Lipid profile in children with Nephrotic syndrome

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.


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/m 2 /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 hyper cholesterolemia 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 . 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: 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.
Pediatric Review: International Journal of Pediatric Research Available online at: www.pediatricreview.in 316|P a g e  There is inverse correlation of total cholesterol, triglyceride, HDL and LDL cholesterol with serum albumin and is statistically significant. 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. 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. 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.  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). 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 childhood by Oetliker 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.
Pediatric Review: International Journal of Pediatric Research Available online at: www.pediatricreview.in 319|P a g e 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.