Pediatric Nephrology

, Volume 20, Issue 10, pp 1410–1415 | Cite as

Altered activity of plasma hemopexin in patients with minimal change disease in relapse

  • Winston W. BakkerEmail author
  • Catharina M. L. van Dael
  • Leonie J. W. M. Pierik
  • Joanna A. E. van Wijk
  • Jeroen Nauta
  • Theo Borghuis
  • Jola J. Kapojos
Original Article


Since an active isoform of plasma hemopexin (Hx) has been proposed to be a potential effector molecule in minimal change disease (MCD), we tested plasma and urine samples from subjects with MCD in relapse (n =18) or in remission (n =23) (after treatment with prednisolone) for presence or activity of Hx. For comparison, plasma or urine from proteinuric subjects with focal and segmental glomerulosclerosis (FSGS, n =11), membranoproliferative glomerulonephritis (MPGN, n =9), IgA nephropathy (n =5) or healthy control donors (n =10), were incorporated into the study. Electrophoresis and Western blotting methods were used for evaluation of the Hx status, whereas protease activity of Hx was tested upon kidney tissue in vitro according to standard methods. The results show (1) a decreased mean titer of plasma Hx exclusively in MCD relapse subjects as compared with MCD in remission (0.21±0.14 mg/ml vs 0.44±0.06 mg/ml; p <0.01). Mean Hx titers in other proteinuric subjects ranged from 0.38±0.05 mg/ml to 0.40± 0.06 mg/ml, whereas, the mean titer of healthy controls was 0.59±0.03 mg Hx/ml; (2) an increased Hx activity (expressed in arbitrary units) exclusively in plasma from MCD relapse subjects (3.3±0.72 vs 1.16±0.56, MCD remission; p <0.01); (3) different Western blot patterns in MCD relapse vs remission plasma; (4) reduced stainability or virtual absence of the 80-kD Hx band in blots of urine from MCD relapse in contrast to urine samples from other proteinuric subjects with FSGS, MPGN, or IgA nephropathy. It is concluded that Hx in MCD relapse subjects may exist in an altered isoform, showing enhanced protease activity as compared with subjects in remission, subjects with other forms of primary glomerulopathy, or healthy control individuals.


Hemopexin Minimal change disease Nephrotic syndrome Proteinuria 



This work was supported by the Dutch Kidney Foundation (Grant C01.1964). We thank Mrs. Rianne Jongman for technical assistance and Mr. Siep Norrman for performing the microphotography


  1. 1.
    Mason PD ( 2003) Minimal change disease and primary focal segmental glomerulosclerosis. In: Johnson RJ, Freehally J (eds) Comprehensive clinical nephrology, 2nd edn. Mosby, New York, pp 271–283Google Scholar
  2. 2.
    Sahali D, Pawlak A, Valanciute A, Grimbert P, Lang P, Remy P, Bensman A, Guellen G (2002) A novel approach to investigation of the pathogenesis of active minimal-change nephritic syndrome using subtracted cDNA library screening. J Am Soc Nephrol 13:1238–1247PubMedGoogle Scholar
  3. 3.
    Van den Berg JG, Nauta J, Aten J, Claessen N, Stordeur P, Florquin S, Davin JCMA, Weening JJ (2002) A possible role of IL-10 in the pathogenesis of minimal change nephrotic syndrome. J Am Soc Nephrol 13:349AGoogle Scholar
  4. 4.
    Ian CI, Chen A, Sum GH, Yu DS, Yen CY, Chen JS, Lin YF (2003) Recurrent minimal change disease post-allograft renal transplant Transplant Proc 35:2888–2890Google Scholar
  5. 5.
    Savin VJ (1993) Mechanisms of proteinuria in noninflammatory glomerular diseases. Am J Kidney Dis 21:347–362PubMedGoogle Scholar
  6. 6.
    Garin DH (2000) Circulating mediators of proteinuria in idiopathic minimal lesion nephrotic syndrome. Pediatr Nephrol 14:872–878CrossRefPubMedGoogle Scholar
  7. 7.
    Glassock RJ (2003) Circulating permeability factors in nephrotic syndrome: a fresh look at an old problem J Am Soc Nephrol 14:541–543Google Scholar
  8. 8.
    Cheung PK, Stulp B, Immenschuh S, Borghuis T, BallerJF, BakkerWW (1999) Is 100KF an isoform of hemopexin? Immunochemical characterization of the vasoactive plasma factor 100KF. J Am Soc Nephrol 10:1700–1708PubMedGoogle Scholar
  9. 9.
    Cheung PK, Klok PA, Baller JF, Bakker WW (2000) Induction of experimental proteinuria in vivo following infusion of human plasma hemopexin. Kidney Int 57:1512–1520CrossRefPubMedGoogle Scholar
  10. 10.
    Kuzelova K, Mrhalova M, Hrkal Z (1997) Kinetics of heme interaction with heme-binding proteins: the effect of heme aggregation state. Biochim Biophys Acta 1336:497–501PubMedGoogle Scholar
  11. 11.
    Vincent SH, Grady RW, Shaklai N, Snider JM, Muller-Eberhard U (1988) The influence of heme-binding proteins in heme-catalyzed oxidations. Arch Biochem Biophys 265:539–550CrossRefPubMedGoogle Scholar
  12. 12.
    Kamboh MI, Bunker CH, Nwankwo MU, Ferrell RE (1993) Hemopexin: a unique genetic polymorphism in populations of African ancestry. Hum Biol 65:655–660PubMedGoogle Scholar
  13. 13.
    Kamboh MI, Ferrell RE (1987) Genetic studies of low-abundance human plasma proteins. VI. Polymorphism of hemopexin. Am J Hum Genet 41:645–653PubMedGoogle Scholar
  14. 14.
    Gutteridge JM (1995) Lipid peroxidation and antioxidants as biomarkers of tissue damage. Clin Chem 41:1819–1828PubMedGoogle Scholar
  15. 15.
    Immenschuh S, Nagae Y, Satoh H, Baumann H, Muller-Eberhard U (1994) The rat and human hemopexin genes contain an identical interleukin-6 response element that is not a target of CAAT enhancer-binding protein isoforms. J Biol Chem 269:12654–12661PubMedGoogle Scholar
  16. 16.
    Immenschuh S, Song DX, Satoh H, Muller-Eberhard U (1995) The type II hemopexin interleukin-6 response element predominates the transcriptional regulation of the hemopexin acute phase responsiveness. Biochem Biophys Res Commun 207:202–208CrossRefPubMedGoogle Scholar
  17. 17.
    Kapojos JJ, Poelstra K, Borghuis T, Banas B, Bakker WW (2004) Regulation of plasma hemopexin activity by stimulated endothelial or mesangial cells. Nephron Physiol 96:1–10CrossRefGoogle Scholar
  18. 18.
    Bakker WW, Kapojos JJ, van den Berg A, Harmsen MC, Klok PA, Borghuis T (2002) Acute leakage of plasma proteins induced by unilateral perfusion of recombinant hemopexin (r-Hx) into the rat kidney. J Am Soc Nephrol 13:664AGoogle Scholar
  19. 19.
    Bakker WW, Borghuis T, Harmsen MC, van den Berg A, Kema IP, Niezen KE, Kapojos JJ (2004) Protease activity of plasma hemopexin. Kidney Int (in press)Google Scholar
  20. 20.
    Bakker WW, Baller JFW, van Luijk WHJ (1988) Increased vasoactivity and enhanced turnover of a kallikrein-like molecule in plasma from subjects with minimal change disease in relapse versus remission. Contrib Nephrol 67:31–36PubMedGoogle Scholar
  21. 21.
    Orasenneau J, Douet P, Massaoubre C, Lustenberger P, Bernard S (1989) An improved pyrogallol red molybdate method for determining total urinary protein. Clin Chem 35:2233–2236PubMedGoogle Scholar
  22. 22.
    Savin VJ, Sharma R, Lovell HV, Welling DJ ( 1992) Measurement of albumin reflection coefficient using isolated rat glomeruli. J Am Soc Nephrol 3:1260–1269PubMedGoogle Scholar
  23. 23.
    Carraro M, Zennaro C, Artero M, Cardiano G, Ghiggeri GM, Musante L, Sirch C, Bruschi M, Faccini L (2004) The effect of proteinase inhibitors on glomerular albumin permeability induced in vitro by serum from patients with idiopathic focal segmental glomerulosclerosis. Nephrol Dial Transplant 19:1969–1975CrossRefPubMedGoogle Scholar
  24. 24.
    Kapojos JJ, van den Berg A, van Goor H, Te Loo MWM, Poelstra K, Borghuis T, Bakker WW (2003) Production of hemopexin by TNFα stimulated human mesangium cells. Kidney Int 63:1681–1686CrossRefPubMedGoogle Scholar

Copyright information

© IPNA 2005

Authors and Affiliations

  • Winston W. Bakker
    • 1
    • 4
    Email author
  • Catharina M. L. van Dael
    • 1
  • Leonie J. W. M. Pierik
    • 1
  • Joanna A. E. van Wijk
    • 2
  • Jeroen Nauta
    • 3
  • Theo Borghuis
    • 1
  • Jola J. Kapojos
    • 1
  1. 1.Departments of Pathology and PediatricsUniversity Medical CenterGroningenThe Netherlands
  2. 2.Department of PediatricsFree University Medical CenterAmsterdamThe Netherlands
  3. 3.Sophia Children’s HospitalRotterdamThe Netherlands
  4. 4.Department of Pathology and Laboratory MedicineUniversity HospitalGroningenThe Netherlands

Personalised recommendations