Determination of the Glomerular Filtration Rate by Identification of Sinistrin Kinetics

Estelberger, Willibald; Petek, W.; Zitta, Sabine; Mauric, Astrid; Horn, Sabine; Holzer, Herwig; Pogglitsch, H

doi:10.1515/cclm.1995.33.4.201

Cited by 17 publications

(26 citation statements)

References 29 publications

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“…In comparison to a two-or a four-compartmental modeling approach (data not shown), serum inulin kinetics could be best characterized by a three-compartment model. Model predictions for the serum compartment (V 1 : 3.5 Ϯ 0.3 l), the total inulin distribution volume (V inulin : 13.0 Ϯ 0.6 l), and the renal clearance were in accordance with previous findings (33)(34)(35). In particular, the model prediction of the renal clearance was in very good agreement with values as determined using the Cockcroft formula (21).…”

Section: Discussionsupporting

confidence: 87%

Physiological Hyperinsulinemia Has No Detectable Effect on Access of Macromolecules to Insulin-Sensitive Tissues in Healthy Humans

et al. 2007

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OBJECTIVE-Physiologically elevated insulin concentrations promote access of macromolecules to skeletal muscle in dogs. We investigated whether insulin has a stimulating effect on the access of macromolecules to insulin-sensitive tissues in humans as well.RESEARCH DESIGN AND METHODS-In a randomized, controlled trial, euglycemic-hyperinsulinemic clamp (1.2 mU ⅐ kg Ϫ1 ⅐ min Ϫ1 insulin) and saline control experiments were performed in 10 healthy volunteers (aged 27.5 Ϯ 4 years, BMI 22.6 Ϯ 1.6 kg/m 2 ). Distribution and clearance parameters of inulin were determined in a whole-body approach, combining primed intravenous infusion of inulin with compartment modeling. Inulin kinetics were measured in serum using open-flow microperfusion in interstitial fluid of femoral skeletal muscle and subcutaneous adipose tissue.RESULTS-Inulin kinetics in serum were best described using a three-compartment model incorporating a serum and a fast and a slow equilibrating compartment. Inulin kinetics in interstitial fluid of peripheral insulin-sensitive tissues were best represented by the slow equilibrating compartment. Serum and interstitial fluid inulin kinetics were comparable between the insulin and saline groups. Qualitative analysis of inulin kinetics was confirmed by model-derived distribution and clearance parameters of inulin. Physiological hyperinsulinemia (473 Ϯ 6 vs. 18 Ϯ 2 pmol/l for the insulin and saline group, respectively; P Ͻ 0.001) indicated no effect on distribution volume (98.2 Ϯ 6.2 vs. 102.5 Ϯ 5.7 ml/kg; NS) or exchange parameter (217.6 Ϯ 34.2 vs. 243.1 Ϯ 28.6 ml/min; NS) of inulin to peripheral insulin-sensitive tissues. All other parameters identified by the model were also comparable between the groups. CONCLUSIONS-Our data suggest that in contrast to studies performed in dogs, insulin at physiological concentrations does not augment recruitment of insulin-sensitive tissues in healthy humans. Diabetes

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Section: Discussionsupporting

confidence: 87%

Physiological Hyperinsulinemia Has No Detectable Effect on Access of Macromolecules to Insulin-Sensitive Tissues in Healthy Humans

et al. 2007

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“…The clearance of sinistrin (C Sinistrin ), a polyfructosan with identical clearance characteristics to inulin, is a validated reference method for the measurements of GFR before and after protein load (Inutest ® , Fresenius Pharma Austria, Linz, Austria). [16,24] The renal functional reserve was measured as the change in GFR after protein load. Time sequences of sinistrin injection, protein load, and measurements of variables have been described in detail in previous studies and are shown in Figure 1.…”

Section: Study Protocolmentioning

confidence: 99%

“…Time sequences of sinistrin injection, protein load, and measurements of variables have been described in detail in previous studies and are shown in Figure 1. [16,[22][23][24][25] Prior to examination, the patients were instructed to maintain a low sodium and protein diet for two days, to fast from midnight onward, and to collect their urine during the preceding 12 hr to assess compliance. On the day of the study, after a rest period of 30 minutes with a fluid intake of 0.5 l of light tea, the first clearance measurement started with the injection of 2500 mg sinistrin and baseline measurements were taken.…”

Section: Study Protocolmentioning

confidence: 99%

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Cystatin C Does Not Detect Acute Changes in Glomerular Filtration Rate in Early Diabetic Nephropathy

et al. 2008

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Background. The measurement of renal functional reserve (acute change in glomerular filtration rate [GFR] after protein load) allows the detection of sub-clinical renal dysfunction and has prognostic implications in diabetes. Our aim was to test cystatin C as an index of GFR and renal functional reserve. Methods. GFR was measured by C Sinistrin at baseline and after protein load in 28 diabetic patients with serum creatinine <1.2 mg/dL. The C Sinistrin was compared with cystatin C, serum creatinine, creatinine clearance, and Cockcroft-Gault formula. Results. Baseline C Sinistrin ranged from 67-172 mL/ min. Regression analysis showed an overall low relationship between C Sinistrin and the indirect markers of GFR. The highest correlation with C Sinistrin was obtained for cystatin C clearance (R 2 = 0.58, r = 0.76, p < 0.001), the 1/serum cystatin C (R 2 = 0.58, r = 0.76, p < 0.001), and serum cystatin C (R 2 = 0.52, r = 0.72, p < 0.001). Renal functional reserve was preserved in 6 of 28 patients. There was no significant change in cystatin C in response to protein load. Conclusion. Wide variation in baseline GFR emphasizes the need for the early detection of renal dysfunction. Cystatin C correlated best with C Sinistrin at baseline, but did not detect renal functional reserve.

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“…The above method, the general solution of the linear dynamic problem comprising both single-injection and constant-infusion experiments and a computational method for identification of the system constants have been developed previously with application to the kinetics of sinistrin as a marker of glomerular filtration (5). Although the same mathematical concept is applied here to the kinetics of jp-aminohippuric acid administered at low doses, the appropriateness of model-linearity and the pertinent protocol-and dose-requirements were investigated separately because of the combined action of glomerular filtration and tubular secretion and, consequently, the possibly concentration-dependent characteristics in the elimination of/7-aminohippuric acid.…”

Section: Introductionmentioning

confidence: 99%

System Identification of the Low-Dose Kinetics of p-Aminohippuric Acid

Estelberger

Zitta²,

Lang³

et al. 1995

CCLM

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Summary: The renal clearance of^-aminohippuric acid, due to tubular secretion in addition to glomerular filtration, can only be determined by kinetic experiments. Maximal information can be gained from observed temporal marker concentration profiles by fitting dynamic mathematical models of the processes involved, such as absorption, distribution, and elimination, to the kinetic data. Thereby the values of the system constants, such as fractional elimination or fractional distribution rates, and their accuracy measures are determined by methods which are based firstly on measured time-dependent data elicited in an individual test object by perturbing inputs and secondly, on mathematical formulations of prior knowledge of the underlying physiological system. Such methods of model adaptation are called system identification.

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Determination of the Glomerular Filtration Rate by Identification of Sinistrin Kinetics

Cited by 17 publications

References 29 publications

Physiological Hyperinsulinemia Has No Detectable Effect on Access of Macromolecules to Insulin-Sensitive Tissues in Healthy Humans

Physiological Hyperinsulinemia Has No Detectable Effect on Access of Macromolecules to Insulin-Sensitive Tissues in Healthy Humans

Cystatin C Does Not Detect Acute Changes in Glomerular Filtration Rate in Early Diabetic Nephropathy

System Identification of the Low-Dose Kinetics of p-Aminohippuric Acid

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