The Renal Excretion of Sucrose in Normal Man; Comparison With Inulin

Steinitz, K

doi:10.1152/ajplegacy.1940.129.2.252

Cited by 13 publications

(3 citation statements)

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“…A further consideration is the renal handling of sucrose. It is known that sucrose in plasma, in contrast to glucose, is subject to limited tubular reabsorption in the kidney and therefore undergoes significant renal excretion . In line with this, in the present study, it was observed that following CSL112 infusion, the majority of the administered sucrose was rapidly cleared from the blood via glomerular filtration.…”

Section: Discussionsupporting

confidence: 87%

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Pharmacokinetics and Safety of CSL112 (Apolipoprotein A‐I [Human]) in Adults With Moderate Renal Impairment and Normal Renal Function

Tortorici

Duffy

Evans

et al. 2018

Clinical Pharm in Drug Dev

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CSL112 (Apolipoprotein A‐I [human]) is an intravenous preparation of apolipoprotein A‐I (apoA‐I), formulated with phosphatidylcholine (PC) and stabilized with sucrose, in development to prevent early recurrent cardiovascular events following acute myocardial infarction (AMI). This phase 1 study was designed to determine if moderate renal impairment (RI) influenced the pharmacokinetics (PK) and safety of CSL112. Thirty‐two subjects, 16 with moderate RI (estimated glomerular filtration rate [eGFR] ≥ 30 and < 60 mL/min/1.73 m 2 ) and 16 age‐, sex‐, and weight‐matched subjects with normal renal function (eGFR ≥ 90 mL/min/1.73 m 2 ) were randomized 3:1 to receive a single infusion of CSL112 2 g (n = 6) or placebo (n = 2), or CSL112 6 g (n = 6) or placebo (n = 2). PK sampling was at prespecified times from 48 hours prior to 144 hours following infusions, with final safety assessments at 90 days. Renal and hepatic safety, and adverse events (AEs) were monitored throughout the study. Plasma apoA‐I and PC PK profiles were similar between renal function cohorts at both doses. For CSL112 6 g mean ± SD apoA‐I AUC 0 ‐ last was 7670 ± 1900 and 9170 ± 2910 mg·h/dL in normal renal function and moderate RI subjects, respectively. Renal apoA‐I clearance was <1% of CSL112 dose. In moderate RI, sucrose clearance was slower; however, approximately 70% was excreted within 48 hours in both renal function cohorts. No CSL112‐related serious AEs or clinically significant renal or hepatic safety changes were observed. Dose adjustment of CSL112 is not required in subjects with moderate RI, supporting its further investigation in AMI patients with moderate RI.

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Section: Discussionsupporting

confidence: 87%

“…The volume of distribution of CSL112 was found to be slightly higher than total plasma volume, indicating that CSL112 undergoes a degree of distribution into extravascular fluids and tissues. To date, the PK of sucrose following CSL112 administration has not been studied; however, it is known that sucrose undergoes significant renal excretion …”

mentioning

confidence: 99%

Pharmacokinetics and Safety of CSL112 (Apolipoprotein A‐I [Human]) in Adults With Moderate Renal Impairment and Normal Renal Function

Tortorici

Duffy

Evans

et al. 2018

Clinical Pharm in Drug Dev

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“…The various substances studied in this investigation have all been employed at one time or another to measure GFR (1,(14)(15)(16)(17)(18). Although all appear satisfactory at normal ITP, with the exception of inulin all leaked from the tubule when pressure was increased, indicating that they are unsatisfactory markers for GFR under these conditions, as we have demonstrated directly in the case of mannitol.…”

Section: Discussionmentioning

confidence: 88%

Renal Tubular Permeability during Increased Intrarenal Pressure

Lorentz¹,

Lassiter²,

Gottschalk³

1972

J. Clin. Invest.

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ABSTR A CT Renal tubular permeability was studied by microinjection techniques during increased intrarenal pressure in anesthetized diuretic rats. Intrarenal pressure, as evidenced by intratubular pressure (ITP), was increased by elevation of ureteral pressure, partial renal venous constriction, or massive saline diuresis. Various combinations of radioactive inulin, creatinine, mannitol, sucrose, and iothalamate in isotonic saline were microinjected into superficial proximal and distal convolutions, and recovery of the isotopes was measured in the urine.Inulin was completely recovered in the urine from the injected kidney at both normal and elevated ITP. Creatinine, mannitol, sucrose, and iothalamate were also completely recovered at normal ITP, but recoveries were significantly lower, averaging 73, 85, 89, and 85%, respectively, after early proximal injection when proximal ITP was increased to 30 ±2 mm Hg by elevation of ureteral pressure. Since transit time is prolonged under these conditions, mannitol recovery was also studied during aortic constriction, which prolongs transit time but lowers ITP. Recovery was complete. A significant loss of mannitol was observed during massive saline diuresis, which shortens transit time but increases ITP. During renal venous constriction producing a proximal ITP of 30 ±2 mm Hg, mannitol recovery was significantly less than 100% even after An abstract of this work appeared in J. Clin. Invest.

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Clearance Techniques

Levinsky

Lieberthal

1992

Comprehensive Physiology

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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 Substances Used as Markers Clearance Methods for Estimation of Renal Plasma Flow Substances Used as Markers p‐Aminohippurate Clearance in Renal Disease Extraction of p‐Aminohippurate as' Index of Medullary Blood Flow Clearance Methods for Analysis of Tubular Function Localization of Water and Sodium Reabsorption Estimation of Proximal Reabsorption from Urine Flow Assessment of Sodium Reabsorption in Diluting Segment Assessment of Sodium Reabsorption in Medullary Ascending Limb Determination of Proximal Reabsorption Using Clearance of Lithium

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The Renal Excretion of Sucrose in Normal Man; Comparison With Inulin

Cited by 13 publications

References 0 publications

Pharmacokinetics and Safety of CSL112 (Apolipoprotein A‐I [Human]) in Adults With Moderate Renal Impairment and Normal Renal Function

Pharmacokinetics and Safety of CSL112 (Apolipoprotein A‐I [Human]) in Adults With Moderate Renal Impairment and Normal Renal Function

Renal Tubular Permeability during Increased Intrarenal Pressure

Clearance Techniques

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