Comparison of Gd‐DTPA and Gd‐BOPTA for studying renal perfusion and filtration

Notohamiprodjo, Mike; Pedersen, Michael; Gläser, Christian; Helck, Andreas; Lodemann, Klaus‐Peter; Jespersen, Bente; Fischereder, Michael; Reiser, Maximilian; Sourbron, Steven

doi:10.1002/jmri.22640

Cited by 19 publications

(6 citation statements)

References 39 publications

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“…Considering the practical difficulties of collecting urine at such short intervals, simulation of tubular concentration using the PBPK modeling can be a useful tool for identify compounds and dosing regimens that would be at risk of crystalluria-AKI. Supporting information could also be obtained from further development and application of high spatial resolution bioimaging techniques (Notohamiprodjo et al, 2011).…”

mentioning

confidence: 99%

Towards Further Verification of Physiologically-Based Kidney Models: Predictability of the Effects of Urine-Flow and Urine-pH on Renal Clearance

Matsuzaki¹,

Scotcher²,

Darwich³

et al. 2018

J Pharmacol Exp Ther

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In vitro-in vivo extrapolation (IVIVE) of renal excretory clearance (CL R ) using the physiologically based kidney models can provide mechanistic insight into the interplay of multiple processes occurring in the renal tubule; however, the ability of these models to capture quantitatively the impact of perturbed conditions (e.g., urine flow, urine pH changes) on CL R has not been fully evaluated. In this work, we aimed to assess the predictability of the effect of urine flow and urine pH on CL R and tubular drug concentrations (selected examples). Passive diffusion clearance across the nephron tubule membrane was scaled from in vitro human epithelial cell line Caco-2 permeability data by nephron tubular surface area to predict the fraction reabsorbed and the CL R of caffeine, chloramphenicol, creatinine, dextroamphetamine, nicotine, sulfamethoxazole, and theophylline. CL R values predicted using mechanistic kidney model at a urinary pH of 6.2 and 7.4 resulted in prediction bias of 2.87-and 3.62-fold, respectively. Model simulations captured urine flow-dependent CL R , albeit with minor underprediction of the observed magnitude of change. The relationship between drug solubility, urine flow, and urine pH, illustrated in simulated intratubular concentrations of acyclovir and sulfamethoxazole, agreed with clinical data on tubular precipitation and crystal-induced acute kidney injury. This study represents the first systematic evaluation of the ability of the mechanistic kidney model to capture the impact of urine flow and urine pH on CL R and drug tubular concentrations with the aim of facilitating refinement of IVIVE-based mechanistic prediction of renal excretion.

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mentioning

confidence: 99%

Towards Further Verification of Physiologically-Based Kidney Models: Predictability of the Effects of Urine-Flow and Urine-pH on Renal Clearance

Matsuzaki¹,

Scotcher²,

Darwich³

et al. 2018

J Pharmacol Exp Ther

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“…The leakage rate and the accuracy and precision of its measurement are likely to depend on the size, shape, and chemical properties of the contrast agent [73], [74], but at present, there is no convincing evidence for selecting a specific GBCA for studies of BBB integrity. On theoretical grounds, one would prefer a contrast agent with a strong T 1 relaxivity, high BBB permeability (compared with the agents listed in Table 1), and long biological half-life to obtain the lowest detection limit for leakage.…”

Section: Review Of Methodology and Harness Recommendationsmentioning

confidence: 99%

Quantifying blood‐brain barrier leakage in small vessel disease: Review and consensus recommendations

Thrippleton

Backes

Sourbron

et al. 2019

Alzheimer's & Dementia

181

216

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Cerebral small vessel disease (cSVD) comprises pathological processes of the small vessels in the brain that may manifest clinically as stroke, cognitive impairment, dementia, or gait disturbance. It is generally accepted that endothelial dysfunction, including blood-brain barrier (BBB) failure, is pivotal in the pathophysiology. Recent years have seen increasing use of imaging, primarily dynamic contrast-enhanced magnetic resonance imaging, to assess BBB leakage, but there is considerable variability in the approaches and findings reported in the literature. Although dynamic contrast-enhanced magnetic resonance imaging is well established, challenges emerge in cSVD because of the subtle nature of BBB impairment. The purpose of this work, authored by members of the HARNESS Initiative, is to provide an in-depth review and position statement on magnetic resonance imaging measurement of subtle BBB leakage in clinical research studies, with aspects requiring further research identified. We further aim to provide information and consensus recommendations for new investigators wishing to study BBB failure in cSVD and dementia.

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“…Gadobenate‐dimeglumine (Gd‐BOPTA), bound to albumin, yields an underestimation by ∼40% of the GFR. This mistake may be due to incomplete glomerular filtration and a decreased magnetic relaxation ability . However, this property plays a role in MR angiography.…”

Section: Renal Fmrimentioning

confidence: 99%