Evaluation of Suitable Polymeric Matrix/Carriers during Loading of Poorly Water Soluble Drugs onto Mesoporous Silica: Physical Stability and In Vitro Supersaturation.

The application of mesoporous carriers in formulations of amorphous solid dispersions (ASDs) has been suggested to enhance the stability of amorphous drugs. However, mesoporous carriers do not demonstrate satisfactory inhibitory effects on the precipitation of active pharmaceutical ingredients (APIs), and the inclusion of an appropriate polymer within ASDs becomes imperative to maintaining drug supersaturation. The aim of this study was to evaluate ternary olanzapine (OLN) ASDs with Syloid 244FP and to find an appropriate polymeric carrier. The polymer's selection criteria were based on the physical stability of the ASDs and the release rate of the drug from the systems. The polymers investigated were hydroxypropylmethyl cellulose (HPMC) and copovidone (coPVP). The formation of ASDs was achievable in all investigated cases, as demonstrated by the complete lack of crystallinity confirmed through both powder X-ray diffraction (pXRD) analysis and differential scanning calorimetry (DSC) for all developed formulations. The solvent shift method was employed to evaluate the ability of the studied carriers to inhibit the precipitation of supersaturated OLN. coPVP emerged as a more suitable precipitation inhibitor compared with HPMC and Syloid 244 FP. Subsequently, in vitro dissolution studies under non-sink conditions revealed a higher degree of supersaturation in ternary systems where coPVP was used as a polymeric carrier, as these systems exhibited, under the examined conditions, up to a 2-fold increase in the released OLN compared with the pure crystalline drug. Moreover, stability studies conducted utilizing pXRD demonstrated that ternary formulations incorporating coPVP and Syloid 244 FP maintained stability for an extended period of 8 months. In contrast, binary systems exhibited a comparatively shorter stability duration, indicating the synergistic effect of coPVP and Syloid 244 FP on the physical stability of the amorphous API. Attenuated total reflectance-Fourier transform infrared (ATR-FTIR) studies showed that the development of stronger molecular interactions can be provided as an explanation for this synergistic effect, as the formation of robust H-bonds may be considered responsible for inhibiting the precipitation of the supersaturated API. Therefore, the incorporation of coPVP into OLN ASDs with Syloid 244 FP is considered a highly promising technique for increasing the degree of OLN supersaturation in in vitro dissolution studies and improving the stability of systems.

Acid-base abnormalities and liver dysfunction.

In addition to the kidneys and lungs, the liver also plays an important role in the regulation of the Acid-Base Equilibrium (ABE). The involvement of the liver in the regulation of ABE is crucial because of its role in lactic acid metabolism, urea production and in protein homeostasis. The main acid-base imbalance that occurs in patients with liver cirrhosis is Respiratory Alkalosis (RAlk). Due to the fact that in these patients additional pathophysiological mechanisms that affect the ABE are present, other disorders may appear which compensate or enhance the primary disorder. Conventional ABE reading models fail to identify and assess the underlying disorders in patients with liver cirrhosis. This weakness of the classical models led to the creation of new physicochemical mathematical models that take into account all the known parameters that develop and affect the ABE. In addition to the RAlk, in patients with liver cirrhosis, metabolic alkalosis (due to hypoalbuminemia), hyponatremic metabolic acidosis, hyperchloremic metabolic acidosis, lactic acidosis and metabolic alkalosis due to urea metabolism are some of the pathophysiological mechanisms that affect the ABE.

Pathophysiology of Drug-Induced Hypomagnesaemia.

Magnesium (Mg2+) is the second most abundant intracellular and fourth extracellular cation found in the body and is involved in a wide range of functions in the human cell and human physiology. Its role in most of the enzyme processes (ATP-ases)-stabilisation of nucleic acids (DNA, RNA), regulation of calcium and potassium ion channels, proliferation, glucose metabolism and apoptosis-make it one of the most important cations in the cell. Three pathogenetic mechanisms are mainly implicated in the development of hypomagnesaemia: reduced food intake, decreased intestinal absorption and increased renal excretion of Mg2+. This review presents the function of Mg2+, how it is handled in the kidney and the drugs that cause hypomagnesaemia. The frequency and the number of drugs like diuretics and proton-pump inhibitors (PPIs) that are used daily in medical practice are discussed in order to prevent and treat adverse effects by providing an insight into Mg2+ homeostasis.

Partially hydrolyzed polyvinyl alcohol for fusion-based pharmaceutical formulation processes: Evaluation of suitable plasticizers.

The present study evaluates the effect of several pharmaceutical plasticizers on the thermo-physical and physicochemical properties of partially hydrolyzed poly(vinyl alcohol) (PVA) used in fusion-based pharmaceutical formulation processes. Specifically, the effect of mannitol (MAN), sorbitol (SOR), sucrose (SUC), anhydrous citric acid (CA), triethyl citrate (TEC) and low-molecular weight polyethylene glycol (PEG400) on PVA's melting properties, physical state and thermal degradation was evaluated via differential scanning calorimetry (DSC), powder X-ray diffractometry (pXRD) and thermo-gravimetric analysis (TGA). Results showed that the use of MAN, SOR, SUC and PEG400 led to the reduction of PVA's melting onset temperature, while MAN, SUC, CA and SOR were amorphously dispersed within PVA's matrix, and the addition of SUC and CA resulted in significant reduction of PVA's crystallinity. TGA results showed the formation of thermally highly unstable PVA mixtures in the cases of CA and TEC (degradation started from ~150 °C and ~125 °C, respectively), while significant molecular interactions were identified by FTIR in the cases of PVA-MAN, PVA-SOR and PVA-SUC. Hot-stage polarized microscopy (HSM) revealed PVA's melt miscibility only with MAN and SOR, while melt flow index (MFI) measurements showed that the use of MAN, SOR and PEG400 resulted in a significant improvement of PVA's melt flow properties. Finally, MD simulations were in close agreement with the experimental observations, indicating that they can be considered as a promising tool for the theoretical modelling of such systems.

Crystallization tendency of APIs possessing different thermal and glass related properties in amorphous solid dispersions.

The correlation between glass forming ability (GFA) and several thermophysical or physicochemical properties of APIs with the formation and the physical stability of amorphous solid dispersions (ASDs) was evaluated in the present study. Eight poorly water-soluble APIs belonging in different GFA classes (i.e. a) GFA Class I: Carbamazepine, CBZ, b) GFA Class II: Agomelatine, AGO, Aprepitant, APT, Rivaroxaban, RIV, and c) GFA Class III: Indomethacin, IND, Pioglitazone, PIO, Piroxixam, PIR, and Simvastatin, SIM) were tested, in addition to six commonly used matrix-carriers (namely povidone, PVP, hydroxypropyl cellulose, HPC-SL, copovidone, coPVP, Soluplus®, SOL, and gelatin) in order to prepared ASDs via film casting approach. Results using polarized light microscopy (PLM) showed a similar drug crystallization tendency from ASDs independently of their GFA classification, glass stability or glass fragility. X-ray diffraction analysis verified the formation and the physical stability of ASD (independently of GFA class) when a suitable matrix-carrier was selected (i.e. SOL for AGO, RIV and SIM, PVP for APT, CBZ and IND, coPVP for PIO and gelatin for PIR). Further attempts to correlate some physicochemical properties (i.e. component's binding affinity and miscibility) with the formation and the crystallization tendency of the prepared ASDs showed no apparent correlation in regards to the different drug GFA classes. Finally, the evaluation of molecular interactions via FTIR analysis also failed to adequately distinguish the differences in regards to the formation and the physical stability of the prepared systems.

Rivaroxaban polymeric amorphous solid dispersions: Moisture-induced thermodynamic phase behavior and intermolecular interactions.

The present study evaluates the physical stability and intermolecular interactions of Rivaroxaban (RXB) amorphous solid dispersions (ASDs) in polymeric carriers via thermodynamic modelling and molecular simulations. Specifically, the Flory-Huggins (FH) lattice solution theory was used to construct thermodynamic phase diagrams of RXB ASDs in four commonly used polymeric carriers (i.e. copovidone, coPVP, povidone, PVP, Soluplus, SOL and hypromellose acetate succinate, HPMCAS), which were stored under 0%, 60% and 75% relative humidity (RH) conditions. In order to verify the phase boundaries predicted by FH modelling (i.e. truly amorphous zone, amorphous-amorphous demixing zones and amorphous-API recrystallization zones), samples of ASDs were examined via polarized light microscopy after storage for up to six months at various RH conditions. Results showed a good agreement between the theoretical and the experimental approaches (i.e. coPVP and PVP resulted in less physically-stable ASDs compared to SOL and HPMCAS) indicating that the proposed FH-based modelling may be a useful tool in predicting long-term physical stability in high humidity conditions. In addition, molecular dynamics (MD) simulations were employed in order to interpret the observed differences in physical stability. Results, which were verified via differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR), suggested the formation of similar intermolecular interactions in all cases, indicating that the interaction with moisture water plays a more crucial role in ASD physical stability compared to the formation of intermolecular interactions between ASD components.

The Effect of Dialysis Modality and Membrane Performance on Native Immunity in Dialysis Patients.

Chronic Kidney Disease (CKD) is characterized by immune activation with development of chronic inflammation. However, immune deficiency also exists in CKD patients. The number and the activity of Natural Killer cells (NK-cells) are influenced by the biocompatibility of various dialysis membranes. In this study we investigated the effect of dialysis modality and membrane type on NK-cell number and on phagocytic activity of neutrophils in patients on different dialysis methods. Sixty patients were included in the study and divided in three groups of 20 patients each. Patients on conventional hemodialysis using Low Flux membrane (cHD-LF) were included in Group I, patients on conventional dialysis using High Flux membrane (cHD-HF) were included in Group II and patients treated by on-line hemodiafiltration with High Flux polysulphone membrane (on-line HDF) were included in Group III. Native immunity was investigated using the number of NK-cells and the phagocytic activity of neutrophils. NK-cells count was significantly lower (p<0.001) in the three groups of dialyzed patients in comparison to healthy subjects. However, no significant difference was observed in the NK-cells count among patients treated by conventional dialysis using Low or High Flux membrane and patients treated by on-line hemodiafiltration. Similarly, although the phagocytic activity of neutrophils was significantly decreased in all patients on dialysis (p<0.001), no difference related to the dialysis modality or membrane performance was observed. A strong positive correlation was recognized between parathormone blood levels and number of NK-cells (r=0.305, p<0.01). In conclusion, an impairment of the native immunity represented by NK cell number and phagocytic activity of neutrophils is observed in patients on dialysis. Dialysis modality and membrane performance do not influence the native immunity of dialyzed patients. However, parathormone blood levels are possibly involved in the development of immune system disturbances in such patients.

Molecular modelling and simulation of fusion-based amorphous drug dispersions in polymer/plasticizer blends.

A realistic molecular description of amorphous drug-polymer-plasticizer matrices, suitable for the preparation of amorphous solid dispersions (ASDs) with the aid of fusion-based techniques, was evaluated. Specifically, the incorporation of two model drugs (i.e. ibuprofen, IBU, and carbamazepine, CBZ) having substantially different thermal properties and glass forming ability, on the molecular representation of polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (SOL)/polyethylene glycol (PEG, working as a plasticizer) molecular and thermal properties were evaluated with the aid of classical molecular dynamics (MD) and docking simulations. Results showed good agreement between molecular modelling estimations and experimentally determined properties. Specifically, the computed Tg values that resulted from MD simulations for IBU-SOL/PEG and CBZ-SOL/PEG (53.8 and 54.2 °C, respectively) were in reasonable agreement with the corresponding values resulting from differential scanning calorimetry (DSC) measurements (49.8 and 50.1 °C), while both molecular modelling and experimental obtained results suggested miscibility among system components. Additionally, interactions between CBZ and SOL observed during MD simulations were verified by FTIR analysis, while MD simulations of the hydration process suggested strong molecular interactions between IBU-SOL and CBZ-SOL.

Estimation of Residual Peritoneal Volume Using Technetium-99m Sulfur Colloid Scintigraphy.

Residual peritoneal volume (RPV) may contribute in the development of ultrafiltration failure in patients with normal transcapillary ultrafiltration. The aim of this study was to estimate the RPV using intraperitoneal technetium-99m Sulfur Colloid (Tc). Twenty patients on peritoneal dialysis were studied. RPV was estimated by: 1) intraperitoneal instillation of Tc (RPV-Tc) and 2) classic Twardowski calculations using endogenous solutes, such as urea (RPV-u), creatinine (RPV-cr), and albumin (RPV-alb). Each method's reproducibility was assessed in a subgroup of patients in two consecutive measurements 48 h apart. Both methods displayed reproducibility (r = 0.93, p = 0.001 for RPVTc and r = 0.90, p = 0.001 for RPV-alb) between days 1 and 2, respectively. We found a statistically significant difference between RPV-Tc and RPV-cr measurements (347.3 ± 116.7 vs. 450.0 ± 67.8 ml; p =0.001) and RPV-u (515.5 ± 49.4 ml; p < 0.001), but not with RPV-alb (400.1 ± 88.2 ml; p = 0.308). A good correlation was observed only between RPV-Tc and RPV-alb (p < 0.001). The Tc method can estimate the RPV as efficiently as the high molecular weight endogenous solute measurement method. It can also provide an imaging estimate of the intraperitoneal distribution of RPV.

Non-secreting benign glucagonoma diagnosed incidentally in a patient with refractory thrombocytopenic thrombotic purpura: report of a case.

Thrombotic thrombocytopenic purpura (TTP) is a rare hematologic disorder, which may be idiopathic or secondary to a variety of diseases. However, there are very few reports of TTP in the context of pancreatic neoplasms. We report a case of relapsing TTP after initial treatment with plasmapheresis, corticosteroids, and rituximab, in a 59-year-old woman. During diagnostic work-up, a pancreatic lesion 35 × 25 mm in size was discovered incidentally and splenopancreatectomy was performed. The pathological diagnosis was benign glucagonoma. The hematological symptoms resolved completely after the procedure and 3 years later, the patient is well with no sign of recurrence of TTP or glucagonoma. To our knowledge, this represents the first documented case of a non-secreting benign pancreatic neuroendocrine tumor (glucagonoma) associated with TTP that is refractory to standard treatment.

Patient clearance time (tp) with different vascular access types.

BACKGROUND/AIMS: The dialysis delivered dose is limited by the rate at which urea can be transferred from the different body compartments. The time needed to clear the peripheral compartments of the body has been called the patient clearance time (tp). The aim of the study was to compare delivered dialysis dose using the tp index between patients dialyzed through a permanent central venous catheter (CVC) and patients with an arteriovenous fistula (AVF). METHODS: The study included 48 stable hemodialyzed patients. Patients were classified into two groups according to their vascular access type. The first group included 24 patients dialyzed through a permanent CVC and the second group consisted of 24 patients with a mature AVF. The following parameters were calculated twice for each patient: tp, Kt/V adjusted for the tp. RESULTS: tp was lower in the AVF dialysis modality than in CVC (26 ± 7 vs. 42 ± 14 min, p<0.001) while the (eqKt/V)tp was higher in AVF than in CVC dialysis (1.36 ± 0.11 vs. 1.19 ± 0.13, p<0.001). CONCLUSIONS: The patient clearance time is lower in AVF than in CVC dialysis, and this is accompanied by a higher delivered dialysis dose.

The impact of hemodialysis on the dispersion of ventricular repolarization.

BACKGROUND: Sudden cardiac death is prevalent in chronic hemodialysis (HD) patients while the dialysis process may have arrhythmogenic potential. We sought to examine the effect of HD on conventional electrocardiographic parameters as well as on novel indexes of repolarization, given that increased spatial dispersion of repolarization is related to ventricular arrhythmias. METHODS: We recorded clinical, echocardiographic, and laboratory parameters as well as electrocardiographic indexes before and after a single HD session. Specifically, we calculated the QTc interval, the QRS duration, the T peak-to-end (Tpe) interval, and the Tpe/QT ratio. RESULTS: The study population consisted of 66 chronic HD patients (mean age: 68.9 ± 11.8 years, 40 males). Heart rate, blood pressure, QRS duration, QTc interval, and QT dispersion did not change significantly after the HD session. However, the Tpe interval and the Tpe/QT ratio increased significantly (80 [65-90] ms vs 85 [77.5-100] ms; P = 0.04, and 0.21 [0.18-0.24] vs 0.25 [0.21-0.28]; P = 0.05, respectively). Correlation analysis and multiple regression analysis failed to show significant associations between the baseline parameters and the baseline values of Tpe and Tpe/QT or between the change of the laboratory parameters during HD and the corresponding change of the Tpe and the Tpe/QT values. No significant arrhythmias were observed during the HD sessions. CONCLUSIONS: HD induces an increase in novel markers of spatial dispersion of ventricular repolarization. Whether the assessment of these indexes of heterogeneity of repolarization at baseline or their change during HD has a prognostic value with regard to future untoward events, remains to be elucidated.

Mononuclear leukocyte apoptosis and inflammatory markers in patients with chronic kidney disease.

BACKGROUND/AIM: Increased apoptosis along with enhanced inflammation has been reported in hemodialysis and pre-dialysis patients. However, there is limited information at which stage during the progression of chronic kidney disease (CKD) the balance between pro- and anti-apoptotic mechanisms is disturbed and inflammatory response is activated. The aim of this study was to investigate possible alterations in apoptotic and inflammatory markers during CKD (stages 1-4) progression and the probable interactions between them. METHODS: In a cross-sectional study, 152 steady-state CKD outpatients (83 males, 55%) with mean estimated glomerular filtration rate 46 (29-76) ml/min/1.73 m(2) were studied. Apoptosis was assessed in peripheral blood mononuclear cells by estimating Bcl-2 expression, annexin V-propidium iodine staining and serum soluble Fas (sFas) and Fas-ligand. Serum levels of C-reactive protein, tumor necrosis factor-α (TNF-α), interleukin-6 and plasma levels of fibrinogen were measured as markers of inflammation. RESULTS: Bcl-2 expression was found to decrease significantly in both lymphocytes and monocytes from CKD stage 1 to 4. In contrast, the activity of sFas increased significantly and so did the levels of TNF-α and fibrinogen. The majority of these alterations occurred as soon as patients entered stage 3 of CKD. A multivariate regression analysis demonstrated that CKD remained a significant predictor of the aggregate of the assessed markers. CONCLUSIONS: Apoptosis appeared to increase across CKD stages 1-4, and this was associated with increased proinflammatory activity.

Inorganic phosphorus homeostasis during the first hour of dialysis.

BACKGROUND/AIM: Hyperphosphatemia is a well-recognized complication of chronic kidney disease, and phosphorus kinetics during hemodialysis (HD) remains a vague area of investigation. We studied the inorganic phosphorus homeostasis during the first hour of an HD session. MATERIALS/METHODS: Twelve patients were studied twice, in two consecutive HD sessions. Total (TPR), extracellular (EPR), and intracellular (IPR) phosphorus mass removal was determined using the direct dialysate quantification (DDQ) method. Alterations of serum inorganic phosphorus (sP), erythrocyte intracellular phosphorus (P(ERY)), and 2,3-diphosphoglycerate (2,3-DPG) concentrations were measured before HD initiation and at 1, 2, 3, 4, 5, 10, 30, and 60 min. RESULTS: The contribution of IPR to TPR was negative in the first 10 min of both HD sessions (-27.2 ± 6.5 and -26.4 ± 58 mmol, respectively, p = ns) while the contribution of the IPR to TPR increased as the time elapsed. Intracellular phosphorus and 2,3-DPG remained almost unchanged during the 60 min of HD session. CONCLUSIONS: Unchanged P(ERY) concentration during the first hour of an HD session does not reject the hypothesis of a simultaneous efflux and influx of phosphorus from/to intracellular compartment.

Switch from conventional to every other day hemodialysis: a comparison pilot study.

Fluid and solute fluctuations during the week are the main drawbacks of conventional hemodialysis (cHD) in patients' outcomes. The aim of our study was to evaluate the influence of every other day hemodialysis (eodHD) on clinical and laboratory parameters and to compare to that of cHD. Eighteen patients on cHD were included in the study. Nine patients (group I) were randomly switched to eodHD, while the rest (group II) remained on their regular cHD. By the end of the study (12 months) we observed a reduction in body weight followed by a parallel reduction in predialysis mean blood pressure by 7 mm Hg in group I (p<0.05) and the number of antihypertensives. Moreover, a reduction in left ventricular mass and an increment of ejection fraction was observed in group I. Hemoglobin levels remained stable in both groups, but erythropoietin dose was reduced in eodHD group. Dialysis delivered dose (dpKt/V) was higher and urea rebound phenomenon was less in group I. Finally, an improvement in uremia related and postdialysis symptoms was observed in the same group of patients. Our results showed that eodHD improved patients' clinical and biochemical status and therefore might have advantages in patients' outcomes compared with cHD.

Correction of anemia with erythropoietin in chronic kidney disease (stage 3 or 4): effects on cardiac performance.

BACKGROUND: It is not clear whether the correction of anemia with erythropoietin (rhuEpo) in patients with chronic kidney disease (CKD) has any benefit on cardiac function and geometry. Most studies are based on indices of systolic function and left ventricular mass (LVM) and the results are conflicting. PATIENTS AND METHODS: We sought to investigate the effect of rhuEpo on LV systolic and diastolic performance using conventional and novel echocardiographic indices. Thirty one patients with CKD (stage 3 or 4) were included. Fifteen patients (group I) treated with rhuEpo targeting at Hb >or=13.0 g/dL, while the remaining (group II) were not treated. Clinical and laboratory parameters were recorded at baseline and 1 year later. Ejection fraction (EF) and LVM were carefully determined. Diastolic function was assessed by mitral inflow indices (E and A wave velocities, Edt deceleration time and E/A) and novel indices of mitral annulus motion using Tissue Doppler Imaging (Em, Am, and E/Em). An index of global cardiac function (Tei) was also calculated. RESULTS: At baseline, the 2 groups had comparable clinical and laboratory characteristics. After 1 year, a significant improvement in Hb levels (13.6 +/- 1.2 vs 10.3 +/- 1.2 g/dL, p < 0.05) as well as in systolic and diastolic function indexes was observed in group I compared to group II patients: EF (70.5 +/- 7.6 vs 63.4 +/- 9.3%, p < 0.05), LVM (116.5 +/- 34.9 vs 155.6 +/- 51.6 g/m(2), p < 0.05), Edt (233.9 +/- 98.6 vs 166.9 +/- 45.1 ms, p < 0.05), Tei index (0.35 +/- 0.12 vs 0.51 +/- 0.17, p < 0.01) and E/Em (9.7 +/- 2.4 vs 14.8 +/- 5.2, p < 0.05), respectively. Blood pressure and heart rate did not show significant changes. CONCLUSIONS: Correction of anemia with rhuEpo in patients with CKD seems to improve cardiac performance and geometry.

Corticosteroids and ciclosporin A in idiopathic membranous nephropathy: higher remission rates of nephrotic syndrome and less adverse reactions than after traditional treatment with cytotoxic drugs.

BACKGROUND/AIM: Idiopathic membranous nephropathy, the most common cause of nephrotic syndrome in adults, has been traditionally treated with corticosteroids and cytotoxic drugs. Ciclosporin A (CsA) is used in resistant cases, but also as a first-line treatment, due to the serious side effects of cytotoxic drugs. In this study, the remission rates of nephrotic syndrome and the incidence of side effects of corticosteroids and low CsA doses are compared with those after treatment with cytotoxic drugs. METHODS: Seventy-seven nephrotic patients with well-preserved renal function who were treated with methylprednisolone and CsA (n = 46) or cytotoxic drugs (n = 31) were studied. The effects of treatments were estimated on the basis of remission rates of nephrotic syndrome and preservation of the renal function. RESULTS: Remission (complete or partial) of nephrotic syndrome was observed in 85% of the patients treated with CsA and in 55% of the patients treated with cytotoxic drugs (p < 0.01). Deterioration of the renal function, more common in patients with multiple relapses and interstitial fibrosis, was observed in 26 and 23% of the patients, respectively (p = NS). Serious side effects and discontinuation of treatment were more frequent in patients treated with cytotoxic drugs (10 vs. 4%). CONCLUSION: The combination of corticosteroids with CsA represents a better regimen for patients having idiopathic membranous nephropathy, since it is associated with higher remission rates of nephrotic syndrome and less severe side effects than corticosteroids and cytotoxic drugs.

Acute effect of heparin on lipid parameters in patients on renal replacement therapy.

Dialyzer membrane and the type of heparin used can influence lipid parameters. However, there are limited and debatable data concerning lipid alterations during a single hemodialysis session. Moreover, the role of hemoconcentration after every hemodialysis session confuses the real effect of the heparin on lipid profile. We investigated the acute effect of heparin administration on lipids in hemodialysis patients, but on an off-hemodialysis day in order to eliminate any effect of ultrafiltration. We studied six patients on hemodialysis, six patients on peritoneal dialysis, and six healthy persons. The study was performed in two phases (1 week apart). In phase A, we used unfractionated heparin (5000 IU, intravenous), whereas in phase B, low-molecular-weight heparin (3500 anti-FXa, intravenous) was used. Total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and Lp(a) were estimated before and 1, 2, 3, and 4 hours after heparin administration. We observed a reduction only in triglycerides (at the first, second, and third hour) in both phases in all groups. The other lipid parameters were not affected. In conclusion, acute administration of both types of heparin seems to affect only triglyceride levels in patients on renal replacement therapy.

Oxidative stress is progressively enhanced with advancing stages of CKD.

BACKGROUND: Oxidative stress appears to have a central role in the pathophysiological process of uremia and its complications, including cardiovascular disease. However, there is little evidence to suggest how early oxidative stress starts developing during the progression of chronic kidney disease (CKD). The aim of this study is to assess oxidative stress activity in a cross-sectional study of patients with CKD stages 1 to 4. METHODS: Eighty-seven steady patients (47 men, 40 women) with a median age of 62 years (range, 28 to 84 years) and mean estimated glomerular filtration rate (eGFR) of 57 mL/min (0.95 mL/s) were studied. Levels of plasma 8-isoprostanes (8-epiPGF2a) and serum total antioxidant status (TAS) were used as markers of oxidative stress. 8-epiPGF2a levels were determined by using an enzyme-linked immunosorbent assay method, whereas a chromatometric method was used to determine TAS. RESULTS: Plasma 8-epiPGF2a levels increased significantly as CKD stages advanced (P < 0.001). There was a highly significant inverse correlation between 8-epiPGF2a level and GFR (P < 0.01). Serum TAS levels also increased in a similar fashion (P < 0.009) and showed a significant inverse correlation with GFR (P < 0.01). 8-epiPGF2a and TAS levels showed a positive correlation (P < 0.05). Multiple regression analysis showed that the most significant predictor variable for 8-epiPGF2a level was eGFR, whereas the association between eGFR and TAS was affected strongly by confounding variables, mainly uric acid level. CONCLUSION: Oxidative stress appears to increase as CKD progresses and correlates significantly with level of renal function. Increased TAS seems to be dependent on several confounding variables, including increased uric acid levels, and therefore does not seem to be a reliable method for assessing the antioxidant capacity of patients with CKD. These results suggest that larger studies using the correct markers to assess the timing and complex interplay of oxidative stress and other risk factors during the progression of CKD should be carried out.