Massive plasma arginine vasopressin (AVP) removal during hemofiltration stimulates AVP secretion in humans.

Arginine vasopressin (AVP) was measured in the plasma and its ultrafiltrate in 11 patients with end-stage renal failure treated by hemofiltration. Nineteen liters of ultrafiltrate were produced in 170 min and continuously replaced by an isoosmotic substitution fluid to maintain constant body weight. Plasma and ultrafiltrate AVP concentrations were not significantly different and did not change with time. The AVP clearance rate due to hemofiltration was 114 +/- 2.6 (+/- SE) ml/min, which represented more than two thirds of the predicted MCR in these patients. Corrected plasma osmolality, body weight, mean blood pressure, hematocrit, and PRA did not change during the hemofiltration session. These results indicate that there is a compensatory increase in AVP production which maintains plasma AVP unchanged in response to the increased MCR resulting from hemofiltration. The responsible stimulus could be a direct effect of the decrease in plasma AVP on the AVP-secreting neurones. Alternatively, ultrafiltration itself, via the hemodynamic changes it produces or the loss of an unrecognized inhibitory substance, may be the stimulus to AVP secretion.

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.

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.

Worldwide demographics and future trends of the management of renal failure in the elderly.

Aging will be a serious social problem in the future. The number of patients of 75 years and over with end-stage renal disease (ESRD) is bound to increase. The time has come to pay greater attention to their problems before and during dialysis treatment. Prevention of ESRD is an important challenge, especially in the field of vascular diseases which are the main cause of ESRD in the elderly. The exact number of elderly patients who will require dialysis in the next few years is difficult to foresee. It is only when the incidence of patients starting dialysis at 75 and over levels off that we may assume that elderly patients are no longer rejected from treatment; we could then assess the actual need in dialysis facilities. In elderly dialysis patients, mortality remains high. Improvements in geriatric medicine and dialysis techniques should contribute to better results in future years. As it is almost impossible to predict the survival and how an elderly patient will adapt to treatment, it appears more ethical to propose a trial of dialysis treatment, except in cases of severe dementia or malignancy. This large acceptance rate implies admitting that withdrawal from dialysis must sometimes be considered.

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)

Steady state pharmacokinetics of zopiclone during multiple oral dosing (7.5 mg nocte) in patients with severe chronic renal failure.

Zopiclone is a new hypnotic cyclopyrrolone with a short elimination half-life (5.3 h). The pharmacokinetic profile of this drug was studied in 7 chronic renal failure (CRF) patients given 7.5 mg nocte for 7 consecutive nights. The pharmacokinetic values obtained were compared with the corresponding values found in healthy young volunteers given the same repeated dosage regimen. C max and T max were not significantly different between the two groups but the C min of unchanged zopiclone (at 24 h) post-dosing was significantly (p less than 0.001) higher in CRF patients (8.16 +/- 5.34 ng/ml) than in healthy volunteers (1.90 +/- 0.82 ng/ml). The AUC values in CRF patients were also significantly increased during the seventh day (742 +/- 212 h ng/ml) compared to healthy subjects (408 +/- 66.5 h ng/ml) and the elimination half-life of zopiclone was also longer in CRF patients (about 8 h) than in the reference group (about 5 h). Nevertheless, the accumulation ratios remained similar in the two groups (1.09 +/- 0.18 in CRF patients and 1.02 +/- 0.2 in healthy subjects). Thus no evident accumulation of zopiclone appeared in the CRF patients. As in the healthy subjects, no metabolites were detected in the plasma of the CRF patients although at steady state the urinary excretion of zopiclone and its N-oxide and N-desmethyl derivatives (2.03% +/- 1.52% and 1.99 +/- 0.65% of the dose, respectively) was significantly decreased compared to healthy subjects (3.7% +/- 2.1% and 32.6% +/- 4.5%, respectively). Zopiclone thus represents a safe alternative to benzodiazepine hypnotic therapy in patients with renal impairment.

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.

Computerized patient management in a nephrology department.

An integrated approach is described for the computerized management of a nephrology department. On a medical point of view, the system comprises a minimum medical record for every patient, different specialized records and knowledge bases presently covering hypertension, diabetes and chronic renal failure. From a technical point of view, the methodology used integrates data and knowledge management techniques. Various individual reports facilitate patient management. For hypertensive patients, an expert system is combined with the record system. The results of a preliminary evaluation are reported and future developments considered.

[Renovascular hypertension with renal failure: value of renal revascularization]. / HTA rénovasculaire avec insuffisance rénale: intérêt de la revascularisation rénale.

The purpose of this work was to determine the effects of renal revascularization on blood pressure and renal function in 9 patients with arterial stenosis involving both kidneys (7) or a solitary kidney (2). There were five women and four men with a mean (SD) age for 64.5 +/- 7 years. The duration of hypertension ranged from 2 to 28 years (mean = 12 +/- 8). Blood pressure ranged from 210/100 to 260/150 mmHg, despite the use of three or more antihypertensive agents in 7 cases. The serum creatinine level, on presentation, ranged from 160 to 265 mumol/l (mean = 198 +/- 30 mumol/l). Intravenous pyelograms were not suggestive of renovascular disease in 4 of 7 cases. Digital angiography or arteriography demonstrated severe stenosis of the artery of the solitary kidney in 2 patients, severe bilateral atherosclerotic disease in 7 patients, three of them had complete occlusion of a main renal artery. During hospitalization, therapy with captopril (5 patients) or minoxidil (1 patient) lowered blood pressure in 3 cases, but induced a marked increase in serum creatinine level in 4 cases. In two patients, medically treated, severe and rapidly progressive impairment of renal function was observed. The seven remaining patients underwent surgical revascularization (two after unfructuous percutaneous transluminal angioplasty). One died 45 days later. Blood pressure control with diastolic blood pressure of 100 mmHg or less was achieved in the other six, although each patient continued to require antihypertensive medication (bitherapy: 2, monotherapy: 4).(ABSTRACT TRUNCATED AT 250 WORDS)

[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.

[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.

[End-stage chronic renal failure in myeloma: results of dialysis]. / Insuffisance rénale chronique terminale du myélome: résultats de l'épuration extrarénale.

Nowadays, maintenance dialysis can be proposed to patients suffering from myeloma with end-stage chronic renal failure. We report here data from eight patients dialysed either by hemo- (6) or peritoneal dialysis (2), together with chemotherapy in half of them. Six patients died; the longest survival has been about 6 years. The main cause of morbidity was sepsis, especially in peritoneal dialysis patients; therefore we now favour hemodialysis in patients exposed to aggressive chemotherapy. We think dialysis justified in all cases, including those with high tumor mass, in order to expect the effect of chemotherapy; then, provided good response to drugs, further survival can be consistently improved. Once on maintenance dialysis, main drawbacks for these patients are cardiovascular complications (AL amyloidosis) and above all anemia; the latter however can be markedly improved, thanks to erythropoietin therapy which provides these patients with much better quality of life.

[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.

[Treatments with synthetic antithyroid drugs during pregnancy. Evaluation of the neonatal thyroid function. 25 cases]. / Traitements par antithyroïdiens de synthèse au cours de la grossesse. Evaluation de la fonction thyroïdienne néonatale. 25 observations.

Twenty-four hyperthyroid women were treated with antithyroid drugs during 25 pregnancies. The thyroid function of the 21 children who lived was evaluated by standard clinical and laboratory methods. In 8 of these, T3, T4 and TSH were assayed between birth and the 5th day, with timed samplings during the first hours of life. There was no hypothyroxinaemia at birth, but the T4 peak was delayed; T3 was normal. The TSH peak was abnormal in 3 children, one of whom presented with clinical hypothyroidism. All abnormal findings disappeared spontaneously during the first few days of life, except for one child with congenital Grave's disease who had to be treated. On a 6 months to 6 years follow-up all children had normal growth and psychomotor development.

[Extrarenal clearance in HIV-infected patients with chronic kidney failure. Experience in a hospital center]. / Epuration extrarénale des insuffisants rénaux chroniques infectés par le VIH. Expérience d'un centre.

In HIV-infected patients with end-stage renal failure maintenance dialysis raises multiple problems, the most important of these being the quality and duration of life in these patients and the risk of contaminating other HIV negative patients under dialysis and/or members of the medical-nursing staff. In this study the results obtained in 14 patients treated in one single centre over a 5-year period are analyzed. Nine patients (group I) had end-stage renal failure consecutive to HIV-associated nephropathy: 5 died after 2 to 30 months (mean 9.2 +/- 5.2) of dialysis, while 4 patients were alive at the end of the study with a mean follow-up of 23.8 +/- 8.8 months (5 to 50). Five patients (group II) had end-stage renal failure consecutive to a nephropathy unrelated to HIV: only 1 female patient died 29 months after she was found to be seropositive; the remaining 4 patients were alive at the end of the study with a mean 47.5 +/- 5.5 months (33 to 58) of follow-up. Ten patients were found to have a less than 8 g/dl Hb anaemia which was corrected in the 4 patients who received recombinant human erythropoietin. Out of the 9 patients treated with zidovudine (300 mg/day) 6 had haematological side-effects. Throughout this study, there was no contamination of HIV negative patients or members of the medical-nursing staff. In these 2 groups, the survival of HIV positive patients dialysed for chronic renal failure seems to have been conditioned by the stage of HIV infection at the time when maintenance dialysis was instituted.

[Value of the kidney revascularization in renovascular hypertension with kidney failure]. / Intérêt de la revascularisation rénale dans l'hypertension rénovasculaire avec insuffisance rénale.

The effects of renal revascularization on blood pressure and renal function were evaluated in 8 hypertensive patients with renal impairment and renal artery stenosis in both kidneys (6 cases) or in a solitary kidney (2 cases). Mean age was 66 +/- 7 years. The mean duration of arterial hypertension was 13 +/- 8 years. In spite of treatment with 3 antihypertensive drugs (or more in 5 cases) blood pressure values ranged from 170-90 to 260-150 mmHg. Adding captopril (in 3 cases) or minoxidil (in 1 case) resulted in control of hypertension in 1 patient and further deterioration of renal function in 2. Two patients underwent surgery after failure of percutaneous transluminal angioplasty. There were 6 revascularizations and 2 nephrectomies with contralateral revascularization. One patient died post-operatively. In the remaining 7 patients, the hypertension was controlled with one or two drugs and the renal function remained stable or improved over a mean follow-up period of 2 years. We consider that these results warrant radiological exploration in all patients, even old, with renal impairment and drug-resistant hypertension. Renal revascularization must be performed as early as possible in view of the rapid degradation of renal function under medical treatment in these patients.

Extra-hospital dialysis: the patient is at risk, not the method.

Since dialysis was introduced thirty years ago, nephrologists have sought to diversify treatment strategies with the double aim of offering patients better psychosocial rehabilitation and containing the cost of treatment; this latter aim has been the cornerstone of development in haemodialysis, which in western countries now offers access to treatment for all patients with chronic renal insufficiency. The risk to life during a dialysis session is currently very small indeed. Such fatalities as do occur reflect on the one hand on various medical complications, the incidence of which is largely predictable because of the field involved, and on the other hand on unforeseeable accidents which are highly exceptional. We consider that the risk is not significantly higher in the absence of a physician (as in extra-hospital dialysis procedures) or a nurse (as in home dialysis) than where treatment is given in a fully equipped dialysis centre, provided that there is a prior selection of patients both with respect to their age and their extra-renal pathology.

[Different strategies of substitute treatment of end-stage chronic kidney failure by dialysis]. / Les différentes stratégies de traitement substitutif de l'insuffisance rénale chronique terminal par dialyse.

The development, diversification and improvement of haemodialysis and transplantation techniques have radically altered the prognosis of end-stage chronic renal failure, a condition that is still inexorably lethal in many countries. In France, it is estimated that up to 20,000 patients are being kept alive by these treatments, including transplantation. The available follow-up data show that a survival of 30 years, and perhaps more, can now be expected, at the cost of cardiovascular and osteo-articular complications the incidence and severity of which should be reduced in the years to come. It is by a carefully planned recourse, based on each patient's clinical status and occupation, to the whole range of these complementary treatments that survival time and quality will be further improved.

[Chronic kidney failure in the elderly]. / L'insuffisance rénale chronique des sujets âgés.

Ageing does not spare the kidneys but, remarkably, renal impairment is virtually asymptomatic as homaeostasis remains ensured. Nevertheless, in routine practice physicians must take into account the "physiological" renal insufficiency of the elderly. In old people with chronic renal impairment the diagnostic and therapeutic approaches are special, owing to the age-related risks attached to both paraclinical examinations and treatments. Yet in certain subjects treatment can be remarkably effective and prevent the progression to terminal uraemia, and this justifies the detection and exploration of renal insufficiency in elderly patients. In the last few years, iterative dialysis programmes have been made available to third or even fourth age patients who had reached the so-called end-stage renal failure. The results are encouraging, but there are still purely medical questions concerning the measures to be taken in priority and the numerous organization problems to be solved for optimal management of these patients.