Peritoneal Homocysteine Clearance is Inefficient in Peritoneal Dialysis Patients

2000 ◽  
Vol 20 (6) ◽  
pp. 766-771 ◽  
Author(s):  
David W. Johnson ◽  
Troy D. Kay ◽  
David A. Vesey ◽  
Nicole Isbel ◽  
Scott B. Campbell ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Protein Binding ◽  
Plasma Protein Binding ◽  
Plasma Protein ◽  
Tertiary Care ◽  
Plasma Concentrations ◽  
Elevated Plasma ◽  
C Reactive Protein ◽  
Protein Loss ◽  
Reactive Protein

Objectives To investigate the degree and the determinants of peritoneal homocysteine (Hcy) clearance and to compare measured Hcy clearance with the Hcy clearance predicted based on molecular weight (MW). Design Cross-sectional observational analysis. Setting Tertiary care institutional dialysis center. Patients Sixty-five stable peritoneal dialysis (PD) patients. Outcome Measures Fasting blood and 24-hour pooled dialysate effluents were collected for determination of peritoneal clearances of Hcy (CpHcy), urea (CpUr), and creatinine (CpCr). The dialysate-to-plasma creatinine ratio at 4 hours (D/P Cr 4 h) and levels of red cell folate, B12, ferritin, and C-reactive protein (CRP) were measured concurrently. Observed CpHcy was compared with predicted clearance, based on Hcy plasma protein binding and the relative molecular weights of Hcy, urea, and creatinine. Results Plasma concentrations of Hcy averaged 24.6 ± 1.1 μmol/L and were elevated above the upper limit of normal in 59 (91%) patients. The mean dialysate concentration of Hcy was 2.9 ± 0.3 μmol/L, equating to a daily peritoneal elimination of 34.6 ± 3.6 μmol. Observed CpHcy was closely approximated by predicted CpHcy (8.7 ± 0.6 L/week/1.73 m2 vs 9.0 ± 0.3 L/week/1.73 m2 respectively, p = 0.55). Patients maintained on automated PD ( n = 5) had a CpHcy similar to that of patients treated with continuous ambulatory peritoneal dialysis (8.9 ± 1.0 L/week/1.73 m2 vs 8.7 ± 0.6 L/week/1.73 m2, p = 0.92). The CpHcy was significantly correlated with C-reactive protein (CRP), D/P creatinine, CpUr, CpCr, and peritoneal protein loss, but not with plasma Hcy, albumin, B12, ferritin, age, dialysis duration, peritonitis episodes, or daily dialysate effluent volume. By multivariate analysis, the only variables that remained significant independent predictors of CpHcy were CRP and D/P Cr 4 h. High and high-average transporters had a higher CpHcy than low and low-average transporters (9.7 ± 0.8 L/week/1.73 m2 vs 7.0 ± 0.7 L/week/1.73 m2, p < 0.05), despite comparably elevated plasma Hcy concentrations [25.2 ± 1.5 μmol/L vs 23.4 ± 1.6 μmol/L, p = nonsignificant (NS)]. Conclusions Elevated plasma concentrations of Hcy are not efficiently reduced by PD. The relatively low peritoneal clearance of Hcy is largely accounted for by a high degree of plasma protein binding and is significantly influenced by peritoneal membrane permeability.

Apparent Valproic Acid Neurotoxicity in a Hypoalbuminemic Patient

1993 ◽  
Vol 27 (1) ◽  
pp. 32-35 ◽  
Author(s):  
Barry E. Gidal ◽  
D. Michael Collins ◽  
Brad R. Beinlich
Keyword(s):  
Valproic Acid ◽  
Protein Binding ◽  
Plasma Protein Binding ◽  
Plasma Protein ◽  
Plasma Concentrations ◽  
Free Fraction ◽  
Laboratory Evaluation ◽  
Neurologic Symptoms ◽  
Drug Concentrations ◽  
Dependent Protein

OBJECTIVE: To report a case of possible neurotoxicity caused by markedly elevated free valproic acid (VPA) plasma concentrations. CASE SUMMARY: A patient with a history of a mixed-type seizure disorder that had been treated with oral VPA 1000 mg four times daily for the previous two years was admitted to the neurology service with the chief complaint of increasing difficulty in walking and involuntary muscle jerks that were new in onset. The patient was hypersomnolent and dysarthric. The total plasma VPA concentration was 103 μg/mL, which was only slightly above the recommended therapeutic range (50–100 μg/mL). VPA free fraction and free plasma concentrations, however, were unexpectedly elevated (26 percent, 26.8 μg/mL, respectively). Further laboratory evaluation revealed a serum albumin concentration of 33 g/L. The neurologic symptoms resolved upon VPA dosage reduction. DISCUSSION: VPA displays concentration-dependent protein binding, resulting in disproportionate increases in drug free fraction with increasing drug concentration. This effect may be magnified in patients with decreased plasma protein-binding capacity. The plasma protein-binding kinetics of VPA are reviewed and the implications for therapeutic drug monitoring are discussed. CONCLUSIONS: It is likely that the markedly elevated free VPA plasma concentrations contributed to the neurologic symptoms displayed in this patient. In patients with decreased albumin concentrations, failure to recognize concentration-dependent protein binding, as well as exclusive reliance upon total drug concentrations, may lead to erroneous pharmacokinetic and therapeutic interpretations.

PLASMA PROTEIN BINDING, PLASMA CONCENTRATIONS, AND EFFECTS OF DIPHENYLHYDANTOIN IN MAN

1971 ◽  
Vol 179 (1 Drug Metaboli) ◽  
pp. 723-728 ◽  
Author(s):  
Lars Lund ◽  
Per Knut Lunde ◽  
Anders Rane ◽  
Olof Borga ◽  
Folke Sjöqvist
Keyword(s):  
Protein Binding ◽  
Plasma Protein Binding ◽  
Plasma Protein ◽  
Plasma Concentrations

Possible therapeutic interventions in COVID-19 induced ARDS by cotinine as an ACE-2 promoter and AT-1R blocker

2020 ◽  
Vol 20 ◽  
Author(s):  
Tarun Sharma ◽  
Sidharth Mehan
Keyword(s):  
Protein Binding ◽  
Plasma Protein Binding ◽  
Plasma Protein ◽  
Distress Syndrome ◽  
Therapeutic Interventions ◽  
Promising Candidate ◽  
Angiotensin Converting Enzyme 2 ◽  
Proinflammatory Effect ◽  
Pulmonary Permeability

: In these challenging times of the pandemic, as coronavirus disease 2019 (COVID-19) has taken over the planet, its complications such as acute respiratory distress syndrome (ARDS) have the potential to wipe out a large portion of our population. Whereas a serious lack of ventilators, vaccine being months away makes the condition even worse. That's why promising drug therapy is required. One of them was suggested in this article. It is the angiotensin-converting enzyme-2 (ACE-2) to which the COVID-19 virus binds and upon downregulation of which the pulmonary permeability increases and results in the filling of alveoli by proteinaceous fluids, which finally results in ARDS. ARDS can be assisted by angiotensinII type-1 receptor (AT-1R) blocker and ACE-2 upregulator. AT-1R blocker will prevent vasoconstriction, the proinflammatory effect seen otherwise upon its activation. ACE-2 upregulation will ensure less formation of angiotensin II, vasodilatory effects due to the formation of angiotensin (1-7), increased breakdown of bradykinin at lung level. Overall, decreased vasoconstriction of vessels supplying lungs and decreased vasodilation of lung tissues will ensure decreased pulmonary permeability and eventually relieve ARDS. It should also be considered that all components of the reninangiotensin-aldosterone system (RAAS) are located in the lung tissues. A drug with the least plasma protein binding is required to ensure its distribution across these lung tissues. Cotinine appears to be a promising candidate for COVID-19- induced ARDS. It acts across the board and acts as both an AT-1R blocker, ACE-2 upregulator. It also has a weak plasma protein binding that helps to spread through the lung tissues. In this review, we summarized that cotinine, along with COVID-19 virus replication blocker anti-virals, may prove to be a promising therapy for the treatment of COVID-19 induced ARDS.

scholarly journals Ultrafiltration Method for Plasma Protein Binding Studies and Its Limitations

Processes ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 382
Author(s):  
Camelia-Maria Toma ◽  
Silvia Imre ◽  
Camil-Eugen Vari ◽  
Daniela-Lucia Muntean ◽  
Amelia Tero-Vescan
Keyword(s):  
Protein Binding ◽  
Plasma Protein Binding ◽  
Plasma Protein ◽  
Specific Binding ◽  
Critical Role ◽  
Volume Ratio ◽  
Binding Studies ◽  
Experimental Conditions ◽  
Key Aspects

Plasma protein binding plays a critical role in drug therapy, being a key part in the characterization of any compound. Among other methods, this process is largely studied by ultrafiltration based on its advantages. However, the method also has some limitations that could negatively influence the experimental results. The aim of this study was to underline key aspects regarding the limitations of the ultrafiltration method, and the potential ways to overcome them. The main limitations are given by the non-specific binding of the substances, the effect of the volume ratio obtained, and the need of a rigorous control of the experimental conditions, especially pH and temperature. This review presents a variety of methods that can hypothetically reduce the limitations, and concludes that ultrafiltration remains a reliable method for the study of protein binding. However, the methodology of the study should be carefully chosen.

Chronic Induction of C-Reactive Protein by Hemodialysis, but Not by Peritoneal Dialysis Therapy

1996 ◽  
Vol 16 (2) ◽  
pp. 158-162 ◽  
Author(s):  
Marion Haubitz ◽  
Reinhard Brunkhorst ◽  
Eike Wrenger ◽  
Peter Froese ◽  
Matthias Schulze ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Renal Insufficiency ◽  
Chronic Renal Insufficiency ◽  
Inflammatory Activity ◽  
C Reactive Protein ◽  
Dialysis Therapy ◽  
Dialysis Treatment ◽  
Reactive Protein ◽  
Before And After ◽  
Patient Groups

Objective Evaluation of the inflammatory activity in patients on chronic peritoneal dialysis (PD) and patients on chronic hemodialysis (HD) in comparison to patients with chronic renal insufficiency without dialysis treatment and healthy volunteers. Design Open, non randomized prospective study. Setting Nephrology Department, including HD and PD therapy in a university hospital. Patients Twenty -four patients on chronic PD, 21 patients on chronic HD therapy using a cuprophan dialyzer, 16 patients with chronic renal insufficiency without dialysis treatment, and 33 healthy volunteers; 8 additional patients before and after initiation of chronic HD therapy. All patients and controls were without infection or immunosuppressive therapy. Main Outcome Measures As a marker of the inflammatory activity in the different patient groups, C-reactive protein (CAP) was measured serially using a sensitive, enzyme-Iinked, immunosorbent assay in order to detect values below the detection limit of standard assays. Results All patient groups had CAP levels higher than the normal controls (p < 0.01). Patients on HD had CAP levels significantly higher than PD patients (p < 0.01) whose levels were comparable to patients without dialysis therapy. Accordingly, longitudinal measurements before and after initiation of chronic HD showed a significant increase in CAP levels after the beginning of HD treatment (p < 0.04). Conclusions The results suggest that induction of the inflammatory activity is lower during PD compared to HD, since stimulation by the dialyzer membrane, dialysate buffer, or bacterial fragments in the dialysate is avoided. This observation might indicate a possible lower risk of long-term complications in patients with PD.

Plasma protein binding and blood-free concentrations: which studies are needed to develop a drug?

2011 ◽  
Vol 7 (8) ◽  
pp. 1009-1020 ◽  
Author(s):  
Mario Pellegatti ◽  
Sabrina Pagliarusco ◽  
Lara Solazzo ◽  
Dimitri Colato
Keyword(s):  
Protein Binding ◽  
Plasma Protein Binding ◽  
Plasma Protein
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