The Oxford classification of IgA-nephropathy:
A review based on the Polish renal biopsy registry
Agnieszka Perkowska-Ptasińska1, Małgorzata Węgrowska-Danilewicz,
Marian Danilewicz, Agnieszka Hałoń, Anna Andrzejewska, Krzysztof Okoń,
Henryk Karkoszka.
1Medical
University of Warsaw
 IgA nephropathy is the most common type of chronic
glomerulonephritis in the world.
 Up to 30% of clinically affected patients develop
progressive renal failure, typically through a slow
progression of CKD.
 Non-specific clinical manifestation.
 Diagnosis based on biopsy finding: the recognition of
diffuse mesangial deposits of IgA in glomeruli.
 Kidney biopsy is necessary to recognize IgA-N, but
how much does it tell about the individual patient’s risk
of kidneys insufficiency ?
Several studies devoted to the identification of histopathologic
features that most accurately predict adverse outcome
Boyce NW et al.,
Morphological evaluation based on WHO classification for LN, progression
1986, 112 patients
to ESRD correlated with crescentic disease.
Radford MG et al.,
Glomerular, tubulo-interstitial, vascular scoring.
1997, 148 patients
An independent histopathological predictor of ESRD: total glomerular
score: sum of 6 components scored 0-3 each: mesangial celullarity,
mesangial matrix increase, capillary narrowing or disruption,
glomerulosclerosis, cellular crescents, adhesions
Haas M,
Strong correlation between histologic subclass and renal survival,
1997, 240 patients
with an order I, II (best survival) >III > IV,V.
D’Amico G,
Glomerular sclerosis and interstitial fibrosis - the strongest, most
2004, analysis of the
results of 23 studies
reliable predictors of unfavourable prognosis. More controversial was the
Wakai K et al.,
Advanced histological changes independently increased the risk of ESRD
2006, 2269 patients
in IgA nephropathy patients.
Prognostic score composed of individual scores for clinical characteristics
and histopathological grading (I-IV).
role of crescents and capsular adhesions.
 In a majority of studies tubulointerstitial scarring
was found to be an independent predictor of
progression to ESRD in a multivariate analysis.
 Glomerular lesions were usually found to correlate
significantly with disease progression by univariate
analysis, but rarely were they found to be
independent predictors of such progression by
a multivariate analysis.
 The introduction of composite scoring systems
(such as in Radford’s study) was associated with an
enhancement of the negative predictive value of the
glomerular lesions.
Haas classification
Grade
Glomerular findings
I
Mild increase in mesangial matrix no proliferation, sclerosis,
necrosis
II
FSGS-like,
no proliferation
III
Focal proliferative GN (< 50% glomeruli affected),
with or without necrosis and crescent formation
IV
V
Diffuse proliferative GN (> 50% glomeruli affected),
with or without necrosis and crescent formation
Presence of >40% globally sclerotic glomeruli and/or estimated
tubular loss of >40%,
irrespective of the presence of active glomerular lesions
IgA-N histological grading according to the Joint Committee of the
Research Group on Progressive Renal Disease and the Japanese Society
of Nephrology ( ”the Japanese classification”, Wakai 2006)
Grade
Glomerular findings
Interstitial and vascular
findings
I
Slight mesangial cell proliferation and increased
matrix. No glomerulosclerosis, crescent formation
or adhesion to Bowman’s capsule.
Prominent changes are not seen
in the interstitium, renal tubules
or blood vessels.
II
Slight mesangial cell proliferation and increased
matrix. Glomerulosclerosis, crescent formation or
adhesion to Bowman’s capsule seen in <10% of
glomeruli.
Same as above.
III
Moderate, diffuse mesangial cell proliferation and
increased matrix.
Glomerulosclerosis, crescent formation or adhesion
to Bowman’s capsule seen in 10–30% of glomeruli.
Cellular infiltration is slight in the
interstitium except around some
sclerosed glomeruli. Slight tubular
atrophy, mild vascular sclerosis.
IV
Severe, diffuse mesangial cell proliferation and
Presence of interstitial cellular
increased matrix. Glomerulosclerosis, crescent
infiltration and tubular atrophy, as
formation or adhesion to Bowman’s capsule seen in
well as fibrosis.
>30% of all biopsied glomeruli. When sites of
sclerosis are totalled and converted to global
sclerosis, the glomerulosclerosis rate is >50%.
Hyperplasia or degeneration of
arteriolar walls
Oxford classification of IgA-N
The aim of the Oxford study: to develop a
reproducible pathological classification of IgAN
that would predict the clinical outcome.
 Developed by renal pathologists and nephrologists from the
international IgA nephropathy network and the RPS.
 A study based on 265 patients with at least 1 year of follow-up.
 Initially: selection of pathological variables that had high
interobserver reproducibility and reliability.
 Subsequently: identification of 4 pathological features which,
independently of one another and of the patient’s clinical
parameters, predicted the outcome.
KI (2009) 76
The aim of the PHIGANS study
To discern the prognostic values of histological
IgA-N characteristics defined by:
Oxford, Haas, Japanese classifications, and
PHIGANS – the Polish histological IgA
nephropathy system).
Selection of IgA-N cases:
dataset of the Polish Registry of Nephropathies
Pathologists from the Polish
nephropathological working group
Agnieszka Perkowska-Ptasińska
Małgorzata Danilewicz
Marian Danilewicz
Agnieszka Hałoń
Anna Andrzejewska
Krzysztof Okoń
Henryk Karkoszka
Nephrologists
Ewa Komuda-Leszek
Ilona Kurnatowska
Monika Kraśnicka
Tomasz Hryszko
Mariusz Kusztal
PHIGANS STUDY
Study design: retrospective
Inclusion criteria:
•
biopsy-proven IgA nephropathy recognized not later than in
December 2008 with histological slides available for current
re-evaluation,
•
patients’ age >18 years,
•
at least 12 months post-biopsy follow-up,
•
clinical data available:
- at the time of the biopsy
- 3-6 months after the biopsy
- 1 year after the biopsy
- at the end of the observation
Clinical end points:
Oxford study:
1.
Rate of loss of renal function
(ml/min/1.73 m2 per year),
2.
≥50% loss of renal function or ESRD
(<15 ml/min/1.73 m2) by the end of the follow-up,
Additional end point in PHIGANS study:
3.
eGFR (MDRD) < 60 ml/min/1.73 m2 by the end of
the follow-up.
Histopathological analysis
PHIGANS
Parameters that describe acute/active lesions:
•increased mesangial cellularity (0-3) (GM)
•increased endocapillary cellularity (0-3) (GE)
•glomerular necrosis (%,) (0; 1-25%; 26-50%; >50%)(GN)
•cellular crescents (%,) (0; 1-25%; 26-50%; >50%)(GCC)
Oxford classification
Endocapillary hypercellularity
(absent/present)
Mesangial hypercellularity (≤0,5; >0,5)
Segmental GS (absent/present)
•total interstitial inflammation (0-3) (Ti)
Tubular atrophy/interstitial fibrosis
G sum: GM+GE+GN+GC
(0-25%; 26-50%; >50%)
CG index: G sum/4
Parameters that describe chronic lesions:
•global GS (%), (0; 1-25%; 26-50%; >50%) (GGS)
•segmental GS (%,) (0; 1-25%; 26-50%; >50%) (SGS)
•fibrotic crescents (%) (0; 1-25%; 26-50%; >50%) (GCF)
•tubular atrophy (0-3) (ct)
•interstitial fibrosis (0-3) (ci)
ST sum: GGS+SGS+GCF+ci+ct
ST index: ST sum/5
Biopsy index: G index+ Ti +ST index (0-9)
Characteristics of patient groups
PHIGANS study
Number of patients
Oxford study
(KI (2009) 76)
118
265
47.5%
28 %
Age at the Bx (years)
35 ± 12.4
35 ± 15
Duration of FU (years)
median 4.6 (1.3-30.2)
median 5 (1-22)
78% followed > 3 years
90% followed > 3 years
1.6 (0-16.7)
1.7 (0.5-18.5)
98 ± 9.3
98 ± 18
26 ± 7
25 ± 5
Female
Proteinuria (g/d)
MAP (mmHg)
BMI
PHIGANS study - patients’ clinical characteristics
at different time points
Clinical
parameters
At the time of
Bx
3-6 months
after Bx
1 year after
Tx
At the end of
the follow-up
Serum creatinine
concentration
(mg/dL)
1.1 ± 0.5
1.1 ± 0.5
1.1 ± 0.5
1.2 ± 0.5
GFR
84.4 ± 33.2
81.8 ± 30.7
82.9 ± 33.8
77.8 ± 30.9
Proteinuria:
2.1 ± 2.3
1.5 ± 2.6
0.8 ± 1.1
0.6 ± 0.7
Nephrotic
syndrome:
20.3%
10.2%
3.4%
4.2%
Erytrocyturia:
94.9%
82.2%
75.4%
78.8%
Hematuria:
11.9%
2.54%
2.5%
0,9%
Nephritic
syndrome:
33.1%
20.3%
17.8%
10.2%
BPS
130.4 ± 15
127.9 ± 15
126.8 ± 18.5
127.3 ± 15.9
BPR
81.4 ± 8.7
80.8 ± 9.3
81 ± 10.3
80.5 ± 9.8
MAP
97.7 ± 9.3
96.5 ± 10.1
96.2 ± 11.2
96.1 ± 10.9
BMI
26 ± 6.7
25.8 ± 5.4
26.3 ± 6.8
27.8 ± 11.6
PHIGANS study: pharmaphological supportive treatment
during the time of observation
Before or at the
Within 3-6 months
Within 1 year
At the end of the
time of Bx
after Bx
after Bx
follow-up
AEI
71.2%
82.2%
83.1%
74.6%
ARB
14.4%
22.9%
31.4%
44.9%
Statins
25.4%
36.4%
39%
36.4%
PHIGANS study: pharmaphological treatment
during the time of observation - immunosuppression
Before
or at the time
of Bx
Within 3-6
months after Bx
Within 1 year
after Bx
At the end of
the follow-up
SM boluses
13. 6%
28.8%
5.9%
2.5%
Prednison
29.7%
58.5%
58.5%
46.6%
Cyclophosphamide
7.6%
5.9%
5.9%
7.6%
Azathioprine
3.4%
11.0%
15.6%
5.1%
Cyclosporine
0
0.9%
3.4%
5.1%
IS therapy
PHIGANS study
Results
Oxford study end points:
PHIGANS study end point:
≥50% loss of
renal function
by the end of
the FU
of the FU
7.6%
4.24%
ESRD by
the end
eGFR (MDRD) < 60
ml/min/1.732 m
by the end of the FU
Oxford study
30.51 %
Oxford study end points:
≥50% loss of
renal function
by the end of
the FU
the end of
22%
13%
ESRD by
the FU
Distribution of CKD stages
among patients studied
at the time of BX
Oxford study (KI (2009) 76)
PHIGANS study
CKD stages
CKD stages
28.2%
28%
16.2%
16%
0.9%
1%
60
percentage
percentage
54.7%
35%
57%
40
20
0
I
II
III
stage
IV
35%
49%
I
II
22%
4%
III
IV
60
40
20
0
stage
Distribution of acute/active lesions
Lesion
Endocapillary hypercellularity
PHIGANS study
71.2%
(OX-E, GE)
Mesangial hypercellularity
(OX-M, GM)
Necrosis in glomerular tufts
Interstitial inflammation (ti)
42%
Median of glomeruli
involved: 12%
56.8%
Approximately 93%
8.47% (0.47±1.9)
2.3%
28.8% (2.8±7.6)
45%
median of glomeruli
involved: 0
median of glomeruli
involved: 9%
55.94%
?
(GN st)
Cellular crescents (GCC st)
Oxford study (KI (2009) 76)
(TI 1: 44.92%
TI 2: 11.02%)
Distribution of chronic lesions
Segmental
GS
Oxford study:
Mean number of glomeruli
per biopsy: 18
frequency
PHIGANS study:
Mean number of glomeruli
per biopsy: 21 ± 11.1
-20
20
0
40
60
80
Global
GS
frequency
KI (2009) 76: 534-545
-20
0
20
40
60
80
Distribution of chronic lesions
Oxford study
PHIGANS study
80
60
frequency
interstitial
fibrosis/
tubular
atrophy
1-25% of
cortex area
with ci/ct
40
no ci/ct
26-50% of
cortex area
with ci/ct
20
>50% of
cortex area
with ci/ct
0
0
60
2
3
KI (2009) 76: 534-545
in 1-25%of
glomeruli
50
frequency
Fibrotic
crescents
1
40
30
20
In 25-50%
of glomeruli
10
In >50%of
glomeruli
0
0
1
2
3
PHIGANS study: distribution of pathological grades
according to the Haas and Japanese classifications
Japanese classification
Frequency
Frequency
Haas classification
Results of the statistical analysis
1.
Correlations between the clinical parameters (at Bx) and
histopathological variables defined according to the Oxford, Hass,
Japanese, PHIGANS classifications.
2.
Relation between the clinical (at Bx) as well as histopathological
variables and the outcome defined as eGFR<60 ml/min by the end
of the observation (Cox regression analysis).
3.
Relation between histopathological parameters and progression
defined as eGFR loss≥20% by the end of the observation in pts with
initial eGFR<60 ml/min (univariate analysis).
4.
Relation between the clinical (at Bx) as well as histopathological
variables and the outcome defined as≥50% of eGFR loss or ESRD
by the end of the observation (Cox regression analysis).
5.
Relation between clinical (at Bx) as well as histopathological variables
and the rate of GFR loss (dGFR) (linear regression).
Results of the statistical analysis
1.
Correlations between the clinical parameters (at Bx) and
histopathological variables defined according to the Oxford, Hass,
Japanese, PHIGANS classifications.
2.
Relation between the clinical (at Bx) as well as histopathological
variables and the outcome defined as eGFR<60 ml/min by the end
the observation (Cox regression analysis).
of
3.
Relation between histolopathogical parameters and progression
defined as eGFR loss≥20% by the end of the observation in pts with
initial eGFR<60 ml/min (univariate analysis).
4.
Relation between the clinical (at Bx) as well as histopathological variables
and the outcome defined as≥50% of eGFR loss or ESRD
by the end of the observation (Cox regression analysis).
5.
Relation between clinical (at Bx) as well as histopathological variables and
the rate of GFR loss (dGFR) (linear regression).
Correlations between the clinical parameters (at Bx) and
histopathological variables defined according to Oxford class.
PHIGANS study
MAP
Proteinuria
eGFR
Mesangial hypercellularity (OX-M)
0.04,
0.16
0.03
NS
P=0.008
NS
Endocapillary hypercellularity (OX-E)
P
0.04
NS
0.11
NS
0.12
NS
Segmental glomeruloscelrosis (OX-S)
0.07
0.18
-0.22
P
NS
NS
P=0.016
Tubular atrophy/interstitial fibrosis (OX-T)
0.17
0.18
-0.43
p
NS
P=0.05
p<0.001
Oxford study
MAP
Proteinuria
eGFR
Mesangial hypercellularity (OX-M)
NS
P=0.001
NS
Endocapillary hypercellularity (OX-E)
P=0.008
P=0.01
P=0.001
Segmental glomeruloslclerosis (OX-S)
P=0.04
P=0.004
P=0.003
Tubular atrophy/interstitial fibrosis (OX-T)
P=0.03
NS
<0.001
P
KI (2009) 76: 534-545
Correlations between the clinical parameters (at Bx) and
histopathological variables according to PHIGANS
Active lesions/grading
MAP
Proteinuria
eGFR
Mesangial hypercellularity
0.21
0.06
-0.04
p
0.03
NS
NS
Endocapillary
hypercellularity
-0.008
0.1
0.14
NS
NS
NS
Glomerular necrosis (0-3)
-0.03
0.005
-0.12
p
NS
NS
NS
Cellular crescents (0-3)
0.08
0.33
-0.24
p
NS
0.0003
0.009
G sum
0.14
0.27
-0.12
p
NS
0.003
NS
G index
0.14
0.27
-0.12
p
NS
0.0031
NS
Total inflammation
0.21
0.25
-0.27
p
0.02
0.006
0.0031
p
Correlations between the clinical parameters (at Bx) and
histopathological variables according to PHIGANS
Chronic lesions/staging
MAP
Proteinuria
eGFR
Global glomerulosclerosis (0-3)
0.2
0.23
-0.43
P
Segmental glomerulosclerosis (0-3)
0.03
0.16
0.01
0.36
<0.0001
-0.3
P
Fibrotic crescents (0-3)
NS
0.12
<0.0001
0.19
0.001
-0.09
P
Interstitial fibrosis
NS
0.21
0.04
0.27
NS
-0.09
p
Tubular atrophy
0.02
0.2
0.0035
0.25
NS
-0.44
p
St sum
0.03
0.26
0.0058
0.37
<0.0001
-0.48
p
St index
0.006
0.26
<0.0001
0.37
<0.0001
-0.48
p
0.006
<0.0001
<0.0001
Biopsy index
0.23
0.35
-0.35
p
0.01
<0.0001
<0.0001
PHIGANS study:
correlations between the clinical parameters (at Bx)
and histopathological variables
defined according to the Haas and Japanese classifications
HAAS
classification
MAP
Proteinuria
eGFR
0.15
0.24
-0.31
NS
0.01
0.0007
0.23
0.33
-0.37
0.01
0.0002
<0.0001
p
Japanese
classification
p
Results of the statistical analysis
1.
Correlations between the clinical parameters (at Bx)
and histopathological variables defined according to
the Oxford, Hass, Japanese, PHIGANS classifications.
2.
Relation between the clinical (at Bx) as well as histopathological
variables and the outcome defined as eGFR<60 ml/min
by the end of observation (Cox regression analysis).
3.
Relation between the histopathological parameters and progression
defined as eGFR loss≥20% by the end of observation in pts with initial
eGFR<60 ml/min (univariate analysis).
4.
Relation between the clinical (at Bx) as well as histopathological variables
and the outcome defined as≥50% of eGFR loss or ESRD
by the end of the observation (Cox regression analysis).
5.
Relation between the clinical (at Bx) as well as histopathological variables
and the rate of GFR loss (dGFR) (linear regression).
Relation between the clinical variables (at Bx) and the outcome
defined as eGFR<60 ml/min by the end of FU
- univariate analysis
Cox Regression Model
Variables
HR
CI 95%
p
Nephrotic syndrome
3.3
1.4-1.9
0.006
Nephritic syndrome
2.0
1.0-4.0
0.036
33-71 vs 15-32
2.5
1.1-5.0
0.025
1-4 vs 0.5-1
10.2
3,6-28.6
<0.001
GFR
16-84 vs 85-208
12.7
3.9-41.4
<0.001
Proteinuria
1.6-16.7 vs 0-1.5
3.3
0.1-10
0.003
27-64 vs 17-22
5
1.4-10
0.006
27-64 vs 23-26
3.3
1.3-10
0.015
BPS
136-170 vs 100-120
5
1.7-10
0.001
MAP
100-125 vs 80-93
3.3
1.4-10
0.007
Age
Serum creatinine
BMI
Relation between histopathological variables and the outcome
defined as eGFR<60 ml/min by the end of FU
- a univariate analysis
Cox Regression Model
Variables
HR
CI 95%
p
OX-T
1 vs 0
5.7
3-11
<0.001
Stage of global GS
2 vs 0
9.2
2-40
0.003
Stage of segmental GS
2 vs 0
10.3
2-48
0.003
ct
2 vs 0
36.6
5-290
0.001
1 vs 0
8.4
1.1-64
0.041
2 vs 0
36.7
4.6-291
0.001
1 vs 0
8.4
1.1-65
0.041
1 vs 0
3.3
1.3-8
0.011
1.2-2.2 vs 0-0.6
10
3.3-50
0.001
1.2-2.2 vs 0.7-1
5
2.5-10
<0.001
3.1-5.7 vs 0-1.6
5
1.7-10
0.003
3.1-5.7 vs 1.6-3
2.5
1.3-5
0.011
ci
Ti
ST index
Biopsy index
Relation between the clinical (at Bx) as well as Oxford hist. variables
and the outcome defined as eGFR<60 mil/min by the end of FU
- a multivariate analysis
Cox regression model
Multivariate analysis,
Cox regression model
HR
95% CI
p
OX-T 1 vs 0
3.3
1.6-6.7
0.001
GFR 16-69 vs 95-208
22.7
3.0-171
0.002
GFR 70-94 vs 95-208
4.9
0.6-41.2
0.144
(AIC:267.2
222.7)
frequency
PARAMETERS
included in the
multivariate
regression model
OX-T
GFR 16-69
vs 95-208
GFR 70-94
vs 95-208
Relation between clinical (at Bx) as well as PHIGANS variables
and the outcome defined as a eGFR<60 mil/min by the end of FU
- a multivariate analysis
Cox regression model
Multivariate analysis,
Cox regression model
HR
95% CI
p
Ct 2 vs 0
49.2
2.9847.5
0.007
Ct 1 vs 0
19
1.1-318.4
0.04
GFR 16-69 vs 95-208
32.1
3.5298.2
0.002
GFR 70-94 vs 95-208
7.0
0.7-72.5
0.1
HR
PARAMETERS
included in the
multivariate
regression model
(AIC:267.2 215.6)
Ct2 vs ct0
ct1 vs ct0
GFR 16-69
vs 95-208
GFR 70-94
vs 95-208
Results of the statistical analysis
1.
Correlations between the clinical parameters (at Bx) and
histopathological variables defined according to the Oxford,
Hass, Japanese, PHIGANS classifications.
2.
Relation between the clinical (at Bx) as well as histopathological
variables and the outcome defined as eGFR<60 ml/min
by the end of observation (Cox regression analysis).
3.
Relation between histopathological parameters and progression
defined as eGFR loss≥20% by the end of the observation in
pts with the initial eGFR<60 ml/min (univariate analysis).
4.
Relation between the clinical (at Bx) as well as histopathological
variables and the outcome defined as≥50% of eGFR loss or ESRD
by the end of observation (Cox regression analysis).
5.
Relation between the clinical (at Bx) as well as histopathological
variables and the rate of GFR loss (dGFR) (linear regression).
Relation between histopathological parameters and progression
defined as eGFR loss≥20% by the end of the observation
in pts with the initial eGFR<60 mil/min
- a univariate analysis
OX-T:
0
1
2
OX-T:
0
1 (absent/present)
Relation between histopathological parameters and progression
defined as eGFR loss≥20% by the end of the observation
in pts with the initial eGFR<60 mil/min
- a univariate analysis
ci:
0
1
2
3
GC st:
0
1
2
Results of the statistical analysis
1.
Correlations between the clinical parameters (at Bx) and
histopathological variables defined according to the Oxford,
Hass, Japanese, PHIGANS classifications.
2.
Relation between clinical (at Bx) as well as histopathological
variables and the outcome defined as eGFR<60 ml/min
by the end of the observation (Cox regression analysis).
3.
Relation between histopathological parameters and progression
defined as eGFR loss≥20% by the end of the observation in pts
with the initial eGFR<60 ml/min (univariate analysis).
4.
Relation between clinical (at Bx) as well as histopathological
variables and the outcome defined as≥50% of eGFR loss or
ESRD by the end of observation (Cox regression analysis).
5.
Relation between clinical (at Bx) as well as histopathological
variables and the rate of GFR loss (dGFR) (linear regression).
Relation between the clinical (at Bx) as well as PHIGANS
variables and the outcome defined as≥50% of eGFR loss or ESRD
by the end of the observation
- a univariate analysis
Cox Regression Model
Variables
HR
CI 95%
p
7.2
2.1-24.3
0.001
1-4 vs 0.49-0.98
10
1.7-100
0.015
16.2-84 vs 85-208
5.5
1.2-25.7
0.031
IS therapy (present vs absent)
3.9
1.1-13.4
0.033
Biopsy index
9.1
1,11-90.9
0.02
Nephrotic syndrome
Serum creatinine
GFR
3.1-5.7 vs 0-1.6
Relation between clinical (at Bx) and Oxford histopathological
variables and the outcome defined as ≥50% loss of eGFR or ESRD
by the end of the observation
- a multivariate analysis
(AIC: 76,8 73.5)
Cox regression model
multivariate analysis,
Cox regression model
HR
95% CI
p
OX-T 1 vs 0
1.9
0.5-8.1
0.37
GFR 16-69 vs 95-208
8.4
0-70
0.05
GFR 70-94 vs 95-208
1.9
0.2-21.7
0.6
HR
PARAMETERS
included in the
multivariate
regression model
OX-T
GFR 16-69
vs 95-208
GFR 70-94
vs 95-208
Relation between Haas as well as Japanese classifications
and the outcome – univariate analysis
Cox Regression Model
variables
In univariate analysis
Cox regression analysis revealed
an association between the 4th
stage of the disease according to
Japanese classification
and an end point defined as
GFR< 60 mil/min.
Haas
Japanese
≥50% of
eGFR loss
or ESRD
(p)
GFR< 60
mil/min
Class 5 vs 1
NS
NS
Class 4 vs 1
NS
NS
Class 3 vs 1
NS
NS
Class 2 vs 1
NS
NS
Class 4 vs 1
NS
0.05
Class 3 vs 1
NS
NS
Class 2 vs 1
NS
NS
(p)
Results of the statistical analysis
1.
Correlations between clinical parameters (at Bx) and
histopathological variables defined according to
Oxford, Hass, Japanese, PHIGANS classifications.
2.
Relation between clinical (at Bx) as well as histopathological
variables and the outcome defined as eGFR<60 ml/min
by the end of observation (Cox regression analysis).
3.
Relation between histopathological parameters and progression
defined as eGFR loss≥20% by the end of observation in pts with
initial eGFR<60 ml/min (univariate analysis).
4.
Relation between clinical (at Bx) as well as histopathological
variables and the outcome defined as≥50% of eGFR loss or ESRD
by the end of observation (Cox regression analysis).
5.
Relation between clinical (at Bx) as well as histopathological
variables and the rate of GFR loss (dGFR) (linear regression).
Relation between clinical parameters (at Bx)
and the rate of GFR loss (dGFR)
- linear regression, univariate analysis
GFR at the time of Bx
dGFR
dGFR
Cellular crescents
P=0.06
P<0.0001
Relation between clinical parameters (at Bx)
and the rate of GFR loss (dGFR)
- linear regression, univariate analysis
dGFR
IS therapy
P=0.03
Relation between the activity/stage of the IgAN according
to Haas class. and the rate of GFR loss (dGFR)
- linear regression, multivariate analysis
Haas classification
Parameters in the best
model (AIC: 782.48)
p
Haas classification
GFR
IS therapy
0.04
dGFR
with Haas classification
<0.001
0.002
P=0.04
Relation between the activity/stage of the IgAN according
to Japanese classification and the rate of GFR loss (dGFR)
- linear regression, multivariate analysis
Japanese classification
Parameters in the best
model (AIC: 787.8) with the
p
Japanese classification
GFR
IS therapy
0.02
dGFR
Japanese classification
<0.001
0.004
P=0.02
Relation between clinical as well as Oxford’s histop. variables
and the rate of GFR loss (dGFR)
linear regression, multivariate analysis
p
Endocapillary
hypercellularity (OX-E)
0.113
Mesangial hypercellularity
(OX-M)
0.182
Ttubular atrophy/interst.
fibrosis (OX-T)
0.039
IS therapy
0.004
GFR
OX-T
dGFR
Parameters in the best
model (AIC: 795 )
<0.0001
P=0.04
Relation between clinical as well as PHIGANS variables
and the rate of GFR loss (dGFR)
linear regression, multivariate analysis
p
Biopsy index
0.002
IS therapy
0.004
GFR
dGFR
Parameters in the best
model (AIC: 792 )
Biopsy index
<0.0001
P=0.002
Summary
 eGFR at the time of Bx is the strongest clinical predictor of poor outcome
in IgA nephropathy.
 Among histopathological parameters defined by Oxford classification only
tubular atrophy was found to be a negative prognostic factor in both
univariate and multivartiate analysis with the end-point defined as
eGFR <60 mil/min at the end of FU.
 Among PHIGANS parameters the ones most distinctly associated with the
clinical outcome were those that scored chronic lesions, with the strongest
negative impact of tubulointerstitial scarring and composite scores,
including biopsy index. Those scores have also correlated with the clinical
manifestation of IgA at the time of biopsy (proteinuria and eGFR).
 Japanese and Haas classifications were proved to have a significant
negative impact on dGFR in the multivariate analysis.
Conclusions
 The PHIGANS study has not confirmed the independent predictive value of
glomerular lesions (segmental sclerosis, mesangial and endocapillary
hypercellularity) that was documented by the Oxford study.
 The usage of composite scores makes the impact of glomerular lesions on
the clinical outcome more distinct.
 There were differences in both clinical and pathological characteristics of
patients’ groups in PHIGANS and Oxford studies – to what extent have
these differences caused the results’ discrepancies?