Department of Pharmacology & Clinical Pharmacology, University of Auckland, Auckland, New Zealand.
Department of Anesthesia, Auckland Hospital, Auckland, New Zealand.
CPT Pharmacometrics Syst Pharmacol. 2023 Mar;12(3):401-412. doi: 10.1002/psp4.12924. Epub 2023 Feb 7.
Quantifying the effect of kidney disease on glomerular filtration rate (GFR) is important when describing variability in the clearance of drugs eliminated by the kidney. We aimed to develop a continuous model for renal function (RF) from prematurity to adulthood based on consistent models for fat-free mass (FFM), creatinine production rate (CPR), and GFR. A model for fractional FFM in premature neonates to adults was developed using pooled data from 4462 subjects and 2847 FFM observations. It was found that girls have an FFM higher than that predicted from adult women based on height, total body mass, and sex, and boys have an FFM lower than adult men until around the onset of puberty, when it approaches adult male values. Data from 108 subjects with measurements of serum creatinine (Scr) and GFR were used to construct a model for CPR. Creatinine clearance was predicted using a model for CPR (based on FFM, postmenstrual age, and sex) and Scr that avoids discontinuous predictions between neonates, children, and adults. Individual CPR may then be used with individual Scr to predict the estimated GFR (eGFR; eGFR = CPR/Scr). A previously published model for human GFR based on 1153 GFR observations in 923 subjects without known kidney disease was updated using the model for fractional FFM to predict individual size and age-consistent values for the expected normal GFR (nGFR). Individual renal function was then calculated using RF = eGFR/nGFR.
定量评估肾脏疾病对肾小球滤过率(GFR)的影响对于描述肾脏清除药物的变异性非常重要。我们旨在基于无脂肪质量(FFM)、肌酐生成率(CPR)和 GFR 的一致模型,从早产儿到成年期开发连续的肾功能(RF)模型。使用来自 4462 名受试者和 2847 个 FFM 观察值的汇总数据,开发了一种用于早产儿到成年期的分数 FFM 的模型。结果发现,女孩的 FFM 高于根据身高、总体质量和性别预测的成年女性的 FFM,男孩的 FFM 低于成年男性,直到青春期开始,此时接近成年男性的数值。使用来自 108 名受试者的血清肌酐(Scr)和 GFR 测量值的数据构建了 CPR 模型。使用基于 FFM、绝经后年龄和性别的 CPR 模型(基于 FFM、绝经后年龄和性别)和 Scr 预测肌酐清除率,避免了在新生儿、儿童和成人之间的不连续预测。然后可以使用个体 CPR 和个体 Scr 预测估计的肾小球滤过率(eGFR;eGFR=CPR/Scr)。使用来自 923 名无已知肾脏疾病的受试者的 1153 个 GFR 观察值的先前发表的人类 GFR 模型,通过分数 FFM 模型进行更新,以预测个体大小和年龄一致的预期正常 GFR(nGFR)的数值。然后使用 RF=eGFR/nGFR 计算个体肾功能。