Skip to main content
SpringerLink
Log in

Urinary protein patterns in patients with Balkan endemic nephropathy

  • Nephrology - Original Paper
  • Published:
International Urology and Nephrology Aims and scope Submit manuscript

Abstract

Purpose

Urinary excretion of beta2-microglobulin (beta2-MG), albumin, immunoglobulin G (IgG) and protein was examined in patients with Balkan endemic nephropathy (BEN), glomerulonephritis (GN) and healthy controls.

Methods

The proteins were measured in morning urine samples from 74 patients with BEN, 50 healthy persons and 22 patients with GN.

Results

In BEN patients, median values for albumin, beta2-MG and protein were above upper normal limits, but median IgG was inside normal range. All patients with GN had microalbuminuria (MAU) and half of them had increased urinary beta2-MG, which was also found in eleven patients with increased urinary IgG. In BEN patients, there were significant negative correlations between eGFR and all measured urinary proteins, the composition of which changed during the course of BEN. In patients with eGFR > 60 ml/min/1.73 m2 isolated beta2-MG was the most frequent finding (10/12 patients), but MAU was present in 4/12 patients. In BEN patients with eGFR between 30 and 59 ml/min/1.73 m2, beta2-MG appeared as often as the combination of beta2-MG and albumin and isolated MAU. Out of 49 BEN patients with eGFR > 30 ml/min/1.73 m2 15 had increased urinary IgG either alone (1) or together with beta2-MG (3) or albumin (3) or beta2-MG and albumin (8). In BEN patients with GFR < 30 ml/min/1.73 m2 only 1/25 had isolated beta2-MG but increased urinary IgG with increased beta2-MG, and albumin was the most frequent.

Conclusion

Although low-molecular weight proteinuria was the most frequent urinary finding in BEN patients, MAU was frequently detected in advanced stages of BEN but also in some patients with eGFR > 60 ml/min/1.73 m2. IgG was increasingly found as eGFR decreased.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Stefanović V, Mitić-Zlatković M, Čukuranović R, Miljković P, Pavlović NM, Vlahović P (1991) Β2-microglobulin in patients with Balkan nephropathy and in healthy members of their families. Kidney Int 40(Suppl.34):S21–S26

    Google Scholar 

  2. Čvorišćec D (2000) Early diagnosis of endemic nephropathy. Clin Chim Acta 297:85–91

    Article  PubMed  Google Scholar 

  3. Dimitrov P, Tsolova S, Georgieva R, Bozhilova D, Simeonov V, Bonev A, Karmaus W (2006) Clinical markers in adult offspring of families with and without Balkan endemic nephropathy. Kidney Int 69:723–729

    Article  PubMed  CAS  Google Scholar 

  4. Imamovic G, Batuman V, Sinanovic O, Trnacevic S, Mesic E, Zerem E, Osmanovic E (2008) Microalbuminuria as a possible marker of risk of Balkan endemic nephropathy. Nephrology (Carlton) 13:616–621

    Article  Google Scholar 

  5. D’Amico G, Bazzi C (2003) Pathophysiology of proteinuria. Kidney Int 63:809–825

    Article  PubMed  Google Scholar 

  6. Christensen EI, Birn H, Verroust P, Moestrup SK (1998) Membrane receptors for endocytosis in the renal proximal tubule. Int Rev Cytol 180:237–284

    PubMed  CAS  Google Scholar 

  7. Bakoush O, Grubb A, Rippe B, Tencer J (2001) Urine excretion of protein HC in proteinuric glomerular diseases correlates to urine IgG but not to albuminuria. Kidney Int 60:1904–1909

    Article  PubMed  CAS  Google Scholar 

  8. Stefanovic V, Cukuranovic R, Djordjevic V, Jovanovic I, Lecic N, Rajic M (2009) Tubular marker excretion in children from families with Balkan nephropathy. Pediatr Nephrol 24:2155–2166

    Article  PubMed  Google Scholar 

  9. Stefanović V, Jelaković B, Čukuranović R, Bukvić D, Nikolić J, Lukić L, Gluhovschi G, Toncheva D, Polenaković M, Cosyns JP (2007) Diagnostic criteria for Balkan endemic nephropathy: proposal by an international panel. Ren Fail 29:867–880

    Article  PubMed  Google Scholar 

  10. Djukanović L, Marinković J, Marić I, Ležaić V, Dajak M, Petronić D, Matić M, Bukvić D (2008) Contribution to the definition of diagnostic criteria for Balkan endemic nephropathy. Nephrol Dial Transplant 23:3932–3938

    Article  PubMed  Google Scholar 

  11. National Kidney Foundation (2002) K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification and stratification. Am J Kidney Dis 39(2 Suppl 1):S1–S266

    Google Scholar 

  12. (1999) European best practice guidelines for the management of anaemia in patients with chronic renal failure. Working Party for European Best Practice Guidelines for the Management of Anaemia in Patients with Chronic Renal Failure. Nephrol Dial Transplant 14(Suppl 5):1–50

  13. Schlessinger SD, Tankersley MR, Curtis JJ (1994) Clinical documentation of end-stage renal disease due to hypertension. Am J Kidney Dis 23:655–660

    PubMed  CAS  Google Scholar 

  14. Hall PW, Gaon J, Griggs PC, Piscator M, Popović N, Vasiljević M, Zimonjić B (1967) The use of electrophoretic analysis of urinary protein excretion to identify early involvement in endemic nephropathy. In: Wolstenholme GEW, Knight J (eds) Ciba Foundation Study Group No. 30. The Balkan Nephropathy. Churchill, London, UK, pp 72–83

  15. Bruckner I, Stoica G, Serban M (1967) Studies on urinary proteins. In: Wolstenholme GEW, Knight J (eds) Ciba Foundation Study Group No. 30. The Balkan Nephropathy. Churchill, London, UK, pp 15–20

  16. Radošević Z, Traeger J, Radonić M, Manuel Y, Revillard JP (1968) Etude elctrophoretique de la proteinurie de 31 sujet crates vivant en pays de nephropathie endemique. J Urol Nephrol 74:703–710

    Google Scholar 

  17. Traeger J, Radošević Z, Radonić M, Manuel Y, Keler M, Mihelćić, Čeović S (1972) A study of proteinuria in patients with endemic nephropathy. Second symposium on endemic nephropathy. Sofia. p 9

  18. Bruckner I, Nichifor F, Rusu G (1981) Endemic nephropathy in Romania. In: Strahinjic S, Stefanovic V (eds) Endemic (Balkan) Nephropathy, Proceedings of 4th Symposium, Niš 1979. Institute of Nephrology Haemodialysis, Niš, pp 11–19

  19. Čvorišćec D, Radonić M, Čeović S, Aleraj B (1983) Characteristics of proteinuria in endemic nephropathy. J Clin Chem Clin Biochem 21:569–571

    PubMed  Google Scholar 

  20. Raičević S, Trnačević S, Hranisavljević J, Vučelić D (1991) Renal function, protein excretion, and pathology of Balkan endemic nephropathy. II. Protein excretion. Kidney Int 40(Suppl. 34):S52–S56

    Google Scholar 

  21. Karlsson FA, Lenkei R (1977) Urinary excretion of albumin and beta2-microglobulin in population from an area where Balkan nephropathy is endemic. Scand J Clin Lab Invest 37:169–173

    PubMed  CAS  Google Scholar 

  22. Miljkovic P, Strahinjic S, Hall PW, Djordjevic V, Mitic-Zlatkovic M, Stefanovic V (1991) Urinary protein excretion in children from families with Balkan nephropathy. Kidney Int 40(Suppl 34):S27–S31

    Google Scholar 

  23. Stefanovic V, Cukuranovic R, Mitic-Zlatkovic M, Hall PW (2002) Increased urinary albumin excretion in children from families with Balkan nephropathy. Pediatr Nephrol 17:913–916

    Article  PubMed  Google Scholar 

  24. Stefanović V, Djukanović L, Cukuranović R, Bukvić D, Ležaić V, Marić I, Ogrizović SS, Jovanović I, Vlahovic P, Pešić I, Djordjević V (2011) Beta2-microglobulin and alpha1-microglobulin as markers of Balkan endemic nephropathy, a worldwide disease. Ren Fail 33:176–183

    Article  PubMed  Google Scholar 

  25. Yu Y, Jin H, Holder D, Ozer JS, Villarreal S, Shughrue P, Shi S, Figueroa DJ, Clouse H, Su M, Muniappa N, Troth SP, Bailey W, Seng J, Aslamkhan AG, Thudium D, Sistare FD, Gerhold DL (2010) Urinary biomarkers trefoil factor 3 and albumin enable early detection of kidney tubular injury. Nat Biotechnol 28(5):470–477

    Article  PubMed  CAS  Google Scholar 

  26. Sindjić M (2000) Morphological changes in kidneys affected by endemic nephropathy. In: Radovanović Z, Sindjić M, Polenaković M, Djukanović Lj, Petronić V (eds) Endemic nephropathy. Office for Textbooks and Teaching Aids, Beograd, pp 153–275

  27. Ferluga D, Hvala A, Vizjak A, Trnavcevic S, Halibasic A (1991) Renal function, protein excretion and pathology of Balkan endemic nephropathy. III Light and electron microscopy studies. Kidney Int 40(Suppl 34):S54–S67

    Google Scholar 

  28. Čukuranović R, Stefanović N, Savić V, Stefanović V (1998) Quantitative analysis of renal changes in Balkan endemic nephropathy. Int Urol Nephrol 30:229–236

    Article  PubMed  Google Scholar 

  29. Cosyns J-P, Jadoul M, Squifflet J-P et al (1994) Chinese herbs nephropathy: a clue to Balkan endemic nephropathy? Kidney Int 45:1680–1688

    Article  PubMed  CAS  Google Scholar 

  30. Wedeen RP (1991) Environmental renal disease: lead, cadmium and Balkan endemic nephropathy. Kidney Int Suppl 34:S4–S8

    PubMed  CAS  Google Scholar 

  31. Kazama I, Matsubara M, Michimata M, Suzuki M, Hatano R, Sato H, Ito S (2004) Adult onset Fanconi syndrome: extensive tubulo-interstitial lesions and glomerulopathy in the early stage of Chinese herbs nephropathy. Clin Exp Nephrol 8:283–287

    Article  PubMed  Google Scholar 

  32. Wang Y, Fu W, Wang H, Liang Y, Wang Y, Yao W, Chen W, Li Q, Ying PH, Shi X, Peng W (2012) Renal microvascular injury in chronic aristolochic acid nephropathy and protective effects of Cozaar. Ren Fail 34:60–67

    Article  PubMed  Google Scholar 

  33. Bernard AM, Roels H, Cardenas A, Lauwerys R (1990) Assessment of urinary protein 1 and transferrin as early markers of cadmium nephrotoxicity. Br J Ind Med 47:559–565

    PubMed  CAS  Google Scholar 

  34. Brenner BM, Meyer TW, Hostetter TH (1982) Dietary protein intake and the progressive nature of kidney disease: the role of hemodynamically mediated glomerular injury in the pathogenesis of progressive glomerular sclerosis in aging, renal ablation, and intrinsic renal disease. N Engl J Med 307:652–659

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by Grant No 175092, from the Ministry of Education, Science and Technological Development of Serbia.

Conflict of interest

The authors have declared that no conflict of interest exists.

Author information

Authors and Affiliations

  1. Faculty of Medicine, University of Belgrade, Dr Subotića 8, 11 000, Belgrade, Serbia

    Ljubica Djukanović, Višnja Ležaić & Jelena Marinković

  2. Faculty of Medicine, University of Niš, Nis, Serbia

    Vidosava Djordjević, Rade Čukuranović, Jovana Čukuranović, Milena Rajić & Vladisav Stefanović

  3. Special Hospital for Endemic Nephropathy, Lazarevac, Serbia

    Ivko Marić & Danica Bukvić

Authors
  1. Ljubica Djukanović
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Vidosava Djordjević
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Višnja Ležaić
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Rade Čukuranović
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ivko Marić
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Danica Bukvić
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jelena Marinković
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jovana Čukuranović
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Milena Rajić
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Vladisav Stefanović
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ljubica Djukanović.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Djukanović, L., Djordjević, V., Ležaić, V. et al. Urinary protein patterns in patients with Balkan endemic nephropathy. Int Urol Nephrol 45, 1661–1669 (2013). https://doi.org/10.1007/s11255-013-0499-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11255-013-0499-7

Keywords

Search

Navigation