Changes in Proteinuria and Side Effects of Corticosteroids Alone or in Combination with Azathioprine at Different Stages of IgA Nephropathy

Cristina Sarcina, Carmine Tinelli, Francesca Ferrario, Antonello Pani, Annalisa De Silvestri, Patrizia Scaini, Lucia Del Vecchio, Elena Alberghini, Laura Buzzi, Ivano Baragetti, Claudio Pozzi

Research output: Contribution to journalArticle

Abstract

BACKGROUND AND OBJECTIVE: Time-average proteinuria (TAp) is the strongest predictor of renal survival in IgA nephropathy (IgAN). Little is known about the utility and safety of corticosteroids (CS) to obtain TAp<1 g/d in patients with advanced IgAN. This study sought to evaluate TAp at different degree of baseline renal function and histologic severity during CS use and to investigate treatment safety.

DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We performed one-stage individual-patient data meta-analysis among 325 patients with IgAN enrolled in three prospective, randomized clinical trials. Patients were divided into three groups according to treatment: no treatment (NT; supportive therapy), CS, and CS plus azathioprine (CS+A). Associations of TAp with histologic grading, treatment, and eGFR at baseline were performed with linear regression models for repeated measures. The median follow-up duration was 66.6 months (range, 12-144 months).

RESULTS: In the first 6 months, proteinuria did not change in the NT group and decreased substantially in the other groups(CS: from a mean±SD of 2.20±1.0 to 0.8 [interquartile range, 0.4-1.2] g/d; CS+A: from 2.876±2.1 to 1.0 [interquartile range, 0.5-1.7] g/d), independent of the degree of histologic damage and baseline eGFR. The percentage of patients who maintained TAp<1 g/d was 30.2% in the NT, 67.3% in the CS, and 66.6% in the CS+A group. Thirty-four patients experienced adverse events: none in the NT, 11 (6.4%) in the CS, and 23 (20.7%) in the CS+A group. The risk of developing adverse events increased with decreasing levels of eGFR (from 2.3% to 15.4%). The addition of azathioprine to CS further increased the percentage of patients with adverse events (16.8% versus 5.7% in study 2 and 30.0% versus 15.4% in study 3; overall P<0.001).

CONCLUSIONS: In patients with IgAN, CS can reduce proteinuria and increase the possibility of maintaining TAp<1 g/d, regardless of the stage of CKD and the histologic damage. The risk of major adverse events is low in patients with normal renal function but increases in those with impaired renal function and with the addition of azathioprine.

Original languageEnglish
Pages (from-to)973-81
Number of pages9
JournalClinical journal of the American Society of Nephrology : CJASN
Volume11
Issue number6
DOIs
Publication statusPublished - Jun 6 2016

Fingerprint

Azathioprine
Proteinuria
Immunoglobulin A
Adrenal Cortex Hormones
Kidney
Linear Models
Therapeutics
Safety
Meta-Analysis
Randomized Controlled Trials

Keywords

  • Journal Article

Cite this

Changes in Proteinuria and Side Effects of Corticosteroids Alone or in Combination with Azathioprine at Different Stages of IgA Nephropathy. / Sarcina, Cristina; Tinelli, Carmine; Ferrario, Francesca; Pani, Antonello; De Silvestri, Annalisa; Scaini, Patrizia; Del Vecchio, Lucia; Alberghini, Elena; Buzzi, Laura; Baragetti, Ivano; Pozzi, Claudio.

In: Clinical journal of the American Society of Nephrology : CJASN, Vol. 11, No. 6, 06.06.2016, p. 973-81.

Research output: Contribution to journalArticle

Sarcina, Cristina ; Tinelli, Carmine ; Ferrario, Francesca ; Pani, Antonello ; De Silvestri, Annalisa ; Scaini, Patrizia ; Del Vecchio, Lucia ; Alberghini, Elena ; Buzzi, Laura ; Baragetti, Ivano ; Pozzi, Claudio. / Changes in Proteinuria and Side Effects of Corticosteroids Alone or in Combination with Azathioprine at Different Stages of IgA Nephropathy. In: Clinical journal of the American Society of Nephrology : CJASN. 2016 ; Vol. 11, No. 6. pp. 973-81.
@article{725aced4c4bf458288258fa2074cca35,
title = "Changes in Proteinuria and Side Effects of Corticosteroids Alone or in Combination with Azathioprine at Different Stages of IgA Nephropathy",
abstract = "BACKGROUND AND OBJECTIVE: Time-average proteinuria (TAp) is the strongest predictor of renal survival in IgA nephropathy (IgAN). Little is known about the utility and safety of corticosteroids (CS) to obtain TAp<1 g/d in patients with advanced IgAN. This study sought to evaluate TAp at different degree of baseline renal function and histologic severity during CS use and to investigate treatment safety.DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We performed one-stage individual-patient data meta-analysis among 325 patients with IgAN enrolled in three prospective, randomized clinical trials. Patients were divided into three groups according to treatment: no treatment (NT; supportive therapy), CS, and CS plus azathioprine (CS+A). Associations of TAp with histologic grading, treatment, and eGFR at baseline were performed with linear regression models for repeated measures. The median follow-up duration was 66.6 months (range, 12-144 months).RESULTS: In the first 6 months, proteinuria did not change in the NT group and decreased substantially in the other groups(CS: from a mean±SD of 2.20±1.0 to 0.8 [interquartile range, 0.4-1.2] g/d; CS+A: from 2.876±2.1 to 1.0 [interquartile range, 0.5-1.7] g/d), independent of the degree of histologic damage and baseline eGFR. The percentage of patients who maintained TAp<1 g/d was 30.2{\%} in the NT, 67.3{\%} in the CS, and 66.6{\%} in the CS+A group. Thirty-four patients experienced adverse events: none in the NT, 11 (6.4{\%}) in the CS, and 23 (20.7{\%}) in the CS+A group. The risk of developing adverse events increased with decreasing levels of eGFR (from 2.3{\%} to 15.4{\%}). The addition of azathioprine to CS further increased the percentage of patients with adverse events (16.8{\%} versus 5.7{\%} in study 2 and 30.0{\%} versus 15.4{\%} in study 3; overall P<0.001).CONCLUSIONS: In patients with IgAN, CS can reduce proteinuria and increase the possibility of maintaining TAp<1 g/d, regardless of the stage of CKD and the histologic damage. The risk of major adverse events is low in patients with normal renal function but increases in those with impaired renal function and with the addition of azathioprine.",
keywords = "Journal Article",
author = "Cristina Sarcina and Carmine Tinelli and Francesca Ferrario and Antonello Pani and {De Silvestri}, Annalisa and Patrizia Scaini and {Del Vecchio}, Lucia and Elena Alberghini and Laura Buzzi and Ivano Baragetti and Claudio Pozzi",
note = "Copyright {\circledC} 2016 by the American Society of Nephrology.",
year = "2016",
month = "6",
day = "6",
doi = "10.2215/CJN.02300215",
language = "English",
volume = "11",
pages = "973--81",
journal = "Clinical journal of the American Society of Nephrology : CJASN",
issn = "1555-9041",
publisher = "by the American Society of Nephrology",
number = "6",

}

TY - JOUR

T1 - Changes in Proteinuria and Side Effects of Corticosteroids Alone or in Combination with Azathioprine at Different Stages of IgA Nephropathy

AU - Sarcina, Cristina

AU - Tinelli, Carmine

AU - Ferrario, Francesca

AU - Pani, Antonello

AU - De Silvestri, Annalisa

AU - Scaini, Patrizia

AU - Del Vecchio, Lucia

AU - Alberghini, Elena

AU - Buzzi, Laura

AU - Baragetti, Ivano

AU - Pozzi, Claudio

N1 - Copyright © 2016 by the American Society of Nephrology.

PY - 2016/6/6

Y1 - 2016/6/6

N2 - BACKGROUND AND OBJECTIVE: Time-average proteinuria (TAp) is the strongest predictor of renal survival in IgA nephropathy (IgAN). Little is known about the utility and safety of corticosteroids (CS) to obtain TAp<1 g/d in patients with advanced IgAN. This study sought to evaluate TAp at different degree of baseline renal function and histologic severity during CS use and to investigate treatment safety.DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We performed one-stage individual-patient data meta-analysis among 325 patients with IgAN enrolled in three prospective, randomized clinical trials. Patients were divided into three groups according to treatment: no treatment (NT; supportive therapy), CS, and CS plus azathioprine (CS+A). Associations of TAp with histologic grading, treatment, and eGFR at baseline were performed with linear regression models for repeated measures. The median follow-up duration was 66.6 months (range, 12-144 months).RESULTS: In the first 6 months, proteinuria did not change in the NT group and decreased substantially in the other groups(CS: from a mean±SD of 2.20±1.0 to 0.8 [interquartile range, 0.4-1.2] g/d; CS+A: from 2.876±2.1 to 1.0 [interquartile range, 0.5-1.7] g/d), independent of the degree of histologic damage and baseline eGFR. The percentage of patients who maintained TAp<1 g/d was 30.2% in the NT, 67.3% in the CS, and 66.6% in the CS+A group. Thirty-four patients experienced adverse events: none in the NT, 11 (6.4%) in the CS, and 23 (20.7%) in the CS+A group. The risk of developing adverse events increased with decreasing levels of eGFR (from 2.3% to 15.4%). The addition of azathioprine to CS further increased the percentage of patients with adverse events (16.8% versus 5.7% in study 2 and 30.0% versus 15.4% in study 3; overall P<0.001).CONCLUSIONS: In patients with IgAN, CS can reduce proteinuria and increase the possibility of maintaining TAp<1 g/d, regardless of the stage of CKD and the histologic damage. The risk of major adverse events is low in patients with normal renal function but increases in those with impaired renal function and with the addition of azathioprine.

AB - BACKGROUND AND OBJECTIVE: Time-average proteinuria (TAp) is the strongest predictor of renal survival in IgA nephropathy (IgAN). Little is known about the utility and safety of corticosteroids (CS) to obtain TAp<1 g/d in patients with advanced IgAN. This study sought to evaluate TAp at different degree of baseline renal function and histologic severity during CS use and to investigate treatment safety.DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We performed one-stage individual-patient data meta-analysis among 325 patients with IgAN enrolled in three prospective, randomized clinical trials. Patients were divided into three groups according to treatment: no treatment (NT; supportive therapy), CS, and CS plus azathioprine (CS+A). Associations of TAp with histologic grading, treatment, and eGFR at baseline were performed with linear regression models for repeated measures. The median follow-up duration was 66.6 months (range, 12-144 months).RESULTS: In the first 6 months, proteinuria did not change in the NT group and decreased substantially in the other groups(CS: from a mean±SD of 2.20±1.0 to 0.8 [interquartile range, 0.4-1.2] g/d; CS+A: from 2.876±2.1 to 1.0 [interquartile range, 0.5-1.7] g/d), independent of the degree of histologic damage and baseline eGFR. The percentage of patients who maintained TAp<1 g/d was 30.2% in the NT, 67.3% in the CS, and 66.6% in the CS+A group. Thirty-four patients experienced adverse events: none in the NT, 11 (6.4%) in the CS, and 23 (20.7%) in the CS+A group. The risk of developing adverse events increased with decreasing levels of eGFR (from 2.3% to 15.4%). The addition of azathioprine to CS further increased the percentage of patients with adverse events (16.8% versus 5.7% in study 2 and 30.0% versus 15.4% in study 3; overall P<0.001).CONCLUSIONS: In patients with IgAN, CS can reduce proteinuria and increase the possibility of maintaining TAp<1 g/d, regardless of the stage of CKD and the histologic damage. The risk of major adverse events is low in patients with normal renal function but increases in those with impaired renal function and with the addition of azathioprine.

KW - Journal Article

U2 - 10.2215/CJN.02300215

DO - 10.2215/CJN.02300215

M3 - Article

C2 - 27129712

VL - 11

SP - 973

EP - 981

JO - Clinical journal of the American Society of Nephrology : CJASN

JF - Clinical journal of the American Society of Nephrology : CJASN

SN - 1555-9041

IS - 6

ER -