Maturation of GFR in Term-Born Neonates: An Individual Participant Data Meta-Analysis

BACKGROUND: The evidence from individual studies to support the maturational pattern of GFR in healthy, term-born neonates is inconclusive. We performed an individual participant data (IPD) meta-analysis of reported measured GFR (mGFR) data, aiming to establish neonatal GFR reference values. Furthermore, we aimed to optimize neonatal creatinine-based GFR estimations. METHODS: We identified studies reporting mGFR measured by exogenous markers or creatinine clearance (CrCL) in healthy, term-born neonates. The relationship between postnatal age and clearance was investigated using cubic splines with generalized additive linear mixed models. From our reference values, we estimated an updated coefficient for the Schwartz equation (eGFR [ml/min per 1.73 m(2)]=(k×height [cm])/serum creatinine [mg/dl]). RESULTS: Forty-eight out of 1521 screened articles reported mGFR in healthy, term-born neonates, and 978 mGFR values from 881 neonates were analyzed. IPD were available for 367 neonates, and the other 514 neonates were represented by 41 aggregated data points as means/medians per group. GFR doubled in the first 5 days after birth, from 19.6 (95% CI, 14.7 to 24.6) to 40.6 (95% CI, 36.7 to 44.5) ml/min per 1.73 m(2), and then increased more gradually to 59.4 (95% CI, 45.9 to 72.9) ml/min per 1.73 m(2) by 4 weeks of age. A coefficient of 0.31 to estimate GFR best fitted the data. CONCLUSIONS: These reference values for healthy, term-born neonates show a biphasic increase in GFR, with the largest increase between days 1 and 5. Together with the re-examined Schwartz equation, this can help identify altered GFR in term-born neonates. To enable widespread implementation of our proposed eGFR equation, validation in a large cohort of neonates is required. PURPOSE: The number of patients ≥ 80 years admitted into critical care is increasing. Coronavirus disease 2019 (COVID-19) added another challenge for clinical decisions for both admission and limitation of life-sustaining treatments (LLST). We aimed to compare the characteristics and mortality of very old critically ill patients with or without COVID-19 with a focus on LLST. METHODS: Patients 80 years or older with acute respiratory failure were recruited from the VIP2 and COVIP studies. Baseline patient characteristics, interventions in intensive care unit (ICU) and outcomes (30-day survival) were recorded. COVID patients were matched to non-COVID patients based on the following factors: age (± 2 years), Sequential Organ Failure Assessment (SOFA) score (± 2 points), clinical frailty scale (± 1 point), gender and region on a 1:2 ratio. Specific ICU procedures and LLST were compared between the cohorts by means of cumulative incidence curves taking into account the competing risk of discharge and death. RESULTS: 693 COVID patients were compared to 1393 non-COVID patients. COVID patients were younger, less frail, less severely ill with lower SOFA score, but were treated more often with invasive mechanical ventilation (MV) and had a lower 30-day survival. 404 COVID patients could be matched to 666 non-COVID patients. For COVID patients, withholding and withdrawing of LST were more frequent than for non-COVID and the 30-day survival was almost half compared to non-COVID patients. CONCLUSION: Very old COVID patients have a different trajectory than non-COVID patients. Whether this finding is due to a decision policy with more active treatment limitation or to an inherent higher risk of death due to COVID-19 is unclear

Maturation of glomerular filtration rate in term-born neonates: an individual participant data meta-analysis.

Abstract Background: The evidence from individual studies to support the maturational pattern of glomerular filtration rate (GFR) in healthy term-born neonates is inconclusive. We performed an individual participant data (IPD) meta-analysis of reported measured GFR (mGFR) data aimed to establish GFR reference values in the first month of life. As a secondary objective, we aimed to optimize neonatal creatinine-based GFR estimations in clinical care. Methods: We identified studies reporting mGFR measured by exogenous markers or creatinine clearance (CrCL) in healthy term-born neonates through searching the Pubmed and ClinicalTrials.gov databases. The relationship between postnatal age and individual clearance was investigated using cubic splines with generalized additive linear mixed models. From our reference values, we estimated an updated coefficient for the Schwartz equation (eGFR(ml/min/1.73m2)=(k*height (cm))/serum creatinine(mg/dl)). Results: Fifty out of 1521 screened articles reported mGFR in healthy term-born neonates, and we analyzed 1041 mGFR values from 944 neonates. IPD were available for 367 neonates and the other 577 neonates were represented by 44 aggregated data points as means/medians per cohortgroup. GFR doubled in the first five days after birth from 19.6 (95% CI 14.7;24.6) ml/min/1.73m2 to 40.6 (95% CI 36.7;44.5) ml/min/1.73m2, then more gradually increased to 59.4 (95% CI 45.9;72.9) ml/min/1.73m2 by four weeks of age. A coefficient of 0.31 to estimate GFR best fitted the data. Conclusions: These reference values for healthy term newborns show a biphasic increase in GFR with the largest increase between days 1 and 5. Our mGFR reference values and updated coefficient for the Schwartz equation can help identify acute kidney injury or augmented renal clearance altered GFR in term-born neonates

Glomerular filtration rate in critically ill neonates and children: creatinine-based estimations versus iohexol-based measurements

Background Acute kidney injury (AKI) and augmented renal clearance (ARC), both alterations of the glomerular filtration rate (GFR), are prevalent in critically ill children and neonates. AKI and ARC prevalence estimates are based on estimation of GFR (eGFR) using serum creatinine (SCr), which is known to be inaccurate. We aimed to test our hypothesis that AKI prevalence will be higher and ARC prevalence will be lower in critically ill children when using iohexol-based measured GFR (mGFR), rather than using eGFR. Additionally, we aimed to investigate the performance of different SCr-based eGFR methods.Methods In this single-center prospective study, critically ill term-born neonates and children were included. mGFR was calculated using a plasma disappearance curve after parenteral administration of iohexol. AKI diagnosis was based on the KDIGO criteria, SCr-based eGFR, and creatinine clearance (CrCL). Differences between eGFR and mGFR were determined using Wilcoxon signed-rank tests and by calculating bias and accuracy (percentage of eGFR values within 30% of mGFR values).Results One hundred five children, including 43 neonates, were included. AKI prevalence was higher based on mGFR (48%), than with KDIGO or eGFR (11-40%). ARC prevalence was lower with mGFR (24%) compared to eGFR (38-51%). eGFR equations significantly overestimated mGFR (60-71 versus 41 ml/min/1.73 m(2), p<0.001-0.002). Accuracy was highest with eGFR equations based on age- and sex-dependent equations (up to 59%).Conclusion Iohexol-based AKI prevalence was higher and ARC prevalence lower compared to standard SCr-based eGFR methods. Age- and sex-dependent equations for eGFR (eGFR-Smeets for neonates and eGFR-Pierce for children) best approached measured GFR and should preferably be used to optimize diagnosis of AKI and ARC in this population.Personalised Therapeutic

Glomerular filtration rate in critically ill neonates and children: creatinine-based estimations versus iohexol-based measurements.

BACKGROUND: Acute kidney injury (AKI) and augmented renal clearance (ARC), both alterations of the glomerular filtration rate (GFR), are prevalent in critically ill children and neonates. AKI and ARC prevalence estimates are based on estimation of GFR (eGFR) using serum creatinine (SCr), which is known to be inaccurate. We aimed to test our hypothesis that AKI prevalence will be higher and ARC prevalence will be lower in critically ill children when using iohexol-based measured GFR (mGFR), rather than using eGFR. Additionally, we aimed to investigate the performance of different SCr-based eGFR methods. METHODS: In this single-center prospective study, critically ill term-born neonates and children were included. mGFR was calculated using a plasma disappearance curve after parenteral administration of iohexol. AKI diagnosis was based on the KDIGO criteria, SCr-based eGFR, and creatinine clearance (CrCL). Differences between eGFR and mGFR were determined using Wilcoxon signed-rank tests and by calculating bias and accuracy (percentage of eGFR values within 30% of mGFR values). RESULTS: One hundred five children, including 43 neonates, were included. AKI prevalence was higher based on mGFR (48%), than with KDIGO or eGFR (11-40%). ARC prevalence was lower with mGFR (24%) compared to eGFR (38-51%). eGFR equations significantly overestimated mGFR (60-71 versus 41 ml/min/1.73 m(2), p < 0.001-0.002). Accuracy was highest with eGFR equations based on age- and sex-dependent equations (up to 59%). CONCLUSION: Iohexol-based AKI prevalence was higher and ARC prevalence lower compared to standard SCr-based eGFR methods. Age- and sex-dependent equations for eGFR (eGFR-Smeets for neonates and eGFR-Pierce for children) best approached measured GFR and should preferably be used to optimize diagnosis of AKI and ARC in this population. A higher resolution version of the Graphical abstract is available as Supplementary information

Maturation of glomerular filtration rate in term-born neonates: an individual participant data meta-analysis.

Abstract Background: The evidence from individual studies to support the maturational pattern of glomerular filtration rate (GFR) in healthy term-born neonates is inconclusive. We performed an individual participant data (IPD) meta-analysis of reported measured GFR (mGFR) data aimed to establish GFR reference values in the first month of life. As a secondary objective, we aimed to optimize neonatal creatinine-based GFR estimations in clinical care. Methods: We identified studies reporting mGFR measured by exogenous markers or creatinine clearance (CrCL) in healthy term-born neonates through searching the Pubmed and ClinicalTrials.gov databases. The relationship between postnatal age and individual clearance was investigated using cubic splines with generalized additive linear mixed models. From our reference values, we estimated an updated coefficient for the Schwartz equation (eGFR(ml/min/1.73m2)=(k*height (cm))/serum creatinine(mg/dl)). Results: Fifty out of 1521 screened articles reported mGFR in healthy term-born neonates, and we analyzed 1041 mGFR values from 944 neonates. IPD were available for 367 neonates and the other 577 neonates were represented by 44 aggregated data points as means/medians per cohortgroup. GFR doubled in the first five days after birth from 19.6 (95% CI 14.7;24.6) ml/min/1.73m2 to 40.6 (95% CI 36.7;44.5) ml/min/1.73m2, then more gradually increased to 59.4 (95% CI 45.9;72.9) ml/min/1.73m2 by four weeks of age. A coefficient of 0.31 to estimate GFR best fitted the data. Conclusions: These reference values for healthy term newborns show a biphasic increase in GFR with the largest increase between days 1 and 5. Our mGFR reference values and updated coefficient for the Schwartz equation can help identify acute kidney injury or augmented renal clearance altered GFR in term-born neonates