the oxford classification of iga-nephropathy: a review based on the polish renal biopsy registry...

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



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).



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


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


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).


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

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


freq

uen

cy

OX-T GFR 16-69 GFR 70-94

vs 95-208 vs 95-208



(AIC:267.2 215.6)

Multivariate analysis,


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


Ct2 vs ct0 ct1 vs ct0 GFR 16-69 GFR 70-94 vs 95-208 vs 95-208


HR


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


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).



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




(AIC: 76,8 73.5)

multivariate analysis,


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

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).



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


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?

the oxford classification of iga-nephropathy: a review based on the polish renal biopsy registry...

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patients glomerular

iga nephropathy patients

disease progression

studies glomerular sclerosis

oxford classification

igan histological grading

renal survival

risk of esrd