Abstract
Objective: To
determine the histopathological patterns of glomerulonephritis according to the
clinical presentation.
Methods: This
is a retrospective analysis of light microscopy results of native kidney
biopsies done during the period of January 1st, 2005 until December 31st, 2008. There
were 273 native kidney biopsies performed during this period. Data were
collected from the computer data base of Princess Iman Research and Laboratory Center,
King Hussein
Medical Center,
Amman, Jordan. All biopsies were examined
by our renal histopathologist.
Results: The
most common indication was nephrotic syndrome and the most common cause of
nephrotic syndrome in our patients was membranous glomerulonephritis. The main
cause of subnephrotic proteinuria was minimal change disease and focal and
segmental glomerulosclerosis. Membranoproliferative glomerulonephritis was the
most frequent finding in patients presenting with microscopic hematuria. In
acute nephritis the most common lesions were crescentic, diffuse proliferative
and necrotizing glomerulonephritis. Acute tubular necrosis was the most common
cause of acute kidney injury. Changes of end stage kidney disease were the most
frequent findings in patient with chronic kidney disease. In patients with
systemic lupus erythematosus with renal involvement, the most common lesion was
class IV lupus nephritis.
Conclusion:
Kidney biopsy is an extremely helpful
investigation and it should be performed once indicated. There is a need for a national registry of
kidney biopsies. The histopathological findings are similar to other studies
done in Jordan
and in the neighboring countries.
Key
words: Chronic kidney disease,
Diagnostic procedure, Glomerulonephritis, Kidney biopsy
JRMS
June 2010; 17(2): 5-11
Introduction
Glomerulonephritis (GN) is one of the leading causes
of chronic kidney disease (CKD) and end stage renal disease (ESRD). GN has been
found as the second most common cause of CKD in north of Jordan, the
first being diabetes mellitus.(1) The etiologies of
glomerular insults vary, but include systemic disorders, hereditary diseases,
drugs and toxins besides primary glomerular pathologies.
Accurate
diagnosis of glomerular diseases depends on histopathological examination of
kidney biopsy.
|
Table I. Presentation categories of the study group
|
|
No. of Patients
|
%
|
|
Proteinuria
|
139
|
50.9
|
|
SLE
|
38
|
13.9
|
|
Abnormal KFT
|
53
|
19.4
|
|
Acute Nephritis
|
21
|
7.7
|
|
Hematuria
|
12
|
4.4
|
|
ARF
|
9
|
3.3
|
|
Kidney Donor
|
1
|
0.4
|
|
Total
|
273
|
100
|
|
Table II. Demographic data of the patients
|
Number of patients
|
273
|
|
Male:
Female:
|
134 (49 %)
139 (51%)
|
|
Age: (years)
Range
Average
SD
|
14 - 75
35.36
14.07
|
|
In a patient with renal disease, kidney biopsy
provides tissue that can be used to determine the diagnosis, indicate the
etiology, predict the prognosis, and direct therapy.(2,3,4)
Kidney biopsy is a core procedure in the nephrology
practice. Confidence and competence in
performing this procedure should be one of the goals of training in nephrology,
as in the majority of nephrology training centers in the United States.(5)
Kidney biopsy is indicated in a patient with renal disease when all
the three of the following conditions are met.(6)
1. The cause cannot be determined or
adequately predicted by less invasive diagnostic procedures.
2. The signs and symptoms suggest
parenchymal disease that can be diagnosed by histopathological evaluation.
3. The differential diagnosis includes
diseases that have different treatment, different prognosis or both.
In order for golmerular lesion to be diagnosed with
confidence, kidney biopsy should be adequate (containing six or more glomeruli
for light microscopy). The results of kidney biopsy will help in studying the
natural history of glommerular diseases, identify the patients at risk, and predict
their prognosis.(6)
We present our experience during four years to report
the findings and to compare with previous national, regional and international
studies.
Methods
This is a retrospective analysis of light microscopy
results of native kidney biopsies performed for adult patients in King Hussein
Medical Center,
Amman, Jordan, during the period from January
2005 to December 2008. There were 273 native kidney biopsies.
The results of light microscopy examination of these
biopsies were collected from the computer data base of Princess Iman Research
and Laboratory Center,
King Hussein
Medical Center,
Amman, Jordan. All the biopsies were
examined by our renal histopathologist.
Patients presenting with proteinuria whether nephrotic
(3.5gm or more of urinary proteins per 24 hour), or subnephrotic (less than
3.5gm of urinary proteins per 24 hour) and / or hematuria, unexplained acute
kidney injury, nephritic presentation, or those with unexplained abnormal renal
function were investigated by kidney biopsy. (see Table I)
Patients scheduled for kidney biopsy were admitted to
the hospital at least one day prior to the procedure. Blood pressure and coagulation profile were
deemed normal before the biopsy. The
procedure was performed by an experienced nephrologist under ultrasonograghic
guidance.
Indications for kidney biopsy were:
1. Nephrotic syndrome.
2. Persistent sub-nephrotic proteinuria.
3. Unexplained abnormal kidney function
test.
4. Acute kidney injury.
5. Acute nephritic presentation.
6. Hematuria (after excluding urological
causes).
7. Assessment of serologically confirmed
systemic lupus erythematosus with renal involvement.
8. Evaluation of kidney donor.
A standard procedure in our center is to have three specimens
from each patient for light microscopy, immunoflourescene and electron
microscopy.
Post biopsy, patients were observed for at least 24
hour for vital signs monitoring, development of persistent hematuria and documentation
of their hematocrit level.
Kidney biopsy was not performed for patients with
known cause of renal pathology, i.e. diabetic patients with microvascular
complications, patients with resolving acute kidney injury secondary to
specified causes (medications, prerenal or postrenal causes), furthermore
kidney biopsy
was not performed for patients with contraindication for kidney biopsy such as:
1. Uncorrectable bleeding diathesis
2. Small kidneys (less than 9 cm in length)
3. Multiple bilateral renal cysts or any space occupying lesion (tumor)
4. Significant hydronephrosis
5. Active urinary tract infection
6. An uncooperative patient
7. Solitary kidney
8. Uncontrolled hypertension
Table III. Clinical indications for kidney biopsy
|
|
Male
|
Female
|
Total
|
|
|
Number
|
Age years
Average (SD)
|
Number
|
Age years
Average (SD)
|
Number
|
Age years
Average (SD)
|
|
Nephrotic Syndrome
|
53
|
35.7 (12.6)
|
48
|
36.4 (12.5)
|
101
|
36 (12.5)
|
|
Sub nephrotic proteinuria
|
22
|
36.8 (16.4)
|
16
|
34.8 (14.5)
|
38
|
35.9 (15.4)
|
|
Abnormal KFT
|
30
|
40.6 (15.5)
|
23
|
35.7 (14.2)
|
53
|
38.05 (15)
|
|
Microscopic hematuria
|
8
|
36.5 (17.9)
|
4
|
44 (16.4)
|
12
|
39 (17.7)
|
|
Nephritic syndrome
|
13
|
34.3 (16.2)
|
8
|
31.4 (17.5)
|
21
|
32.4 (15.8)
|
|
Acute renal failure
|
4
|
57 (6.8)
|
5
|
29 (5.2)
|
9
|
41.4 (15.7)
|
|
SLE
|
4
|
33 (11.2)
|
34
|
25.8 (8.2)
|
38
|
26.5 (8.7)
|
|
Evaluation of kidney donor
|
--
|
--
|
1
|
37
|
1
|
37
|
|
Total
|
134
|
|
139
|
|
273
|
|
Results
A total of 273 native kidney biopsies were performed
during the period between January 2005 and December 2008. Female patients were
139 (51%), and age range was 14 – 75 years, with an average of 35.3 years (SD+\-14).
Table II summarizes the patients’ demographic data.
The most frequent indication for the biopsy was
proteinuria found in 139 patients (50.9%), and 101 (72.7%) of these had
nephrotic syndrome. Hematuria was the indication for kidney biopsy in 13
patients (4.8%). One of them was a potential kidney donor for her son, found to
have microscopic hematuria.
Patients with unexplained chronic kidney disease were
53 patients (19.4%), while 21 patients (7.7%) presented with a picture of acute
nephritis. Renal involvement in systemic lupus erythematosus (SLE) was the indication in 38 patient (13.9%) and
unexplained acute renal failure was the indication in nine patients (3.3%) (see
Table III).
Some patients had more than one indication for kidney
biopsy (e.g. proteinuria and hematuria, or proteinuria and impaired kidney
function). Those were put in a group according to the main presenting symptom.
Patients who presented with acute nephritis were the
most serious ones, whether according to clinical picture or to the biopsy
results. Those were 21 patients, 13 males (62%) and eight females (38%). Their
age ranged from 14 to 70 years, with an average of 33.19 years (SD+\-16.2). Their
biopsy results are shown in Table IV.
Patients with unexplained acute kidney injury for whom
kidney biopsy was performed (other than those who presented with acute
nephritis) were nine patients; there were five females (55.6) and four males
(44.4). Their age ranged from 21 to 67 years, with an average of 41.4 year (SD+\-15.8).
Biopsy results are shown in Table V.
Kidney biopsy was done for 13 patients with hematuria
after systemic and urological causes were excluded. There were eight males
(61.5%) and five females (38.5%). Their age ranged from 21 to 75 years with an
average of 39 years (SD+\-17.7). Results of kidney biopsies are shown in Table VI.
Patients presented with unexplained deterioration of
kidney function (chronic kidney disease) with preserved kidney morphology on
ultrasound evaluation were 53 patients, 30 males (56.6%) and 23 females
(43.4%). Their age ranged from 18 to 72 years with an average of 38.5 years (SD
+\-15). Histopathological findings of their kidney biopsies are shown in Table VII.
The majority of the patients presented with nephrotic
syndrome. They were 101 patients, 53 male (52.5%) and 48 female (47.5%). Their
age ranged from 14 to 72 years, with an average of 36 year (SD +\-12.5).
Histopathological findings of their kidney biopsies are shown in Table VIII.
Patients with subnephrotic proteinuria were 38, males
were 22 (57.9%), and females were 16 (42.1%). Age range was 15-70 years, with
an average of 36.4 years (SD+\-15.9).
|
Table IV. Histopathological lesions in patients presenting
with acute nephritis
|
|
No. of Patients
|
%
|
|
Crescentic GN
|
5
|
23.8
|
|
Diffuse proliferative GN
|
5
|
23.8
|
|
Necrotizing GN
|
5
|
23.8
|
|
MPGN
|
2
|
9.5
|
|
Post infectious GN
|
3
|
14.3
|
|
Scleroderma renal crisis
|
1
|
4.8
|
|
Total
|
21
|
100
|
|
Table V. Histopathological lesions in patients presenting
with unexplained acute renal failure
|
|
No. of Patients
|
%
|
|
ATN
|
4
|
44.44
|
|
Resolving ATN
|
2
|
22.22
|
|
Myeloma kidney
|
3
|
33.33
|
|
Total
|
9
|
100
|
|
|
Table VI. Histopathological
lesions in patients presenting with hematuria
|
|
No. of Patients
|
%
|
|
Hypertensive changes
|
1
|
8.3
|
|
IgA nephropathy
|
3
|
25
|
|
MPGN
|
4
|
33.3
|
|
Normal findings
|
2
|
16.7
|
|
Post infectious GN
|
1
|
8.3
|
|
Inadequate specimen
|
1
|
8.3
|
|
Total
|
12
|
100
|
|
Table VII. Histopathological lesions in patients presenting
with chronic kidney disease
|
|
No. of Patients
|
%
|
|
Amyloidosis
|
1
|
1.9
|
|
Chronic GN
|
6
|
11.3
|
|
ESRD
|
23
|
43.4
|
|
Diabetic nephropathy
|
1
|
1.9
|
|
FSGS
|
5
|
9.4
|
|
Hypertensive changes
|
4
|
7.5
|
|
MPGN
|
6
|
11.3
|
|
Interstitial nephritis
|
2
|
3.8
|
|
Ischemic nephropathy
|
1
|
1.9
|
|
Myeloma kidney
|
1
|
1.9
|
|
Inadequate specimen
|
3
|
5.7
|
|
Total
|
53
|
100
|
|
Histopathological findings of their kidney biopsies
are shown in Table IX.
Kidney
biopsy was done for 38 patients with newly diagnosed systemic lupus
erythematosus (SLE) for various indications (acute renal failure, proteinuria,active
urinary sediment). They were 34 females (89.5%) and four males (10.5%). Their age range was 14-55 years, with an
average of 26.5 years (SD+\-8.7). Histopathological findings of their kidney
biopsies are shown in Table X.
Inadequate specimens were obtained in 12 (4.4%)
biopsies out of the total number of our series. These biopsies were either
containing less than six glomeruli, or containing renal medullary tissue, or
non renal tissue. Patients whom biopsies were inadequate were biopsied again
with satisfactory results.
The most common complication of the procedure was pain
at the biopsy site, seen in 53 patients (19.8%). Significant drop in the hematocrit (more than 3% drop from the base line
hematocrit) was seen in three patients (0.01%), one of those three patients
developed gross hematuria, requiring blood transfusion, and none needed any
further intervention apart from ultrasonographic follow up, which showed
subcapsular hematoma that was treated conservatively. None of the patients
developed life threatening complications or loss of renal tissue.
Discussion
Glomerular lesions
manifest clinically
as proteinuria,
hematuria, fluid retention, hypertension, progressive loss of kidney function
of variable severity, or a combination of all these presentations, and occasionally
it may be asymptomatic.
Our purpose was to outline the type of variable
glomerular diseases among patients presented or referred for nephrology care or
opinion at King Hussein Medical
Center. Analysis of the data was done according to
the main presenting symptoms and the main indication for biopsy.
There were 273 adult kidney biopsies during the period
between 1st of January, 2005 until 31st of December,
2008. Surgical specimens, transplant and pediatric kidney biopsies were
excluded.
The largest number of patients for whom kidney
biopsies were performed, were those presenting with the nephrotic syndrome.
These were 101 patients (37%) and this was almost the same percentage as in
previous similar national,(7,8) regional(9)
and international(10,11) studies. This reflects a fairly
common presentation and the
necessity of tissue diagnosis in the management of the nephrotic syndrome. The main histopathological finding was membranous glomerulonephritis (MGN), followed by minimal change disease (MCD), then by focal and segmental glomerulosclerosis (FSGS). These glomerulonephritis are the main causes of the nephrotic syndrome which is similar to what has been described before(7-12) but with a different profile. In some studies the predominant lesion was MCD,(12) while in other it was FSGS.(8,9) However our results are similar to previous finding in Jordan(7) and in Iran.(10)
|
Table VIII. Histopathological lesions in patients presenting
with nephrotic syndrome
|
|
No. of Patients
|
%
|
|
Amyloidosis
|
4
|
3.9
|
|
MCD
|
23
|
22.8
|
|
Membranous GN
|
36
|
35.8
|
|
Diabetic nephropathy
|
6
|
5.9
|
|
FSGS
|
22
|
21.8
|
|
MPGN
|
6
|
5.9
|
|
Post infectious GN
|
1
|
0.9
|
|
Inadequate specimen
|
3
|
2.9
|
|
Total
|
101
|
100
|
|
Table IX. Histopathological lesions in patients presenting
with subnephrotic proteinuria
|
|
No. of Patients
|
%
|
|
Amyloidosis
|
2
|
5.3
|
|
MCD
|
6
|
15.8
|
|
Membranous GN
|
5
|
13.1
|
|
Diabetic nephropathy
|
1
|
2.6
|
|
FSGS
|
6
|
15.8
|
|
Hypertensive changes
|
6
|
15.8
|
|
Interstitial nephritis
|
3
|
7.9
|
|
Inadequate specimen
|
2
|
5.3
|
|
MPGN
|
3
|
7.9
|
|
ESRD
|
1
|
2.6
|
|
Focal proliferative GN
|
1
|
2.6
|
|
Normal
|
2
|
5.3
|
|
Total
|
38
|
100
|
|
|
Table X. Histopathological
lesions in patients presenting with SLE
|
|
No. of Patients
|
%
|
|
Normal
|
1
|
2.6
|
|
Class II
|
2
|
5.3
|
|
Class III
|
7
|
18.4
|
|
Class IV
|
18
|
47.4
|
|
Class V
|
6
|
15.8
|
|
Class VI (ESRD)
|
1
|
2.6
|
|
Inadequate specimen
|
3
|
7.9
|
|
Total
|
38
|
100
|
|
Patients presented with subnephrotic proteinuria
comprised 13.9% of the sample. Their biopsy results showed the main glomerular
lesions as MCD, FSGS and
hypertensive changes as the predominant causes followed by MGN. This is broadly
similar to the etiology of the nephrotic syndrome with a different pattern of
frequency. The mechanism of glomerular injury and proteinuria is similar in the
same disease that may produce nephrotic or subnephrotic proteinuria, the
difference may be due to functional and other associated glomerular insults,(9,13)
or the presence of other co morbid conditions.
Abnormal kidney function test (KFT)
was the indication in 19.4% of the patients. This may represent a selection
bias as patients presenting with known causes of CKD or those who were found to
have small kidneys were not biopsied. However, the primary pathology of
patients presenting with CKD would be of interest, even in patients requiring
renal replacement therapy. This is of particular importance knowing that
certain glomerular pathologies may recur after kidney transplantation. Almost
in half of our patients the glomerular disease was identified. The most common
pathologies identified were MPGN, FSGS and hypertensive nephrosclerosis. This
finding is the same as what has been described in Jordan.(7)
Patients with hematuria (macroscopic or microscopic) not
secondary to urological causes comprised 4.8% of the study group. This is
similar to previous data.(9) MPGN and IgA nephropathy were
the most common causes of glomerular hematuria among our patients. MPGN was the
predominant cause in an Asian study(14) while IgA nephropathy
was the predominant cause in Europe.(15) As compared to the
total number of biopsies performed, those patients with IgA nephropathy are
1.4%, similar to what was reported in Jordan,(1) probably
reflecting high threshold to perform kidney
biopsy in patients
with isolated hematuria.
Our single case of kidney biopsy for a prospective
kidney donor was for a 42 year old healthy female found to have microscopic
hematuria during pre kidney donation for her 10-year old son. All her
investigations were normal including renal angiogram and cystoscopy. Her kidney
biopsy was normal. She donated a kidney for her son and follow up showed normal
kidney function for both of them. (Our study examines only the results of light
microscopy)
Patients’ presenting with the frank nephritic syndrome
were categorized separately from those presenting with acute kidney injury due
to non nephritic causes. This is due to the nature of the glomerular
pathologies leading to nephritic syndrome, which is considered as the most
aggressive of renal diseases requiring advanced and aggressive management.
Nephritic syndrome was the indication in 7.7% of our
patients. As expected, the majority of these cases turned to have aggressive
forms of GN. The most frequent ones were crescentic GN, diffuse proliferative
GN, and necrotizing GN (vasculitis). Similar results, similar age group but
with a greater percentage of patients has been described in other studies.(9,16)
The lower percentage of patients in our study can be attributed to the separation
of patients presenting with the nephritic syndrome from those with non
nephritic acute renal failure. In these cases, it was proved beyond any doubt
that kidney biopsy is an extremely valuable diagnostic procedure in patients
presenting with rapidly declining kidney function, as the early and aggressive
management is highly rewarding.
Acute kidney injury due to non nephritic presentations
was the indication in only 3.3% of patients, probably reflecting selection
bias, as kidney biopsies were performed for patients who did not respond or
showed sluggish response to conventional management to acute kidney injury.
Acute tubular necrosis was the major cause, strikingly
in one third of acute kidney injury cases the cause was myeloma kidney. The
renal involvement in multiple myeloma varies and can be due to many causes and
it has been reported that multiple myeloma may present itself as ARF.(17-20)
Multiple myeloma was mentioned as a cause of CKD in Jordan.(7)
This may represent late referral to nephrology care or unawareness of the
patients of the slow development of the disease process of multiple myeloma
until presenting as renal failure.
Kidney biopsies were performed in 38 patients with
serologically confirmed SLE with
evidence of renal involvement. Renal involvement in SLE
is most likely to occur on its own and these patients need more close follow up
than those without renal involvement.(21) Kidney biopsy in SLE patients with any criteria of renal involvement
was of major benefit as almost half of our lupus patients proved to have the
aggressive class IV lupus nephritis. The management of lupus nephritis is
entirely dependent on histological diagnosis to classify the lesion according
to the International Society of Nephrology/Renal Pathology Society lupus
nephritis classification(22) which carries diagnostic, therapeutic
and prognostic criteria.(23) This was the case with our SLE patients, as in order to reverse or at least retard
the aggressive presentation, aggressive management including immune –
modulating therapy(24-27) was indicated.
Conclusion
Kidney biopsy is an extremely helpful investigation in
the hands of nephrologists. Certainly, it should be performed only when
indicated, and if there are no contraindications. The findings in our study are
similar to previous local and regional studies. In some aspects our findings
differ from those of other international studies, probably due to demographical
or environmental factors. A national registry for kidney biopsy is needed to
determine the frequency of various glomerulonephritis which may help to prevent
or delay the development of advanced stages of CKD.
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