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Research Article | Volume 14 Issue: 4 (Jul-Aug, 2024) | Pages 22 - 37
Prevalence of cardiovascular disease risk factors in childhood nephrotic syndrome in eastern India
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1
Senior resident, DNB Paediatrics, Department of Paediatric Medicine, Dr. B. C. ROY PGIPS, 111, Narkeldanga main road, Phoolbagan, Kankurgachi, Kolkata, 700054.
2
Senior resident, MD paediatrics, Department of Paediatric Medicine, Dr. B. C. ROY PGIPS, 111, Narkeldanga main road, Phoolbagan, Kankurgachi, Kolkata, 700054.
3
Assistant Professor, MD paediatrics, Department of Paediatric Medicine, Dr. B. C. ROY PGIPS, 111, Narkeldanga main road, Phoolbagan, Kankurgachi, Kolkata, 700054.
4
Assistant Professor, MD, DM (Paediatric Cardiology), Department of Cardiology, IPGMER & SSKM Hospital, 244, A.J.C. Bose Road, Kolkata, 700020
Under a Creative Commons license
Open Access
DOI : 10.5083/ejcm
Received
May 8, 2024
Revised
May 24, 2024
Accepted
June 18, 2024
Published
July 8, 2024
Abstract

Introduction: Worldwide, nephrotic syndrome (NS) is a prevalent childhood illness. It is distinguished by elevated proteinuria (nephrotic range > 3.5 g/24 hr), edema, hypoalbuminemia (≤ 2.5 g/dl), and hyperlipidemia. Nephrotic syndromes are thought to affect 12–16 instances out of every 100,000 people; among Indian children, there are at least 150,000–200,000 cases, and an additional 10,000 cases are reported annually. Aims: Estimation of prevalence of risk factors of cardiovascular disease in childhood nephrotic Syndrome in eastern India. Materials and method: This research was conducted using a prospective longitudinal observational design. This study was carried out at the Dr. B. C. Roy Postgraduate Institution of Paediatric Sciences from January 1, 2021, to May 31, 2022. This study covered 54 patients in total. Result: According to our study, all patients [54 (100.0%)] had edema upon enrolment, however, a lesser number of patients experienced relapses throughout the 1-year follow-up, and a greater number of patients [48 (88.9%)] did not have edema at that time, which was statistically significant. (p<.00001). Carotid intima-media thickness measures were found to be statistically significant in most individuals upon one year follow up, with values of 0.05 cm (right) and 0.045 cm (left) and changes in left ventricular diastolic internal diameter, inferior venaceva (IVC) collapsibility were also statistically significant whereas other cardiovascular parameters such as left ventricular mass (LVM) index, Posterior wall thickness, interventricular septal thickness, , relative wall thickness, were not significant. Conclusion: Having the potential to become hypercoagulable Numerous cardiovascular risk factors are taken into consideration while evaluating nephrotic syndrome. While most echocardiographic parameters were found to be statistically insignificant, several clinical and laboratory indicators were found to be significant.

Keywords
INTRODUCTION

Nephrotic syndrome (NS) is a common pediatric ailment throughout the world. Elevated proteinuria (nephrotic range > 3.5 g/24 hr), edema, hypoalbuminemia (≤ 2.5 g/dl), and hyper lipidemia are characteristics that set it apart. An estimated 12–16 instances per 100,000 people are thought to be affected by nephrotic syndromes; children in India account for at least 150,000–200,000 of these cases, and an additional 10,000 are reported each year [1]. Primary renal disease is the most frequent secondary cause of pediatricnephrotic syndrome; systemic illnesses such as lupus or long-term infections such as HIV and hepatitis B and C are less prevalent. Primary glomerular sickness may be caused by a known genetic mutation that affects glomerular basement membrane proteins; however, the exact mechanism causing most instances is unknown and is believed to be connected to the immune system. many glomerular diseases, including minimal change disease. Elevated proteinuria, oedema, and hypoalbuminemia are the hallmarks of nephrotic syndrome, one of the most common kidney disorders affecting adults and children.Nephrotic syndrome affects two to seven new children cases annually, with a frequency of sixteen cases per 100,000 children and three new adult cases per 100,000 persons. Nephrotic syndrome's occurrence in adults is difficult to determine since it typically results from an underlying condition. While the majority of adults and children respond to initial glucocorticoid therapy by entering a clinical remission, 20% of adults and 50% of children either develop clinical steroid resistance throughout the course of their disease or appear with it initially.The probability of several unfavorable outcomes increases significantly if a patient does not experience clinical remission. These issues might be brought on by exposure to the safer alternative drugs that are employed to bring the sickness into remission or by the nephrotic state's enduring tenacity. Membranous nephropathy (MN), focal segmental glomerulosclerosis (FSGS), membranoproliferative glomerulonephritis (MPGN), minimal change disease (MCD), and, to a lesser extent, IgA nephropathy/IgA vasculitis (IgA N/IgAV) all share characteristics with nephrotic syndrome. Many children with steroid-resistant non-small-cell lung disease (NS) progress to chronic kidney disease (CKD), which is known to significantly raise cardiovascular mortality and morbidity in children and adolescents. While uncommon in adults, glomerular disease is a major cause of chronic kidney disease (CKD) in children. In the 854 kids involved in the CKiD (Children's Chronic Kidney Disease) study, it accounted for 29% of all CKD cases [2]. In a similar vein, 186 index kidney transplant patients from the North American Paediatric Trials and joint studies accounted for 31% of all occurrences of end stage renal disease. Among children receiving dialysis, cardiovascular disease (CVD) accounted for 33% to 36% of all fatalities, a proportion that was much higher than in the juvenile population as a whole. When young people with CKD who were formerly children grow up, their risk of having CVD increases significantly. The youthful and knowledgeable panel on population and preventative science that served as the American Heart Association's council for cardiovascular disease was made up of The greatest risk of CVD development is in children with CKD. Many of the risk factors that are generally acknowledged to be atherogenic and to hasten the establishment of adult chronic kidney disease (CKD) are present in children with NS. Thromboembolism, high blood pressure, oxidative stress, recurrent infections, prolonged proteinuria, hypoalbuminemia, toxicity from steroids, and side effects from nonsteroidal medications like calcineurin inhibitors (which can cause nephrotoxic effects, vasculotoxic effects, and hyperlipidemia) are additional risk factors that have been linked to poor endothelial function and adverse cardiovascular outcomes in addition to hyperlipidemia [3]. This is a well-known risk factor for CAD as well as a feature that sets NS apart. Hyperlipidemia and prolonged corticosteroid exposure are common causes of obesity and diabetes mellitus (DM). Hyperlipidemia and proteinuria are frequently sporadic and transient in people with steroid-sensitive nephrotic syndrome (SSNS); however, they might be persistent in patients with steroid-resistant nephrotic syndrome (SRNS) or recurrent relapse (FRNS). [4].

MATERIAL AND METHODS:

This was an institution based prospective longitudinal observational study conducted in a tertiary care health center of eastern India over a span of 1and half year. A total 54 patients of nephrotic syndrome aged 1 to 12 years attending both outpatient nephrology clinic and inpatient pediatric ward were taken into account. Patients having Diabetic mellitus, HIV infection, systemic lupus erythematous, active hepatitis B/C, active cancer, previous solid organ/bone marrow transplant, end-stage renal disease and cardiac disease unrelated to nephrotic syndrome (congenital heart disease, acquired heart disease like kawasaki disease, rheumatic heart disease, or myocarditis) at the time of screening were excluded. Demographic and clinical characterstics along with other variables of interest were estimation glomerular filtration rate (eGFR), serum albumin, urine protein and urine protein to creatinine ratio (UPCR), serum creatinine. Serum and urine creatinine was measured using the Jaffe method, and urine protein with a colorimetric method. Estimated GFR is calculated using the modified Schwartz formula. Blood pressure measurements has been obtained after 5 minutes of rest using a calibrated site-dependent oscillometric device at sitting posture. Patients are considered hypertensive and prehypertensive if the average blood pressure measurement exceeded the 95th and 90th percentile for age, sex and height respectively. According to centers for Disease Control and prevention (CDC) growth chart Weight will be classified as normal (BMI between the 5th percentile to less than the 85th percentile), overweight (BMI from 85th to less than the 95th percentile), or obese (BMI greater than or equal to the 95th percentile). Dyslipidemia at enrollment is defined per the National Heart, Lung and Blood Institute and the kidney disease: Improving Global Outcomes clinical practice guidelines, and included a total cholesterol ≥200 mg/dl, low density lipoprotein ≥130 mg/dl, high density lipoprotein < 40 mg/dl, or triglycerides ≥ 100 mg/dl (age 0-9 years) or ≥ 130 mg/dl (age 10-18 years). At enrolment prevalence of any of the following pre-existing CVD risk factors have been assessed - hypertension, obesity and dyslipidemias, proteinuria, hyperglycemia, prematurity and second-hand smoke exposure, diet etc. Pre-existing CVD diagnoses included coronary artery disease, heart failure, heart arrhythmia, stroke, peripheral vascular disease, aortic aneurysm and valvular heart disease have been obtained from participants’ interviews and previous documents at enrollment visit. All patients were undergone echocardiographic evaluation by means of Vivid S60N ultrasound system. Echocardiography and carotid intima medial thickness (IMT) are performed in all patients. Left ventricle (LV) dimensions has been obtained in the standard M Mode view. The left ventricular mass index (LVMI) (g/m2) has been calculated using the Devereux's formula by the following equation: Left Ventricular Mass (LVM) = 0.80 [1.04 × (interventricular septal thickness + posterior wall thickness + end-diastolic diameter) 3 - (end-diastolic diameter) 3] + 0.6. The LVMI has been calculated as LVM divided by the body surface area (BSA). LVMI > 38 g/H2.7 will be defined as Left ventricular hypertrophy (LVH). Biventricular systolic and diastolic function have been performed with conventional and tissue Doppler method. The IMT is defined as the distance between the first (lumen–intima interface) and the second (media–adventitia interface) echogenic line of the far wall, using a manual cursor placement measurement technique. The measurement was performed at a point 10-20 mm proximal to the common carotid bifurcation at a 10mm distance of far wall, at systolic phase of cardiac contraction [maximum diameter of the common carotid artery (CCA) lumen], in mid-longitudinal plane using maximum acceptable magnification of the image of the far wall. The examination was performed at supine position with a slightly overextended neck after 10 minutes of rest with High resolution B-mode system equipped with a linear array transducer 7.5 Hz. Two measurements were made on each side, and the mean value was calculated separately for each CCA. The internal diameter of CCA was also measured at the same site at both systolic (maximum diameter) and diastolic (minimum diameter) phases in axial image with maximum acceptable magnification by which both near and far wall of the CCA could be seen clearly.

For statistical analysis data were entered into a Microsoft excel spreadsheet and then analyzed by SPSS (version 27.0; SPSS Inc., Chicago, IL, USA) and Graph Pad Prism version 5. Data had been summarized as mean and standard deviation for numerical variables and count and percentages for categorical variables. The prevalence of cardiovascular risk factors has been measured with 95% confidence index (CI). Comparison of means has been done using unpaired t-test. Comparison of proportions has been done by using chi-square test. P value<=0.05 will be considered statistically significant.

This study was approved by institutional ethical committee and ethical standards on human experimentations were complied with and informed consent were taken.

RESULTS:

Table 01: Distribution of Type of NS

Parameters

Frequency

Percent

Type of NS

1st episode

31

57.40%

1st relapse

8

14.80%

2nd relapse

4

7.40%

4th relapse (IFRNS)

2

3.70%

FRNS

8

14.80%

IFRNS

1

1.90%

Total

54

100.00%

Type Of Ns During 1 YR F/UP

1st RELAPSE

1

1.90%

1st RELAPSE ON REMISSION

4

7.40%

2nd Episode on remission

1

1.90%

3rd Relapse (FRNS)

1

1.90%

3rd Relapse (IFRNS)

1

1.90%

FRNS (SDNS)

1

1.90%

No Further Episode, On Remission

33

61.10%

On 2nd Relapse

1

1.90%

SDNS On Relapse

2

3.70%

SDNS On Remission

9

16.70%

Total

54

100.00%

Type of hypertrophy at 1 Year

Concentric Remodeling

8

14.80%

Eccentric Hypertrophy

1

1.90%

Mild Concentric Remodeling

1

1.90%

Normal

44

81.50%

Total

54

100.00%

(LEFT)Carotid intima medial thickness at enrollment

0.045cm

18

33.30%

0.04cm

4

7.40%

0.05cm

32

59.30%

Total

54

100.00%

(RIGHT) Carotid Intima medial thickness at enrollment

0.045cm

22

40.8%

0.04cm

4

7.40%

0.05cm

28

51.90%

Total

54

100.00%

Table 02: Comparison between all parameters

Parameters

At Enrolment

At 1 Year

p-value

N

%

n

%

0.2468

SBP PERCENTILE

>50th

29

53.70%

40

74.07%

>5th &<50th

19

35.20%

11

20.40%

>90th

3

5.55%

2

3.70%

>95th

1

1.90%

0

0.00%

>99th

2

3.70%

1

1.90%

Total

54

100.00%

54

100.00%

DBP PERCENTILE

>50th

27

50.00%

36

66.70%

0.1928

>5th &<50th

3

5.60%

3

5.60%

>90th

10

18.51%

8

14.81%

>95th

7

12.96%

6

11.11%

>99th

7

13.00%

1

1.90%

Total

54

100.00%

54

100.00%

Oedema

Absent

0

0.00%

48

88.90%

<0.0001

Present

54

100.00%

6

11.10%

Total

54

100.00%

54

100.00%

CVS

WNL

54

100.00%

54

100.00%

1.0000

Total

54

100.00%

54

100.00%

Respiratory System

WNL

54

100.00%

54

100.00%

1.0000

Total

54

100.00%

54

100.00%

Gastro intestinal System

WNL

54

100.00%

54

100.00%

1.0000

Total

54

100.00%

54

100.00%

Central nervous System

WNL

54

100.00%

54

100.00%

1.0000

Total

54

100.00%

54

100.00%

Type of hypertrophy

concentric remodelling

11

20.40%

8

14.80%

0.6776

eccentric hypertrophy

1

1.90%

1

1.90%

mild concentric remodelling

0

0.00%

1

1.90%

Normal

42

77.80%

44

81.50%

Total

54

100.00%

54

100.00%

(LEFT)Carotid intima medial thickness

0.045cm

18

33.30%

11

20.40%

0.0259

0.04cm

4

7.40%

0

0.00%

0.05cm

32

59.30%

43

79.60%

Total

54

100.00%

54

100.00%

(RIGHT) Carotid Intima medial thickness

0.045cm

22

40.8%

11

20.40%

0.0044

0.04cm

4

7.40%

0

0.00%

0.05cm

28

51.90%

43

79.60%

Total

54

100.00%

54

100.00%

ECG

WNL

54

100.00%

54

100.00%

1.0000

Total

54

100.00%

54

100.00%

Urine protein

3+

52

96.30%

5

9.30%

<0.0001

4+

2

3.70%

1

1.90%

NIL

0

0.00%

38

70.40%

TRACE

0

0.00%

10

18.50%

Total

54

100.00%

54

100.00%

 

 

Table 03: Mean in all parameters


Parameters

At Enrolment (Mean ± SD)

At 1 Year (Mean ± SD)

P VALUE

BMI

16.0587±2.7015

16.8594± 2.5523

0.1164

LVM (gm)

41.2471± 22.2860

48.9677± 22.7609

0.0778

LVMI (gm/m2)

59.0430± 19.0138

63.0437± 18.1749

0.2258

Posterior wall thickness

5.7776± 1.1544

6.0369± 1.0341

0.2216

Interventricular Septal Thickness

6.4413± 1.5196

6.6485± 1.3777

0.4595

Left Ventricular Diastolic Internal Diameter

28.7689± 4.2920

31.4917± 4.5736

0.0019

Relative Wall Thickness

.4026± .0742

.3822± .0719

0.1498

IVC collapsibility

.4815± .0838

.5270± .0445

0.0006

RBS

81.0556± 7.2200

79.2407± 7.2135

0.1941

Albumin

2.3259± .3127

3.6889± .4800

<0.0001

Serum urea (mg/dl)

38.9074± 20.7276

24.2222± 5.8878

<0.0001

Serum creatinine (mg %)

.5461± .2003

.4481± .1476

0.0046

TG

246.9815± 51.3297

123.0370± 59.2847

<0.0001

TC

419.2037± 88.8221

161.1852± 132.6696

<0.0001

HDL

54.2037± 4.0065

56.4444± 5.8234

0.0217

LDL

199.8519± 39.7532

71.3889± 54.2786

<0.0001

 

In our study, 31 (57.4%) patients had 1st episode NS, 8 (14.8%) patients had1st relapse NS, 4 (7.4%) patients had 2nd relapse NS, 2 (3.7%) patients had 4th relapse (IFRNS) NS, 8 (14.8%) patients had FRNS and 1(1.9%) patient had IFRNS. The value of z is 6.322. The value of p is < .00001. The result is significant at p <.05. In our study, 1 (1.9%) patient had 1st Relapse, 4 (7.4%) patients had 1st relapse on remission, 1 (1.9%) patient had 2nd episode on remission, 1 (1.9%) patient had 3rd relapse (FRNS), 1(1.9%) patient had 3rd relapse (IFRNS), 1(1.9%) patient had FRNS (SDNS), 8(14.8%) patients had no further episode on remission after 1st, 2nd IFRNS and FRNS, 1(1.9%) patient had on 2nd Relapse, 2 (3.7%) patients had SDNS on relapse and 9 (16.7%) patients had SDNS on remission in 1 year follow up. The value of z is 6.6299. The value of p is < .00001. The result is significant at p <.05.

In our study, 8 (14.8%) patients had concentric remodeling type of hypertrophy, 1 (1.9%) patient had eccentric hypertrophy, 1 (1.9%) patient had mild concentric remodeling type of hypertrophy and 44 (81.5%) patients had normal findings on echocardiography at 1 year follow up. The value of z is 8.3927. The value of p is < .6776. The result is not significant as p >.05. In this study, 18 (33.3%) patients had 0.045cm Carotid intima-medial thickness, 4 (7.4%) patients had 0.04cm Carotid intima-medial thickness and 32 (59.3%) patients had 0.05cm (LEFT) Carotid intima-medial thickness at enrollment. The value of z is 5.7155. The value of p is < .0259. The result is significant at p <.05. In this study, 1 (1.9%) patient had 0.045cm Carotid intima-medial thickness, 21 (38.9%) patients had 0.045 cm Carotid intima-medial thickness, 4 (7.4%) patients had 0.04cm Carotid intima-medial thickness at enrolment and 28 (51.9%) patients had 0.05cm (RIGHT) Carotid Intima-medial thickness at enrollment. The value of p is < .0044. The result is significant at p <.05.

SBP PERCENTILE

In At Enrolment, 29 (53.70%) patients had >50th SBP Percentile, 19 (35.20%) patients had >5th &<50th SBP Percentile, 3 (5.55%) patients had >90th SBP Percentile, 1 (1.90%) patient was  >95th  SBP Percentile and 2 (3.70%) patients had >99th SBP Percentile.

In At 1 Year, 40 (74.07%) patients had >50th SBP Percentile, 11 (20.40%) patients had >5th &<50th SBP Percentile, 2 (3.70%) patients had >90th SBP Percentile and 1 (1.90%) patient was  >99th SBP Percentile.

Association of SBP Percentile with Parameters was statistically not significant (p= 0.2468).

 

 

DBP Percentile

In At Enrolment, 27 (50.00%) patients had >50th SBP Percentile, 3 (5.60%) patients had >5th &<50th SBP Percentile, 10 (18.51%) patients had >90th SBP Percentile, 7 (12.96%) patients had   >95th  SBP Percentile and 7 (13.00%) patients had >99th SBP Percentile.

In At 1 Year, 36 (66.70%) patients had >50th SBP Percentile, 3 (5.60%) patients had >5th &<50th SBP Percentile, 8 (14.81%) patients had >90th SBP Percentile, 6 (11.11%) patients had   >95th  SBP Percentile and 1 (1.90%) patient was  >99th SBP Percentile.

Association of DBP Percentile with Parameters was statistically not significant (p=0.1928 ).

Oedema

In At Enrolment, 54 (100.00%) patients had Present.

In At 1 Year, 6 (11.10%) patients had Present.

Association of Oedema with Parameters was statistically significant (p<0.0001).

CVS

In At Enrolment, 54 (100.00%) patients had WNL.

In At 1 Year, 54 (100.00%) patients had WNL.

Association of CVS with Parameters was not statistically significant (p=1.0000 ).

Respiratory System

In At Enrolment, 54 (100.00%) patients had WNL.

In At 1 Year, 54 (100.00%) patients had WNL.

Association of Respiratory System with Parameters was not statistically significant (p=1.0000 ).

Gastro intestinal System

In At Enrolment, 54 (100.00%) patients had WNL.

In At 1 Year, 54 (100.00%) patients had WNL.

Association of Gastro intestinal System with Parameters was not statistically significant (p=1.0000 ).

Central nervous System

In At Enrolment, 54 (100.00%) patients had WNL.

In At 1 Year, 54 (100.00%) patients had WNL.

Association of Central nervous System with Parameters was not statistically significant (p=1.0000 ).

Type of hypertrophy

In At Enrolment, 11 (20.40%) patients had concentric remodelling, 1 (1.90%) patient was concentric remodelling and 42 (77.80%) patients had Normal.

In At 1 Year, 8 (14.80%) patients had concentric remodelling, 1 (1.90%) patient was eccentric hypertrophy,  1 (1.90%) patient was mild concentric remodelling and  44 (81.50%) patients had Normal.

Association of Type of hypertrophy with Parameters was statistically not significant (p=0.6776 ).

(LEFT)Carotid intima-medial thickness

In At Enrolment, 18 (33.30%) patients had 0.045cm   (LEFT)Carotid intima medial thickness, 4 (7.40%) patients had 0.04cm (LEFT)Carotid intima medial thickness and 32 (59.30%) patients had 0.04cm (LEFT)Carotid intima medial thickness.

In At 1 Year, 11 (20.40%) patients had (LEFT)Carotid intima medial thickness and 43 (79.60%) patients had (LEFT)Carotid intima medial thickness.                       

Association of (LEFT)Carotid intima medial thickness with Parameters was statistically significant (p=0.0259 ).

(RIGHT) Carotid Intima medial thickness

In At Enrolment, 22 (40.80%) patients had 0.045cm   (RIGHT) Carotid Intima medial thickness, 4 (7.40%) patients had 0.04cm (RIGHT) Carotid Intima medial thickness and 28 (51.90%) patients had 0.04cm (RIGHT) Carotid Intima medial thickness.

In At 1 Year, 11 (20.40%) patients had (RIGHT) Carotid Intima medial thickness and 43 (79.60%) patients had (RIGHT) Carotid Intima-medial thickness.                  

Association of (RIGHT) Carotid Intima medial thickness with Parameters was statistically significant (p=0.0044).

ECG

In At Enrolment, 54 (100.00%) patients had WNL.                                                                            

In At 1 Year, 54 (100.00%) patients had WNL.                        

Association of ECG with Parameters was statistically not significant (p=1.0000 ).

Urine protein

In At Enrolment, 52 (96.30%) patients had3+ Urine protein and 2 (3.70%) patients had4+ Urine protein.

In At 1 Year, 5 (9.30%) patients had 3+ Urine protein,  1 (1.90%) patient was  4+ Urine protein and 10 (18.50%) patients had 3+ TRACE.

Association of Urine protein with Parameters was statistically significant (p<0.0001).

BMI

In At Enrolment, the mean BMI (mean± s.d.) of patients was 16.0587±2.7015.

In At 1 Year, the mean BMI (mean± s.d.) of patients was 16.8594± 2.5523.

Association of BMI with parameters was statistically not significant ( P = 0.1164).

LVM (gm)

In At Enrolment, the mean LVM (gm)(mean± s.d.) of patients was 41.2471± 22.2860.

In At 1 Year, the mean LVM (gm)(mean± s.d.) of patients was 48.9677± 22.7609.

Association of LVM with parameters was statistically not significant (P = 0.0778).

LVMI (gm/m2)

In At Enrolment, the mean LVMI (gm/m2) (mean± s.d.) of patients was 59.0430± 19.0138.

In At 1 Year, the mean LVMI (gm/m2) (mean± s.d.) of patients was 63.0437± 18.1749.

Association of LVMI with parameters was statistically not significant (P = 0.2258).

Posterior wall thickness

In At Enrolment, the mean Posterior wall thickness (mean± s.d.) of patients was 5.7776± 1.1544.

In At 1 Year, the mean Posterior wall thickness (mean± s.d.) of patients was 6.0369± 1.0341.

Association of Posterior wall thickness with parameters was statistically not significant (P = 0.2216).

Post wall thickness z score

In At Enrolment, the mean Post wall thickness z score (mean± s.d.) of patients was .8443± 1.1930.

In At 1 Year, the mean Post wall thickness z score (mean± s.d.) of patients was .8059± .9754.

Interventricular Septal Thickness

In At Enrolment, the mean Interventricular Septal Thickness (mean± s.d.) of patients was 6.4413± 1.5196.

In At 1 Year, the mean Interventricular Septal Thickness (mean± s.d.) of patients was 6.6485± 1.3777.

Association of IVSD with parameters was statistically not significant (P = 0.4595).

IVSD Z Score

In At Enrolment, the mean IVSD Z Score (mean± s.d.) of patients was 1.9930± 1.4200.

In At 1 Year, the mean IVSD Z Score (mean± s.d.) of patients was 1.8709± 1.2600.

Left Ventricular Diastolic Internal Diameter

In At Enrolment, the mean Left Ventricular Diastolic Internal Diameter (mean± s.d.) of patients was 28.7689± 4.2920.

In At 1 Year, the mean Left Ventricular Diastolic Internal Diameter (mean± s.d.) of patients was 31.4917± 4.5736.

Association of LVDID with parameters was statistically significant (P = 0.0019).

LVIDD Z Score

In At Enrolment, the mean LVIDD Z Score (mean± s.d.) of patients was -1.3091± .9877.

In At 1 Year, the mean LVIDD Z Score (mean± s.d.) of patients was -1.0050± 1.0304.

Relative Wall Thickness

In At Enrolment, the mean Relative Wall Thickness (mean± s.d.) of patients was .4026± .0742.

In At 1 Year, the mean Relative Wall Thickness (mean± s.d.) of patients was .3822± .0719.

Association of Relative wall thickness with parameters was statistically not significant (P = 0.1498).

IVC collapsibility

In At Enrolment, the mean IVC collapsibility (mean± s.d.) of patients was .4815± .0838.

In At 1 Year, the mean IVC collapsibilit (mean± s.d.) of patients was .5270± .0445.

Association of IVC collapsibility with parameters was statistically significant (P = 0.0006).

RBS

In At Enrolment, the mean RBS(mean± s.d.) of patients was 81.0556± 7.2200.

In At 1 Year, the mean RBS(mean± s.d.) of patients was 79.2407± 7.2135.

Association of RBS with parameters was statistically not significant (P = 0.1941).

Albumin

In At Enrolment, the mean Albumin (mean± s.d.) of patients was 2.3259± .3127.

In At 1 Year, the mean Albumin (mean± s.d.) of patients was 3.6889± .4800.

Association of Albumin with parameters was statistically significant (P < 0.0001).

Serum urea (mg/dl)

In At Enrolment, the mean Serum urea (mg/dl) (mean± s.d.) of patients was 38.9074± 20.7276.

In At 1 Year, the mean Serum urea (mg/dl) (mean± s.d.) of patients was 24.2222± 5.8878.

Association of Serum Urea with parameters was statistically significant (P < 0.0001).

Serum creatinine (mg %)

In At Enrolment, the mean Serum creatinine (mg %) (mean± s.d.) of patients was .5461± .2003.

In At 1 Year, the mean Serum creatinine (mg %) (mean± s.d.) of patients was .4481± .1476.

Association of Serum Creatinine with parameters was statistically significant (P = 0.0046).

TG

In At Enrolment, the mean TG (mean± s.d.) of patients was 246.9815± 51.3297.

In At 1 Year, the mean TG (mean± s.d.) of patients was 123.0370± 59.2847.

Association of TG with parameters was statistically significant (P < 0.0001).

TC

In At Enrolment, the mean TC (mean± s.d.) of patients was 419.2037± 88.8221.

In At 1 Year, the mean TC (mean± s.d.) of patients was 161.1852± 132.6696.

Association of TC with parameters was statistically significant (P < 0.0001).

HDL

In At Enrolment, the mean HDL (mean± s.d.) of patients was 54.2037± 4.0065.

In At 1 Year, the mean HDL (mean± s.d.) of patients was 56.4444± 5.8234.

Association of HDL with parameters was statistically significant (P = 0.0217).

LDL

In At Enrolment, the mean LDL (mean± s.d.) of patients was 199.8519± 39.7532.

In At 1 Year, the mean LDL (mean± s.d.) of patients was 71.3889± 54.2786.

Association of LDL with parameters was statistically significant (P < 0.0001).

DISCUSSION

This research was conducted using a prospective longitudinal observational design. This study was carried out at the Dr. B. C. Roy Postgraduate Institution of Paediatric Sciences from January 1, 2021, to May 31, 2022. This study covered 54 patients in total.

Lechner BL et al [5] (2004) found that Despite evidence linking individuals with hyperlipidemia, chronic kidney disease (CKD), or end-stage renal disease (ESRD) to an increased risk of cardiovascular disease (CVD), little research has been done on transient hyperlipidemia or intermittent renal disease caused by relapsing nephrotic syndrome (NS). A 32-year-old man with a family history of cardiovascular disease (CVD), a 41-year-old man with a history of hypertension, diabetes mellitus, increased cholesterol, and heavy smoking, and a 31-year-old man who overdosed on cocaine were the three patients who had experienced myocardial infarction (MI).

In this patient group, the incidence of events (8%) and death from cardiovascular disease (none) are similar to those of individuals in the general population and are lower than those of dialysis patients of the same age.

In our study, male[38(70.4%)]populationwashigherthanthefemale[16(29.6%)]population which was statistically significant. (p<.00001).

We found that, most of the patients had [31 (57.4%)] 1st episode NS (p< .00001). Both 1strelapseNS andFRNS Wherewith equal proportions [8 (14.8%)].

 

Ashoor IF et al [6] (2019) found that Cardiovascular disease is a major cause of morbidity and death for children with chronic renal impairment. At the time of recruitment, the prevalence of newly discovered cardiovascular risk factors, such as proteinuria, premature birth, and exposure to passive smoking, as well as well-known cardiovascular risk factors, such as obesity, hypertension, and high cholesterol, was measured and compared across glomerular disease subtypes. Based on glomerular disease subtype, steroid exposure, and remission status, the frequency of prescriptions for antihypertensive or lipid-lowering drugs, as well as the rates of dyslipidemia screening, were compared across groups. Of those screened, 51% were overweight or obese, 71% had dyslipidemia, and 21% had hypertension. Among the children who were not in remission at the time of inclusion, hypertension and hypercholesterolemia were more prevalent. 14% of youngsters with hypertension were not receiving antihypertensives.

It was found that, higher number of patients hadno further episode (in previous 1st episode,1st relapse, FRNS, SDNS), on remission [33(61.1%)] and we also found that, [25 (46.3%) patients had >50thpercentile both were statistically significant. (p<.00001).

 

Oh, J et al [4] (2002) found that Among those with end-stage renal disease (ESRD), cardiovascular mortality is disproportionately greater among their younger counterparts. Ninety-two percent of the patients had coronary artery calcifications; the average calcium score was more than ten times the 95th percentile across all age groups and genders. Examining the carotid IMT of matching control subjects revealed a significant increase. The IMT and coronary calcium scores were linked with the cumulative durations of dialysis and ESRD, as well as the cumulative serum calcium-phosphate product. The time-averaged mean serum parathyroid hormone, plasma homocysteine, C-reactive protein, and seropositivity for Chlamydia pneumonia were all substantially linked with coronary calcium scores.

We observed that, most of the patients had [36 66.7%)] >50th SBP Percentile at 1 Year, 24(44.4%) patients had >50th percentile in DBP percentile and 36 (66.7%) patients had >50thDBPPercentile at 1yearwhichwerestatisticallysignificant.(p<.00001).

Our study showed that, all patients [54 (100.0%)] had Oedema at enrolment but a few in the 1year follow up as there are a smaller number of relapses, higher number of patients had [48(88.9%)]no Oedemaat 1Yearwhich was statistically significant. (p<.00001)

CVS, Respiratory, GI System, Central nervous system examination at enrollment and at 1yearfollow up was wnl.

We found that, 42 (77.8%) patients had no hypertrophy at enrollment. (p=.00222), which is statistically significant.

Shatat IF et al [7] (2019) found that Arteriosclerosis (HTN) is a common concern for medical professionals who treat children with steroid-sensitive (SSNS) and steroid-resistant nephrotic syndrome (SRNS). In addition to elevated arterial stiffness measurements, children with NS are also more likely to have endothelial dysfunction, increased pulse wave velocity (PWV), impaired glucose metabolism, dyslipidemia, left ventricular hypertrophy (LVH), left ventricular dysfunction, and atherosclerosis, which are risk factors for cardiovascular disease. These risk factors have been associated with adult premature death. The prevalence and etiology of HTN in patients with NS will be covered in this review and treatment of hypertension in adults with NS as well as HTN in children with NS.

We found that, majority number of patients had [44 (81.5%)] no hypertrophy at 1 Year and 0.05cm (LEFT) Carotid in timamedial thickness at enrollment [32(59.3%)] both were statistically significant. (p<.00001).

Groothoff JW et al [8] (2002) found that Growing arterial stiffness is one risk factor for mortality in people with end-stage renal disease (ESRD) over 40. Every surviving adult Dutch patient aged 0 to 14 years who developed ESRD between 1972 and 1992 was enrolled for cardiac and carotid artery ultrasonography as well as blood pressure monitoring. Of the 187 individuals who met the qualifying criteria, thirty-seven received carotid and cardiac artery ultrasonography. 29.0 years old is the average age (20.7 to 40.6). The patients' intima media thickness was similar to that of the controls, but they had higher stiffness parameterβ (4.2 versus 3.8; 95% CI, 0.05 to 0.68; P<0.001), an increased elastic incremental modulus Einc (0.35 versus 0.27 kPa•103; 95% CI, 0.02 to 0.12; P<0.001), and a lower mean artery wall distensibility DC (40.0 vs 45.0 kPa−1 • 10−3; 95% CI, −9.1 to −0.8; P<0.001).

Oh J et al [4] (2002) found that Among those with end-stage renal disease (ESRD), cardiovascular mortality is disproportionately greater among their younger counterparts. High-resolution ultrasound was used to quantify the intima-media thickness (IMT) of the carotid arteries, and a CT scan with ECG gating was used to assess the degree of calcification in the coronary arteries. In all age categories and genders combined, the average calcium score was over 10 times the 95th percentile, and 92 percent of the patients exhibited coronary artery calcifications. Examining the carotid IMT of matching control subjects revealed a significant increase. The cumulative durations of dialysis and ESRD, as well as the cumulative serum calcium-phosphate product, were correlated with the IMT and coronary calcium scores.

Hooman N et al [9] (2013) found that Renal syndrome patients frequently utilize immunosuppressive drugs, which raises their blood pressure, cholesterol, and risk of atherosclerosis. They looked at carotid measurements in kids with nephrotic syndrome as possible early indicators of atherosclerosis. Children with nephrotic diseases had a mean carotid intima-media thickness (mm) of 0.42 (±.14), whereas controls had a mean cIMT of 0.37 (±.08) (p-value <.05). Following the use of log transformation, the carotid intima-media thickness varied considerably (p-value <.001) across individuals diagnosed with nephrotic disease. Therefore, the factor influencing cIMT(P<.05.5) was the duration of the illness. Half of the children with nephrotic disorders exhibited left ventricular hypertrophy on echocardiography. It was associated (P<.05) with both systolic hypertension and carotid stiffness.

It was discovered that the majority of patients [28 (51.9%)] had medial thickness of the carotid intima measuring 0.05 cm on the left at enrollment [43 (79.6%)], and 0.05 cm on the right at enrollment [43 (79.6%)]. It showed statistical significance. (p<.00001).

Hooman N et al [9] (2013) found that People with renal syndrome have a higher risk of developing atherosclerosis due to their high blood pressure, high cholesterol, and frequent use of immunosuppressive medications. They examined carotid measures as potential early markers of atherosclerosis in children with nephrotic syndrome. Between 2008 and 2011, 51 children with a history of nephrotic syndrome were included in the study. The mean carotid intima-media thickness (mm) in children with nephrotic disorders was 0.42 (±.14), whereas the mean cIMT in controls was 0.37 (±.08) (p-value <.05). After a log transformation, general linear multivariate analysis revealed that carotid intima-media thickness varied significantly among nephrotic patients (p-value <.001). As a result, the factor influencing cIMT was the duration of the illness (P<.05.

We observed that, all patients [54 (100.0%)] ECG was normal at enrolment and at1 Year.

And we also found that, most of the patients had 3+ Urine protein at enrollment [52 (96.3%)] which was statistically significant. (p<.00001)

Ray EC et al [10] (2015) found that Salt retention is one of the primary clinical signs of nephrotic syndrome. For quite some time, there have been discussions over the storage of salt in this particular setting. Even in the absence of renin-angiotensin-aldosterone pathway activation, some individuals with nephrotic syndrome show significant salt retention. This might be a sign of underlying renal insufficiency that impacts the excretion of salt.  The processes by which elements present in nephrotic urine activate sodium transporters have been clarified by a recent study. These mechanisms not only provide new avenues for managing blood pressure and edema in the context of nephrotic syndrome, but they also probably play a role in the development of hypertension, which can be difficult to control in the condition.

Wang C Setal [11] (2017) found that there is a lack of information on sequelae, hospitalization risk factors, and outpatient therapy for children diagnosed with nephrotic syndrome (NS). Approximately 50% of the patients had problems with urine protein monitoring and non-adherence to prescriptions. With a median rate of 0.5 hospitalizations per patient year, the majority of patients (71%) had at least one hospital stay. An average patient stayed in the hospital for 4.0 (3.8) days.

Ku E et al [2] (2018) found that Anorexia and malnutrition are associated with poor outcomes in children with chronic kidney disease (CKD). There was a mean decrease in BMI z score of 0.13 (95% CI, 0.09-0.17) with each additional 10 mL/min/1.73 m2 drop in eGFR until it reached <35 mL/min/1.73 m2. When the eGFR was less than 35 mL/min/1.73 m2, there was a statistically significant departure from the weight trajectory (P < 0.001). Children and adolescents with substantial weight loss (defined as a decline in BMI z score > 0.2 each year) had 3.28 (95% CI, 1.53-7.05) times higher risks of end-stage renal disease (ESRD) once their eGFR fell to <35 mL/min/1.73 m2. Those with constant BMI z scores, on the other hand, had a shift in BMI z score of 0-0.1, annually.

In our study, the mean SBP at enrolment (mmhg) of patients was [95.2963± 8.6409], SBP at1Year (mmhg) [96.9259±6.7624], DBP at enrolment (mmhg) [64.0926±7.9224], DBP at1 Year (mmhg) [63.9074±5.6075].

BMI at enrolment (kg/m2) [16.0587± 2.7015], BMI at 1 Year (kg/m2) [16.8594± 2.5523].this is not statistically significant.

LVM at enrolment (gm) [41.2471± 22.2860] and LVM at 1 Year (gm) [48.9677± 22.7609]. This is also not statistically significant.

We found that, the mean LVM index at enrolment (gm/m2) of patients was [59.0430±19.0138], LVM index at 1 Year (gm/m2) [63.0437±18.1749]. Not statistically significant.

Posterior wall thickness at enrollment (mm) [5.7776± 1.1544], Post wall thickness z score at enrollment [.8443± 1.1930], Posterior wall thickness at 1 Year (mm) [6.0369± 1.0341], Post wall thicknesses Z score at 1year [.8059± .9754]. This is not statistically significant,

Interventricular Septal Thickness at enrollment (mm) [6.4413± 1.5196], IVSD Z SCORE at enrollment (mm) [1.9930±1.4200], Interventricular Septal Thickness at 1 Year (mm) [6.6485± 1.3777] and IVSD Z SCORE at 1 yr [1.8709± 1.2600]. This is not statistically significant.

It was found that, the mean Left Ventricular Diastolic Internal Diameter at enrollment (mm) of patients was [28.7689±4.2920], LVIDDZSCORE at enrollment [1.3091±.9877], which was statistically significant.

Ventricular Diastolic Internal Diameter at 1 Year (mm) [31.4917±4.5736], LVIDDZSCORE at 1 year [1.0050± 1.0304].This comparison was statistically significant.

Relative Wall Thickness at enrollment [.4026± .0742], Relative Wall Thickness at 1 Year [.3822±.0719]. Not statistically significant.

IVC collapsibility at enrollment (%) [.4815±.0838], IVC collapsibility at 1 Year (%) [.5270±.0445] was statistically significant as there were more patients in 1 year follow up. Whose IVC collapsibility was more than 50%.

RBS at enrollment (mg/dl) [81.0556± 7.2200] and mean RBS at 1 year (mg/dl) [79.2407±7.2135]. Not statistically significant.

Appel GB et al [3] (1985) found that although hyperlipidaemia is a common feature of the nephrotic syndrome, the distribution of cholesterol among plasma lipoproteins and the mechanism responsible for the increased hepatic production of lipoprotein lipids are yet unknown. The levels of total plasma cholesterol showed a strong negative correlation with the levels of plasma albumin (r = -0.528) and oncotic pressure (r = -0.674), but not with viscosity (r = +0.319). Rather than fluctuations in plasma viscosity, the greater hepatic synthesis of lipoprotein lipids appears to be the result of reduced plasma albumin concentration or oncotic pressure.

Hilmanto D et al [12] (2022) found that Nephrotic syndrome (NS) is one of the most common kidney diseases that afflict kids. NS symptoms such edema, hypoalbuminemia, hyperlipidaemia, and severe proteinuria might cause systemic disease. The heart, kidneys, thyroid hormone, infections, and teeth are the main organs affected by childhood neurotoxicity. In order to properly manage patients' health, healthcare providers need to avoid certain problems.

Our study showed that, the mean SGOT at enrolment (U/l) of patients was [52.4259±39.1738], SGPT at enrolment (U/l) [74.8333±101.4167], ALP at enrolment (U/l) [111.7407±78.7078]. Mild elevation during the course of the disease but not significant.

Albumin at enrollment (gm/dl) [2.3259± .3127], Albumin at 1 year (gm/dl) [3.6889± .4800].More patients had hypo-albuminuria during enrollment, which is statistically significant.

The concentration of serum urea (mg/dl) was [38.9074± 20.7276] and at one year f/up [24.2222± 5.8878] elevated levels during the illness enrollment process, although wnl.

Serum creatinine (mg %) [.5461± .2003], Serum creatinine (mg %) 1 year f/up [.4481± .1476].Not statistically significant.

TG at enrolment (mg/dl) [246.9815±51.3297], TC at enrolment (mg/dl) [419.2037±88.8221], HDL at enrolment (mg/dl) [54.2037±4.0065], LDL at enrolment (mg/dl) [199.8519±39.7532], TG at 1 Year (mg/dl) [123.0370±59.2847], TC at 1 Year (mg/dl) [161.1852±132.6696], HDL at 1 Year (mg/dl) [56.4444±5.8234] and LDL at 1 Year (mg/dl) [71.3889±54.2786]. This is statistically significant.

Our study showed that, most of patients had>5th &<50th SBP PERCENTILE in At Enrolment Group [19(35.20 %)] compared to At 1 Year Group [11(20.40%)] but this was not statistically significant (p=0.2468).

We observed that, higher number of patients had>50th DBP PERCENTILE in At 1 Year Group [36(66.70%)] compared to At Enrolment Group [27            (50.00%)] but this was not statistically significant (p=0.1928).

We examined that, more number of patients had Oedema in At Enrolment Group [54(100.00%)] compared to At 1 Year Group [6(11.10%)] but this was statistically significant (p<0.0001).

Our study showed that, equal patients had WNL CVS in At Enrolment Group and At 1 Year Group [54(100.00%)] but this was not statistically significant (p=1.0000).

Our study showed that, equal patients had WNL Respiratory System in At Enrolment Group and At 1 Year Group [54(100.00%)] but this was not statistically significant (p=1.0000).

Our study showed that, equal patients had WNL Gastro intestinal System in At Enrolment Group and At 1 Year Group [54(100.00%)] but this was not statistically significant (p=1.0000).

Our study showed that, equal patients had WNL Central nervous System in At Enrolment Group and At 1 Year Group [54(100.00%)] but this was not statistically significant (p=1.0000).

We observed that, higher number of patients had concentric remodelling in At 1 Year Group [44(81.50%)] compared to At Enrolment Group [42(77.80%)] but this was not statistically significant (p=0.6776).

We examined that, more number of patients had 0.05cm (LEFT) Carotid intima medial thickness in At 1 Year Group [43(79.60%)] compared to At Enrolment Group [32(59.30%)] but this was not statistically significant (p=0.0259).

We examined that, more number of patients had 0.05cm (RIGHT) Carotid Intima medial thickness in At 1 Year Group [43 (79.60%)] compared to At Enrolment Group [28         (51.90%)] but this was not statistically significant (p=0.0044).

Our study showed that, equal patients had WNL ECG in At Enrolment Group and At 1 Year Group [54(100.00%)] but this was not statistically significant (p=1.0000).

We examined that, more number of patients had 3+ Urine protein in At Enrolment Group [52(96.30%)] compared to At 1 Year Group [5(9.30%)] but this was statistically significant (p<0.0001).

In our study, BMI was higher in At 1 Year Group [16.8594± 2.5523] compared to At Enrolment Group [16.0587±2.7015].

We found that, LVM (gm) was higher in At 1 Year Group [48.9677± 22.7609] compared to At Enrolment Group [41.2471± 22.2860].

In our study, LVM (gm/m2) was higher in At 1 Year Group [63.0437± 18.1749] compared to At Enrolment Group [59.0430± 19.0138].

We found that, Posterior wall thickness was higher in At 1 Year Group [6.0369± 1.0341] compared to At Enrolment Group [5.7776± 1.1544].

In our study, Post wall thickness z score was higher in At Enrolment Group [.8443± 1.1930] compared to At 1 Year Group [.8059± .9754].

We found that, Interventricular Septal Thickness was higher in At 1 Year Group [6.6485± 1.3777] compared to At Enrolment Group [6.4413± 1.5196].

In our study, IVSD Z Score was higher in At Enrolment Group [1.9930± 1.4200] compared to At 1 Year Group [1.8709± 1.2600].

We found that, Left Ventricular Diastolic Internal Diameter was higher in At 1 Year Group [31.4917± 4.5736] compared to At Enrolment Group [28.7689± 4.2920].

In our study, LVIDD Z Score was higher in At 1 Year Group [-1.0050± 1.0304] compared to At Enrolment Group [-1.3091± .9877].

We found that, Relative Wall Thickness was higher in At Enrolment Group [.4026± .0742] compared to At 1 Year Group [.3822± .0719].

In our study, IVC collapsibility was higher in At Enrolment Group [.5270± .0445] compared to At 1 Year Group [.4815± .0838].

We found that, RBS was higher in At Enrolment Group [81.0556± 7.2200] compared to At 1 Year Group [79.2407± 7.2135].

In our study, Albumin was higher in At Enrolment Group [3.6889± .4800] compared to At 1 Year Group [2.3259± .3127].

We found that, Serum urea (mg/dl) was higher in At Enrolment Group [38.9074± 20.7276] compared to At 1 Year Group [24.2222± 5.8878].

In our study, Serum creatinine (mg %) was higher in At 1 Year Group [.5461± .2003] compared to At Enrolment Group [.4481± .1476].

We found that, TG was higher in At Enrolment Group [246.9815± 51.3297] compared to At 1 Year Group [123.0370± 59.2847].

In our study, TC was higher in At Enrolment Group [419.2037± 88.8221] compared to At 1 Year Group [161.1852± 132.6696].

We found that, HDL was higher in At 1 Year Group [56.4444± 5.8234] compared to At Enrolment Group [54.2037± 4.0065].

In our study, LDL was higher in At Enrolment Group [199.8519± 39.7532] compared to At 1 Year Group [71.3889± 54.2786].

CONCLUSION

In conclusion, while underlying dyslipidaemia indicates a clear cardiovascular risk in nephrotic syndrome, there is no significant change in echocardiographic measures, other than medial carotid intimal thickness, when patients are followed up a year later. When it came to clinico-laboratory indicators, the changes in lipid derangement and blood pressure were statistically significant both at enrolment and follow-up. A longer-term follow-up is advised for individuals with a few forms of nephrotic syndrome who advance to FRNS, SDNS, or SRNS. These patients have a complex treatment course that requires ongoing monitoring for possible cardiovascular risk.

REFERENCES
  1. Chavers BM, Herzog CA. The spectrum of cardiovascular disease in children with predialysis chronic kidney disease. Advances in chronic kidney disease. 2004 Jul 1;11(3):319-27.
  2. Ku E, Kopple JD, McCulloch CE, Warady BA, Furth SL, Mak RH, Grimes BA, Mitsnefes M. Associations between weight loss, kidney function decline, and risk of ESRD in the chronic kidney disease in children (CKiD) cohort study. American journal of kidney diseases. 2018 May 1;71(5):648-56.
  3. Appel GB, Blum CB, Chien S, Kunis CL, Appel AS. The hyperlipidemia of the nephrotic syndrome: Relation to plasma albumin concentration, oncotic pressure, and viscosity. New England Journal of Medicine. 1985 Jun 13;312(24):1544-8.
  4. Oh J, Wunsch R, Turzer M, Bahner M, Raggi P, Querfeld U, Mehls O, Schaefer F. Advanced coronary and carotid arteriopathy in young adults with childhood-onset chronic renal failure. Circulation. 2002 Jul 2;106(1):100-5.
  5. Lechner BL, Bockenhauer D, Iragorri S, Kennedy TL, Siegel NJ. The risk of cardiovascular disease in adults who have had childhood nephrotic syndrome. Pediatric Nephrology. 2004 Jul;19:744-8.
  6. Ashoor IF, Mansfield SA, O'Shaughnessy MM, Parekh RS, Zee J, Vasylyeva TL, Kogon AJ, Sethna CB, Glenn DA, Chishti AS, Weaver DJ. Prevalence of cardiovascular disease risk factors in childhood glomerular diseases. Journal of the American Heart Association. 2019 Jul 16;8(14):e012143.
  7. Shatat IF, Becton LJ, Woroniecki RP. Hypertension in childhood nephrotic syndrome. Frontiers in pediatrics. 2019 Jul 16;7:287.
  8. Groothoff JW, Gruppen MP, Offringa M, de Groot E, Stok W, Bos WJ, Davin JC, Lilien MR, Van de Kar NC, Wolff ED, Heymans HS. Increased arterial stiffness in young adults with end-stage renal disease since childhood. Journal of the American Society of Nephrology. 2002 Dec 1;13(12):2953-61.
  9. Hooman N, Isa-Tafreshi R, Otukesh H, Mostafavi SH, Hallaji F. Carotid artery function in children with idiopathic nephrotic syndrome. Nefrología (English Edition). 2013 Sep 1;33(5):650-6.
  10. Ray EC, Rondon-Berrios H, Boyd CR, Kleyman TR. Sodium retention and volume expansion in nephrotic syndrome: implications for hypertension. Advances in chronic kidney disease. 2015 May 1;22(3):179-84.
  11. Wang CS, Yan J, Palmer R, Bost J, Wolf MF, Greenbaum LA. Childhood nephrotic syndrome management and outcome: a single center retrospective analysis. International Journal of Nephrology. 2017;2017(1):2029583.
  12. Hilmanto D, Mawardi F, Lestari AS, Widiasta A. Disease-associated systemic complications in childhood nephrotic syndrome: a systematic review. International Journal of Nephrology and Renovascular Disease. 2022 Feb 25:53-62.
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