Pediatr Nephrol
DOI 10.1007/s00467-014-2915-3
ORIGINAL ARTICLE
Urinary CD80 levels as a diagnostic biomarker
of minimal change disease
Chen Ling & Xiaorong Liu & Ying Shen & Zhi Chen &
Jianfeng Fan & Yeping Jiang & Qun Meng
Received: 11 March 2014 / Revised: 16 June 2014 / Accepted: 14 July 2014
# IPNA 2014
Abstract
Background Early diagnosis of minimal change disease
(MCD) in nephrotic syndrome (NS) patients remains chal-
lenging. Doctors often make a diagnosis of MCD using inva-
sive renal biopsy. CD80, a transmembrane protein, is present
on podocytes in a number of experimental models of NS.
Urinary CD80 levels are significantly elevated in MCD but
not in focal segmental glomerulosclerosis (FSGS) or other
glomerulopathies. The purpose of this study was to investigate
the feasibility of using urinary CD80 levels as a biomarker for
the diagnosis of MCD.
Materials and methods A total of 165 subjects, 129 men and
36 women, were enrolled in this study. Urinary samples were
collected from 37 patients with MCD, 27 patients with FSGS,
30 patients with other glomerulopathies, and 71 healthy peo-
ple. Using ELISA, experimental values were compared with
those produced by kidney biopsy samples.
Results The concentration of urinary CD80 was significantly
higher in the active MCD group (689.66±378.21 ng/g creat-
inine) than in the FSGS group (123.49±167. 88 ng/g creati-
nine, P<0.00), other glomerulopathies group (152.37±220.
14 ng/g creatinine, P<0.001) and the control group (81.83±
23.01 ng/g creatinine; P<0.001). A cutoff value of 328.98
(ng/g creatinine) was proposed, with a sensitivity of 81.1 %
and specificity of 94.4 %. The area under the receiver
operating characteristic (ROC) curve for the urinary
Xiaorong Liu and Ying Shen contributed equally to this work and should
be considered as co-corresponding authors
C. Ling : X. Liu (*) : Y. Shen (*) : Z. Chen : J. Fan : Y. Jiang :
Q. Meng
Department of Nephrology, Beijing Children’s Hospital affiliated to
Capital Medical University, West District Nan Li Shi Lu 56th,
Beijing 100045, China
e-mail: desin2000@sina.com
e-mail: 15210938018@163.com
CD80 to diagnose MCD was 0.925 (95 % confidence
interval: 0.873–0.978).
Conclusions This experiment has preliminarily confirmed
urinary CD80 as a non-invasive diagnostic biomarker. It
may have significant value in the diagnosis of MCD.
Keywords MCD . FSGS . CD80 . Children
Introduction
Minimal change disease (MCD) is by far the most
common cause of nephrotic syndrome in children [1].
It accounts for approximately 80–90 % of cases. The
second most common type of nephrotic syndrome in
children is focal segmental glomerulosclerosis (FSGS),
which accounts for 10 % of cases [1]. Most MCD
children who present nephrotic syndrome respond to
corticosteroid therapy, but some are steroid-dependent
or steroid-resistant [2]. In contrast, most patients with
FSGS are relatively resistant to corticosteroid therapy,
which indicates a risk of progression to end-stage renal
disease (ESRD). Other glomerular diseases (such as IgA
nephropathy and membranous nephropathy) can also
present with nephrotic syndrome [1]. However, the
treatment and prognosis for MCD, FSGS, and other
glomerulopathies differ considerably. Currently, the gold
standard for conforming MCD is kidney biopsy. But
this method is invasive and complicated and so rarely
used on inpatient children, especially those seeing a
doctor for the first time [3]. Another method of diag-
nosing MCD would be very useful.
CD80 (also called B7-1) is a transmembrane protein
expressed on the surfaces of B cells and other antigen-
presenting cells. It works as a costimulatory signal and
activates T cells by binding to the receptor CD28. It

also inhibits T cell activation by binding to CTLA-4 [4].
CD80 can be induced to expression on podocytes, caus-
ing actin reorganization and proteinuria [5, 6]. In 2009,
Garin et al. reported significantly higher levels of CD80
in the urine samples of subjects with MCD than in
those in FSGS patients, MCD patients in remission,
and patients with other glomerulopathies [7, 8].
However, this difference has not been confirmed in an
independent patient cohort [9].
Taking the hypothesis that urinary CD80 could be used as a
functional marker for early diagnosis in MCD, the current
study was designed to assess the clinical utility of urinary
CD80 as a diagnostic biomarker when used with ELISA.
This method was compared with kidney biopsy, which is the
conventional method of diagnosing MCD, FSGS, and other
glomerular diseases.
Materials and methods
Patients
A total of 165 subjects, 129 men and 36 women,
participated in this study. They were divided into four
groups, MCD, FSGS, other glomerulopathy, and control
groups. The MCD group contained 37 patients, the
FSGS group 27, the other glomerulopathy group 30
patients (membranoproliferative glomerulonephritis (n=
7), membranous nephropathy (n=5), IgA nephropathy
(n=10), SLE (n=5), acute glomerular nephritis (n=3),
and the control group 71 healthy people. Subjects with
renal dysfunction were excluded (serum creatinine
>1.5 mg/dl or glomerular filtration rate<60 ml/min).
All patients underwent renal biopsy at the Beijing
Children’s Hospital between 2011 and 2013. The indi-
cations for biopsy in the children with MCD were
refractory nephrotic syndrome including steroid-
resistant NS, steroid-dependent NS, and frequent re-
lapse. The diagnoses of various kidney diseases were
based on criteria established by the International Study
for Kidney Diseases in Children [10].
Patients were considered active if they had edema, a
serum albumin level of<3.0 g/dl, and a urinary protein/
creatinine (mg/mg) ratio of>2.0. Patients were consid-
ered to be in remission, if they had no edema and their
urinary protein/creatinine ratio was<0.40 in a random
urine sample.
The present study was approved by the institutional review
board of the Beijing Municipal Science and Technology
Commission and the Capital Medical University Institutional
Review Board. All participants provided written informed
consent before participation.
Pediatr Nephrol
Urine samples
A single and naturally voided midstream urine sample
was obtained prospectively from all subjects. Each urine
sample (20 ml) was directly collected into a sterile
plastic tube and then centrifuged not more than an hour
after collection at 2,000 × g for 10 min at 4 °C to
remove cell debris and particulate matter. It was then
stored at −80 °C for further analysis. All samples were
brought to room temperature before use. All urine sam-
ples were stored for a minimum of 1 day and a maxi-
mum of 1 month before analysis.
Urinary CD80 measurements
Urinary CD80 was measured using a commercially available
ELISA kit (Bender MedSystems, Burlingame, CA, USA).
Urinary creatinine and protein and serum albumin were mea-
sured using an auto-analyzer.
Statistical analysis
For continuous variables with a normal distribution,
descriptive results were presented as mean and standard
deviation (SD). The t test for unpaired samples was
used to analyze the differences between groups. For
continuous variables with a skewed distribution, descrip-
tive results were expressed as a median and a range.
The Mann–Whitney U test and the two-sample
Kolmogorov–Smirnov test were used to evaluate the
differences between groups. Discrete (categorical) vari-
ables were compared using the Chi-squared (χ2) test.
The differences among groups were compared using a
one-way analysis of variance for three groups. A receiv-
er operating characteristic (ROC) curve was constructed
and the area under the ROC curve (AUC) was calculat-
ed to assess the predictive strength. Optimal cutoff
points to maximize both sensitivity and specificity were
also determined. Differences with P values<0.05 were
considered statistically significant. Statistical analysis
was performed with SPSS (version 17.0 for Windows;
SPSS, Chicago, IL, USA).
Results
Clinical characteristics of patients
The clinical characteristics of all patients are shown in Table 1.
Samples from 37 patients with MCD, 27 with FSGS, 30 with
other glomerulopathies, and 71 healthy people were
collected for this ELISA analysis. Analysis of the
Pediatr Nephrol

Table 1 Demographic characteristics of patients with minimal change disease (MCD), patients with focal segmental glomerulosclerosis (FSGS),
patients with other glomerular diseases, and controls

Characteristics MCD group FSGS group Other Control P value

Cases (n) 37 27 30 71
Weight (kg) 21.80±13.96 25.61±9.71 27.90±13.94 24.98±13.06 >0.05
Age (years) 5.9±3.9 6.8±3.8 7.8±3.4 6.1±3.8 >0.05
Gender (n)
Male 31 21 21 56 >0.05
Female 6 6 9 15
Serum albumin (g/dl) 1.6±0.7 2.5±0.9 2.9±0.9 3.8±0.9 >0.05
Up/Uc ratio 6.7±3.6 4.3±6.1 2.7±3.4 1.8±1.8 <0.05
Prednisone 36 27 20 0

Measurement data are presented as the mean±standard deviation

P values refer to comparisons of the MCD and FSGS groups, MCD and other glomerular disease groups, and FSGS and other glomerulopathies groups

patient data showed there to be no statistically signifi- However, there were significant differences in serum
cant differences in the most of clinical characteristics albumin and Up/Uc. Most of the patients in the three
(e.g., age, gender, and weight) among the four groups. experimental groups had taken prednisone or other

Table 2 Characteristics of the patients with focal segmental glomerulosclerosis

Patient Gender Age (years) Serum albumin (g/l) Up/Uc ratio Subtype Dose of prednisone (mg/kg/day) Urinary CD80 (ng/g creatinine)

1 Male 7.9 18.1 4.4 NOS 0.8 128.82

2 Male 7.9 14.2 5.2 NOS 0.65 74.71
3 Female 5.9 24 2.4 Cellular 1.5 10.36
4 Male 2.7 37.9 1.5 Tips None 221.84
5 Male 0.9 19.7 3 NOS 1.4 40.03
6 Male 1.8 21.5 2.4 Tips 0.8 465.74
7 Male 2.8 21.9 2.8 Tips 1.5 163.94
8 Male 3.4 16.8 2.7 Cellular 1.6 33.2
9 Male 2.6 11.3 5 Tips 2 69.56
10 Female 14.6 21.2 3.7 FSGS 1.7 8.71
11 Female 13.2 15.4 4.7 Tips 1.5 574.25
12 Female 12.6 11.4 6.8 NOS 2 0
13 Male 9.3 31.5 33.4 NOS 0.7 372.55
14 Male 3.7 33.4 1.2 NOS 0.4 59.26
15 Female 8.1 39.1 0.8 NOS 0.5 0
16 Male 12.7 29 2 FSGS 0.4 3.8
17 Male 4.4 12 7.2 NOS 2 259.47
18 Male 6.6 34.4 1.9 NOS 0.8 64.42
19 Male 4.7 20.1 2.5 Tips 1 512.16
20 Male 4.7 20.1 2.7 NOS 1 96.49
21 Male 6.9 34.4 3.3 NOS 0.6 48.28
22 Male 4.9 17.6 4.2 NOS 1.6 17.78
23 Male 3.9 19 2.9 NOS 2 5.88
24 Male 5.7 36.7 0.4 Cellular 0.8 43.21
25 Male 6.9 34.4 0.6 NOS 0.7 0
26 Female 3.6 18.2 4.3 NOS 2 22.83
27 Male 12 13.6 5 NOS 2 37.04

NOS not otherwise specified

 Pediatr Nephrol

Table 3 Characteristics of the patients with minimal change disease

Patient Gender Age (years) Serum albumin (g/l) Up/Ur ratio Dose of prednisone (mg/kg/day) Urinary CD80 (ng/g creatinine)

1 Male 2.8 21.5 7.2 2 11.75

2 Female 3.9 18.6 5.5 2 170.37
3 Male 8.2 35.2 1.9 1.5 1,058.35
4 Female 3.9 18.6 6.3 2 140.5
5 Male 2.9 16.2 6.8 2 566.53
6 Male 6.9 25.3 2.4 2 173.02
7 Male 3.9 13.1 7.9 2 986.18
8 Male 1.8 13 11 2 449.82
9 Male 3.4 13.5 7.9 1.5 177.07
10 Female 5.1 25.1 3.5 1.8 541.05
11 Male 2 11 12.4 2 971.96
12 Male 15.7 13.4 8.8 2 1,264.15
13 Male 11 13.2 5.7 2 455.45
14 Male 2.5 17.7 3.5 1.6 640.78
15 Male 8.1 17.6 2.4 2 879.1
16 Female 1.7 12.7 6.9 2 246.93
17 Male 7 12.3 6.8 2 716.98
18 Male 2.8 12.5 5.4 2 550.37
19 Male 4.3 13.1 6.3 1.8 1,232.34
20 Male 9.3 10 6.6 2 806.17
21 Male 3.8 10.7 4.1 2 547.75
22 Male 11.1 18 3.3 1.4 1,026.11
23 Male 3.9 13.5 4 2 627.74
24 Female 3.4 12.6 5.9 2 1,214.08
25 Male 4.2 9.9 10.8 2 1,627.14
26 Male 6.9 15.6 11.3 2 799.71
27 Male 7.2 13.8 17.1 2 912.05
28 Male 3.3 19.5 2.5 1.7 947.82
29 Male 4.2 9.9 13 1 774.64
30 Male 7.1 17.7 11 1.7 760.73
31 Female 0.5 10.4 2 2 1,087.58
32 Male 1.7 14.4 11 1.6 480.28
33 Male 2 16.3 5.2 2 677.17
34 Male 2.4 18.4 4.7 1.5 666.5
35 Male 1.7 9.3 9.9 1.4 947.82
36 Male 1.3 19.8 4.2 1.2 340.16
37 Male 6.9 29.3 2 1 41.37

immunosuppressive agents. The effect of taking medi-
cine on the results was ignored (Tables 2, 3 and 4).
Minimal change disease; focal segmental glomerulosclerosis
Measurement of urinary CD80 expression
To explore the changes in urinary CD80 expression in
MCD patients, ELISA analysis was used on the 165
urine samples from the MCD patients, FSGS patients,
other glomerulopathy patients, and controls. The con-
centration of urinary CD80 was significantly higher in
the active MCD group (689.66±378.21 ng/g creatinine)
than in the FSGS group (123.49±167.88 ng/g creati-
nine, P<0.001), other glomerulopathies group (152.37±
220.14 ng/g creatinine, P < 0.001), and control group
(81.83± 23.01 ng/g creatinine, P <0.001; Fig. 1). The
concentration of urinary CD80 showed no significant
difference among FSGS patients, other glomerulopathy
patients, and controls (P>0.001). The mean values were
Pediatr Nephrol

Table 4 Characteristics of the patients with other glomerulopathies

Patient Gender Age (years) Serum albumin (g/l) Up/Ur ratio Type Dose of prednisone (mg/kg/day) Urinary CD80
(ng/g creatinine)

1 Male 8 34.5 0.7 IgA 0.6 67.46

2 Male 3.8 21.6 2.8 IgA 1 498.82
3 Male 7.3 25.6 2 IgA 0.7 33.46
4 Male 4.6 36.4 0.1 IgA 0.5 175.09
5 Male 2.3 37.9 0.1 IgA 0.5 275.5
6 Male 9.3 11 0.2 IgA 1.5 735.09
7 Male 4.6 24.5 2.1 IgA 1 6.79
8 Female 7.4 42 0.3 IgA 0 0
9 Male 9.3 35 0.9 IgA 0.8 43.85
10 Male 6.6 16.9 2.3 IgA 0.8 5.7
11 Female 4.1 16.9 3.4 SLE 2 913.6
12 Male 8.11 19.6 2.8 SLE 1 49.38
13 Female 14.9 24.5 1.8 SLE 1 19.42
14 Male 5.8 21.6 3.1 SLE 1.5 304.05
15 Male 5.9 10.2 8.8 SLE 2 7.76
16 Male 3.3 34.8 0.2 MN 1 133.56
17 Male 6.8 34.8 0.2 MN 1.5 245.61
18 Male 5.8 32.2 1.5 MN 0.9 3.67
19 Male 9 18.1 4.6 MN 1.1 0
20 Male 3.9 12.3 3.3 MN 1 12.62
21 Male 7.6 28.6 3.3 AGN 0 68.62
22 Female 7.1 40.6 0.1 AGN 0 49.03
23 Female 12.7 37.2 2 AGN 0 0
24 Male 10 44.3 0.1 MPGN 0 279.6
25 Male 16 35 0.3 MPGN 0 110.29
26 Male 2.3 20.6 2.3 MPGN 1.6 54.69
27 Female 10.9 44.7 0.1 MPGN 0 262.17
28 Male 6.11 24.8 1.8 MPGN 0.8 132.08
29 Male 9 32.5 1.6 MPGN 1 49.71
30 Female 5.6 31.1 2.3 MPGN 1.3 33.46

IgA immunoglobulin A, SLE systemic lupus erythematosus, MN membranous nephropathy, MPGN membranoproliferative glomerulonephritis, AGN
atubular glomeruli nephropathy

334.58±208.92 ng/g creatinine for all patients with tip Discussion

lesions and 38.54 ng/g creatinine (5.36, 80.16) in the
NOS patients. Urinary CD80 was higher in tip lesions
than in NOS (P<0.05).
Urinary as a biomarker for MCD
After quantitative analysis of 165 urine samples by ELISA,
ROC curves were used to assess the potential utility of urinary
CD80 detection in patients with MCD. The area under the
ROC curve of urine CD80 levels for the diagnosis of MCD
was 0.925 (95 % confidence interval, 0.873–0.978). The
analysis rendered an optimal cutoff value of 328.98 ng/g
creatinine corresponding to 81.1 % sensitivity and 94.4 %
specificity (Fig. 2).
There is a need for an accurate, high-quality biomarker that
can be used to differentiate MCD from FSGS and other
glomerular diseases. In this cohort, results showed that, using
a cutoff value of 328.98 ng/g creatinine, urinary CD80
allowed observers to distinguish MCD from FSGS and other
glomerulopathies with an AUC of 0.925 and an opti-
mized sensitivity of 81.1 % and specificity of 94.4 %.
This showed urinary CD80 to be a suitable biomarker
for the diagnosis of MCD, confirming findings previ-
ously reported by Garin et al. [7, 8].
This is the first large-scale, single-center study to
show that urinary CD80 is a suitable diagnostic bio-
marker of human MCD. CD80 is a transmembrane
 Pediatr Nephrol

Fig. 1 Mean urinary

concentration of CD80 in 37
patients with minimal change
disease (MCD) compared with
that of 27 patients with focal
segmental glomerulosclerosis
(FSGS), 20 patients with other
glomerular diseases, and 71
healthy controls. Patients with
MCD had significantly higher
urinary CD80 levels than patients
with FSGS, patients with other
glomerular diseases, and healthy
controls (P<0.001)

protein expressed on many antigen-presenting cells. It
participates in some humoral and cellular immunity
reactions [4]. Beyond its traditionally recognized func-
tion, CD80 was recently found to be expressed on
podocytes as well [6, 10]. The expression level of
CD80 on podocytes increases under the induction of
LPS, puromycin, or genetic deficiency. This expression
is independent of CD80 expression on lymphocytes [6,
11]. This changes the permeability of the glomerular
filtration barrier, and can cause proteinuria [12, 13].
Under normal circumstances, CD80 expression is only
transiently increased and proteinuria is minimal.
Fig. 2 Receiver operating characteristic (ROC) curve analysis for urinary
CD80 as a marker for the diagnosis of MCD
However, in MCD patients, there is a defect in CD80
podocyte autoregulation. This defect causes persistent
CD80 expression and persistent proteinuria [13].
Urinary CD80 levels have been shown to be higher
in MCD patients in relapse than in MCD patients in
remission and FSGS patients [7–9]. It has also been
proven that urinary CD80 in MCD patients comes from
podocyte rather than from blood free CD80 or renal
tubular epithelial cells [7, 8]. However, two criteria
must be met to confirm the results reported by Garin
et al. First, the MCD and FSGS patient groups must
differ significantly in terms of age (mean 6 vs 36 years)
and gender (60 male vs 18 % female). Second, in order
to prove the specificity of urinary CD80 for MCD, a
control population with different kinds of glomerular
diseases is necessary [9].
The current experiment is age- and gender-matched
(Table 1). The other glomerulopathy group contained patients
with other kinds of glomerular disease, such as
membranoproliferative glomerulonephritis, membranous ne-
phropathy, IgA nephropathy, lupus nephritis, and acute glo-
merular nephritis. Concentrations of urinary CD80 were
found to be higher than the cutoff value in IgA patients (2
out of 10) and lupus nephritis patients (1 out of 5). The
maximum uria-CD80 is not only a product of MCD.
Lupus nephritis is a CD80 disorder [14, 15].
However, in the current study, urinary CD80 was only
high in 1 of the 5 lupus subjects. Urinary CD80 levels
are difficult to interpret in patients with SLE, because of
reported elevated serum CD80 levels in these patients
unrelated to the activity of the disease [16]. Here, pa-
tients with SLE were excluded before urinary CD80 was
used to diagnose MCD.
Results showed that 4 out of 27 FSGS patients had values
near or exceeding the cutoff value. This was observed in 3 tip
Pediatr Nephrol
lesion types and 1 type not otherwise specified (NOS), but not
in perihilar, cellular, or collapsing types. The relationship
between MCD and primary FSGS has remained controversial
[17]. The tip variant and MCD show similar clinical manifes-
tations and both can progress to renal damage and CKD,
although this is not common. It has been postulated that the
tip lesion type may represent a response to heavy proteinuria
and may be a form of MCD [17–21]. The current results are
consistent with this hypothesis. The data collected here sug-
gest that tip lesions and MCD are a continuum of one disease,
but MCD and FSGS are two different diseases.
It has been reported that serum soluble urokinase-type
plasminogen activator receptor (suPAR) is significantly ele-
vated in FSGS patients [22]. This may be useful as a biomark-
er to help differentiate between MCD and FSGS. A single-
center, large-scale experiment on the use of SuPAR in the
diagnosis of FSGS is currently underway. However, this bio-
marker remains controversial [23]. The experiment may pro-
vide useful information.
The current study also has limitations. First, although a
urine CD80 cutoff with good sensitivity and specificity was
identified, larger studies are needed to validate it to the point at
which it could replace renal biopsy. Second, although it had
been proven that urine contains full-length CD80 rather than
the short-CD80 found in serum, serum CD80 was not record-
ed for FSGS patients or patients with other glomerular dis-
eases [8]. Whether the CD80 in the urine of these patients
comes from renal tissue or serum must be determined.
In conclusion, the current study demonstrated that urinary
CD80 levels were significantly higher in patients with MCD
than in patients with other conditions or in healthy controls.
This showed urinary CD80 to be a suitable biological marker
for the diagnosis of MCD, with cutoff values of 328.98 (ng/g
creatinine) and a sensitivity of 81.1 % and specificity of
94.4 %. Further studies are warranted to examine the patho-
genic mechanisms underlying elevated CD80 in FSGS and
other glomerulopathies.
Acknowledgements We would like to thank the staff of the Beijing
Children’s Hospital Laboratory for technical assistance. This work was
supported by the Research on the Application of Capital Clinical Char-
acteristics Program of Beijing Municipal Science and Technology Com-
mission (Z121107001012052).
Conflict of interest The authors have no conflicts of interest to declare.
References
1. International Study of Kidney Disease in Children (1978) Nephrotic
syndrome in children: prediction of histopathology from clinical and
laboratory characteristics at time of diagnosis. A report of the
International Study of Kidney Disease in Children. Kidney Int 13:
159–165
2. International Study of Kidney Disease in Children (1981)
The primary nephrotic syndrome in children. Identification
of patients with minimal change nephrotic syndrome from
initial response to prednisone. A report of the
International Study of Kidney Disease in Children. J
Pediatr 98:561–564
3. Rianthavorn P, Kerr SJ, Chiengthong K (2014) Safety of
pediatric percutaneous native kidney biopsy and factors
predicting bleeding complications. Nephrology (Carlton) 19:
143–148
4. Greenwald RJ, Freeman GJ, Sharpe AH (2005) The B7 family
revisited. Annu Rev Immunol 23:515–548
5. Chang JM, Hwang DY, Chen SC, Kuo MC, Hung CC, Hwang SJ,
Tsai JC, Chen HC (2013) B7-1 expression regulates the hypoxia-
driven cytoskeleton rearrangement in glomerular podocytes. Am J
Physiol Renal Physiol 304:F127–F136
6. Reiser J, von Gersdorff G, Loos M, Oh J, Asanuma K, Giardino L,
Rastaldi MP, Calvaresi N, Watanabe H, Schwarz K, Faul C, Kretzler
M, Davidson A, Sugimoto H, Kalluri R, Sharpe AH, Kreidberg JA,
Mundel P (2004) Induction of B7-1 in podocytes is associated with
nephrotic syndrome. J Clin Invest 113:1390–1397
7. Garin EH, Diaz LN, Mu W, Wasserfall C, Araya C, Segal M, Johnson
RJ (2009) Urinary CD80 excretion increases in idiopathic minimal-
change disease. J Am Soc Nephrol 20:260–266
8. Garin EH, Mu W, Arthur JM, Rivard CJ, Araya CE, Shimada M,
Johnson RJ (2010) Urinary CD80 is elevated in minimal change
disease but not in focal segmental glomerulosclerosis. Kidney Int
78:296–302
9. Kistler AD, Reiser J (2010) Maximal ‘CD80-uria’ with minimal
change. Kidney Int 78:236–238
10. Churg J, Habib R, White RH (1970) Pathology of the nephrotic
syndrome in children: a report for the International Study of Kidney
Disease in Children. Lancet 760:1299–1302
11. Reiser J, Mundel P (2004) Danger signaling by glomerular
podocytes defines a novel function of inducible B7-1 in the
pathogenesis of nephrotic syndrome. J Am Soc Nephrol 15:
2246–2248
12. Eto N, Wada T, Inagi R, Takano H, Shimizu A, Kato H, Kurihara H,
Kawachi H, Shankland SJ, Fujita T, Nangaku M (2007) Podocyte
protection by darbepoetin: preservation of the cytoskeleton and
nephrin expression. Kidney Int 72:455–463
13. Shimada M, Araya C, Rivard C, Ishimoto T, Johnson RJ, Garin EH
(2011) Minimal change disease: a “two-hit” podocyte immune dis-
order? Pediatr Nephrol 26(4):645–649
14. Kow NY, Mak A (2013) Costimulatory pathways: physiology and
potential therapeutic manipulation in systemic lupus erythematosus.
Clin Dev Immunol 2013:245928
15. Merrill JT (2013) Co-stimulatory molecules as targets for treatment
of lupus. Clin Immunol 148(3):369–375
16. Wong CK, Lit LC, Tam LS, Li EK, Lam CW (2005) Aberrant
production of soluble costimulatory molecules CTLA-4, CD28,
CD80 and CD86 in patients with systemic lupus erythematosus.
Rheumatology 44:989–994
17. Meyrier A, Niaudet P (2005) Minimal changes and focal
segmental glomerulosclerosis. In: Davison AM, Cameron SJ,
Grunfeld JP, Ponticelli C, Ritz E, Winearls C, Van Ypersele C
(eds) Textbook of clinical nephrology. Oxford University
Press, Oxford, pp 439–469
18. Haas M, Yousefzadeh N (2002) Glomerular tip lesion in minimal
change nephropathy: a study of autopsies before 1950. Am J Kidney
Dis 39:1168–1175
19. Howie AJ, Brewer DB (1984) The glomerular tip lesion: a previously
undescribed type of segmental glomerular abnormality. J Pathol 142:
205–220
20. Howie AJ, Lee SJ, Green NJ, Newbold KM, Kizaki T, Koram A,
Richards NT, Michael J, Adu D (1993) Different clinicopathological

types of segmental sclerosing glomerular lesions in adults. Nephrol
Dial Transplant 8:590–599
21. D’Agati VD, Kaskel FJ, Falk RJ (2011) Focal segmental
glomerulosclerosis. N Engl J Med 365:2398–2411
22. Sinha A, Bajpai J, Saini S, Bhatia D, Gupta A, Puraswani M, Dinda
AK, Agarwal SK, Sopory S, Pandey RM, Hari P, Bagga A (2014)
Serum-soluble urokinase receptor levels do not distinguish focal
Pediatr Nephrol
segmental glomerulosclerosis from other causes of nephrotic syn-
drome in children. Kidney Int 85:649–658
23. Cara-Fuentes G, Wei C, Segarra A, Segarra A, Ishimoto T, Rivard C,
Johnson RJ, Reiser J, Garin EH (2014) CD80 and suPAR in
patients with minimal change disease and focal segmental
glomerulosclerosis: diagnostic and pathogenic significance.
Pediatr Nephrol 29:1363–1371