De‐indexed estimated glomerular filtration rates: A simple step towards improving accuracy of drug dosing of renally excreted medications in moderate to severe obesity

Vlasschaert, Caitlyn; Thibodeau, Stephane; Parmar, Malvinder S

doi:10.1111/nep.13621

Cited by 7 publications

(13 citation statements)

References 8 publications

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“…We did not include the race coefficient for MDRD and CKD-EPI ( 20 ). For MDRD and CKD-EPI, we additionally calculated body surface area (BSA)-deindexed eGFR, multiplying eGFR by KTR’s individual BSA ( 21 ), divided by 1.73 m 2 ( 22 , 23 ). To indicate stability or decline of graft function, respectively, eGFR (CKD-EPI) slopes ( 24 ) were calculated for the last 5 years of the 20-year period, i.e., 15–20 years post-transplant.…”

Section: Methodsmentioning

confidence: 99%

Entering the Third Decade After Kidney Transplantation: Excellent Graft Function Refers to Superior Graft but Not Patient Survival

Reimann¹,

Nilsson²,

Wuethrich³

et al. 2022

Transpl Int

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Kidney transplant recipients (KTRs) with ultralong-term survival represent a growing, yet insufficiently studied patient cohort. In this single-center retrospective study, we analyzed 248 ultralong-term survivors (≥20 years). KTRs were classified into those with superior graft function (defined as eGFR ≥45 ml/min + proteinuria ≤300 mg/day + eGFR-slope ≤ 2 ml/min/1.73 m2/year) and inferior graft function regarding the risk of CKD progression. 20 years post-transplant, median eGFR was 54 ml/min (11–114), proteinuria 200 mg/24 h (0–7,620), eGFR decline 0.45 ml/min/1.73 m2/year (11.7 6.5) and DSA had been detected in 19.7% of KTRs. We identified 96 KTRs (38.7%) with superior (group 1) and 152 KTRs (61.3%) with inferior graft function (group 2). Donation after cardiac death, female sex, glomerulonephritis as primary disease, and early TCMR were independently associated with inferior graft function. Graft survival was significantly better in group 1 compared to group 2 (LogRank, p < 0.001). Besides group affiliation (HR 20.515, p = 0.003), multivariable analysis identified DSA development (HR 3.081, p = 0.023) and donor age (HR 1.032, p = 0.024) as independent factors. Interestingly, there was no significant difference in patient survival (LogRank, p = 0.350). In ultralong-term survivors, excellent graft function refers to superior graft survival but does not extend ultimate patient survival. DSA-formation should be taken seriously even in the ultralong-term.

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Section: Methodsmentioning

confidence: 99%

Entering the Third Decade After Kidney Transplantation: Excellent Graft Function Refers to Superior Graft but Not Patient Survival

Reimann¹,

Nilsson²,

Wuethrich³

et al. 2022

Transpl Int

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“…When used for medication dosing in obese or underweight patients, the indexed eGFR should be adjusted for the patient's actual BSA to avoid incorrect dosing, as their BSA differs from a standardised BSA. 16…”

Section: Equations To Estimate Kidney Functionmentioning

confidence: 99%

“…The Cockcroft-Gault (CG) equation estimates creatinine clearance (CrCl) as a surrogate marker of a patient's kidney function and was published in 1976. 16 This equation was ground-breaking for its ability to estimate a patient's CrCl using a single serum creatinine concentration and without having to collect urine, as is required for measured CrCl (mCrCl). The benefits were considered highest for supporting dosing of potentially nephrotoxic medicines.…”

Section: Cockcroft-gault Equationmentioning

confidence: 99%

Estimation of kidney function for medication dosing in adult patients with chronic kidney disease: a practice update

Mirkov,

Scuderi,

Lloyd

et al. 2023

Pharmacy Practice and Res

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Chronic kidney disease (CKD) is a major health concern with a growing disease burden and inequalities in access to treatments. Glomerular filtration rate (GFR) is accepted as the best overall measure of kidney function and is considered the most important measure for medications cleared by the kidneys. In clinical practice, equations that estimate GFR using validated prediction equations are routinely used. This practice update was developed by a Working Group comprising clinical pharmacists representing the Society of Hospital Pharmacists of Australia (SHPA) Specialty Practice streams of Nephrology, Oncology and haematology, Critical care and Infectious diseases. It is intended to provide practical recommendations for clinical pharmacists who use equations to estimate GFR for medication dosing decisions. The limitations of the various equations in use — such as the Chronic Kidney Disease Epidemiology Collaboration (CKD‐EPI), the Cockcroft–Gault equation and Modification of Diet in Renal Disease — are summarised and compared to direct measures of kidney function using exogenous markers. The CKD‐EPI equation is recommended to be used routinely as a primary measure of kidney function. Dose adjustments should also consider medication‐specific, patient‐related, and disease‐related characteristics. Kidney function and the response to therapy should be continuously assessed by monitoring the signs, symptoms and disease outcomes, the emergence of adverse reactions or medication‐induced disorders and use therapeutic drug monitoring (if available) to adjust doses accordingly.

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“…The least biased body size descriptor in the calculation of CLCR CG [30] in obese patients was reported to be ABW, based on a retrospective study including 3678 patients with stable renal function [31]. CLCR CG based on other body size descriptors (ideal, lean, or total body weight) and predicted glomerular filtration rate via the Modification of Diet in Renal Disease (MDRD) equation [32] and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) [33] equation (untransformed and "de-indexed", i.e., de-normalized [34] via individual predicted body surface area [35]) were also evaluated. ABW in male and female individuals was calculated according to Erstad [36].…”

Section: Impact Of Body Size Descriptors and Renal Function On Meropenem Pharmacokineticsmentioning

confidence: 99%

Comparative Plasma and Interstitial Tissue Fluid Pharmacokinetics of Meropenem Demonstrate the Need for Increasing Dose and Infusion Duration in Obese and Non-obese Patients

et al. 2021

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Background and Objectives A quantitative evaluation of the PK of meropenem, a broad-spectrum β-lactam antibiotic, in plasma and interstitial space fluid (ISF) of subcutaneous adipose tissue of obese patients is lacking as of date. The objective of this study was the characterisation of meropenem population pharmacokinetics in plasma and ISF in obese and non-obese patients for identification of adequate dosing regimens via Monte-Carlo simulations. Methods We obtained plasma and microdialysate concentrations after administration of meropenem 1000 mg to 15 obese and 15 non-obese surgery patients from a prospective clinical trial. After characterizing plasma-and microdialysis-derived ISF pharmacokinetics via population pharmacokinetic analysis, we simulated thrice-daily (TID) meropenem short-term (0.5 h), prolonged (3.0 h), and continuous infusions. Adequacy of therapy was assessed by the probability of pharmacokinetic/ pharmacodynamic (PK/PD) target attainment (PTA) analysis based on time unbound concentrations exceeded minimum inhibitory concentrations (MIC) on treatment day 1 (%fT > MIC ) and the sum of PTA weighted by relative frequency of MIC values for infections by pathogens commonly treated with meropenem. To avoid interstitial tissue fluid concentrations below MIC for the entire dosing interval during continuous infusions, a more conservative PK/PD index was selected (%fT > 4 × MIC ). Results Adjusted body weight (ABW) and calculated creatinine clearance (CLCR CG_ABW ) of all patients (body mass index [BMI] = 20.5-81.5 kg/m 2 ) explained a considerable proportion of the between-patient pharmacokinetic variability (15.1-31.0% relative reduction). The ISF:plasma ratio of %fT > MIC was relatively similar for MIC ≤ 2 mg/L but decreased for MIC = 8 mg/L over ABW = 60-120 kg (0.50-0.20). Steady-state concentrations were 2.68 times (95% confidence interval [CI] = 2.11-3.37) higher in plasma than in ISF, supporting PK/PD targets related to four times the MIC during continuous infusions to avoid suspected ISF concentrations constantly below the MIC. A 3000 mg/24 h continuous infusion was sufficient at MIC = 2 mg/L for patients with CLCR CG_ABW ≤ 100 mL/min and ABW < 90 kg, whereas 2000 mg TID prolonged infusions were adequate for those with CLCR CG_ABW ≤ 100 mL/min and ABW > 90 kg. For MIC = 2 mg/L and %fT > MIC = 95, PTA was adequate in patients over the entire investigated range of body mass and renal function using a 6000 mg continuous infusion. A prolonged infusion of meropenem 2000 mg TID was sufficient for MIC ≤ 8 mg/L and all investigated ABW and CLCR CG_ABW when employing the PK/PD target %fT > MIC = 40. Short-term infusions of 1000 mg TID were sufficient for CLCR CG_ABW ≤ 130 mL/min and distributions of MIC values for Escherichia coli, Citrobacter freundii, and Klebsiella pneumoniae but not for Pseudomonas aeruginosa. Conclusions This analysis indicated a need for higher doses (≥ 2000 mg) and prolonged infusions (≥ 3 h) for obese and nonobese patients at MIC ≥ 2 mg/L. Higher PTA was achieved with prolonged i...

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De‐indexed estimated glomerular filtration rates: A simple step towards improving accuracy of drug dosing of renally excreted medications in moderate to severe obesity

Cited by 7 publications

References 8 publications

Entering the Third Decade After Kidney Transplantation: Excellent Graft Function Refers to Superior Graft but Not Patient Survival

Entering the Third Decade After Kidney Transplantation: Excellent Graft Function Refers to Superior Graft but Not Patient Survival

Estimation of kidney function for medication dosing in adult patients with chronic kidney disease: a practice update

Comparative Plasma and Interstitial Tissue Fluid Pharmacokinetics of Meropenem Demonstrate the Need for Increasing Dose and Infusion Duration in Obese and Non-obese Patients

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