الفهرس 
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Abstract
SUMMARY
Chronic kidney disease (CKD) is a major health problem in most developed and developing countries, in which the prevalence continues to increase each year worldwide with an increasing incidence and prevalence. In the past 2 decades, the incidence of chronic kidney disease in children has steadily increased too.
Chronic kidney disease (CKD) also is a major risk factor for many morbidities, including cardiovascular disease, cerebrovascular disease and bleeding, and hence cardiovascular mortality.
Pediatric chronic kidney disease (CKD) also is associated with disturbance of glucose metabolism & insulin receptor sensitivity leading to impaired glucose tolerance & insulin resistance (IR), which are potential risk factors for cardiovascular disease (CVD). Hyperinsulinemia and IR are not extensively investigated in children with CKD, especially in different stages of CKD
Therefore, insulin resistance may be an important therapeutic target for reduction of cardiovascular mortality in patients with CKD
Serum leptin levels in CKD pediatric patients remain controversial especially in pediatric patient and its full pathophysiology with insulin resistance in CKD patients not yet clearly understood
We aimed in this cross-sectional study to determine insulin resistance in different stages of CKD by HOMA-IR and the association with other potential cardiovascular markers such as lipids and leptin level.
This study was carried out at pediatric dialysis,nephrology unit and nephrology department children’s hospital and, radiology department(for Echocardiography for cardiac function assessment & measuring the left ventricular mass Doppler U/S to measure carotid intimal media thickness for both common & internal carotid arteries, bilaterally) Faculty of Medicine, Ain Shams University and included A total of 87 children and adolescents with chronic kidney disease (CKD); (29 CKD stage 2-4, pre-dialysis group & 29 CKD stage 5, dialysis group) & 29 age & gender matched controls were enrolled in the current cross-sectional study.
. Careful medical history was taken in the form of age, sex, durations of the disease & dialysis, Patients known with diabetes or positive family history of type1DM were excluded from the start. Both oral and written consents were obtained from patients and their caregivers according to the guidelines of Institutional Review Board (IRB) of college of medicine with approval number of FMASU M S 330 / 2020. Assay of fasting insulin & fasting glucose were done by withdrawing 3ml of blood serum (was withdrawn before dialysis session in dialysis group) after fasting for at 8 hours, where specimens were analyzed by Roche Modular P chemistry analyzer (Roche Diagnostics, 9115 Hague Road, Indianapolis, IN 46250). Hyperinsulinemia was defined as fasting insulin levels ≥ 15 mU/ml. Homeostasis model assessment of insulin resistance (HOMA-IR) using fasting insulin & fasting glucose for the equation of {fasting insulin (µU/ml) × fasting plasma glucose (mg/dl)]/405}, where IR was considered if HOMA-IR ≥ 4.39 (upper 2.5 percentiles or >2 SDs above mean HOMA-IR for normal-weight children);
In our study, the most common aetiology of CKD among our patients was congenital anomalies of Kidney & urinary tract (CAKUT). The baseline weight, height, & body mass index (BMI) of the patients’ groups were significantly lower than the control group. Both systolic (SBP) &diastolic blood pressures (DBP) were significantly higher among patients in comparison to the control group.
The study finding are serum triglycerides & total cholesterol levels were significantly higher in both CKD compared to controls, while in predialysis groups, high LDL cholesterol & low HDL cholesterol were statistically significant when compared to both dialysis & controls p<0.001, <0.001, 0.002, 0.001 respectively). Our CKD patients had statistically significant iron deficiency anemia, hypocalcemia & hypoalbuminemia when the controls. The median fasting insulin (ulU\ml) was 6.2 (2.7 - 10) in CKD5d patients, 7.7 (6.4 - 8.6) in CKD2-4 & 4.9 (2.8 - 11.9) in controls, with no significant difference between them (p=0.7). The mean fasting glucose was 96.03 ± 23.88, 93.45 ± 20.89 & 88.52 ± 7.88 mg/dl respectively, with no statically significant difference between all of them (p=0.31). We had 11 (12.64%) CKD pediatric patients with insulin resistance, where HOMA-IR was >4.39, where 6 (6.89%) patients CKD5d & 5 (5.7%) patients CKD2-4, with significant difference between CKD patients & controls (p=0.039), nevertheless, the baseline median HOMAR-IR was insignificantly differed between all the 3 groups (p=0.64). The measured serum leptin in our CKD patients was normal in 87.4% & abnormally high in 12.6% (2, 6.9% dialysis patients & 9, 31.03% predialysis patients). The median serum leptin level was higher in predialysis group compared to dialysis group; however, it did not reach statistical significance when compared to both dialysis & control subjects (p=0.20)
Echocardiography were done for our patients & revealed statistically higher ejection fraction % in predialysis group compared to dialysis one (p<0.001), while left ventricular systolic dysfunction was reported in 8 (27.59%) dialysis patients & 5 (17.24%) predialysis patients, while diastolic dysfunction was a 5 (17.24%) dialysis patients & 4 (13.79%) in non-dialysis, left ventricular hypertrophy 10 (34.48%) in dialysis patients & 8 (27.59%) in non-dialysis, with insignificant difference between them (p=0.345,1.00,0.57 respectively).
We had assessed the vascular status of all studied groups by measuring the carotid intimal wall thickness assessment, where it was higher in dialysis group compared to predialysis & controls, with median range (mm) of right CCA, ICA, left CCA, ICA of 0.39 (0.32 - 0.48), 0.32 (0.25 - 0.4), 0.36 (0.31 - 0.45) and 0.32 (0.27 - 0.42) respectively, with significant difference between all of them (p=<0.001, <0.001, <0.001, <0.001).
CONCLUSIONS & RECOMMENDATIONS
Hyperinsulinemia, hyperleptinemia & insulin resistance were not uncommon in different stages of CKD in pediatric patients. Insulin resistance was associated with high risk of cardiovascular abnormalities, nevertheless, no similar finding was found with leptin. In the view of these, we recommend screening of pediatric CKD patients for IR, for early diagnosis & proper intervention, hence, insulin resistance may be an important therapeutic target for reduction of cardiovascular mortality in patients with CKD. Also, we recommend a future larger, multi-centric study for proper estimation of insulin resistance in different stages of CKD by HOMA-IR. Further research is needed to gain a more comprehensive insight into studying leptin level in CKD patients and its effect on cardiovascular function.