Puberty is the process of transition from childhood into adolescence, signaling the readiness of the human body for reproduction. The Hypothalamic-Pituitary Gonadotropin axis plays the primary role in initiating the puberty, where the hypothalamus secrets gonadotropin releasing hormone (GnRH) in a pulsatile manner, which in turn stimulates the release of luteinizing hormone (LH), and follicle stimulating hormone (FSH) from the anterior lobe of the pituitary gland, and in a final step these hormones stimulate the gonads to release their sex hormones (Testosterone and Estradiol) .

Chronic illnesses can affect this physiological process resulting in delayed puberty . Delayed puberty is defined as the lack of pubertal signs until the age of 13 years in girls, and the age of 14 years in boys. Delayed puberty is classified into two categories according to their cause; central gonadotropin deficiency (hypogonadotropic hypogonadism) and this type comprises delayed puberty due to chronic illness, while the second category of delayed puberty is due to gonadal disorders (hypergonadotropic hypogonadism).

Delayed puberty is common among pediatric patients with chronic kidney disease (CKD) - where glomerular filtration rate (GFR) is less than 60 ml/min per 1.73 m2. Previous studies suggested that, the cyclic pattern of GnRH release is lost in patients with CKD resulting in impairment of gonadotropins secretion from the anterior pituitary gland. Multiple hormonal factors had been proposed to be responsible for the pubertal delay in patients with CKD, the most prominent of which is the increasing levels of prolactin, LH and GnRH (4). Prolactin normally inhibits the release of GnRH from hypothalamus thus inhibiting the initiation of puberty and it was found to increase in patients with CKD secondary to increased production, slightly decreased clearance and decreased responsiveness to the hypothalamic inhibition of prolactin secretion.

Furthermore, recent studies reported that the Kisspeptin protein play an important role in the regulation and control of normal puberty, As it was found that the Kisspeptin neurons (the rostral periventricular region of the third ventricle (RP3V) and arcuate nucleus (ARC), are found in close association with the GnRH releasing neurons in the hypothalamus suggesting that these neurons might play a crucial role in activating and restoring the pulsatile release of GnRH, It was also found that inactivating mutations of the gene encoding for kisspeptin were associated with hypogonadotropic hypogonadism.

Inclusion Criteria:Children and Adolescents aged 8 to 18 years, diagnosed with CKD and attending the pediatric nephrology clinic and the pediatric dialysis unit at Sohag University Hospital will be included.

In addition, Age- and sex-matched controls will be included from children and adolescents attending the general pediatric clinic at Sohag University Hospital for acute non-serious illnesses.

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Exclusion Criteria: Pediatric post-renal transplant recipients and patients receiving hormonal replacement therapy for endocrinopathies and cases with any other associated chronic illness will be excluded from the study.

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Children and Adolescents aged 8 to 18 years, diagnosed with CKD