Glomerular hyperfiltration in children with cancer: prevalence and a hypothesis

Kwatra, Neha; Meany, Holly J.; Ghelani, Sunil J.; Zahavi, David J.; Pandya, Nayan; Majd, Massoud

doi:10.1007/s00247-016-3733-5

Cited by 27 publications

(36 citation statements)

References 19 publications

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“…27 and H.J.M. 28 ). Institution 1 applied the Chantler correction to its measurements, 23 designed to partly offset the overestimation that occurs when using the single-slope method to calculate GFR, and found the mean ± standard deviation (SD) GFR in children with cancer to be 114 ± 36 mL/min/1.73m 2 .…”

Section: Resultsmentioning

confidence: 94%

“…To illustrate the magnitude of this variation in published reports, Figure shows the distribution of GFR data from two separate children's hospitals that had previously reported their observations (subject level data kindly provided by co‐authors B.B . and H.J.M …”

Section: Resultsmentioning

confidence: 99%

“…Histogram of glomerular filtration rates obtained in populations of children with cancer at two separate institutions . While there are some differences in the pediatric cancer populations studied, the mean ± SD reported GFR was 114 ± 36 mL/min/1.73m 2 from institution 1, which applied a correction factor to partially adjust for known methodologic errors that result in GFR overestimation, and 142 ± 46 mL/min/1.73m 2 from institution 2, which did not apply a correction factor ( P < 0.001)…”

Section: Resultsmentioning

confidence: 99%

“…A limited number of reports have characterized GFR in children with newly diagnosed cancer as being most consistent with a hyperfilterable state . Although hyperfiltration may occur in some children with cancer, the wide variation in population ranges observed in similar populations of children with cancer points to a systematic methodologic error in measurement or calculation.…”

Section: Discussionmentioning

confidence: 99%

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Fundamental problems with pediatric adaptive dosing of carboplatin using nuclear‐medicine‐based estimates of renal function

Adamson

Veal

Womer

et al. 2019

Pediatric Blood & Cancer

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Background Carboplatin is often adaptively dosed based on glomerular filtration rate (GFR), usually estimated by nuclear medicine tests. At least five pediatric adaptive dosing formulas have been developed. In an effort to standardize dosing in Children's Oncology Group protocols, we explored methodologic variation in GFR estimation and adaptive‐dosing formula performance. Procedure Nuclear medicine GFR data from published series of ≥100 children with cancer were compared. Data from patients for whom body surface area, weight, GFR, and tracer half‐life were available were used to compare formulas. Results Differences in methods used to estimate GFR in children with cancer resulted in highly variable population results, with median GFRs ranging from 96 to 150 mL/min/1.73m2. The choice of adaptive formula had a major impact on calculated dose. When targeting an area under the curve of 7.9 mg/mL • min, the median difference between the formula yielding the lowest and highest carboplatin dose for individual subjects was 289 (range 96‐1 737) mg/m2. Conclusions Wide variation in GFR obtained with nuclear‐medicine‐based tests in children with cancer primarily results from systematic methodologic errors. Formulas for calculating carboplatin dose produce additional and substantial variation that may place children with cancer at unnecessary risk for excessive toxicity or underdosing. These findings indicate a need for the development of a uniform, validated method for GFR determination in children that should be utilized in all centers. Currently, adaptive dosing of carboplatin based on GFR has serious limitations and in most clinical settings should arguably not be used in place of body‐surface‐area‐based dosing.

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Section: Resultsmentioning

confidence: 94%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Fundamental problems with pediatric adaptive dosing of carboplatin using nuclear‐medicine‐based estimates of renal function

Adamson

Veal

Womer

et al. 2019

Pediatric Blood & Cancer

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“…1 A new dosing regimen derived from a population pharmacokinetic (PK) analysis and using a loading dose, was implemented in our unit. 2 We aimed to investigate if the new regimen results in improved vancomycin exposure (target trough 10-15 mg/L).…”

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confidence: 99%

O13 Improved early vancomycin exposure in neonates using a population pharmacokinetic model-based vancomycin dosing regimen

et al. 2019

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BackgroundWe previously documented that 2 published vancomycin dosing regimens resulted in subtherapeutic exposure in 66.3 and 76.2% of neonates.1 A new dosing regimen derived from a population pharmacokinetic (PK) analysis and using a loading dose, was implemented in our unit.2 We aimed to investigate if the new regimen results in improved vancomycin exposure (target trough 10–15 mg/L).MethodsClinical data and early (24 h after start) vancomycin therapeutic drug monitoring (TDM) in neonates receiving vancomycin for medical reasons, were retrospectively collected and pooled with 2 historical cohorts [cohort 1 (2011, n=193 observations), dosing based on postmenstrual age (PMA) and creatininemia and cohort 2 (2012, n=101 observations), dosing based on PMA and postnatal age (PNA)]. The new regimen [cohort 3 (2018, n=71 observations)] consists of a loading dose, followed by dosing based on birthweight, PNA and ibuprofen co-treatment [2]. Clinical characteristics and early TDM were compared across the cohorts using the Kruskal-Wallis Test. Results were significant if p< 0.05.ResultsClinical characteristics (cohort 1, 2 and 3 respectively) did not differ significantly across the cohorts. Median (IQ range) GA was 32.8 (28.4–37.6), 32.1 (28.5–37.5), 28 (26–38) weeks with p=0.097; PNA 13 (6–26), 12 (7–23), 14 (10–25) days with p=0.15 and creatininemia 0.43 (0.33–0.55), 0.49 (0.33–0.65), 0.45 (0.32–0.57) mg/dL with p=0.15. Median vancomycin trough level was 7.8 (5.1–11.3), 5.8 (4.1–8.7), 13.3 (9.9–17.3) mg/L with p< 0.0001. With the new regimen, 25.4% of trough levels was < 10 mg/L, 40.8% >15 mg/L, and 33.8% was on target, versus 23.3 and 19.8% on target in cohort 1 and 2 respectively.ConclusionA population PK model-based vancomycin dosing regimen using a loading dose, resulted in improved neonatal vancomycin exposure. Although only 25% of trough levels was subtherapeutic, dosing optimalisation for cases with supratherapeutic exposure is also needed, as well as further prospective validation.ReferencesVandendriessche, et al. Curr Ther Res Clin Exp 2014.Janssen, et al. AAC 2015.Disclosure(s)Nothing to disclose

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Glomerular filtration rate in children and young adults with haemato‐oncological disease and infection is best described by three‐compartment iohexol model

Soeorg

Karu

Saks

et al. 2021

Pediatric Blood & Cancer

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Background: Children with cancer and infection may develop glomerular hyperfiltration. With the aim to determine the prevalence of glomerular hyperfiltration in children and young adults with haemato‐oncological disease and infection, we developed population pharmacokinetic model of iohexol. We further aimed to assess the accuracy of estimated glomerular filtration rate (eGFR) equations and single‐ or two‐point measured GFR (mGFR) formulas compared with GFR based on iohexol clearance from our population pharmacokinetic model (iGFR). Procedure: Hospitalised patients (0.5–25 years) with haemato‐oncological disease and infection were included if their eGFR was ≥80 ml/min/1.73 m2 at the screening visit. Iohexol plasma concentrations were described by population pharmacokinetic model. Bias, precision and accuracy of 23 eGFR equations and 18 mGFR formulas were calculated. Results: Total of 32 iohexol administrations were performed in 28 patients. Median (range) eGFR was 136 ml/min/1.73 m2 (74–234) and age 15.1 years (0.8–26.0). Three‐compartment model with allometric scaling of central, one peripheral compartment and clearance (with power 0.75) to weight fitted the best. Median (range) iGFR was 103 ml/min/1.73 m2 (68–140). All except one eGFR equation overestimated GFR. Lund–Malmö revised eGFR equation performed the best, followed by Gao equation. Of single‐ or two‐point mGFR formulas, 15 overestimated iGFR. Modified Jacobsson formula at 5.5 hours performed the best, followed by Fleming formula at 3 hours. Conclusions: In children and young adults with haemato‐oncological disease and infection, renal function is best described by iohexol clearance from three‐compartment pharmacokinetic model, while eGFR equations and single‐ and two‐point mGFR formulas overestimate iGFR.

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Glomerular hyperfiltration in children with cancer: prevalence and a hypothesis

Cited by 27 publications

References 19 publications

Fundamental problems with pediatric adaptive dosing of carboplatin using nuclear‐medicine‐based estimates of renal function

Fundamental problems with pediatric adaptive dosing of carboplatin using nuclear‐medicine‐based estimates of renal function

O13 Improved early vancomycin exposure in neonates using a population pharmacokinetic model-based vancomycin dosing regimen

Glomerular filtration rate in children and young adults with haemato‐oncological disease and infection is best described by three‐compartment iohexol model

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