Skip to main content

Advertisement

Log in

Adiponectin in children and young adults with focal segmental glomerulosclerosis

  • Original Article
  • Published:
Pediatric Nephrology Aims and scope Submit manuscript

Abstract

Background

Adiponectin is an adipokine that is elevated in kidney disease. Evidence suggests that adiponectin exerts a direct effect on the podocyte and may play a role in the pathogenesis of proteinuria. The objectives of this study were to characterize serum and urine adiponectin levels over time in patients with focal segmental glomerulosclerosis (FSGS) and to evaluate the role of baseline levels of adiponectin as a predictor of clinical remission.

Methods

This was a study of 60 individuals, ages 3–38 years, with steroid-resistant FSGS enrolled in the FSGS clinical trial. Serial measurements of serum and urine adiponectin were obtained at baseline and 26 and 52 weeks.

Results

Participants were of mean age 19.4 ± 10.2 years (50 % male, 33 % black). Serum adiponectin (baseline mean 14.3 ± 6.6 μg/ml) and urine adiponectin:creatinine (Uadp/cr) (baseline mean 126.8 ± 178.9 μg/ml) directly correlated with proteinuria at all time points (r = 0.37–0.81; all p < 0.05). Proteinuria, hypoalbuminemia, and hyperlipidemia were significant independent predictors of greater serum adiponectin and Uadp/cr in multivariate analysis. Lower tertiles of baseline serum adiponectin were associated with greater response to treatment at 52 weeks when adjusted for age, sex, body mass index (BMI) z score, and estimated glomerular filtration rate (eGFR) [odds ratio (OR) 0.48; 95 % confidence interval (CI) 0.26–0.91, p = 0.023). For log Uadp/cr, the OR for remission was 0.43 (95 % CI 0.21–0.89, p = 0.02) at 52 weeks. However, when baseline urine protein:creatinine was added to the models, the relationships were no longer significant.

Conclusions

Serum and urine adiponectin levels were directly associated with proteinuria and paralleled changes in proteinuria over time in children and young adults with FSGS. Although baseline adiponectin was lower in responders, response to treatment in patients with FSGS was not associated with serum and urine adiponectin levels but, rather, was related to proteinuria.

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

Similar content being viewed by others

References

  1. Yamauchi T, Kamon J, Ito Y, Tsuchida A, Yokomizo T, Kita S, Sugiyama T, Miyagishi M, Hara K, Tsunoda M, Murakami K, Ohteki T, Uchida S, Takekawa S, Waki H, Tsuno NH, Shibata Y, Terauchi Y, Froguel P, Tobe K, Koyasu S, Taira K, Kitamura T, Shimizu T, Nagai R, Kadowaki T (2003) Cloning of adiponectin receptors that mediate antidiabetic metabolic effects. Nature 423:762–769

    Article  CAS  PubMed  Google Scholar 

  2. Hotta K, Funahashi T, Arita Y, Takahashi M, Matsuda M, Okamoto Y, Iwahashi H, Kuriyama H, Ouchi N, Maeda K, Nishida M, Kihara S, Sakai N, Nakajima T, Hasegawa K, Muraguchi M, Ohmoto Y, Nakamura T, Yamashita S, Hanafusa T, Matsuzawa Y (2000) Plasma concentrations of a novel, adipose-specific protein, adiponectin, in type 2 diabetic patients. Arterioscler Thromb Vasc Biol 20:1595–1599

    Article  CAS  PubMed  Google Scholar 

  3. Lim HS, Tayebjee MH, Tan KT, Patel JV, Macfadyen RJ, Lip GY (2005) Serum adiponectin in coronary heart disease: ethnic differences and relation to coronary artery disease severity. Heart 91:1605–1606

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  4. Matsubara M, Maruoka S, Katayose S (2002) Decreased plasma adiponectin concentrations in women with dyslipidemia. J Clin Endocrinol Metab 87:2764–2769

    Article  CAS  PubMed  Google Scholar 

  5. Chen MP, Tsai JC, Chung FM, Yang SS, Hsing LL, Shin SJ, Lee YJ (2005) Hypoadiponectinemia is associated with ischemic cerebrovascular disease. Arterioscler Thromb Vasc Biol 25:821–826

    Article  CAS  PubMed  Google Scholar 

  6. Mahmud A, Feely J (2005) Adiponectin and arterial stiffness. Am J Hypertens 18:1543–1548

    Article  CAS  PubMed  Google Scholar 

  7. Beauloye V, Zech F, Tran HT, Clapuyt P, Maes M, Brichard SM (2007) Determinants of early atherosclerosis in obese children and adolescents. J Clin Endocrinol Metab 92:3025–3032

    Article  CAS  PubMed  Google Scholar 

  8. Ouchi N, Ohishi M, Kihara S, Funahashi T, Nakamura T, Nagaretani H, Kumada M, Ohashi K, Okamoto Y, Nishizawa H, Kishida K, Maeda N, Nagasawa A, Kobayashi H, Hiraoka H, Komai N, Kaibe M, Rakugi H, Ogihara T, Matsuzawa Y (2003) Association of hypoadiponectinemia with impaired vasoreactivity. Hypertension 42:231–234

    Article  CAS  PubMed  Google Scholar 

  9. Sethna CB, Leonard MB, Gallagher PR, Meyers KE (2009) Serum adiponectin levels and ambulatory blood pressure monitoring in pediatric renal transplant recipients. Transplantation 88:1030–1037

    Article  CAS  PubMed  Google Scholar 

  10. Menon V, Li L, Wang X, Greene T, Balakrishnan V, Madero M, Pereira AA, Beck GJ, Kusek JW, Collins AJ, Levey AS, Sarnak MJ (2006) Adiponectin and mortality in patients with chronic kidney disease. J Am Soc Nephrol 17:2599–2606

    Article  CAS  PubMed  Google Scholar 

  11. Drechsler C, Krane V, Winkler K, Dekker FW, Wanner C (2009) Changes in adiponectin and the risk of sudden death, stroke, myocardial infarction, and mortality in hemodialysis patients. Kidney Int 76:567–575

    Article  CAS  PubMed  Google Scholar 

  12. Becker B, Kronenberg F, Kielstein JT, Haller H, Morath C, Ritz E, Fliser D, Group MS (2005) Renal insulin resistance syndrome, adiponectin and cardiovascular events in patients with kidney disease: the mild and moderate kidney disease study. J Am Soc Nephrol 16:1091–1098

    Article  CAS  PubMed  Google Scholar 

  13. Ho GJ, Lee CJ, Chen YC, Hsu BG (2014) Hypoadiponectinemia correlates with arterial stiffness in kidney transplantation patients. Clin Exp Nephrol. doi:10.1007/s10157-014-1010-1

    PubMed  Google Scholar 

  14. Zoccali C, Mallamaci F, Tripepi G, Benedetto FA, Cutrupi S, Parlongo S, Malatino LS, Bonanno G, Seminara G, Rapisarda F, Fatuzzo P, Buemi M, Nicocia G, Tanaka S, Ouchi N, Kihara S, Funahashi T, Matsuzawa Y (2002) Adiponectin, metabolic risk factors, and cardiovascular events among patients with end-stage renal disease. J Am Soc Nephrol 13:134–141

    Article  CAS  PubMed  Google Scholar 

  15. Kollerits B, Fliser D, Heid IM, Ritz E, Kronenberg F, Group MS (2007) Gender-specific association of adiponectin as a predictor of progression of chronic kidney disease: the Mild to Moderate Kidney Disease Study. Kidney Int 71:1279–1286

    Article  CAS  PubMed  Google Scholar 

  16. Jorsal A, Tarnow L, Frystyk J, Lajer M, Flyvbjerg A, Parving HH, Vionnet N, Rossing P (2008) Serum adiponectin predicts all-cause mortality and end stage renal disease in patients with type I diabetes and diabetic nephropathy. Kidney Int 74:649–654

    Article  CAS  PubMed  Google Scholar 

  17. Rao M, Li L, Tighiouart H, Jaber BL, Pereira BJ, Balakrishnan VS, Group HS (2008) Plasma adiponectin levels and clinical outcomes among haemodialysis patients. Nephrol Dial Transplant 23:2619–2628

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  18. Bakkaloglu SA, Soylemezoglu O, Buyan N, Funahashi T, Elhan AH, Peru H, Fidan K, Yilmaz S, Hasanoglu E (2005) High serum adiponectin levels during steroid-responsive nephrotic syndrome relapse. Pediatr Nephrol 20:474–477

    Article  PubMed  Google Scholar 

  19. Zoccali C, Mallamaci F, Panuccio V, Tripepi G, Cutrupi S, Parlongo S, Catalano F, Tanaka S, Ouchi N, Kihara S, Funahashi T, Matsuzawa Y (2003) Adiponectin is markedly increased in patients with nephrotic syndrome and is related to metabolic risk factors. Kidney Int Suppl: S98–102

  20. Tacke F, Wustefeld T, Horn R, Luedde T, Srinivas Rao A, Manns MP, Trautwein C, Brabant G (2005) High adiponectin in chronic liver disease and cholestasis suggests biliary route of adiponectin excretion in vivo. J Hepatol 42:666–673

    Article  CAS  PubMed  Google Scholar 

  21. Halberg N, Schraw TD, Wang ZV, Kim JY, Yi J, Hamilton MP, Luby-Phelps K, Scherer PE (2009) Systemic fate of the adipocyte-derived factor adiponectin. Diabetes 58:1961–1970

    Article  PubMed Central  PubMed  Google Scholar 

  22. Koshimura J, Fujita H, Narita T, Shimotomai T, Hosoba M, Yoshioka N, Kakei M, Fujishima H, Ito S (2004) Urinary adiponectin excretion is increased in patients with overt diabetic nephropathy. Biochem Biophys Res Commun 316:165–169

    Article  CAS  PubMed  Google Scholar 

  23. Rovin BH, Song H, Hebert LA, Nadasdy T, Nadasdy G, Birmingham DJ, Yung Yu C, Nagaraja HN (2005) Plasma, urine, and renal expression of adiponectin in human systemic lupus erythematosus. Kidney Int 68:1825–1833

    Article  CAS  PubMed  Google Scholar 

  24. Sharma K, Ramachandrarao S, Qiu G, Usui HK, Zhu Y, Dunn SR, Ouedraogo R, Hough K, McCue P, Chan L, Falkner B, Goldstein BJ (2008) Adiponectin regulates albuminuria and podocyte function in mice. J Clin Invest 118:1645–1656

    PubMed Central  CAS  PubMed  Google Scholar 

  25. Ohashi K, Iwatani H, Kihara S, Nakagawa Y, Komura N, Fujita K, Maeda N, Nishida M, Katsube F, Shimomura I, Ito T, Funahashi T (2007) Exacerbation of albuminuria and renal fibrosis in subtotal renal ablation model of adiponectin-knockout mice. Arterioscler Thromb Vasc Biol 27:1910–1917

    Article  CAS  PubMed  Google Scholar 

  26. Nakamaki S, Satoh H, Kudoh A, Hayashi Y, Hirai H, Watanabe T (2011) Adiponectin reduces proteinuria in streptozotocin-induced diabetic Wistar rats. Exp Biol Med (Maywood) 236:614–620

    Article  CAS  Google Scholar 

  27. Gipson DS, Trachtman H, Kaskel FJ, Greene TH, Radeva MK, Gassman JJ, Moxey-Mims MM, Hogg RJ, Watkins SL, Fine RN, Hogan SL, Middleton JP, Vehaskari VM, Flynn PA, Powell LM, Vento SM, McMahan JL, Siegel N, D’Agati VD, Friedman AL (2011) Clinical trial of focal segmental glomerulosclerosis in children and young adults. Kidney Int 80:868–878

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  28. Gipson DS, Trachtman H, Kaskel FJ, Radeva MK, Gassman J, Greene TH, Moxey-Mims MM, Hogg RJ, Watkins SL, Fine RN, Middleton JP, Vehaskari VM, Hogan SL, Vento S, Flynn PA, Powell LM, McMahan JL, Siegel N, Friedman AL (2011) Clinical trials treating focal segmental glomerulosclerosis should measure patient quality of life. Kidney Int 79:678–685

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  29. Schwartz GJ, Haycock GB, Edelmann CM Jr, Spitzer A (1976) A simple estimate of glomerular filtration rate in children derived from body length and plasma creatinine. Pediatrics 58:259–263

    CAS  PubMed  Google Scholar 

  30. Cockcroft DW, Gault MH (1976) Prediction of creatinine clearance from serum creatinine. Nephron 16:31–41

    Article  CAS  PubMed  Google Scholar 

  31. (2004) The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents. Pediatrics 114:555–576

  32. James PA, Oparil S, Carter BL, Cushman WC, Dennison-Himmelfarb C, Handler J, Lackland DT, LeFevre ML, MacKenzie TD, Ogedegbe O, Smith SC Jr, Svetkey LP, Taler SJ, Townsend RR, Wright JT Jr, Narva AS, Ortiz E (2014) Evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA 311:507–520

    Article  CAS  PubMed  Google Scholar 

  33. Tsioufis C, Dimitriadis K, Chatzis D, Vasiliadou C, Tousoulis D, Papademetriou V, Toutouzas P, Stefanadis C, Kallikazaros I (2005) Relation of microalbuminuria to adiponectin and augmented C-reactive protein levels in men with essential hypertension. Am J Cardiol 96:946–951

    Article  CAS  PubMed  Google Scholar 

  34. Barlovic DP, Zaletel J, Prezelj J (2009) Adipocytokines are associated with renal function in patients with normal range glomerular filtration rate and type 2 diabetes. Cytokine 46:142–145

    Article  CAS  PubMed  Google Scholar 

  35. Tamba S, Nakatsuji H, Kishida K, Noguchi M, Ogawa T, Okauchi Y, Nishizawa H, Imagawa A, Nakamura T, Matsuzawa Y, Funahashi T, Shimomura I (2010) Relationship between visceral fat accumulation and urinary albumin-creatinine ratio in middle-aged Japanese men. Atherosclerosis 211:601–605

    Article  CAS  PubMed  Google Scholar 

  36. Takahashi M, Otsubo S, Uchida K, Yumura W, Nitta K (2007) Association between serum adiponectin levels and arteriolosclerosis in IgA nephropathy patients. Intern Med 46:453–459

    Article  PubMed  Google Scholar 

  37. Hayakawa K, Ohashi H, Yokoyama H, Yoshida G, Okada M, Minatoguchi S (2009) Adiponectin is increased and correlated with the degree of proteinuria, but plasma leptin is not changed in patients with chronic glomerulonephritis. Nephrology (Carlton) 14:327–331

    Article  CAS  Google Scholar 

  38. Kamimura MA, Canziani ME, Sanches FR, Velludo CM, Carrero JJ, Bazanelli AP, Draibe SA, Cuppari L (2012) Variations in adiponectin levels in patients with chronic kidney disease: a prospective study of 12 months. J Bras Nefrol 34:259–265

    Article  PubMed  Google Scholar 

  39. Fujita H, Morii T, Koshimura J, Ishikawa M, Kato M, Miura T, Sasaki H, Narita T, Ito S, Kakei M (2006) Possible relationship between adiponectin and renal tubular injury in diabetic nephropathy. Endocr J 53:745–752

    Article  CAS  PubMed  Google Scholar 

  40. Jorsal A, Petersen EH, Tarnow L, Hess G, Zdunek D, Frystyk J, Flyvbjerg A, Lajer M, Rossing P (2013) Urinary adiponectin excretion rises with increasing albuminuria in type 1 diabetes. J Diabet Complications 27:604–608

    Article  Google Scholar 

  41. Nishimura R, Morimoto A, Matsudaira T, Miyashita Y, Sano H, Shirasawa T, Takahashi E, Tajima N (2007) Ratio of high-, medium-, and low-molecular weight serum adiponectin to the total adiponectin value in children. J Pediatr 151:545–547, 547 e541-542

    Article  CAS  PubMed  Google Scholar 

  42. Iwashima Y, Katsuya T, Ishikawa K, Ouchi N, Ohishi M, Sugimoto K, Fu Y, Motone M, Yamamoto K, Matsuo A, Ohashi K, Kihara S, Funahashi T, Rakugi H, Matsuzawa Y, Ogihara T (2004) Hypoadiponectinemia is an independent risk factor for hypertension. Hypertension 43:1318–1323

    Article  CAS  PubMed  Google Scholar 

  43. Matsubara M, Maruoka S, Katayose S (2002) Inverse relationship between plasma adiponectin and leptin concentrations in normal-weight and obese women. Eur J Endocrinol 147:173–180

    Article  CAS  PubMed  Google Scholar 

  44. Bakkaloglu SA, Soylemezoglu O, Buyan N, Oktar SO, Funahashi T, Pasaoglu H, Elhan AH, Peru H, Hasanoglu E (2006) Adiponectin levels and arteriosclerotic risk factors in pediatric renal transplant recipients. Pediatr Transplant 10:187–192

    Article  CAS  PubMed  Google Scholar 

  45. Cammisotto PG, Bendayan M (2008) Adiponectin stimulates phosphorylation of AMP-activated protein kinase alpha in renal glomeruli. J Mol Histol 39:579–584

    Article  CAS  PubMed  Google Scholar 

  46. Ahima RS (2008) Linking adiponectin to proteinuria. J Clin Invest 118:1619–1622

    PubMed Central  CAS  PubMed  Google Scholar 

  47. Furuhashi M, Ura N, Higashiura K, Murakami H, Tanaka M, Moniwa N, Yoshida D, Shimamoto K (2003) Blockade of the renin-angiotensin system increases adiponectin concentrations in patients with essential hypertension. Hypertension 42:76–81

    Article  CAS  PubMed  Google Scholar 

  48. Yilmaz MI, Sonmez A, Caglar K, Celik T, Yenicesu M, Eyileten T, Acikel C, Oguz Y, Yavuz I, Vural A (2007) Effect of antihypertensive agents on plasma adiponectin levels in hypertensive patients with metabolic syndrome. Nephrology (Carlton) 12:147–153

    Article  CAS  Google Scholar 

  49. Christou GA, Kiortsis DN (2014) The role of adiponectin in renal physiology and development of albuminuria. J Endocrinol 221:R49–R61

    Article  CAS  PubMed  Google Scholar 

  50. Branten AJ, Vervoort G, Wetzels JF (2005) Serum creatinine is a poor marker of GFR in nephrotic syndrome. Nephrol Dial Transplant 20:707–711

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We acknowledge the patients and institutions that participated in the FSGS Clinical Trial. We also acknowledge the biorepository and data repository, as well as the NIDDK/NIH for supporting the trial.

Conflict of interest

The authors declare no conflict of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Christine B. Sethna.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sethna, C.B., Boone, V., Kwok, J. et al. Adiponectin in children and young adults with focal segmental glomerulosclerosis. Pediatr Nephrol 30, 1977–1985 (2015). https://doi.org/10.1007/s00467-015-3146-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00467-015-3146-y

Keywords

Navigation