THE OXFORD CLASSIFICATION
OF IgA NEPHROPATHY: SINGLE
CENTRE EXPERIENCE
Petrusevska G., Jasar G., Grcevska
L., Kostadinova S., Bogdanovska
M.*, Nikolov V., Polenakovic M.
Macedonia
INTRODUCTION
 The diagnosis of IgA nephropathy, the commonest
glomerular disease worldwide, is defined by the
presence of mesangial IgA-dominant immune deposits
within glomeruli in the absence of systemic
disorders1,2,3,4,6.
 This criterion is the reason for a wide range of
histological changes in IgA nephropathy (IgAN) and a
different outcome of the renal disease 1,5,7.
INTRODUCTION
 Biopsy appearances may range from:
 normal glomeruli by optical microscopy;
 severe crescentic glomerulonephritis;
 sclerosing glomerulonephritis.
 Some biopsies present dominant diffuse mesangial
proliferation and the other focal proliferative changes
with different degrees of tubulointerstitial changes.
INTRODUCTION
 Thus many authors in the past tried to make a
usefull classification, comparing the
histopathological findings with clinical features and
the outcome of the disease7,8,9,10.
 None has achieved widespread acceptance,
because of a lack of definitions, and inclusion of
both active and chronic lesions in the definitions of
single categories.
 There is continuing discussion as to wheather
pathological features seen on renal biopsy
contribute additional prognostic information in
addition to the clinical features.
INTRODUCTION
 The aim of the new Oxford classification 11,12,13 was to
identify specific pathological features that can predict
the risk of progression of renal disease in IgAN.
 Six of the pathological variables were identified as
having an independent value in predicting renal
outcome: 1) the mesangial hypercellularity score;
percentage of glomeruli showing, 2) segmental
sclerosis, 3) endocapillary hypercelullarity or 4)
cellular/fibrocellular crescents;5) percentage of tubular
atrophy/interstitial fibrosis and 6) arteriosclerosis score.
 These features were recommended to be taken into
account for predicting an outcome independent of the
clinical features both at the time of presentation and
during follow-up.
AIMS
 The aim of our study was:
 To define the presence of the histopathological
variables recommended by Oxford classification in
Macedonian patients with diagnosed IgAN.

To corelate the value of these pathologic variables
and outcome of the disease in this group of
patients with IgAN.
 To determine the survival in two groups of patients:
those with nephrotic syndrome (defined as
proteinuria> 3g/daily) and immunosupression and
the other group of patients, with mild clinical
features and without immunosupression.
PATIENTS AND METHODS
 The study had a retrospective character on cases with
biopsy-proven IgAN at the Institute of pathology and
Laboratory for cytology and histopathology, Institute
of oncology, Medical faculty in Skopje, admitted at the
University Nephrology Department.
 Histological variables were analysed according to the
histopathological reports because of long period
survey analysis.
 The diagnosis of IgAN includded: 1) demonstration of
mesangial IgA deposition by DIF in isolation or as the
predominant immunoglobulin and the lack of clinical
or serological evidence of systemic lupus
erythematosus, Henoch-Scoenlein purpura, or liver
disease; 2) standard histological analysis of the renal
biopsies on HE, PAS, Trichrome Mason,
Silvermethenamine-Jones stained sections; and 3)
Electron microscopy performed in 6% of the patients,
and semithin sections in about 70%.
SELECTION OF THE PATIENTS
 Histopathological reports and the clinical data at
the onset and during follow-up were obtained from
the in-patient and out-patient files of the patients at
the University Nephrology Department which
covers renal disease patients in all area of R.
Macedonia (about 2,000,000 people).
 Ninety eight adult patients were classified as having
IgA nephropathy during the period 1976-2006.
 40 adult patients (25 male, 15 female,>15 years)
were selected for the study, patients with more than
10 glomeruli at optical microscopy and with a
follow-up of more than 3 years.
 We used four pathological variables proposed by
the Oxford Classification as it is presented in Table
1.
Table 1.: Definition of pathological variables used in the classification of IgAN.
Variable
Definition
Score
M0=<5
Mesangial hypercelullarity
The score is the mean score for
all glomeruli
M1>5
Segmental
glomerulosclerosis
Any amount of the tuft involved in
S0 – absent
sclerosis, but not involving the
whole tuft
S1 - present
Endocapillary
hypercelullarity + cellular/
/fibrocellular crescents
Hypercelullarity due to increased
number of cells within glomerular E0 – absent
capillary lumina
E1 - present
Tubular atrophy/interstitial
fibrosis
Percentage of cortical area
involved by th tubule atrophy or
interstitial fibrosis, whichever is
greater
0-25% = T0
26-50%= T1
>50% = T2
Statistics
 Statistics included:
 Student`s T test, Spearman`s test and Mann-Whitney U
Wilcoxon test to compare histological scoring and
duration of follow-up without end-stage renal disease.
 Histopathological score and survival were compared
separately 1) in all 40 patients, independently of clinical
signs and treatment; 2) 12 patients with nephrotic
syndrome (defined as proteinuria> 3g/daily) and
immunosupression were analysed separately, and 3) the
other 28 patients, with mild clinical features and without
immuniosupression, were also analysed separately.
 The Kaplan-Mayer test was performed to determine the
survival of the patients.
Table 2: RESULTS: Histological findings in whole group of 40 pts
Histological changes in IgAN
No. of
ESRD
ESRD
Mesangial hypercelullarity (MH)
4/8
8 years
Segmental glomerulosclerosis (SGS)
1/2
6 years
Endocapillary hypercelullarity (EH)
0/2
-
Tubular atrophy/interstitial fibrosis
0
-
MH +SGS
6/9
5.2 years
MH + SGS + TA/IF
2/2
3 years
MH + EH
2/4
6.5 years
MH + SGS +EH
2/2
7 years
MH + SGS + EH + TA/IF
2/2
4.5 years
Slightly increased mesangial celullarity
1/9
12 years
RESULTS: Overall survival of the whole group of 40 pts)
 The average survival of the whole group was 10.8+/7.47 years (M+/-SD).
 Twenty from forty (50%) of the patients experienced
end stage renal disease after a period of 3-12 years.
 Pathological variables and follow-up of all 40
patients according to the recommendation of the
Oxford classification are presented at Table 3.
 Mesangial hypercelullarity was confirmed to be
associated with the renal outcome (p=0.047), as
well as glomerular sclerosis (p=0.009),
endocapillary hypercellularity (p=0.001) and tubular
atrophy/interstitial fibrosis (p=0.045)
Table 3: Influence of the histological variables to the renal outcome
Variable
Score
ESRD
p
Mesangial hypercelullarity
M0=<5 = 13 pts
2 pts
P=0.047
M1>5 = 27pts
18 pts
S0 – absent = 23 pts
7 pts
S1 – present = 17 pts
13 pts
E0 – absent = 30 pts
13 pts
E1 – present = 10 pts
6 pts
T0 = 0-25% = 36 pts
16 pts
T1 = 26-50% = 4 pts
4 pts
T2 >50% = 0 pts
0
Segmental
glomerulosclerosis
Endocapillary
hypercelullarity
Tubular atrophy/interstitial
fibrosis
P=0.009
P=0.001
P=0.045
Results of Group I patients (without nephrotic syndrome)
 This group consisted of 28 patients with clinically
normal renal function, without hypertension and
nephrotic syndrome at presentation. Thirteen from 28
(46.1%) of these patients, in contrast to mild clinical
features at presentation, presented end-stage renal
disease during follow up.
 Mesanagial hypercelullarity didn`t correlate with renal
survival in this separated group of patients (p=0.053
Mann Whitney, p=0.49 Spearman test). Segmental
glomerulosclerosis significantly correlated with the
outcome of the disease (p=0.007 Mann Whitney, p=0.006
Spearman test). Endocapillary hypercelullariry (p=0.351,
p=0.32) as well as tubular atrophy/interstitial fibrosis
(p=0.071, p=0.105) did not correlated with the renal
outcome.
Table 3: Influence of the histological variables to the renal outcome
Variable
Score
ESRD
p
Mesangial hypercelullarity
M0=<5 = 11pts
2 pts
p=0.053
M1>5 = 17 pts
11 pts
p=0.49
S0 – absent = 18 pts
5 pts
p=0.007
S1 – present = 10 pts
8 pts
p=0.006
E0 – absent = 25 pts
10 pts
p=0.351
E1 – present = 3 pts
2 pts
P=0.032
T0 = 0-25% = 27 pts
12 pts
p=0.071
T1 = 26-50% = 1 pts
1 pts
p=0.105
T2 >50% = 0 pts
0
Segmental
glomerulosclerosis
Endocapillary
hypercelullarity
Tubular atrophy/interstitial
fibrosis
Results of Group II patients (with nephrotic syndrome)
 Group II consisted of 12 patients with severe clinical
features at presentation and necessary
immunosuppression.
 Seven from 12 (58.3%) developed terminal phase of
chronic renal failure during follow-up.
 Renal survival was not associated with mesangial
hypercelullarity (Man Whitney p=0.606, Spearman test
p=0.607); with glomerular sclerosis (p=0.343, p=0.302)
and endocapillary hypercelullarity (p=0.53; p=0.533),
 But it was associated with the degree of chronic
tubulointerstitial changes (p=0.018, p-0.016).
Table 3: Influence of the histological variables to the renal outcome
Variable
Score
ESRD
p
Mesangial hypercelullarity
M0=<5 = 2 pts
0 pts
p=0.606
M1>5 = 10 pts
7 pts
p=0.607
S0 – absent = 5 pts
0 pts
p=0.343
S1 – present = 7 pts
7 pts
p=0.302
E0 – absent = 5 pts
3 pts
p=0.53
E1 – present = 7 pts
4 pts
P=0.533
T0 = 0-25% = 9 pts
4 pts
p=0.018
T1 = 26-50% = 3 pts
2 pts
p=0.016
T2 >50% = 0 pts
0
Segmental
glomerulosclerosis
Endocapillary
hypercelullarity
Tubular atrophy/interstitial
fibrosis
Survival of both groups of patients with IgA nephropathy
 It can be seen that there was noted significant
difference in survival between those two group of
patients.
 Glomerular sclerosis was a poor prognostic pathologic
variable in the patients without nephrotic syndrome, and
tubulointerstitial changes in ones with nephrotic
syndrome.
DISCUSSION
 Many authors have tried to correlate clinical signs and
histological features in IgAN7,8,9,10, 14,15,16.
 Gross hematuria was frequently associated with mild
glomerular lesions and a favourable clinical course; on
the other hand, the presence of heavy proteinuria at the
onset was frequently associated with severe histology
and progressive renal disease.
DISCUSSION
 Severe histology was also associated with already
decreased renal function and/or hypertension at the time
of biopsy. Many authors believe that the histologic type
of glomerular lesions appears to be the best predictive
index in IgAN.
 The folowing factors were regarded as histological
parameters of progressive damage in IgAN: severe
mesangial proliferation, frequent sclerotic glomeruli,
crescents higher proportions of glomerular adhesions,
vascular sclerosis and marked interstitial fibrosis
(8,9,14). They are all causally correlated with each other
in portending a poor prognosis.
DISCUSSION
 Several histologic grading systems have been used in
the past8,17,18. These pathological systems used to
classify renal lesions in IgAN, can be divided into two
groups: lumped and split.
 The lumped systems assess the overall severity of
histological lesions, found in glomerular, tubular,
interstitial and arteriolar compartments, as in the
widely-used classification of Lee and Haas8,18. The split
systems use semiquantitative severity grading of
lesions in each of the four compartments and permit
the elaboration of a global or aggreagate score for each
compartment
DISCUSSION
 Lesions of focal and segmental hyalinosis and
sclerosis were described as very specific for
progression and so in our previous report we measured
the sclerotic glomerular area and combined it with the
semiquantitaive score of the tubulointerstitial changes
in order to predict the progression19.
 In general, the agreement among various
classifications is only reached when considering renal
disease already progressed to sclerosis.
DISCUSSION
 The new Oxford classification11,12,13 documented by
univariate and multivariate analysis that the following
lesions resulted as independently predictive of clinical
outcome: mesangial hypercelullarity score,
endocapillary hypercelullarity, segmental
glomerulosclerosis and tubular atrophy/interstitial
fibrosis. Necrotizing and crescentic lesions were not
evaluated because of their rarity. Our results taking
into consideration only those four histological
variables presented the same results, a higher total
score – a more progressive disease.
 Our group consisted of 40 patients of different age,
different clinical presentations and different treatment
depending on the presence of nephrotic syndrome,
and these four variables proposed by the Oxford
classification were important for the outcome of the
disease.
In memory to

Prof.dr. Georgi Zografski, pathologist, Laboratory for cytology and
histopathology, Institute of Oncology
Geographic position of R. Macedonia
and the church of St. Kaneo in Ohrid
WELCOME in Ohrid, 12-16 October