Targets for adapting intravenous iron dose in hemodialysis: a proof of concept study.

BACKGROUND: Intravenous iron is widely used to control anemia in dialysis patients and limits costs related to erythropoiesis-stimulating agents (ESA). Current guidelines do not clearly set upper limits for serum ferritin (SF) and transferrin saturation (TSAT). International surveys such as the Dialysis Outcomes and Practice Patterns Study (DOPPS) showed that this lack of upper limits potentially led nephrologists to prescribe iron infusions even for patients with a high SF. Recent publications have suggested a risk of short- and long-term adverse effects related to iron overload. We conducted a proof of concept study to assess the impact of reducing intravenous iron administration. METHODS: In a prospective 8-month study conducted in a hospital dialysis unit, we assessed the impact of a strategy designed to reduce iron infusions. Instead of the usual strategy targeting 30-50% TSAT irrespective of SF, intravenous iron was administered if and only if TSAT was below 20% and SF below 200 µg/L. Routine practices for ESA remained unchanged: hemoglobin target 10-12 g/dL; ESA delivered monthly and dose corrected by 25% as necessary; ESA discontinued temporarily if hemoglobin >13 g/dL; methoxy polyethylene glycol-epoetin beta generally used. Tests were ordered monthly to monitor hemoglobin. Intravenous iron was administered weekly and ESA monthly. Baseline and 6-month TSAT, SF and hemoglobin levels were compared. RESULTS: Six-month data were available for 45 patients (31 M/14 F; 67.6 ± 14.0 y; 53.9 ± 85.7 months on dialysis). Patients experienced the following comorbidities: ischemic heart disease (n = 29, 44%), diabetes mellitus (n = 14; 31%), malignant disease (n = 11; 24%), transplantation (n = 11; 24%) and severe heart failure (n = 6; 13%). The mean weekly dose of iron declined from 77.8 ± 87.6 to 24.4 ± 52.9 mg per patient (p = 0.0003). SF decreased from 947.7 ± 1056.4 to 570.7 ± 424.4 µg/L (p = 0.0001), and TSAT from 41.5 ± 22.4 to 32.6 ± 13.7% (p = 0.01). Hemoglobin levels remained stable (11.13 ± 1.05 vs. 11.00 ± 1.16 g/dL, p = 0.54) as did ESA dose (126.4 ± 91.9 vs. 108.2 ± 112.7 µg/28 days, p = 0.07). CONCLUSIONS: Our study suggests that a regular hemoglobin level can be maintained using regular ESA doses combined with intravenous iron doses adapted to TSAT and SF thresholds lower than those used in routine practice. This strategy reduces the risk of iron overload.

Smoking cessation guidelines: evidence-based recommendations of the French Health Products Safety Agency.

Tobacco use is the leading preventable cause of death in developed countries. Millions of smokers are willing to stop, but few of them are able to do so. Clinicians should only use approaches that have demonstrated their efficacy in helping patients to stop smoking. This article summarizes the evidence-based major findings and clinical recommendations for the treatment of tobacco dependence of the French Health Products Safety Agency (AFSSAPS). Clinicians should enquire about the smoking status of each patient and provide information about health consequence of smoking and effective treatments available. These treatments include counseling (mainly individual or social support and behavioral and cognitive therapy) and pharmacological treatment with either nicotine replacement therapy (NRT) or bupropion LP. Pharmacological treatments should be used only for proven nicotine dependence, as assessed by the Fagerstrom test for Nicotine Dependence. The choice of pharmacologic treatment depends of the patient's preference and history and of the presence of contra-indications. The clinician should start with a single agent, but these treatments may be used in combination. Smoking behavior is a chronic problem that requires long-term management and follow-up. Access to intensive treatment combining pharmacological treatment and extensive behavioral and cognitive therapy should be available for highly dependent patients.

Schönlein-henoch purpura in children and adults: diagnosis, pathophysiology and management.

Schönlein-Henoch syndrome is a form of systemic small-vessel vasculitis, characterised by vascular and/or mesangial immunoglobulin A1 deposits. The main clinical manifestations are vascular purpura, predominating on the lower limbs, and articular, gastrointestinal and renal symptoms. Pulmonary, cardiac, genital and neurological symptoms have also be observed. The syndrome usually affects children, whereas it is rare in adults. The frequency of renal involvement varies between individual studies (from 20 to 100%). Renal manifestations are usually mild and transient, although chronic nephropathies may occur. Overall, an estimated 2% of children with Schönlein-Henoch purpura progress to renal failure and up to 20% of children with nephritis treated in specialised centres require haemodialysis. The renal prognosis appears to be worse in adults. Aetiological investigations are required, as a triggering factor is found in approximately half the patients (e.g. viral, bacterial and parasitic infections, drugs, toxins, systemic diseases and cancer). Dapsone has beneficial effects on cutaneous, gastrointestinal and articular manifestations in adults, especially those with chronic forms. Corticosteroids may be useful for refractory abdominal pain. Methylprednisolone pulse therapy, immunosuppressive drugs (e.g. cyclophosphamide and azathioprine), plasma exchange and polyclonal immunoglobulin therapy are beneficial in very rare life-threatening forms of the disease and in rare instances where renal function is compromised.

Increased intestinal intra-epithelial T lymphocytes in primary glomerulonephritis: a role of oral tolerance breakdown in the pathophysiology of human primary glomerulonephritides?

BACKGROUND: There is increasing evidence that some organ-specific and generalized autoimmune diseases in humans might be related to a breakdown of oral tolerance. We explored this hypothesis in human primary glomerulonephritides. We prospectively counted intraepithelial T lymphocytes in the duodenal mucosa (as a marker of rupture of oral tolerance), together with IgA1 and IgA2 mucosal plasma cells, in patients with primary glomerulonephritides. METHODS: We investigated eight adults with immune-complex glomerulopathy (membranous nephropathy+membranoproliferative glomerulonephritis), 16 adults with an idiopathic nephrotic syndrome, and 25 adults with IgA nephropathy. Patients with glomerulonephritides were compared to two control groups: group 1 consisted of nine healthy adults; group 2 comprised five adults with coeliac disease before dietary gluten withdrawal or during a clinical relapse related to gluten ingestion. (The latter disease is associated with increased numbers of intraepithelial T lymphocytes, and a breakdown of oral tolerance to gliadins is involved in the pathogenesis of coeliac disease). Duodenal fibroscopy was performed under neuroleptanalgesia. Four to six endoscopic biopsy specimens were taken from the second duodenum. Intraepithelial T lymphocytes were blindly counted on paraffin sections stained with haematein-eosin-saffron (HES), within the epithelium of a villus in a zone with at least 100 cells. Mucosal IgA1 and IgA2 plasma cells were blindly counted in a mucosal tissue unit by using specific mouse monoclonal antibodies directed against IgA1 and IgA2, with alkaline phosphatase anti-alkaline phosphatase (APAAP) revelation. As values were not normally distributed, we used non-parametric analysis of variance with the Kruskal-Wallis test, and compared median values by using the non-parametric Mann-Whitney test. RESULTS: Intraepithelial T lymphocytes were significantly more abundant in patients with primary glomerulonephritides and coeliac disease than in healthy controls (P < 0.0001 in the Kruskal-Wallis test): healthy controls, median 11 (range 4.65-16); immune complex glomerulopathy, 27.45*** (15-93); idiopathic nephrotic syndrome, 16.5** (9-26.5); IgA nephropathy, 26.10*** (11.3-47.5); coeliac disease, 55*** (20-80) (*P <0.05; **P <0.01; ***P < 0.005, Mann-Whitney test). No difference was found in the number of duodenal IgA1 and IgA2 plasma cells between controls and patients with primary glomerulonephritides. IgA1 and IgA2 plasma cells were increased in patients with coeliac disease. CONCLUSION: The significant increase in intestinal intraepithelial T lymphocytes in primary glomerulonephritides suggests a pathophysiological role of oral tolerance breakdown.

Imbalances in serum proinflammatory cytokines and their soluble receptors: a putative role in the progression of idiopathic IgA nephropathy (IgAN) and Henoch-Schönlein purpura nephritis, and a potential target of immunoglobulin therapy?

Following recent experimental data suggesting an aggravating effect of circulating proinflammatory cytokines on the histological lesions of IgAN, we studied changes in serum proinflammatory cytokines and their soluble receptors and antagonists in patients treated with polyvalent immunoglobulins (15 with severe nephropathy who had indicators of poor prognosis: heavy proteinuria, hypertension, altered renal function and Lee's histological grade III or IV; and 14 with moderate forms of IgAN who had permanent albuminuria > 300 mg/day and < 2000 mg/day, Lee's histological grade II and a glomerular filtration rate > 70 ml/min) in comparison with healthy controls (n = 20) and patients with non-IgA nephritides (n = 50). These were measured by means of specific immunometric assays before and after 9 months of immunoglobulin therapy. Total tumour necrosis factor (TNF) serum and IL-6 levels were elevated in IgAN patients before therapy, relative to controls, and normalized after immunoglobulin therapy. Levels of soluble TNF receptor of type I (sR55) and type II (sR75) increased on immunoglobulin therapy. TNF index alpha-55,75 used to assess biologically available TNF-alpha (ratio of total TNF-alpha divided by levels of soluble TNF receptors sR55 and sR75) was elevated before therapy and was below healthy control values after 9 months of immunoglobulin administration. Levels of serum IL-1 receptor antagonist were low prior to immunoglobulin administration in patients with severe forms of IgAN, and normalized on therapy. Serum interferon-gamma was unmodified. The histological activity index correlated with serum total TNF-alpha, TNF index alpha-55,75 and serum IL-6 levels, whereas proteinuria correlated with serum total TNF-alpha and TNF index alpha-55,75 but not with serum IL-6. These data suggest that the overproduction of proinflammatory cytokine is unbalanced by their natural antagonists in IgAN and Henoch-Schönlein syndrome. This process may play a role in the progression of the disease and be one of the targets of immunoglobulin therapy.

Type I membranoproliferative glomerulonephritis and HCV infection.

Type I membrano-proliferative glomerulonephritis (MPGN) is secondary to chronic bacterial, parasitic, viral (HB) infections, to autoimmune disorders or primary or malignant haemopathies. MPGN are thought to be linked to the deposition of immune complexes preformed in the circulation or formed in situ in the glomeruli. A link between HCV and type I MPGN was reported for the first time in 1993. In some patients, the renal clinical pattern is the most obvious (nephrotic syndrome) whereas in others liver disease or cryoglobulinaemia prevail. A risk factor of HCV infection exists in 80% of cases. Renal biopsy and scanning electron microscopy usually substantiate cryoglobulinaemia. Circulating cryoglobulins are most often detected, usually of type II. CH50 is decreased in 90% of patients and rheumatoid factors have been found in two-thirds of patients. The cryoprecipitate contains viral RNA and anti-HCV antibodies. The viral RNA is nearly always found in the cryoprecipitate. Analysing the viral genotype does not elicit predominance of any particular type. Viral genome detection in renal biopsy specimens appears to be technically difficult. Type I MPGN secondary to HCV infection appear to be improved by interferon-alpha therapy but treatment suspension is immediately followed by the recurrence of viraemia and nephrotic syndrome. Serological tests to detect anti-HCV antibodies and viral RNA by PCR in type I MPGN, so far considered as 'primary', are scarce and produce conflicting results: there might be a link between those glomerulopathies and HCV infection in the USA and in Japan only, not in Europe.

Immunomodulation with low-dose immunoglobulins for moderate IgA nephropathy and Henoch-Schönlein purpura. Preliminary results of a prospective uncontrolled trial.

Recently, our group has shown that a 3-month course of intravenous immunoglobulin (2 g/kg/monthly) followed by 6 months of intramuscular immunoglobulins (IMIG, 16.5%, 0.35 ml/kg every 15 days) was able to slow or to stop the decline in the glomerular filtration rate, to reduce proteinuria, hematuria, leukocyturia and the histological index of activity on renal biopsy in patients with severe forms of IgA nephropathy (IGAN) and Henoch-Schönlein purpura (HSP). The aim of this open prospective trial was to evaluate the efficacy and safety of low-dose immunoglobulin therapy in moderate IGAN and HSP with permanent proteinuria. Fourteen patients with moderate IGAN [idiopathic IGAN: n = 11; chronic idiopathic HSP: n = 3] and permanent albuminuria were treated with polyvalent IMIG (16.5%) for 9 months (0.35 ml/kg once a week for 1 month, followed by 0.35 ml/kg every 15 days for a further 8 months). Eligibility criteria in the study were Lee histological stage I, II or III, albuminuria between 300 and 2,000 mg/day and a glomerular filtration rate > 70 ml/min/1.73 m2. IMIG were well tolerated and only 1 patient withdrew from the trial. No viral, renal or immunological side effects were observed. IMIG induced a significant decrease in albuminuria as well as in the histological activity index in the 11 cases in which a follow-up biopsy was performed. There was also a decrease in serum IgA, serum beta 2-microglobulin and IgA immune complex levels, and an increase in serum IgG1 levels. Twelve of the 13 evaluable patients improved during treatment.

Prevention of thrombotic complications of the nephrotic syndrome by the low-molecular-weight heparin enoxaparin.

The nephrotic syndrome (NS) carries one of the highest risks of thrombotic complications. Consequently, over the last 15 years, some nephrologists have treated patients risk (i.e. those with albuminemia < 20 g/l and membranous nephropathy) with anticoagulants: either subcutaneous heparin (Kakkar protocol) or antivitamin K. Low-molecular-weight heparin (LMWH) has a longer plasma half-life and better bioavailability than standard heparin and can thus be administered as a single daily injection. LMWH also carries a lower risk of hemorrhage. We prospectively studied the safety and efficacy of the LMWH Enoxaparin for preventive anticoagulation in NS. In a preliminary study, 10 adult nephrotic patients with biological markers of thrombosis risk (severe hypoalbuminemia and/or anomalies of the fibrinolytic pathway and/or deficiency in coagulation inhibitors) were given 40 mg (4,000 U) of Enoxaparin daily for at least 3 months; 3 patients were treated for 3 months, 1 for 6 months and 6 for 12 months. Patients were assessed for silent thrombosis, using renal vein Doppler ultrasonography, lower leg vein Doppler ultrasonography and lung ventilation-perfusion scintigraphy, before entry to the trial and subsequently at 3-month intervals. As LWMH caused no obvious side effects and no thrombosis was observed during the pilot study, we then placed 55 adult nephrotic patients free of thrombosis on the same treatment. Patients were seen according to the usual calendar required by their individual illnesses. At each examination, patients were assessed for clinical signs and symptoms of thrombosis and side effects; plasma D-dimer and urinary fibrin-fibrinogen degradation products were also measured at each visit.(ABSTRACT TRUNCATED AT 250 WORDS)

[Mediastinal parathyroid adenoma. Localization by scintigraphy with methoxy-isobutylisonitrile]. / Adénome parathyroïdien médiastinal. Localisation par scintigraphie au méthoxy-isobutyl isonitrile.

Cases of inaccessible mediastinal parthyroid adenomas are rare (1% of parathyroid tumours). Previously, when the localization had been confirmed by imaging techniques, we performed exploratory cervicotomy, followed by sternotomy after explorations had been completed. This procedure required two operations and sternotomy sometimes gave blank results. We therefore prospectively evaluated technitium-99m labelled methoxy-isobutyl isonitrile scintigraphy to localize an adenoma in the anterior mediastinum. A 39-year-old patient was hospitalized for primary hyperparathyroidism which had caused nephrocalcinosis and decalcification. Serum calcium was 130 g/L and phosphorus 16 mg/L. Cervical echography, thallium scintigraphy and computed tomography were negative. Scintigraphy with technitium-99m labelled methoxy-isobutyl isonitrile visualized a tumoural formation in the upper mediastinum near the ascending aorta. Magnetic resonance imaging centered on this zone revealed a 13 x 8 mm formation. Cervicosternotomy was performed initially. A 280 mg parathyroid adenoma was removed. The three other parathyroid glands were found to be normal. Follow-up was uneventful and the serum levels of calcium and phosphorus rapidly returned to normal. This preliminary case has demonstrated that methoxy-isobutyl-isonitrile scintigraphy can be an effective first intention exploration for primary hyperparathyroidism. Further results should indicate its sensitivity and specificity.

High-dose immunoglobulin therapy for severe IgA nephropathy and Henoch-Schönlein purpura.

OBJECTIVE: To determine if polyvalent IgG is promising therapy for severe IgG nephropathy. DESIGN: Open prospective cohort study. SETTING: Referral nephrology unit. PATIENTS: 11 adult patients with severe IgA nephropathy (9 who had idiopathic disease and 2 who had Henoch-Schönlein purpura) and indicators of poor prognosis. INTERVENTION: Patients were given high-dose immunoglobulins (2 g/kg each month) for 3 successive months, followed by intramuscular immunoglobulins (preparation content, 16.5%; 0.35 mL/kg every 15 days) for another 6 months. MEASUREMENTS: Histologic changes were analyzed by comparing pre- and post-therapy renal biopsy specimens blindly, using an activity index (14-point scale), a sclerosis index (10-point scale), and a semiquantitative immunofluorescence test of immune deposits. Proteinuria, hematuria, leukocyturia, enzymuria, and global renal function (creatinine and polyfructosan clearances) were evaluated before and after intervention. RESULTS: Proteinuria (median level before intervention, 5.20 g/d; median level after intervention, 2.25 g/d), hematuria, and leukocyturia decreased substantially. The decrease in glomerular filtration rate was greatly slowed or stopped (median rate of decline in glomerular filtration before, -3.78 mL/min per month; after, 0 mL/min per month). The histologic index of activity (median index before, 5; after, 2) and the staining intensity of glomerular IgA and C3 deposits also decreased. Immunoglobulin therapy was well tolerated. CONCLUSIONS: Immunoglobulin therapy may be effective in treating severe IgA nephropathy and protecting renal function. However, prospective controlled trials must confirm these preliminary results.

Pneumocystis carinii pneumonia in the course of connective tissue disease: report of 34 cases.

OBJECTIVE: To determine the circumstances, the clinical features and the outcome of Pneumocystis carinii pneumonia (PCP) in human immunodeficiency virus (HIV)-free patients with connective tissue diseases (CTD). METHODS: Retrospective analysis of all cases referred 10 medical units in the last 10 years. RESULTS: A total of 34 cases of PCP in patients with CTD were studied (Wegener's granulomatosis, n = 12; systemic lupus erythematosus, n = 6; polyarteritis nodosa, n = 4; poly/dermatomyositis, n = 5; others, n = 7). The majority of patients (25/34 patients; 74%) presented PCP during the first 8 months following the diagnosis of CTD. At the time of diagnosis of PCP, most patients (32/34; 94%) were receiving corticosteroids (mean prednisone equivalent dose: 1.2 mg/kg/day) associated in 24 cases with cytotoxic agents (cyclophosphamide, n = 19; methotrexate, n = 5). Most patients were lymphocytopenic at the onset of PCP: 91% (31/34) of patients had fewer than 1.5 x 10(9)/l circulating lymphocytes and 76% (26/34) had fewer than 0.8 x 10(9)/l. The mean duration of prodromal symptoms was 6 days: this is much shorter than for AIDS associated PCP. Half the patients required intensive care for respiratory failure. Mortality was high (11/34 patients; 32%) although deaths were partly due to infections acquired in intensive care units. Among the 23 survivors, 10 (43%) received secondary prophylaxis for PCP and 13 (57%), received the usual therapeutic regimen. No relapse has been observed in either group with a mean followup of 22 months. CONCLUSION: Although rare, PCP must be considered in patients with any type of CTD and receiving cytotoxic agents and corticosteroids, particularly if they are lymphocytopenic. Thus, bronchoalveolar lavage must be rapidly performed in patients with CTD presenting with fever, pulmonary infiltrates, hypoxemia and lymphopenia.

Split tolerance in chimeric GVH mice.

The i.v. inoculation of parental spleen cells into unirradiated adult F1 hybrid mice results in a graft-versus-host reaction (GVHR). In the strain combination B10D2 --> (B10.BRx B10.D2) F1, this reaction is associated with thymic injury and transient but profound cellular immune deficiency. We further analysed the immune status of these mice 60 days after GVHR induction. Phenotypic studies of spleen cells showed that these mice were repopulated with parental lymphocytes resulting in a high degree of chimerism (85%). At this time, the mice looked healthy and recovered a normal cytotoxic T cell response (CTL) against allogeneic cells. GVH chimeric splenocytes were unresponsive against F1 hybrid cells in mixed lymphocyte culture (MLC), but exhibited anti-F1 CTL reactivity. We also analysed the anti-F1 reactivity of these mice in vivo. GVH chimeric splenocytes were unable to induce GVHR after injection into a new F1 hybrid and F1 GVH mice specifically rejected F1 bone marrow (BM) cells after lethal irradiation. Grafting a neonatal parental thymus prevented the rejection of F1 BM cells and restored CTL alloreactivity. It is concluded that the chimeric state induced by GVHR is associated with a split tolerance and that a radiosensitive thymic-dependent mechanism is involved in maintaining self-tolerance in these mice.

Proteinuria selectivity index--prognostic value in lipoid nephrosis and related diseases.

In order to predict the steroid response in lipoid nephrosis (LN), we studied age, sex, proteinuria level, histological features and proteinuria selectivity index (SI; ratio between IgG and transferrin clearances) in 52 LN cases (minimal-change disease: n = 39; focal glomerulosclerosis+IgM nephropathy: n = 13). The multivariate analysis showed that age, sex and proteinuria level were not contributive, whereas histology and SI were. The predictive value of SI was much higher than that of histological type (McFadden's r2: 47% vs. 22%, p < 0.001). Thus, SI should be systemically assessed in idiopathic nephrotic syndrome for reviewing the pathologic classification obtained by histology. However, if its prognostic value is lower than that of selectivity, initial renal biopsy remains necessary for diagnosis in adults.

[Immunodeficiency caused by graft versus host reaction. Extra-thymic effect of thymus in restoring immunity]. / Déficit immunitaire lié à la réaction du greffon contre l'hôte. Influence extra-thymique du thymus dans la restauration de l'immunité.

Cell-mediated immunity in lethally irradiated graft-versus-host mice can be restored after repopulation with syngeneic bone marrow cells and thymus grafting. The thymus is not only required for the maturation of T lymphocytes, but also for the inhibition of a radioresistant mechanism resulting in lymphoid cell rejection.

Monoclonal immunoglobulins in patients with renal transplants: characterization, evolution and risk factors.

Gammopathies were found to be present in 25 (13%) of 192 HIV-negative renal transplant recipients with more than 30 months follow-up prospectively investigated for monoclonal or oligoclonal immunoglobulins (mIg) by agarose gel electrophoresis and immunofixation. Eleven patients had only one monoclonal band, whereas 14 had two or more bands. Of these bands, 60% were IgG kappa, 29% IgG lambda and 11% IgM lambda or kappa, and 90% did not exceed 2 g/l. Most gammopathies occurred early post-transplant (median 5 months) and they were always transient. Some predisposing factors for mIg emergence could be identified: 1. age, but only in women, 2. duration of dialysis, 3. occurrence of prior cytomegalovirus infection, and 4. immunosuppressive regimen including cyclosporine. Serological evidence for active EBV infection was obtained in ten patients, but in six cases infection occurred subsequent to the finding of mIg. In eight patients, the clinical course was characterised by severe infection or tumours (one Kaposi's sarcoma, one B-cell brain lymphoma). The present findings and experimental studies support the view that the development of mIg in renal transplant patients is associated with a failure of regulatory T-cell function. This T-B-cell imbalance requires a careful follow-up in these patients.

[Monoclonal immunoglobulins in kidney transplantation. Characterisation, evolution and risk factors]. / Immunoglobulines monoclonales en transplantation rénale. Caractérisation, évolution et facteurs de risque.

Sera from 192 consecutive HIV negative renal transplant patients with more than 6 months follow-up were investigated for monoclonal or oligoclonal immunoglobulins (mIg) by immunoelectrophoresis or immunofixation. Gammapathy was present in 25 patients (13 percent). Eleven patients had only one monoclonal band, whereas 14 had two or more bands. Sixty percent were IgG K, 29 percent IgG lambda and 11 percent IgM lambda or K. Ninety percent of these mIg did not exceed 2 g/l; mIg appeared within 2-27 months following the transplantation (mean time-lag 8 +/- 6.4 months). The mIg were often transient: 20 disappeared within 1-33 months, most of them (14) being absent after 1 year of follow-up. Some risk factors for mIg could be identified: the patient's age (a risk factor only in women); the duration of dialysis; the occurrence of prior CMV infection; treatment with cyclosporine. The persistence of mIg was characterised by one or more of the followings: high titer of mIg, EBV infection or reactivation, inability to switch from IgM to IgG CMV antibodies. No significant association was found with the hepatitis B surface antigenemia, previous infection with hepatitis C or the number of rejection episodes. In 6 patients, the clinical course was characterised by severe infection or tumours. Although long-term follow ups are not yet available, patients in whom one or more mIg have been demonstrated should be carefully followed.

[Silent myocardial ischemia during hemodialysis in patients with chronic renal insufficiency]. / L'ischémie myocardique silencieuse au cours de l'hémodialyse des insuffisants rénaux chroniques.

A prospective search for episodes of silent myocardial ischaemia (SMI) was carried out during sessions of haemodialysis in 62 patients with chronic renal failure and was positive in 37.1% of the cases. The occurrence of SMI is correlated with the number of cardiovascular risk factors (p = 0.008) and particularly with diabetes (p = 0.012), smoking (p = 0.007) and age (p = 0.02), as well as with the type of nephropathy that had caused the renal failure (p = 0.02). During a 6-month follow-up two patients died; both had silent myocardial ischaemia on Holter recordings. In these anaemic patients, haemodialysis might sensitize the detection of ischaemia by the concomitant occurrence of hypotensive, hypovolaemic or hypoxic episodes, thus playing a aggravating role. The existence of such episodes characterizes a subgroup of patients at high cardiovascular risk for whom the prognosis and the best therapeutic approach remain to be determined.