Consistent methods for fat‐free mass, creatinine clearance, and glomerular filtration rate to describe renal function from neonates to adults

Abstract

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.

A physiological approach to renal clearance: From premature neonates to adults

“…models for FFM and maturation leading to a standard GFR estimate of 6.96 L/h. 8 F size is a factor for size using NFM, 4 F mat,PMA is a factor for maturation based on post-menstrual age (PMA) and F mat,PNA is a factor for maturation based on post-natal age (PNA), which describes a post-natal transition component of maturation. F mat,PMA is defined in terms of TM 50 , the maturation half time, ie the PMA at 50% of the fully mature adult value of 1, and Hill, a parameter that describes the steepness of the maturation curve (Equation 5).…”

“…Before adulthood is reached (PNA < =20 years), a method for predicting CPR GFR has been described. 8 CPR GFR can be predicted in adults using a method based on the estimated renal component of aminoglycoside clearance. 11 The estimated GFR (eGFR) can then be predicted using CPR GFR and Scr (Equation 8).…”

“…A conversion factor of 0.748 was used to convert Jaffe Scr measurements to the more specific enzymatic equivalent. 8 Scr is not reliable as a predictor of eGFR immediately after birth because most Scr in a neonate is derived from the mother. An estimate of creatinine half-life 8 can be used to predict how long it will take for most of the maternally derived creatinine to be eliminated from the neonate, for example after four neonatal creatinine halflives.…”

“…18 RF differs from the more general term "kidney function" by proposing a quantitative measure of the efficiency of all functions of the kidney that may be linked with renal solute elimination. RF is a quantity independent of size, body composition, maturation and post-natal transition effects when these factors are consistently accounted for in both eGFR and nGFR, as described in O'Hanlon et al 8 This can be expressed as a continuous function to predict RF from premature neonates to adults.…”

Perioperative Acetaminophen Dosing in Obese Children

“…NFM requires the determination of Ffat. While the impact of this parameter (Ffat) has been established for the renal elimination pathway over a broad range of ages from premature neonates to adults [ 69 ], it has only been determined for a handful of drugs [ 68 , 70 , 71 ], one of which is acetaminophen [ 72 ]. The parameter Ffat was estimated as 1 for volume (i.e., TBW) and 0.82 for clearance.…”