Clinical and Experimental Nephrology

, Volume 19, Issue 3, pp 436–442 | Cite as

Serum galectin-3 levels were associated with proteinuria in patients with Familial Mediterranean Fever

  • Hakki Yilmaz
  • Osman Inan
  • Tahir Darcin
  • Mukadder Ayse Bilgic
  • Ali Akcay
Original Article

Abstract

Background

The most common and pernicious complication of Familial Mediterranean fever (FMF) is renal amyloidosis, usually affecting the kidneys, leading to end-stage renal failure. FMF-related renal amyloidosis needed to be diagnosed early. Optimal colchicine dose is effective in preventing and reversing renal amyloidosis. Galectin-3, profibrotic mediator, has regulatory functions in inflammation, fibrosis and tumorigenesis. Galectin-3 is a strong prognostic marker for heart failure. Galectin-3 plays role in diabetic nephropathy and chronic kidney disease. The aim of the study is to investigate whether galectin-3 is related to proteinuria and amyloidosis in FMF.

Methods

Seventy-five FMF patients who have no exclusion criteria and healthy controls (n = 36) were included. Serum galectin-3 was measured and morning spot urine was collected for determination of the protein/creatinine ratio (PCR).

Results

Serum Galectin-3 levels were significantly higher in FMF patients than the control group [969.66 (3825) pg/mL vs. 238 (921) pg/mL, respectively; P<0.001]. We classified into two groups: Group1 (n = 48) had FMF patients with proteniuria, Group2 (n = 27) had FMF patients without proteinuria. Group1 had higher levels of galectin-3 than Group2 [1106(3812) pg/mL vs. 867.3(1433) pg/mL, P < 0.001]. Galectin-3 levels were correlated with PCR in whole group and FMF group (r = 0.785, P < 0.001 and r = 0.803, P < 0.001). In ROC curve, best cutoff value = 581.50 pg/mL was used to detect proteinuria (sensitivity = 91.7 %, specificity = 71.4 %, AUC = 0.879) and optimal cutoff value = 1458.00 pg/mL was an indicator of nephrotic-range proteinuric (sensitivity = 100 %, specificity = 92.1 %, AUC = 0.983).

Conclusion

Galectin-3 is associated with proteinuria and renal amyloidosis in FMF. Galectin-3 may play role in pathogenesis of amyloidosis.

Keywords

Galectin-3 Proteinuria Renal amyloidosis FMF 

Notes

Conflict of interest

All the authors have declared no competing interest.

References

  1. 1.
    Soriano A, Manna R. Familial Mediterranean fever: new phenotypes. Autoimmun Rev. 2012;12:31–7.PubMedCrossRefGoogle Scholar
  2. 2.
    Portincasa P, Scaccianoce G, Palasciano G. Familial Mediterranean fever: a fascinating model of inherited autoinflammatory disorder. Eur J Clin Invest. 2013;43(12):1314–27.PubMedCrossRefGoogle Scholar
  3. 3.
    Onen F. Familial Mediterranean fever. Rheumatol Int. 2006;26:489–96.PubMedCrossRefGoogle Scholar
  4. 4.
    Lidar M, Livneh A. Familial Mediterranean fever: clinical, molecular and management advancements. Neth J Med. 2007;65(9):318–24.PubMedGoogle Scholar
  5. 5.
    Pinney JH, Lachmann HJ. Systemic AA amyloidosis. Subcell Biochem. 2012;65:541–64.PubMedGoogle Scholar
  6. 6.
    Sohar E, Gafni J, Pras M, Heller H. Familial Mediterranean fever. A survey of 470 cases and review of the literature. Am J Med. 1967;43(2):227–53.PubMedCrossRefGoogle Scholar
  7. 7.
    Pras M, Bronshpigel N, Zemer D, Gafni J. Variable incidence of amyloidosis in familial Mediterranean fever among different ethnic groups. Johns Hopkins Med J. 1982;150:22–6.PubMedGoogle Scholar
  8. 8.
    Tunca M, Akar S, Onen F, Ozdogan H, Kasapcopur O, Yalcinkaya F, Tutar E, Ozen S, Topaloglu R, Yilmaz E, Arici N, Bakkaloglu A, Besbas N, Akpolat T, Dinc A, Erken E, Turkish FMF study group. Familial Mediterranean fever in Turkey. Results of a nationwide multicenter study. Medicine. 2005;84:1–11.PubMedCrossRefGoogle Scholar
  9. 9.
    Ben-Chetrit E, Levy M. Familial Mediterranean fever. Lancet. 1998;351:659–64.PubMedCrossRefGoogle Scholar
  10. 10.
    Drenth JP, van der Meer JW. Hereditary periodic fever. N Engl J Med. 2001;345(24):1748–57.PubMedCrossRefGoogle Scholar
  11. 11.
    de Boer RA, Voors AA, MuntendamP, vanGilstWH, van Veldhuisen DJ. Galectin-3: a novel mediator of heart failure development and progression. Eur J Heart Fail. 2009;11:811–7.PubMedCrossRefGoogle Scholar
  12. 12.
    Henderson NC, Sethi T. The regulation of inflammation by galectin-3. Immunol Rev. 2009;230(1):160–71.PubMedCrossRefGoogle Scholar
  13. 13.
    Pugliese G, Pricci F, Iacobini C, Leto G, Amadio L, Barsotti P, Frigeri L, Hsu DK, Vlassara H, Liu F-T, Di Mario U. Accelerated diabetic glomerulopathy in galectin-3/AGE receptor 3 knockout mice. FASEB J. 2001;15(13):2471–9.PubMedCrossRefGoogle Scholar
  14. 14.
    Iacobini C, Amadio L, Oddi G, Ricci C, Barsotti P, Missori S, Sorcini M, Di Mario U, Pricci F, Pugliese G. Role of galectin-3 in diabetic nephropathy. J Am Soc Nephrol. 2003;14:S264–70.PubMedCrossRefGoogle Scholar
  15. 15.
    Henderson NC, Mackinnon AC, Farnworth SL, Kipari T, Haslett C, Iredale JP, Liu FT, Hughes J, Sethi T. Galectin-3 expression and secretion links macrophages to the promotion of renal fibrosis. Am J Pathol. 2008;172:288–98.PubMedCentralPubMedCrossRefGoogle Scholar
  16. 16.
    Dang Z, MacKinnon A, Marson LP, Sethi T. Tubular atrophy and interstitial fibrosis after renal transplantation is dependent on galectin-3. Transplantation. 2012;93:477–84.PubMedCrossRefGoogle Scholar
  17. 17.
    O’Seaghdha CM, Hwang SJ, Ho JE, Vasan RS, Levy D, Fox CS. Elevated galectin-3 precedes the development of CKD. J Am Soc Nephrol. 2013;24:1470–7.PubMedCentralPubMedCrossRefGoogle Scholar
  18. 18.
    Friedman EA, Brittain E, Su YR, LeBoeuf J, Sawyer D, Lenihan D. Markedly elevated galectin-3 levels in cardiac amyloidosis may indicate significant fibrosis. J Cardiac Fail. 2013;19(8):S63.CrossRefGoogle Scholar
  19. 19.
    Livneh A, Langevitz P, Zemer D, Zaks N, Kees S, Lidar T, et al. Criteria for the diagnosis of familial Mediterranean fever. Arthr Rheum. 1997;40:1879–85.CrossRefGoogle Scholar
  20. 20.
    Pras E, Livneh A, Balow JE, Kastner DL, Pras M, Langevitz P. Clinical differences between North African and Iraqi Jews with familial Mediterranean fever. Am J Med Genet. 1998;75:216–9.PubMedCrossRefGoogle Scholar
  21. 21.
    Schwab SJ, Christensen RL, Dougherty K, Klahr S. Quantitation of proteinuria by the use of protein-to-creatinine ratios in single urine samples. Arch Intern Med. 1987;147(5):943–4.PubMedCrossRefGoogle Scholar
  22. 22.
    Ginsberg JM, Chang BS, Matarese RA, Garella S. Use of single voided urine samples to estimate quantitative proteinuria. N Engl J Med. 1983;309(25):1543–6.PubMedCrossRefGoogle Scholar
  23. 23.
    Hanley JA, McNeil BJ. The meaning and use of the area under a receiver operating characteristic (ROC) curve. Radiology. 1982;143:29–36.PubMedCrossRefGoogle Scholar
  24. 24.
    Matsunaga N, Anan I, Rosenberg P, Nagai R, Lundström O, Horiuchi S, Ando Y, Suhr OB. Advanced glycation end product is implicated in amyloid-related kidney complications. Scand J Clin Lab Invest. 2005;65(4):263–72.PubMedCrossRefGoogle Scholar
  25. 25.
    Bohle A, Wehrmann M, Eissele R, von Gise H, Mackensen-Haen S, Muller C. The long-term prognosis of AA and AL renal amyloidosis and the pathogenesis of chronic renal failure in renal amyloidosis. Pathol Res Pract. 1993;189:316–31.PubMedCrossRefGoogle Scholar
  26. 26.
    Sen S, Sarsik B. A proposed histopathologic classification, scoring, and grading system for renal amyloidosis: standardization of renal amyloid biopsy report. Arch Pathol Lab Med. 2010;134(4):532–44.PubMedGoogle Scholar
  27. 27.
    Ben-Zvi I, Livneh A. Chronic inflammation in FMF: markers, risk factors, outcomes and therapy. Nat Rev Rheumatol. 2011;7(2):105–12.PubMedCrossRefGoogle Scholar
  28. 28.
    Yalçinkaya F, Cakar N, Acar B, Tutar E, Güriz H, Elhan AH, Oztürk S, Kansu A, Ince E, Atalay S, Girgin N, Doğru U, Aysev D, Ekim M. The value of the levels of acute phase reactants for the prediction of familial Mediterranean fever associated amyloidosis: a case control study. Rheumatol Int. 2007;27(6):517–22.PubMedCrossRefGoogle Scholar
  29. 29.
    Düzova A, Bakkaloğlu A, Beşbaş N, Topaloğlu R, Özen S, Özaltin F, Başsoy Y, Yilmaz E. Role of A-SAA in monitoring subclinical inflammation and in colchicines dosage in familial Mediterranean fever. Clin Exp Rheum. 2003;21:509–14.Google Scholar
  30. 30.
    Gillmore JD, Lovat LB, Persey MR, Pepys MB, Hawkins PN. Amyloid load and clinical outcome in AA amyloidosis in relation to circulating concentration of serum amyloid A protein. Lancet. 2001;358:24–9.PubMedCrossRefGoogle Scholar
  31. 31.
    Yalcinkaya F, Turner N. Glomerular lesions other than amyloidosis in patients with FMF. Nephrol Dial Transplant. 1999;14:21–3.PubMedCrossRefGoogle Scholar
  32. 32.
    Akpolat T, Akpolat I, Karagoz F, et al. Familial Mediterranean fever and glomerulonephritis and review of the literature. Rheumatol Int. 2004;24:43–5.PubMedCrossRefGoogle Scholar
  33. 33.
    Said R, Hamzeh Y, Said S, et al. Spectrum of renal involvement in FMF. Kidney Int. 1992;41:414–9.PubMedCrossRefGoogle Scholar

Copyright information

© Japanese Society of Nephrology 2014

Authors and Affiliations

  • Hakki Yilmaz
    • 1
  • Osman Inan
    • 2
  • Tahir Darcin
    • 3
  • Mukadder Ayse Bilgic
    • 1
  • Ali Akcay
    • 1
  1. 1.Department of Internal Medicine, Section of Nephrology, School of MedicineTurgut Ozal UniversityAnkaraTurkey
  2. 2.Department of Internal MedicineYenimahalle State HospitalAnkaraTurkey
  3. 3.Department of Internal MedicineAgri State HospitalAgriTurkey

Personalised recommendations