Chronic Renal Failure Subjects Research Articles

Evaluation of minerals, urea, and creatinine in chronic renal failure

Evaluation of minerals, urea, and creatinine in chronic renal failure - IJCBR- Print ISSN No: - 2394-6369 Online ISSN No:- 2394-6377 Article DOI No:- 10.18231/j.ijcbr.2019.094, International Journal of Clinical Biochemistry and Research-Int J Clin Biochem Res

Virtual touch IQ elastography in evaluation of Achilles tendon in patients with chronic renal failure

To evaluate the sonoelastographic changes in the Achilles tendon in patients with chronic renal failure (CRF) using virtual touch imaging quantification (VTIQ) elastography. Twenty-six patients undergoing three hemodialysis sessions per week and 26 subjects admitted to our institution between January 2016 and April 2016 were included in this prospective study. The characteristics and body mass index of the patients were noted. Ultrasonography was performed parallel to the long axis of the bilateral Achilles tendons during relaxation of the legs using the Siemens Acuson S3000™ ultrasound device (Siemens HealthCare, Erlangen, Germany). Tendon thickness was reviewed, and tissue stiffness was quantitatively assessed using VTIQ elastography. Independent samples t test and Mann-Whitney U test were used for statistical analyses. The median values of shear wave velocities of the Achilles tendon in patients with CRF were 7.19m/s (4.23-9.77m/s) on the right and 6.98m/s (4.00-9.82m/s) on the left, while they were 5.11m/s (4.09-8.82m/s) on the right and 5.36m/s (4.05-8.80m/s) on the left in controls. The stiffness of the Achilles tendons in patients with CRF was found to be higher than that in controls (right: P < 0.001, left: P = 0.004). There was no statistically significant difference in tendon thickness between the CRF and control groups (P > 0.05). The thickness and stiffness of tendon can be effectively evaluated with sonoelastography. The thickness of the Achilles tendon did not significantly differ between the patients with CRF and healthy subjects. However, the stiffness of the Achilles tendon measured with VTIQ elastography was demonstrated to be increased in the patients with CRF.

Neurobehavioral Alterations and Brain Creatine Kinase System Changes in Chronic Renal Failure Induced Male Wistar Rats: Impact of Erythropoietin Supplementation

Chronic renal failure (CRF) is a rapidly growing global health problem and it causes anaemia and cognitive impairment. Recombinant Human erythropoietin (rHu-Epo) has been a promising role in the management of anaemia in CRF subjects and it is well documented. It also shown as a remarkable neuroprotection in both cell cultures and in animal models. Creatine kinase (CK) plays a key role in energy metabolism and its activity found in cytoplasm of several human tissues; major sources of CK include skeletal muscle, myocardium and brain. Studies show brain energy metabolism is key to neuronal cell function and cognitive health. The aim of this study is to investigate the impact of rHu-Epo on CRF induced changes in CK system in serum and brain regions of experimental animals and to test its significance in neurobehavioral changes. Experimental design is divided into two phases to find out the variation between simultaneous and post rHu-Epo Treatment in CRF induced male wistar rats. At the end of 40 days, animals were sacrificed uniformly. In both phases, CK level in serum and selected brain regions such as cerebellum, cerebral cortex and hippocampus were determined by spectrophotometric method and hematological parameters (RBC, Hb, PCV, MCV, MCH, MCHC) were also determined. In results, decreased creatine kinase activity in brain regions and its increased level in serum observed in CRF induced animals. Neurobehavioral changes and alterations in hematological parameters were also seen in CRF induced animals. Supplementation of rHu-Epo in both simultaneous and post treatment group reversed the CRF induced changes including neurobehavioral alterations, significantly. In this study, the protective role of Epo supplementation on CRF induced changes in CK system in both brain and serum and its correlation with neurobehavioral changes were seen along with its antianemic effect.

Evaluating the utility of plasma Atherogenic Index among several atherogenic parameters in patients with chronic renal Failure on maintenance hemodialysis

Background: Patients with chronic renal failure undergoing longterm hemodialysis (HD) are prone to atherosclerosis and at increased risk of developing cardiovascular diseases.Objective: The objective of this study is to compare atherogenic index of plasma (AIP) in predicting the risk of cardiovascular disease (CVD) in patients with chronic renal failure (CRF) on regular hemodialysis, when associated with other chronic diseases.Patients and methods: A total of forty male patients with CRF on hemodialysis, matched in, age, body mass index BMI, and duration of hemodialysis were enrolled. They were grouped as group 1 (G1) includes eleven subjects with CRF without (hypertension and / or diabetes) groups 2 (G2) fourteen CRF subjects with hypertension and group 3 (G3) fifteen CRF subjects with diabetes. As a control group, eighteen healthy male subjects were included with special exclusion criteria. The plasma total cholesterol TC, triglyceride TG, and high density lipoprotein-cholesterol HDL-C were estimated using spectrophotometry methods. While low density lipoprotein-cholesterol LDL-c, and AIP were calculated using special formulas. Statistical analysis was performed by the student t-test.Results: The results of the study revealed significant increase in TC and TG, with significant decrease in HDL-c for all patient groups compared to control. No significant difference in LDL-c of G1 compared to control was found, while significant increase in LDL-c of G2 and G3 was found when compared to G1 or control. The AIP values were (0.42 ± 0.19 vs 0.43 ± 0.17; P&gt;0.05) for G1 and G2 respectively, that showed no significant difference of atherogenic risk between these groups.Conclusions: These results concluded that AIP seems to be superior to LDL-c in predicting the risk for CVD in CRF groups on hemodialysis and those at the highest risk when CRF coupled with diabetes.

Effect of hemodialysis (HD) on intraocular pressure, ocular surface, and macular change in patients with chronic renal failure

The main objective of hemodialysis (HD) is to correct the excessive accumulation and abnormal distribution of body fluid. Therefore, changes in the systemic hemodynamic parameters and in the ocular fluid volume and composition can occur during a single HD session. The aim of this study is to evaluate the short-term changes in the ophthalmologic findings after HD. Thirty eyes of 30 patients with chronic renal failure (CRF) undergoing HD were analyzed. The subjects were categorized into two groups according to the cause of CRF. Detailed ophthalmologic examinations were performed immediately before and after HD. The relationships between the systemic hemodynamic changes and the ophthalmologic changes during a single HD session were evaluated. The results show that a body fluid correction after HD involves a change in the plasma colloid osmotic pressure. The mean intraocular pressure (IOP) decreased after HD with a mean decrease of 2.4 ± 2.1 mmHg and the central corneal thickness decreased with a mean change of 6.9 ± 5.4 μm. After HD, the ocular surface changed significantly; the tear break-up time (TBUT) and basal tear secretion (Schirmer's test) decreased, whereas the keratoepitheliopathy score increased. The macular thickness measured by spectral domain optical coherence tomography (SD-OCT) decreased after HD. The mean decrease in the central subfield thickness was 7.4 ± 9.9 μm. The ocular surface changes after HD affected the visual acuity and examination quality. A significant correlation was found between the changes in the systemic hemodynamic parameters and those in the ophthalmologic findings, except for the retinal thickness. The changes in the ophthalmologic findings after HD were consistent and significant in all CRF subjects. These changes correlated with the increase in plasma colloid osmotic pressure. HD can correct the volume and composition of ocular fluid. Therefore, it can affect the ophthalmologic findings in a short period of time. In addition, for good examination quality, it is recommended that an ophthalmologic examination in CRF patients be performed on a non-dialysis day or prior to HD on a dialysis day. Furthermore, for accurate comparison of examination results, the time interval from an HD session to an ophthalmologic examination must be considered.

Voice in Chronic Renal Failure

Chronic renal failure affects various body systems, one of which is the respiratory system. Because respiration is the prime source for speech, vocal dysfunctions are expected to be present in patients with chronic renal failure. The present study attempts to shed light on the changes in acoustic and aerodynamic characteristics of voice, if any, in patients with chronic renal failure. Phonation of sustained vowel /a/ was subjected to acoustic analysis using VAGHMI software (Voice and Speech Systems, Bangalore, Karnataka, India). Sustained phonation of /a/, /s/, and /z/ was recorded for the purpose of aerodynamic analysis. Independent t test was used to find the significant difference between the twogroups. Chronic renal failure subjects showed significant deviation in frequency, perturbation, and aerodynamicmeasures when compared with normal subjects. These results are discussed with respect to the underlying pathophysiology.

Circulating Renin Angiotensin System in Childhood Chronic Renal Failure: Marked Increase of Angiotensin-(1–7) in End-Stage Renal Disease

The aim of the present study was to evaluate plasma renin activity (PRA) and Angiotensin (Ang) levels [Ang I, Ang II and Ang-(1-7)] to examine the circulating Renin-Angiotensin System (RAS) in renal disease among children with different forms and stages of chronic renal failure (CRF). Subjects were divided as follows: 32 normotensive healthy subjects, 23 normotensive CRF subjects, 34 hypertensive CRF subjects and 21 subjects with end-stage renal disease (ESRD). Radioimmunoassays for PRA (ngAngI/mL/h) and angiotensin (pg/mL) measurements were performed on all subjects. PRA, Ang I, Ang II and Ang-(1-7) levels were significantly higher in hypertensive CRF subjects when compared with normotensive CRF and healthy subjects (p < 0.05 for all comparisons). No differences were observed between normotensive CRF and healthy subjects. ESRD subjects exhibited a dramatic increase in Ang-(1-7) (25-fold higher than control values). In hypertensive CRF subjects, treatment with angiotensin-converting enzyme inhibitors (ACEi) increased (1.4-fold) plasma Ang-(1-7) and decreased (2.4-fold) Ang II. In ESRD, the use of ACEi produced a similar (1.5-fold) elevation of Ang-(1-7), but no changes in plasma Ang II. Our data showed different circulating RAS profiles between hypertensive and in normotensive CRF subjects. Marked changes in plasma Ang-(1-7) were associated with the presence of hypertension and progression of kidney dysfunction.

Paraoxonase activity and antibodies to oxidized-LDL in chronic renal failure patients on renal replacement therapy.

Serum paraoxonase (PON1) and antibodies to oxidized-LDL (anti ox-LDL) were measured in chronic renal failure subjects on renal replacement therapy such as hemodialysis (HD) peritoneal dialysis (PD) and transplantation (Txp). Paraoxonase activity was significantly lower in HD and PD group (P<0.001) than in control subjects. In transplant patients, paraoxonase activity was not significantly different from that of controls. Antibodies to ox-LDL was significantly higher in HD, PD and Transplant patients (P<0.0001) compared to control subjects. High titers of antibodies were observed in the HD group compared to the PD and Transplant subjects. A decrease in paraoxonase activity and high titers of Antibodies to ox-LDL in the dialysis group suggest a decreased cardio protective effect of HDL and enhanced risk of premature cardiovascular complications. Whereas in case of transplant subjects, there seems to be restoration of PON1 activity, but elevated levels of anti-oxLDL could still be a potential atherogenic factor. Hence, we propose that estimation of these two parameters can be used as a useful index to measure the cardiac risk in the above patient category.

Left ventricular diastolic dysfunction in patients with chronic renal failure: impact of diabetes mellitus

Left ventricular (LV) hypertrophy and LV diastolic dysfunction are cardiac changes commonly observed in patients with chronic renal failure (CRF) as well as hypertension. Although the impairment of LV diastolic function in patients with diabetes mellitus has been shown, little is known about the specific effect of diabetes on LV diastolic function in patients with CRF. The present study was designed to investigate the impact of diabetic nephropathy on LV diastolic dysfunction, independent of LV hypertrophy, in CRF patients. In 67 patients with non-dialysis CRF as a result of chronic glomerulonephritis (n = 33) or diabetic nephropathy (n = 34), and 134 hypertensive patients with normal renal function, two-dimensional and Doppler echocardiographic examinations were performed, and LV dimension, mass, systolic function, and diastolic function were evaluated. LV mass was increased and LV diastolic dysfunction was advanced in subjects with CRF compared with hypertensive controls. In the comparison of echocardiographic parameters between the two groups of CRF patients, i.e. chronic glomerulonephritis and diabetic nephropathy groups, all indices of LV diastolic function were more deteriorated in the diabetic nephropathy group than in the chronic glomerulonephritis group, although LV structure including hypertrophy and systolic function did not differ between the groups. In a multiple regression analysis, the presence of diabetes (i.e. diabetic nephropathy group) was a significant predictor of LV diastolic dysfunction in CRF subjects, independent of other influencing factors such as age, blood pressure, renal function, anaemia and LV hypertrophy. The present findings suggest that LV diastolic dysfunction, independent of LV hypertrophy, is specifically and markedly progressed in patients with CRF as a result of diabetic nephropathy.

Rituximab Inhibits the In Vivo Primary and Secondary Antibody Response to a Neoantigen, Bacteriophage phiX174

The response to primary immunization in patients treated with Rituximab (RIT) is not clear. We studied the in vivo antibody response of chronic renal failure (CRF) patients to the neoantigen bacteriophage phiX174 given alone or after ablation with RIT. Eighteen CRF subjects received two immunizations with phiX174 separated by 6 weeks. Nine subjects received a single dose of RIT. The intensity and immunoglobulin isotype of the antibody response (K(v)) were measured post-infusion. In addition, three subjects previously immunized and treated with RIT underwent a third and fourth immunization with phiX174 and a tetanus control 2 years later. RIT significantly decreased peak K(v) responses when compared to both historic non-CRF controls and to CRF subjects. CRF itself decreased peak K(v) responses compared to non-CRF controls. Percent-ratio of anti-phage IgM to IgG was significantly decreased in RIT treated subjects. One of three subjects treated with RIT was found to have developed a partial B cell tolerance to phiX174 administration 2 years later. RIT decreases antibody production and isotype switching to neoantigens and might be useful to prevent antibody response to therapeutic drugs and to newly transplanted organs.

Monocyte Apoptosis in Uremia Is Normalized with Continuous Blood Purification Modalities

Uremia is associated with a state of immune dysfunction. Dysregulation of homeostasis may be directly related to abnormal apoptosis regulation in uremia, which is crucial for the maintenance of the biological system. We demonstrated that plasma from three groups of uremic subjects, i.e. hemodialysis (HD) patients, peritoneal dialysis (PD) patients and patients with predialysis chronic renal failure (CRF), has different apoptotic potential on U937 monocytes. The plasma of HD and CRF subjects when incubated with U937 cells induced higher levels of apoptosis compared with that of PD and control subjects (HD 26.08 ± 11.39, CRF 24.87 ± 9.07, PD 12.13 ± 4.51, controls 11.69 ± 4.02). Furthermore, the phagocytic ability of U937 cells incubated with the various plasma demonstrated an impaired response in the HD and CRF subjects (HD 27.56 ± 6.67, CRF 30.24 ± 9.08, PD 36.55 ± 9.80, controls 40.04 ± 6.98). These results suggest that continuous blood purification, such as in PD, may have advantages over intermittent therapies in removing uremic apoptotic molecules and potentially maintaining biological function and homeostasis.

Membrane Distillation of Human Plasma Ultrafiltrate and its Theoretical Applications to Haemodialysis Techniques

Membrane Distillation (MD) is a technique that allows the extraction of water from aqueous solutions. The basic principle is that vapour, but not liquid water, can pass through hydrophobic micro-porous membranes, along a temperature gradient, with consequent separation of water from solutes. In this study we evaluated the possibility to utilise MD to extract water from Plasma Ultrafiltrate (PU) of patients with Chronic Renal Failure (CRF). The experiments were carried out in vitro by a hydro-phobic polypropylene hollow-fibre distillation module; PU was obtained by a CRF patient utilising a high permeability polisulphone membrane. The results show that water can be extracted by MD from PU of CRF subjects at a constant rate and that none of the substances analysed in PU was able to pass through the polypropilene membrane. In the future MD could integrate extra-corporeal blood purification techniques allowing the re-utilisation of plasmatic water thus ameliorating the treatment of uraemia.

Accelerated degradation of adenine nucleotide in erythrocytes of patients with chronic renal failure.

Recently, we have shown that erythrocytes obtained from patients with chronic renal failure (CRF) exhibited an increased rate of ATP formation from adenine as a substrate. Thus, we concluded that this process was in part responsible for the increase of adenine nucleotide concentration in uremic erythrocytes. There cannot be excluded however, that a decreased rate of adenylate degradation is an additional mechanism responsible for the elevated ATP concentration. To test this hypothesis, in this paper we compared the rate of adenine nucleotide breakdown in the erythrocytes obtained from patients with CRF and from healthy subjects. Using HPLC technique, we evaluated: (1) hypoxanthine production by uremic RBC incubated in incubation medium: (a) pH 7.4 containing 1.2 mM phosphate (which mimics physiological conditions) and (b) pH 7.1 containing 2.4 mM phosphate (which mimics uremic conditions); (2) adenine nucleotide degradation (IMP, inosine, adenosine, hypoxanthine production) by uremic RBC incubated in the presence of iodoacetate (glycolysis inhibitor) and EHNA (adenosine deaminase inhibitor). The erythrocytes of healthy volunteers served as control. The obtained results indicate that adenine nucleotide catabolism measured as a hypoxanthine formation was much faster in erythrocytes of patients with CRF than in the cells of healthy subjects. This phenomenon was observed both in the erythrocytes incubated at pH 7.4 in the medium containing 1.2 mM inorganic phosphate and in the medium which mimics hyperphosphatemia (2.4 mM) and metabolic acidosis (pH 7.1). The experiments with EHNA indicated that adenine nucleotide degradation proceeded via AMP-IMP-Inosine-Hypoxanthine pathway in erythrocytes of both patients with CRF and healthy subjects. Iodoacetate caused a several fold stimulation of adenylate breakdown. Under these conditions: (a) the rate of AMP catabolites (IMP + inosine + adenosine + hypoxanthine) formation was substantially higher in the erythrocytes from patients with CRF; (b) in erythrocytes of healthy subjects degradation of AMP proceeded via IMP and via adenosine essentially at the same rate; (c) in erythrocytes of patients with CRF the rate of AMP degradation via IMP was about 2 fold greater than via adenosine. The results presented in this paper suggest that adenine nucleotide degradation is markedly accelerated in erythrocytes of patients with CRF.

Chronic Renal Failure: Leukocyte Rheology and Polymorphonuclear Cytosolic Ca2+ Concentration

SummaryIn a group of subjects with chronic renal failure (CRF), we evaluated the leukocyte rheological activity, expressed as the filtration rate, the polymorphonuclear (PMN) membrane fluidity and the PMN cytosolic Ca2+ content. Using the St. George's Piltrometer, we determined the filtration rate of unfractionated, mononuclear and PMN leukocytes. Using the fluorescent probe 1.4-(trimethylamino)-phenyl-4-phenyl-hexatriene (TMA-DPH), we examined the PMN membrane fluidity and, using the Fura 2-AM, the PMN cytosolic Ca2+ content. Prom the results obtained, it is evident that only the initial relative flow rate of unfractionated leukocytes was significantly reduced in subjects with CRF, while the filtration parameters of mononuclear and PMN cells did not distinguish normals from CRF subjects. No variation was evident for the PMN membrane fluidity, while the PMN cytosolic Ca2+ content was significantly increased in CRF subjects. In these subjects no correlation was found between leukocyte filtration parameters, PMN membrane fluidity, PMN cytosolic Ca2+ content and plasma parameters (blood urea nitrogen and serum creatinine), reflecting the degree of the CRF. In conclusion, in CRF subjects the abnormality of the leukocyte flow properties was restricted to the initial flow rate of unfractionated leukocytes, whereas the increase of PMN cytosolic Ca2+ content might be attributed to PMN activation.

Insulin-Like Growth Factor–I Treatment to Enhance Renal Function in Advanced Chronic Renal Failure

Because of the potential for IGF-1 to enhance renal function in advanced chronic renal failure (CRF) we set out to determine whether IGF-1 can induce a sustained increase in renal function in patients with near end-stage renal failure. To this end we first examined the impact of CRF on the pharmacokinetics of IGF-1 and then we examined the effect of prolonged IGF-I treatment on the renal function of patients with an average GFR of 17mL/min/1.73m2. Interestingly the metabolic clearance rate of IGF-1 in CRF subjects was similar to that in normal subjects even though the total serum IGF-1 levels rose to higher maximum levels. This increase was due to a reduced volume of IGF-1 distribution, a consequence of the elevated serum IGF binding proteins in CRF subjects. Treatment with IGF-I (60 mg/kg twice daily sc) for 31 days resulted in a 14% and 18% increase in the inulin and PAIL clearances respectively (n = 6 patients). These parameters returned to basal levels on stopping treatment. Serum immunoreactive IGFBP-3 levels fell and IGFBP-2 and -3 levels rose during IGF-1 therapy. Adverse effects were mild, of short duration and easily manage-able. Thus IGF-I pharmacokinetics are largely unchanged in CRF and the administration of IGF-1 produces a modest improvement in the GFR. These results appear to justify more extensive examination of the therapeutic role of IGF-1 in the treatment of CRF.

Pharmacokinetics of insulin-like growth factor-1 in advanced chronic renal failure

Information regarding the impact of chronic renal failure (CRF) on IGF-1 serum clearance is limited. Thus we evaluated the pharmacokinetics of insulin-like growth factor-1 (IGF-1) in six normal adults and six adults with advanced CRF (serum creatinine 7 +/- 0.8 mg/dl). All subjects were given 80 micrograms/kg recombinant human IGF-1 s.c. and blood was sampled over 48 hours. Baseline total serum IGF-1 levels were similar in both groups, but peak levels were elevated significantly in CRF; this was apparently related to the reduced distribution volume in CRF subjects. CRF did not affect the metabolic clearance rate (MCR) of total serum IGF-1. Immunoreactive IGF binding protein-3 (IGFBP-3) levels were greater in CRF. Western immunoblots revealed that the apparent increase in IGFBP-3 was largely due to an increase in immunoreactive fragments. IGFBP-3 protease activity was not increased. Thus IGFBP fragment accumulation likely reflects reduced fragment clearance. Western ligand blots revealed elevated 30 and 34 kDa IGFBP levels and IGFBP products in CRF serum. Serum acid labile subunit levels were unchanged in CRF. Peak free IGF-1 levels and the MCR of free IGF-1 did not differ between groups. In both groups the MCR of free IGF-1 exceeded the MCR of total IGF-1 by approximately 30-fold. These data suggest that in CRF patients receiving s.c. IGF-1: (a) total serum IGF-1 levels are increased as a result of elevated circulating IGFBPs that may restrict the distribution of IGF-1 beyond plasma; (b) serum free IGF-1 levels are not altered; and (c) the IGF-1 MCR is unchanged in CRF. Thus, in advanced CRF, apart from a reduction in the total IGF-1 volume of distribution the pharmacokinetics of IGF-1 are largely unaltered.

Circadian blood pressure variation versus renal function

Several published reports describe an abnormal circadian blood pressure profile in chronic renal failure subjects. Factors other than renal failure, including age, diagnosis of diabetes mellitus, autonomic dysfunction, and race, also may affect circadian blood pressure profiles. To further elucidate the relationship between renal function and circadian blood pressure variation, we compared day/night circadian blood pressure changes in three groups of male veteran hypertensive patients: group A, creatinine clearance (CC) > 80 mL/min, n = 20; group B, CC 20 to 80 mL/min, n = 19; and group C, CC < 20 mL/min, n = 14. We use postural changes in catecholamines, renin, and aldosterone as a measure of autonomic function. No significant difference in day/night percent change in systolic, diastolic, mean arterial pressure (MAP), or heart rate was seen by renal function group. Regression analysis using age, diagnosis of diabetes mellitus, postural hormonal changes, and creatinine clearance found race to be the only significant predictor of the day/night percent change in MAP, ( P < 0.05). Compared with whites, black subjects had higher nocturnal heart rates ( P = 0.01); smaller day/night heart rate changes ( P = 0.03); significantly higher diastolic blood pressure ( P = 0.01); and a trend toward smaller day/night change in diastolic blood pressure ( P = 0.06). In conclusion, renal function level does not influence day/night blood pressure changes. The blunting or reversal of the normal circadian blood pressure pattern seen in some chronic renal failure hypertensive subjects may be attributable to the association between chronic renal failure and cofactors associated with abnormal circadian blood pressure, including black race and possibly severity of atherosclerosis.

The Pharmacokinetics and Pharmacodynamics of Methylprednisolone in Chronic Renal Failure.

Methylprednisolone (MP) pharmacokinetics and its directly suppressive effects on cortisol secretion, circulating T-cells, and basophils in blood were compared in six chronic renal failure (CRF) subjects and six healthy controls after an IV administration of MP 0.6 mg kg(minus sign1) as the sodium succinate ester. The CRF subjects were studied between hemodialysis treatments. The total clearance of methylprednisolone sodium succinate (the prodrug) was reduced by 40% in CRF; however, the pharmacokinetics of methylprednisolone remained unchanged. Methylprednisolone clearance was approximately 280 ml h(minus sign1) kg(minus sign1) and volume of distribution was about 1.1 L kg(minus sign1). Physiological pharmacodynamic models were applied for the immediate effects of MP, based on the premise that receptor binding is followed by rapid suppression of the secretion of cortisol and recirculation of basophils, T-helper cells, and T-suppressor cells, which persist until inhibitory concentrations (IC(50)) of methylprednisolone disappear. The difference in IC(50) for each pharmacodynamic parameter was not statistically significant, suggesting no difference in the responsiveness of these factors to methylprednisolone in CRF. As the pharmacokinetics of other corticosteroids are altered in CRF, the lack of pharmacokinetic and pharmacodynamic changes of methylprednisolone may engender a therapeutic advantage for this corticosteroid in CRF.

Decreased O2 consumption by PMNL from humans and rats with CRF: role of secondary hyperparathyroidism.

Bactericidal ability of polymorphonuclear leukocytes (PMNL) is impaired in chronic renal failure (CRF). This function of PMNL is mediated by the generation of oxidizing radicals and the latter event requires O2 consumption by these cells. The present study examined both basal and FMLP-stimulated rise in cytosolic calcium ([Ca2+]i) and O2 consumption of PMNL from normal subjects and hemodialysis patients and from CRF rats, and evaluated the potential role of secondary hyperparathyroidism of CRF on these properties of PMNL. Basal levels of [Ca2+]i were significantly higher, and FMLP-induced increments in [Ca2+]i were significantly lower in PMNL of both humans and rats with CRF than in normals. Basal and FMLP-stimulated O2 consumption were significantly lower in CRF subjects and rats than in normals. These derangements were prevented by prior parathyroidectomy of CRF rats or by their treatment with verapamil from day one of CRF. Also, therapy of rats with pre-existing CRF with this drug reversed the abnormalities in [Ca2+]i and in O2 consumption of PMNL. The data indicate that: (1) CRF is associated with derangements in the homeostasis of [Ca2+]i of PMNL and their oxygen consumption, (2) these abnormalities are, most likely, mediated by the state of secondary hyperparathyroidism of CRF, and (3) verapamil, which blocks the PTH-induced entry of calcium into cells, and prevents as well as reverses these PMNL dysfunctions. These results implicate the excess PTH of CRF in the genesis of the defective bactericidal function of PMNL, and assign a new dimension to PTH toxicity in CRF.

Glucose and amino acid metabolism in chronic renal failure: effect of insulin and amino acids.

The effects of hyperinsulinemia and hyperaminoacidemia on glucose and amino acid metabolism were examined in 16 control and 13 chronic renal failure (CRF) patients under two conditions: 1) euglycemic hyperinsulinemia and 2) amino acid infusion. All studies were performed with continuous indirect calorimetry and [1-14C]leucine infusion. In CRF patients insulin-mediated whole body glucose metabolism was reduced by 35% (4.41 +/- 0.50 vs. 6.76 +/- 0.73 mg.kg-1.min-1, P less than 0.01), primarily due to a decrease in nonoxidative glucose disposal (1.70 +/- 0.70 vs. 4.32 +/- 0.60 mg.kg-1.min-1, P less than 0.01); glucose oxidation was similar in both groups. In the postabsorptive state total leucine turnover (1.56 +/- 0.06 vs. 1.75 +/- 0.06), leucine oxidation (0.25 +/- 0.01 vs. 0.30 +/- 0.01), and nonoxidative leucine disposal (1.29 +/- 0.06 vs. 1.40 +/- 0.07 mumol.kg-1.min-1) were reduced in CRF vs. control subjects (all P less than 0.05). In response to hyperinsulinemia, endogenous leucine flux (index of proteolysis), leucine oxidation, nonoxidative leucine disposal (NOLD) (index of protein synthesis), and net leucine flux into protein were similar in CRF and control subjects. In contrast, the ability of hyperaminoacidemia to enhance NOLD (1.54 +/- 0.11 vs. 2.10 +/- 0.10 mumol.kg-1.min-1, P less than 0.01) and net leucine balance (0.27 +/- 0.05 vs. 0.41 +/- 0.05, P less than 0.05) was reduced in CRF patients.(ABSTRACT TRUNCATED AT 250 WORDS)