Effects of canrenone on Na+,K+ ATPase activity, arterial pressure and plasma potassium concentration in uremic hemodialyzed patients.
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Biomedical subjects
Publications and source records attributed to M Formica.
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Peripheral and peritoneal lymphocytes were assayed by numerical tests in adults on peritoneal dialysis. T lymphocytes were classified by monoclonal antibodies (OKT3, OKT4, OKT8) and B lymphocytes by the presence of surface immunoglobulins, using the immunofluorescence technique. Peripheral T cells showed no significant change from the normal, except for T suppressor cells which increased in patients with 2 or more peritonitis episodes. Examination of peritoneal lymphocytes showed a significant reduction in S-IgA lymphocytes (B cells bearing IgA receptors) and an increase in T-suppressor cells (OKT8+) in patients who developed peritonitis in the follow-up study. The implications of these results are discussed with particular reference to susceptibility to peritonitis.
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A test for the measurement of trace urinary albumin concentrations, which is suitable for the detection of microalbuminuria, was developed. The technique is an indirect enzyme-linked assay (ELISA) in which a fixed amount of anti-albumin antibody is placed into polystyrene tubes coated with human albumin, together with the urine sample to be tested. The albumin in the test specimen competes with the solid-phase albumin for binding to the added antibody. The test is precise (inter- and intra-assay coefficients of variation were 8.2% and 7.8%, respectively), accurate (mean recovery 102-106% for two human albumin preparations), and sensitive (detection limit 0.9 micrograms/ml). These characteristics are not dissimilar from those of the radioimmunoassay reported in the literature, with the advantages of being completely safe, easy to perform, and not requiring expensive equipment. Using this assay the urinary albumin excretion in 20 normal subjects was found to be 2.5 +/- 2.2 micrograms/min (range 0.9-7.5 micrograms/min) after 8 hours of bed rest and 4.5 +/- 5.7 micrograms/min (range 1.5-2.0 micrograms/min) after 8 hours of moderate physical activity.
Neutrophil oxidative metabolism was prospectively assessed in 9 consecutive patients undergoing cardiopulmonary bypass (CPB) with polypropylene hollow fiber oxygenators for open cardiac operations. Blood samples were collected at 10, 20, and 30 min of CPB. The generation of oxygen-free radicals by neutrophils was measured as luminol-enhanced chemiluminescence after stimulation with opsonized Zymosan and Phorbol Myristate Acetate. A significant increase in light emission was detected by using both the chemiluminescence stimulators. These data suggest that the contact of patient blood with foreign surfaces during cardiopulmonary bypass results in activation of phagocyte cells.
On March 2001 the regular quality control test of the water used for dialysis in an urban centre using a reverse osmosis system revealed a high level of organo-halogenated contamination. The compounds implicated were: trichloroethylene (trielene) [M.Wt. 131 D], tetrachloroethylene, trichloromethane (chloroform) [M.Wt. 121 D], chlorodibromomethane. The dialysis unit was closed. Water samples were analysed in duplicate. The table shows the values (in ppm or microgram/l) obtained for chloroform at the given times: March 8th, altered sample; March 12th, confirmation sample; March 16th, after osmosis membranes change; March 22nd, after carbon filtration replacement; March 26th, after softener resins substitution. The AAMI doesn't recommend any value for organo-halogenated compounds in dialysis water. In the past, the European Pharmacopoeia and the Italian Health Ministry released some reference values for tap water, values which were extended to water used for dialysis. The values are 1 ppm as reference value, 30 ppm as maximum accepted value for the sum of all organo-halogenated compounds, and 10 ppm as the recommended value. In conclusion, the problem was solved by progressive replacement of the components of the water treatment system, even though the real cause remained undetermined. No clinical symptom was recorded and no level of chloroform or trielene was detected in patients' sera despite the low molecular weight and low protein binding of the compounds. A strict control of the water quality and a more comprehensive and updated reference guide are needed for better and safer dialysis delivery.
BACKGROUND: Acute renal failure induced by contrast agents represents the third cause of acute nephropathy in hospitalized patients. Some mediators are potentially involved in this process: recent data underscored the role of oxidising agents and prophylactic administration of NAC showed a lower incidence of acute renal damage after using contrast agents. METHODS: We analyzed 100 patients consecutively undergoing coronary angiography and/or transluminal angioplasty: the study group was given NAC orally at a dose of 600 mg twice daily, on the day before and on the day of administration of the contrast agent, together with hydration, while the control group was given only the hydration protocol with hypotonic saline. RESULTS: Twenty patients had baseline serum creatinine concentrations > 1.2 mg/dL (mild renal insufficiency group). The mean dose of contrast agent (Iodixanol; Visipaque 320, Nycomed) was 203 mL/procedure, with no statistical difference between groups. Among the patients with normal renal function, 5.7% in the NAC group and 8.8% in the control group had baseline serum creatinine concentrations above 0.3 mg/dL after 48 hours (p=NS). In patients with mild renal failure, 16.6% in the NAC group and 0% in the control group had serum creatinine concentrations > 0.5 mg/dL at 48 h (p=NS). We found no significant differences in serum creatinine values at 48 hours vs. baseline in anyone (NAC group with normal renal function or mild renal insufficiency, control group with normal renal function or mild renal insufficiency). Similarly, serum creatinine values at either baseline or after 48 hours were not significantly different in patients with normal renal function (NAC vs. control group) and with mild renal failure. CONCLUSIONS: Our study showed no potential advantage in the prevention of acute nephropathy, induced by high volumes of contrast agent, through the administration of NAC in patients with normal renal function and mild renal failure. However, the NAC dose used in our study might not be sufficient in balancing the contrast agent volume employed in these procedures.
BACKGROUND: Septic shock represents an emerging pathology and sepsis and its complications are the main cause of death in medical and surgical intensive care units. Single-target therapeutic trials failed to demonstrate any benefit, suggesting that the unselective removal of different mediators may be a more appropriate approach. METHODS: We evaluated a new technique (CPFA) combining a plasma-adsorption (with plasma filter and sorbent cartridge) with a traditional 'slow' extracorporeal treatment on 10 patients, 7 men and 3 women (mean age 53.8+/-16.3), all on mechanical ventilation, with septic shock and multiorgan failure. To identify easily comparable clinical data, the hemodynamic parameters of the patients were monitored with a recently developed, minimally invasive technology, Pulsion PiCCO . RESULTS: We obtained significant improvement of pre- versus post-treatment mean arterial pressure 77.2+/-12.5 vs. 83.3+/-14.1 mmHg (p<0.0001), cardiac index 4.03+/-0.89 vs. 3.46+/-0.82 L/m2/min (p<0.0001), indexed systemic vascular resistances 1388+/-496 vs. 1753+/-516 dynes x sec/cm5 (p<0.0001), PaO2/FiO2 ratio 204+/-87 vs. 232+/-81 (p<0.0001), and norepinephrine requirements 0.13+/-0.07 vs. 0 y/kg/min after a mean of 5.3+/-2.7 consecutive treatments. The survival at day 28 was 90%. Seven patients were discharged from the intensive care unit after a mean of 37.8+/-24 days (range 10-93). CONCLUSIONS: Our data suggest a promising role for CPFA in improving hemodynamics and correcting vasoparalysis in septic shock. Moreover, the noninvasive monitoring of hemodynamic parameters with PiCCO could become a useful tool for estimating the effect of treatment and gaining easily comparable data in different patients.
HFR is an integrated hemodiafiltration system that utilizes a double chamber filter to separate convection from diffusion. The ultrafiltrate is regenerated by passage through a sorbent cartridge made up of resin and activated carbon. A small percentage of patients using this technique had gastrointestinal symptoms that included nausea/vomiting, diarrhea and/or stomach cramps approximately 1-2 hours after the start of HFR. We undertook a series of investigations to try and elucidate the cause of these reactions. Since the majority of the patients were taking ACE inhibitors, attention was focused on contact phase activation. Healthy and uremic plasma were incubated with different components of the HFR circuit. The activated carbon caused a moderate activation of factor XII and production of kallikrein, while there was no activation for the lines, double filter or resin. Patients taking ACE inhibitors may be at risk for treatments involved with contact phase activation as ACE inhibitors also block the degradation of bradykinin. A new sorbent cartridge has now been developed that contains only resin.
HFR is a hemodiafiltration method with regeneration of the ultrafiltrate. It consists of a double chamber filter that separates convection from diffusion. The ultrafiltrate exits from the convective filter, passes through a sorbent cartridge where uremic toxins bind to the sorbent. The "purified" ultrafiltrate is then returned to the patient. This study undertook a series of in vitro and ex vivo experiments to optimize the conditions for maximal adsorption and treatment efficacy. An emphasis was placed on a resin only cartridge as previous studies suggested that some patients may be sensitive to the activated carbon, particularly if they are taking ACE inhibitors.
Adsorbent therapies have become increasingly popular over the last several years as they permit an additional method to selectively or non-selectively remove toxins. Adsorbents offer a unique removal strategy as they have an extremely high adsorption capacity due to their great surface area. This paper describes experiments that utilized a synthetic divinylbenzene styrenic resin cartridge to remove uremic toxins from chronic renal failure patients. The resin-only cartridge was tested as an alternative after a small number of patients (primarily taking ACE inhibitors) experienced gastrointestinal problems using hemodiafiltration with on-line regeneration (HFR). Subsequent laboratory evidence suggested that the particular carbon used in the cartridge was able to activate contact phase activation. This could potentially cause problems in patients taking ACE inhibitors, as they are unable to degrade bradykinin efficiently. The resin-only cartridge was tested in at 6 centers throughout Italy and included patients that had experienced previous reactions to the carbon-resin cartridge. At the conclusion of the study, no adverse reactions were reported and the cartridge exhibited excellent removal of b2 microglobulin and angiogenin.
Several techniques are currently available in the continuous renal replacement therapy (CRRT) spectrum, adhering to different clinical conditions and illness severity. Commercially available machines have become more user-friendly, even for non-dialysis staff however, nephrologists need specific knowledge to give an adequate prescription that must be different from chronic hemodialysis. Competence and experience in the technical possibilities of CRRT lead to an individual ultra-filtration and treatment dose prescription. Clearances of solutes with different molecular weight can be modulated by coupling (combining) diffusion and convection, and by changing the fluid infusion rate. In addition, CRRT has an important impact on metabolism with its cooling effect, removal of nourishing substances and modification of electrolytic and acid-base balance. In septic patients standard CRRT has no specific indications in the absence of acute renal failure. Other extracorporeal therapies, such as high volume hemofiltration coupled with plasma filtration-adsorption (CPFA), have been developed aiming for a major influence on sepsis evolution. The versatility of CRRT has great value not only in adapting the treatment schedule to clinical conditions, but also in performing extracorporeal therapies in a wide array of logistical circumstances.
A new hemodiafiltration technique, acetate free biofiltration (AFB), has been recently introduced in the treatment of chronic uremia. It is performed with a buffer free dialysate and a simultaneous infusion in post-dilution mode of a sodium bicarbonate solution (concentration 145-166 mEq/l; infusion rate 1.2-2 l/h). A polyacrylonitrile hollow fiber AN69 HF 1.2 sqm dialyzer is employed. In acute studies pCO2 remains stable throughout the treatment, as well as pCO2. We have found a significant inverse correlation between delta[HCO3-] pre and post treatment and basal [HCO3-] (r = -0.88; p less than 0.001), with an excellent correction of uremic acidosis, avoiding post dialytic alkalosis. Our long term experience on 6 patients followed up to 31 months, allows us to consider AFB as a feasible and safe treatment, offering a good correction of uremic acidosis and an excellent hemodynamic tolerance. We propose AFB as a competitive technique with respect to bicarbonate hemodialysis, hemodiafiltration and standard biofiltration.
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