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Hypercalciuria Differential Diagnoses

  • Author: Stephen W Leslie, MD, FACS; Chief Editor: Vecihi Batuman, MD, FACP, FASN  more...
 
Updated: Nov 26, 2015
 
 

Diagnostic Considerations

The following conditions are included in the differential diagnosis of hypercalciuria:

  • Dent disease
  • Hypercalcemia
  • Hypercalcemic nephropathy
  • Hyperoxaluria
  • Hyperparathyroidism
  • Hypervitaminosis D
  • Hypophosphatemia
  • Nephrocalcinosis
  • Nephrolithiasis
  • Acute renal colic
  • Osteoporosis
  • Pyelonephritis
  • Rickets
  • Sarcoidosis
  • Uric acid stones
  • Urinary tract infection
  • Urolithiasis
  • Wilms tumor
  • Xanthinuria

Differential Diagnoses

 
 
Contributor Information and Disclosures
Author

Stephen W Leslie, MD, FACS Founder and Medical Director, Lorain Kidney Stone Research Center; Associate Professor of Surgery, Creighton University School of Medicine, Chief of Urology, Creighton University Medical Center

Stephen W Leslie, MD, FACS is a member of the following medical societies: American College of Surgeons, American Urological Association, National Kidney Foundation, Ohio State Medical Association

Disclosure: Nothing to disclose.

Coauthor(s)

Sahar Fathallah-Shaykh, MD Associate Professor of Pediatric Nephrology, University of Alabama at Birmingham School of Medicine; Consulting Staff, Division of Pediatric Nephrology, Medical Director of Pediatric Dialysis Unit, Children's of Alabama

Sahar Fathallah-Shaykh, MD is a member of the following medical societies: American Society of Nephrology, American Society of Pediatric Nephrology

Disclosure: Nothing to disclose.

Chief Editor

Vecihi Batuman, MD, FACP, FASN Huberwald Professor of Medicine, Section of Nephrology-Hypertension, Tulane University School of Medicine; Chief, Renal Section, Southeast Louisiana Veterans Health Care System

Vecihi Batuman, MD, FACP, FASN is a member of the following medical societies: American College of Physicians, American Society of Hypertension, American Society of Nephrology, International Society of Nephrology

Disclosure: Nothing to disclose.

Acknowledgements

Sahar Fathallah-Shaykh, MD Assistant Professor in Pediatric Nephrology, University of Alabama at Birmingham School of Medicine; Consulting Staff, Division of Pediatric Nephrology, Medical Director of Pediatric Dialysis Unit, Children's of Alabama

Sahar Fathallah-Shaykh, MD is a member of the following medical societies: American Society of Nephrology and American Society of Pediatric Nephrology

Disclosure: Medscape Reference Honoraria Other

Frederick J Kaskel, MD, PhD Director of the Division and Training Program in Pediatric Nephrology, Vice Chair, Department of Pediatrics, Montefiore Medical Center and Albert Einstein School of Medicine

Frederick J Kaskel, MD, PhD is a member of the following medical societies: American Academy of Pediatrics, American Association for the Advancement of Science, American Pediatric Society, American Physiological Society, American Society of Nephrology, American Society of Pediatric Nephrology, American Society of Transplantation, Eastern Society for Pediatric Research, Federation of American Societies for Experimental Biology, International Society of Nephrology, NationalKidneyFoundation, New York Academy of Sciences, Renal Physicians Association, Sigma Xi, and Society for Pediatric Research

Disclosure: Nothing to disclose.

Craig B Langman, MD The Isaac A Abt, MD, Professor of Kidney Diseases, Northwestern University, The Feinberg School of Medicine; Division Head of Kidney Diseases, The Ann and Robert H Lurie Children's Hospital of Chicago

Craig B Langman, MD is a member of the following medical societies: American Academy of Pediatrics, American Society of Nephrology, and International Society of Nephrology

Disclosure: NIH Grant/research funds None; Raptor Pharmaceuticals, Inc Grant/research funds None; Alexion Pharmaceuticals, Inc. Grant/research funds None

Richard Neiberger, MD, PhD Director of Pediatric Renal Stone Disease Clinic, Associate Professor, Department of Pediatrics, Division of Nephrology, University of Florida College of Medicine and Shands Hospital

Richard Neiberger, MD, PhD is a member of the following medical societies: American Academy of Pediatrics, American Federation for Medical Research, American Medical Association, American Society of Nephrology, American Society of Pediatric Nephrology, Christian Medical & Dental Society, Florida Medical Association, International Society for Peritoneal Dialysis, International Society of Nephrology, National Kidney Foundation, New York Academy of Sciences, Shock Society, Sigma Xi, Southern Medical Association, Southern Society for Pediatric Research, and Southwest Pediatric Nephrology Study Group

Disclosure: Nothing to disclose.

Deogracias Pena, MD Medical Director of Dialysis, Department of Pediatrics, Cook Children's Medical Center; Clinical Associate Professor, Texas Tech University Health Sciences Center

Deogracias Pena, MD is a member of the following medical societies: American Academy of Pediatrics, American Medical Association, and American Society of Pediatric Nephrology

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Martha K Terris, MD, FACS Professor, Department of Surgery, Section of Urology, Director, Urology Residency Training Program, Medical College of Georgia; Professor, Department of Physician Assistants, Medical College of Georgia School of Allied Health; Chief, Section of Urology, Augusta Veterans Affairs Medical Center

Martha K Terris, MD, FACS is a member of the following medical societies: American Cancer Society, American College of Surgeons, American Institute of Ultrasound in Medicine, American Society of Clinical Oncology, American Urological Association, Association of Women Surgeons, New York Academy of Sciences, Society of Government Service Urologists, Society of University Urologists, Society of Urology Chairpersons and Program Directors, and Society of Women in Urology

Disclosure: Nothing to disclose.

Taylor S Troischt, MD Clinical Assistant Professor of Pediatrics, West Virginia University Hospitals; Medical Director, Cheat Lake Physicians

Taylor S Troischt, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, and Phi Beta Kappa

Disclosure: Nothing to disclose.

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

References
  1. Moreira Guimarães Penido MG, de Sousa Tavares M, Campos Linhares M, Silva Barbosa AC, Cunha M. Longitudinal study of bone mineral density in children with idiopathic hypercalciuria. Pediatr Nephrol. 2012 Jan. 27(1):123-30. [Medline].

  2. Nacaroglu HT, Demircin G, Bülbül M, Erdogan O, Akyüz SG, Caltik A. The association between urinary tract infection and idiopathic hypercalciuria in children. Ren Fail. 2013. 35(3):327-32. [Medline].

  3. Madani A, Kermani N, Ataei N, Esfahani ST, Hajizadeh N, Khazaeipour Z, et al. Urinary calcium and uric acid excretion in children with vesicoureteral reflux. Pediatr Nephrol. 2012 Jan. 27(1):95-9. [Medline].

  4. Silverberg SJ, Lewiecki EM, Mosekilde L, Peacock M, Rubin MR. Presentation of asymptomatic primary hyperparathyroidism: proceedings of the third international workshop. J Clin Endocrinol Metab. 2009 Feb. 94(2):351-65. [Medline].

  5. Schwaderer AL, Srivastava T, Schueller L, Cronin R, Mahan JD, Hains D. Dietary modifications alone do not improve bone mineral density in children with idiopathic hypercalciuria. Clin Nephrol. 2011 Nov. 76(5):341-7. [Medline].

  6. Vezzoli G, Soldati L, Gambaro G. Update on primary hypercalciuria from a genetic perspective. J Urol. 2008 May. 179(5):1676-82. [Medline].

  7. Curhan GC, Willett WC, Speizer FE, Stampfer MJ. Twenty-four-hour urine chemistries and the risk of kidney stones among women and men. Kidney Int. 2001 Jun. 59(6):2290-8. [Medline].

  8. Zwart SR, Parsons H, Kimlin M, Innis SM, Locke JP, Smith SM. A 250 µg/week dose of vitamin D was as effective as a 50 µg/d dose in healthy adults, but a regimen of four weekly followed by monthly doses of 1250 µg raised the risk of hypercalciuria. Br J Nutr. 2013 Apr 18. 1-7. [Medline].

  9. Parks JH, Coe FL, Evan AP, Worcester EM. Clinical and laboratory characteristics of calcium stone-formers with and without primary hyperparathyroidism. BJU Int. 2009 Mar. 103(5):670-8. [Medline].

  10. Srivastava T, Alon US. Pathophysiology of hypercalciuria in children. Pediatr Nephrol. 2007 Oct. 22(10):1659-73. [Medline].

  11. Worcester EM, Coe FL. New insights into the pathogenesis of idiopathic hypercalciuria. Semin Nephrol. 2008 Mar. 28(2):120-32. [Medline]. [Full Text].

  12. Nesterova G, Malicdan MC, Yasuda K, Sakaki T, Vilboux T, Ciccone C, et al. 1,25-(OH)2D-24 Hydroxylase (CYP24A1) Deficiency as a Cause of Nephrolithiasis. Clin J Am Soc Nephrol. 2013 Apr. 8(4):649-57. [Medline]. [Full Text].

  13. Dimke H, Desai P, Borovac J, Lau A, Pan W, Alexander RT. Activation of the Ca(2+)-sensing receptor increases renal claudin-14 expression and urinary Ca(2+) excretion. Am J Physiol Renal Physiol. 2013 Mar 15. 304(6):F761-9. [Medline].

  14. Vezzoli G, Terranegra A, Soldati L. Calcium-sensing receptor gene polymorphisms in patients with calcium nephrolithiasis. Curr Opin Nephrol Hypertens. 2012 Jul. 21(4):355-61. [Medline].

  15. Pipili C, Oreopoulos DG. Vitamin d status in patients with recurrent kidney stones. Nephron Clin Pract. 2012. 122(3-4):134-8. [Medline].

  16. Park SY, Mun HC, Eom YS, Baek HL, Jung TS, Kim CH, et al. Identification and characterization of D410E, a novel mutation in the loop 3 domain of CASR, in autosomal dominant hypocalcemia and a therapeutic approach using a novel calcilytic, AXT914. Clin Endocrinol (Oxf). 2013 May. 78(5):687-93. [Medline].

  17. Luyckx VA, Leclercq B, Dowland LK, Yu AS. Diet-dependent hypercalciuria in transgenic mice with reduced CLC5 chloride channel expression. Proc Natl Acad Sci U S A. 1999 Oct 12. 96(21):12174-9. [Medline]. [Full Text].

  18. Duffey BG, Pedro RN, Kriedberg C, Weiland D, Melquist J, Ikramuddin S, et al. Lithogenic risk factors in the morbidly obese population. J Urol. 2008 Apr. 179(4):1401-6. [Medline].

  19. Ayoob R, Wang W, Schwaderer A. Body fat composition and occurrence of kidney stones in hypercalciuric children. Pediatr Nephrol. 2011 Dec. 26(12):2173-8. [Medline].

  20. Domrongkitchaiporn S, Ongphiphadhanakul B, Stitchantrakul W, Piaseu N, Chansirikam S, Puavilai G, et al. Risk of calcium oxalate nephrolithiasis after calcium or combined calcium and calcitriol supplementation in postmenopausal women. Osteoporos Int. 2000. 11(6):486-92. [Medline].

  21. Rodman JS, Mahler RJ. Kidney stones as a manifestation of hypercalcemic disorders. Hyperparathyroidism and sarcoidosis. Urol Clin North Am. 2000 May. 27(2):275-85, viii. [Medline].

  22. Whalley NA, Martins MC, Van Dyk RC, Meyers AM. Lithogenic risk factors in normal black volunteers, and black and white recurrent stone formers. BJU Int. 1999 Aug. 84(3):243-8. [Medline].

  23. Maloney ME, Springhart WP, Ekeruo WO, et al. Ethnic background has minimal impact on the etiology of nephrolithiasis. J Urol. Jun 2005. 173(6):2001-4.

  24. Rodgers AL, Lewandowski S. Effects of 5 different diets on urinary risk factors for calcium oxalate kidney stone formation: evidence of different renal handling mechanisms in different race groups. J Urol. 2002 Sep. 168(3):931-6. [Medline].

  25. Zerwekh JE. Bone disease and hypercalciuria in children. Pediatr Nephrol. 2010 Mar. 25(3):395-401. [Medline].

  26. Leslie S. Calcium and stone disease. Savitz GR, Leslie SW, eds. The Kidney Stones Handbook. 2nd ed. Roseville, Calif: Four Geez Press; 2000. 73-94.

  27. Corbin Bush N, Twombley K, Ahn J, Oliveira C, Arnold S, Maalouf NM, et al. Prevalence and spot urine risk factors for renal stones in children taking topiramate. J Pediatr Urol. 2013 Jan 31. [Medline]. [Full Text].

  28. Vachvanichsanong P, Malagon M, Moore ES. Recurrent abdominal and flank pain in children with idiopathic hypercalciuria. Acta Paediatr. 2001 Jun. 90(6):643-8. [Medline].

  29. Alon US, Berenbom A. Idiopathic hypercalciuria of childhood: 4- to 11-year outcome. Pediatr Nephrol. 2000 Sep. 14(10-11):1011-5. [Medline].

  30. Escribano J, Balaguer A, Martin R, Feliu A, Espax R. Childhood idiopathic hypercalciuria--clinical significance of renal calyceal microlithiasis and risk of calcium nephrolithiasis. Scand J Urol Nephrol. 2004. 38(5):422-6. [Medline].

  31. Arrabal-Polo MA, Arias-Santiago S, de Haro-Muñoz T, Lopez-Ruiz A, Orgaz-Molina J, Gonzalez-Torres S, et al. Effects of aminobisphosphonates and thiazides in patients with osteopenia/osteoporosis, hypercalciuria, and recurring renal calcium lithiasis. Urology. 2013 Apr. 81(4):731-7. [Medline].

  32. Fellström B, Backman U, Danielson B, Wikström B. Treatment of renal calcium stone disease with the synthetic glycosaminoglycan pentosan polysulphate. World J Urol. 1994. 12(1):52-4. [Medline].

  33. Norman RW, Scurr DS, Robertson WG, Peacock M. Inhibition of calcium oxalate crystallisation by pentosan polysulphate in control subjects and stone formers. Br J Urol. 1984 Dec. 56(6):594-8. [Medline].

  34. Senthil D, Subha K, Saravanan N, Varalakshmi P. Influence of sodium pentosan polysulphate and certain inhibitors on calcium oxalate crystal growth. Mol Cell Biochem. 1996 Mar 9. 156(1):31-5. [Medline].

  35. Prié D, Blanchet FB, Essig M, Jourdain JP, Friedlander G. Dipyridamole decreases renal phosphate leak and augments serum phosphorus in patients with low renal phosphate threshold. J Am Soc Nephrol. 1998 Jul. 9(7):1264-9. [Medline].

  36. Lemann J Jr, Pleuss JA, Gray RW, Hoffmann RG. Potassium administration reduces and potassium deprivation increases urinary calcium excretion in healthy adults [corrected]. Kidney Int. 1991 May. 39(5):973-83. [Medline].

  37. Martini LA, Cuppari L, Cunha MA, Schor N, Heilberg IP. Potassium and sodium intake and excretion in calcium stone forming patients. J Ren Nutr. 1998 Jul. 8(3):127-31. [Medline].

  38. Sebastian A, Hernandez RE, Portale AA, Colman J, Tatsuno J, Morris RC Jr. Dietary potassium influences kidney maintenance of serum phosphorus concentration. Kidney Int. 1990 May. 37(5):1341-9. [Medline].

  39. Curhan GC, Willett WC, Rimm EB, Stampfer MJ. A prospective study of dietary calcium and other nutrients and the risk of symptomatic kidney stones. N Engl J Med. 1993 Mar 25. 328(12):833-8. [Medline].

  40. Hiatt RA, Ettinger B, Caan B, Quesenberry CP Jr, Duncan D, Citron JT. Randomized controlled trial of a low animal protein, high fiber diet in the prevention of recurrent calcium oxalate kidney stones. Am J Epidemiol. 1996 Jul 1. 144(1):25-33. [Medline].

  41. Xu H, Zisman AL, Coe FL, Worcester EM. Kidney stones: an update on current pharmacological management and future directions. Expert Opin Pharmacother. 2013 Mar. 14(4):435-47. [Medline].

  42. Yendt ER, Gagne RJ, Cohanim M. The effects of thiazides in idiopathic hypercalciuria. Am J Med Sci. Apr 1966. 251(4):449-60.

  43. Howard JE, Thomas WC, Mukai T, et al. The calcification of cartilage by urine, and a suggestion for therapy in patients with certain kinds of calculi. Trans Assoc Am Physicians. 1962. 75:301-6.

  44. Breslau NA, Padalino P, Kok DJ, Kim YG, Pak CY. Physicochemical effects of a new slow-release potassium phosphate preparation (UroPhos-K) in absorptive hypercalciuria. J Bone Miner Res. 1995 Mar. 10(3):394-400. [Medline].

  45. Michaut P, Prié D, Amiel C, Friedlander G. Dipyridamole for renal phosphate leak?. N Engl J Med. 1994 Jul 7. 331(1):58-9. [Medline].

  46. Neer RM, Arnaud CD, Zanchetta JR, Prince R, Gaich GA, Reginster JY, et al. Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N Engl J Med. 2001 May 10. 344(19):1434-41. [Medline].

  47. Bushinsky DA, Laplante K, Asplin JR. Effect of cinacalcet on urine calcium excretion and supersaturation in genetic hypercalciuric stone-forming rats. Kidney Int. May 2006. 69(9):1586-92.

  48. Charytan C, Coburn JW, Chonchol M, et al. Cinacalcet hydrochloride is an effective treatment for secondary hyperparathyroidism in patients with CKD not receiving dialysis. Am J Kidney Dis. Jul 2005. 46(1):58-67.

  49. Dong BJ. Cinacalcet: An oral calcimimetic agent for the management of hyperparathyroidism. Clin Ther. Nov 2005. 27(11):1725-51.

  50. Lindberg JS, Culleton B, Wong G, et al. Cinacalcet HCl, an oral calcimimetic agent for the treatment of secondary hyperparathyroidism in hemodialysis and peritoneal dialysis: a randomized, double-blind, multicenter study. J Am Soc Nephrol. 16(3). Mar 2005:800-7.

  51. Cinacalcet: new drug. Secondary hyperparathyroidism: where are the clinical data?. Prescrire Int. 2006 Jun. 15(83):90-3. [Medline].

  52. Strohmaier WL, Schlee-Giehl K, Bichler KH. Osteocalcin response to calcium-restricted diet: a helpful tool for the workup of hypercalciuria. Eur Urol. 1996. 30(1):103-7. [Medline].

  53. Yousefichaijan P, Sharafkhah M, Cyrus A, Rafeie M. Therapeutic Efficacy of Hydrochlorothiazide in Primary Monosymptomatic Nocturnal Enuresis in Boys With Idiopathic Hypercalciuria. Nephrourol Mon. 2015 Sep. 7 (5):e29127. [Medline].

  54. Lee CT, Ng HY, Lee YT, Lai LW, Lien YH. The role of calbindin-D28k on renal calcium and magnesium handling during treatment with loop or thiazide diuretics. Am J Physiol Renal Physiol. 2015 Nov 18. ajprenal.00057.2015. [Medline].

  55. Pak CY, Odvina CV, Pearle MS, Sakhaee K, Peterson RD, Poindexter JR, et al. Effect of dietary modification on urinary stone risk factors. Kidney Int. 2005 Nov. 68(5):2264-73. [Medline].

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Calcium-rich foods.
Table 1. Definitions of Hypercalciuria
Diet Definition
Regular diet (unrestricted)Women: Urinary excretion >250 mg calcium (6.2 mmol/24 h)



Men: Urinary excretion >275-300 mg calcium (7.5 mmol/24 h)



Urinary excretion >4 mg calcium (0.1 mmol) per kilogram of body weight per day



Urinary concentration >200 mg calcium per liter



Restricted diet (400 mg calcium, 100 mEq sodium)Urinary excretion >200 mg calcium per day
Urinary excretion >3 mg calcium per kilogram of body weight per day
Table 2. Hypercalciuria Simplified Test Guideline
Hypercalciuria Diagnosis Urinary Calcium on 400-mg Calcium Diet



(Normal = < 200 mg/24 h)



Fasting Calcium/Creatinine Ratio



(Normal = < 0.11)



Post–Calcium Load Calcium/Creatinine Ratio



(Normal = < 0.20)



NormalNormalNormalNormal
Absorptive type IHighNormalHigh
Absorptive type IINormalNormalHigh
Absorptive type III (renal phosphate leak)HighHighHigh
Renal leakHighHighHigh
Resorptive (hyperparathyroidism)HighHighHigh
Table 3. Calcium-Loading Test Interpretation Guide
Criteria Absorptive Type I



Vitamin D–Dependent (Classic Form)



Absorptive Type I



Vitamin D–Dependent (Variant Form)



Absorptive Type II



Dietary Calcium Responsive



Absorptive Type III



(Renal Phosphate Leak)



Renal Calcium Leak Resorptive
Urinary calcium on regular diet*HighHighHighHighHighHigh
Urinary calcium on low-calcium dietHighHighNLHighHighHigh
Urinary calcium fastingNLHighNLHighHighHigh
Urinary calcium after 1-g calcium load§HighHighNLHighHighHigh
Serum PO4 (fasting)NLNLNLLowNL or highLow
Serum calcium (fasting)NLNL or highNLNL or highNL or lowHigh
Serum PTHNL or lowNL or lowNLLowHighHigh
Serum PTH after 1-g calcium loadNL or lowNL or lowNLLowHighHigh
Serum vitamin D-3 (calcitriol)NLHighNLHighHighHigh
Fasting normocalciuria while on ketoconazoleNoYesNoYesNoNo
Bone calcium densityNLNL or lowNLNL or lowLowLow
NL = normal; PO4 = phosphate; PTH = parathyroid hormone.



* Regular diet is unrestricted calcium and sodium intake. Normal upper limit calciuria is < 4 mg/kg body weight per day.



Low-calcium diet is 400 mg calcium and 100 mEq of sodium per day. Normal upper limit calciuria is < 200 mg/day.



Fasting is a 12-hour fast. Normal upper limit is < 0.11 mg calcium/mg creatinine.



§ After 1-g calcium load, normal upper limit is < 0.20 mg calcium/mg creatinine.



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