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Biomedical subjects

C Mion

Publications and source records attributed to C Mion.

At least 19 recordsLinked to original sources

[Recombinant human erythropoietin in uremic patients in substitute treatment].

The recent availability of Recombinant Human Erythropoietin (EPO) has radically stirred-up diagnosis and therapeutical approach of anemia in dialysis patients. By correcting anemia in a dose related manner in virtually all dialysis patients, clinical use of EPO has confirmed its remarkable efficiency. Correction of anemia marked by a rapid improvement in "well being" of patients is also objectively associated with the correction of most of the debilatating multiple organs dysfunction due to the uremic state. Hypertension is one of the more frequent and worrying complication associated with EPO therapy. Optimal use of EPO, integrating administration route and frequency of injections, will reduce the EPO doses needed and minimize cost and side-effects incidence. EPO represents a major advance in the treatment of chronic uremia. EPO opens a new therapeutic era offering for the first time a substitute to a kidney endocrine failure.

Erythropoietin

Platelet-activating factor production during hemodialysis: effect of BN 52021.

Platelet activating factor (PAF) production and platelet-lipoxygenase activity were studied during hemodialysis (HD) with cuprophane membranes. Six patients were treated with first-use dialyzers (FU), and 6 patients with reused dialyzers (RU). In a random and double-blind design, 2 HD were performed for each patient, with or without BN 52021 pretreatment, a selective PAF antagonist. Platelet and leukocyte counts were performed before pretreatment and 30 min before HD starting (T-30), at the beginning of HD (T0) and after 15 and 30 min of HD (T15, T30). PAF production was analyzed by direct phase HPLC. To determine platelet-lipoxygenase activity, 12-HETE was detected by reverse phase high performance liquid chromatography (HPLC) after blood stimulation by the ionophore A23187. In the FU group, PAF and 12-HETE were produced during the first 30 min of HD. After BN 52021 pretreatment, PAF production was suppressed and platelet-lipoxygenase activity reduced. In the RU group, neither PAF nor 12-HETE production occurred, and BN 52021 had no effect. We conclude that PAF, which was involved in both platelet and leukocyte activation that occurred during hemodialysis, can be considered as a bio-incompatibility marker.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid

The effects of reprocessing high-flux polysulfone dialyzers with peroxyacetic acid on beta 2-microglobulin removal in hemodiafiltration.

The reuse of dialyzers is widely practiced, especially in the United States. Despite this, the effects of reuse on the efficacy of removal of solutes and more recently proteins such as beta 2-microglobulin (beta 2M) are the subject of much debate. There is considerable evidence to suggest that reuse after cleansing and sterilizing with formalin, with or without bleach, maintains dialyzer performance. In this study, we have examined peroxyacetic acid use as the cleansing and sterilizing agent using Renatron machines. We analyzed reuse in 24 patients using polysulfone membranes in a hemodiafiltration (HDF) unit over a 2-year period. The mean maximum number of uses achieved was 20.1 +/- 0.5. Several factors considered clinically to influence the number of reuses achievable (hemoglobin, white blood cell, and platelet levels, erythrocyte sedimentation rate [ESR], and fibrinogen and total protein levels) were found not to influence the maximum number of uses obtainable. We then assessed prospectively the performance of 26 polysulfone dialyzers after peroxyacetic acid reprocessing up to 20 times, particularly with regard to their ability to remove beta 2M. We report that this combination of polysulfone membranes reprocessed with peroxyacetic acid used for HDF up to 20 times exhibits a maintained high level removal of compounds beyond a molecular weight (MW) of 12,000. Any secondary membrane formation that occurs appears not to influence the subsequent removal of beta 2M. Thus, we would recommend the use of peroxyacetic acid for reprocessing dialyzers in a safe and efficacious manner.

Adult

Failure of a daily haemofiltration programme using a highly permeable membrane to return beta 2-microglobulin concentrations to normal in haemodialysis patients.

In an attempt to return to normal serum beta 2-microglobulin levels in a group of seven ESRD patients, a programme of daily HF with highly permeable AN69 membranes was undertaken. Pre-HF beta 2-M serum levels stabilized after 4 days at 20 mg/l, only 40% lower than the initial concentration. A total of 985 +/- 20 mg beta 2-M was removed over the week. The beta 2-M release rate averaged 97 micrograms/min with a broad range of values (63-128 micrograms/min). beta 2-M release peaked at 602 micrograms/min 1 h after the end of the HF session before returning to baseline by 12 h post-HF. We conclude that a return to normal blood beta 2-M concentrations in ESRD patients seems quite unrealistic despite a highly intensive extracorporeal therapy. Therefore other therapeutic alternatives have to be designed to prevent or cure beta 2-M amyloidosis.

Adsorption

Whole blood serotonin levels are markedly elevated in patients on dialytic therapy.

The normal range for whole blood serotonin levels in chronic renal failure patients has not been defined. As serotonin may be implicated in platelet abnormalities, hypo- and hypertension and itch in dialysis patients, serotonin whole blood levels were measured in a group of patients with chronic renal failure and/or who were dialysis dependent. The levels were elevated in 12 patients with moderate (mean serum creatinine 335 +/- 54 mumol/l) chronic renal failure (270 +/- 46 micrograms/l) compared to 11 normals (163 +/- 17 micrograms/l, p less than 0.05; quoted normal range less than 300 micrograms/l) but did not correlate with serum creatinine levels. There was a marked elevation in serotonin levels in dialyzed patients, including those on hemodialysis (polysulfone, n = 6, 747 +/- 234 micrograms/l; cuprophane membranes, n = 6, 708 +/- 198 micrograms/l), hemodiafiltration (n = 12, 695 +/- 130 micrograms/l) and especially peritoneal dialysis (n = 6, 1,148 +/- 162 micrograms/l). All results were significant (p less than 0.01) compared to normals and compared to the nondialyzed group (p less than 0.05). The level of serotonin decreased during hemodialysis regardless of the membrane used. There was no positive correlation of serotonin levels with pruritus or hypertension, although there was a negative correlation with systolic blood pressure. The reference range for serotonin whole blood levels needs to be broadened when considering dialyzed patients.

Adult

Biochemical characterization of serum and urinary beta 2 microglobulin in end-stage renal disease patients.

Since the identification of beta 2 microglobulin (beta 2-M) in haemodialysis-associated amyloidosis, the biochemical characterization of the different forms of beta 2-M has been sought by several groups. New beta 2-M isoforms (pI 5.1 and lower) have been identified in amyloid deposits, and it has been suggested that they are of pathogenetic importance. The finding of N-terminal proteolysed beta 2-M in amyloid deposits prompted the hypothesis that proteolysis would render beta 2-M more amyloidogenic. Finally, a 'novel beta 2-M' (pI 5.2) with a single amino acid replacement (Asn by Asp at position 17) has been reported as possibly specific for patients with dialysis associated amyloidosis, and consequently proposed as 'the amyloidogenic' form. We purified beta 2-M from serum of a newly haemodialysed patient and from urine of a transplanted patient in the early recovery period. Both patients were clinically amyloid free. Three pure isoforms were obtained from serum (pI 5.7, 5.3, and 5.1) and only two from urine (5.7 and 5.3). Further purification of each isoform was obtained by HPLC in a C4 column. Sequence analysis showed that all isoforms had an intact N-terminus. Tryptic digestion of the serum isoforms was performed after alkylation with iodoacetic acid and the peptides were isolated by HPLC in a C18 column. The 5.3 and 5.1 isoforms had identical peptide patterns with the appearance of an early peak missing in the 5.7 form. The sequence of this peptide showed a replacement of the D 42 (Asp 42) by N (Asn) after K41 (Lys 41).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

[Hemodiafiltration with on-line production of bicarbonate infusate: 5 years of clinical experience].

Despite its potential advantages HDF has not gained large clinical acceptance among nephrologist due to its technical complexity and to the large quantity of pharmaceutical substitution fluid needed. HDF with on-line production of substitution fluid from dialysate simplifies the procedure and reduces the cost of treatment session. We treated regularly 13 high risk and/or non-compliant patients (9 males, 4 females) with HDF for 46 +/- 17 months. HDF program consisted of 3 sessions weekly lasting 210 +/- 10 mn with blood flow rate 350 +/- 20 ml/mn and fluid volume exchange of 20 liters/session. High flux dialyzers (HF80, Filtral 16) were reused 6 to 13 times automatically on a Renatron machine with peroxyacetic acid solution as sole cleaning and disinfecting agent. Microbiologic quality of infusate was assessed by membrane filtration culturing method and LAL endotoxin determination. 3937 HDF sessions were performed. 57.140 I of substitution fluid were infused IV to patients. Eight pyrogenic reactions were observed: 2 due to septicemia related to catheter infection and 6 from unknown origin. Adequacy of program was achieved in all patients. Blood pressure control was satisfactorily obtained without antihypertensive medication in 12/13 patients. Effective weekly integrated urea clearances was 150 +/- 15 l/wk, KT/V index was 1.50 +/- 0.10, urea TAC 20 +/- 2 mM/l and protein catabolic rate 1.40 +/- 0.10 g/kg/24 h. We conclude that HDF with on-line production of bicarbonate substitution fluid is a safe and highly efficient method cost-competitive with bicarbonate HD, which offers an interesting alternative for renal replacement therapy.

Adult

[Parvovirus B19 infection revealed by acute renal insufficiency].

Human adult Parvovirus B19 infection is a well known disease most frequently seen in haematology and cancerology. To our knowledge, however, renal involvement in this context has never been reported. A case of severe infection caused by this virus is reported, where multiple organ involvement is associated with acute renal failure. The outcome was favourable with temporary dialysis and symptomatic treatment. Mechanisms of renal failure, presumably multifactorial, are discussed in the light of this case.

Acute Kidney Injury

[Prognostic factors of success in renal transplantation].

From January 1984 to January 1989, 139 kidneys were retrieved from 74 brain dead donors in our institution. The transplantation was performed either locally (79), or in an other French institution (40). The five year actuarial survival rate, for the 139 kidneys retrieved in Montpellier, was 65 percent. Many factors about the donor, the retrieval and the recipient, which may affect the graft survival, were entered in a Cox multivariate analysis. The minimal follow up duration was 18 months. The risk factors studied included: donor parameters (age, sex, cause of death, haemodynamic parameters and renal function); retrieval parameters (kidney alone or multiorgan harvesting, discoloration and renal perfusion quality); organ characteristics (multiple arteries and cold ischemia time); recipients parameters (age, sex, prior transplantation, local transplantation or not, and HLA matching). A first multivariate analysis included only pretransplant risk factors. The risk factors for graft loss, as identified by the Cox model, were in the order: donor's age (P = 0.03), arterial pressure (P = 0.01), prior transplantation of the recipient (P = 0.01) and kidney discoloration quality during the retrieval (P = 0.008). Early post transplant parameters were included within this Cox model (poor early renal function, need for dialysis, serum creatinine level at one week). The need for dialysis therefore was identified as the main predictive value (P = 0.002). The 4 other risk factors, selectioned in the first model, always remained significant.

Actuarial Analysis

[Coronary ischemia after kidney transplantation in patients over 60 years of age].

Many elderly patients (aged over 60) are waiting for renal allograft but are considered a risk population for myocardial infarction or sudden cardiac death. Between 1987 and January 1st, 1990, 22 elderly patients (16 men and 6 women; mean age 63.4 +/- 0.7 years; range 60-69 years) underwent cadaveric kidney transplantation. Twenty patients had been on haemodialysis for 4.8 +/- 1 years (range: 1-16.3), one had been on peritoneal dialysis for 5 years and one had developed chronic rejection of a previous cadaveric allograft. Among these 22 patients, 6 (27 percent) developed antibodies directed against the random lymphocyte panel and one had a second transplant. Cardiovascular risk factors were systematically estimated, including medical history, cervical arterial Doppler, echocardiography and stress thallium testing (STT). Coronary angiography was performed if there was evidence of myocardial ischaemia. STT did not show any coronary disease in 16 patients and was not maximal (less than 60 percent of maximal theoretical stress) in 4 patients. In 2 patients, STT showed myocardial ischaemia: one, with a history of angina, underwent coronary angiography and angioplasty; the other had silent ischaemia and refused coronary angiography. Two patients died of myocardial infarction. One of them was the patient with silent ischaemia and positive STT test. The patient with angioplasty had a successful transplantation 20 months later, without any cardiovascular complication. After 9 to 32 months of follow-up, 19 patients have functioning allografts (mean serum creatinine level 151 +/- 6 mumol/l). One patient lost his kidney from urinary fistula. Eight patients (36 percent) developed acute rejection and all responded to intravenous corticosteroids. No immunological transplant loss was observed. After 18 months, the graft actuarial survival rate was 85 percent. We conclude that elderly patients free of clinical or silent myocardial ischaemia are good transplant recipients. The cardiovascular risk could be prevented by using STT during the pretransplant screening. If the STT is not maximal or shows coronary ischaemia, coronary angiography is mandatory.

Actuarial Analysis

[Functional reversibility of chronic cyclosporine nephrotoxicity in patients after kidney transplantation].

The long term use of cyclosporin in renal transplant recipients may be complicated by chronic nephrotoxicity, evidenced by renal functional deterioration and suggestive histological lesions. In 11 renal transplant recipients treated with cyclosporin since 28 +/- 5.8 months, we reduced (n = 6) or stopped (n = 5) this drug after chronic nephrotoxicity was diagnosed. Five months later, we conducted hemodynamic studies and observed significant increases in renal plasma flow (I131 hippuran clearance from 239.5 +/- 106 to 327 +/- 50 ml/min/1.73 m2) and glomerular filtration rate (DTPA-TC clearance from 43 +/- 15 to 67 +/- 10 ml/min/1.73 m2) and a decrease in renal vascular resistances. We suggest that cyclosporin-associated chronic nephrotoxicity is accompanied by some degree of reversible vasoconstriction, or that histological lesions, particularly cyclosporin arteriolopathy, can disappear after cyclosporin withdrawal.

Chronic Disease

[Dilated cardiomyopathy during post-partum hemolytic and uremic syndrome (HUS)].

A 24-year-old woman presented a severe HUS followed 3 months later by a cardiac failure diagnosed echographically as a dilated cardiomyopathy. The patient was hemodialysed and successfully transplanted. Later course of dilated cardiomyopathy was favourable. Review of literature confirms the rare and severe nature of cardiac lesions occurring in the course of HUS. We suggest a related pathophysiology concerning these two entities.

Adult

[Urea kinetic model analysis in dialysis: from theory to practice].

Urea kinetic modeling (UKM) has been originally proposed by F. Gotch and J. Sargent as a guide to optimize and individualize the dialysis prescription in uremic patients. In a recent report, the US National Cooperative Dialysis Study group, showed the power of this approach compared to conventional methods. It was also concluded that dialysis adequacy could be predicted with a high success rate by determining three parameters; uremia represented by the Urea Time Averaged Concentration, dialysis dose defined as KT/V ratio, and dietary protein intake calculated from the urea generation rate. In spite of its potential usefulness, UKM has not gained clinical acceptance among nephrologists since it appeared always complicated due to its mathematical formulation or cumbersome to be used routinely in dialyzed patients. In this paper the authors will bring the reader from basic concepts to practical use of UKM to guide dialysis strategy. Limits of validity and difficulty in using this approach are also discussed. It is concluded that UKM by using very simple and basic parameters is a practical, and very powerful tool for assessing the dialysis adequacy and nutritional status of dialyzed patients. Direct quantification from dialysate (or ultrafiltrate) collection appeared a simple and precise method which should avoided multiple blood sampling.

Humans