ósea en mujeres con nefrolitiasis hipercalciúrica. Rev Nefrol Dial Traspl. 2013;33(4):180-7.
35) Zanchetta JR, Rodríguez G, Negri AL, del Valle E, Spivacow FR. Bone mineral density in patients with hypercalciuric nephrolithiasis. Nephron. 1996;73(4):557-60. doi: 10.1159/000189140.
36) Ceylan K, Topal C, Erkoc R, Sayarlioglu H, Can S, Yilmaz Y, et al. Effect of indapamide on urinary calcium excretion in patients with and without urinary stone disease. Ann Pharmacother. 2005;39(6):1034-8. doi: 10.1345/aph.1E544.
Published
2021-09-21
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Spivacow FR, del Valle EE, Rojas Pérez PA. Idiopathic hypercalciuria: diagnosis, classification, and treatment. Rev Nefrol Dial Traspl. [Internet]. 2021Sep.21 [cited 2024Dec.22];41(3):184-91. Available from: http://revistarenal.org.ar/index.php/rndt/article/view/680
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