Determination of Low Glomerular Filtration Rate Using Iohexol Clearance

Frennby, Bo; Sterner, Gunnar; Almén, Torsten; Hagstam, Karl‐Erik; Jacobsson, Lars

doi:10.1097/00004424-199406001-00079

Cited by 14 publications

(12 citation statements)

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“…It is most likely that because of the high doses used in human studies, an absorptive mechanism was never observed, and iohexol was supposed to be suitable as a filtration marker. Most studies in human subjects were performed with doses between 3 and 7 g, resulting in initial plasma concentrations of approximately 1000 times higher than used in our IPK experiments (Frennby et al, 1994;Lindblad & Berg, 1994). According to our results, at these concentrations renal clearance will indeed be determined only by glomerular filtration.…”

Section: Discussionsupporting

confidence: 51%

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Glomerular filtration and saturable absorption of iohexol in the rat isolated perfused kidney

Masereeuw

Moons

Smits

et al. 1996

British J Pharmacology

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1 The renal handling of iohexol was examined in the rat isolated perfused kidney (IPK) over a perfusate concentration range of 5-20 Mg ml-'. 2 At a concentration of 5 Mg ml-', a ratio of renal clearance over clearance by glomerular filtration (CIR/GF) of 0.63 + 0.06 could be determined. This ratio increased until 1.02+0.06 at 20 Mg ml-, indicating that a saturable mechanism is involved in the luminal disappearance of the drug. 3 Pretreatment of the kidneys with polylysine, probenecid or diatrizoate resulted in a significantly enhanced clearance of iohexol, probably due to inhibition of membrane binding. Renal clearance data were fitted to a kinetic model including filtration into the primary urine followed by saturable absorption at the luminal membrane. An absorption constant, KA, of 7.3 + 1.3 Mg ml-', and a maximum rate of absorption, VA,MaX, of 1.4+0.1 Mg min-' were determined. 4 lohexol accumulated in kidney tissue, reaching a concentration of 2 to 7.5 times the perfusate concentration. In freshly isolated proximal tubular cells and kidney cortex mitochondria, iohexol reduced the uncoupled respiratory rate at a concentration comparable to the highest tissue concentration found in the IPK. 5 In conclusion, iohexol is not only filtered by the kidney but also reabsorbed via a saturable mechanism, which results in tubular accumulation. Intracellularly sequestered iohexol may affect mitochondrial oxidative metabolism. Our results indicate that iohexol is not a true filtration marker.

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Section: Discussionsupporting

confidence: 51%

“…In these studies the contrast agent was supposed to be handled by the kidney in a fashion similar to inulin, implying that neither secretion nor reabsorption occurred (Frennby et al, 1994;Lindblad & Berg, 1994).…”

mentioning

confidence: 99%

Glomerular filtration and saturable absorption of iohexol in the rat isolated perfused kidney

Masereeuw

Moons

Smits

et al. 1996

British J Pharmacology

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“…One could argue that when plasma clearance is used, only an overestimation of true GFR exists, especially in persons with reduced kidney function (52). However, early studies suggest that tubular secretion of iohexol is negligible (53,54). An overestimation would increase the magnitude of the difference between our mGFR and eGFRs.…”

Section: Discussionmentioning

confidence: 99%

Two Novel Equations to Estimate Kidney Function in Persons Aged 70 Years or Older

Schaeffner¹,

Ebert²,

Delanaye³

et al. 2012

Ann Intern Med

526

452

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Background: In older adults, current equations to estimate glomerular filtration rate (GFR) are not validated and may misclassify elderly persons in terms of their stage of chronic kidney disease. Objective: To derive the Berlin Initiative Study (BIS) equation, a novel estimator of GFR in elderly participants. Design: Cross-sectional. Data were split for analysis into 2 sets for equation development and internal validation. Setting: Random community-based population of a large insurance company. Participants: 610 participants aged 70 years or older (mean age, 78.5 years). Intervention: lohexol plasma clearance measurement as gold standard. Measurements: GFR, measured as the plasma clearance of the endogenous marker iohexol, to compare performance of existing equations of estimated GFR with measured GFR of the gold standard; estimation of measured GFR from standardized creatinine and cystatin C levels, sex, and age in the learning sample; and comparison of the BIS equations (BIS1: creatinine-based; BIS2: creatinine-and cystatin C-based) with other estimating equations and determination of bias, precision, and accuracy in the validation sample. Results:The new BIS2 equation yielded the smallest bias followed by the creatinine-based BIS1 and CockcroftGault equations. All other equations considerably overestimated GFR. The BIS equations confirmed a high prevalence of persons older than 70 years with a GFR less than 60 mL/min per 1.73 m 2 (BIS1, 50.4%; BIS2, 47.4%; measured GFR, 47.9%). The total misclassification rate for this criterion was smallest for the BIS2 equation (11.6%), followed by the cystatin C equation 2 (15.1%) proposed by the Chronic Kidney Disease Epidemiology Collaboration. Among the creatinine-based equations, BIS1 had the smallest misclassification rate (17.2%), followed by the Chronic Kidney Disease Epidemiology Collaboration equation (20.4%). Limitation: There was no validation by an external data set. Conclusion: The BIS2 equation should be used to estimate GFR in persons aged 70 years or older with normal or mild to moderately reduced kidney function. If cystatin C is not available, the BIS1 equation is an acceptable alternative. Primary Funding Source: Kuratorium für Dialyse und Nierentransplatation (KfH) Foundation of Preventive Medicine.

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“…They are all small hydrophilic molecules excreted by passive glomerular filtration. Cellular uptake is less than 1-2% [3]. Even in anuric patients the extrarenal excretion is no more than 2% [3].…”

Section: \Np{t) = -X 2 T + Lnbmentioning

confidence: 91%

Renal function and the excretion of contrast agents

Dawson

Peters²

1996

The British Journal of Radiology

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The renal excretion of intravascular iodinated X-ray and gadolinium chelate MR contrast is examined theoretically. An expression is derived for the proportion of an administered dose of such an agent excreted in any given time in the face of varying levels of renal function. It is shown that a family of curves may be generated from which an estimate of this proportion for any time may be made. Some circumstances in which such knowledge may be useful are briefly discussed.

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Determination of Low Glomerular Filtration Rate Using Iohexol Clearance

Cited by 14 publications

References 0 publications

Glomerular filtration and saturable absorption of iohexol in the rat isolated perfused kidney

Glomerular filtration and saturable absorption of iohexol in the rat isolated perfused kidney

Two Novel Equations to Estimate Kidney Function in Persons Aged 70 Years or Older

Renal function and the excretion of contrast agents

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