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Renal biomarkers of acid excretion capacity: relationships with body fatness and blood pressure

Abstract

Background

Overweight and higher BMI are known to be related to increased blood pressure (BP) and additionally associate with lowered urine pH values even at comparable total daily acid loading. Since a reduced urine pH level at a given total acid load indicates an impaired renal net acid excretion capacity (NAEC) and renal function also relates to BP, we hypothesized that NAEC may be one mediator of the body fat–BP association.

Methods

Ammonium, titratable acid, pH, creatinine, and urea were measured in 24-h urine samples among 9–15-year-old adolescents of the DONALD Study. NAEC was determined as residual of the body surface area-corrected net acid excretion on urine pH (NAEC1) or body surface area-corrected ammonium excretion on urine pH (NAEC2). Markers of body fatness were determined anthropometrically and systolic and diastolic BP sphygmomanometrically. Multilinear regressions were used to examine cross-sectionally the body fat–NAEC and prospectively the NAEC1–BP associations.

Results

All body fat parameters were inversely associated with both NAEC1 and NAEC2 among youth (P ≤ 0.01). In a separate prospective analyses, to check for possible mediation, higher adolescent NAEC1 was significantly associated with lower systolic BP in male adults only (P = 0.04), but this association was attenuated to a trend (P = 0.07) in multivariable-adjusted models.

Conclusions

Independent of systemic acid load, NAEC, i.e., the kidney’s function to eliminate acids is reduced with higher body fatness, and may also contribute as a mediator in the body fatness–BP relation.

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Fig. 1: Relationship of NAE and 24-h urine pH.
Fig. 2: Means of acid excretion capacity indices in tertiles of body fat measures.

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Data availability

The datasets generated and/or analyzed during the current study are not publicly available, but are available from the corresponding author on reasonable request.

References

  1. Muntner P, He J, Cutler JA, Wildman RP, Whelton PK. Trends in blood pressure among children and adolescents. J Am Med Assoc. 2004;291:2107–13.

    Article  CAS  Google Scholar 

  2. Flores-Huerta S, Klünder-Klünder M, La Reyes de Cruz L, Santos JI. Increase in body mass index and waist circumference is associated with high blood pressure in children and adolescents in Mexico city. Arch Med Res. 2009;40:208–15.

    Article  Google Scholar 

  3. Gundogdu Z. Relationship between BMI and blood pressure in girls and boys. Public Health Nutr. 2008;11:1085–8.

    Article  Google Scholar 

  4. Hua Y, Krupp D, Esche J, Remer T. Increased body fatness adversely relates to 24-hour urine pH during childhood and adolescence: evidence of an adipo-renal axis. Am J Clin Nutr. 2019;109:1279–87.

    PubMed  Google Scholar 

  5. Pigna F, Sakhaee K, Adams-Huet B, Maalouf NM. Body fat content and distribution and urinary risk factors for nephrolithiasis. Clin J Am Soc Nephrol. 2014;9:159–65.

    Article  CAS  Google Scholar 

  6. Song JH, Doo SW, Yang WJ, Song YS. Influence of obesity on urinary pH with respect to sex in healthy Koreans. Urology. 2011;78:1244–7.

    Article  Google Scholar 

  7. Remer T, Berkemeyer S, Rylander R, Vormann J. Muscularity and adiposity in addition to net acid excretion as predictors of 24-h urinary pH in young adults and elderly. Eur J Clin Nutr. 2007;61:605–9.

    Article  CAS  Google Scholar 

  8. Murakami K, Sasaki S, Takahashi Y, Uenishi K. Association between dietary acid-base load and cardiometabolic risk factors in young Japanese women. Br J Nutr. 2008;100:642–51.

    Article  CAS  Google Scholar 

  9. Zhang L, Curhan GC, Forman JP. Diet-dependent net acid load and risk of incident hypertension in United States women. Hypertension. 2009;54:751–5.

    Article  CAS  Google Scholar 

  10. van den Berg E, Hospers FAP, Navis G, Engberink MF, Brink EJ, Geleijnse JM, et al. Dietary acid load and rapid progression to end-stage renal disease of diabetic nephropathy in Westernized South Asian people. J Nephrol. 2011;24:11–7.

    Article  Google Scholar 

  11. Dhondup T, Qian Q. Acid-base and electrolyte disorders in patients with and without chronic kidney disease: an update. Kidney Dis (Basel). 2017;3:136–48.

    Article  Google Scholar 

  12. Wesson DE, Simoni J, Broglio K, Sheather S. Acid retention accompanies reduced GFR in humans and increases plasma levels of endothelin and aldosterone. Am J Physiol Ren Physiol. 2011;300:F830–7.

    Article  CAS  Google Scholar 

  13. Jha R, Muthukrishnan J, Shiradhonkar S, Patro K, Harikumar K, Modi KD. Clinical profile of distal renal tubular acidosis. Saudi J Kidney Dis Transpl. 2011;22:261–7.

    PubMed  Google Scholar 

  14. Manz F, Wentz A, Lange S. Factors affecting renal hydrogen ion excretion capacity in healthy children. Pediatr Nephrol. 2001;16:443–5.

    Article  CAS  Google Scholar 

  15. Berkemeyer S, Vormann J, Günther ALB, Rylander R, Frassetto LA, Remer T. Renal net acid excretion capacity is comparable in prepubescence, adolescence, and young adulthood but falls with aging. J Am Geriatr Soc. 2008;56:1442–8.

    Article  Google Scholar 

  16. Garibotto G, Verzola D, Sofia A, Saffioti S, Menesi F, Vigo E, et al. Mechanisms of renal ammonia production and protein turnover. Metab Brain Dis. 2009;24:159–67.

    Article  CAS  Google Scholar 

  17. Peralta CA, Whooley MA, Ix JH, Shlipak MG. Kidney function and systolic blood pressure new insights from cystatin C: data from the Heart and Soul Study. Am J Hypertens. 2006;19:939–46.

    Article  CAS  Google Scholar 

  18. Kroke A, Manz F, Kersting M, Remer T, Sichert-Hellert W, Alexy U, et al. The DONALD Study. History, current status and future perspectives. Eur J Nutr. 2004;43:45–54.

    Article  Google Scholar 

  19. Cole TJ, Flegal KM, Nicholls D, Jackson AA. Body mass index cut offs to define thinness in children and adolescents: international survey. Br Med J. 2007;335:194.

    Article  Google Scholar 

  20. Krupp D, Westhoff TH, Esche J, Remer T. Prospective relation of adolescent citrate excretion and net acid excretion capacity with blood pressure in young adulthood. Am J Physiol Ren Physiol. 2018;315:F1228–F1235.

    Article  CAS  Google Scholar 

  21. Slaughter MH, Lohman TG, Boileau RA, Horswill CA, Stillman RJ, van Loan MD, et al. Skinfold equations for estimation of body fatness in children and youth. Hum Biol. 1988;60:709–23.

    PubMed  CAS  Google Scholar 

  22. Neuhauser H, Schienkiewitz A, Rosario AS, Dortschy R, Kurth B-M. Referenzperzentile für anthropometrische Maßzahlen und Blutdruck aus der Studie zur Gesundheit von Kindern und Jugendlichen in Deutschland (KiGGS). Reference percentiles for anthropometric measures and blood pressure from the study on the health of children and adolescents in Germany (KiGGS). 2013.

  23. Krupp D, Shi L, Remer T. Longitudinal relationships between diet-dependent renal acid load and blood pressure development in healthy children. Kidney Int. 2014;85:204–10.

    Article  CAS  Google Scholar 

  24. Remer T, Neubert A, Maser-Gluth C. Anthropometry-based reference values for 24-h urinary creatinine excretion during growth and their use in endocrine and nutritional research. Am J Clin Nutr. 2002;75:561–9.

    Article  CAS  Google Scholar 

  25. Lüthy C, Moser C, Oetliker O. Dreistufige Säure-Basen-Titration im Urin. [Acid-base determination of urine in 3 steps]. Med Lab (Stuttg).1977;30:174–81.

    PubMed  Google Scholar 

  26. Weiner ID, Mitch WE, Sands JM. Urea and ammonia metabolism and the control of renal nitrogen excretion. Clin J Am Soc Nephrol. 2015;10:1444–58.

    Article  CAS  Google Scholar 

  27. Weiner ID, Verlander JW. Renal ammonia metabolism and transport. Compr Physiol. 2013;3:201–20.

    PubMed  PubMed Central  Google Scholar 

  28. Jüppner H. Phosphate and FGF-23. Kidney Int. 2011;79121:S24–7.

    Article  CAS  Google Scholar 

  29. Bell DSH. Beware the low urine pH–the major cause of the increased prevalence of nephrolithiasis in the patient with type 2 diabetes. Diabetes Obes Metab. 2012;14:299–303.

    Article  CAS  Google Scholar 

  30. Patel ND, Ward RD, Calle J, Remer EM, Monga M. Vascular disease and kidney stones: abdominal aortic calcifications are associated with low urine pH and hypocitraturia. J Endourol. 2017;31:956–61.

    Article  Google Scholar 

  31. Neuhauser HK, Thamm M, Ellert U, Hense HW, Rosario AS. Blood pressure percentiles by age and height from nonoverweight children and adolescents in Germany. Pediatrics. 2011;127:e978–88.

    Article  Google Scholar 

  32. Zhu Q, Scherer PE. Immunologic and endocrine functions of adipose tissue: implications for kidney disease. Nat Rev Nephrol. 2018;14:105–20.

    Article  CAS  Google Scholar 

  33. Lloyd LJ, Langley-Evans SC, McMullen S. Childhood obesity and risk of the adult metabolic syndrome: a systematic review. Int J Obes (Lond). 2012;36:1–11.

    Article  CAS  Google Scholar 

  34. Goodwin JE, Geller DS. Glucocorticoid-induced hypertension. Pediatr Nephrol. 2012;27:1059–66.

    Article  Google Scholar 

  35. Hunter RW, Bailey MA. Glucocorticoids and 11β-hydroxysteroid dehydrogenases: mechanisms for hypertension. Curr Opin Pharm. 2015;21:105–14.

    Article  CAS  Google Scholar 

  36. Phisitkul S, Khanna A, Simoni J, Broglio K, Sheather S, Rajab MH, et al. Amelioration of metabolic acidosis in patients with low GFR reduced kidney endothelin production and kidney injury, and better preserved GFR. Kidney Int. 2010;77:617–23.

    Article  CAS  Google Scholar 

  37. Adeva MM, Souto G. Diet-induced metabolic acidosis. Clin Nutr. 2011;30:416–21.

    Article  CAS  Google Scholar 

  38. Taylor EN, Mount DB, Forman JP, Curhan GC. Association of prevalent hypertension with 24-hour urinary excretion of calcium, citrate, and other factors. Am J Kidney Dis. 2006;47:780–9.

    Article  CAS  Google Scholar 

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Acknowledgements

We thank our colleagues in the DONALD laboratory, and the anthropometric and dietary section for their dedicated technical assistance and performing all the detailed measurements. Particular thanks deserve our DONALD participants without whom such examinations in healthy free-living subjects during growth and later adulthood would never be possible.

Funding

The DONALD Study is funded by the Ministry of Innovation, Science and Research of North Rhine-Westphalia, Germany. This article is published as part of a supplement sponsored by NuOmix-Research K.S. The conference was financially supported by Protina Pharmazeutische GmbH, Germany and Sirius Pharma, Germany, and organized by NuOmix-Research K.S. Neither company had any role in writing of the paper.

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Contributions

All authors contributed to the designing of the research; DK and YH were responsible for statistical analyses and together with T.R. and JE for interpretation of the results. DK and YH were responsible for writing the paper together with TR; TR and DK have primary responsibility for the final content. All authors were involved in revising the paper critically and approved the final version.

Corresponding author

Correspondence to Thomas Remer.

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Conflict of interest

JE has received consulting fees from Nutricia North America, Inc. Remaining authors declare no conflict of interest.

Ethics

Ethical approval was obtained from the Ethics Committee of the University of Bonn, Germany. All assessments were performed with parental and grown-up children’s consent.

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Krupp, D., Hua, Y., Esche, J. et al. Renal biomarkers of acid excretion capacity: relationships with body fatness and blood pressure. Eur J Clin Nutr 74 (Suppl 1), 76–82 (2020). https://doi.org/10.1038/s41430-020-0696-2

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