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Genetical, histological, and clinical characteristics of IgA-negative mesangioproliferative glomerulopathy

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Abstract

Background

Mesangioproliferative glomerulopathy (MesPGN) is a well-defined pathohistological entity. However, the clinical characteristics and prognosis have not been fully established in patients without immunoglobulin (Ig)A (N-IgAN) in contrast to patients with IgA nephropathy (IgAN).

Methods

A total of 837 consecutive patients underwent renal biopsies. Among them, 465 patients were diagnosed with MesPGN by light microscopy. With immunofluorescent study and electron microscopy (EM), 344 were diagnosed as having IgAN. Among the rest, 84 patients who had no immunofluorescence evidence of IgA and no deposits in EM were defined as N-IgAN. We compared the clinical characteristics, histological findings, and genotypes of the angiotensin-converting enzyme (ACE) gene and plasminogen activator inhibitor-1 gene between IgAN and N-IgAN patients.

Results

Urinary protein excretion and the degree of hematuria were significantly lower in N-IgAN than IgAN patients (0.50 vs. 0.82 g/day; P = 0.01), (1.33 vs. 2.50; P < 0.001, respectively). Creatinine clearance was higher in N-IgAN than IgAN patients (89.4 vs. 74.4 ml/min; P < 0.001). Histopathologically, N-IgAN patients had significantly less advanced glomerular and tubulointerstitial lesions than IgAN patients. Pathological grades in patients with untreated IgAN were more advanced in a time-dependent manner, whereas there was no relationship between histological grades and time of illness in N-IgAN patients. Frequency of the DD genotype of the ACE gene was significantly lower in N-IgAN (DD/ID+II = 8/76) than IgAN (24/90) patients.

Conclusions

IgA-negative MesPGN is a distinct type of glomerulopathy with a benign renal prognosis. Insertion/deletion polymorphisms of the ACE gene may play some role in the genesis and progression of MesPGN.

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References

  1. Bohle A, Wehrmann M, Bogenschutz O, Batz C, Vogi W, Schmitt H, et al. The long-term prognosis of the primary glomerulonephritis. A morphological and clinical analysis. Pathol Res Pract. 1992;188:908–24.

    CAS  PubMed  Google Scholar 

  2. Kobayashi Y, Tateno S, Hiki Y, Shigematsu H. IgA nephropathy: prognostic significance of proteinuria and histological alterations. Nephron. 1983;34:146–53.

    Article  CAS  PubMed  Google Scholar 

  3. Chida Y, Tomura S, Takeuchi J. Renal survival rate of IgA nephropathy. Nephron. 1985;40:189–94.

    Article  CAS  PubMed  Google Scholar 

  4. Schena FP. A retrospective analysis of the natural history of primary IgA nephropathy worldwide. Am J Med. 1990;89:209–15.

    Article  CAS  PubMed  Google Scholar 

  5. D’Amico G. Influence of clinical and histological features on actuarial renal survival in adult patients with idiopathic IgA nephropathy, membranous nephropathy and membranoproliferative glomerulonephritis: survey of the recent literature. Am J Kidney Dis. 1992;20:315–23.

    PubMed  Google Scholar 

  6. Lee DY, Kim W, Kang SK, Koh GY, Park SK. Angiotensin-converting enzyme gene polymorphism in patients with minimal-change nephrotic syndrome and focal segmental glomerulosclerosis. Nephron. 1997;77:471–3.

    Article  CAS  PubMed  Google Scholar 

  7. Gaillard MC, Mahadeva R, Lomas DA. Identification of DNA polymorphisms associated with the V type alpha1-antitrypsin gene. Biochim Biophys Acta. 1999;1444:166–70.

    CAS  PubMed  Google Scholar 

  8. Frishberg Y, Toledano H, Becker-Cohen R, Feigin E, Halle D. Genetic polymorphism in paraoxonase is a risk factor for childhood focal segmental glomerulosclerosis. Am J Kidney Dis. 2000;36:1253–61.

    Article  CAS  PubMed  Google Scholar 

  9. Yorioka T, Suehiro T, Yasuoka N, Hashimoto K, Kawada M. Polymorphism of the angiotensin converting enzyme gene and clinical aspects of IgA nephropathy. Clin Nephrol. 1995;44:80–5.

    CAS  PubMed  Google Scholar 

  10. Yoshida H, Mitarai T, Kawamura T, Kitajima T, Miyazaki Y, Nagasawa R, et al. Role of the deletion of polymorphism of the angiotensin converting enzyme gene in the progression and therapeutic responsiveness of IgA nephropathy. J Clin Invest. 1995;96:2162–9.

    Article  CAS  PubMed  Google Scholar 

  11. Harden PN, Geddes C, Rowe PA, McIlroy JH, Boulton-Jones M, Rodger RS, et al. Polymorphisms in angiotensin-converting-enzyme gene and progression of IgA nephropathy. Lancet. 1995;345:1540–2.

    Article  CAS  PubMed  Google Scholar 

  12. Suzuki H, Sakuma Y, Kanesaki Y, Eiro M, Asahi K, Sanada H, et al. Close relationship of plasminogen activator inhibitor-1 4G/5G polymorphism and progression of IgA nephropathy. Clin Nephrol. 2004;62:173–9.

    CAS  PubMed  Google Scholar 

  13. Cambien F, Poirier O, Lecerf L, Evans A, Cambou JP, Arveiler D, et al. Deletion polymorphism in the gene for angiotensin-converting enzyme is a potent risk factor for myocardial infarction. Nature. 1992;359:641–4.

    Article  CAS  PubMed  Google Scholar 

  14. Ludwig E, Corneli PS, Anderson JL, Marshall HW, Lalouel JM, Ward RH. Angiotensin-converting enzyme gene polymorphism is associated with myocardial infarction but not with development of coronary stenosis. Circulation. 1995;91:2120–4.

    CAS  PubMed  Google Scholar 

  15. Uemura K, Nakura J, Kohara K, Miki T. Association of ACE I/D polymorphism with cardiovascular risk factors. Human Genet. 2000;107:239–42.

    Article  CAS  Google Scholar 

  16. Schena FP, D’Altri C, Cerullo G, Manno C, Gesualdo L. ACE gene polymorphism and IgA nephropathy: an ethnically homogeneous study and a meta-analysis. Kidney Int. 2001;60:732–40.

    Article  CAS  PubMed  Google Scholar 

  17. Suzuki S, Suzuki Y, Kobayashi Y, Harada T, Kawamura T, Yoshida H, et al. Insertion/deletion polymorphism in ACE gene is not associated with renal progression in Japanese patients with IgA nephropathy. Am J Kidney Dis. 2000;35:896–903.

    Article  CAS  PubMed  Google Scholar 

  18. Pei Y, Scholey J, Thai K, Suzuki M, Cattran D. Association of angiotensinogen gene T235 variant with progression of immunoglobin A nephropathy in Caucasian patients. J Clin Invest. 1997;100:814–20.

    Article  CAS  PubMed  Google Scholar 

  19. Schimidt SE, Sttier R, Hartung G, Stein J, Bahnisch AJ, Woodroffe AR, et al. No association of converting enzyme insertion/deletion polymorphism with immunoglobulin A glomerulonephritis. Am J Kidney Dis. 1995;26:727–31.

    Article  Google Scholar 

  20. Sakai H, Abe K, Kobayashi Y, Koyama A, Shigematsu H, Harada T, et al. Joint Committee of Ministry of Health and Welfare of Japan and Japanese Society of Nephrology. Clinical guidelines of IgA nephropathy. Jpn J Nephrol. 1995;37:417–21.

    CAS  Google Scholar 

  21. Churg J, Sobin LH. Renal disease: classification and atlas of glomerular disease. Tokyo, Japan: Igaku-shoin; 1982.

    Google Scholar 

  22. Walburger DK, Afonina IA, Wydro R. An improved real time PCR method for simultaneous detection of C282Y and H63D mutations in the HFE gene associated with hereditary hemochromatosis. Mutat Res. 2001;432:69–78.

    CAS  PubMed  Google Scholar 

  23. Kuriki M, Asahi K, Asano K, Sakurai K, Eiro M, Suzuki H, et al. Steroid therapy reduces mesangial matrix accumulation in advanced IgA nephropathy. Nephrol Dial Transplant. 2003;18:1311–5.

    Article  CAS  PubMed  Google Scholar 

  24. Ohishi M, Fujii K, Minamino T, Higaki J, Kamitani A, Rakugi H, et al. A potent genetic risk factor for restenosis. Nature Genet. 1993;5:324–5.

    Article  CAS  PubMed  Google Scholar 

  25. Higashimori K, Zhao Y, Higaki J, Kamitani A, Katsuya T, Nakura J, et al. Association analysis of a polymorphism of the angiotensin converting enzyme gene with essential hypertension in the Japanese population. Biochem Biophys Res Commun. 1993;191:399–404.

    Article  CAS  PubMed  Google Scholar 

  26. Rigat B, Hubert C, Alhenc-Gelas F, Cambien F, Corvol P, Soubrier F. An insertion/deletion polymorphism in the angiotensin I-converting enzyme gene accounting for half the variance of serum enzyme levels. J Clin Invest. 1990;86:1343–6.

    Article  CAS  PubMed  Google Scholar 

  27. Singhal PC, Santiago A, Satriano J, Hays RM, Schlondorff D. Effects of vasoactive agents on uptake of immunoglobulin G complexes by mesangial cells. Am J Physiol. 1990;258:F589–96.

    CAS  PubMed  Google Scholar 

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Correspondence to Tetsuo Katoh.

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Owada, K., Suzuki, H., Katoh, T. et al. Genetical, histological, and clinical characteristics of IgA-negative mesangioproliferative glomerulopathy. Clin Exp Nephrol 14, 56–62 (2010). https://doi.org/10.1007/s10157-009-0243-x

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  • DOI: https://doi.org/10.1007/s10157-009-0243-x

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