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Evaluation of carotid intima media thickness in children with idiopathic nephrotic syndrome | Italian Journal of Pediatrics


This study was designed to evaluate the CIMT in children with idiopathic nephrotic syndrome and its correlation with dyslipidemia and other risk factors.

In this study, the body weight and BMI were significantly higher in NS patients as compared to the healthy controls (p-value = 0.01 and 0.001 respectively). Similar results were reported by other studies [14,15,16,17,18]. This finding can be attributed to the excess weight gain during treatment with steroids which can persist even after its discontinuation and usually associated with dyslipidemia that can increase the cardiovascular risk [19].

In our study, the mean systolic blood pressure was significantly higher in patients than controls but no significant difference in the mean diastolic blood pressure was found between patients and controls. However, Paripović et al. [20] found no differences in both mean systolic and diastolic blood pressure between the two groups. Hooman et al. [21] and Chaubey et al. [22] found significantly higher both mean systolic and diastolic blood pressure in patients than controls.

Among our patients, 35% were found to have hypertension as compared to 12% of patients reported by Ahmed et al. [18].

Total serum cholesterol and triglyceride levels were significantly higher in cases than controls. Similar results were reported by other studies [10, 17]. High lipid profile could have a role in the pathogenesis of increased oxidative stress in children with NS through synthesis of atherogenic factors such as malondialdehyde [23].

In this study, 17 out of 40 patients (42.5%) had high total serum cholesterol (> 200 mg/dL) and TG levels. Paripović et al. [20] reported similar percentage of patients having hypercholesterolemia (17 out of 40 patients; 42.5%) but a slightly lower percentage having high TG level (35%). Similarly, in a study by Candan et al. [24] high total cholesterol (> 200 mg/dL) was noted in 54% of patients.

On stratification of the patients according to their response to steroids, patients with SDNS had significantly higher mean duration of the disease (p-value = 0.01), number of relapses (p-value< 0.001). However, Ahmed et al. [18] didn’t find any significant difference between their NS groups as regards the mean duration of disease. In our study, patients with SRNS had significantly higher mean albumin creatinine ratio in urine (ACR) (p-value = 0.009) which is in agreement with the findings by Ahmed et al. [18].

CIMT is a marker for the evaluation of atherosclerosis secondary to risk factors as hypertension, hyperlipidemia, and endothelial dysfunction [25]. In the current study, CIMT was significantly higher in children with NS as compared to controls across all age groups. Similar results were reported by other studies [17, 18, 21, 24]. Correspondingly, Mehta et al. [26] in their study, conducted on 66 children with NS and 128 age and sex matched healthy controls, found that CIMT was significantly higher in NS especially in the age above 4 years. In consonance with our study, Kari et al. [27] reported higher CIMT in children with SRNS than the controls.

However, unlike our results, Kniazewska et al. [10] didn’t find significant differences in CIMT between 30 children previously treated for nephrotic syndrome versus 30 healthy children as a control group. In their study, the inclusion required being in remission free of steroids for at least 4 years in contrary to our study which included children with NS on current treatment with steroids or other immunosuppressive agents. Also, Rahul et al. [16] reported no significant difference in the mean CIMT between cases and controls.

Our study revealed significantly higher mean CIMT in the SDNS group than other NS groups. Unlike our results, Ahmed et al. [18] did not find any significant difference in the CIMT between different steroid response groups. Also Rahul et al. [16] and Youssef et al. [17] found no significant difference in CIMT between patients with IFRNS, FRNS, SDNS, and SRNS. Paripović et al. [20] also reported no significant difference in CIMT between patients with SDNS and SRNS. The discrepancy between our study and those studies could be attribuated to the fact that the SDNS group had higher disease duration and number of relapses than other groups and since CIMT, as discussed later, was found to be positively correlated to disease duration and number of relapses, our study revealed higher CIMT in the SDNS group.

We didn’t find any significant difference in CIMT between different renal histopathological results. Similarly, Ahmed et al. [18] reported no difference in CIMT between children with MCD and FSGS.

In the current study, the mean CIMT was significantly higher among patients receiving non-steroid immunosuppressive therapy at the time of evaluation than those receiving steroids alone (p-value = 0.003). However, unlike our results, Paripović et al. [20] didn’t find any significant difference in the mean CIMT between these 2 groups of patients.

There was also a statistically significant higher mean CIMT among cases who received combined or serially immunosuppressive agents of CYP, CNI & MMF (p-value = 0.04). It appears from our data that the mean CIMT becomes progressively higher with combination of immunosuppressive therapy. However, more number of cases have to be included in further studies to confirm this assumption.

We didn’t find significant difference in CIMT between patients with nephrotic syndrome receiving CNI (n = 17) and those not receiving CNI (n = 23) (0.492 ± 0.05 versus 0.466 ± 0.04 respectively; P-value = 0.07). In consonance with our results, other studies [16, 20] didn’t find significant difference in CIMT between these 2 groups.

In our study, there was a significant positive correlation between CIMT and disease duration. Similar to our results, Hooman et al. [21] found that CIMT was correlated to disease duration longer than 2 years. Also other studies [10, 18, 20, 21, 26] reported similar results.

The number of relapses in our study showed a statistically significant positive correlation with CIMT. Other studies [10, 26] had also reported similar results but no correlation was reported by Paripović et al. [20].

In our study, CIMT was also positively correlated to advancing patients’ age (r = 0.45, p = 0.004) which is in consonance with Mehta et al. [26] study. A negative, but statistically insignificant correlation was noted between CIMT and serum albumin. Mehta et al. [26] found the similar finding. There was a significant positive correlation between CIMT and BMI. Litwin et al. [28] and Paripović et al. [20] reported a similar finding. However, unlike our study, There was no correlation between CIMT and BMI in Mehta et al. [26] study.

Development of early atherosclerosis in children with nephrotic syndrome could be attributed to long periods of dyslipidemia even during remission of nephrotic syndrome [10]. When CIMT was compared with total serum cholesterol and TG levels, we found no correlation between them. Similar findings were reported by other studies [17, 18, 20, 21, 29, 30]. Also, Mehta et al. [26] found no correlation of CIMT with LDL, HDL, triglyceride, and VLDL, however a statistically insignificant negative correlation with total serum cholesterol was found. However, other studies [10, 22, 31] found that total serum cholesterol, LDL cholesterol, and serum triglyceride level had positive and significant correlation with CIMT.

Systemic hypertension is a risk factor for the development of renal injury and cardiovascular disease [32]. In the present study there was a significant positive correlation between CIMT and diastolic blood pressure. However, CIMT was not correlated to systolic blood pressure. Chaubey et al. [22] showed a significant positive correlation between systolic blood pressure, diastolic blood pressure and CIMT. Ahmed et al. [18] had not found any correlation of CIMT to blood pressure, and this could be because only 12.2% of their NS children were hypertensive. Also, Hooman et al. [21] had shown weak positive correlation between blood pressure and CIMT.

Paripović et al. [20] reported a link between CIMT and ambulatory blood pressure parameters (both daytime and night-time systolic blood pressure), while there was no significant association with office blood pressure. This is consistent with a study by Flynn et al. [33] showing that ambulatory blood pressure monitoring provides superior assessment of blood pressure in comparison with office measurements.

The main limitation of this study is the lack of long-term follow up to see the changes in CIMT over a period of time and lack of studying the effect of cumulative dose of steroids on CIMT. We did not investigate carotid function including distensibility, stiffness and elasticity.



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