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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 CD80 to diagnose MCD was 0.925 (95 % confidence


Background Early diagnosis of minimal change disease interval: 0.873–0.978).
(MCD) in nephrotic syndrome (NS) patients remains chal- Conclusions This experiment has preliminarily confirmed
lenging. Doctors often make a diagnosis of MCD using inva- urinary CD80 as a non-invasive diagnostic biomarker. It
sive renal biopsy. CD80, a transmembrane protein, is present may have significant value in the diagnosis of MCD.
on podocytes in a number of experimental models of NS.
Urinary CD80 levels are significantly elevated in MCD but Keywords MCD . FSGS . CD80 . Children
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 Introduction
the diagnosis of MCD.
Materials and methods A total of 165 subjects, 129 men and Minimal change disease (MCD) is by far the most
36 women, were enrolled in this study. Urinary samples were common cause of nephrotic syndrome in children [1].
collected from 37 patients with MCD, 27 patients with FSGS, It accounts for approximately 80–90 % of cases. The
30 patients with other glomerulopathies, and 71 healthy peo- second most common type of nephrotic syndrome in
ple. Using ELISA, experimental values were compared with children is focal segmental glomerulosclerosis (FSGS),
those produced by kidney biopsy samples. which accounts for 10 % of cases [1]. Most MCD
Results The concentration of urinary CD80 was significantly children who present nephrotic syndrome respond to
higher in the active MCD group (689.66±378.21 ng/g creat- corticosteroid therapy, but some are steroid-dependent
inine) than in the FSGS group (123.49±167. 88 ng/g creati- or steroid-resistant [2]. In contrast, most patients with
nine, P<0.00), other glomerulopathies group (152.37±220. FSGS are relatively resistant to corticosteroid therapy,
14 ng/g creatinine, P<0.001) and the control group (81.83± which indicates a risk of progression to end-stage renal
23.01 ng/g creatinine; P<0.001). A cutoff value of 328.98 disease (ESRD). Other glomerular diseases (such as IgA
(ng/g creatinine) was proposed, with a sensitivity of 81.1 % nephropathy and membranous nephropathy) can also
and specificity of 94.4 %. The area under the receiver present with nephrotic syndrome [1]. However, the
operating characteristic (ROC) curve for the urinary treatment and prognosis for MCD, FSGS, and other
glomerulopathies differ considerably. Currently, the gold
standard for conforming MCD is kidney biopsy. But
Xiaorong Liu and Ying Shen contributed equally to this work and should this method is invasive and complicated and so rarely
be considered as co-corresponding authors used on inpatient children, especially those seeing a
C. Ling : X. Liu (*) : Y. Shen (*) : Z. Chen : J. Fan : Y. Jiang : doctor for the first time [3]. Another method of diag-
Q. Meng nosing MCD would be very useful.
Department of Nephrology, Beijing Children’s Hospital affiliated to CD80 (also called B7-1) is a transmembrane protein
Capital Medical University, West District Nan Li Shi Lu 56th,
expressed on the surfaces of B cells and other antigen-
Beijing 100045, China
e-mail: desin2000@sina.com presenting cells. It works as a costimulatory signal and
e-mail: 15210938018@163.com activates T cells by binding to the receptor CD28. It
Pediatr Nephrol

also inhibits T cell activation by binding to CTLA-4 [4]. Urine samples


CD80 can be induced to expression on podocytes, caus-
ing actin reorganization and proteinuria [5, 6]. In 2009, A single and naturally voided midstream urine sample
Garin et al. reported significantly higher levels of CD80 was obtained prospectively from all subjects. Each urine
in the urine samples of subjects with MCD than in sample (20 ml) was directly collected into a sterile
those in FSGS patients, MCD patients in remission, plastic tube and then centrifuged not more than an hour
and patients with other glomerulopathies [7, 8]. after collection at 2,000 × g for 10 min at 4 °C to
However, this difference has not been confirmed in an remove cell debris and particulate matter. It was then
independent patient cohort [9]. stored at −80 °C for further analysis. All samples were
Taking the hypothesis that urinary CD80 could be used as a brought to room temperature before use. All urine sam-
functional marker for early diagnosis in MCD, the current ples were stored for a minimum of 1 day and a maxi-
study was designed to assess the clinical utility of urinary mum of 1 month before analysis.
CD80 as a diagnostic biomarker when used with ELISA.
This method was compared with kidney biopsy, which is the Urinary CD80 measurements
conventional method of diagnosing MCD, FSGS, and other
glomerular diseases. 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.
Materials and methods
Statistical analysis
Patients
For continuous variables with a normal distribution,
A total of 165 subjects, 129 men and 36 women, descriptive results were presented as mean and standard
participated in this study. They were divided into four deviation (SD). The t test for unpaired samples was
groups, MCD, FSGS, other glomerulopathy, and control used to analyze the differences between groups. For
groups. The MCD group contained 37 patients, the continuous variables with a skewed distribution, descrip-
FSGS group 27, the other glomerulopathy group 30 tive results were expressed as a median and a range.
patients (membranoproliferative glomerulonephritis (n= The Mann–Whitney U test and the two-sample
7), membranous nephropathy (n=5), IgA nephropathy Kolmogorov–Smirnov test were used to evaluate the
(n=10), SLE (n=5), acute glomerular nephritis (n=3), differences between groups. Discrete (categorical) vari-
and the control group 71 healthy people. Subjects with ables were compared using the Chi-squared (χ2) test.
renal dysfunction were excluded (serum creatinine The differences among groups were compared using a
>1.5 mg/dl or glomerular filtration rate<60 ml/min). one-way analysis of variance for three groups. A receiv-
All patients underwent renal biopsy at the Beijing er operating characteristic (ROC) curve was constructed
Children’s Hospital between 2011 and 2013. The indi- and the area under the ROC curve (AUC) was calculat-
cations for biopsy in the children with MCD were ed to assess the predictive strength. Optimal cutoff
refractory nephrotic syndrome including steroid- points to maximize both sensitivity and specificity were
resistant NS, steroid-dependent NS, and frequent re- also determined. Differences with P values<0.05 were
lapse. The diagnoses of various kidney diseases were considered statistically significant. Statistical analysis
based on criteria established by the International Study was performed with SPSS (version 17.0 for Windows;
for Kidney Diseases in Children [10]. SPSS, Chicago, IL, USA).
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 Results
urinary protein/creatinine ratio was<0.40 in a random
urine sample. Clinical characteristics of patients
The present study was approved by the institutional review
board of the Beijing Municipal Science and Technology The clinical characteristics of all patients are shown in Table 1.
Commission and the Capital Medical University Institutional Samples from 37 patients with MCD, 27 with FSGS, 30 with
Review Board. All participants provided written informed other glomerulopathies, and 71 healthy people were
consent before participation. 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- other glomerulopathy patients, and controls. The con-
cine on the results was ignored (Tables 2, 3 and 4). centration of urinary CD80 was significantly higher in
the active MCD group (689.66±378.21 ng/g creatinine)
Minimal change disease; focal segmental glomerulosclerosis than in the FSGS group (123.49±167.88 ng/g creati-
nine, P<0.001), other glomerulopathies group (152.37±
Measurement of urinary CD80 expression 220.14 ng/g creatinine, P < 0.001), and control group
(81.83± 23.01 ng/g creatinine, P <0.001; Fig. 1). The
To explore the changes in urinary CD80 expression in concentration of urinary CD80 showed no significant
MCD patients, ELISA analysis was used on the 165 difference among FSGS patients, other glomerulopathy
urine samples from the MCD patients, FSGS patients, 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 There is a need for an accurate, high-quality biomarker that
than in NOS (P<0.05). can be used to differentiate MCD from FSGS and other
glomerular diseases. In this cohort, results showed that, using
Urinary as a biomarker for MCD a cutoff value of 328.98 ng/g creatinine, urinary CD80
allowed observers to distinguish MCD from FSGS and other
After quantitative analysis of 165 urine samples by ELISA, glomerulopathies with an AUC of 0.925 and an opti-
ROC curves were used to assess the potential utility of urinary mized sensitivity of 81.1 % and specificity of 94.4 %.
CD80 detection in patients with MCD. The area under the This showed urinary CD80 to be a suitable biomarker
ROC curve of urine CD80 levels for the diagnosis of MCD for the diagnosis of MCD, confirming findings previ-
was 0.925 (95 % confidence interval, 0.873–0.978). The ously reported by Garin et al. [7, 8].
analysis rendered an optimal cutoff value of 328.98 ng/g This is the first large-scale, single-center study to
creatinine corresponding to 81.1 % sensitivity and 94.4 % show that urinary CD80 is a suitable diagnostic bio-
specificity (Fig. 2). 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 However, in MCD patients, there is a defect in CD80
participates in some humoral and cellular immunity podocyte autoregulation. This defect causes persistent
reactions [4]. Beyond its traditionally recognized func- CD80 expression and persistent proteinuria [13].
tion, CD80 was recently found to be expressed on Urinary CD80 levels have been shown to be higher
podocytes as well [6, 10]. The expression level of in MCD patients in relapse than in MCD patients in
CD80 on podocytes increases under the induction of remission and FSGS patients [7–9]. It has also been
LPS, puromycin, or genetic deficiency. This expression proven that urinary CD80 in MCD patients comes from
is independent of CD80 expression on lymphocytes [6, podocyte rather than from blood free CD80 or renal
11]. This changes the permeability of the glomerular tubular epithelial cells [7, 8]. However, two criteria
filtration barrier, and can cause proteinuria [12, 13]. must be met to confirm the results reported by Garin
Under normal circumstances, CD80 expression is only et al. First, the MCD and FSGS patient groups must
transiently increased and proteinuria is minimal. 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.
Fig. 2 Receiver operating characteristic (ROC) curve analysis for urinary Results showed that 4 out of 27 FSGS patients had values
CD80 as a marker for the diagnosis of MCD 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 2. International Study of Kidney Disease in Children (1981)
The primary nephrotic syndrome in children. Identification
in perihilar, cellular, or collapsing types. The relationship
of patients with minimal change nephrotic syndrome from
between MCD and primary FSGS has remained controversial initial response to prednisone. A report of the
[17]. The tip variant and MCD show similar clinical manifes- International Study of Kidney Disease in Children. J
tations and both can progress to renal damage and CKD, Pediatr 98:561–564
3. Rianthavorn P, Kerr SJ, Chiengthong K (2014) Safety of
although this is not common. It has been postulated that the
pediatric percutaneous native kidney biopsy and factors
tip lesion type may represent a response to heavy proteinuria predicting bleeding complications. Nephrology (Carlton) 19:
and may be a form of MCD [17–21]. The current results are 143–148
consistent with this hypothesis. The data collected here sug- 4. Greenwald RJ, Freeman GJ, Sharpe AH (2005) The B7 family
revisited. Annu Rev Immunol 23:515–548
gest that tip lesions and MCD are a continuum of one disease,
5. Chang JM, Hwang DY, Chen SC, Kuo MC, Hung CC, Hwang SJ,
but MCD and FSGS are two different diseases. Tsai JC, Chen HC (2013) B7-1 expression regulates the hypoxia-
It has been reported that serum soluble urokinase-type driven cytoskeleton rearrangement in glomerular podocytes. Am J
plasminogen activator receptor (suPAR) is significantly ele- Physiol Renal Physiol 304:F127–F136
6. Reiser J, von Gersdorff G, Loos M, Oh J, Asanuma K, Giardino L,
vated in FSGS patients [22]. This may be useful as a biomark-
Rastaldi MP, Calvaresi N, Watanabe H, Schwarz K, Faul C, Kretzler
er to help differentiate between MCD and FSGS. A single- M, Davidson A, Sugimoto H, Kalluri R, Sharpe AH, Kreidberg JA,
center, large-scale experiment on the use of SuPAR in the Mundel P (2004) Induction of B7-1 in podocytes is associated with
diagnosis of FSGS is currently underway. However, this bio- nephrotic syndrome. J Clin Invest 113:1390–1397
7. Garin EH, Diaz LN, Mu W, Wasserfall C, Araya C, Segal M, Johnson
marker remains controversial [23]. The experiment may pro-
RJ (2009) Urinary CD80 excretion increases in idiopathic minimal-
vide useful information. change disease. J Am Soc Nephrol 20:260–266
The current study also has limitations. First, although a 8. Garin EH, Mu W, Arthur JM, Rivard CJ, Araya CE, Shimada M,
urine CD80 cutoff with good sensitivity and specificity was Johnson RJ (2010) Urinary CD80 is elevated in minimal change
identified, larger studies are needed to validate it to the point at disease but not in focal segmental glomerulosclerosis. Kidney Int
78:296–302
which it could replace renal biopsy. Second, although it had 9. Kistler AD, Reiser J (2010) Maximal ‘CD80-uria’ with minimal
been proven that urine contains full-length CD80 rather than change. Kidney Int 78:236–238
the short-CD80 found in serum, serum CD80 was not record- 10. Churg J, Habib R, White RH (1970) Pathology of the nephrotic
ed for FSGS patients or patients with other glomerular dis- syndrome in children: a report for the International Study of Kidney
Disease in Children. Lancet 760:1299–1302
eases [8]. Whether the CD80 in the urine of these patients 11. Reiser J, Mundel P (2004) Danger signaling by glomerular
comes from renal tissue or serum must be determined. podocytes defines a novel function of inducible B7-1 in the
In conclusion, the current study demonstrated that urinary pathogenesis of nephrotic syndrome. J Am Soc Nephrol 15:
CD80 levels were significantly higher in patients with MCD 2246–2248
12. Eto N, Wada T, Inagi R, Takano H, Shimizu A, Kato H, Kurihara H,
than in patients with other conditions or in healthy controls. Kawachi H, Shankland SJ, Fujita T, Nangaku M (2007) Podocyte
This showed urinary CD80 to be a suitable biological marker protection by darbepoetin: preservation of the cytoskeleton and
for the diagnosis of MCD, with cutoff values of 328.98 (ng/g nephrin expression. Kidney Int 72:455–463
creatinine) and a sensitivity of 81.1 % and specificity of 13. Shimada M, Araya C, Rivard C, Ishimoto T, Johnson RJ, Garin EH
(2011) Minimal change disease: a “two-hit” podocyte immune dis-
94.4 %. Further studies are warranted to examine the patho- order? Pediatr Nephrol 26(4):645–649
genic mechanisms underlying elevated CD80 in FSGS and 14. Kow NY, Mak A (2013) Costimulatory pathways: physiology and
other glomerulopathies. potential therapeutic manipulation in systemic lupus erythematosus.
Clin Dev Immunol 2013:245928
15. Merrill JT (2013) Co-stimulatory molecules as targets for treatment
Acknowledgements We would like to thank the staff of the Beijing of lupus. Clin Immunol 148(3):369–375
Children’s Hospital Laboratory for technical assistance. This work was 16. Wong CK, Lit LC, Tam LS, Li EK, Lam CW (2005) Aberrant
supported by the Research on the Application of Capital Clinical Char- production of soluble costimulatory molecules CTLA-4, CD28,
acteristics Program of Beijing Municipal Science and Technology Com- CD80 and CD86 in patients with systemic lupus erythematosus.
mission (Z121107001012052). Rheumatology 44:989–994
17. Meyrier A, Niaudet P (2005) Minimal changes and focal
Conflict of interest The authors have no conflicts of interest to declare. 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
References 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
1. International Study of Kidney Disease in Children (1978) Nephrotic 19. Howie AJ, Brewer DB (1984) The glomerular tip lesion: a previously
syndrome in children: prediction of histopathology from clinical and undescribed type of segmental glomerular abnormality. J Pathol 142:
laboratory characteristics at time of diagnosis. A report of the 205–220
International Study of Kidney Disease in Children. Kidney Int 13: 20. Howie AJ, Lee SJ, Green NJ, Newbold KM, Kizaki T, Koram A,
159–165 Richards NT, Michael J, Adu D (1993) Different clinicopathological
Pediatr Nephrol

types of segmental sclerosing glomerular lesions in adults. Nephrol segmental glomerulosclerosis from other causes of nephrotic syn-
Dial Transplant 8:590–599 drome in children. Kidney Int 85:649–658
21. D’Agati VD, Kaskel FJ, Falk RJ (2011) Focal segmental 23. Cara-Fuentes G, Wei C, Segarra A, Segarra A, Ishimoto T, Rivard C,
glomerulosclerosis. N Engl J Med 365:2398–2411 Johnson RJ, Reiser J, Garin EH (2014) CD80 and suPAR in
22. Sinha A, Bajpai J, Saini S, Bhatia D, Gupta A, Puraswani M, Dinda patients with minimal change disease and focal segmental
AK, Agarwal SK, Sopory S, Pandey RM, Hari P, Bagga A (2014) glomerulosclerosis: diagnostic and pathogenic significance.
Serum-soluble urokinase receptor levels do not distinguish focal Pediatr Nephrol 29:1363–1371