European Journal of Cardiovascular Medicine

Nephrotic syndrome is a clinical entity characterized by massive proteinuria, hypoalbumimia, edema and hyperlipidemia with or without hypertension, haematuria and azotemia. By definition nephrotic syndrome has the following criteria as per ISKDC (International Study of kidney Diseases in Children) there should be proteinuria (more than 3gm / day / 1.73 m2 of body surface area or 40 mg/hr/m2), hypoproteinemia (less than 2.5 gm %) edema and hyperlipidemia (serum cholesterol level more than 220 mg%).  
Abnormal lipid metabolism is common in patients with renal disease.1,2,3 This effect is most prominent in nephrotic syndrome, where marked elevations in the plasma levels of cholesterol, LDL, triglycerides and lipoprotein(a) often occur.4 Hypoalbuminemia, increased lipoprotein synthesis and decreased lipoprotein lipase activity are described by various workers.5  

Total HDL-cholesterol levels are usually normal or reduced in nephrotic syndrome and there is often a pronounced decline in the cardioprotective HDL2 fraction. The mechanism by which this occurs is unclear, but elevations in the plasma concentration of cholesteryl ester transfer protein in nephrotic patients may contribute by shuttling cholesteryl esters from HDL2 to very low density lipoproteins.6,7 The concentration of plasma apolipoproteins in the nephrotic syndrome generally reflects the alterations in lipoprotein metabolism. Thus, there are elevated levels of apo B, C-II, and E, which are associated with VLDL and LDL; on the other hand, the levels of the major apolipoproteins associated with HDL, apo A-I and A-II, are usually normal.8 Plasma free fatty acids (FFA) are reduced probably due to their binding to albumin although their concomitant increase in lipids results in normal fatty acid concentration.9 Also there is some evidence that at least in the nephrotic syndrome in childhood, the lipid abnormalities may persist into remission in between relapses.10 Hence, aim of this study was to study was performed to observe the pattern of lipid profile in the children with idiopathic nephrotic syndrome and the effect of treatment on the same. 

This present observational, cross-sectional study of 40 cases of nephrotic syndrome children aged between 2-8 years was 
carried out from June 2022 to July 2023.  
Study population and sampling technique : The study was conducted among the child population with nephrotic  syndrome attending paediatric renal clinical or outpatient/ inpatient department of Paediatrics of Medical College & Hospital, Kolkata, West Bengal, India were included in the study. 
Sample size : Estimated sample size was 40. Prevalence of hyponatremia in pneumonia is 6%. Sample size is calculated by 4pq/l2 [p- 6%, q- (100-6), l- 4%]. 
Inclusion criteria : Children aged between 2-8 years with H/O generalised edema in Paediatric outpatient or inpatient department were screened for inclusion for our study. Detailed history taking and clinical examination were done as per prescribed proforma or protocol. 
Exclusion criteria : Children presenting with generalised edema but not fulfilling  the above criteria or showing  some additional symptoms/ signs for which these cases were excluded from the study. 
After initial selection from history taking and clinical examination, some routine baseline investigations were performed. With strong suspicion and supportive baseline investigations we proceeded for next step investigation to confirm the diagnosis. After provisional selection on clinical ground and supportive baseline investigations, final selection of study group were done by confirmation of the final diagnosis of idiopathic nephrotic syndrome. Some patients were treated with a course of antibiotics for urinary or respiratory or any other source of infection. Anti tubercular drugs were given cases where clinical history, chest X-ray or Mantoux test were suggestive of tuberculosis. The results of estimation of different fraction of lipid profile were recorded in individual proformas containing particulars of the child and also in the grand chart.  
Data Analysis plan- Data was analyzed using Statistical Package for Social Sciences, version 20 (SPSS). All the data in the grand chart were analysed statistically with the help of mean, standard deviation (S.D) paired/unpaired ‘t’ value and ‘P’ value (Probability value) for determination of significance. 

This study was performed amongst 40 children between 2-8 years of age of both sexes suffering from idiopathic nephrotic 
syndrome. 

Table 1: Clinical data showing age & sex distribution in 40 children under the study (n=40) Age (yr) Sex Total Percentage (%) M F 2 - 4 12 9 21 52 4– 6 7 5 12 30 6– 8 3 4 7 18 Total 22 18 40 100 It was observed that more than 50% of children under this study were in the age group between 2-4 years. 30% were in between 4+ -6 years and remaining 18% cases were in between 6+ to 8 years. Sex distribution was not significant and M : F ratio was almost 1 : 1. (Table 1) Table 2 : Categorisation and their distribution in 40 nephrotic children under study. Nephrotic category No of children (n) Percent (%) F.E 10 25 I.R 26 65 F.R 4 10 n = No. of children. FE-First Episode.I.R – Infrequent relapser, F.R – Frequent relapse. The children under study were categorised into 3 groups according to the number and frequency of nephrotic episodes at the time of presentation – 1) First Episode (FE) or 1st attack 2) Infrequent Relapser (I.R.) those children presented at their second or subsequent relapses when the number of relapses is less than 2 within 6 months or less than three within one year and (3) Frequent Relapser (FR) are those children presented at their 2nd or subsequent relapses when the number is two or more within 6 months or three or more within one year. Number of nephrotic children presented during first episode (FE) was 10 (25%). Majority (65%) were under the category of infrequent relapser (I:R) and only 4 children (10%) were frequent relapse. (Table 2) Table 3: Distribution of nephrotic children against their serum albumin and serum cholesterol level during both stages (before & after treatment) of nephrotic activity. Serum albumin (gm/dl) No. of children During relapse During remission <1.5 4(10%) NIL 1.5 – 2.5 25 (62 %) 3 (7%) 2.6 – 3.5 9 (23%) 22. (55%) >3.5 2 (5%) 15 (38%) Total Serum cholesterol (mg/dl) <220 mg% Nil 24 (60%) 220 – 400 29 (73%) 16 (40%) 401 – 550 6 (15%) Nil >550 5 (12%) Nil Serum albumin estimation of all children was done prior to therapy and after remission following steroid therapy. It was observed that maximum number of nephrotics (62%) during relapse showed their serum albumin level between 1.5 - 2.5 gm/dl. 9 cases out of 40 children (23%) were in between 2.5- 3.5 gm/dl. Only 4 cases (10%) showed their serum albumin below < 1.5 gm /dl and 2 cases (5%) exceptionally showed their serum albumin more than 3.5 gm /dl. It was also observed that the serum albumin scenario had been radically changed after remission among the same children and most cases restored their near normal serum albumin level. Only 3 cases (7%) showed below 2.5 gm/ dl even after therapy but level below 1.5 gm/ dl was not found in any case. Total serum cholesterol is an important component of lipid profile study and this was estimated during relapse and after remission. In this study, there was no single case of untreated nephrotics during 

Since long it is well established that hyperlipidaemia is one of the characteristic features of nephrotic syndrome and now becomes a criteria in the definition of that disorder. Here in this study we have found that not only serum total cholesterol was elevated in every cases of nephrotic syndrome but also other fractions of serum lipids and some fractions of lipoproteins and apoproteins were also elevated. 
In the present study, we have found that among 20 control children the fasting mean cholesterol value was about 132 mg / dl whereas among 40 nephrotic syndrome patients, the fasting mean total cholesterol value was above 370 mg / dl. The elevated value among nephrotic syndrome patients was statistically significant. 
Regarding the study of triglyceride level in serum among normal children the mean value was about 109 mg / dl whereas among the nephrotic syndrome children during relapse the mean value of that lipid was about 310 mg / dl which was statistically very significant similar to change of cholesterol value in nephrotic children. Some cases of nephrotics showed their triglyceride level about 5 times the normal value. Baxter JH in 196211 and Glossock et.al in 198112 showed that total serum cholesterol is almost always increased in nephrotic syndrome except in mild cases. In our present study, we have found an elevated total cholesterol level in every case of nephrotic syndrome. In 5 cases the values were more than 550 mg / dl i.e 4- 5 times the normal value. Same observation was made by Appel G et al in 198513, Gherardi et al in 197714; Chan M et al in 198115, Sokolovskaya et al in 198416. In our study also, the phospholipid and triglyceride level showed an elevation manyfold of the normal level in this similar manner in respect of change of the cholesterol profile among nephrotic children. 
In the study of Baxter JH in 196211, it was observed that cholesterol/ phospholipid ratio may be increased upto 1.6 from normal control value of 0.80. In our study, the cholesterol / phospholipid ratio among nephrotic children during relapse was increased to 1. 08 compared to matched control value of 0.80.  
Baxter in 196211, Kekki and Nikkila in 197117, Jensen in 196718 and Oetliker et al 198019 showed that the serum triglyceride level remained normal in a significant number of nephrotic cases. But our study showed that almost every case of nephrotic children showed an increased triglyceride level in their serum. This variation may be due to a difference in the age group of nephrotics among which this study was performed. 
Appel et al in 198520, Zelleruelo et al in 198421, Baxter in 196022, Gherardi et al in 197714 showed in their study that these is a significant negative correlation between plasma albumin and total triglyceride and cholesterol concentration. In our study we have also observed that there is a significant but weak inverse correlation between serum albumin and total serum cholesterol concentration among nephrotic syndrome children during relapse.  
The study of previous investigators showed a much variation of HDL cholesterol concentration in their serum – it may be decreased, normal or even be increased. Gherardi et al in 197714, De Mendoza et al in 197623, Oetliker et al in 198019.

Lopes Virella et al 1979²⁴ reported that HDL cholesterol concentration in serum are increased in nephrotic syndrome. Our study also showed that most cases of nephrotic syndrome in relapse showed an elevated HDL level than control.

In our study, the mean serum Apo- A1 concentration among contral children was about 86 mg / dl whereas the Apo- A1 value among nephrotic syndrome children in relapse was about 90 mg / dl. Zhang H et al in 1994²⁵ showed a decrease in Ao- A1 concentration among 45 children of nephrotic syndrome with normal renal function but our result showed a mild increase in serum Apo – A1 concentration.

 Some cases of nephrotics showed their Apo- B value in their serum 2 –3 times the normal value. Zhang et al in 1994, D’ Amico et al in 1991²⁶ reported in their studies that serum concentration of Apo – B among nephrotic children was significantly raised which is consistent with the result of our present study.

Our study is similar to the result observed by Zhang et al in 1994²⁵ and D’ Amico et al in 1991²⁶. Like the HDL / LDL ratio, the Apo A1 / Apo B ratio carries a significance of development of atherosclerotic cardiovascular disorder in the long run.

Zilleruelo et al in 1984²¹ found that a significant number of nephrotic patients in remission who had persistently abnormal serum lipid values (mainly increases in cholesterol and LDL) and the reason for the continuous elevation of these lipids was not clear but in general it was associated with prolonged disease and frequent relapses. In this study, we also observed that most of the serum lipids persistently elevated even after remission and this was more pronounced among the frequent relapsers and was minimum among the subgroup of nephrotic syndrome patients presented during their 1^st attack.

Zhang et al in 1994²⁵, Zelleruelo et al in 1984¹⁰ observed that the ratio of HDL to LDL or Apo A1 to ApoB which had been decreased significantly during relapse and this low value persistently maintained upto remission among most of the nephrotic patients. The same observation was found in our study and it was especially pronounced among frequent relapser group.

Most of the fractions of serum lipids, lipoproteins and apoproteins are significantly increased in idiopathic nephrotic syndrome in children. The severity of hyperlipidaemia increases with the number and / frequency of episodes. A significant negative correlation between serum albumin and serum cholesterol concentration was observed in this study. The early identification of persistent hyperlipidaemia in nephrotic syndrome children could provide a better understanding of pathogenetic factors of the disease itself and of its progression and possible tendency towards atherosclerosis and chronic renal disease

Acknowledgements : Authors would like to acknowledge the patients who participated in this research study. 

Funding: No funding sources 

Conflict of interest: None declared 

Ethical approval:  The study was approved by the institutional ethics committee 

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