Lipid profile in children with Nephrotic syndrome

Chavan S.1, Salunkhe S.2, Singh A.3, Agarkhedkar S.4, Suhas Sodal5, Jadhav R.6

1Dr. Sanjay Chavan, Professor, 2Dr. Shradha Salunkhe, Associate Professor, 3Dr. Anshuman Singh, Senior Resident, 4Dr. Sharad Agarkhedkar, Professor and Head of  Department, 5Dr. Suhas Sodal, Assistant Professor, 6Dr. Renuka Jadhav, Professor, all authors are affiliated with Dr. D.Y. Patil Medical College, Hospital And Research Center, Dr. D. Y. Patil Vidyapeeth Society,  Pimpri, Pune. Maharashtra, India.

Corresponding Author: Dr. Shradha Salunkhe, Associate Professor, Dr D.Y. Patil Medical College Hospital and Research Center, Pimpri, Pune, Maharashtra. India. Email Id: salunkheshradha@gmail.Com

Abstract

Background: To  study  the  derangement  of  serum  lipid  profile  in children 2 to 12 years with  nephrotic  syndrome. Methods: 50 children 2 to 12 years with nephrotic syndrome were identified. Patients were classified as remission, relapse and newly diagnosed. Lipid Profile was measured. Patients were followed-up after 4 weeks of steroid therapy. Results: Out of all the 50 subjects screened, 25 (50%) subjects had high total cholesterol, 26 (52%) had high triglyceride, 8 (16%) had abnormal HDL cholesterol and 25 (50%) had high LDL cholesterol. After 4 weeks of steroid therapy though there was significant reduction in lipid components. Conclusion: Our study shows that in nephrotic syndrome, there is generalised hyperlipidemia and hypoalbuminemia. Serum cholesterol, triglycerides and LDL cholesterol were deranged in almost all subjects. In cases in relapse after 4 weeks of steroid therapy there is persistent raised total cholesterol, triglycerides and LDL cholesterol, which may predispose to the development of atherosclerosis in near future.

Keywords: Nephrotic syndrome, Hyperlipidemia, hypoalbuminemia, steroid

Manuscript received: 6th June 2018, Reviewed: 16th June 2018
Author Corrected: 24th June 2018, Accepted for Publication: 30th June 2018

Introduction

Nephrotic syndrome is primarily a paediatric disorder and is 15 times more common in children than adults. The incidence is 2-3/100,000 children per year; and the majority of affected children will have steroid-sensitive minimal change disease. The characteristic features of nephrotic syndrome are heavy proteinuria (>3.5 g/24 hr in adults or 40 mg/m2/hr in children), hypoalbuminemia (<2.5 g/dl), oedema, and hyperlipidemia (serum cholesterol >200mg/dl). Hyperlipidemia  is  recognised  as  a  common  finding  in  patients  with  nephrotic syndrome  since  1917, when  hypercholesterolemia  was  described  as  a  feature  of   nephrotic  syndrome [1].

Hyperlipidemia  is  usually  observed  during  the  active  phase  of  the  disease  and  disappears  with  resolution of proteinuria. However, it  may  persist in  some  cases,  leading  to  increase  risk  of  atherosclerosis  in  later  life and development of progressive renal injury [2]. Hence  close  monitoring  of  lipid  levels  during  remission  of  nephrotic  syndrome  is  necessary  to  select  high  risk  patients [3]  Children with Nephrotic Syndrome are  at  an  increase  risk  for  cardio  vascular  disease  due  to  the  hyperlipidemia  present  in  them.  

Hyperlipidemia  is  not  always  connected  with  nephrotic  disease  activity  and  may  sometimes  persist  for  long  time,  especially  in  frequently  relapsing  nephrotic  syndrome.  Though  after  steroid  treatment  the  lipid  profile  shows  lower  values  than  in  active  state,  no  normalisation  of  indices  were  observed  in  remission[4].

The  present  study  is  designed  to  study  the  spectrum  of  serum  lipid  profile abnormalities  in children  with  nephrotic  syndrome.

Materials and Methods

Aims and Objectives: To  study  the  derangement  of  serum  lipid  profile  in children 2 to 12 years with  nephrotic  syndrome .

Type of study: Prospective case study

Sample size: 50 cases fulfilling the inclusion criteria

Place of study: Dr. D.Y.Patil Medical College, Hospital and Research Center, Pimpri, Pune- 18

Inclusion Criteria: Following parameters were considered for inclusion of cases in present study:
•    Age group between 2 years to 12 years
•    Idiopathic nephrotic syndrome
•    Relapsing nephrotic syndrome
•    Frequent relapses nephrotic syndrome
•    Steroid dependence nephrotic syndrome
•    Steroid resistant nephrotic syndrome

Exclusion Criteria
•    Age less than 2 years and more than 12 years
•    Familial hyperlipidemia
•    Presence of any disease other than Nephrotic syndrome like persistent hypertension, renal tumours, cardiovascular disorders etc

Methodology: All the children fulfilling the inclusion criteria were identified and selected for study after obtaining written informed consent. The sample population were recruited from the outpatient clinic or in patient’s ward of Dr. D. Y. Patil Medical College, Hospital and Research Centre, Pimpri, Pune. A detailed history was taken and samples were taken for further investigations. Patients were classified as remission, relapse and newly diagnosed. Children with oedema, low serum albumin and urinary protein of more than 40 mg/m/hour or 3+/4+ protein were considered as nephrotic syndrome or relapse. Patients were considered in remission when urine albumin was nil or trace or proteinuria less than 4 mg/m2 /hour for three consecutive days. Patients were classified as remission, relapse and newly diagnosed.

Blood was collected in fasting state in the early morning and the samples were analysed for serum total proteins, serum albumin, serum globulin, blood urea, serum creatinine and lipid profile (total cholesterol, triglycerides, LDL, VLDL, HDL). Lipid profile was measured at the admission to the hospital and again in remission.  

The Serum Lipid was measured by: Total cholesterol: measured by CHOD-PAP Method, Triglycerides: measured by GPO-TINDER Method,HDL and LDL Cholesterol: measured by Polyvinyl Sulfonic Acid (PVS) and Polyethylene Glycol Methyl Ether (PEGME) coupled classic precipitation method. Serum proteins were measured by Biurate Method. The renal functions were measured by Urease Method. Creatinine clearance was calculated by: Cockcroft-Gault equation.  
Creatinine clearance = [140-age (years)]* weight(kg)]/ [72* s.creatinine(mg/dl)]              
Multiply by 1 for male
0.85    or female

The UPCR: Urine protein was measured by – Pyragalol method and Urine creatinine was measured by Jaffe w/o deproteinization. (UPCR- urine protein creatinine ratio)

Patients in relapse and newly diagnosed cases were followed-up after 4 weeks of steroid therapy and samples for serum protein and serum lipid were taken.

Treatment protocol: First episode: 60 mg/m2 /day daily (maximum dose 80mg divided into 2-3 doses) prednisolone for 6 weeks, followed by 40 mg/m2 /day alternate day as a single morning dose for 6 weeks.

Relapse cases 60 mg/m2 /day daily (maximum dose 80 mg divided into 2-3 doses) prednisolone until child enters remission, followed by 40 mg/m2 /day alternate day as a single morning dose for 6 weeks.

Stastical analysis: The collected data were analysed using the SSPS software (Statistical Package for the Social Sciences, version 2.1). p values less than 0.05 were considered statistically significant.

Results

In the study there were 40% of children in the 2-4 years of age group, 36% between 4-8 years of age group and 24% between 8-12 years. In the study there were 56% males and 44% females, suggesting a male predominance.

Cases were classified into relapse, remission and new cases. 46% cases were in relapse, 40 % in remission and 14 % were newly diagnosed cases. Out of 23 subjects in relapse 18 (78.25%) were frequent relapsers, 4 (17.49%) of infrequent relapse while 1 (4.35%) was having steroid resistance.

Out of 50 cases screened 29 (58%) subjects had periorbital oedema, 21 (42%) had ascites, 14 (28%) had oliguria, 13 (26%) had generalised oedema, 9 (18%) had pallor, 4 (8%) had hypertension and 1 (2%) had peritonitis.

Table-1: Derangement of serum lipids of children in study group

Lipid profile

No of cases

Percentage (n=50)

Sr. Cholesterol

25

50

Sr. Triglyceride

26

52

Sr. HDL

8

16

Sr. LDL

25

50

Out of all the 50 subjects screened 25 (50%) had elevated total cholesterol levels, 26 (52%) had elevated triglyceride levels, 8 (16%) had deranged HDL cholesterol levels and 25 (50%) had elevated LDL Cholesterol levels.

Table-2: Correlation between Sr. Albumin and lipid profile in study group

Correlation between Sr. Albumin

r Value

P Value

Sr. Cholesterol

-0.74

<0.0001

Sr. Triglyceride

-0.43

<0.005

Sr. HDL

-0.31

<0.05

Sr. LDL

-0.49

<0.0001

There is inverse correlation of total cholesterol, triglyceride, HDL and LDL cholesterol with serum albumin and is statistically significant.

Table-3: Correlation between Creatinine clearance and lipid profile in study group

Correlation between Creatinine clearance

r Value

P Value

Sr. Cholesterol

0.12

>0.05

Sr. Triglyceride

0.24

>0.05

Sr. HDL

-0.04

>0.05

Sr. LDL

0.19

>0.05

There was positive correlation of total cholesterol, triglyceride and LDL cholesterol with creatinine clearance but was statistically not significant. There was negative correlation of HDL cholesterol and was statistically not significant.

Table-4: Showing number of subjects with derangement of lipid parameters Pre steroid after 4 weeks of steroid therapy

Lipid Parameters

No of cases (presteroid)

Percentage (n=30)

No of cases

Percentage(n=30)

Total cholesterol

25

83.33

10

33.33

Triglyceride

23

76.66

08

26.66

HDL

06

20

01

3.33

LDL

24

80

13

43.33

The above table compares number of subjects with derangements in lipid parameters pre steroid and post steroid. After 4 weeks of steroid therapy though there were significant reductions in lipid components in all the subjects, total cholesterol was still above normal limit in 10 (33.33%) subjects, triglycerides in 8 (26.66%) subjects, HDL cholesterol was decreased in 1 (3.33%) subject and LDL cholesterol was increased in 13 (43.33%) subjects.

Table-5: Showing number of subjects with derangement of lipid parameters in subjects in remission

Lipid Parameters

No of cases

Percentage(n=20)

Total cholesterol

00

00

Triglyceride

03

15

HDL

02

10

LDL

01

05

Out of 20 subjects in remission, triglyceride was above normal limit in 3 (15%) subjects, HDL cholesterol was decreased in 2 (10%) subject and LDL cholesterol was increased in 1 (5%) subjects. Total cholesterol was normal in all the subjects.

Table-6:  Comparison of lipid profile with patients in remission with patients in relapse

Lipid profile

Remission

t Value

P Value

Yes (n=20)

No (n=30)

Mean

SD

Mean

SD

Sr. Cholesterol

132.90

30.682

386.87

143.565

7.77

<0.0001

Sr. Triglyceride

94.55

54.033

347.03

300.077

3.71

<0.001

Sr. HDL

41.10

8.032

54.03

17.641

3.07

<0.005

Sr. LDL

87.50

17.163

248.03

150.670

4.73

<0.0001

Serum lipid of patients in remission and relapse were compared. Total cholesterol, triglyceride, HDL cholesterol and LDL cholesterol were high in relapse and were statistically significant.

Table-7:  Comparison of protein, albumin, and globulin at relapse and follow up in study group

Parameter

At Relapse (n=30)

At follow up (n=30)

t Value

P Value

Mean

SD

Mean

SD

Sr. Protein

5.07

0.79

6.54

0.51

13.43

<0.0001

Sr. Albumin

2.57

0.74

3.92

0.26

10.87

<0.0001

Sr. Globulin

2.53

0.59

2.72

0.39

1.54

>0.05

Serum proteins were evaluated after 4 weeks of steroid therapy and were found to be significantly high (6.54mg %) which was statistically significant (p<0.0001), serum albumin was also high (3.92mg %) and statistically significant (p<0.0001), Serum globulin was also high (2.72) but was statistically not significant (p>0.05).

Table-8:  Comparison of lipid profile at relapse and after1month follow up in study group

Lipid profile

At Relapse (n=30)

At follow up (n=30)

t Value

P Value

Mean

SD

Mean

SD

Sr. Cholesterol

386.87

143.565

194.07

50.316

8.73

<0.0001

Sr. Triglyceride

347.03

300.077

169.60

92.289

4.11

<0.0001

Sr. HDL

54.03

17.641

50.73

9.340

1.15

>0.05

Sr. LDL

248.03

150.670

133.73

57.197

4.95

<0.0001

Serum lipids were evaluated after 4 weeks of steroid therapy and were found to be significantly lower and were statistically significant.

Discussion

This  study  was  designed  to  study  the  derangement  of  serum  lipid  profile  in patients  with  nephrotic  syndrome  and  to  know  whether  any  correlation  exists  between  serum  lipid  and  albumin as hyperlipidemia may persist in some cases, leading to increased risk of atherosclerosis in later life.                           

It was observed that there is inverse correlation of serum albumin with total cholesterol, LDL cholesterol and triglycerides. When serum albumin was low (mean = 2.57 mg %) total cholesterol (mean = 386.87 mg %) was high as observed in patients in relapse phase of nephrotic syndrome, which was statistically significant (p<0.0001). Inverse correlation was also found with LDL cholesterol (mean = 248.03 mg %), and triglycerides (mean = 347.03 mg %) (Table 1).In a study on lipoprotein metabolism in nephrotic syndrome in childhoodbyOetliker et al significant negative correlations were shown between plasma albumin and cholesterol (r = -0.85, p less than 0.005) and between plasma albumin and low density lipoprotein (LDL) - apoprotein B (ApoB) (r=-0.84, p less than 0.005)[5].

We compared creatinine clearance with total cholesterol (p>0.05), LDL cholesterol (p>0.05), Triglyceride (p>0.05) and HDL (p>0.05). The correlation is statistically not significant (p>0.05). In a study on serum creatinine is a poor marker of GFR in nephrotic syndrome by Amanda et al they found that serum creatinine is a poor marker of GFR in nephrotic syndrome [6].

In our study there was significant rise in total cholesterol (mean = 386.87 mg %) in patients in relapse phase of nephrotic syndrome as compared to total cholesterol (mean = 132.90 mg %) in patients in remission and was statistically very significant (p<0.0001).

Similarly  LDL cholesterol (mean = 150.67 mg % ), triglycerides (mean = 347.03 mg% ) in patients in relapse phase was high as compared to LDL cholesterol (mean = 87.50 mg % ), triglycerides (mean = 94.55 mg %) in patients in remission (table 4). This was statistically significant (p<0.0001) and (p<0.001) respectively. Arije et al in his study on plasma lipids and lipoproteins cholesterol distributions in nephrotic syndrome patients during short term steroid treatment, had similar observations in his study [7]. We observed a positive correlation between serum total cholesterol, LDL cholesterol and triglycerides and was statistically highly significant (p <0.001).  It was also observed in studies on lipid abnormalities in the nephrotic syndrome by David et al [8] and low density lipoprotein levels in children with nephrotic syndrome by Benakappaet al[9].

There was direct correlation of serum albumin with HDL cholesterol observed in our study. When serum albumin was low HDL cholesterol was also low. The correlation is statistically significant (p<0.05). In a study on serum lipid profiles during onset and remission of steroid sensitive nephrotic syndrome in children done by Sreenivasa B et al, they also observed inverse relation between serum albumin and cholesterol and was highly significant (p=0.000).[10]  Patients in relapse phase of the disease were followed up after 4 weeks of steroid therapy. There was significant reduction in total cholesterol, LDL cholesterol and triglycerides.

Total cholesterol (mean = 194.07 mg %), LDL cholesterol (mean = 133.73 mg %), triglycerides (mean = 169.60 mg %) were significantly lower in follow up after 4 weeks of steroid therapy (table 12) and was statistically significant with all the above parameters had (p<0.0001). Similar observations were also made by other researchers (Mac Lean and Robson et al [11] in their study on a simple method for determining selectivity of proteinuria, Wanner et al [12] in a study on elevated plasma lipoprotein (a) in patients with nephrotic syndrome and Joven et al [13] in a study on Pattern of hyperlipoproteinaemia in human nephrotic syndrome). After 4 weeks of steroid therapy though there were significant reductions in lipid components in all the subjects, total cholesterol was still above normal limit in 10 (33.33%) subjects, triglycerides in 8 (26.66%) subjects, HDL cholesterol was decreased in 1 (3.33%) subject and LDL cholesterol was increased in 13 (43.33%) subjects.

Of 20 subjects in remission, triglyceride was above normal limit in 3 (15%) subjects, HDL cholesterol was decreased in 2 (10%) subject and LDL cholesterol was increased in 1 (5%) subjects. Total cholesterol was normal in all the subjects.

23 patients were in relapse and of them 18 (78.25%) were frequent relapse and 1(4.35%) subject was steroid resistant nephrotic syndrome. Of all the subjects, 4 subjects in the relapse phase were found to have hypertension.

Therefore, the raised levels of various lipid parameters, frequent relapsers, steroid resistant nephrotic syndrome and children with hypertension concomitantly predispose these children for increased risk of atherosclerosis and thrombosis in future.

Conclusion

Our study shows that in nephrotic syndrome, there is generalised hyperlipidemia and hypoalbuminemia. Serum cholesterol, triglycerides and LDL cholesterol were deranged in almost all subjects in relapse phase of nephrotic syndrome. Few subjects in remission phase also had deranged cholesterol, triglycerides and LDL cholesterol.

In cases of relapse after 4 weeks of steroid therapy there is persistent raised total cholesterol (33.33%), triglycerides (26.66%) and LDL (43.3%) cholesterol, which may predispose to the development of atherosclerosis in near future. However, all the children require long term follow-up before any conclusion can be drawn.

What does this study add? The raised levels of various lipid parameters, frequent relapsers, steroid resistant nephrotic syndrome and children with hypertension concomitantly predispose these children for increased risk of atherosclerosis and thrombosis in future.

Atherosclerosis occurs due to narrowing of vessels which takes years to develop. However, the process of atherosclerosis begins in childhood, is usually mild and progresses over a period of time. So it is unusual for children or teenagers to have a heart attack or stroke as a result of atherosclerosis. In some children, atherosclerosis worsens rapidly, increasing the risk of heart disease, and less commonly, stroke in early adult life.

Long term follow up of these patients are required, for detection of complications if any, and possibility of therapeutic interventions.

Contribution by authors: Dr. Anshuman Singh and Dr.SuhasSodal have collected the data. Dr Renuka Jadhav have compiled the data. Dr. Sanjay Chavan and Dr. Shradha Salunkhe have analyzed the data and written the manuscript.  Dr Sharad Agarkhedkar (H.O.D) has constantly guided throughout the study.

Acknowledgements:I am thankful to the children involved in this study and their parents, without their cooperation it would not have been possible to complete this study.


Ethical Approval: The study was carried out after the approval from the Institutional Ethical Committee of Dr.D.Y.Patil Medical College, Hospital and Research Center, Pimpri, Pune.

Funding: Nil, Conflict of interest: None initiated,
Perission from IRB: Yes

References

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How to cite this article?

Chavan S, Salunkhe S, Singh A, Agarkhedkar S, Suhas Sodal, Jadhav R. Lipid profile in children with Nephrotic syndrome. Int J Pediatr Res. 2018;5(6):314-319.doi:10.17511/ijpr.2018.6.03.