Measurement Of Plasma Clearance Research Articles

#2422 Iohexol plasma clearance measurement protocol standardization—a consensus of the European Kidney Function Consortium

Abstract Background and Aims International consensus supports the development of standardized protocols for measured glomerular filtration rate (mGFR) to facilitate the adoption of mGFR determination in both clinical and research settings. Method The European Kidney Function Consortium (EKFC) convened an international group of mGFR experts. The working group performed an extensive literature search to inform the development of recommendations for mGFR determination using one-compartment plasma clearance models and iohexol as the exogenous filtration marker. Iohexol was selected as it is non-radio labeled, inexpensive, widely available, and can be assayed at a central laboratory. Other commonly used non-radio labeled tracers have been (inulin) or are soon to be (iothalamate) discontinued. A plasma clearance model was selected as it requires no timed urine collections. A one-compartment model was preferred to a two compartment model as it requires fewer samples. The resulting recommendations were based on published evidence complemented by expert opinion. Results Recommendations include practical advice for patients and health professionals, preparation, administration and safety aspects of iohexol, laboratory analysis, blood sample collection and sample timing for both multiple and single sample protocols, description of the mGFR mathematical calculations as well as implementation strategies (Fig.). EKFC will provide materials such as patient information sheets, standard operating procedures, a study protocol template, and support for mGFR calculation. Conclusion Members of the EKFC have evaluated the evidence and formulated recommendations that include all aspects of iohexol plasma clearance measurement using a one compartment model. *Author list on behalf of the European Kidney Function Consortium (EKFC).

Association between plasma aldosterone concentration and intraglomerular hemodynamics in primary aldosteronism.

In primary aldosteronism (PA), aldosterone could affect glomerular hemodynamics by elevating renal vascular resistance and glomerular capillary pressure. However, the relationship between plasma aldosterone concentrations (PAC) and glomerular hemodynamics including efferent arteriolar resistance (Re), afferent arteriolar resistance (Ra) in humans is still unclear. The aim of this study was to investigate the relationships of PAC with intraglomerular hemodynamic parameters in patients with PA. An observational study of glomerular hemodynamics was performed using simultaneous measurements of plasma clearance of para-aminohippurate and inulin (Cin; glomerular filtration rate (GFR)) in 17 patients with PA. Kidney function was evaluated by Cin, estimated GFR based on serum creatine (eGFRcre) and serum cystatin C (eGFRcys) and creatine clearance (Ccr). Intraglomerular hemodynamic parameters, including Re, Ra, and intraglomerular hydrostatic pressure (Pglo) were calculated using Gomez's formulae. In the 17 PA cases, PAC was significantly correlated with Cin (rho=0.752, p=0.001) and eGFRcys (rho=0.567, p=0.018), but was not correlated witheGFRcreand Ccr. PAC was also significantly correlated with Pglo, Re, and urinary protein/day (rho=0.775, p=0.0004, rho=0.625, p=0.009, and rho=0.625, p=0.007, respectively). Multivariable regression analysis showed that PAC was significantly associated with Cin and Re. In comparing aldosterone producing adenoma (APA) and non-APA cases, Cin was significantly elevated in APA (p=0.037), whereas eGFRcre, eGFRcys, and Ccr were not. Re tended to be higher in APA (p=0.064). These results suggest high aldosterone cause glomerular hyperfiltration by constricting Re. Cin, but not eGFRcre and Ccr, may be useful for evaluating kidney function in PA.

Estimating Analytical Errors of Glomerular Filtration Rate Measurement.

Few studies are available on how to optimize time points for sampling and how to estimate effects of analytical uncertainty when glomerular filtration rate (GFR) is calculated. We explored the underlying regression mathematics of how analytical variation of a kidney filtration marker affects 1-compartment, slope-and-intercept GFR calculations, using 2 or 3 time points following a bolus injection, and used this to examine the results from 731 routine 3-point iohexol plasma clearance measurements. GFR calculations inflated analytical uncertainty if the time points were taken too late after the bolus injection and too close after each other. The uncertainty in GFR calculation was, however, the same as the analytical uncertainty if optimal time points were used. The middle of the 3 samples was of little value. The first sample should be taken as early as possible after the distribution phase. Sampling before the patient specific half-life of the kidney filtration marker resulted in an exponential error inflation whereas no error inflation was seen when sampling occurred later than 2 half-lives. Theoretical GFR uncertainty could be lowered 2.6-fold if individually optimized time points for sampling had been used in our 731 clearance measurements. Using Taylor expansions to approximate the moments of transformed random variables, the uncertainty of an individual GFR measurement could be calculated in a simple enough way to be applicable by laboratory software. We provide a theoretical foundation to select patient-optimal time points that may both limit errors and allow calculation of GFR uncertainty.

Measurement of glomerular filtration rate using a reference method

Direct measurement methods of glomerular filtration rate (GFR) are considered as the gold standard to assess kidney function. Following the withdrawal of the Proinuline Serb® specialty by the French National Health Surveillance Agency, iohexol remains the most suitable marker to replace inulin as the marker for GFR in France. The assay is performed by high performance liquid chromatography (HPLC) coupled with ultraviolet (UV) detection or by mass spectrometry. Plasma clearance measurement is the protocol of choice: single-sample protocols dominate, but multiple-sample protocols may be more accurate in specific situations to improve accuracy. In some cases, urinary clearance protocols may be proposed. National and international recommendations suggest using a GFR measurement as a confirmatory test in cases where the creatinine-based estimated GFR is inappropriate, ie clinical situations characterized by a significant alteration of muscle mass or volume distribution. The indications retained by the working group were graded according to the level of recommendations. The essential indications are the evaluation of living kidney donor, the monitoring of kidney allograft function at one year post-transplantation, drugs with narrow therapeutic range (anticoagulant, chemotherapy) in patients with inadequate estimation of GFR by creatinine and clinical research.

Iohexol plasma clearance for measuring glomerular filtration rate in clinical practice and research: a review. Part 1: How to measure glomerular filtration rate with iohexol?

While there is general agreement on the necessity to measure glomerular filtration rate (GFR) in many clinical situations, there is less agreement on the best method to achieve this purpose. As the gold standard method for GFR determination, urinary (or renal) clearance of inulin, fades into the background due to inconvenience and high cost, a diversity of filtration markers and protocols compete to replace it. In this review, we suggest that iohexol, a non-ionic contrast agent, is most suited to replace inulin as the marker of choice for GFR determination. Iohexol comes very close to fulfilling all requirements for an ideal GFR marker in terms of low extra-renal excretion, low protein binding and in being neither secreted nor reabsorbed by the kidney. In addition, iohexol is virtually non-toxic and carries a low cost. As iohexol is stable in plasma, administration and sample analysis can be separated in both space and time, allowing access to GFR determination across different settings. An external proficiency programme operated by Equalis AB, Sweden, exists for iohexol, facilitating interlaboratory comparison of results. Plasma clearance measurement is the protocol of choice as it combines a reliable GFR determination with convenience for the patient. Single-sample protocols dominate, but multiple-sample protocols may be more accurate in specific situations. In low GFRs one or more late samples should be included to improve accuracy. In patients with large oedema or ascites, urinary clearance protocols should be employed. In conclusion, plasma clearance of iohexol may well be the best candidate for a common GFR determination method.

Accurate and precise plasma clearance measurement using four 99mTc-DTPA plasma samples over 4 h.

ObjectivesGlomerular filtration rate can be measured as the plasma clearance (CL) of a glomerular filtration rate marker despite body fluid disturbances using numerous, prolonged time samples. We desire a simplified technique without compromised accuracy and precision.Materials and methodsWe compared CL values derived from two plasma concentration curve area methods – (a) biexponential fitting [CL (E2)] and (b) Tikhonov adaptively regularized gamma variate fitting [CL (Tk-GV)] – for 4 versus 8 h time samplings from 412 99mTc-DTPA studies in 142 patients, mostly paediatric patients, with suspected fluid disturbances.ResultsCL (Tk-GV) from four samples/4 h and from nine samples/8 h, both accurately and precisely agreed with the standard, which was taken to be nine samples/8 h CL from (noncompartmental) numerical integration [CL (NI)]. The E2 method, four samples/4 h, and nine samples/8 h median CL values significantly overestimated the CL (NI) values by 4.9 and 3.8%, respectively.ConclusionCompared with the standard, CL (E2) from four samples/4 h and from nine samples/8 h proved to be the most inaccurate and imprecise method examined, and can be replaced by better methods for calculating CL. The CL (Tk-GV) can be used to reduce sampling time in half from 8 to 4 h and from nine to four samples for a precise and accurate, yet more easily tolerated and simplified test.

Iohexol plasma clearance measurement in older adults with chronic kidney disease-sampling time matters.

Accurate and precise measurement of GFR is important for patients with chronic kidney disease (CKD). Sampling time of exogenous filtration markers may have great impact on measured GFR (mGFR) results, but there is still uncertainty about optimal timing of plasma clearance measurement in patients with advanced CKD, for whom 24-h measurement is recommended. This satellite project of the Berlin Initiative Study evaluates whether 24-h iohexol plasma clearance reveals a clinically relevant difference compared with 5-h measurement in older adults. In 104 participants with a mean age of 79 years and diagnosed CKD, we performed standard GFR measurement over 5 h (mGFR300) using iohexol plasma concentrations at 120, 180, 240 and 300 min after injection. With an additional sample at 1440 min, we assessed 24-h GFR measurement (mGFR1440). Study design was cross-sectional. Calculation of mGFR was conducted with a one compartment model using the Brochner-Mortensen equation to calculate the fast component. mGFR values were compared with estimated GFR values (MDRD, CKD-EPI, BIS1, Revised Lund-Malmö and Cockcroft-Gault). In all 104 subjects, mGFR1440 was lower than mGFR300 (23 ± 8 versus 29 ± 9 mL/min/1.73 m(2), mean ± SD; P < 0.001). mGFR1440 was highly correlated with mGFR300 (r = 0.9). The mean absolute difference mGFR300 - mGFR1440 was 5.9 mL/min/1.73 m(2) corresponding to a mean percentage difference of 29%. In individuals with eGFRCKD-EPI ≤ 30 mL/min/1.73 m(2), percentage difference of mGFR300 and mGFR1440 was even higher (35%). To predict mGFR1440 from mGFR300, we developed the correction formula: mGFR1440 = -2.175 + 0.871 × mGFR300 (1-fold standard error of estimate: ±2.3 mL/min/1.73 m(2)). The GFR estimating equation with the best accuracy and precision compared with mGFR300 and mGFR1440 was the Revised Lund Malmö. In elderly CKD patients, measurement of iohexol clearance up to 5 h leads to a clinically relevant overestimation of GFR compared with 24-h measurement. In clinical care, this effect should be bore in mind especially for patients with considerably reduced GFR levels. A new correction formula has been developed to predict mGFR1440 from mGFR300. For accurate GFR estimates in elderly CKD patients, we recommend the Revised Lund Malmö equation.

Validation and impact of a new technique for assessment of glomerular filtration rate in patients with liver disease.

Previously we have proposed a technique for the measurement of plasma clearance in patients with ascites. The impact of using the technique was assessed and the results compared with those from a reference technique in 111 patients having glomerular filtration rate measurements as part of their workup for liver transplantation. Results of calculations using the new technique were compared with plasma clearance measurements obtained using a conventional slope-intercept technique and with clearance measurements based on urine collection. Discrepancies between the results of plasma clearance and urinary clearance assessments were investigated by using an uncollimated gamma camera to measure the total retention of the tracer. Conventional slope-intercept calculations overestimated clearance compared with the new technique by more than 20% in 21% of the patients. Significant differences between the results of the two methods were more likely in patients with more severe ascites. Results of urine collection-based measurements of Cr-51 EDTA clearance were frequently significantly lower than measurements using the new technique, whereas measurements of urinary clearance of creatinine were higher. Gamma camera measurements suggest that discrepancies between total and urinary clearance of Cr-51 EDTA are due to incomplete urine collection. The new technique is a practical method for assessment of kidney function and should be used in patients with liver disease who have or may have ascites.

Initial Evaluation of (99m)Tc(CO)3(ASMA) as a Renal Tracer in Healthy Human Volunteers.

Preclinical studies in rats showed that two of (99m)Tc(CO)3(ASMA) isomers (rac- and L-ASMA) had pharmacokinetic properties equivalent to that of (131)I-OIH, the radiopharmaceutical standard for the measurement of effective renal plasma flow. The aim of this study was to evaluate the pharmacokinetics of (99m)Tc(CO)3(ASMA) isomers in healthy human subjects. Three ASMA ligands (rac-, L- and D-ASMA) were labeled with (99m)Tc(CO)3 using an IsoLink kit (Covidien), and each formed (99m)Tc(CO)3(ASMA) tracer was co-injected with (131)I-OIH into healthy human subjects followed by sequential imaging, plasma clearance measurements and timed urine collection. Plasma protein binding, red cell uptake and percent injected dose in the urine were determined. Urine from each group of volunteers was analyzed for metabolites by HPLC. Image quality was excellent with all three agents. Each (99m)Tc(CO)3(ASMA) preparation was excreted unchanged in the urine. The plasma clearance ratio ((99m)Tc(CO)3(ASMA)/(131)I-OIH) was 81 ± 3% for D-ASMA compared to only 20 ± 4% for L-ASMA and 37 ± 7% for rac-ASMA; the 81% clearance ratio for D-ASMA isomer is still ∼ 30% higher than the (99m)Tc-MAG3/(131)I-OIH clearance ratio (∼50-60%). Red cell uptake was similar for all three tracers (6-9%), and all tracers had a relatively rapid renal excretion; at 3h, the (99m)Tc(CO)3(ASMA)/(131)I-OIH urine ratio was 100 ± 3% for D-ASMA, 80 ± 2% for L-ASMA and 88 ± 1% for rac-ASMA. The renal excretion characteristics of (99m)Tc(CO)3(D-ASMA) in humans are superior to those of the other two (99m)Tc(CO)3(ASMA) isomers studied, but are still inferior to (131)I-OIH, even though there was no difference in the clearance of two of (99m)Tc(CO)3(ASMA) isomers and (131)I-OIH in rats. The work described here demonstrates the sensitivity in in vivo biological behavior of (99m)Tc(CO)3(ASMA) isomers to their subtle structural differences.

Relationship between serum TSH levels and intrarenal hemodynamic parameters in euthyroid subjects

Low thyroid function may be associated with a reduced glomerular filtration rate (GFR) calculated on the basis of creatinine metabolism. Thyroid hormone directly affects serum creatinine in muscle and low thyroid function might exert a similar direct effect in the kidney. The goal of the study was to evaluate this possibility by assessment of the inulin-based GFR and to examine the mechanism underlying the reduction of GFR. Renal and glomerular hemodynamics were assessed by simultaneous measurements of plasma clearance of para-aminohippurate (CPAH) and inulin (Cin) in 26 patients with serum creatinine <1.00 mg/dl and without thyroid disease. All subjects were normotensive with or without antihypertensive treatment and were kept in a sodium-replete state. Renal and glomerular hemodynamics were calculated using Gomez's formulae. Serum TSH, including within the normal range (0.69-4.30 μIU/ml), was positively correlated with vascular resistance at the afferent arteriole (Ra) (r=0.609, P=0.0010), but not at the efferent arteriole (Re). Serum TSH was significantly and negatively correlated with renal plasma flow (RPF), renal blood flow (RBF), and GFR (r=-0.456, P=0.0192; r=-0.438, P=0.0252; r=-0.505, P=0.0086 respectively). In multiple regression analysis, serum TSH was significantly positively associated with Ra after adjustment for age and mean blood pressure. These findings suggest that low thyroid function, even within the normal range, is associated with reduced RPF, RBF, and GFR, which might be caused by a preferential increase in Ra.

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

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. To derive the Berlin Initiative Study (BIS) equation, a novel estimator of GFR in elderly participants. Cross-sectional. Data were split for analysis into 2 sets for equation development and internal validation. Random community-based population of a large insurance company. 610 participants aged 70 years or older (mean age, 78.5 years). Iohexol plasma clearance measurement as gold standard. 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. The new BIS2 equation yielded the smallest bias followed by the creatinine-based BIS1 and Cockcroft-Gault 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 m2 (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%). There was no validation by an external data set. 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. Kuratorium für Dialyse und Nierentransplatation (KfH) Foundation of Preventive Medicine.

Routine Determination of GFR in Renal Transplant Recipients by HPLC Quantification of Plasma Iohexol Concentrations and Comparison With Estimated GFR

Estimated glomerular filtration rate (eGFR) methods are not sufficiently reliable in renal transplant recipients (RTR) and should be replaced by iohexol plasma clearance measurement. However, this method has poor availability in health centers. The aim of our study was to develop a high-performance liquid chromatography (HPLC) method for plasma iohexol measurement in routine practice and to evaluate its plasma clearance as a reference of GFR. We developed an HPLC method using UV detection. We evaluated sample storage conditions to provide recommendations for routine practice. Then, we compared GFRbased on plasma iohexol clearance (GFR-iohexol) to eGFR using modification of diet in renal disease, Cockcroft and Gault, and CDK-EPIequations in 40 RTR. The method was validated over a concentration range of 15-300 μg/l. Excellent linearity (r > 0.998), inter- and intraday precision (CV < 3.3%), and accuracy (>96.8%) were complied with ICH guidelines. We also demonstrated excellent samples stability (9 days). Although eGFR methods are not references in RTR, we found a correct concordance between eGFR and GFR-iohexol in our population. To conclude, our method is simple, rapid, accurate, and reliable for routine clinical and research use especially in RTR.

A semipopulation input function for quantifying static and dynamic 18F-fluoride PET scans

We describe a semipopulation input function for evaluating bone plasma clearance from static and dynamic (18)F-fluoride PET scans. The semipopulation input function was derived by fitting an exponential curve to venous plasma measurements obtained 30-60 min after injection and adding a population residual curve representing the bolus peak scaled for injected activity and adjusted for time of peak counts. The residual curve was found from nine postmenopausal women who had continuous arterial blood samples and venous samples taken every 10 min. The precision errors of plasma clearance measurements derived from the semipopulation input function using Patlak analysis and the Hawkins compartmental model were compared with the precision errors for four image-derived input functions using data from 20 women who had undergone repeated dynamic PET scans. Venous and arterial concentrations were equal by 30 min after injection. The exponential fitted to the 30-60-min venous data accounted for 76% of the total 0-60 min area under the curve, and the SD of the area under the residual curve was 2.6% of the total 0-60 min area under the curve. For Patlak analysis, the precision error (% coefficient of variation) was 13.0% using the semipopulation input function compared with 14.9-21.7% using the four image-derived input functions. For the Hawkins model the equivalent figures were 14.5 and 20.1-30.9%, respectively. Accurate and precise measurements of bone plasma clearance were obtained when (18)F-fluoride PET scans were analysed using an input function obtained by adding a population residual curve to the exponential obtained from venous blood samples taken 30-60 min after injection.

Precision of 18F-fluoride PET skeletal kinetic studies in the assessment of bone metabolism

We assessed the precision of lumbar spine (18)F-PET measurements based on 58 scans performed on 20 postmenopausal women. The percentage coefficient of variation (%CV) (95% confidence interval) was 9.2% (7.5-11.8) for standardised uptake values, 11.7% (9.5-14.9) for plasma clearance measurements using the Patlak method and 14.5% (11.7-18.5) for plasma clearance measurements using the Hawkins three-compartment model. (18)F-Fluoride positron emission tomography ((18)F-PET) is a non-invasive technique that allows the assessment of regional bone turnover in patients with metabolic bone disease. Knowledge of the precision errors of (18)F-PET measurements is important for planning the number of subjects required for research studies. Twenty osteoporotic postmenopausal women had (18)F-PET scans of the lumbar spine at 0, 6 and 12 months after stopping long-term bisphosphonate treatment. No significant changes in the PET measurements were seen over the 12-month period, and the data were deemed suitable for a precision study. Precision errors were evaluated for standardised uptake values (SUVs) and for the fluoride plasma clearance to bone mineral (K (i)) determined using the Patlak and Hawkins methods. Precision errors were expressed as the %CV and were calculated for the mean L1-L4 region and for individual vertebrae. %CV (95% confidence interval) for the L1-L4 region was 9.2% (7.5-11.8) for SUV, 11.7% (9.5-14.9) for K (i) measured using the Patlak method and 14.5% (11.7-18.5) for K (i) measured using the Hawkins method. There was no significant difference between precision errors obtained for the L1-L4 region and those obtained for a single vertebra. SUV measurements showed the smallest precision error followed by the Patlak method, while the Hawkins method gave the largest error. Measuring a smaller region of interest did not increase the precision error, suggesting that the factor determining the errors may be scanner calibration.

Validation of image-derived arterial input functions at the femoral artery using 18F-fluoride positron emission tomography

The use of image-derived arterial input functions (IDAIF) for the dynamic quantification of bone metabolism using 18F-fluoride positron emission tomography 18F-PET is an attractive alternative to direct arterial blood sampling. (a) To validate a method for obtaining the IDAIF by imaging the femoral artery against a method for deriving the IDAIF at the aorta that was previously validated against direct arterial sampling. (b) To compare the accuracy of bone plasma clearance measurements (Ki) at the total hip site obtained using the femoral artery IDAIF against Ki values at the same site obtained using the aorta IDAIF. Twelve healthy postmenopausal women with a mean age of 62.6 years (range, 52.3-70.6 years) had 60-min dynamic 18F-PET scans of the lumbar spine and proximal femur 2 weeks apart. The femoral artery IDAIF was obtained from the proximal femur scan using four different algorithms: (a) fixed partial volume correction (PVC) method; (b) variable PVC method; (c) Chen method; and (d) Cook-Lodge method. The aorta IDAIF was obtained from the lumbar spine scan using a previously validated method and the respective Ki values in the hip were used to assess the performance of each of the femoral artery algorithms. When the femoral artery IDAIF methods were compared with the aorta IDAIF in terms of the area under the curve AUC values calculated in 4-min time intervals over 0-60 min, the absolute root mean square errors were: (a) fixed PVC, 0.52; (b) variable PVC, 0.54; (c) Chen, 0.72; and (d) Cook-Lodge, 0.49 in MBq s/ml. There were small, but statistically significant differences, in the Ki values found by all four femoral artery IDAIF methods when compared with the figures obtained using the aorta IDAIF. Bland-Altman plots of Ki values showed the best agreement for the fixed PVC method with a standard deviation of 0.0020 ml/min/ml, followed by variable PVC, Cook-Lodge and Chen method with standard deviations of 0.0022, 0.0024 and 0.0042 ml/min/ml, respectively. We have demonstrated that it is possible to measure regional bone turnover at the hip without the need to perform direct arterial sampling to acquire the arterial input function (AIF). The differences in the Ki values obtained at the hip by using aorta IDAIF and any of the four image-based AIF methods at the femoral artery were small and clinically insignificant. The performance of fixed PVC, variable PVC and Cook-Lodge method was similar although the latter was less robust than the other two methods.

Does pravastatin increase chylomicron remnant catabolism in postmenopausal women with type 2 diabetes mellitus?

We investigated the effects of pravastatin on chylomicron remnant catabolism measured with a 13C stable isotope breath test and plasma apolipoprotein (apo) B-48 and remnant-like particle (RLP)-cholesterol in postmenopausal women with type 2 diabetes mellitus. Nineteen postmenopausal women with type 2 diabetes were randomized to receive 40 mg/day pravastatin or no treatment for 6 weeks followed by a 2-week washout period, and crossed over for a further 6 weeks. Fractional catabolic rate (FCR) of a chylomicron remnant-like emulsion was determined from 13CO2 enrichment in the breath and plasma using isotope-ratio mass spectrometry and multicompartmental modelling. Plasma apo B-48 and RLP-cholesterol concentrations were also measured as static markers of chylomicron remnant metabolism. Pravastatin significantly reduced plasma concentrations of cholesterol (5.9 +/- 0.3 vs. 4.8 +/- 0.2 mmol/l; P < 0.001), low density lipoprotein (LDL)-cholesterol (3.5 +/- 0.2 vs. 2.6 +/- 0.2 mmol/l; P < 0.001), triglyceride (2.1 +/- 0.3 vs. 1.7 +/- 0.2 mmol/l; P = 0.017), non-high density lipoprotein (HDL)-cholesterol (4.4 +/- 0.3 vs. 3.3 +/- 0.2 mmol/l; P < 0.001), lathosterol/total cholesterol ratio (2.6 +/- 0.2 vs. 2.0 +/- 0.3, P = 0.035), apo B-100 (1.1 +/- 0.1 vs. 0.8 +/- 0.1 g/l; P = 0.001), apo B-48 (4.8 +/- 0.9 vs. 3.3 +/- 0.6 mg/l; P = 0.016), and RLP-cholesterol (31.4 +/- 8.2 vs. 18.6 +/- 4.6 mg/dl; P = 0.024). Pravastatin was also associated with an increase in sitosterol/total cholesterol ratio (2.8 +/- 0.3 vs. 3.1 +/- 0.3, P = 0.029). Chylomicron remnant-like emulsion catabolism was not, however, significantly altered by pravastatin estimated by either breath or plasma clearance measurements. In postmenopausal women, pravastatin decreases plasma concentrations of remnant lipoproteins by a mechanism that may relate chiefly to inhibition of remnant production, but this requires further evaluation.

Serum cystatin C for assessment of glomerular filtration rate in pregnant and non-pregnant women. Indications of altered filtration process in pregnancy

Serum cystatin C is believed to reflect the glomerular filtration rate (GFR) more closely than serum creatinine in many contexts and a reference interval for serum cystatin C in term pregnancy has been defined to enable its use also in pregnant women. However, serum cystatin C levels were not found to be decreased in term pregnancy, though GFR of low molecular mass substances is known to increase by at least 40% by the third trimester. The aim of this study was therefore to determine whether serum cystatin C is a reliable GFR marker also in pregnant women. GFR was determined by measurement of plasma clearance of iohexol in 48 previously healthy women in their third trimester and in 12 healthy nonpregnant women, and was compared with their serum levels of cystatin C and creatinine. Both serum cystatin C and creatinine levels were significantly related to GFR for both pregnant and non-pregnant women. However, the correlation between cystatin C and GFR was set at different levels for pregnant and nonpregnant women. Our results indicate a physiological difference between the filtration processes in kidneys of pregnant and non-pregnant women, whether it is size-dependent, configuration-dependent or charge-dependent. Nevertheless, serum cystatin C seems to reflect GFR reliably in both non-pregnant and pregnant, healthy and hypertensive women.

40-Year-Old Man With Anemia, Chronic Low Back Pain, and Hypoalbuminemia

40-Year-Old Man With Anemia, Chronic Low Back Pain, and Hypoalbuminemia

Evaluation of hepatic function using 99mTc-galactosyl human serum albumin (GSA) scintigraphy: comparison with antipyrine plasma clearance

99mTc-galactosyl human serum albumin (GSA) is a new scintigraphy agent which binds specifically to asialoglycoprotein receptors on hepatocytes, and can be used to evaluate hepatic function. Indocyanine green (ICG) is hepatic blood flow-dependent, while antipyrine plasma clearance is independent of blood flow and thus antipyrine plasma clearance is an excellent parameter with which to assess liver function. In this study, we investigated the relationship between GSA examination and antipyrine plasma clearance to assess the usefulness of GSA in evaluating metabolic function of the liver. Studies were performed on 22 patients with liver diseases. Antipyrine plasma clearance measurement, ICG testing and biochemical analysis of blood were performed at the same time as GSA examination. GSA HH15 and antipyrine plasma clearance showed a good correlation ( r = −0.702, P < 0.0005). On the other hand, ICGR15 showed a poor correlation with antipyrine plasma clearance ( r = 0.449, P < 0.05). The results of this study suggest, that hepatic function determined using GSA is more closely related to the metabolic capacity of hepatocytes than to hepatic blood flow.

Commentary: renal nuclear medicine. Report on a joint meeting of the BIR's Nuclear Medicine Sub-Committee in association with the IPEMB Radionuclide Special Interest Group, held at the British Institute of Radiology, London, on 22 February 1996.

A joint one day meeting, organized by the IPEMB Radionuclide Special Interest Group and the BIR Nuclear Medicine Sub-Committee, examined the state of the art with regard to measurement and intervention in renal nuclear medicine. The pressures from clinical audit, accreditation and medico-legal issues demand greater standardization of guidelines and protocols. There are many tests available and departments differ in personnel, access to radio-pharmaceuticals, age of equipment and physics support. Despite the variation in techniques employed, radionuclide methodology is well suited to the study of kidney function using plasma clearance measurements and/or imaging with renography or renal cortical scanning.