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Renal tubular dysfunction in children with systemic lupus erythematosus

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Abstract

Renal tubular and glomerular function was studied in patients under 18 years of age with childhood-onset systemic lupus erythematosus (SLE) in relation to disease activity in two groups: patients with clinical or laboratory evidence of lupus nephritis and those without (lupus non-nephritis). We reviewed 11 patients with lupus non-nephritis and 10 patients with lupus nephritis over a 12-month period. The measured glomerular filtration rates had a tendency to be lower in the lupus nephritis group. Glomerular dysfunction was manifest in the lupus nephritis group with elevated urinary albumin/creatinine ratios (P <0.001). Markers of tubular function were measured and compared with data from 94 controls. The lupus nephritis group had elevated urinary NAG [ N -acetyl-β- d -glucosaminidase (P =0.001)] and RBP [retinol-binding protein (P =0.03)] levels. Tubular dysfunction with elevated urinary NAG levels was present in 2 lupus non-nephritis patients with no evidence of glomerular disease. The cohort of patients in this study was followed and 2 lupus non-nephritis patients with the highest urinary RBP levels developed evidence of glomerular dysfunction and biopsy-proven lupus nephritis. Evidence of tubular dysfunction in lupus non-nephritis patients may help to identify lupus nephritis prior to the onset of albuminuria.

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References

  1. Tan EM, Cohen AS, Fries JF, Masi AT, McShane DJ, Rothfield NF, Schaller JG, Talal N, Winchester RJ (1982) The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 25:1271–1277

    CAS  PubMed  Google Scholar 

  2. Hochberg MC (1997) Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 9:1725

    Google Scholar 

  3. Hagelberg S, Lee Y, Bargman J, Mah G, Schneider R, Laskin C, Eddy A, Gladman D, Urowitz M, Hebert D, Silverman E (2002) Longterm followup of childhood lupus nephritis. J Rheumatol 29:2635–2642

    PubMed  Google Scholar 

  4. Tucker LB, Menon S, Schaller JG, Isenberg DA (1995) Adult- and childhood onset systemic lupus erythematosus: a comparison of onset, clinical features, serology, and outcome. Br J Rheumatol 34:866–872

    CAS  PubMed  Google Scholar 

  5. Kaufman DB, Laxer RM, Silverman ED, Stein L (1986) Systemic lupus erythematosus in childhood and adolescence—the problem, epidemiology, incidence, susceptibility, genetics and prognosis. Curr Probl Pediatr 16:555–624

    Google Scholar 

  6. Lacks S, White P (1990) Morbidity associated with childhood systemic lupus erythematosus. J Rheumatol 17:941–945

    CAS  PubMed  Google Scholar 

  7. Jacobs JC (1977) Treatment of systemic lupus erythematosus in childhood. Arthritis Rheum 20:304−307

    CAS  PubMed  Google Scholar 

  8. Churg J, Sobin LH (1982) Glomerulonephritis of systemic disease: lupus nephritis. In: Churg J, Sobin LH (eds) Renal disease. Classification and atlas of glomerular disease. Igaku-Shoin, Tokyo, pp 127–149

  9. Malleson PN (1989) The role of the renal biopsy in childhood onset systemic lupus erythematosus: a viewpoint. Clin Exp Rheumatol 7:563–566

    CAS  PubMed  Google Scholar 

  10. Esdaile JM, Joseph L, Mackenzie T, Kashgarian M, Hayslett JP (1994) The benefit of early treatment with immunosuppressive agents in lupus nephritis. J Rheumatol 21:2046–2051

    CAS  PubMed  Google Scholar 

  11. Meislin AG, Rothfield N (1968) Systemic lupus erythematosus in childhood. Analysis of 42 cases, with comparative data on 200 adult cases followed concurrently. Pediatrics 42:37–49

    CAS  PubMed  Google Scholar 

  12. Comerford FR, Cohen AS (1967) The nephropathy of systemic lupus erythematosus: an assessment by clinical, light and electron microscopic criteria. Medicine (Baltimore) 46:425

    Google Scholar 

  13. Woolf A, Croker B, Osofsky SG, Kredich DW (1979) Nephritis in children and young adults with systemic lupus erythematosus and normal urinary sediment. Pediatrics 64:678–685

    CAS  PubMed  Google Scholar 

  14. Weis LS, Pachman LM, Potter EV, Lewy PR, Jennings RB, Herdson PB (1977) Occult lupus nephropathy: a correlated light, electron and immunofluorescent microscopic study. Histopathology 1:401–419

    CAS  PubMed  Google Scholar 

  15. Mahajan SK, Ordonez NG, Feitelson PJ, Lim VS, Spargo BH, Katz AI (1977) Lupus nephropathy without clinical renal involvement. Medicine (Baltimore) 56:493–501

  16. Kozeny GA, Barr W, Bansal VK, Vertuno LL, Fresco R, Robinson J, Hano JE (1987) Occurrence of renal tubular dysfunction in lupus nephritis. Arch Intern Med 147:891–895

    Article  CAS  PubMed  Google Scholar 

  17. Sesso R, Rettori R, Nishida S, Sato E, Ajzen H, Pereira AB (1994) Assessment of lupus nephritis activity using urinary retinol-binding protein. Nephrol Dial Transplant 9:367–371

    Google Scholar 

  18. Dillon SC, Taylor GM, Shah V (1998) Diagnostic value of urinary retinol binding protein in childhood nephrotic syndrome. Pediatr Nephrol 12:643–647

    Article  CAS  PubMed  Google Scholar 

  19. Smith GC, Winterborn MH, Taylor CM, Lawson N, Guy M (1994) Assessment of retinol-binding protein excretion in normal children. Pediatr Nephrol 8:148–150

    CAS  PubMed  Google Scholar 

  20. Piqueras AI, Shah V, Hulton SA, Barratt TM, Dillon MJ (1993) Tubular proteinuria in steroid sensitive multi-relapsing nephrotic syndrome. Clin Nephrol 40:26–30

    CAS  PubMed  Google Scholar 

  21. Gibb DM, Tomlinson PA, Dalton NR, Turner C, Shah V, Barratt TM (1989) Renal tubular proteinuria and microalbuminuria in diabetic patients. Arch Dis Child 64:129–134

    Google Scholar 

  22. Hay EM, Bacon PA, Gordon C, Isenberg DA, Maddison P, Snaith ML, Symmons DP, Viner N, Zoma A (1993) The BILAG index: a reliable and valid instrument for measuring clinical disease activity in systemic lupus erythematosus. Q J Med 86:447–458

    CAS  PubMed  Google Scholar 

  23. Morris MC, Allanby CW, Toseland P, Haycock GB, Chantler C (1982) Evaluation of a height/plasma creatinine formula in the measurement of glomerular filtration rate. Arch Dis Child 57:611–615

    Google Scholar 

  24. Hill GS, Delahousse M, Nochy D, Mandet C, Bariety J (2001) Proteinuria and tubulointerstitial lesions in lupus nephritis. Kidney Int 60:1893–1903

    Article  CAS  PubMed  Google Scholar 

  25. Hurtado A, Asato C, Escudero E, Stromquist CS, Urcia J, Hurtado ME, La Cruz S de, Wener MH, Zavala R, Johnson RJ (1999) Clinicopathologic correlations in lupus nephritis in Lima, Peru. Nephron 83:323–330

    Article  CAS  PubMed  Google Scholar 

  26. Jacobsen S, Starklint H, Petersen J, Ullman S, Junker P, Voss A, Rasmussen JM, Tarp U, Poulsen LH, Overeem Hansen G van, Skaarup B, Hansen TM, Podenphant J, Halberg P (1999) Prognostic value of renal biopsy and clinical variables in patients with lupus nephritis and normal serum creatinine. Scand J Rheumatol 28:288–299

    Article  CAS  PubMed  Google Scholar 

  27. Singh AK, Ucci A, Madias NE (1996) Predominant tubulointerstitial lupus nephritis. Am J Kidney Dis 27:273–278

    CAS  PubMed  Google Scholar 

  28. Yamamoto T, Nagase M, Hishida A, Honda N (1993) Interstitial inflammatory and chronic tubulointerstitial lesions in lupus nephritis: comparison with those in IgA nephropathy. Lupus 2:261–268

    CAS  PubMed  Google Scholar 

  29. Wei CH, Ho YS, Chou BL, Sheu LF, Shieh SD, Chen A, Tu YC (1993) Lupus nephritis, emphasizing tubulointerstitial lesions: a clinico-pathological analysis. Chin Med J (Taipei) 51:27–32

    Google Scholar 

  30. Park MH, D’Agati V, Appel GB, Pirani CL (1986) Tubulointerstitial disease in lupus nephritis: relationship to immune deposits, interstitial inflammation, glomerular changes, renal function, and prognosis. Nephron 44:309–319

    CAS  PubMed  Google Scholar 

  31. O’Dell JR, Hays RC, Guggenheim SJ, Steigerwald JC (1985) Tubulointerstitial renal disease in systemic lupus erythematosus. Arch Intern Med 145:1996–1999

    Google Scholar 

  32. Guy JM, Brammah TB, Holt L, Bernstein RM, McMurray JR, Tieszen K, Cooper RG (1997) Urinary excretion of albumin and retinol binding protein in systemic lupus erythematosus. Ann Clin Biochem 34:668–674

    PubMed  Google Scholar 

  33. Borg EJ ter, Jong PE de, Meijer SS, Kallenberg CG (1991) Tubular dysfunction in proliferative lupus nephritis. Am J Nephrol 11:16–22

    PubMed  Google Scholar 

  34. Tsai CY, Wu TH, Yu CL, Lu JY, Tsai YY (2000) Increased excretions of beta-2 microglobulin, IL-6, and IL-8 and decreased excretion of Tamm-Horsfall glycoprotein in urine of patients with active lupus nephritis. Nephron 85:207–214

    Article  CAS  PubMed  Google Scholar 

  35. Cook ME, Wallin JD, Thakur VD, Kadowitz PJ, McNamara DB, Garcia MM, Lipani JA, Poland M (1997) Comparative effects of nabumetone, sulindac, and ibuprofen on renal function. J Rheumatol 24:1137–1144

    CAS  PubMed  Google Scholar 

  36. Mohrmann M, Ansorge S, Schmich U, Schonfeld B, Brandis M (1994) Toxicity of ifosfamide, cyclophosphamide and their metabolites in renal tubular cells in culture. Pediatr Nephrol 8:157–163

    CAS  PubMed  Google Scholar 

  37. Cortes-Hernandez J, Ordi-Ros J, Labrador M, Segarra A, Tovar JL, Balada E, Vilardell-Tarres M (2003) Predictors of poor renal outcome in patients with lupus nephritis treated with combined pulses of cyclophosphamide and methylprednisolone. Lupus 12:287–296

    Article  CAS  PubMed  Google Scholar 

  38. Sinniah R, Khan TN (1999) Renal tubular basement membrane changes in tubulointerstitial damage in patients with glomerular diseases. Ultrastruct Pathol 23:359–368

    Article  CAS  PubMed  Google Scholar 

  39. Alexopoulos E, Seron D, Hartley RB, Cameron JS (1990) Lupus nephritis: correlation of interstitial cells with glomerular function. Kidney Int 37:100–109

    CAS  PubMed  Google Scholar 

  40. Esdaile JM, Levinton C, Federgreen W, Hayslett JP, Kashgarian M (1989) The clinical and renal biopsy predictors of long-term outcome in lupus nephritis: a study of 87 patients and review of the literature. Q J Med 72:779–833

    CAS  PubMed  Google Scholar 

  41. Schwartz MM, Fennell JS, Lewis EJ (1982) Pathologic changes in the renal tubule in systemic lupus erythematosus. Hum Pathol 13:534–547

    CAS  PubMed  Google Scholar 

  42. De Albuquerque DA, Saxena V, Adams DE, Boivin GP, Brunner HI, Witte DP, Singh RR (2004) An ACE inhibitor reduces Th2 cytokines and TGF-beta-1 and TGF-beta-2 isoforms in murine lupus nephritis. Kidney Int 65:846–859

    Article  PubMed  Google Scholar 

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Acknowledgements

V.S. was supported by John Herring and Friends Research Fund (Child Health Research Appeal Trust).

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Authors and Affiliations

  1. Nephro-Urology Unit, Institute of Child Health, 30 Guilford Street, London, WC1N 1EH, UK

    Stephen D. Marks, Vanita Shah & Michael J. Dillon

  2. Department of Paediatric Rheumatology, Great Ormond Street Hospital for Children NHS Trust, Great Ormond Street, London , WC1N 3JH, UK

    Clarissa Pilkington & Patricia Woo

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  1. Stephen D. Marks
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  2. Vanita Shah
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  3. Clarissa Pilkington
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  4. Patricia Woo
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  5. Michael J. Dillon
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Correspondence to Stephen D. Marks.

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Marks, S.D., Shah, V., Pilkington, C. et al. Renal tubular dysfunction in children with systemic lupus erythematosus. Pediatr Nephrol 20, 141–148 (2005). https://doi.org/10.1007/s00467-004-1707-6

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  • DOI: https://doi.org/10.1007/s00467-004-1707-6

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