Urate transport in human red blood cells. Activation by ATP.

Urate transport in human erythrocytes were measured and compared to previous observations by other authors regarding inorganic anions, especially chloride. Conclusions wwere as follows: 1. Urate influx as a function of increasing concentrations showed saturation kinetics. 2. The effects of pH and of several passive anion transport inhibitors such as dinitrofluorobenzene, sodium salicylate, sodium benzoate and phenylbutazone suggest that urate and chloride are transported by different mechanisms. 3. Urate influx seems to depend on intracellular glycolysis. The results obtained on red blood cells after glycolysis inhibition agree with those obtained on ghosts where metabolism does not take place. 4. The large drop in urate influxes into erythrocytes in the presence of a glycolysis inhibitor and of a passive ion transport inhibitor seems to argue in favour of a dual urate transport mechanism, one for passive diffusion and the other connected with glycolysis. 5. The drop in the urate influx into ghosts in the absence of ATP suggests that the latter might intervene in urate transport by human red cell membranes.

Comparing outcomes in renal replacement therapy: how should we correct for case mix?

The need to evaluate the effectiveness of clinical practice to justify expensive therapy in the face of financial constraints in all areas of health care delivery makes it necessary to identify groups of patients who are likely to benefit most from treatment. Various risk stratification methods have been used for analyzing survival probabilities for patients receiving renal replacement therapy. Complicated risk stratification methods produce large numbers of risk groups of small sizes, which makes comparison between individual centers difficult. We compared three simple methods of risk stratification, that divided patients into low-, medium-, and high-risk groups, in a cohort of 1,407 patients who commenced renal replacement therapy in five European countries during a 7-year period. Method 1 considered age (>55 years) and diabetes alone; method 2 used a higher age limit (>70 years) and comorbid illnesses, including those other than diabetes; and method 3 used only the number of comorbidities (none, 1, or > or =2) for stratification. Kaplan-Meier survival curves were constructed for comparison between risk groups and Cox's regression model used to assess strength of relationship with mortality. Although patient survival was significantly different between the low-, medium-, and high-risk groups using all three methods, Cox's regression analysis showed that method 2 provided the greatest discrimination between risk groups. In predicting mortality, method 2 (based on comorbidities and age) showed the highest sensitivity and specificity (84% and 80%, respectively) compared with method 1 (80% and 74%) and method 3 (64% and 82%). Validation of this approach in other populations in a prospective study is required before this method, which takes into account the influences of both age and comorbidity for risk stratification, can be used for comparing survival data and for presenting results of renal replacement therapy.

Inhibition of (-) [125I]-iodocyanopindolol binding to rat lung beta adrenoceptors by uremic plasma ultrafiltrates.

Numerous data have suggested that beta-adrenoceptor-mediated responses were decreased in uremia and that parathormone could be implicated in this phenomenon. In a previous paper we have shown that the beta2 receptor density of mononuclear cells of uremic patients is significantly increased despite a significant increase in plasma epinephrine, suggesting that an endogenous substance could interfere and disregulate the beta 2 receptor density. In order to further evaluate this phenomenon we have firstly studied the influence of one non uremic and five uremic plasma ultrafiltrates on the binding of (-)-[125I]iodocyanopindolol using rat lung beta adrenoceptors. The results show that uremic plasma ultrafiltrates induce a decrease in the Bmax value without any variation on the Kd value. In a second step we have assessed the ability of human synthetic 1-34 and 53-84 parathormone to interact directly with beta-adrenoceptors. No variation in the (-)-[125I]iodocyanopindolol binding parameters was observed. These results suggest that an uremic endogenous substance might interfere on the beta adrenergic receptors and that the alteration in the beta-adrenergic response in uremia is probably not due to a direct action of parathormone on the beta-adrenoceptors.

Impaired regulation of beta 2-adrenergic receptor density in mononuclear cells during chronic renal failure.

Previous investigations have suggested that beta-adrenoceptor-mediated responses were decreased in uremia. To evaluate this phenomenon further, beta 2-receptor density in mononuclear cells, plasma catecholamines and plasma parathyroid hormone were studied in two groups of normotensive patients: group U, twenty-five chronic uremic patients with end-stage renal failure; group C, twenty-eight control subjects. Each group was divided into three age and sex-matched subgroups. Beta 2-receptor density was determined using (-)125 iodocyanopindolol. Despite a significant increase in plasma epinephrine in the group of uremic patients, there was a significant increase in beta 2-adrenoceptor density. On the other hand the uremic state did not influence (-)125 iodocyanopindolol binding affinity and plasma norepinephrine. Parathyroid hormone, as expected, was significantly elevated in all the uremic subgroups. It can be concluded that the uremic state is associated with an unexpected upregulation of beta 2-receptor density in mononuclear cells. The role of an endogenous beta-blocking substance is suggested.

Uric acid transport characteristics in human erythrocytes.

Taken all together the results show that the RBC transport of U.A. seems to be partly of passive nature, closely similar to others mineral or organic anions, and partly of active nature related to compound of the membrane playing a role in cellular metabolism. It remains to be precised the role of the membrane itself and to characterize the membrane site which could be responsible of a part of the transport of U.A. through erythrocyte membrane.

[Cardiac surgery under extracorporeal circulation in patients with chronic renal insufficiency. Apropos of 4 cases and review of the literature]. / Chirurgie cardiaque sous circulation extra-corporelle chez les insuffisants rénaux chroniques. A propos de 4 observations et revue de la littérature.

Four cases of cardiac valve replacement in patients with chronic renal failure are reported. The problem of surgery under cardiopulmonary bypass in these patients are discussed with respect to 36 other previously reported cases. Of this lot of 40 cases, 33 (82,5 p.100) underwent valve replacement (21 aortic, 9 mitral, 1 mitral and aortic, and 2 unspecified), 26 (79 p.100) for valvular lesions due to infective endocarditis. Coronary revascularisation was performed in 6 cases (15 p.100) and pericardectomy in 1 case. Operative mortality was within acceptable limits (4 deaths) ; the overall mortality was 10 cases. Valvular lesions due to endocarditis were the main cause of death (9 cases). A session of haemodialysis is performed 12 hours preoperatively. Post-operative care is directed to the control of the fluid balance, the neutralisation of metabolic acidosis with alkaline fluids (sodium lactate) and the correction of hyperkalaemia by kayexalate. In addition, dialysis is required between the 24 th post-operative hour and the 3 rd day. The main indications for cardiac surgery under cardiopulmonary bypass in patients with renal failure are valve replacement for infective endocarditis where the operative decision should be made early on, and aorto-coronary bypass grafting, the selection criteria for which should be very strict.

[Total parathyroidectomy with reimplantation: treatment of choice of hyperparathyroidism secondary to renal insufficiency : report on 24 cases (author's transl)]. / Parathyroïdectomie totale avec réimplantation. Traitement de choix de l'hyperparathyroïdisme secondaire chez l'insuffisant rénal. A propos de 24 observations.

Results in a series of 24 total parathyroidectomies with immediate reimplantation in patients with chronic renal insufficiency are described, and the advantages of this method discussed. This technique avoids the complications of sub-total parathyroidectomy, and the very rare failures can be easily treated by local excision if it is velated to recurrence of hyperparathyroidism, or by further reimplantations in cases of hypoparathyroidism. Grafts are possible during a second stage, after several months of freezing, but a limit of 9 months should be suspected. This method is proposed as a routine measure in all cases of parathyroid hyperplasia.

[Donnan equilibrium and kinetics of uric acid transport across human erythrocyte membrane]. / Equilibre de Donnan et cinétique du transport de l'acide urique par la membrane de l'hématie humaine

The study of the effects of varying pH and ionic composition of external solution on the uric acid ratio (see article) for human erythrocytes at equilibrium and on its permeability constant shows that the distribution of uric acid agrees with the laws of the Gibbs-Donnan equilibrium and its passage across the human erythrocyte membrane with the law of ionic diffusion.

[Compensatory renal hypertrophy in rats. II. Possible regulatory role of renal inhibitory substance]. / Hypertrophie compensatrice du rein chez le rat. II. Rôle régulateur possible d'une substance rénale inhibitrice

Clear supernatant from kidney homogenate injected to an uninephrectomized rat inhibits specifically the incorporation of tritiated thymidine by compensating kidney. This result agrees with the speculation of autoregulation of kidney growth.

[A case of arterial hypertension imputable to an estroprogestational contraceptive. Implication of the renin-angiotensin-aldosterone system]. / Etude d'un cas d'hypertension artérielle imputable à la prise d'un contraceptif oestroprogestatif. Implication du système rénine-angiotensine-aldostérone.

PIP: A 44-year old woman without history of hypertension in her 4 pregnancies was hospitalized for hemoptysia and found to have hypertension 230/120 to 250/150: she had been taking 2 tablets of Lyndiol (5 mg lynestrenol and .15 mg mestranol) daily for 2 years without medical supervision. Findings included: hypokalemia (2.5 mEq/1), hyperchloremia (105 mEq/1), elevated aldosterone excretion (27 m cg/24 hours), low plasma renin activity (5 ng/1/minute). The initial diagnosis of an aldosterone secreting tumor was discarded and the oral contraceptive incriminated when her blood pressure fell, her lab finding normalized and she lost 3 kg within 6 weeks while on a normal diet. Several weeks after her blood pressure had remained 140/80 to 150/90, she was hospitalized again and given 2 tablets of Lyndiol daily while consuming a diet of 100 mEq sodium per day. The only change was a definite increase in plasma renin substrate from 1300-2300 ng/ml. The authors suggested that the hypertension observed in some pill users is due to hyper-aldo-steronism not resulting from stimulation of the renin-angiotensin system.^ieng

[Change in DNA synthesis during compensatory hypertrophy in rat kidney. Stimulating factor in serum]. / Etude de la variation de synthèse de l'ADN au cours de l'hypertrophie compensatrice du rein chez le rat. Recherche d'un facteur sérique stimulant

DNA synthesis by the kidneys was studied in young rats by incorporation of tritiated thymidine. Peak of DNA synthesis was observed as soon as 24 hr after uninephrectomy. No significative difference was observed between control rats and those receiving various doses of serum obtained from uninephrectomized or sham operated rats. Serum of uninephrectomized rats did not increase DNA synthesis in kidney slices in vitro.

[Compensatory hypertrophy of the kidney. I. - Search for the existence of a renal inhibitory substance (author's transl)]. / Hypertrophie compensatrice du rein. I. - Recherche sur l'existence d'une substance rénale inhibitrice

In view of the theory of autoregulation of cell multiplication in a growth organ, we attempted to inhibit renal tubular cell hyperplasia in the remaining kidney 48 hours after controlateral nephrectomy. To do this we drew up a method of measurement of hyperplasia by measuring the rate of uptake of tritiated thymidine in the organ undergoing compensatory growth. We then injected renal cytosol. Whereas the rate of uptake of tritiated thymidine doubles in the growing kidney compared with control animals, the intravenous administration of renal cytosol reduces the renal uptake of the tracer to its basal level. We correlated this observation with the microscopic count of mitotic figures, and noted the existence of parallel fluctuations. Our results seem to support the initial working hypothesis but they do not exclude the possibility of a more complex regulatory mechanism in which serum stimulant factors may also play a role.

[Compensatory renal hypertrophy. II. - Search for a serum stimulant factor (author's transl)]. / L'hypertrophie compensatrice rénale. II. - Recherche d'un facteur sérique stimulant

In order to demonstrate in the uninephrectomised rat possible circulating serum factors which might induce an increase in the rate of synthesis of DNA in the remaining kidney, we injected intravenously to 125 g rats serum from similar rats uninephrectomised 24 to 48 hours previously. The injections preceded the administration of tritiated thymidine by 13 hours (1.5 ml), 5 hours (1 ml), or 2 hours (1 ml) depending on each group. The parameter studied was the radioactivity of the acid-insoluble fraction of 100 mg of kidney. We observed in uninephrectomised animals receiving no injection of serum that the rate of uptake of the tracer in the remaining kidney doubles 48 hours after nephrectomy but this uptake by the kidneys of unoperated rats is not modified by the injection of serum from similar rats whether uninephrectomised or not. Furthermore the addition of serum from uninephrectomised rats to slices of normal kidney under incubation does not modify the rate of synthesis of DNA. All these results are not in favour of a serum factor regulating compensatory renal hypertrophy.

[Renal functions and extracorporeal circulation]. / Fonctions rénales et circulation extracorporelle

During 76 extracorporeal circulations (CEC) carried out for open heart operations using an identical protocol, the authors carried out renal function tests from the time of administration of the anesthetic to the post-operative period. Various periods may be distinguished: pre-operative, anesthesia induction (CEC 1, CEC 2) post induction (CEC 1, post CEC 2) finally, the post-operative period (post-operative 1 to 4). As far as renal hemodynamics are concerned, the authors made the following observations: constant reduction in thiosulphate clearance and endogenous creatinine clearance, which reflect glomerular filtration. Reduction in PAH clearance, which reflects renal perfusion. Taking into consideration changes in the hematocrit, one may consider that there is a reduction in renal blood flow at all stages of anesthesia. Taking into consideration concomitant variations in blood pressure, one may calculate that intrarenal resistances are increased. The diuresis/minute increases in very great proportions during induction of anesthesia. Plasma osmolality also increases, urinary osmolality becomes reduced and osmolar clearance rises. The ratio between osmolar clearance and creatinine clearance rises. The clearance of free water rises from negative values. The serum sodium becomes slightly reduced, and sodium diuresis increases. Serum potassium becomes slightly reduced and urinary potassium rises. The interpretation of these phenomena is difficult and should take into consideration the experimental conditions. Comparison with published results shows that there are definite differences depending on whether pure or diluted blood is used. It is however, possible to seek the role of the anesthetic, the thoracotomy or the extracorporeal circulation itself and its load, quite independent of prior changes due to decompensation or not of the congenital heart disease, whether or not it has been treated. The study of these changes in renal function permits one to understand better the precariousness of renal perfusion during extracorporeal circulation, imperfectly corrected by osmotic diuresis and responsible for transient and reversible renal hypofunction, liable to lead however, in cases of complications and prolonged low blood flow, to organic renal failure.

[The beneficial role of blood transfusion and preganancy in the survival of renal allografts]. / Rôle bénéfique des transfusions sanguines et des grossesses dans la survie des allogreffes rénales.

This analysis involves 93 cases of transplants of non-related cadaver kidneys. The result was better (p = 0.02 at 1 year) in recipients transfused before the graft (73 cases) than in those who had not been trasfused (20 cases). However, this latter group had a shorter average period of haemodialysis (p = 0.05 than the first. The benefits of pre-immunisation appear from 1 to 2 transfusions or 1 pregnancy onwards (p = 0.02 at 1 year). Subjects transfused during the 6 months prior to the transplant had a graft which was functional more often than those who had been more than 6 months before the operation (p = 0.01 at 6 months). These results would be in favour of routine small quantity transfusions, approximately every six months in patients undergoing haemodialysis and on a waiting list for transplantation.

Bacteremia in patients on chronic hemodialysis. A multicenter prospective survey.

A prospective epidemiologic survey of bacterial infections in chronic hemodialysis patients was conducted from September 1, 1989 to February 28, 1990 in 27 dialysis units. Of the 1,455 patients enrolled in the study, 55 presented 63 episodes of bacteremia (incidence of 0.7 bacteremia per 100 patient-months). The portal of entry of sepsis was the vascular access in 50.8% of the episodes. The causative microorganisms were most often gram-positive cocci (69.8%). 23% of the teremic patients had a serum ferritin > 1,000 micrograms/l versus 7% of the nonbacteremic infected patients (p = 0.005). 39.7% of the patients had undergone a surgical operation during the month preceding the bacteremia. Eight patients had a recurrence during the study period and 8 had a metastatic localization: spondylodiscitis 2, septic pulmonary embolus 2, endocarditis 1, arthritis 1, liver abscess 1 and endophthalmia 1. 66% of the episodes required a hospitalization that lasted an average of 20 days. Mortality rate was 6.3%. This prospective study showed a trend towards a reduction in incidence and mortality of bacteremia in patients on chronic hemodialysis.

[Silicone deposits in macrophages of patients on chronic hemodialysis]. / Dépôts de silicone dans les macrophages chez les patients en hémodialyse chronique.

A retrospective study was carried out in search of silicone deposits in 11 periodic hemodialysis patients (1 liver biopsy, 4 splenectomies and 6 autopsies) treated between 12 and 60 months with equipment containing a silicone pump segment. Silicone particles were found in the macrophage cells of all patients, especially in the liver and spleen, but also in lymph nodes, bone marrow and even an artery wall. In some cases, macrophage response had formed sarcoid-like granulomas. Silicone deposits in 3 patients were associated with a hypersplenism syndrome totally or partially improved by splenectomy. No relationship could be established between foreign material in the liver and clinical or biological abnormalities. Three patients who had died subsequent to peritoneal dialysis or hemodialysis involving polyvinyl chloride materials served as controls. No silicone inclusions were found in their tissues at autopsy.