[The point about...uremia and cancer]. / Le point sur ... urémie et cancer.

There have been long-lasting controversies as to whether uremic patients are prone to develop cancer. Recent epidemiological data support a small, but significant increase of various solid tumors, particularly those known to be induced by viruses. Paradoxically, either younger or female patients are the most exposed to the risk of cancer. In addition to factors linked to the underlying renal disease (e.g. analgesic abuse, "chinese herbs" or immunosuppressive drugs), uremia per se can enhance carcinogenesis through many different pathways: retention of various carcinogens; abnormalities of nucleic acids; decreased immune response; metabolic and nutritional changes (hyperhomocysteinemia, iron or selenium depletion...); deleterious effects of oxidative stress secondary to bioincompatibility reactions during dialysis. However, except for the ultrasonographic diagnosis of cystderived renal carcinoma, which has been shown beneficial in the younger patients, there should be no routine cancer screening peculiar to uremic patients.

Induction versus noninduction in renal transplant recipients with tacrolimus-based immunosuppression.

BACKGROUND: The aim of this study was to compare the efficacy and safety of induction treatment with antithymocyte globulins (ATG) followed by tacrolimus therapy with immediate tacrolimus therapy in renal transplant recipients. METHODS: This 12-month, open, prospective study was conducted in 15 centers in France and 1 center in Belgium; 309 patients were randomized to receive either induction therapy with ATG (n=151) followed by initiation of tacrolimus on day 9 or immediate tacrolimus-based triple therapy (n=158). In both study arms, the initial daily tacrolimus dose was 0.2 mg/kg. Steroid boluses were given in the first 2 days and tapered thereafter from 20 mg/day to 5 mg/day. Azathioprine was administered at 1-2 mg/kg per day. RESULTS: At month 12, biopsy-confirmed acute rejections were reported for 15.2% (induction) and 30.4% (noninduction) of patients (P=0.001). The incidence of steroid-sensitive acute rejections was 7.9% (induction) and 22.2% (noninduction)(P=0.001). Steroid-resistant acute rejections were reported for 8.6% (induction) and 8.9% (noninduction) of patients. A total of nine patients died. Patient survival and graft survival at month 12 was similar in both treatment groups (97.4% vs. 96.8% and 92.1% vs. 91.1%, respectively). Statistically significant differences in the incidence of adverse events were found for cytomegalovirus (CMV) infection (induction, 32.5% vs. noninduction, 19.0%, P=0.009), leukopenia (37.3% vs. 9.5%, P<0.001), fever (25.2% vs. 10.1%, P=0.001), herpes simplex (17.9% vs. 5.7%, P=0.001), and thrombocytopenia (11.3% vs. 3.2%, P=0.007). In the induction group, serum sickness was observed in 10.6% of patients. The incidence of new onset diabetes mellitus was 3.4% (induction) and 4.5% (noninduction). CONCLUSION: Low incidences of acute rejection were found in both treatment arms. Induction treatment with ATG has the advantage of a lower incidence of acute rejection, but it significantly increases adverse events, particularly CMV infection.

Multicenter trial of one HLA-DR-matched or mismatched blood transfusion prior to cadaveric renal transplantation.

BACKGROUND: The beneficial effect of blood transfusions before cadaveric renal transplantation on allograft survival, although previously well documented, has become controversial in light of their adverse effects. Recently, it has been suggested that their clinical benefits are due to HLA-DR sharing between the blood donor and recipient. METHODS: In this prospective study, 144 naive patients were randomly assigned to receive one unit of blood matched for one-HLA-DR antigen (N = 49), or one unit of mismatched blood (N = 48), or to remain untransfused (N = 47). Graft survival and acute rejection rate were analyzed in 106 cadaveric renal allograft recipients receiving the same immunosuppressive protocol. RESULTS: Graft survival was similar in the three groups at one and five years: 91.7 and 80% in untransfused patients, 90.3 and 79.3% in patients transfused with one DR-antigen-matched unit, and 92.3 and 83.7% in patients transfused with HLA-mismatched blood. The difference in the incidence of six-month post-transplant acute rejections was not statistically significant in the three groups: 12 out of 36, 33.3% in nontransfused patients; 6 out of 31, 19.4% in patients transfused with one DR-matched blood; and 13 out of 39, 33.3% in patients transfused with mismatched blood. CONCLUSION: The results of our prospective randomized trial showed that in a population of naive patients, one transfusion mismatched or matched for one HLA-DR antigen given prior to renal transplantation had no significant effect on the incidence and severity of acute rejection, and did not influence overall long-term graft outcome. Considering the potentially deleterious adverse effects of blood transfusions, the costs, and the considerable logistical efforts required to select and type blood donors, such a procedure cannot be recommended in a routine practice for patients awaiting cadaveric kidney transplantation.

Lp(a) is increased in hemodialysis patients according to the type of dialysis membrane: a 2-year follow-up study.

AIMS: Patients with chronic renal failure treated by hemodialysis develop lipoprotein abnormalities that may contribute to their increased risk ofatherosclerosis. This study shows lipid parameter follow-up procedure according to the type of dialysis membrane in an unselected population of 33 hemodialysis patients. PATIENTS AND METHODS: The study included 33 patients with end-stage renal disease and 110 healthy blood bank donors of Tenon Hospital. Cholesterol and triglycerides were determined by enzymatic methods, apoA-I, apoB by immunoturbidimetry and Lp(a) by immunonephelemetry. Apo(a) phenotyping was performed by agarose gel electrophoresis followed by immunoblotting. Patients and controls subjects were estimated by Student's t- and chi2-tests. RESULTS: Patients dialyzed with low-flux membranes had Lp(a) concentrations higher than patients dialyzed with high-flux membranes. Patients dialyzed with polyacrylonitrile membranes (AN 69) had an apoA-I concentration significantly lower than patients dialyzed with hemophane or polysulfone membranes. We also confirmed some of the lipid abnormalities and high Lp(a) concentrations in ESRD patients. CONCLUSION: These results may contribute to a more rational choice of the dialysis membrane in hemodialysis patients.

Failing arteriovenous hemodialysis fistulas: assessment with magnetic resonance angiography.

RATIONALE AND OBJECTIVES: The authors sought to evaluate prospectively magnetic resonance angiography (MRA) versus fistulography in the detection and characterization of complications associated with malfunctioning hemodialysis access fistulas (arteriovenous fistulas [AVF]). METHODS: Nineteen patients with clinical AVF dysfunction were studied by MRA and fistulography. Data from each study were collected prospectively and analyzed in a blinded manner. RESULTS: The main diagnosis was stenosis in eight patients, thrombosis in five patients (mural thrombosis with preserved flow in one), aneurysm without stenosis in two patients, and normal AVF in four patients. A hazy flow void, assumed to be related to turbulence, was observed in normal arterial anastomoses. When flow void was considered as a criterion of stenosis or thrombosis, one false-positive and one false-negative MRA study were determined, yielding a sensitivity and specificity of 92% and 86%, respectively. CONCLUSIONS: Magnetic resonance angiography is a feasible and sensitive technique with which to portray suspected malfunctioning hemodialysis access fistulas.

Diagnostic accuracy and prognostic value of combined dipyridamole-exercise thallium imaging in hemodialysis patients.

BACKGROUND: Non-invasive detection of coronary artery disease in dialysis patients, a major cause of mortality, often remains difficult. The aim of the study was to test the diagnostic and prognostic accuracies of combined dipyridamole-exercise thallium imaging in dialysis patients. METHODS: Dipyridamole-exercise thallium imaging and coronary angiography were both performed prospectively in 60 asymptomatic hemodialysis patients who were followed up, long term, by recording any major coronary event. RESULTS: Coronary angiography was abnormal in 13 patients (21%), and there was abnormal thallium uptake in 17 patients. Sensitivity, specificity, positive and negative predictive values, and overall accuracy of thallium to detect a coronary artery disease were 92, 89, 71, 98 and 90%, respectively. After a median follow-up of 2.8 years, 12 patients experienced at least one major coronary event (4 cardiac deaths, 5 myocardial infarctions and 3 revascularizations). Eight of the 17 patients with abnormal thallium uptake (47%) suffered a coronary event, compared to only 4 of the 43 patients (9%) with a normal thallium uptake (P < 0.001). The positive prognostic predictive value of thallium imaging was 47% and its negative predictive value was 91%. The probability of survival free of coronary events was significantly higher in patients with normal thallium uptake than in those with abnormal thallium uptake (crude risk ratio 7.6; P < 0.001) even after adjustment for several risk factors for cardiovascular disease (adjusted risk ratio 9.2; P < 0.005). CONCLUSION: In dialysis patients, combined dipyridamole-exercise thallium imaging is an accurate method for detecting coronary stenosis and for predicting future coronary events.

Relationship between left ventricular hypertrophy, myocardial contractility, and load conditions in hemodialysis patients: an echocardiographic study.

Left ventricular hypertrophy (LVH) is common and is an independent cardiac risk factor in dialysis patients. The aim of this study was to assess hemodynamic determinants of LVH and, more particularly, the relationship between left ventricular mass, myocardial contractility, and load conditions. Eighty dialysis patients aged 51 +/- 15 years were prospectively studied by echocardiography. LVH was detected in 62 patients (78%). Left ventricular mass was significantly correlated to both end-diastolic volume (r = 0.54; P < 0.001) and end-systolic stress/end-systolic volume, an index of contractility (r = -0.66; P < 0.001), but not to systolic blood pressure or end-systolic stress, both indexes of afterload. Thus, in dialysis patients, the degree of LVH is significantly correlated with the severity of both left ventricular dilatation and contractile myocardial failure, but not with left ventricular afterload.

[Complications of treatment by dialysis]. / Les complications des traitements par dialyse.

Only 30 years ago, the inevitable short-term outcome in patients with end-stage renal disease was death. Today, the widespread development of dialysis-transplantation programs and extended indications have totally revolutionalized the situation, yet despite great progress, quality of life and life expectancy remain inferior in uremic patients. Cardiovascular disease is the main cause of mortality, 50% of all deaths in chronic dialysis patients resulting from complex mechanisms leading to left ventricular hypertrophy, coronary artery disease and atheroma of the great vessels. A large number of factors are involved in disease progression including age, genetic factors and personal health status prior to dialysis as well as the nature of the initial renal disease and dialysis-related metabolic and cardiac output disorders among others. Morbidity is also higher in dialysis patients, mainly due to altered blood volume and pressure which respond variably to treatment. Other conditions include rythm disorders, diabetes, potassium depletion, hypoxemia. Angina is frequent and ischemia can occur in several territories, including the mesentery as reported by Hachache et of in this issue of La Presse Médicale. Prognosis depends heavily on events which occur prior to dialysis and thus on close collaboration between the nephrology team, the family physician and other specialists who must coordinate their efforts to identify early curable renal diseases and correctly manage moderate disease to prevent progression and avoid emergency dialysis situations.

Effects of long-term treatment with recombinant human erythropoietin on physiologic inhibitors of coagulation.

Recombinant human erythropoietin (rHu-EPO) in the treatment of renal anemia might predispose to an increased risk of thrombotic complications. In an attempt to comprehend the involvement of the physiologic inhibitors of coagulation in this process, we studied 2 groups of hemodialysis patients. Group I included 21 patients receiving a starting dose of 90 IU/kg/week s.c., and group II included 17 patients without rHu-EPO. The following coagulation tests were performed before rHu-EPO treatment, and after 1, 6 and 12 months: prothrombin time; activated partial fistula thromboplastin time; fibrinogen; plasminogen activity; antithrombin III activity; protein C activity; total and free protein S antigens, and C4b binding protein. Only the latter three parameters were changed in group 1, while high baseline levels of protein S antigens were found in both groups. A decrease in total and free protein S was observed within 1 month of treatment. At the 6th month total protein S returned to near pretreatment values, whereas a significant fall in free protein S (p = 0.007) was observed. All three parameters returned to near baseline values by 12 months. These results suggest that protein S activity can be altered at the beginning of EPO therapy, a change that under favoring circumstances might contribute to the thrombotic events reported during the early phase of rHu-EPO treatment.

[Diagnostic value of myocardial thallium stress scintigraphy in the detection of coronary artery disease in patients undergoing chronic hemodialysis]. / Valeur diagnostique de la scintigraphie myocardique au thallium sous stimulation dans la détection de la maladie coronarienne chez l'hémodialysé chronique.

Atherosclerotic heart disease is the leading cause of death in patients with end stage renal disease, but its non invasive detection remains difficult because of a low efficacy of exercise testing. The aim of the study was to evaluate diagnostic accuracy of thallium myocardial imaging after dipyridamole combined with exercise. Forty two chronic dialysis patients (34 men, 8 women) aged 55 +/- 11 years (range: 36 to 75) without symptom of angina nor myocardial infarction were studied. In each patient, an echocardiography, a myocardial scintigraphy with dipyridamole combined with symptom-limited exercise, and coronarography were performed. A coronary heart disease was diagnosed by coronarography in 10 patients (4.5 and 1 respectively with 1, 2 and 3 vessels diseased). Echocardiography detected a left ventricular hypertrophy (LVH) in 26 patients and a regional asynergia in 14 patients. A positive scintigraphy was present in 11 patients. Three false-positive and 2 false-negative on scintigraphy were noted. Sensibility, specificity, positive predictive value and negative predictive value were respectively evaluated at 80, 73, 73 and 93%. All the five patients with either false-positive or false-negative scintigraphy exhibited a LVH. CONCLUSION. In chronic dialysis patients, coronary heart disease may be detected by thallium myocardial imaging after dipyridamole combined with exercise.

[How to diagnose and treat peritoneal infections in patients with terminal chronic renal insufficiency treated by peritoneal dialysis]. / Comment diagnostiquer et traiter les infections péritonéales chez les malades en insuffisance rénale chronique terminale traités par dialyse péritonéale?

There have been improvements in the technique of peritoneal dialysis (PD) over the last ten years. However, peritoneal infections remain the major complication associated with this treatment, and the risk of infection cannot be accurately predicted. Nevertheless, it is widely accepted that simple connections should be replaced by improved systems of connection, and that patient training is important. Peritoneal infection should be suspected when the dialysate is turbid, whether or not associated with peritoneal irritation. None of the various techniques used for the culture of dialysates has been shown to be either more sensitive or more specific than any of the others. Thus, collaboration between the physicians supervising the dialysis and microbiologists is necessary to choose the culture techniques best adapted. The sensitivity should be at least 85 to 90%. If the sensitivity is lower, the techniques used should be reconsidered. There have been several hundred publications assessing treatments of peritoneal infections associated with PD. However, no particular antibiotic treatment has been demonstrated to be systematically superior. The use of associated antibiotics seems to be preferable initially, until the causative agent has been identified. For example, vancomycin with a third generation cephalosporin seems to be the association of choice, because of its efficacy, tolerance and ease of use. The optimal duration of treatment has not been established by randomised study, but 10 days is commonly used for Gram-positive infections, and longer for Gram-negative. Whatever the treatment used, the success rate should be at least 80 to 90%. Randomised trials with sufficiently large numbers of patients are required to determine the indications and delay before withdrawal of the DP catheter in cases of peritonitis which do not respond to antibiotics.

The management of uraemia in the elderly: treatment choices.

The particularity of geriatric medicine and the lack of information due to the fact that geriatric nephrology dates back only 10 years explains why the management of chronic uraemia among the elderly presents itself as a succession of difficult dilemmas. (1) Should causes of chronic renal failure be systematically determined and treated? Risk-benefit assessments of the investigations and treatments involved in preventing or slowing down the evolution to end-stage renal disease (ESRD) are required to answer this question. (2) In cases of ESRD, should dialysis always be considered? The fact that life expectancy is limited for the aged does not justify depriving them of treatment. Nevertheless, in some borderline situations, conservative treatment may be preferable. (3) When should dialysis be started? Currently the mortality before the 90th day of dialysis is very high among elderly patients. To improve results it is probably necessary to determine appropriate criteria for starting treatment before complications occur. (4) What is the best method for the first treatment? There is much controversy about the respective advantages of haemodialysis and peritoneal dialysis. The choice depends on the individual's medical and social conditions. (5) Should dialysis treatment be stopped, and, if so, in this case, when? The large acceptance rate of elderly patients for dialysis implies that withdrawal of treatment must sometimes be considered. Fears linked to this dilemma probably explain why some physicians choose to exclude elderly patients from dialysis. It seems to us more ethical to treat this group of patients and assume responsibility for stopping treatment should it be necessary.

[Possible indications for human recombinant growth hormone in adults: current data and future perspectives]. / Indications possibles de l'hormone de croissance humaine recombinante chez l'adulte: données actuelles et perspectives d'avenir.

Growth hormone (GH) secretion persists during adulthood with mostly metabolic effects, stimulating lipolysis and protein synthesis. Besides GH-deficient patients, other adult patients might in the future benefit from recombinant GH (rhGH) therapy. These conditions would mainly include: 1. Highly catabolic states in intensive-care patients (conflicting results); 2. Osteoporosis, because of significant, although moderate improvement in bone density; 3. Aging: compensating for age-related GH-deficiency has yielded positive results concerning nutritional status; in the elderly however, the risk of side-effects, above all hypervolemia, should not be overlooked; 4. Uremia, frequently associated with poor nutritional status: preliminary results in hemodialysis patients are certainly encouraging; rhGH coupled with intradialytic parenteral nutrition might be particularly efficient. Treatment of uremic patients before end-stage renal failure seems also to be contemplated since, in spite of hyperfiltration and glomerulosclerosis observed in rats receiving high doses of rhGH, no case of worsened renal failure has ever been reported in pre-dialysis children treated for stunted growth.

Autoimmune haemolytic anaemia after ABO-match, ABDR full match kidney transplantation.

We report a case of autoimmune haemolysis after an ABO- and ABDR-identical kidney transplantation which leads to the discussion of the role of cyclosporin A (CsA). A 46-year-old woman with end-stage renal disease and no history of auto-immune disease received an ABO- and ABDR-identical first renal allograft from a cadaver donor. On day 16, while on a heavy sequential immunosuppressive regimen including anti-thymoglobulins, azathioprine (Aza), prednisolone (Pred) and CsA, she developed an autoimmune haemolysis with positive Coombs test, IgM+C type. Elution of antierythrocyte antibodies did not enable us to identify any specificity. Haemolysis lasted 45 days before haemoglobin slowly increased after CsA had been greatly reduced. Direct antiglobulin tests remained positive 5 months after transplantation and became negative the following month. Eight months after the transplantation the patient had a normal haemoglobin level and normal renal function. Although the typing of autoantibodies was not possible, our data suggest that this patient's haemolysis may be related to the clonal development of donor B lymphocytes in the recipient, favoured by an HLA A-B-DR identity and post-transplant CsA therapy, as exceptionally reported in the literature.

Fungal peritonitis in patients on peritoneal dialysis.

Fungal peritonitis (FP) is a serious complication of peritoneal dialysis, both in terms of morbidity and mortality. Available data on the effectiveness of fluconazole in eradicating FP without catheter removal are still controversial. We reviewed 20 FP cases that occurred among 325 patients who underwent peritoneal dialysis in our center between January 1984 and January 1992, in order to establish whether a profile of patients at risk of developing FP could be identified and to evaluate the effectiveness of fluconazole in treating FP (7 cases). Age, sex, a particular cause of end-stage renal disease, and the presence of diabetes did not correlate significantly with the development of FP. The risk of FP increased in patients on immunosuppressive treatment. Sixteen of our 20 patients had bacterial peritonitis during the month before they developed FP. Nineteen were treated with antibiotics. Neither the type of bacterial organism isolated during the bacterial peritonitis preceding FP nor modality and duration of antibiotic treatment correlated significantly with the development of FP. Patients who subsequently developed FP were more frequently treated with antibiotics while in hospital (p < 0.001). Candida species accounted for 15 of our 20 FP cases (75%), with Candida albicans being by far the most common isolate. Treatment strategies varied among the 20 patients. The combination of intravenous or intraperitoneal administration of 5-fluorocytosine and oral administration of fluconazole was used in 7 cases: only 1 patient was cured without catheter removal, 1 patient died within the first 4 days of treatment, removal of peritoneal catheter was necessary in the other 5 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Plasma atrial natriuretic factor and blood pressure drops during hemodialysis.

The potential role of atrial natriuretic factor (ANF) in blood pressure (BP) drops during hemodialysis (HD) has been examined in 30 patients with end-stage chronic renal failure. Echocardiographic measurements and evaluation of cardiac parasympathetic function were performed prior to HD sessions, simultaneously with hormonal determinations. The plasma ANF level was correlated with the peak value of the E wave and the Doppler index of the left ventricular preload and was more elevated in 'denervated' than in intact patients. During the HD sessions, the BP fell in 18 patients (group 1) and remained stable in 12 others (group 2), despite similar weight losses. Both groups differed by the basal values of plasma ANF, greater in group 1 than in group 2 (100.0 +/- 13.3 vs. 65.7 +/- 3.4 fmol/ml; p < 0.05). The magnitude of plasma ANF decrease was identical in both groups despite the BP decrease in group 1 at the end of the session. These results suggest that the ANF release depends not only on hemodynamics but also on cardiac innervation in dialyzed patients and that high plasma ANF levels are implied in the BP drops during HD session.

[Doppler echocardiographic evaluation of physical properties of the aorta and left ventricular geometry in normotensive hemodialyzed patients]. / Etude par échocardiographie doppler des propriétés physiques de l'aorte et de la géométrie ventriculaire gauche chez des patients hémodialysés normotendus.

Twenty-five patients undergoing hemodialysis therapy with a normal blood pressure (16 men, 9 women, age = 54 +/- 14 years) and 25 sex and age-matched healthy normotensive subjects were examined by doppler-echocardiography. Pulse wave velocity (PWV) in the thoracic descending aorta, diameter of the ascending aorta (AD), left ventricular mass (m), thickness-radius ratio (th/r), shortening fraction (SF), end systolic pressure-diameter ratio (P/D) and the ratio of late and early mitral velocity (A/E) were obtained. Pulse wave velocity, SF, P/D, were not significantly different in the 2 groups whereas AD, m, th/r, and A/E were significantly larger in dialysis patients than in controls (both, p < 0.001). These results indicate that in patients treated by hemodialysis with a normal blood pressure, a concentric left ventricular hypertrophy is associated with a normal aortic stiffness, suggesting a depressed myocardial contractility.

Improvement of severe secondary hyperparathyroidism in dialysis patients by intravenous 1 alpha(OH) vitamin D3, oral CaCO3 and low dialysate calcium.

Seventeen patients (9 men, 8 women; aged 27 to 75 years) who were on chronic hemodialysis for 1 to 14 years were included in the study because they had severe hyperparathyroidism diagnosed by elevated plasma alkaline phosphatase and on plasma intact PTH levels more than twice the upper limit of normal. They had been previously treated with various combinations of oral calcium and/or Al(OH)3 as phosphate binders, oral 1 alpha(OH) vitamin D3 metabolites and a dialysate calcium concentration (DCa) of 1.6 to 1.75 mmol/liter. When i.v. alpha calcidol was introduced DCa was reduced to 1.25 mmol/liter and CaCO3 taken with the meal was used as the sole phosphate binder. alpha calcidol was i.v. injected after the third dialysis of the week at a dose up to 4 micrograms per dialysis in order to obtain a predialysis plasma concentration of Ca at 2.5 +/- 0.2 and PO4 between 1.5 and 2 mmol/liter. All the other treatments were discontinued. During the six months of follow-up, the mean weekly dose of alpha calcidol was 6 micrograms and CaCO3 700 +/- 50 mmol. Plasma calcium (PCa) increased moderately from 2.35 to 2.47 mmol/liter (P < 0.05) whereas plasma PO4 (PPO4) did not significantly increase (1.56/1.64 mmol/liter). Total alkaline phosphatase and its bone isoenzyme activity decreased significantly to normal values [respectively from 186 to 83 IU (normal: 135) and from 102 to 32 IU (normal < 33)] whereas plasma intact PTH decreased from 485 to 125 pg/ml (normal < 55).(ABSTRACT TRUNCATED AT 250 WORDS)