In-depth Review
Natural history of idiopathic IgA nephropathy: Role of clinical and histological prognostic factors*,**

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Abstract

Idiopathic immunoglobulin A nephropathy is characterized by an extreme variability in clinical course and sometimes by the unpredictability of the ultimate outcome. Among the numerous studies published in the last 15 years that have calculated the actuarial renal survival and tried to individuate the prognostic role of the clinical and histological features present at the onset of the disease or the time of biopsy, we chose to analyze critically the results of the most valid (30 studies). Actuarial renal survival at 10 years in adults was between 80% and 85% in most of the European and Asian studies, but it was less in studies from the United States and exceeded 90% in the few studies of children. Concordance existed in this selected literature that impairment of renal function, severe proteinuria, and arterial hypertension are the strongest and more reliable clinical predictors of an unfavorable outcome. However, analysis of the prognostic value of morphological lesions was more difficult because they have been characterized in some studies using an overall score or histological classes of progressively more severe involvement and, in others, using a semiquantitative grading of individual glomerular, tubular, interstitial, and vascular changes. In adult patients, a high score of glomerular and tubulointerstitial lesions, corresponding to classes IV and V of the Lee or Haas classifications, predicted a more rapid progression. When single lesions were analyzed separately, glomerulosclerosis and interstitial fibrosis appeared to be the strongest, most reliable predictors of unfavorable prognosis. More controversial was the role of crescents and capsular adhesions. None of the immunohistological features was found to be a risk factor for progression in the more accurate statistical analyses. The same histological features predicted outcome in children, although the severity of lesions at the time of biopsy was usually less than that in adults. However, in the single patient, even the evaluation of these prognostic markers sometimes fails to correctly predict outcome, probably because of the heterogeneity of the disease and the discontinuous activity of some injuring mechanisms during its course.

Section snippets

Actuarial renal survival in adults

Eighteen studies (Table 1) performed in different geographic areas on large relatively nonselected cohorts of adult patients in which the actuarial renal survival rate at 10 years was calculated by using life-time survivorship analysis were selected.In Table 1, together with the results of this analysis, some relevant demographic data and clinical features at the time of presentation are listed. This included prevalence of renal insufficiency, arterial hypertension, severe proteinuria, and

Actuarial renal survival in children

Definitely less numerous are the studies of outcome for sufficiently large cohorts of pediatric patients, and their results do not clearly establish whether the renal survival rate of children is better than that of adults.

To our knowledge, only three studies have compared the outcome of cohorts of adult and pediatric patients who underwent biopsy by the same investigators.17, 21, 24 Kusumoto et al17 in Japan reported a 10-year actuarial renal survival of approximately 80% (Table 1) in a cohort

Clinical, histological, and genetic prognostic factors in adults and children

Among the numerous studies of clinical and histological predictors of an unfavorable outcome in adult patients with IgA nephropathy, we selected, according to the criteria previously mentioned, 25 studies in which a univariate analysis of the various risk factors, each independently considered, was performed, usually comparing renal survival rates calculated according to the method of Kaplan and Meier.4, 5, 6, 9, 10, 12, 16, 18, 19, 21, 22, 23, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43 In only 16

Conclusive comments

The data on the predictive value of the various clinical, histological, and genetic factors for the progression of IgA nephropathy discussed in the previous sections deserve some commentary.

The four strongest predictors of an unfavorable outcome listed in Table 2 are nonspecific markers of severity, valid for all glomerular diseases, as already stressed by the author.2, 58

The presence of arterial hypertension at presentation, another clinical marker of severity, loses part of its statistical

References (64)

  • C Bazzi et al.

    Characterization of proteinuria in primary glomerulonephritides. SDS-PAGE patterns: Clinical significance and prognostic value of low-molecular-weight (“tubular”) proteins

    Am J Kidney Dis

    (1997)
  • JI Roodnat et al.

    What do we really know about the long-term prognosis of IgA-nephropathy?

    J Nephrol

    (1991)
  • G D’Amico et al.

    Prognostic indicators in idiopathic IgA mesangial nephropathy

    Q J Med

    (1986)
  • D Droz et al.

    Primary IgA nephropathy: Prognostic factors

    Contrib Nephrol

    (1984)
  • LH Noel et al.

    Primary IgA nephropathy: From the first described cases to the present

    Semin Nephrol

    (1987)
  • M Velo et al.

    Natural history of IgA nephropathy in patients followed up for more than ten years in Spain

    Semin Nephrol

    (1987)
  • O Bogenschütz et al.

    IgA nephritis: On the importance of morphological and clinical parameters in the long-term prognosis of 239 patients

    Am J Nephrol

    (1990)
  • S Rekola et al.

    IgA nephropathy: A retrospective evaluation of prognostic indices in 176 patients

    Scand J Urol Nephrol

    (1989)
  • S Rekola et al.

    Development of hypertension in IgA nephropathy as a marker of a poor prognosis

    Am J Nephrol

    (1990)
  • PA Johnston et al.

    Clinico-pathological correlations and long-term follow-up of 253 United Kingdom patients with IgA nephropathy. A report from the MRC Glomerulonephritis Registry

    Q J Med

    (1992)
  • KM Nicholls et al.

    The clinical course of mesangial IgA associated nephropathy in adults

    Q J Med

    (1984)
  • LS Ibels et al.

    IgA nephropathy: Analysis of the natural history, important factors in the progression of renal disease, and a review of the literature

    Medicine

    (1994)
  • KT Woo et al.

    The natural history of IgA nephritis in Singapore

    Clin Nephrol

    (1986)
  • Y Kusumoto et al.

    Long-term prognosis and prognostic indices of IgA nephropathy in juvenile and adult Japanese

    Clin Nephrol

    (1987)
  • R Katafuchi et al.

    An important role of glomerular segmental lesions on progression of IgA nephropathy: A multivariate analysis

    Clin Nephrol

    (1994)
  • M Yagame et al.

    Value of pathological grading in prediction of renal survival in IgA nephropathy

    Nephrology

    (1996)
  • MG Radford et al.

    Predicting renal outcome in IgA nephropathy

    J Am Soc Nephrol

    (1997)
  • Y Yaguchi et al.

    Comparative studies of clinicopathologic changes in patients with adult- and juvenile-onset of IgA nephropathy

    J Nephrol

    (1994)
  • T Linné et al.

    Course of renal function in IgA glomerulonephritis in children and adolescents

    Acta Pediatr Scand

    (1982)
  • M Lévy et al.

    Berger’s disease in children. Natural history and outcome

    Medicine

    (1985)
  • S Hattori et al.

    Clinicopathological correlation of IgA nephropathy in children

    Am J Nephrol

    (1985)
  • SP Andreoli et al.

    IgA nephropathy in children: Significance of glomerular basement membrane deposition of IgA

    Am J Nephrol

    (1986)
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    *

    Supported in part by European Union Concerted Action Grant no. BMH4-CT98-3631 (DG12-SSMI) and by the Associazione per la Ricerca in Nefrologia.

    **

    Address reprint requests to Giuseppe D’Amico, MD, Department of Nephrology and Urology, San Carlo Borromeo Hospital, Via Pio II, 3, 20153 Milano, Italy. E-mail: [email protected]

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