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.
Development of a vaccine to limit the impact of antibiotic resistant Neisseria gonorrhoeae is now a global priority. Serum bactericidal antibody (SBA) is a possible indicator of protective immunity to N. gonorrhoeae, but conventional assays measure colony forming units (CFU), which is time-consuming. A luminescent assay that quantifies ATP as a surrogate measure of bacterial viability was tested on N. gonorrhoeae strains FA1090, MS11 and P9-17 and compared to CFU-based readouts. There was a linear relationship between CFU and ATP levels for all three strains (r > 0.9). Normal human serum (NHS) is a common source of complement for SBA assays, but needs to be screened for non-specific bactericidal activity. NHS from 10 individuals were used for serum sensitivity assays-sensitivity values were significantly reduced with the ATP method for FA1090 (5/10, p < 0.05) and MS11 (10/10, p < 0.05), whereas P9-17 data were comparable for all donors. Our results suggest that measuring ATP underestimates serum sensitivity of N. gonorrhoeae and that the CFU method is a better approach. However, mouse anti-P9-17 outer membrane vesicles (OMV) SBA titres to P9-17 were comparable with both methods (r = 0.97), suggesting this assay can be used to rapidly screen sera for bactericidal antibodies to gonococci.
Aim: Renal function is an important covariate to describe variability in clearance of renally eliminated drugs. Estimating glomerular filtration rate (GFR) should account for differences in size, age and body composition consistently when using GFR to determine drug dosage. We aimed to develop a continuous model for renal function from prematurity to adulthood based on models for fat free mass (FFM), creatinine production rate (CPR) and GFR. Methods: A model for fractional FFM in premature neonates to adults was developed using pooled data from 4462 subjects and 2847 FFM observations. Data from 108 subjects with measurements of serum creatinine and GFR were used to construct a model for CPR by assuming that CLcr is equal to GFR. A previously published model for human GFR was updated using the model for fractional FFM and accounting for the effects of maturation and birth. Together these models were used to predict renal function. Results: Girls have a FFM larger than that predicted from adult women based on height, weight and sex. Boys have a FFM lower than adult men predicted FFM until around the onset of puberty, when it approaches adult values. CPR can be predicted using FFM, post menstrual age and sex and avoids discontinuous predictions between neonates, children and adults. The updated model for GFR maturation was used to describe expected normal GFR. Renal function calculated from the ratio of individual CLcr to normal GFR. Conclusion: Continuous models for FFM, CPR and GFR predict renal function independent of age and size.
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