nach oben

Journal of Nephrology

Erschienen in:

01.06.2016 | Original Article

Prognostic value of endocapillary hypercellularity in IgA nephropathy patients with no immunosuppression

verfasst von: Aron Chakera, Clare MacEwen, Shubha S. Bellur, La-or Chompuk, Daniel Lunn, Ian S. D. Roberts

Erschienen in: Journal of Nephrology | Ausgabe 3/2016

Einloggen, um Zugang zu erhalten

Abstract

Aim

Interpretation of retrospective clinicopathological studies of IgA nephropathy (IgAN) has been confounded by immunosuppression bias. In published validation studies of the Oxford Classification of IgAN, an average of 33 % of patients received non-randomised steroid and/or cytotoxic therapy. In order to determine the true impact of proliferative lesions on the natural history of IgAN, analysis of patient cohorts that have received no immunosuppression is required.

Methods

We performed a retrospective single centre study of patients with IgAN managed without immunosuppressive therapy. Biopsies were scored according to the Oxford Classification. The primary outcomes were renal survival or a rapid loss of renal function defined as a decline in eGFR of >5 ml/min/year.

Results

237 patients with IgAN were identified with a mean follow-up of 82 months. 200 had biopsies available for review, of which 156 were adequate for scoring using the Oxford Classification. 9/156 patients (5.8 %) received some immunosuppressive therapy, mostly for unrelated conditions: these were excluded. In multivariate COX regression, including histological and clinical data, the only independent predictors of time to ESRD were baseline eGFR (HR 0.96 per ml/min increase, p = 0.018), baseline proteinuria (HR 1.36 per doubling, p = 0.004) and endocapillary hypercellularity (HR 4.75 for E1 compared to E0, p < 0.001). Independent predictors of a rapid decline in eGFR were proteinuria (OR 1.45 per doubling, p = 0.006), endocapillary hypercellularity (OR 3.41 for E1 compared to E0, p = 0.025) and tubular atrophy/interstitial fibrosis (OR 8.77 for T2 compared to T0, p = 0.006).

Conclusions

In a cohort of IgAN patients receiving no immunosuppression, endocapillary proliferation and tubular atrophy/interstitial fibrosis are independent predictors of rate of loss of renal function. The lack of predictive value of E score in other clinicopathological studies is most likely a result of immunosuppression-associated bias. Our findings provide evidence to support immunosuppressive treatment of endocapillary-pattern IgAN.

Nur mit Berechtigung zugänglich

Berthoux FC, Mohey H, Afiani A (2008) Natural history of primary IgA nephropathy. Semin Nephrol 28:4–9CrossRefPubMed

Barbour SJ, Reich HN (2012) Risk stratification of patients with IgA nephropathy. Am J Kidney Dis Off J Nat Kidney Foundation 59:865–873CrossRef

Haas M (1997) Histologic subclassification of IgA nephropathy: a clinicopathologic study of 244 cases. Am J Kidney Dis Off J Nat Kidney Foundation 29:829–842CrossRef

Lee SM, Rao VM, Franklin WA, Schiffer MS, Aronson AJ, Spargo BH et al (1982) IgA nephropathy: morphologic predictors of progressive renal disease. Hum Pathol 13:314–322CrossRefPubMed

Katafuchi R, Ikeda K, Mizumasa T, Tanaka H, Ando T, Yanase T et al (2003) Controlled, prospective trial of steroid treatment in IgA nephropathy: a limitation of low-dose prednisolone therapy. Am J Kidney Dis Off J Natl Kidney Found 41:972–983CrossRef

Pozzi C, Bolasco PG, Fogazzi GB, Andrulli S, Altieri P, Ponticelli C et al (1999) Corticosteroids in IgA nephropathy: a randomised controlled trial. Lancet 353:883–887CrossRefPubMed

Roberts IS, Cook HT, Troyanov S, Alpers CE, Amore A, Barratt J et al (2009) The Oxford classification of IgA nephropathy: pathology definitions, correlations, and reproducibility. Kidney Int 76:546–556CrossRefPubMed

Cattran DC, Coppo R, Cook HT, Feehally J, Roberts IS, Troyanov S et al (2009) The Oxford classification of IgA nephropathy: rationale, clinicopathological correlations, and classification. Kidney Int 76:534–545CrossRefPubMed

Roberts IS (2013) Oxford classification of immunoglobulin A nephropathy: an update. Curr Opin Nephrol Hypertens 22:281–286CrossRefPubMed

10.

Shi S-F, Wang S-X, Jiang L, LV J-C, Liu L-J, Chen Y-Q, et al (2011) Pathologic predictors of renal outcome and therapeutic efficacy in IgA nephropathy: validation of the Oxford classification. Clin J Am Soc Nephrol 6:2175–2184CrossRefPubMedPubMedCentral

11.

Glassock RJ, Winearls C (2009) Ageing and the glomerular filtration rate: truths and consequences. Trans Am Clin Climatol Assoc 120:419–428PubMedPubMedCentral

12.

Wetzels JF, Kiemeney LA, Swinkels DW, Willems HL, den Heijer M (2007) Age- and gender-specific reference values of estimated GFR in Caucasians: the Nijmegen Biomedical Study. Kidney Int 72:632–637CrossRefPubMed

13.

Davies DF, Shock NW (1950) Age changes in glomerular filtration rate, effective renal plasma flow, and tubular excretory capacity in adult males. J Clin Investig 29:496–507CrossRefPubMedPubMedCentral

14.

Herzenberg AM, Fogo AB, Reich HN, Troyanov S, Bavbek N, Massat AE et al (2011) Validation of the Oxford classification of IgA nephropathy. Kidney Int 80:310–317CrossRefPubMed

15.

D’Amico G, Minetti L, Ponticelli C, Fellin G, Ferrario F, Barbiano di Belgioioso G et al (1986) Prognostic indicators in idiopathic IgA mesangial nephropathy. Q J Med. 59:363–378PubMed

16.

Berthoux F, Mohey H, Laurent B, Mariat C, Afiani A, Thibaudin L (2011) Predicting the risk for dialysis or death in IgA nephropathy. J Am Soc Nephrol 22:752–761CrossRefPubMedPubMedCentral

17.

Radford MG Jr, Donadio JV Jr, Bergstralh EJ, Grande JP (1997) Predicting renal outcome in IgA nephropathy. J Am Soc Nephrol 8:199–207PubMed

18.

Walsh M, Sar A, Lee D, Yilmaz S, Benediktsson H, Manns B et al (2010) Histopathologic features aid in predicting risk for progression of IgA nephropathy. Clin J Am Soc Nephrol 5:425–430CrossRefPubMedPubMedCentral

19.

Shen XH, Liang SS, Chen HM et al (2015) Reversal of active glomerular lesions after immunosuppressive therapy in patients with IgA nephropathy: a repeat-biopsy based observation. J Nephrol. 28:441–449CrossRefPubMed

20.

Shi SF, Wang SX, Jiang L, Lv JC, Liu LJ, Chen YQ et al (2011) Pathologic predictors of renal outcome and therapeutic efficacy in IgA nephropathy: validation of the oxford classification. Clin J Am Soc Nephrol. 6:2175–2184CrossRefPubMedPubMedCentral

21.

Park KS, Han SH, Kie JH, Nam KH, Lee MJ, Lim BJ et al (2014) Comparison of the Haas and the Oxford classifications for prediction of renal outcome in patients with IgA nephropathy. Hum Pathol 45:236–243CrossRefPubMed

22.

Coppo R, Troyanov S, Bellur S, Cattran D, Cook HT, Feehally J et al (2014) VALIGA study of the ERA-EDTA Immunonephrology Working Group. Validation of the Oxford classification of IgA nephropathy in cohorts with different presentations and treatments. Kidney Int 86:828–836CrossRefPubMedPubMedCentral

23.

El Karoui K, Hill GS, Karras A et al (2011) Focal segmental glomerulosclerosis plays a major role in the progression of IgA nephropathy. II. Light microscopic and clinical studies. Kidney Int 79:643–654CrossRefPubMed

24.

Wetzels JF, Willems HL, den Heijer M (2008) Age- and gender-specific reference values of estimated glomerular filtration rate in a Caucasian population: results of the Nijmegen Biomedical Study. Kidney Int 73:657–658CrossRefPubMed

25.

Turin TC, Coresh J, Tonelli M, Stevens PE, de Jong PE, Farmer CKT et al (2013) Change in the estimated glomerular filtration rate over time and risk of all-cause mortality. Kidney Int 83:684–691CrossRefPubMed

26.

McClurkin C Jr, Phan SH, Hsu CH, Patel SR, Spicker JK, Kshirsagar AM et al (1990) Moderate protection of renal function and reduction of fibrosis by colchicine in a model of anti-GBM disease in the rabbit. J Am Soc Nephrol 1:257–265PubMed

27.

Seron D (2009) Interstitial fibrosis and tubular atrophy in renal allograft protocol biopsies as a surrogate of graft survival. Transplant Proc 41:769–770CrossRefPubMed

28.

Hsieh C, Chang A, Brandt D, Guttikonda R, Utset TO, Clark MR (2011) Predicting outcomes of lupus nephritis with tubulointerstitial inflammation and scarring. Arthritis Care Res 63:865–874CrossRef

29.

Le W, Zeng CH, Liu Z, Liu D, Yang Q, Lin RX et al (2012) Validation of the Oxford classification of IgA nephropathy for pediatric patients from China. BMC Nephrol 13:158CrossRefPubMedPubMedCentral

30.

Wu Q, Tanaka H, Hirukawa T, Endoh M, Fukagawa M (2012) Characterization and quantification of proliferating cell patterns in endocapillary proliferation. Nephrol Dial Transplant 27:3234–3241CrossRefPubMed

31.

World Health Organization., Sabaté E. Adherence to long-term therapies : evidence for action. Geneva: World Health Organization 2003

Titel: Prognostic value of endocapillary hypercellularity in IgA nephropathy patients with no immunosuppression
verfasst von: Aron Chakera
Clare MacEwen
Shubha S. Bellur
La-or Chompuk
Daniel Lunn
Ian S. D. Roberts
Publikationsdatum: 01.06.2016
Verlag: Springer International Publishing
Erschienen in: Journal of Nephrology / Ausgabe 3/2016
Print ISSN: 1121-8428
Elektronische ISSN: 1724-6059
DOI: https://doi.org/10.1007/s40620-015-0227-8

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Springer Medizin

Prognostic value of endocapillary hypercellularity in IgA nephropathy patients with no immunosuppression

Abstract