Skip to main content
Log in

Adjustment for body mass index and calcitrophic hormone levels improves the diagnostic accuracy of the spot urine calcium-to-creatinine ratio

  • Original Article
  • Published:
Osteoporosis International Aims and scope Submit manuscript

Abstract

Summary

Providers diagnose hypercalciuria using a 24-hour or random urine samples. We compared calcium measurements from paired 24-hour and morning urine samples; measurements correlated poorly. We developed a formula to correct random urine calcium levels. Corrected levels showed excellent agreement with 24-hour measurements. Until validation, providers should diagnose hypercalciuria using 24-hour tests.

Introduction

Hypercalciuria is a risk factor for osteoporosis and nephrolithiasis. The 24-hour urine calcium (24HUC) measurement is the gold standard to diagnose hypercalciuria, but the spot urine calcium-to-creatinine ratio (SUCCR) is more convenient. Although authors claim they are interchangeable, we observed inconsistencies during the conduct of a clinical trial. Therefore, we systematically evaluated agreement between the tests.

Methods

During a 28-inpatient calcium absorption studies in 16 postmenopausal women, we simultaneously collected paired fasting morning and 24-hour urine specimens.

Results

We found moderate correlation between paired SUCCR and 24HUC specimens (r = 0.57, p = 0.002), but the SUCCR underestimated 24HUC by a mean of 83 mg (Bland–Altman). We diagnosed hypercalciuria (24HUC >250 mg) in eight specimens using the 24HUC, but only in two specimens using the SUCCR (25% sensitivity). We developed a regression model to predict 24HUC using SUCCR, parathyroid hormone, body mass index, and 1,25(OH)2D. The model improved diagnostic sensitivity to 100% and decreased Bland–Altman bias of the SUCCR to +0.06 mg/kg/24-hour.

Conclusions

We conclude that the SUCCR underestimates urine calcium loss and does not reliably diagnose hypercalciuria. A formula derived from multivariate regression incorporating other readily measurable variables greatly improved the SUCCR’s accuracy. Future studies must verify this correction before clinical implementation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Park S, Pearle MS (2007) Pathophysiology and management of calcium stones. Urol Clin North Am 34:323–334

    Article  PubMed  Google Scholar 

  2. Adams JS, Song CF, Kantorovich V (1999) Rapid recovery of bone mass in hypercalciuric, osteoporotic men treated with hydrochlorothiazide. Ann Intern Med 130:658–660

    CAS  PubMed  Google Scholar 

  3. Strohmaier WL, Hoelz KJ, Bichler KH (1997) Spot urine samples for the metabolic evaluation of urolithiasis patients. Eur Urol 32:294–300

    CAS  PubMed  Google Scholar 

  4. Topal C, Algun E, Sayarlioglu H, Erkoc R, Soyoral Y, Dogan E et al (2008) Diurnal rhythm of urinary calcium excretion in adults. Ren Fail 30:499–501

    Article  CAS  PubMed  Google Scholar 

  5. Gokce C, Gokce O, Baydinc C, Ilhan N, Alasehirli E, Ozkucuk F et al (1991) Use of random urine samples to estimate total urinary calcium and phosphate excretion. Arch Intern Med 151:1587–1588

    Article  CAS  PubMed  Google Scholar 

  6. Ghazali S, Barratt TM (1974) Urinary excretion of calcium and magnesium in children. Arch Dis Child 49:97–101

    Article  CAS  PubMed  Google Scholar 

  7. Colon-Emeric CS, Saag KG (2006) Osteoporotic fractures in older adults. Best Pract Res Clin Rheumatol 20:695–706

    Article  PubMed  Google Scholar 

  8. Brazier M, Kamel S, Maamer M, Agbomson F, Elesper I, Garabedian M et al (1995) Markers of bone remodeling in the elderly subject: effects of vitamin D insufficiency and its correction. J Bone Miner Res 10:1753–1761

    Article  CAS  PubMed  Google Scholar 

  9. Suitor C, Meyers L (2006) Dietary reference intakes research synthesis—workshop summary. Food and Nutrition Board. The National Academies Press, Washington, D.C

    Google Scholar 

  10. Hansen KE, Jones AN, Lindstrom MJ, Davis LA, Engelke JA, Shafer MM (2008) Vitamin d insufficiency: disease or no disease? J Bone Miner Res 23:1052–1060

    Article  CAS  PubMed  Google Scholar 

  11. Bingham CT, Fitzpatrick LA (1993) Noninvasive testing in the diagnosis of osteomalacia. Am J Med 95:519–523

    Article  CAS  PubMed  Google Scholar 

  12. Institute of Medicine FaNB (1999) Dietary reference intakes: calcium, phosphorus, magnesium, vitamin D, and flouride. National Academy Press, Washington, D.C

    Google Scholar 

  13. Abrams SA (1999) Using stable isotopes to assess mineral absorption and utilization by children. Am J Clin Nutr 70:955–964

    CAS  PubMed  Google Scholar 

  14. Yilmaz G, Yilmaz FM, Hakligor A, Yucel D (2008) Are preservatives necessary in 24-hour urine measurements? Clin Biochem 41:899–901

    Article  CAS  PubMed  Google Scholar 

  15. Scott PJ, Hurley PJ (1968) Demonstration of individual variation in constancy of 24-hour urinary creatinine excretion. Clin Chim Acta 21:411–414

    Article  CAS  PubMed  Google Scholar 

  16. Paterson N (1967) Relative constancy of 24-hour urine volume and 24-hour creatinine output. Clin Chim Acta 18:57–58

    Article  CAS  PubMed  Google Scholar 

  17. Cote AM, Firoz T, Mattman A, Lam EM, von Dadelszen P, Magee LA (2008) The 24-hour urine collection: gold standard or historical practice? Am J Obstet Gynecol 199(625):e621–e626

    Google Scholar 

  18. Bingham SA, Cummings JH (1985) The use of creatinine output as a check on the completeness of 24-hour urine collections. Hum Nutr, Clin Nutr 39:343–353

    CAS  Google Scholar 

  19. Bland JM, Altman DG (1986) Statistical methods for assessing agreement between two methods of clinical measurement. Lancet 1:307–310

    CAS  PubMed  Google Scholar 

  20. Chandhoke PS (2007) Evaluation of the recurrent stone former. Urol Clin North Am 34:315–322

    Article  PubMed  Google Scholar 

  21. Curhan GC, Willett WC, Speizer FE, Stampfer MJ (2001) Twenty-four-hour urine chemistries and the risk of kidney stones among women and men. Kidney Int 59:2290–2298

    CAS  PubMed  Google Scholar 

  22. Heaney RP, Recker RR, Ryan RA (1999) Urinary calcium in perimenopausal women: normative values. Osteoporos Int 9:13–18

    Article  CAS  PubMed  Google Scholar 

  23. Nordin BE (1959) Assessment of calcium excretion from the urinary calcium/creatinine ratio. Lancet 2:368–371

    Article  CAS  PubMed  Google Scholar 

  24. Isaacson LC, Jackson WP (1963) The urinary excretion of calcium and magnesium, with special reference to the urinary calcium/creatinine ratio and calcium/osmolar ratio. Clin Sci 24:223–227

    CAS  PubMed  Google Scholar 

  25. Wills MR (1969) The urinary calcium-creatinine ratio as a measure of urinary calcium excretion. J Clin Pathol 22:287–290

    Article  CAS  PubMed  Google Scholar 

  26. Matsushita K, Tanikawa K (1987) Significance of the calcium to creatinine concentration ratio of a single-voided urine specimen in patients with hypercalciuric urolithiasis. Tokai J Exp Clin Med 12:167–171

    CAS  PubMed  Google Scholar 

  27. Lambers TT, Bindels RJ, Hoenderop JG (2006) Coordinated control of renal ca2+ handling. Kidney Int 69:650–654

    Article  CAS  PubMed  Google Scholar 

  28. Siener R, Glatz S, Nicolay C, Hesse A (2004) The role of overweight and obesity in calcium oxalate stone formation. Obes Res 12:106–113

    Article  CAS  PubMed  Google Scholar 

  29. Taylor EN, Curhan GC (2006) Body size and 24-hour urine composition. Am J Kidney Dis 48:905–915

    Article  CAS  PubMed  Google Scholar 

  30. Wolff AE, Jones AN, Hansen KE (2008) Vitamin d and musculoskeletal health. Nat Clin Pract Rheumatol 4:580–588

    Article  CAS  PubMed  Google Scholar 

  31. Butani L, Kalia A (2004) Idiopathic hypercalciuria in children—how valid are the existing diagnostic criteria? Pediatr Nephrol 19:577–582

    Article  PubMed  Google Scholar 

Download references

Acknowledgment

We thank Dr. Don Schalch for his advice and guidance during the preparation of this manuscript.

Conflicts of interest

None.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to K. E. Hansen.

Additional information

Grant support from Jackson Foundation, NIH (K23 AR050995), GCRC (NCRR M01 RR03186), a Junior Career Development Award in Geriatric Medicine (T. Franklin Williams Scholar Award, Atlantic Philanthropies, American College of Rheumatology Research and Education Foundation), and a New Investigator Grant from the Medical Education and Research Committee of the Wisconsin Partnership Program. This paper is based on work conducted in part in the William S. Middleton Veterans’ Hospitals’ Geriatrics, Research, Education, and Clinical Center and is GRECC manuscript #2009-10.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Jones, A.N., Blank, R.D., Lindstrom, M.J. et al. Adjustment for body mass index and calcitrophic hormone levels improves the diagnostic accuracy of the spot urine calcium-to-creatinine ratio. Osteoporos Int 21, 1417–1425 (2010). https://doi.org/10.1007/s00198-009-1058-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00198-009-1058-z

Keywords

Navigation