In crescentic IgA nephropathy, fractional excretion of IgG in combination with nephron loss is the best predictor of progression and responsiveness to immunosuppression

Claudio Bazzi, Virginia Rizza, Sara Raimondi, Daniela Casellato, Pietro Napodano, Giuseppe D'Amico

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Background and objectives: The aim of this study was to evaluate the relationship between proteinuric markers (urinary excretion of IgG, α2-macroglobulin, α1-microglobulin) and serum creatinine (sCr), histologic lesions, progression, and immunosuppression responsiveness in crescentic IgA nephropathy. Design, setting, participants, & measurements: Fractional excretion of IgG (FEIgG) and of α1-microglobulin and urinary excretion of α2-macroglobulin were evaluated in 37 patients, 23 treated with steroids and cyclophosphamide. For assessment of the effective tubular load of proteins in surviving nephrons, new markers that take into account not only the absolute excretion value but also nephron loss were obtained dividing proteinuric markers for percentage of nonobsolescent glomeruli (surviving glomeruli [SG]). For each parameter, low- and high-risk groups were defined according to cutoffs with the highest sensitivity and specificity for progression (ESRD/doubling sCr) assessed by receiver operating characteristic analysis; follow up was 60 ± 40 mo. Results: FEIgG/SG is the most powerful progression predictor: 5 versus 83% in all patients; in treated patients, 0 versus 89%, increased to 0 versus 100% by sCr and FEIgG/SG in combination (low risk: both markers or only one below cutoff (n = 15); high risk: both markers above cutoff (n = 8). The nonprogressors showed at last observation 65% proteinuria reduction and 10% sCr reduction. Conclusions: In crescentic IgA nephropathy, FEIgG/SG, which evaluates altered size selectivity in relation to nephron loss, is the best progression predictor. In treated patients, progression prediction was increased by FEIgG/SG and sCr in combination. Treatment may be restricted to low-risk patients.

Original languageEnglish
Pages (from-to)929-935
Number of pages7
JournalClinical Journal of the American Society of Nephrology
Volume4
Issue number5
DOIs
Publication statusPublished - May 1 2009

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Nephrons
Immunosuppression
Immunoglobulin A
Immunoglobulin G
Creatinine
Macroglobulins
Serum
Proteinuria
ROC Curve
Cyclophosphamide
Chronic Kidney Failure
Steroids
Observation
Sensitivity and Specificity
Proteins

ASJC Scopus subject areas

  • Medicine(all)
  • Critical Care and Intensive Care Medicine
  • Epidemiology
  • Nephrology
  • Transplantation

Cite this

In crescentic IgA nephropathy, fractional excretion of IgG in combination with nephron loss is the best predictor of progression and responsiveness to immunosuppression. / Bazzi, Claudio; Rizza, Virginia; Raimondi, Sara; Casellato, Daniela; Napodano, Pietro; D'Amico, Giuseppe.

In: Clinical Journal of the American Society of Nephrology, Vol. 4, No. 5, 01.05.2009, p. 929-935.

Research output: Contribution to journalArticle

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abstract = "Background and objectives: The aim of this study was to evaluate the relationship between proteinuric markers (urinary excretion of IgG, α2-macroglobulin, α1-microglobulin) and serum creatinine (sCr), histologic lesions, progression, and immunosuppression responsiveness in crescentic IgA nephropathy. Design, setting, participants, & measurements: Fractional excretion of IgG (FEIgG) and of α1-microglobulin and urinary excretion of α2-macroglobulin were evaluated in 37 patients, 23 treated with steroids and cyclophosphamide. For assessment of the effective tubular load of proteins in surviving nephrons, new markers that take into account not only the absolute excretion value but also nephron loss were obtained dividing proteinuric markers for percentage of nonobsolescent glomeruli (surviving glomeruli [SG]). For each parameter, low- and high-risk groups were defined according to cutoffs with the highest sensitivity and specificity for progression (ESRD/doubling sCr) assessed by receiver operating characteristic analysis; follow up was 60 ± 40 mo. Results: FEIgG/SG is the most powerful progression predictor: 5 versus 83{\%} in all patients; in treated patients, 0 versus 89{\%}, increased to 0 versus 100{\%} by sCr and FEIgG/SG in combination (low risk: both markers or only one below cutoff (n = 15); high risk: both markers above cutoff (n = 8). The nonprogressors showed at last observation 65{\%} proteinuria reduction and 10{\%} sCr reduction. Conclusions: In crescentic IgA nephropathy, FEIgG/SG, which evaluates altered size selectivity in relation to nephron loss, is the best progression predictor. In treated patients, progression prediction was increased by FEIgG/SG and sCr in combination. Treatment may be restricted to low-risk patients.",
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AU - Rizza, Virginia

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AU - Napodano, Pietro

AU - D'Amico, Giuseppe

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AB - Background and objectives: The aim of this study was to evaluate the relationship between proteinuric markers (urinary excretion of IgG, α2-macroglobulin, α1-microglobulin) and serum creatinine (sCr), histologic lesions, progression, and immunosuppression responsiveness in crescentic IgA nephropathy. Design, setting, participants, & measurements: Fractional excretion of IgG (FEIgG) and of α1-microglobulin and urinary excretion of α2-macroglobulin were evaluated in 37 patients, 23 treated with steroids and cyclophosphamide. For assessment of the effective tubular load of proteins in surviving nephrons, new markers that take into account not only the absolute excretion value but also nephron loss were obtained dividing proteinuric markers for percentage of nonobsolescent glomeruli (surviving glomeruli [SG]). For each parameter, low- and high-risk groups were defined according to cutoffs with the highest sensitivity and specificity for progression (ESRD/doubling sCr) assessed by receiver operating characteristic analysis; follow up was 60 ± 40 mo. Results: FEIgG/SG is the most powerful progression predictor: 5 versus 83% in all patients; in treated patients, 0 versus 89%, increased to 0 versus 100% by sCr and FEIgG/SG in combination (low risk: both markers or only one below cutoff (n = 15); high risk: both markers above cutoff (n = 8). The nonprogressors showed at last observation 65% proteinuria reduction and 10% sCr reduction. Conclusions: In crescentic IgA nephropathy, FEIgG/SG, which evaluates altered size selectivity in relation to nephron loss, is the best progression predictor. In treated patients, progression prediction was increased by FEIgG/SG and sCr in combination. Treatment may be restricted to low-risk patients.

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