Plasma Clearance Method Research Articles

Autonomic Neuropathy Predicts Deterioration in Glomerular Filtration Rate in Patients With IDDM

To evaluate whether autonomic neuropathy predicts deterioration in glomerular filtration rate in IDDM patients. A prospective study in which 35 IDDM patients have been followed for 10-11 yr. Autonomic nerve function tests included heart-rate reactions to deep breathing (expiration-to-inspiration ratio) and to tilt (acceleration and brake indexes). GFR was evaluated by the 51Cr-EDTA plasma clearance method. At entry to the study, no significant differences were noted in age (39 +/- 2 [mean +/- SE] vs. 42 +/- 4 yr), duration of diabetes (20 +/- 3 vs. 23 +/- 4 yr), supine blood pressures (120/79 +/- 3/2 mmHg vs. 121/78 +/- 6/3 mmHg), and GFR (113 +/- 6 vs. 107 +/- 3 ml.min-1.1.73 m-2) between 20 patients with and 15 without autonomic neuropathy (age-corrected criteria). After 10-11 yr, GFR had decreased significantly (22 +/- 4 ml.min-1.1.73 m-2, P < 0.001) in patients with autonomic neuropathy but not (8 +/- 5 ml.min-1.1.73 m-2, NS) in patients without. In keeping with this, GFR decreased more than expected (difference in GFR/expected decrease in GFR) in patients with autonomic neuropathy, compared with those without (4.46 +/- 0.98 vs. 0.48 +/- 0.73, P < 0.005). Autonomic neuropathy predicts future deterioration in GFR in IDDM patients.

An accurate practical method for estimating GFR in clinical studies using a constant subcutaneous infusion

Glomerular filtration rate (GFR) is the standard measure of renal function and serial measurements often are used to describe the course of renal disease in clinical studies including controlled clinical trials. Serum creatinine (Sr), commonly used to estimate renal function, is now recognized as insufficiently accurate for this purpose [1, 2]. The reference standard for estimating GFR is the renal clearance of inulin (C1). The plasma C1, derived from steady state level and input rate, is equally suitable [3]. Although inulin is the ideal marker, isotopic and unlabeled iothalamate are both used to estimate GFR from the renal ['1—6] or plasma [5, 7, 8] clearance of iothalamate (Cr0). Even these clearance methods, however, are sufficiently time consuming and expensive to constitute an impediment to accurately estimating GFR in clinical studies, particularly in children. Plasma clearance is measured either by giving a single bolus injection of a marker and measuring its fractional disappearance rate from plasma [9] (single-injection plasma clearance) or by infusing a marker to a steady state and measuring its input rate divided by its plasma concentration [101 (steady-state plasma clearance). Either of the two plasma clearance methods is preferred in children or patients with voiding dysfunction because collecting timed urine samples as required for renal clearances often is impractical. We describe a method for measuring the steady-state plasma C10. lothalamate is delivered subcutaneously from a very accurate portable pump at a constant rate for a calculated minimum infusion time. Clearance is calculated from input rate and the steady state plasma level.

A Comparison of Inulin, Paraaminohippuric Acid, and Endogenous Creatinine Clearances as Measures of Renal Function in Neonatal Foals

The glomerular filtration rate (GFR) was estimated in eight full-term neonatal foals by the single injection inulin plasma clearance method at two days of age, the continuous infusion plasma and urinary clearance methods at three days of age, and the 12-hour endogenous creatinine clearance method at four days of age. The effective renal plasma flow (ERPF) was estimated simultaneously by the single injection para-aminohippuric acid (PAH) plasma clearance method in the eight two-day old foals and the continuous PAH infusion plasma and urinary clearance method in the eight three-day old foals. The GFR (+/- 1 SEM), as determined from the single injection plasma clearance method, was 2.30 +/- 0.34 mL/kg/min; by continuous infusion plasma clearance 2.56 +/- 0.30 mL/kg/min; by continuous infusion urinary clearance 2.82 +/- 0.32 mL/kg/min; and by 12-hour endogenous creatinine clearance 2.81 +/- 0.55 mL/kg/min. Effective renal plasma flow (+/- 1 SEM) measured by the single injection plasma clearance method was 15.22 +/- 1.5 mL/kg/min, by continuous infusion plasma clearance was 18.21 +/- 2.0 mL/kg/min. and by continuous infusion urinary clearance it was 11.95 +/- 1.9 mL/kg/min. The results of these methods were not statistically different. On a per kilogram body weight basis, the full-term neonatal foal's GFR and ERPF was determined to be comparable with adult equine GFR and ERPF.

Pathophysiology of gastrointestinal mucosal permeability

The intestinal mucosa is composed of multiple barriers to the lumen-to-blood transport of solutes, including the unstirred water and mucous layers, the apical and basolateral cell membranes of the epithelial cell, the paracellular junctions, the interstitial matrix, and the capillary and lymphatic endothelia. The epithelial barrier appears effectively to restrict the movement of solutes with a radius as low as 3 A, yet it also permits limited permeation by molecules as large as albumin (36 A radius). There is evidence to suggest that the restrictive properties of the gastrointestinal mucosa are significantly altered under various physiological and pathological conditions, and measurement of plasma (or luminal) clearances of water-soluble molecules has proved to be a popular method for studying intestinal permeability. The aim of this review is to discuss the concept of the plasma clearance method, methodological aspects of the technique, factors that influence plasma-to-lumen clearance measurements (e.g. solute size, blood flow, and permeability of the epithelial cell barrier), and advantages and disadvantages of the clearance method. Finally, application of the clearance technique to the study of ischaemia/reperfusion-, ethanol-, and FMLP-induced mucosal injury will be described.

Glomerular filtration rate and the kinetics of 123I-metaiodobenzylguanidine.

We have recently reported evidence that the calcium antagonist nifedipine can improve the tumour retention of 131I-metaidobenzylguanidine (131I-MIBG) in patients with malignant phaeochromocytoma. During studies of the pharmacological modification of tumour MIBG kinetics, it is important to distinguish clearly between a direct effect on MIBG cellular retention by a pharmaceutical, and secondary effects due, for example, to a change in glomerular filtration rate (GFR). In order to provide the fundamental kinetic data required for the numerical modelling of the effect of nifedipine on tumour MIBG kinetics, we have investigated the influence of GFR on MIBG plasma and renal kinetics. The 123I-MIBG plasma curve and MIBG renal plasma clearance rate were studied in ten patients, ranging from subjects without biochemical or scintigraphic evidence of phaeochromocytoma to individuals with widely disseminated metastatic disease. GFR was measured using the 99mTc-DTPA plasma clearance method. In four cases, the studies were repeated with the patients taking oral nifedipine. Statistically significant correlations were found between GFR and the MIBG plasma concentration. MIBG renal plasma clearance rate and the early (0 to 5 min) renal excretion of MIBG. The data permit the evaluation of the plasma integral during the first few min following bolus injection, a quantity important in the numerical modelling of tumour kinetics. GFR was found to have a major influence on whole-body MIBG kinetics, but there was also evidence of the effect of the metastatic tumour burden.

Measurement of glomerular filtration rate in adults: accuracy of five single‐sample plasma clearance methods

After an intravenous injection of a tracer that is removed from the body solely by filtration in the kidneys, the glomerular filtration rate (GFR) can be determined from its plasma clearance. The method requires a great number of blood samples but collection of urine is not needed. In the present investigation the total plasma clearance of 51Cr-EDTA (ethylenediaminetetra-acetate) was assessed from 13 blood samples taken 5-300 min post-injection in 44 adult patients with GFR greater than 15 ml min-1. In 34 of these patients the plasma clearance of 99Tcm-DTPA (diethylenetriaminepenta-acetate) was determined simultaneously. Using these clearance values as reference the accuracy of six simplified methods were studied: five single-sample methods and one five-sample method. The standard error of estimate (SEE) of the single-sample methods ranged from 4.2 to 7.5 ml min-1 using EDTA, and from 3.8 to 6.3 ml min-1 using DTPA. SEE of the five-samples method was 3.0 ml min-1 (EDTA) and 3.1 ml min-1 (DTPA). The single-sample methods given by Christensen & Groth (1986) and by Tauxe (1986) are recommended for daily use, as SEE was small even at low GFR values. In patients with GFR less than 80 ml min-1, in whom a highly accurate determination is needed, a multiple samples method is recommended, e.g., Brøchner-Mortensen (1972).

Estimation of glomerular filtration rate using 99mTc-DTPA and the gamma camera.

Two methods of glomerular filtration rate estimation have been evaluated, based on the intravenous administration of 99mTc-DTPA and the measurement of renal time activity curves by means of a computer linked gamma camera. A single 20 min plasma sample was also required. These methods were designed to minimize the component of error arising from decay statistics. One method was based on using a constant fraction of the cardiac activity in lieu of a perirenal region of interest for the background correction, the other was based on deconvolution by a constrained least squares technique. The first method, based on modifying the background correction, led to poor results (residual standard deviation 18.9 ml/min when compared with the plasma clearance method). The second method, based on constrained least squares deconvolution, worked as well as previously reported methods (residual standard deviation 14.5 ml/min) and appears suitable for clinical use.

Experience with a standardized bromsulfalein plasma clearance method as a sensitive test of liver function

Experience with a standardized bromsulfalein plasma clearance method as a sensitive test of liver function