Browsing by Author "Meier, Daniel"

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    Discordance between estimated and measured changes in plasma volume among patients with acute heart failure
    (Wiley, 2022) Swolinsky, Jutta S.; Tuvshinbat, Enkhtuvshin; Leistner, David M.; Edelmann, Frank; Knebel, Fabian; Nerger, Niklas P.; Lemke, Caroline; Roehle, Robert; Haase, Michael; Costanzo, Maria Rosa; Rauch, Geraldine; Mitrovic, Veselin; Gasanin, Edis; Meier, Daniel; McCullough, Peter A.; Eckardt, Kai-Uwe; Molitoris, Bruce A.; Schmidt-Ott, Kai M.; Medicine, School of Medicine
    Aims: In acute heart failure (AHF), changes of venous haemoglobin (Hb) concentrations, haematocrit (Hct), and estimated plasma volume (ePV) have been proposed as surrogates of decongestion. These estimates are based on the theoretical assumptions that changes of Hb concentrations and Hct are driven by the intravascular volume status and that the intravascular Hb pool remains stable. The objective of this study was to assess the relationship of changes of measured plasma volume (mPV) with changes of Hb, Hct, and ePV in AHF. Methods and results: We studied 36 AHF patients, who received two sequential assessments of mPV, measured red cell volume (mRCV) and measured total blood volume (mTBV) (48 h apart), during the course of diuretic therapy using a novel visible fluorescent injectate (VFI) technique based on the indicator dilution principle. Changes of ePV were calculated based on the Kaplan-Hakim or Strauss formula. AHF patients receiving diuretics (median intravenous furosemide equivalent 160 mg/48 h) displayed a wide range of changes of mPV (-25.4% to +37.0%). Changes in mPV were not significantly correlated with changes of Hb concentration [Pearson's r (r) = -0.241, P = 0.157], Hct (r = -0.307, P = 0.069), ePVKaplan-Hakim (r = 0.228, P = 0.182), or ePVStrauss (r = 0.237, P = 0.163). In contrast to theoretical assumptions, changes of mTBV were poorly correlated with changes of Hb concentrations and some patients displayed unanticipated variability of mRCV, suggesting an unstable intravascular red cell pool. Conclusions: Changes of Hb or Hct were not reflective of directly measured changes of intravascular volume status in AHF patients. Basing clinical assessment of decongestion on changes of Hb or Hct may misguide clinical decision-making on an individual patient level.
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    A Novel Fluorescent Clinical Method to Rapidly Quantify Plasma Volume
    (Karger Publishers, 2019) Molitoris, Bruce A.; George, Anthony G.; Murray, Patrick T.; Meier, Daniel; Reilly, Erinn S.; Barreto, Erin; Sandoval, Ruben M.; Rizk, Dana V.; Shaw, Andrew D.; Peacock, W. Frank; Medicine, School of Medicine
    Objectives To determine the performance of a rapid fluorescent indicator technique for measuring plasma volume (PV). Methods This was an open-label, observational evaluation of a two-component intravenous visible fluorescent dye technique to rapidly measure PV in 16 healthy subjects and 16 subjects with chronic kidney disease (8 stage 3 and 8 stage 4 CKD), at 2 clinical research sites. The method consisted of a single intravenous injection of 12 mg of a large 150-kDa carboxy-methyl dextran conjugated to a fluorescent rhodamine-derived dye as the PV marker (PVM), and 35 mg of a small 5-kDa carboxy-methyl dextran conjugated to fluorescein, the renal clearance marker. Dye concentrations were quantified 15 min after the injections for initial PV measurements using the indicator-dilution principle. Additional samples were taken over 8 h to evaluate the stability of the PVM as a determinant of PV. Blood volumes (BV) were calculated based on PV and the subject’s hematocrit. Pharmacokinetic parameters were calculated from the plasma concentration data taken over several days using noncompartmental methods (Phoenix WinNonlin®). Linear correlation and Bland-Altman plots were used to compare visible fluorescent injectate-measured PV compared to Nadler’s formula for estimating PV. Finally, 8 healthy subjects received 350 mL infusion of a 5% albumin solution in normal saline over 30 min and a repeat PV determination was then carried out. Results PV and BV varied according to weight and body surface area, with PV ranging from 2,115 to 6,234 mL and 28.6 to 41.9 mL/kg when weight adjusted. Both parameters were stable for > 6 h with repeated plasma measurements of the PVM. There was no difference between healthy subjects and CKD subjects. Overall, there was general agreement with Nadler’s estimation formula for the mean PV in subjects. A 24-h repeat dose measurement in 8 healthy subjects showed PV variability of 98 ± 121 mL (mean = 3.8%). Additionally, following an intravenous bolus of 350 mL of a 5% albumin solution in normal saline in 8 healthy subjects, the mean (SD) measured increase in PV was 356 (±50.0) mL post-infusion. There were no serious adverse events reported during the study. Conclusions This minimally invasive fluorescent dye approach safely allowed for rapid, accurate, and reproducible determination of PV, BV, and dynamic monitoring of changes following fluid administration.
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    Serum creatinine and cystatin C‐based estimates of glomerular filtration rate are misleading in acute heart failure
    (Wiley, 2021) Swolinsky, Jutta S.; Nerger, Niklas P.; Leistner, David M.; Edelmann, Frank; Knebel, Fabian; Tuvshinbat, Enkhtuvshin; Lemke, Caroline; Roehle, Robert; Haase, Michael; Costanzo, Maria Rosa; Rauch, Geraldine; Mitrovic, Veselin; Gasanin, Edis; Meier, Daniel; McCullough, Peter A.; Eckardt, Kai-Uwe; Molitoris, Bruce A.; Schmidt-Ott, Kai M.; Medicine, School of Medicine
    Aims: We aimed to test whether the endogenous filtration markers serum creatinine or cystatin C and equation-based estimates of glomerular filtration rate (GFR) based on these markers appropriately reflect changes of measured GFR in patients with acute heart failure. Methods: In this prospective cohort study of 50 hospitalized acute heart failure patients undergoing decongestive therapy, we applied an intravenous visible fluorescent injectate (VFI), consisting of a low molecular weight component to measure GFR and a high molecular weight component to correct for measured plasma volume. Thirty-eight patients had two sequential GFR measurements 48 h apart. The co-primary endpoints of the study were safety of VFI and plasma stability of the high molecular weight component. A key secondary endpoint was to compare changes in measured GFR (mGFR) to changes of serum creatinine, cystatin C and estimated GFR. Results: VFI-based GFR measurements were safe and consistent with plasma stability of the high molecular weight component and glomerular filtration of the low molecular weight component. Filtration marker-based point estimates of GFR, when compared with mGFR, provided only moderate correlation (Pearson's r, range 0.80-0.88, depending on equation used), precision (r2 , range 0.65-0.78) and accuracy (56%-74% of estimates scored within 30% of mGFR). Correlations of 48-h changes GFR estimates and changes of mGFR were significant (P < 0.05) but weak (Pearson's r, range 0.35-0.39). Observed decreases of eGFR by more than 15% had a low sensitivity (range 38%-46%, depending on equation used) in detecting true worsening mGFR, defined by a >15% decrease in mGFR. Conclusions: In patients hospitalized for acute heart failure, serum creatinine- and cystatin C-based predictions performed poorly in detecting actual changes of GFR. These data challenge current clinical strategies to evaluate dynamics of kidney function in acute heart failure.