P260
USE OF SIMPLE PATHOLOGICAL MEASUREMENTS MAY HELP PREDICT
KIDNEY SURVIVAL IN PATIENTS WITH PAUCI-IMMUNE NECROTIZING
GLOMERULONEPHRITIS PRESENTING WITH SEVERE KIDNEY DYSFUNCTION
Day, C1, Howie, A2, Nightingale, P3, Shabir, S1, Adu, D1, Savage, C4, Hewins, P1.
1
Department of Nephrology, University Hospital Birmingham Foundation Trust,
2
Department of Pathology, University College London, 3Wellcome Trust Clinical
Research Facility, University Hospital Birmingham Foundation Trust, 4Division of
Immunity & Infection, University of Birmingham
INTRODUCTION: ANCA-associated small vessel vasculitides cause rapidly progressive,
pauci-immune necrotizing glomerulonephritis (PNGN). Routine use of immunosuppressive
therapies has dramatically improved prognosis but significant morbidity and mortality remain
as a result of both disease and treatment. Presenting serum creatinine is correlated with
outcome but at least some patients with severe kidney disease recover independent kidney
function with treatment. Meanwhile, a sizable proportion of patients with PNGN are elderly
with significant co-morbidity and particularly vulnerable to adverse effects of prolonged
immunosuppressive therapy. We have previously described a simple morphometric measure of
chronic damage that assesses the whole area of renal cortex in a biopsy specimen (the index of
chronic damage) and reported the utility of the index in a large cohort of PNGN patients (Day
et al Am J Kid Dis 2009 epub). In the present study, we examined the value of pathological
measurements in predicting kidney survival in PNGN patients according to the degree of
presenting kidney dysfunction.
METHODS: The ability of the index of chronic damage and glomerular morphology to predict
progression to end-stage kidney disease (ESKD) were examined on the presenting renal biopsy
in a cohort of 390 consecutive patients at a single teaching hospital with PNGN. Median
follow-up was 166 weeks (range 1 day to 1256 weeks). If a patient did not progress to ESKD
they were censored at either death or last follow-up, the latter being at least two years after
presentation. To assess the impact of serum creatinine on the performance of pathological
measurements, the cohort was separated into two halves by the median creatinine (339µmol/L).
Multivariable survival analyses were performed using stepwise Cox regression with creatinine
as a continuous variable. Pathological measurements were divided into quartiles to make hazard
ratios more clinically useful.
RESULTS: In the whole cohort, univariable analyses demonstrated that creatinine at
presentation, index of chronic damage and percentage normal glomeruli were all associated
with progression to ESKD whereas in the multivariable analysis creatinine (p<0.001 HR 1.19
95% CI 1.13-1.25) and % normal glomeruli (p<0.001 HR 0.47 95% CI 0.31-0.71) were the best
predictors of ESKD. Among patients presenting with a serum creatinine <339µmol/L, neither
index of chronic damage nor percentage normal glomeruli provided additional predictive
information. However, among those presenting with a serum creatinine >339µmol/L, patients
in the fourth group of index of chronic damage (most extensive chronic damage) (p=0.01 HR
1.97 95%CI 1.16-3.34) and those in the first quartile of percentage of normal glomeruli (fewest
normal glomeruli) (p<0.001 HR 4.33 95%CI 1.98-9.48) had significantly worse kidney
outcomes compared to those in the respective least damaged quartiles.
CONCLUSION: Serum creatinine at presentation is the best predictor of renal outcome in
PNGN meaning that additional assessement will have greatest potential utility in patients with
more severe renal dysfunction. Accordingly, we demonstrate that simple quantitative
measurements of glomerular morphology and chronic damage may be prognostically helpful
and could be used to aid appropriate use of immunosuppressive therapies.