Histopathologic features aid in predicting risk for progression of IgA nephropathy.
OBJECTIVE
IgA nephropathy (IgAN) is the most common primary glomerular disease worldwide. Accurately identifying patients who are at risk for progressive disease is challenging. The extent to which histopathologic features improves prognostication is uncertain.


METHODS
We studied a retrospective cohort with biopsy-proven IgAN in Calgary, Canada. Renal biopsies were reviewed by a nephropathologist with histopathologic data abstracted using a standardized form. The primary outcome was the composite of doubling of serum creatinine, ESRD, or death. Spline models defined significant levels of interstitial fibrosis, glomerulosclerosis, hypertension, proteinuria, and creatinine. The prognostic significances of clinical and histopathologic parameters were determined using Cox proportional hazards models.


RESULTS
Data from 146 cases were available for analysis with a median follow-up of 5.8 years. Greater than 25% interstitial fibrosis, >40% glomerular sclerosis, and a systolic BP >150 mmHg were risk thresholds. In univariable analyses, baseline creatinine, proteinuria, systolic BP, glomerular sclerosis, interstitial fibrosis, and crescentic disease were predictors of the primary outcome. In multivariable models adjusted for clinical characteristics, interstitial fibrosis (hazard ratio [HR]2.7; 95% confidence interval [CI] 1.2 to 6.0), glomerular sclerosis (HR 2.6; 95% CI 1.2 to 4.5), and crescents (HR 2.4; 95% CI 1.2 to 5.1) remained independent predictors of the primary outcome and significantly improved model fit compared with clinical characteristics alone.


CONCLUSIONS
Baseline histopathologic parameters are independent predictors of adverse outcomes in IgAN even after taking into consideration clinical characteristics. Relatively small degrees of interstitial fibrosis confer an increased risk for progressive IgAN.
Walsh
Michael
M
Division of Nephrology, Foothills Medical Centre, Calgary, AB, T2N 0L9, Canada. mwwalsh@ucalgary.ca
Sar
Aylin
A
Lee
Diane
D
Yilmaz
Serdar
S
Benediktsson
Hallgrimur
H
Manns
Braden
B
Hemmelgarn
Brenda
B
D000328:Adult; D000416:Alberta; D001284:Atrophy; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D016009:Chi-Square Distribution; D003404:Creatinine / Q000097:blood; D018450:Disease Progression; D005260:Female; D005355:Fibrosis; D005922:Glomerulonephritis, IGA / Q000097:blood / Q000150:complications / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000473:pathology; D007676:Kidney Failure, Chronic / Q000097:blood / Q000209:etiology* / Q000401:mortality / Q000473:pathology; D007678:Kidney Glomerulus / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D011507:Proteinuria / Q000209:etiology / Q000473:pathology; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D012598:Sclerosis; D013997:Time Factors
D015415:Biomarkers; D003404:Creatinine