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Biomedical subjects

Claudio Ronco

Publications and source records attributed to Claudio Ronco.

At least 127 records · Page 7Linked to original sources
PubMed2003

Mononuclear leukocyte apoptosis in haemodialysis patients: the role of cell thiols and vitamin E.

BACKGROUND: An increased apoptotic rate of peripheral blood mononuclear leukocytes (PBMLs) in haemodialysis (HD) patients has been reported in several studies, but its underlying mechanisms remain poorly understood. Oxidant stress is a well known cause of cell damage, and several lines of evidence suggest that it might influence the induction and signalling steps of mononuclear cell apoptosis through different mechanisms so as to provoke disturbances of the intracellular pool of thiols (SHi). In this study, we investigated the in vitro apoptotic rate and SHi of PBMLs in end-stage renal disease (ESRD) patients on HD or peritoneal dialysis (PD). METHODS: Apoptosis and SHi were evaluated in vitro in PBMLs obtained from 40 ESRD patients (HD, n = 30 and PD, n = 10) and 10 healthy controls. A subgroup of HD patients was also studied before and after 1 month of treatment with a vitamin E-coated dialyser (CL-E). Cell thiols and viability were also assessed in the monocyte-like cell line U937 and PBMLs after incubation in the presence of uraemic plasma with or without supplementation of the antioxidants vitamin E (70 micro M) or N-acetyl-cysteine (NAC) (0.5 mM). RESULTS: After 24 h in culture, the PBMLs of HD patients, but not those of CAPD patients, showed an apoptotic rate twice that of healthy controls and a 40% decrease of SHi levels (P < 0.01 in both). A negative correlation between the apoptotic rate and SHi was observed in both patients and controls (r = 0.648, P < 0.001). Plasma and ultrafiltrate samples from HD patients contained solutes (mainly in the low-middle molecular weight range) able to trigger apoptosis and oxidative stress in U937 cells. The treatment of HD patients with CL-E, as well as the in vitro supplementation of U937 cells with vitamin E or NAC during the exposure to uraemic plasma, decreased the rate of apoptosis and partially restored SHi. CONCLUSIONS: This study showed an association between an increased apoptotic rate and decreased SHi in PBML of HD patients, but not of CAPD patients. These changes are partially due to different pro-apoptogens that accumulate in the plasma and are at least partially prevented by exogenous antioxidants able to restore SHi, such as vitamin E or thiol suppliers.

Aged↗
PubMed2003

The pathogenesis of septic acute renal failure.

PURPOSE OF REVIEW: Acute renal failure is a serious condition that affects as many as 20% of ICU patients. The most common causes of acute renal failure in the ICU patient are severe sepsis and septic shock. The mortality of acute renal failure in septic critically ill patients remains high despite our increasing ability to support vital organs. This is partly the result of our poor understanding of the pathogenesis of sepsis-induced renal dysfunction. Accordingly, a review of our current understanding of the pathogenesis of septic acute renal failure is timely and relevant. RECENT FINDINGS: Throughout the past half century, acute renal failure of acute illness has essentially been considered a hemodynamic disease caused by kidney ischemia, a view derived by findings in animal models. Unfortunately most such models are greatly deficient in that they do not reproduce the high cardiac output, low systemic vascular resistance state typically seen during human sepsis. Furthermore, most models inducing so-called acute tubular necrosis are based on ischemia-reperfusion (renal artery clamping), an event with little relevance to human sepsis. Recent research highlights a new possible and emerging concept for the pathogenesis of septic acute renal failure: acute apoptosis. This concepts fits well with the typical paucity of histologic changes seen in so-called acute tubular necrosis and with growing evidence of a role for apoptosis in organ injury during sepsis and inflammation in general. Furthermore, the authors present evidence that some potential treatments recently shown to affect the mortality of critically ill patients, (activated protein C, intensive insulin treatment, and low-volume mechanical ventilation) might have antiapoptotic activity. SUMMARY: This review suggests that, on the evidence available, septic acute renal failure is more likely to be an immune or toxic state rather than simply a hemodynamic condition. The authors speculate that future insights into its pathogenesis might lead to a paradigm shift away from the concept of acute tubular necrosis, which has never been convincingly shown in sepsis, to that of acute tubular apoptosis.

Acute Kidney Injury↗
PubMed2003

Prevention of acute renal failure in the critically ill.

Acute renal failure (ARF) is a common and important complication of critical illness and many interventions have been proposed to prevent it. The pathogenesis of acute renal failure during critical illness is poorly understood. Animal models are based on the induction of renal ischemia and do not reflect the dominance of sepsis as a cause of ARF in the clinical arena. Although biological rationale exists for several interventions, none have been shown to be effective in large randomized double-blind multicentre trials. The only interventions with close to level I evidence are confined to the attenuation of radiocontrast nephropathy. The effect on such interventions is, however, of limited clinical relevance to critically ill patients. The maintenance of adequate intravascular filling, cardiac output and renal perfusion pressure and the avoidance of hypoxemia, marked anemia and nephrotoxins remain the only justifiable interventions at this time.

Acute Kidney Injury↗
PubMed2003

Methods and reproducibility of measurement of resistivity in the calf using regional bioimpedance analysis.

UNLABELLED: The usefulness of regional bioimpedance analysis (RBIA) in determining the dry weight in dialysis patients is currently being investigated. The aim of this study was to evaluate the reproducibility of measurement of resistivity in the calf. METHODS: Twenty-five normal subjects and 10 patients undergoing regular hemodialysis were studied. Four electrodes inserted into a blood pressure cuff were placed on the calf. Bioimpedance was continuously measured over 3- to 5-min periods (Xitron Hydra). After a resting period of 1 min, cuff pressure was increased to above the systolic blood pressure (SBP) for a few seconds to expel excess ECF fluid and then deflated. The effect on recordings of moving the electrodes 2 cm higher and then 2 cm lower than the normal position was studied in 8 normal subjects. In a second study of reproducibility, post-dialysis measurements were made twice in 10 patients who maintained the same post-dialysis target weight throughout the study period. RESULTS: The mean resting resistivity rho(0) in normal subjects was 532.6 +/- 95 omega.cm rising to 583.9 +/- 99.7 omega.cm when cuff pressure was applied rho(p). The average values of rho(0) and rho(p) in patients post-dialysis were 489 +/- 74 and 537 +/- 77 respectively showing that there were no significant differences in rho(0) and rho(p) between normal subjects and patients post-dialysis. The mean values of change in resistivity when the electrodes were shifted between the lowest and highest positions on the calf were -3.66 +/- 4.45 and -1.44 +/- 3.82%, respectively. Repeat measurement of resistivity in patients post-dialysis varied by 2.04 +/- 2.29% while post-dialysis body weight varied by 0.17 +/- 0.47%. CONCLUSION: In this study, resistivity measurement by RBIA at the calf showed similar levels of fluid loading in patients post-dialysis as in normal subjects. This study also showed that change in electrode position resulted in a mean change in resistivity of <5% and repeated measurements showed a change in resistivity <3% while body weight changes were <0.2%. This technique appears to have an acceptable level of reproducibility for its application to the assessment of patient hydration.

Adult↗
PubMed2003

Sorbents in acute renal failure and the systemic inflammatory response syndrome.

Renal replacement therapy in acute renal failure is currently focused on the use of modifications of dialysis (continuous arteriovenous hemofiltration and hemodiafiltration) to remove middle molecular weight toxins, consisting of small proteins, and cytokines involved in the systemic inflammatory response syndrome (SIRS). Conventional high-flux dialyzers are not efficient at removing these molecules, prompting the investigation of sorbents to augment or replace dialysis. Sorbents have been developed to modulate SIRS by targeting cytokines such as IL-1, IL-6, IL-10, IL-18 and TNF, among others. Extensive pre-clinical studies are underway to demonstrate the clinical utility and safety of either adding sorbent hemoadsorption devices to hemodialysis, or the use of such devices alone in SIRS, sepsis, acute renal failure, cardiopulmonary bypass and end-stage renal disease.

Acute Kidney Injury↗
PubMed2003

Slow continuous intracorporeal plasmapheresis for acute fluid overload.

Intermittent dialysis is still the predominant treatment for acute or chronic renal insufficiency in the USA despite increasing evidence that slower and longer fluid management therapies are more beneficial to the patient. We have investigated the use of slow continuous intracorporeal plasmapheresis (SCIP) as a more efficient and hemodynamically stable alternative means of treating acute fluid overload. In this paper we discuss preliminary observations on the safety of SCIP catheter insertion, fluid removal, extraction and pathology in Yorkshire pigs. SCIP catheters removed plasma for extracorporeal plasma water removal without significant gross or histopathological changes. Blood chemistry and cell counts remained stable during therapy. Toxicological studies indicated no pyrogenicity, hemolysis, cytotoxicity, acute systemic toxicity, delayed-type hypersensitivity, or blood recalcification coagulation inhibition. Intracutaneous extracts caused only mild irritation. SCIP therapy appears to be safe for use in the removal of plasma and plasma water from experimental animals.

Acute Disease↗
PubMed2003

Blood purification in non-renal critical illness.

Extracorporeal therapies designed to remove substances from the circulation now include hemodialysis, hemofiltration, hemoadsorption, plasma filtration, cell-based therapies and combinations of any of the above. In recent years, there have been considerable advances in our understanding and technical capabilities, but consensus over the optimal way, and under what conditions to use these therapies does not exist. Consequently, we have initiated a series of conferences under the auspices of the Acute Dialysis Quality Initiative (ADQI). ADQI aims at establishing an evidence-based appraisal and set of consensus recommendations to standardize care and direct further research. The results of previous consensus conferences are available on-line at www.ADQI.net. ADQI conferences have focused on research and management of renal disease. However, extracorporeal therapies are being used or investigated in the management of many other disease processes including systemic inflammation, liver disease, cardiac disease and thrombotic diseases.

Animals↗
PubMed2003

Coupled plasma filtration adsorption: rationale, technical development and early clinical experience.

The adjuvant treatment of sepsis remains a major therapeutic challenge. Blood purification is theoretically appealing if the humoral theory of sepsis is accepted as the basis for intervention. In this setting, blood purification would provide a broad-based restoration of humoral homeostasis thereby avoiding both excessive inflammation and counterinflammation. Several techniques of blood purification have been tried or are under active investigation. One of these is the so-called coupled plasma filtration adsorption (CPFA). CPFA is a novel extracorporeal blood purification therapy aimed at nonselectively reducing the circulating levels and activities of both pro- and anti-inflammatory mediators during sepsis and multiorgan failure. In vitro studies have shown CPFA to be effective in binding a broad range of such mediators proving its technical efficacy. Subsequent animal models have shown a beneficial effect on survival in endotoxemia. These studies have provided the necessary technical developments and biologic rationale for initial human studies. Two phase I/IIa clinical studies have now been performed. Both studies have shown that CPFA improves blood pressure and restores immune function in patients with severe sepsis and multiorgan dysfunction. In this article, we will discuss some of the basic principles involved in sorbent technology, and how these may contribute to treatment efficacy, review animal experiments with CPFA and finally discuss the results of recent human studies and their implications.

Adsorption↗
PubMed2002

The first international consensus conference on continuous renal replacement therapy.

BACKGROUND: Management of acute renal failure (ARF) in the critically ill is extremely variable and there are no published standards for the provision of renal replacement therapy in this population. We sought to review the available evidence, make evidence-based practice recommendations, and delineate key questions for future study. METHODS: We undertook an evidence-based review of the literature on continuous renal replacement therapy (CRRT) using MEDLINE searches. We determined a list of key questions and convened a 2-day consensus conference to develop summary statements via a series of alternating breakout and plenary sessions. In these sessions, we identified supporting evidence and generated practice guidelines and/or directions for future research. RESULTS: Of the 46 questions considered, we found consensus for 20. We found inadequate evidence for 21 questions and for the remaining five we found data but no consensus. Full versions of workgroup findings are available on the Internet at http://www.ADQI.net. CONCLUSIONS: Despite limited data, broad areas of consensus exist for use of CRRT and guideline development appears feasible. Equally broad areas of disagreement also exist and additional basic and applied research in acute renal failure is needed.

Acute Kidney Injury↗