Division of Pediatrics, Department of Health Sciences, Università del Piemonte Orientale, V. Solaroli 17, 28100, Novara, Italy.
Pediatric Nephrology, Dialysis and Transplant Unit, Fondazione Cà Granda IRCCS, Ospedale Maggiore Policlinico, Milan, Italy.
Pediatr Nephrol. 2018 Apr;33(4):661-672. doi: 10.1007/s00467-017-3840-z. Epub 2017 Nov 18.
Impairment in orexigenic/anorexigenic hormone balance may be key in the pathogenesis of protein energy wasting in children with chronic kidney disease (CKD). Measurement of ghrelin and obestatin concentrations in children with CKD would help assess the potential contribution of these hormones to uremic protein energy wasting.
This was a cross-sectional case-control study. Acylated and unacylated ghrelin and obestatin were measured in 42 children on conservative treatment (CT), 20 children on hemodialysis, 48 pediatric renal transplant (RTx) recipients and 43 controls (CTR) (mean age 11.9, range 5-20 years). Weight, height and bicipital, tricipital, subscapular and suprailiac folds were measured, and the body mass index-standard deviation score (BMI-SDS), percentage of fat mass and fat-free mass were calculated. Urea and creatinine were measured and the glomerular filtration rate (GFR) calculated.
Unacylated ghrelin level was higher in patients than controls (p = 0.0001), with the highest levels found in hemodialysis patients (p = 0.001 vs. CKD-CT, p = 0.0001 vs. RTx, p < 0.0001 vs. CTR). Obestatin level was significantly higher in patients on hemodialysis than those on conservative treatment, RTx recipients and controls (p < 0.0001 in each case). Unacylated ghrelin negatively correlated with weight-SDS (p < 0.0001), BMI-SDS (p = 0.0005) and percentage fat mass (p = 0.004) and positively correlated with percentage fat-free mass (p = 0.004). Obestatin concentration negatively correlated with weight-SDS (p = 0.007). Unacylated ghrelin and obestatin concentrations positively correlated with creatinine and urea and inversely with eGFR, even after adjustments for gender, age, puberty and BMI-SDS (p < 0.0001 for each model).
Unacylated ghrelin and obestatin, negatively related to renal function, seem to be promising inverse indicators of nutritional status in children with CKD. Potential therapeutic implications in terms of optimization of their removal in patients on hemodialysis could be hypothesized.
在慢性肾脏病（CKD）患儿中，食欲激素平衡的损害可能是蛋白能量消耗发病机制的关键。测量 CKD 患儿的 ghrelin 和 obestatin 浓度有助于评估这些激素对尿毒症蛋白能量消耗的潜在贡献。
这是一项横断面病例对照研究。在 42 名接受保守治疗（CT）的儿童、20 名血液透析患儿、48 名儿科肾移植（RTx）受者和 43 名对照者（CTR）（平均年龄 11.9 岁，范围 5-20 岁）中测量酰化和非酰化 ghrelin 和 obestatin。测量体重、身高和肱二头肌、三头肌、肩胛下角和髂嵴皮褶，并计算体重指数标准差评分（BMI-SDS）、体脂百分比和去脂体重。测量尿素和肌酐，并计算肾小球滤过率（GFR）。
未酰化 ghrelin 水平在患者中高于对照组（p=0.0001），血液透析患者的水平最高（p=0.001 与 CKD-CT，p=0.0001 与 RTx，p<0.0001 与 CTR）。与接受保守治疗、RTx 受者和对照组的患者相比，血液透析患者的 obestatin 水平显著更高（p<0.0001）。未酰化 ghrelin 与体重 SDS（p<0.0001）、BMI-SDS（p=0.0005）和体脂百分比（p=0.004）呈负相关，与去脂体重百分比（p=0.004）呈正相关。obestatin 浓度与体重 SDS（p=0.007）呈负相关。未酰化 ghrelin 和 obestatin 浓度与肌酐和尿素呈正相关，与 eGFR 呈负相关，即使在性别、年龄、青春期和 BMI-SDS 调整后也是如此（每个模型 p<0.0001）。
与肾功能呈负相关的未酰化 ghrelin 和 obestatin 似乎是 CKD 患儿营养状况的有前途的负向指标。可以假设在血液透析患者中优化其清除以达到治疗目的的潜在治疗意义。
