close

Вход

Забыли?

вход по аккаунту

?

s-0036-1586406

код для вставкиСкачать
159
Journal of Pediatric Biochemistry 2 (2012) 159–162
DOI 10.3233/JPB-2012-00051
IOS Press
Serum lipids and lipoprotein(a) levels in
children with idiopathic nephrotic syndrome
Om P. Mishraa , Rajniti Prasada,∗, Divya Atria , Surya K. Singhb and Ziledar Alic
a
Departments of Pediatrics, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India
Departments of Endocrinology and Metabolism, Institute of Medical Sciences, Banaras Hindu University,
Varanasi, India
c
Departments of Biochemistry, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India
b
Revised 30 January 2012
Accepted 10 February 2012
Abstract. The present study was carried out prospectively to evaluate serum lipids and lipoprotein(a) levels in children with
nephrotic syndrome during the active phase of disease and during a remission. Serum lipids and lipoprotein(a) levels were
measured in 40 children, aged 2–10 years, during the active phase of nephrotic syndrome; 25 with a first attack, 9 infrequent
relapsers and 6 frequent relapsers, and during remission and in 20 healthy age-matched controls. The mean serum lipids and
lipoprotein(a) levels were significantly raised during the active phase of nephrotic syndrome (p < 0.001). The values were
relatively higher in relapsers. The lipids and lipoprotein(a) levels decreased during a remission but were significantly higher (p <
0.05) than controls. Serum lipids had a negative correlation with serum albumin and lipoprotein(a) had a positive correlation
with proteinuria (r = 0.5246, p < 0.01) but no correlation with serum albumin. The elevated lipids and lipoprotein(a) in both
the active phase of nephrotic syndrome and during remission suggest a possible predisposition to atherosclerosis in future.
Keywords: Lipids, lipoprotein(a), nephrotic syndrome, relapsers
1. Introduction
The elevation of serum lipid levels is an integral component of idiopathic nephrotic syndrome in childhood.
There is an increase in the serum levels of cholesterol,
triglycerides, low-density lipoprotein (LDL) and verylow-density lipoproteins (VLDL) in the active phase of
disease [1]. The high-density lipoprotein (HDL) may
be normal, low or high [1–3]. The proposed mechanisms contributing to dyslipidemia include over production and impaired catabolism of apolipoprotein Bcontaining lipoproteins [4].
Increased levels of serum lipoprotein (a) [Lp(a)] have
been reported in the active phase of the nephrotic syndrome [5,6]. This is due to overproduction of apo-B,
which leads to an increased number of LDL particles
∗ Corresponding
author: Dr. Rajniti Prasad, Department of Pediatrics, Institute of Medical Sciences, Banaras Hindu University,
Varanasi 221 005, India. Tel.: +91 542 2367677; Fax: +91 542
2367568; E-mail: rajnitip@gmail.com.
to be converted into Lp(a) [6]. However, the levels
may remain either elevated [5] or decreased during remission [6]. Further, the Lp(a) concentration has been
found to be an independent risk factor for relapse of
nephrotic syndrome, indicating its prognostic significance [7].
There is a paucity of reports regarding variation in the
serum Lp(a) levels especially in patients with nephrotic
syndrome. As children with nephrotic syndrome may
have a number of relapses of varying duration, the persistent elevation of lipoproteins could predispose the
patients to early onset of atherosclerosis. Therefore,
the present study was undertaken to evaluate the serum
lipids as well as Lp(a) levels during the active phase of
idiopathic nephrotic syndrome and during remission of
the disease.
2. Materials and methods
Forty children with idiopathic nephrotic syndrome,
aged 2–10 years, who reported to the Pediatric Nephrol-
1879-5390/12/$27.50  2012 – IOS Press and the authors. All rights reserved
Downloaded by: Vanderbilt University. Copyrighted material.
Received 2 January 2012
O.P. Mishra et al. / Serum lipids and lipoprotein(a) in nephritic syndrome
ogy Clinic of the Department of Pediatrics, Institute of
Medical Sciences, Banaras Hindu University, Varanasi,
India were studied. The diagnosis was based on
generalized edema, proteinuria 40 mg/m2 /hr, hypoalbuminemia 2.5 g/dL, hypercholesterolemia 200 mg/dL and absence of any systemic disease known
to produce nephrotic syndrome. All the patients were
responsive to prednisolone therapy.
Patients with gross hematuria, persistent hypertension, azotemia and steroid non-responders were excluded. Renal biopsy was not performed in any of the patients. Twenty healthy age-matched children served as
controls. The study was approved by the institutions
ethics committee.
2.1. Treatment and follow up
First Episode Nephrotic Syndrome (FANS): Prednisolone 60 mg/m2 /24 hr, in divided doses for 6 weeks
and then 40 mg/m2 on alternate days as single dose for
another 6 weeks.
Infrequent Relapsing Nephrotic Syndrome (IRNS)
and Frequent Relapsing Nephrotic Syndrome (FRNS):
Prednisolone 60 mg/m2 /24 hr, in divided doses until
remission, followed by 40 mg/m2 on alternate days as
single dose for 4 weeks in IRNS and for 9–12 months
in tapering doses (minimum of 0.5 mg/kg) in FRNS
patients.
During the course of therapy, patients were regularly
followed and the response to therapy was assessed by
measuring with a spot urine protein via the heat precipitation test and a 24 hour urinary protein. The serum
lipids and Lp(a) level were measured in study subjects
at the time of diagnosis and in remission (proteinuria of
< 4 mg/m2 /hr or negative or trace by the heat precipitation test for three consecutive days), for more then
four weeks following the completion of therapy.
2.2. Collection and preservation of serum
A fasting sample of 5 mL of blood was collected taking all aseptic precautions by venipuncture, transferred
to a sterile test tube and left to clot at room temperature.
After clot retraction, serum was transferred by a sterile pipette to a sterile Kahn tube, centrifuged and kept
frozen at −20◦C in a refrigerator after adding a pinch
of sodium azide as preservative. Serum triglycerides,
cholesterol, HDL, LDL and VLDL were measured by
standard procedures (Chema Diagnostic Commercial
Kit, Italy and Accurex Biomedical Pvt. Ltd. Mumbai).
2.3. Estimation of Lp(a)
Serum Lp(a) was estimated by Turbidimetric immunoassay using QUANTIA-Lp(a) commercial kit
(Tulip Diagnostics Pvt. Ltd., Goa, India). Test samples were mixed with the activation buffer (R1 ) and
anti Lp(a) antibody solution (R2 ) and allowed to react
at 37◦ C. The presence of Lp(a) in the test specimen
resulted in the formation of an insoluble complex producing a turbidity, which was measured at wavelength
of 340 nm by spectrophotometer, which corresponded
to the concentration of Lp(a).
2.4. Statistical analysis
Data was analyzed using SPSS software version 15.
Student t-test was used to analyze the data for statistical significance. The correlation and regression coefficients were also calculated among different parameters.
3. Results
There were 40 (28 males) active nephrotic syndrome patients (ANS), aged 2 to 10 years (mean 5.7 ±
2.5 years). Out of the 40 ANS patients, 25 were FANS,
9 IRNS and 6 FRNS. Twenty healthy age-matched children (mean 5.5 ± 2.3 years) serve as controls. Both
patients and controls belonged to the same ethnic group
and had normal nutritional status according to Gomez’s
classification [8]. All study patients had normal renal function and were steroid responsive, achieving a
remission within 14.8 ± 10.2 days after the start of
treatment.
The mean serum triglycerides, cholesterol, HDL,
LDL, VLDL and Lp(a) in controls and patients with
nephrotic syndrome are reported in Table 1. Serum
lipids were significantly elevated in ANS patients as
well as in its sub-groups as compared to controls. The
mean value of triglycerides and VLDL were significantly elevated in FANS (p < 0.05) as compared to
IRNS, while other parameters did not differ significantly among different subgroups of ANS patients.
There was significant reductions in the mean value
of lipids and Lp(a) during remission in comparison to
their corresponding ANS as paired samples, but the level was elevated in comparison to the controls (Table 2).
Serum lipids had a negative correlation with serum albumin in ANS patients (Table 3). Eighteen of 40 (45%)
patients had serum Lp(a) levels above 30 mg/dL during remission. The serum Lp(a) had a positive correlation with proteinuria (r = 0.5246, p < 0.01) but no
correlation with serum albumin.
Downloaded by: Vanderbilt University. Copyrighted material.
160
O.P. Mishra et al. / Serum lipids and lipoprotein(a) in nephritic syndrome
161
Table 1
Serum lipids and Lp(a) in controls and active nephrotic syndrome (mean ± SD)
Groups
No of
cases
Controls
20
Active Nephrotic 40
Triglycerides
(mg/dL)
93.4 ± 48.3
427.6 ± 173.7∗∗
Cholesterol
(mg/dL)
105.3 ± 29.1
473.8 ± 107.6∗∗
HDL
(mg/dL)
21.6 ± 10.4
80 ± 5.4∗∗
LDL
(mg/dL)
64.9 ± 21.1
293.9 ± 110.8∗∗
VLDL
(mg/dL)
18.7 ± 9.7
85.5 ± 34.8∗∗
Lp (a)
(mg/dL)
30.4 ± 19.9
76.3 ± 28.1∗∗
Syndrome
(A)FANS
(B)IRNS
(c)FRNS
475.1 ± 139.3∗∗
311.1 ± 31.7∗
464 ± 288.6∗∗
503.3 ± 112.4∗∗
442.38 ± 74.1∗∗
441.7 ± 127.9∗∗
80.9 ± 5.6
78.6 ± 5.7∗∗
79.5 ± 4.8∗∗
327.4 ± 104∗∗
249.5 ± 106.5∗∗
269.2 ± 123.8∗∗
95 ± 27.8∗∗
62.2 ± 6.3∗
92.8 ± 57.7∗∗
72.8 ± 27.9∗∗
76.0 ± 29.8∗
85.3 ± 29.1∗∗
25
9
6
FANS: First Episode Nephrotic Syndrome, IRNS: Infrequent Relapsing Nephrotic Syndrome and FRNS: Frequent Relapsing Nephrotic Syndrome.
∗ p-value < 0.01, ∗∗ p-value < 0.001.
Groups
Controls (A)
Active nephrotic syndrome (B)
Remission (C)
B vs C
C vs A
No of
cases
20
40
40
Triglycerides
(mg/dL)
93.4 ± 49.3
427.6 ± 173.7
183.0 ± 141.2
< 0.001
< 0.01
Cholesterol
(mg/dL)
105.3 ± 29.1
473.8 ± 107.6
240.9 ± 172.1
< 0.001
< 0.001
HDL
(mg/dL)
21.6 ± 10.4
80.0 ± 5.4
66.9 ± 17.5
< 0.001
< 0.001
LDL
(mg/dL)
64.9 ± 21.1
293.9 ± 110.8
143.7 ± 141.6
< 0.001
< 0.01
VLDL
(mg/dL)
18.7 ± 9.7
85.5 ± 34.8
36.6 ± 28.2
< 0.001
< 0.01
Lp (a)
(mg/dL)
30.4 ± 19.3
76.3 ± 28.1
44.6 ± 35.6
< 0.001
< 0.05
FANS: First episode Nephrotic Syndrome, IRNS: Infrequent Relapsing Nephrotic Syndrome and FRNS: Frequent Relapsing Nephrotic Syndrome.
Table 3
Correlation of serum triglycerides, cholesterol,HDL, LDL, VLDL and Lp(a) with serum albumin in active nephrotic syndrome (n = 40)
Parameters (mg/dL)
Triglycerides
Cholesterol
HDL
LDL
VLDL
Lp(a)
Mean ± SD
427.6 ± 173.7
473.8 ± 107.6
80.0 ± 5.4
293.9 ± 110.8
85.5 ± 34.8
76.3 ± 28.1
Serum albumin (1.8 ± 0.4 gm/dL)
Correlation coefficient (r)
SE of “r”
p-value
Regression coefficient (b)
−0.5942
0.1548
< 0.001
−274.96
−0.5856
0.1560
< 0.001
−172.09
−0.4794
0.1689
< 0.01
−6.21
−0.4411
0.1727
< 0.05
−110.89
−0.5942
0.1548
< 0.001
−54.99
−0.1170
0.1911
NS
−7.45
“a”value
891.97
761.95
90.82
492.74
178.32
89.62
FANS: First Episode Nephrotic Syndrome, IRNS: Infrequent Relapsing Nephrotic Syndrome and FRNS: Frequent Relapsing Nephrotic Syndrome.
4. Discussion
The elevated levels of triglycerides, cholesterol,
HDL, LDL and VLDL in ANS patients and its persistence in remission are in accordance to the observations
of previous authors [1,3]. Further, it was found that
FANS and FRNS patients behaved in a similar manner
in relationship to lipid parameters, with both groups
having a relatively high values in comparison to IRNS
group. Mahmud [8] also reported hyperlipidemia at
remission and concluded that serum total cholesterol
may be regarded as predictor of relapse in children
with idiopathic nephrotic syndrome. Querfeld [1] also
reported raised lipid parameters in relapsers.
The raised Lp(a) levels in the active state have been
demonstrated by previous workers [5,6]. The relapsers
showed relatively higher mean levels in comparison to
the first episode, but the differences were statistically non-significant. Kawasaki [7] observed increased
Lp(a) levels both in infrequent as well as frequent relapsers and the latter had significantly higher levels
(p < 0.01) than the former and the authors found that
Lp(a) concentration could be an independent risk factor for relapse of nephrotic syndrome in children. Noto [6] also reported decreased levels of Lp(a) in the
remission stage of nephrotic patients. It was noted that
45% of patients had Lp(a) levels above 30 mg/dL (cutoff value for increased risk of atherogenesis) and most
of them were relapsers. Garnotel [5] found increased
Lp(a) levels in 66% of relapsers in the active phase and
persistence of elevated levels in 44% of their cases in
the remission period. Thus, the abnormal levels are
found in both the active phase as well as the remission
phase of relapsing patients. Kniazewska also emphasized the importance of regular laboratory tests, not
only for cholesterol and its fractions but also for Apo
A1, Apo B and HCY2 in children treated for idiopathic
nephritic syndrome. They also recommended evalua-
Downloaded by: Vanderbilt University. Copyrighted material.
Table 2
Serum triglycerides, cholesterol, HDL, LDL, VLDL and Lp(a) in controls, active nephrotic syndrome and in remission (mean ± SD)
tion of intima-media thickness of the carotid arteries in
frequent relapsers [9].
The increased Lp(a) levels in childhood with active nephrotic syndrome are mainly related to hypoalbuminemia, probably through a mechanism involving
apo-B over production, which leads to an increased
number of LDL particles to be converted into Lp(a) [6,
10]. However, persistence of increased Lp(a) levels
above 30 mg/dL indicate that some other pathogenetic
mechanism is involved rather than increase in synthesis, particularly during remission when serum albumin
levels get normalized. The positive relationship between the serum Lp(a) levels and proteinuria was in accordance with the finding of Hong and Yang [11] who
also reported a significant direct correlation of Lp(a)
with urinary proteins levels (r = 0.675, p < 0.0001).
This suggests that alterations in Lp(a) may be the result of the degree of proteinuria rather than the serum
albumin concentration in active disease. Furthermore,
its persistence during the remission phase in relapsers
points towards a high risk of atherogenesis in future [12,
13]. The role of these circulating factors in the pathogenesis of frequent relapses is also demonstrated by
therapeutic efficacy of LDL-apheresis [14,15]. However, it would require long term follow up to detect
if there are atherosclerotic complications of nephrotic
syndrome and to assess if lipid lowering agents would
provide good metabolic control in these patients.
[3]
[4]
[5]
[6]
[7]
[8]
[9]
[10]
[11]
[12]
[13]
References
[14]
[1]
[2]
Querfeld U, Gnasso A, Haberbosch W, Augustin J, Scharer
K. Lipoprotein profiles at different stages of the nephrotic
syndrome. Eur J Pediatr 1988;147(3):233-238.
Valeri A, Gelfand J, Blum C, Appel GB. Treatment of the
hyperlipidemia of the nephrotic syndrome: a controlled trial.
Am J Kidney Dis 1986;8(6):388-396.
[15]
Oetliker O, Mordasini R, Lutschg J, Riesen W. Lipoprotein
metabolism in nephrotic syndrome in children. Pediatr Res
1980;14(1):64-66.
Orth SR, Ritz E. The nephrotic syndrome. N Engl J Med 1998;
338(17):1202-1211.
Garnotel R, Roussel B, Pennaforte F, Randoux A, Gillery P.
Changes in serum lipoprotein(a) levels in children with corticosensitive nephrotic syndrome. Pediatr Nephrol 1996;10(6):
699-701.
Noto D, Barbagallo CM, Cascio AL, Cefalu AB, Cavera G,
Caldarella R, et al. Lipoprotein(a) levels in relation to albumin
concentration in childhood nephrotic syndrome. Kidney Int
1999;55(6):2433-2439.
Kawasaki Y, Suzuki J, Nozawa R, Suzuki S, Suzuki H. Prediction of relapse by plasma lipoprotein(a) concentration in
children with steroid – sensitive nephrotic syndrome. Nephron
2002;92(4):807-811.
Mahmud S, Jahan S, Hossain MM. Hyperlipidemia in childhood idiopathic nephrotic syndrome during initial remission
and relapse. Mymensingh Med J 2011;20(3):402-406.
Kniazewska MH, Obuchowicz AK, Wielkoszyński T,
Zmudzińska-Kitczak J, Urban K, Marek M, et al. Atherosclerosis risk factors in young patients formerly treated for idiopathic nephrotic syndrome. Pediatr Nephrol 2009;24(3):549554.
Muls E, Rossence M, Daneels R, Schurgors M, Boelaert J.
Lipoprotein distribution and composition in human nephrotic
syndrome. Atherosclerosis 1985;54(2):225-237.
Hong SY, Yang DH. Lipoprotein(a) levels and fibrinolytic
activity in patients with nephrotic syndrome. Nephron 1995;
69(2):125-130.
Joven J, Simo JM, Vilella E, Camps J, Espinel E, Villabona C.
Accumulation of atherogenic remnants and lipoprotein(a) in
the nephrotic syndrome: relation to remission of proteinuria.
Clin Chem 1995;41(6 Pt 1):908-913.
Wanner C, Rader D, Bartens W, Kramer J, Brewer HB,
Schollmeyer P, et al. Elevated Plasma lipoprotein(a) in patients
with the nephrotic syndrome. Ann Intern Med 1993;119(4):
263-269.
Kobayashi T, Ando Y, Umino T, Miyata Y, Muto S, Hironaka
M, et al. Complete remission of minimal-change nephrotic
syndrome induced by apheresis monotherapy. Clin Nephrol
2006;65(6):423-426.
De Palo T, Giordano M, Bellantuono R, Colella V, Troise D,
Palumbo F, et al. Therapeutic apheresis in children: Experience in a pediatric dialysis center. Int J Artif Organs 2000;
23(12):834-839.
Downloaded by: Vanderbilt University. Copyrighted material.
O.P. Mishra et al. / Serum lipids and lipoprotein(a) in nephritic syndrome
162
Документ
Категория
Без категории
Просмотров
2
Размер файла
116 Кб
Теги
1586406, 0036
1/--страниц
Пожаловаться на содержимое документа