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The link between the fibroblast growth factor-23—klotho—vitamin D3 axis and the renin—angiotensin—aldosterone axis in the development and progression of obesity-related kidney disease

The Egyptian Journal of Internal Medicine volume 25, pages 75–79 (2013)Cite this article

Abstract

Introduction and aim of the work

Obesity is established as an important contributor of increased diabetes mellitus, hypertension and cardiovascular disease, all of which can promote chronic kidney disease (CKD). Recently, there is a growing appreciation that even in the absence of these risks, obesity itself significantly increases CKD and accelerates its progression. The aim of this work is to evaluate the link between Renin-Angiotensin-Aldosterone System (RAAS) and FGF23-Klotho-1,25D3 axis and their impact in obese and non-obese CKD patients.

Patients and methods

In a cross sectional randomized multi centers study, two hundred twenty six CKD patients stage III and IV (eGFR20–60 ml/min/m2) have enrolled in this study as follows: group I; 87 non diabetic CKD patients aged 20–40 years with body mass index (BMI) between 20–25 kgm/m2; group II; 130 non diabetic CKD patients aged 20–40 years with (BMI) >30 kgm/m2 and group III; 89 CKD patients aged >60 years. All patient have been tested for plasma leptinlevels, 1,25-dihydrocholicalciferole (1,25D3), plasmaparathormone (PTH) Serum calcium (Ca), serum phosphorus (PO4), and plasma FGF-23 , plasma renin activity (PRA), plasma angiotensinogen receptor 1 & 2 (AT1 & AT2) and plasma aldosterone (ALD) and pulse wave velocity (PWV).

Results

The eGFR was significantly reduced in the obese group II (eGFR = 37.7 ± 13.6) when compared with eGFR of the lean group I (eGFR = 49.3 ± 7.51) were P < 0.001, but not significant when compared with the old age group III (eGFR = 41.0 ± 13.47). The obese group II shows significant increase in the ALD/PRA ratio when compared with the lean group I and old age group III (43.23 ± 14.9) for group II vs 11.29 ± 4.1 for group I, P < 0.001 and 24.91 ± 12.1 for group III, P < 0.05 ). Regarding the FGF23-Klotho-vitD3 axis, its components of the obese group II (FGF23 259.55 ± 138.6 Ru/ml; PTH 77.63 ± X32.4 pg/ml; S.PO 4.74 ± 1.61 mg/dl) were significantly elevated when compared to the lean group I (FGF23 132.81 ± 126.1 Ru/ ml; PTH 59.18 ± 24.7 pg/ml; S.PO4 3.85 ± 0.92 mg/dl); the P values were <0.001, <0.01 and <0.05 respectively , while when compared with the old age group III (FGF23 179.33 ± 237.4 Ru/ml; PTH 70.94 ± 15.26 pg/ml; S.PO4 4.09 ± 0.42 mg/dl), values were of less significance. Plasma insulin levels were significantly high in the obese group II (insulin = 13.73 ± 2.38fg/l) than the lean group I (insulin = 5.59 ± 2.31 fg/l) and P < 0.001 and in group III p. insulin level was 10.7 ± 1.68 (P < 0.05).

Conclusion

Obesity per se is an independent risk factor in the development and progression of chronic kidney disease specially in young age patients.

References

  1. Goncalves Torres MRS, Cardoso LG, de Abreu VG, Sanjuliani AF, Francischetti EA. Temporal relation between body mass index and renal function in individuals with hypertension and excess body weight. Nutrition 2009; 25:914–919.

    Article  PubMed  Google Scholar 

  2. Nomura I, Kato J, Kitamura K. Association between body mass index and chronic kidney disease: a population-based, cross-sectional study of a Japanese community. Vasc Health Risk Manag 2009; 5:315–320.

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Munkhaugen J, Lydersen S, Widerøe TE, Hallan S. Prehypertension obesity and risk of kidney disease: 20-year follow-up of the HUNT I study in Norway. Am J Kidney Dis 2009; 54:638–646.

    Article  PubMed  Google Scholar 

  4. Muntner P, Winston J, Uribarri J, Mann D, Fox CS. Overweight, obesity and elevated serum cystatin C levels in adults in the United States. Am J Med 2008; 121:341–348.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Praga M. Obesity – a neglected culprit in renal disease. Nephrol Dial Transplant 2002; 1 7:1157–1159.

    Article  Google Scholar 

  6. Bagby SP. Obesity-initiated metabolic syndrome and the kidney: a recipe for chronic kidney disease? J Am Soc Nephrol 2004; 15:2775–2791.

    Article  PubMed  Google Scholar 

  7. Sharma K, Ramachandrarao S, Qiu G, Usui HK, Zhu Y, Dunn SR, et al. Adiponectin regulates albuminuria and podocyte function in mice. J Clin Invest 2008; 118:1645–1656.

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Kambham N, Markowitz GS, Valeri AM, Lin J, DAgati VD. Obesity-related glomerulopathy: an emerging epidemic. Kidney Int 2001; 59:1498–1509.

    Article  CAS  PubMed  Google Scholar 

  9. Wolf G, Hamann A, Han DC, Helmchen U, Thaiss F, Ziyadeh FN, et al. Leptin stimulates proliferation and TGF-β expression in renal glomerular endothelial cells: potential role in glomerulosclerosis. Kidney Int 1999; 56:860–872.

    Article  CAS  PubMed  Google Scholar 

  10. Levey AS, Coresh J, Bolton K, Culleton B, Harvey KS, Ikizler TA, et al. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification and stratification. Am J Kidney Dis 2002; 39 (Suppl 1): i-ii + S1–S266.

    Google Scholar 

  11. National Center for Health Statistics. Serum leptin data and documentation. NHANES III, National Center for Health Statistics; 2002.

  12. Bandaru P, Shankar A. Association between plasma leptin levels and diabetes mellitus. Metab Syndr Relat Disord 2011; 9:19–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Mulatero P, Rabbia F, Milan A, Paglieri C, Morello F, Chiandussi L, et al. Drug effects on aldosterone/plasma renin activity ratio in primary aldosteronism. Hypertension 2002; 40:897–902.

    Article  CAS  PubMed  Google Scholar 

  14. Lu H, Boustany Kari CM, Daugherty A, Cassis LA. Angiotensin II increases adipose angiotensinogen expression. Am J Physiol Endocrinol Metab 2007; 292:E1280–E1287.

    Article  CAS  PubMed  Google Scholar 

  15. Sato A, Saruta T. Aldosterone-induced organ damage: plasma aldosterone level and inappropriate salt status. Hypertens Res 2004; 27:303–310.

    Article  CAS  PubMed  Google Scholar 

  16. Forman JP, Williams JS, Fisher NDL. Plasma 25-hydroxyvitamin D and regulation of the renin–angiotensin system in humans. Hypertension 2010; 55:1283–1288.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Burgess ED, Hawkins RG, Watanabe M. Interaction of 1,25-dihydroxyvitamin D and plasma renin activity in high renin essential hypertension. Am J Hypertens 1990; 3 (12 I): 903–905.

    Article  CAS  PubMed  Google Scholar 

  18. Nagase M, Fujita T. Aldosterone and glomerular podocyte injury. Clin Exp Nephrol 2008; 12:233–242.

    Article  CAS  PubMed  Google Scholar 

  19. De Paula RB, Da Silva AA, Hall JE. Aldosterone antagonism attenuates obesity-induced hypertension and glomerular hyperfiltration. Hypertension 2004; 43:41–47.

    Article  CAS  PubMed  Google Scholar 

  20. Bomback AS, Klemmer PJ. Renal injury in extreme obesity: the important role of aldosterone. Kidney Int 2008; 74:1216.

    Article  CAS  PubMed  Google Scholar 

  21. Hunley TE, Ma LJ, Kon V. Scope and mechanisms of obesity-related renal disease. Curr Opin Nephrol Hypertens 2010; 19:227–234.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Resnick LM, Muller FB, Laragh JH. Calcium-regulating hormones in essential hypertension: relation to plasma renin activity and sodium metabolism. Ann Intern Med 1986; 105:649–654.

    Article  CAS  PubMed  Google Scholar 

  23. Tomaschitz A, Pilz S, Ritz E, Grammer T, Drechsler C, Boehm BO, et al. Independent association between 1,25-dihydroxyvitamin D, 25-hydroxyvitamin D and the renin–angiotensin system. The Ludwigshafen Risk and Cardiovascular Health (LURIC) study. Clin Chim Acta 2010; 411 (17–18): 1354–1360.

    Article  CAS  PubMed  Google Scholar 

  24. Park CW, Oh YS, Shin YS, Kim CM, Kim YS, Kim SY, et al. Intravenous calcitriol regresses myocardial hypertrophy in hemodialysis patients with secondary hyperparathyroidism. Am J Kidney Dis 1999; 33:73–81.

    Article  CAS  PubMed  Google Scholar 

  25. De Borst MH, Vervloet MG, Ter Wee PM, Navis G. Cross talk between the renin–angiotensin–aldosterone system and vitamin D–FGF-23–klotho in chronic kidney disease. J Am Soc Nephrol 2011; 22:1603–1609.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Wolf G, Chen S, Han DC, Ziyadeh FN. Leptin and renal disease. Am J Kidney Dis 2002; 39:1–11.

    Article  CAS  PubMed  Google Scholar 

  27. Wolf G, Ziyadeh FN. Leptin and renal fibrosis. Contrib Nephrol 2006; 151:175–183.

    Article  PubMed  Google Scholar 

  28. Okpechi IG, Pascoe MD, Swanepoel CR, Rayner BL. Microalbuminuria and the metabolic syndrome in non-diabetic black Africans. Diab Vasc Dis Res 2007; 4:365–367.

    Article  PubMed  Google Scholar 

  29. Okpechi IG, Rayner BL, Van Der Merwe L, Mayosi BM, Adeyemo A, Tiffin N, et al. Genetic variation at selected SNPs in the leptin gene and association of alleles with markers of kidney disease in a Xhosa population of South Africa. PLoS One 2010; 5:e9086.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Department of Nephrology, Sahel Teaching Hospital, Hegaz Nephrology Center, 20, Tahreer St, Doki, 11511, Giza, Egypt

    Wael F. Nassar (MD), Mustafa A. Mustafa, Mohammad H. Hafez, Abdekbaser Saad, Mohammad Anan & Malaka Fouad

  2. Department of Nephrology, Clinical Pathology, Cairo University, Giza, Egypt

    Uomna Kamel

  3. Department of Clinical Pathology, Cairo University, Giza, Egypt

    Mahmud Temraz

  4. Department of Nephrology, Ahmad Maher Teaching Hospital, Cairo, Egypt

    Mahmud Temraz

  5. Department of Nephrology, October 6th University, 6th of October City, Egypt

    Mustafa A. Mustafa & Uomna Kamel

  6. Department of Nephrology, Zagazig University, Zagazig, Egypt

    Yaser Hendi & Amir Elokely

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  1. Wael F. Nassar
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Correspondence to Wael F. Nassar.

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Nassar, W.F., Mustafa, M.A., Kamel, U. et al. The link between the fibroblast growth factor-23—klotho—vitamin D3 axis and the renin—angiotensin—aldosterone axis in the development and progression of obesity-related kidney disease. Egypt J Intern Med 25, 75–79 (2013). https://doi.org/10.7123/01.EJIM.0000428342.18515.07

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  • DOI: https://doi.org/10.7123/01.EJIM.0000428342.18515.07

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