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Abnormal distal renal tubular acidification in patients with low bone mass: prevalence and impact of alkali treatment

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Abstract

Chronic acid retention is known to promote bone dissolution. In this study, 23 % of patients with osteopenia/osteoporosis were diagnosed with abnormal distal renal tubular acidification (dRTA), a kidney dysfunction leading to chronic acid retention. Treating those patients with alkali-therapy shows improvement in bone density. To evaluate the prevalence of abnormal distal renal tubular acidification in patients with low bone mass (LBM) and the impact of additional alkali treatment on bone density in patients with concomitant LBM and dRTA,183 patients referred for metabolic evaluation of densitometrically proven low bone mass were screened for abnormal distal renal tubular acidification between 2006 and 2013. In all LBM urine pH (U-pH) was measured in the 2nd morning urines after 12 h of fasting. If U-pH was ≥5.80, LBM underwent a 1-day ammonium chloride loading, and U-pH was remeasured the next morning. If U-pH after acid loading did not drop below 5.45, patients were diagnosed with abnormal distal renal tubular acidification. Normal values were obtained from 21 healthy controls. All LBM with dRTA were recommended alkali citrate in addition to conventional therapy of LBM, and follow-up DXAs were obtained until 2014. 85 LBM underwent NH4Cl loading. 42 LBM patients were diagnosed with incomplete dRTA (idRTA; prevalence 23.0 %). During follow-up (1.6–8 years) of idRTA-LBM patients, subjects adhering to alkali treatment tended to improve BMD at all sites measured, whereas BMD of non-adherent idRTA patients worsened/remained unchanged. (1) About one out of four patients with osteopenia/osteoporosis has idRTA. (2) Upon NH4Cl loading, idRTA patients do not lower urine pH normally, but show signs of increased acid-buffering by bone dissolution. (3) In idRTA patients with low bone mass on conventional therapy, additional long-term alkali treatment improves bone mass at lumbar spine and potentially at other bone sites. (4) All patients with low bone mass undergoing metabolic evaluation should be screened for idRTA.

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References

  1. Eiam-Ong S, Kurtzman NA (1994) Metabolic acidosis and bone disease. Miner Electrolyte Metab 20:72–80

    CAS  PubMed  Google Scholar 

  2. Bushinsky DA (2002) Integration of calcium metabolism in the adult. In: Coe FL, Favus MJ (eds) Disorders of bone and mineral metabolism, 2nd edn. Lippincott, Philadelphia, pp 381–396

    Google Scholar 

  3. Krieger NS, Sessler NE, Bushinsky DA (1992) Acidosis inhibits osteoblastic and stimulates osteoclastic activity in vitro. Am J Physiol 262:F442–F448

    CAS  PubMed  Google Scholar 

  4. Maurer M, Riesen W, Muser J, Hulter HN, Krapf R (2003) Neutralization of western diet inhibits bone resorption independently of K intake and reduces cortisol secretion in humans. Am J Physiol 284:F32–F40

    CAS  Google Scholar 

  5. Sebastian A, Harris ST, Ottaway JH, Todd KM, Morris jr RC (1994) Improved mineral balance and skeletal metabolism in postmenopausal women treated with potassium bicarbonate. N Engl J Med 330:1776–1781

    Article  CAS  PubMed  Google Scholar 

  6. Gluck SL (1998) Acid–base. Lancet 352:474–479

    Article  CAS  PubMed  Google Scholar 

  7. Hess B (2006) Acid–base metabolism: implications for kidney stone formation. Urol Res 34:134–138

    Article  CAS  PubMed  Google Scholar 

  8. Rodríguez Soriano J (2002) Renal tubular acidosis: the clinical entity. J Am Soc Nephrol 13:2160–2170

    Article  PubMed  Google Scholar 

  9. Domrongkitchaiporn S, Pongsakul C, Stitchantrakul W et al (2001) Bone mineral density and histology in distal renal tubular acidosis. Kidney Int 59:1068–1093

    Article  Google Scholar 

  10. Osther PJ, Bollerslev J, Hansen AB, Engel K, Kildeberg P (1993) Pathophysiology of incomplete renal tubular acidosis in recurrent renal stone formers: evidence of disturbed calcium, bone and citrate metabolism. Urol Res 21:169–173

    Article  CAS  PubMed  Google Scholar 

  11. Weger W, Kotanko P, Weger M, Deutschmann H, Skrabal F (2000) Prevalence and characterization of renal tubular acidosis in patients with osteopenia and osteoporosis and in non-porotic controls. Nephrol Dial Transplant 15:975–980

    Article  CAS  PubMed  Google Scholar 

  12. Wrong O, Davies HEF (1959) The excretion of acid in renal disease. Quart J Med 28:259–313

    CAS  PubMed  Google Scholar 

  13. Walsh SB, Shorley DG, Wrong OM, Unwin RJ (2007) Urinary acidification assessed by simultaneous furosemide and fludrocortisone treatment: an alternative to ammonium chloride. Kidney Int 71:1310–1316

    Article  CAS  PubMed  Google Scholar 

  14. Hess B, Michel R, Takkinen R, Ackermann D, Jaeger Ph (1994) Risk factors of low urinary citrate in calcium nephrolithiasis: low vegetable fibre intake and low urine volume to be added to the list. Nephrol Dial Transplant 9:642–649

    Article  CAS  PubMed  Google Scholar 

  15. Levey AS, Coresh J, Balk E et al (2003) National Kidney Foundation guidelines for chronic kidney disease: evaluation, classification, and stratification. Ann Intern Med 139:137–147

    Article  PubMed  Google Scholar 

  16. Arampatzis S, Röpke-Rieben B, Lippuner K, Hess B (2012) Prevalence and densitometric characteristics of incomplete distal renal tubular acidosis in men with recurrent calcium nephrolithiasis. Urol Res 40:53–59

    Article  CAS  PubMed  Google Scholar 

  17. Israni AK, Kasiske BL (2012) In: Taal ML et al. (eds) Brenner & Rector’s the kidney, chap. 25, Vol 1, 9th edn. Elsevier Saunders, Philadelphia, pp 868–896

  18. Peacock M, Nordin BEC (1968) Tubular reabsorption of calcium in normal and hypercalciuric subjects. J Clin Pathol 21:353–358

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Seeman E (2003) Physiology of aging-invited review: pathogenesis of osteoporosis. J Appl Physiol 95:2142–2151

    Article  PubMed  Google Scholar 

  20. Sornay-Rendu E, Boutroy S, Munoz F, Delmas P (2007) Alterations of cortical and trabecular architecture are associated with fractures in postmenopausal women, partially independent of decreased BMD measured by DXA: the OFELY study. J Bone Miner Res 22:425–433

    Article  PubMed  Google Scholar 

  21. Pongchaiyakul C, Domrongkitchaiporn S, Stitchantrakul W, Chailurkit L, Rajatanavin R (2004) Incomplete renal tubular acidosis and bone mineral density: a population survey in an era of endemic renal tubular acidosis. Nephrol Dial Transplant 19:3029–3033

    Article  PubMed  Google Scholar 

  22. Fabris A, Bernich P, Abaterusso C, Marchionna N, Canciani C, Nouvenne A, Zamboni M, Lupo A, Gambaro G (2009) Bone disease in medullary sponge kidney and effect of potassium citrate treatment. Clin J Am Soc Nephrol 4:1974–1979

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Gregory NS, Kumar R, Stein EM, Alexander E, Christos P, Bockman RS, Rodman JS (2015) Potassium citrate decrease bone resorption in postmenopausal women with osteopenia: a randomized, double- blind clinical trial. Edocr Pract 21:1380–1386

    Article  Google Scholar 

  24. Dawson-Hughes B, Harris SS, Palermo NJ, Gilhooly CH, Shea MK, Fielding RA, Ceglia L (2015) Potassium bicarbonate supplementation lowers bone turnover and calcium excretion in older men and women: a randomized dose-finding trial. J Bone Miner Res 30:2103–2111

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Jehle S, Hulter HN, Krapf R (2013) Effect of potassium citrate on bone density, microarchitectures, and fracture risk in healthy older adults without osteoporosis: a randomized controlled trial. J Clin Endocrinol Metab 98:207–217

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

We kindly thank R. Theiler, M.D., Zurich for critically reviewing the manuscript. The technical assistance of Kirsten Sitzmann and Sabine Matter in organizing and executing the study is greatly acknowledged.

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Correspondence to Bernhard Hess.

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Sromicki, J.J., Hess, B. Abnormal distal renal tubular acidification in patients with low bone mass: prevalence and impact of alkali treatment. Urolithiasis 45, 263–269 (2017). https://doi.org/10.1007/s00240-016-0906-5

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  • DOI: https://doi.org/10.1007/s00240-016-0906-5

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