Clearance Techniques

Levinsky, Norman G.; Lieberthal, Wilfred

doi:10.1002/cphy.cp080105

Cited by 19 publications

(24 citation statements)

References 178 publications

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“…It is important to stress that quite different functions were assessed in the 2 studies, neither of which provides an unequivocal assessment of TAL function. We used a water loading protocol to assess TAL function, but because free water is generated by solute reabsorption in both the water impermeable cortical segment of the TAL and in the DCT, we cannot distinguish between those segments (2). However, based on the observed effects of furosemide and thiazides on free water clearance in humans (5) and the lack of a significant defect in concentrating ability in human genetic disorders with markedly impaired NCC activity (6), the TAL is thought to be quantitatively much more important than the DCT.…”

Section: Discussionmentioning

confidence: 99%

“…In addition to helping to concentrate urine, the cortical TAL NKCC2 (in concert with the Na,Cl cotransporter [NCC] in the water-impermeable segments of the distal convoluted tubule [DCT]) generates free water by the net reabsorption of ions from tubular fluid, and a racial difference in NKCC2 activity could therefore affect the ability to dilute urine. Tubular diluting capacity can be characterized by measuring free water generation during water loading (2), and we report here the results of 2 experimental studies of renal responses to water loading in blacks and whites.…”

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confidence: 99%

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Whites Excrete a Water Load More Rapidly Than Blacks

2009

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Abstract-A recent report demonstrated a racial difference in response to furosemide compatible with increased ion reabsorption in the thick ascending limb of the loop of Henle in blacks. Urinary dilution is another function of the loop-diuretic-sensitive Na,K,2Cl cotransporter in the thick ascending limb, and racial differences in urinary diluting capacity have not been reported previously. We assessed diluting segment (cortical thick ascending limb and distal convoluted tubule) function in black and white normotensives in 2 studies using a water-loading approach. In both studies, we found that whites excreted a water load more rapidly than blacks. In the first study, the final free water clearance rates (meanϮSD) were 7.3Ϯ4.7 mL/min in whites (nϭ17, 7 females and 10 males) and 3.8Ϯ3.6 mL/min in blacks (nϭ14, 9 females and 5 males; PϽ0.03). In the second study, final free water clearance rates were 8.3Ϯ2.6 mL/min in whites (nϭ17, 8 females and 9 males) and 6.4Ϯ1.8 mL/min in blacks (nϭ11, 8 females and 3 males; PϽ0.01). We found no evidence of a racial difference in renal proximal tubular fluid reabsorption as assessed by renal endogenous lithium clearance or in plasma vasopressin level that could explain the difference in free water excretion. We conclude that our observations are most consistent with a lower capacity of ion reabsorption in the renal diluting segment in blacks. Key Words: kidney Ⅲ water Ⅲ race Ⅲ renal tubule Ⅲ ion Ⅲ vasopressin C hun et al 1 recently demonstrated a racial difference in response to furosemide compatible with increased activity of the loop-diuretic-sensitive Na,K,2Cl (NKCC2) cotransporter in the thick ascending limb (TAL) of the loop of Henle in blacks compared with whites. In addition to helping to concentrate urine, the cortical TAL NKCC2 (in concert with the Na,Cl cotransporter in the water-impermeable segments of the distal convoluted tubule) generates free water by the net reabsorption of ions from tubular fluid, and a racial difference in NKCC2 activity could, therefore, affect the ability to dilute urine. Tubular diluting capacity can be characterized by measuring free water generation during water loading, 2 and we report here the results of 2 experimental studies of renal responses to water loading in blacks and whites. MethodsBoth studies were approved by the University of Michigan Institutional Review Board, and all of the subjects gave written informed consent. For both studies, we recruited subjects by public advertisement from Ann Arbor, Michigan, and the surrounding area. Subjects were healthy normotensive black and white (non-Hispanic) men and women, aged 18 to 50 years. As per National Institutes of Health guidelines, race was self-determined. Normotensive status was established during a screening visit as a systolic blood pressure of Ͻ140 mm Hg and a diastolic blood pressure of Ͻ90 mm Hg for the average of 2 seated auscultatory blood pressure measurements performed by an experienced observer. A general health history was obtained and a physical examination perfor...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Whites Excrete a Water Load More Rapidly Than Blacks

2009

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“…Maximal free water clearance techniques have been used, but their validity has been questioned (Levinsky & Levy, 1973). The lithium clearance method offers a simple, non-invasive quantitative method to estimate sodium delivery from the proximal tubule (Thomsen, 1984) and has since been used extensively to assess the site of action in the nephron of various natriuretic and antinatriuretic agents in man Seidelin et al, 1989).…”

Section: Discussionmentioning

confidence: 99%

Lithium does not alter the renal response to a pressor dose of tyramine in man.

Lang

Rahman

Struthers

1991

Brit J Clinical Pharma

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Renal clearance of lithium has been used as a marker of proximal tubular function in man. Recently, lithium pre-treatment has been shown to interfere with the natriuretic actions of some natriuretic agents in man. We have therefore investigated the effects of oral lithium carbonate (500 mg) on the natriuretic response to a pressor dose of tyramine (15 ,ug kg-' min-') in six normal volunteers. Lithium had no effect on baseline sodium excretion, nor did it affect the tyramine-induced increase in blood pressure and subsequent natriuresis. These results show that oral lithium carbonate (500 mg) does not appear to interfere with the pressure natriuretic response to tyramine in man.

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“…As Levinsky and Levy [8] indicated, the use of venous blood could be a pitfall in clearance studies. We thus decided to assess whether the blood levels of all radiopharmaceuticals in arterial blood samples and those encountered in venous blood samples are the same.…”

Section: Introductionmentioning

confidence: 99%

Simultaneous technetium-99 MAG3, iodine-131-orthoiodohippurate and iodine-125 iothalamate clearance and biodistribution after bolus injection in rats

Casadevall

Turull

Piera³

et al. 2000

Biopharm. Drug Dispos.

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A bolus injection multiple blood sampling method was developed for the simultaneous measurement of blood and plasma clearance of three radiopharmaceuticals in rats. Technetium-99m mercaptoacetyltriglycine ([(99m)Tc]MAG(3)) and iodine-131-orthoiodohippurate ([(131)I]OIH) were used as makers of effective renal blood flow (ERBF), and iodine-125 iothalamate ([(125)I]IOT) was used as a marker of glomerular filtration rate (GFR). These methods can be easily performed in rats without arterial catheterization. Tissue biodistribution was studied in four groups of rats subjected to the following: group A, renal pedicle isolation (sham-operated); group B, ligature of one kidney pedicle; group C, ligature of both renal pedicles; and group D, ligature of both kidney pedicles and the bile duct. Renal clearance of [(99m)Tc]MAG(3) was greater than [(131)I]OIH and both agents were cleared faster than ([(125)I]-IOT). Either of the two markers of ERBF may be used in experimental studies, but it should be borne in mind that these are relative measurements of kidney performance. [(99m)Tc]MAG(3) and [(125)I]-IOT showed bile excretion in healthy rats, so they cannot completely fulfill the requirements for use as markers of ERBF. When renal function was impaired experimentally, [(99m)Tc]MAG(3) and [(125)I]-IOT were excreted in bile and [(131)I]OIH was secreted in the intestine. Thus, while the markers of ERBF and GFR may be reliable under normal physiological conditions, they may give progressively more erroneous values as renal function deteriorates.

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Clearance Techniques

Abstract: The sections in this article are: History Limitations of Clearance Methods Technical Considerations Constant‐Infusion Technique Other Techniques Single‐Injection (Single‐Shot) Technique Clearance Methods for Estimation of Glomerular Filtration Rate … Show more

Cited by 19 publications

References 178 publications

Whites Excrete a Water Load More Rapidly Than Blacks

Whites Excrete a Water Load More Rapidly Than Blacks

Lithium does not alter the renal response to a pressor dose of tyramine in man.

Simultaneous technetium-99 MAG3, iodine-131-orthoiodohippurate and iodine-125 iothalamate clearance and biodistribution after bolus injection in rats

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