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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 outcomeBoyce NW et al.,
1986, 112 patients
Morphological evaluation based on WHO classification for LN,
progression to ESRD correlated with crescentic disease.
Radford MG et al.,
1997, 148 patients
Glomerular, tubulo-interstitial, vascular scoring.
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,
1997, 240 patients
Strong correlation between histologic subclass and renal
survival,
with an order I, II (best survival) >III > IV,V.
D’Amico G,
2004, analysis of the results of 23 studies
Glomerular sclerosis and interstitial fibrosis - the strongest,
most reliable predictors of unfavourable prognosis. More
controversial was the role of crescents and capsular adhesions.
Wakai K et al.,
2006, 2269 patients
Advanced histological changes independently increased the risk of ESRD
in IgA nephropathy patients.
Prognostic score composed of individual scores for clinical characteristics
and histopathological grading (I-IV).
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 Diffuse proliferative GN (> 50% glomeruli affected), with or without necrosis and crescent formation
VPresence 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 tubulesor blood vessels.
II Slight mesangial cell proliferation and increased matrix. Glomerulosclerosis, crescent formation or adhesion to Bowman’s capsule seen in <10% ofglomeruli.
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
increased matrix. Glomerulosclerosis, crescent
formation or adhesion to Bowman’s capsule seen in
>30% of all biopsied glomeruli. When sites of
sclerosis are totalled and converted to global
sclerosis, the glomerulosclerosis rate is >50%.
Presence of interstitial cellular
infiltration and tubular atrophy, as
well as fibrosis.
Hyperplasia or degeneration of
arteriolar walls
Oxford classification of IgA-N
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.
The aim of the Oxford study: to develop a reproducible pathological classification of IgAN that would predict the clinical 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).
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
Selection of IgA-N cases:
dataset of the Polish Registry of Nephropathies
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:
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,
Oxford study:
3. eGFR (MDRD) < 60 ml/min/1.73 m2 by the end of
the follow-up.
Additional end point in PHIGANS study:
Histopathological analysis PHIGANS Oxford classification
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)
•total interstitial inflammation (0-3) (Ti)
G sum: GM+GE+GN+GC
CG index: G sum/4
Endocapillary hypercellularity
(absent/present)
Mesangial hypercellularity (≤0,5;
>0,5)
Segmental GS (absent/present)
Tubular atrophy/interstitial fibrosis
(0-25%; 26-50%; >50%)
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 Oxford study (KI (2009)
76)
Number of patients 118 265
Female 47.5% 28 %
Age at the Bx (years) 35 ± 12.4 35 ± 15
Duration of FU (years) median 4.6 (1.3-30.2)
78% followed > 3 years
median 5 (1-22)
90% followed > 3 years
Proteinuria (g/d) 1.6 (0-16.7) 1.7 (0.5-18.5)
MAP (mmHg) 98 ± 9.3 98 ± 18
BMI 26 ± 7 25 ± 5
PHIGANS study - patients’ clinical characteristics at different time points Clinical
parametersAt the time
of Bx3-6 months
after Bx1 year after
TxAt 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
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
AEI 71.2% 82.2% 83.1% 74.6%
ARB 14.4% 22.9% 31.4% 44.9%
Statin
s
25.4% 36.4% 39% 36.4%
PHIGANS study: pharmaphological supportive treatment during the time of observation
IS therapyBefore 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%
PHIGANS study: pharmaphological treatment during the time of observation - immunosuppression
Results
Oxford study end points:
≥50% loss of renal function by the end of
the FU
ESRD by
the end
of the
FU
7.6% 4.24%
PHIGANS study end point:
eGFR (MDRD) < 60 ml/min/1.732 m
by the end of the FU
30.51 %
PH
IGA
NS
stu
dyO
xfo
rd s
tudy
Oxford study end points:
≥50% loss of renal
function by the end of
the FU
ESRD by
the end
of the FU
22% 13%
Distribution of CKD stages among patients studied
at the time of BX
CKD stages
0
20
40
60
I II III IV
stage
perc
enta
ge
35% 49% 22% 4%
PHIGANS study Oxford study (KI (2009) 76)
54.7% 28.2% 16.2% 0.9%35%
CKD stages
0
20
40
60
I II III IV
stage
perc
enta
ge
57% 28% 16% 1%
Distribution of acute/active lesions
Lesion PHIGANS study Oxford study (KI (2009)
76)
Endocapillary
hypercellularity (OX-E, GE)71.2%
42%
Median of glomeruli involved: 12%
Mesangial hypercellularity
(OX-M, GM)56.8% Approximately 93%
Necrosis in glomerular tufts
(GN st)8.47% (0.47±1.9) 2.3%
Cellular crescents (GCC st)
28.8% (2.8±7.6)
median of glomeruli involved: 0
45%
median of glomeruli involved: 9%
Interstitial inflammation (ti)55.94%
(TI 1: 44.92%
TI 2: 11.02%)
?
-20 0 20 40 60 80
freq
uen
cy
Distribution of chronic lesions
PHIGANS study:Mean number of glomeruli
per biopsy: 21 ± 11.1
Oxford study:Mean number of glomeruli
per biopsy: 18
freq
uen
cy
-20 0 20
40 60 80
Segmental
GS
Global
GS
KI (2009) 76: 534-545
Distribution of chronic lesions
Oxford study
interstitial fibrosis/ tubular atrophy
Fibrotic crescents
KI (2009) 76: 534-545
PHIGANS study
1-25% of cortex area with ci/ct
26-50% of cortex area with ci/ct
>50% of cortex area with ci/ct
no ci/ct
80
60
40
20
0 0 1 2 3
freq
uenc
y
0 1 2 3
60
50
40
30
20
10
0
freq
uenc
y
in 1-25% ofglomeruli
In 25-50% of glomeruli
In >50% ofglomeruli
PHIGANS study: distribution of pathological
grades according to the Haas and Japanese
classifications
Haas classification
Fre
qu
en
cy
Japanese classification
Fre
qu
en
cy
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
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 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)
P
0.04,
NS
0.16
P=0.008
0.03
NS
Endocapillary hypercellularity (OX-E)
P
0.04
NS
0.11
NS
0.12
NS
Segmental glomeruloscelrosis (OX-S)
P
0.07
NS
0.18
NS
-0.22
P=0.016
Tubular atrophy/interstitial fibrosis (OX-T)
p
0.17
NS
0.18
P=0.05
-0.43
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
KI (2009) 76: 534-545
Active lesions/grading MAP Proteinuria eGFR
Mesangial hypercellularity
p
0.21
0.03
0.06
NS
-0.04
NS
Endocapillary hypercellularity
p
-0.008
NS
0.1
NS
0.14
NS
Glomerular necrosis (0-3)
p
-0.03
NS
0.005
NS
-0.12
NS
Cellular crescents (0-3)
p
0.08
NS
0.33
0.0003
-0.24
0.009
G sum
p
0.14
NS
0.27
0.003
-0.12
NS
G index
p
0.14
NS
0.27
0.0031
-0.12
NS
Total inflammation
p
0.21
0.02
0.25
0.006
-0.27
0.0031
Correlations between the clinical parameters (at Bx) and histopathological variables according to
PHIGANS
Chronic lesions/staging MAP Proteinuria eGFR
Global glomerulosclerosis (0-3)
P
0.2
0.03
0.23
0.01
-0.43
<0.0001
Segmental glomerulosclerosis (0-3)
P
0.16
NS
0.36
<0.0001
-0.3
0.001
Fibrotic crescents (0-3)
P
0.12
NS
0.19
0.04
-0.09
NS
Interstitial fibrosis
p
0.21
0.02
0.27
0.0035
-0.09
NS
Tubular atrophy
p
0.2
0.03
0.25
0.0058
-0.44
<0.0001
St sum
p
0.26
0.006
0.37
<0.0001
-0.48
<0.0001
St index
p
0.26
0.006
0.37
<0.0001
-0.48
<0.0001
Biopsy index
p
0.23
0.01
0.35
<0.0001
-0.35
<0.0001
Correlations between the clinical parameters (at Bx) and histopathological variables according to
PHIGANS
MAP Proteinuria eGFR
HAAS classification
p
0.15
NS
0.24
0.01
-0.31
0.0007
Japanese classification
p
0.23
0.01
0.33
0.0002
-0.37
<0.0001
PHIGANS study: correlations between the clinical parameters (at Bx) and histopathological variables defined according to the Haas and Japanese
classifications
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).
Results of the statistical analysis
Relation between the clinical variables (at Bx) and the outcome defined as eGFR<60 ml/min by the end of FU
- univariate analysis
VariablesCox Regression Model
HR CI 95% p
Nephrotic syndrome 3.3 1.4-1.9 0.006
Nephritic syndrome 2.0 1.0-4.0 0.036
Age 33-71 vs 15-32 2.5 1.1-5.0 0.025
Serum creatinine 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
BMI
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
Relation between histopathological variables and the outcome defined as eGFR<60 ml/min by the end of FU
- a univariate analysis
VariablesCox Regression ModelHR 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
ci 2 vs 0 36.7 4.6-291 0.001
1 vs 0 8.4 1.1-65 0.041
Ti 1 vs 0 3.3 1.3-8 0.011
ST index1.2-2.2 vs 0-0.6 10 3.3-50 0.001
1.2-2.2 vs 0.7-1 5 2.5-10 <0.001
Biopsy index3.1-5.7 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
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
PARAMETERS included in the
multivariate regression model
(AIC:267.2 222.7)
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
Cox regression model
freq
uen
cy
OX-T GFR 16-69 GFR 70-94
vs 95-208 vs 95-208
PARAMETERS included in the
multivariate regression model
(AIC:267.2 215.6)
Multivariate analysis,
Cox regression model
HR 95% CI p
Ct 2 vs 0 49.2 2.9-847.5 0.007
Ct 1 vs 0 19 1.1-318.4 0.04
GFR 16-69 vs 95-208 32.1 3.5-298.2 0.002
GFR 70-94 vs 95-208 7.0 0.7-72.5 0.1
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
Ct2 vs ct0 ct1 vs ct0 GFR 16-69 GFR 70-94 vs 95-208 vs 95-208
Cox regression model
HR
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).
Results of the statistical analysis
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
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).
Results of the statistical analysis
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
Variables
Cox Regression Model
HR CI 95% p
Nephrotic syndrome 7.2 2.1-24.3 0.001
Serum creatinine 1-4 vs 0.49-0.98 10 1.7-100 0.015
GFR 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 3.1-5.7 vs 0-1.6 9.1 1,11-90.9 0.02
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
PARAMETERS included in the
multivariate regression model
(AIC: 76,8 73.5)
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
Cox regression model
HR
OX-T GFR 16-69 GFR 70-94
vs 95-208 vs 95-208
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.
variables
Cox Regression Model
≥50% of eGFR loss or ESRD
(p)
GFR< 60 mil/min
(p)
Haas Class 5 vs 1 NS NS
Class 4 vs 1 NS NS
Class 3 vs 1 NS NS
Class 2 vs 1 NS NS
Japanese Class 4 vs 1 NS 0.05
Class 3 vs 1 NS NS
Class 2 vs 1 NS NS
Relation between Haas as well as Japanese classifications
and the outcome – univariate 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).
Results of the statistical analysis
Relation between clinical parameters (at Bx) and the rate of GFR loss (dGFR)
- linear regression, univariate analysis
P=0.06 P<0.0001
dG
FR
GFR at the time of Bx
Cellular crescents
dG
FR
Relation between clinical parameters (at Bx) and the rate of GFR loss (dGFR)
- linear regression, univariate analysis
P=0.03
IS therapyd
GF
R
Relation between the activity/stage of the IgAN according to Haas class. and the rate of GFR loss
(dGFR) - linear regression, multivariate analysis
P=0.04
0.002IS therapy
<0.001GFR
0.04Haas classification
p
Parameters in the
best model (AIC:
782.48) with Haas
classification
dG
FR
Haas classification
Relation between the activity/stage of the IgAN according to Japanese classification and the rate of
GFR loss (dGFR) - linear regression, multivariate analysis
P=0.02
0.004IS therapy
<0.00
1
GFR
0.02Japanese classification
p
Parameters in the best
model (AIC: 787.8) with
the Japanese
classification
Japanese classification
dG
FR
Relation between clinical as well as Oxford’s histop. variables and the rate of GFR loss (dGFR)
linear regression, multivariate analysis
Parameters in the best model (AIC: 795 )
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 <0.0001 P=0.04
OX-T
dG
FR
Relation between clinical as well as PHIGANS variables and the rate of GFR loss (dGFR)
linear regression, multivariate analysis
Parameters in the best model (AIC: 792 )
p
Biopsy index 0.002
IS therapy 0.004
GFR <0.0001
dG
FR
Biopsy index
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?