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The distribution of different diseases, considered as mortality and morbidity causes, is a crucial clue to the knowledge of the epidemiological charachteristics of a population. Aim of the present study was to assess the distribution of different causes of death in two cohorts of dialysis patients, affected by diabetic nephropathy or by all other forms of renal diseases and to compare the incidence of the different causes of death in dialysis patients and overall population.

The aim of this study was to analyze Na,Li countertransport in erythrocytes from adolescents with insulin dependent diabetes mellitus (IDDM) and to see if those with elevated values present distinct clinical features, in particular as regards arterial pressure and urinary albumin excretion (UAE). Twenty-nine adolescents with IDDM (17 males, 12 females, mean age 15 +/- 0.6 years, mean diabetes duration 11.4 +/- 0.7 years) and fifteen healthy age-matched control subjects (8 males, 7 females, age 14.5 +/- 1 years) were investigated. Diabetic adolescents had a RBC Na,Li countertransport activity higher than age matched normal controls; geometric mean 283 (95% limits 259-340) vs. 193 (169-252) mumol/l RBC/h; p less than 0.01. Seven out of 29 subjects had values higher than the 95th percentile of normal subjects (Counter +). Both systolic and diastolic arterial pressures were significantly higher in Counter + than in Counter - patients. No significant differences were found as regards age, body mass index, diabetes duration, HbA1c, fructosamine, serum potassium, triglycerides, creatinine clearance and UAE. The logarithm of systolic pressure was independently positively correlated with ln Na,Li countertransport (r = 0.38; p less than 0.05), ln [Nai] (r = 0.38; p less than 0.05), and ln body mass index (r = 0.5; p less than 0.01) in diabetic patients. The main finding of this study is that diabetic adolescents with a high erythrocyte Na,Li countertransport rate have an arterial pressure significantly higher than patients with normal Na,Li countertransport fluxes.

La mortalite cardiovasculaire reste tres importante chez l’insuffisant renal dialyse. Diamant alpin est une etude de cohorte, prospective et multicentrique (CHU, CHG et centres prives, n = 8) menee en France, Italie et Suisse incluant 279 patients au moment de la prise en charge en dialyse. Les objectifs de l’etude'sont la recherche de FDR cliniques ou biologiques (phenotype et genotype), en particulier l’hyperho-mocystinemie. Critere de jugement La mortalite et la morbidite cardiovasculaires (coronaire, AOMI, AVC) survenant lors du suivi systematique dans les deux ans. Population Cent soixante dix-sept hommes et 102 femmes âges en mediane de 66 ans (de 22 a 92 ans). Quatre-vingt-dix pour cent de ces patients etaient hypertendus, 29 % presentaient une dyslipidemie traitee, 29 % un diabete et 18 % fumaient au moment de la prise en charge en dialyse. En consequence, 26 % des patients avaient une localisation de maladie atheromateuse a expression clinique (essentiellement coronaire) et 16 % avaient 2 localisations de maladie atheromateuse. Une nephropathie vasculaire etait en cause pour 30 % des patients. Methode statistique Kaplan meyer, test du Log rank et modele de Cox ; p Resultats La probabilite de survenue d’un evenement cardiovasculaire est de 24 % a un an et de 35 % a deux ans. En analyse multivariee, les facteurs de risque cliniques de survenue d’un evenement cardiovasculaire sont les antecedents connus d’atteinte atheromateuse (OR = 5 si deux localisations connues et OR = 2 si une seule localisation connue) et l’âge superieur a 75 ans (OR = 1,7). Sur le plan biologique, une CRP > 10 mg/1 et un taux de Lp(a) > 300 mg/1 sont associes a un OR de 1,7. Un taux d’homocystinemie > a 30 μmoles/1 est associe a un OR de 2,5. Les patients homozygotes pour la MTHFR ont un OR de 1,7. Cette caracteristique genetique est particulierement informative si le taux d’homocystinemie est a 30 μg/1 (OR = 0,9 NS). Les autres genotypes etudies (enzyme de conversion de l’angiotensine, PAI, ApoE) ne sont pas significatifs. Conclusion Cette etude confirme le haut niveau de risque cardiovasculaire des patients pris en charge en dialyse. Parmi les FDR identifies, un taux d’homocystinemie superieur a 30 mg/1 est un FDR independant. Compte tenu du contexte d’insuffisance renale, le seuil usuel de 14 μ/1 doit donc etre modifie pour l’homocystine.

The intracellular concentration of Na+ ([Na+i]) and the Na+ efflux mediated by the Na+, K+ pump were evaluated in red blood cells from 9 patients on hemofiltration, 8 on hemodialysis, 9 on continuous ambulatory peritoneal dialysis (CAPD) and 12 normal subjects. [Na+i] was elevated in CAPD patients only. The rate constant for pump-mediated sodium efflux was close to normal in hemofiltration patients, and significantly reduced in hemodialysis (p +, K+ pump activity of normal red blood cells. Among our uremic patients those on hemofiltration showed a red blood cell Na+, K+ pump activity close to that of normal subjects, possibly related to the absence in their plasma of a circulating pump inhibitor, that seems invariably present in plasma from hemodialysis and CAPD patients.

32 patients (22 biopsed) with lupus nephritis (LN) were observed for circulating immune complexes (IC). Solid phase Clq (SPClq) and polyethylene glycol (PEG) precipitation tests were used. The patients were studied during the clinical follow-up in different phases of disease activity. Comparative studies between each histological class of LN and corresponding forms of idiopathic glomerulonephritis (IGN) were made: no significant differences were found between either mesangial LN and stalk mesangial IGN, or between focal proliferative LN an focal proliferative IGN. However, a significant difference was found for SPClq data between diffuse proliferative LN and mesangiocapillary IGN, and between membranous LN and membranous IGN. LN, with an acute nephritic syndrome and hypocomple-mentemia, displayed SPClq data significantly above the levels of IC found in IGN with similar clinical features. IC serum data would seem an important element for the diagnosis and the clinical management of patients affected by LN.

The acute effects of both acetate and bicarbonate hemodialysis on erythrocyte transmembrane sodium fluxes were investigated in 15 patients with chronic uremia. We observed a significance (p less than 0.01) stimulation of the Na+,K+ pump in both procedures, with a significant correlation to the amount of fluid removed during hemodialysis (r = 0.56, p less than 0.03). Outward Na+ cotransport fluxes significantly rose (p less than 0.05) after acetate hemodialysis and decreased (p less than 0.05) after bicarbonate hemodialysis. Minor and not significant pre- and posthemodialysis bidirectional changes were observed as regards the intraerythrocyte Na+ and K+ concentration, passive Na+ and K+ permeability, and Na+,Li+ countertransport. Hemodialysis may acutely affect the erythrocyte sodium pump and cotransport fluxes, possibly through the modulation of hormonal factors triggered by the extracellular volume changes.

Erythrocyte Na,K pump activity and arterial hypertension in uremic dialyzed patients. We have evaluated in 26 uremic patients [21 on hemodialysis, 5 on continuous ambulatory peritoneal dialysis (CAPD)], 11 normotensive, and 15 hypertensive (MAP > 110mm Hg) patients the following properties: a) erythrocyte (RBC) Na concentration [Nai] and ouabain-sensitive and -resistant Na effluxes; b) the effect of uremic sera on ouabain-sensitive Na efflux in normal RBC; c) serum digoxin-like immunoreactivity; d) cardiac index and total peripheral resistance. In 19 healthy subjects a) and c) were also evaluated. RBC Na,K pump activity was lower in uremic patients than in normal subjects (P < 0.0005), and lower in hypertensive (P < 0.02) than in normotensive patients. Serum from uremic patients inhibited ouabain-sensitive Na efflux in normal RBC, the inhibition being correlated with both the rate constant for ouabain-sensitive Na efflux (r = -0.67; P < 0.005) and [Nai] (r = 0.43; P < 0.05) of RBC of patients from whom the serum was obtained. Inhibition of ouabain-sensitive Na efflux was significantly higher with serum from hypertensive than from normotensive patients (P < 0.05). Serum digoxin-like immunoreactivity was present in all uremic patients (0.402 ± 0.054 ng/ml in normotensive and 0.428 ± 0.040 ng/ml in hypertensive, P = ns), while it was not detectable in normal subjects. Hypertensive patients had peripheral resistance significantly higher than normotensive (P < 0.05), while cardiac index was similar in both groups. A strong inverse correlation was found between the rate constant for ouabain-sensitive Na efflux in RBC and total peripheral resistance (r = -0.76; P < 0.0001). In conclusion: 1) Hypertensive uremic dialyzed patients have lower erythrocyte Na,K pump activity as compared with normotensive, and higher levels of a specific circulating Na,K pump inhibitor; 2) reduced sodium transport by Na,K pump is strongly correlated with increased total peripheral resistance, thus suggesting a role in the pathogenesis of arterial hypertension in patients with chronic uremia undergoing hemodialysis or CAPD; 3) a digoxin-like immunoreactive material is detectable in uremic sera, but it does not have a close relationship to Na,K pump inhibitor.

1. Intracellular Na+ concentration [Na+]i and Na+ extrusion catalysed by sodium, potassium-activated adenosine triphosphatase (Na+, K+-pump) were evaluated in erythrocytes from 21 obese children and 20 normal weight- and age-matched controls. 2. Obese children showed a significantly decreased Vmax for Na+, K+-pump-mediated Na+ efflux (5638 ± 338 vs 7597 ±335 μmol h−1 litre−1 of cells mean±SEM, P = 0.01), while [Na+]i (9.3±0.3 vs 9.1 ± 0.5 mmol/litre of cells, mean±SEM, NS) and Na+ efflux in fresh cells (2380± 153 vs 2533 ± 180 μmol h−1 litre−1 of cells, mean ±sem, NS) were similar in both groups. 3. Mean diastolic blood pressure was significantly higher in obese children than in controls, although both groups were normotensive (73.8 ± 1.3 vs 66.2 ±1.9 mmHg, mean ± sem, P = 0.009). 4. Abnormal Na+, K+-pump activity is present in individuals with idiopathic obesity. 5. The possible link between obesity and blood pressure regulation may be mediated through modifications in Na+, K+-pump activity.

Canrenone is the main active metabolite1 of the diuretic and antihypertensive drugs spironolactone and canrenoate-K, and competes with aldosterone for a common cytosolic receptor in distal and collecting tubules of the nephron.2 In addition it has recently been demonstrated that canrenone in vitro may directly interfere with ouabain-sensitive Na+,K+ pump (Na+,K+ adenosine triphosphatase), acting as a partial agonist at the digitalis receptor site. 3,4 Moreover Garay et al.4 showed that canrenone is able to restimulate in vitro the Na+,K+ pump of human red blood cells (RBC) blocked by high concentrations of ouabain.

Corticosteroids have multiple effects on the movement and functional capabilities of inflammatory or immunologically reactive cells, on various soluble factors, on vascular and tissue responses. There is a different sensitivity of various populations and sub-populations of cells to the corticosteroid modulation. These mechanisms are still under discussion, but the final effects appear to support the use of corticosteroids in certain patients with idiopathic glomerulonephritis (GN).

1. The effects of a 2 litre intravenous infusion of saline (0.9% NaCl solution) over 3 h on erythrocyte transmembrane sodium transport were studied in 12 normal human subjects. 2. After saline infusion a significant (P < 0.01) reduction of both outward Na+, K+ pump- and Na+, K+ cotransport-mediated Na+ effluxes was observed. The Na+, Li+ countertransport rate and the passive Na+ permeability did not change. 3. The incubation of the subjects' erythrocytes, obtained on a separate occasion, with their own plasma taken after the saline infusion, induced an inhibition of both Na+, K+ pump and Na+, K+ cotransport outward sodium fluxes. The percentage decrease after incubation was closely correlated with the percentage reduction induced by the saline infusion in vivo (r = 0.93 for the pump and r = 0.96 for cotransport; P < 0.01). 4. These data suggest that extracellular fluid volume expansion affects the release of circulating factors modulating sodium transport by the Na+, K+ pump and by Na+, K+ cotransport.

In 38 uraemic dialysed patients (17 normotensive, 21 hypertensive) we measured (1) erythrocyte sodium concentration [Nai] and ouabain-sensitive sodium efflux, and (2) arterial pressure, cardiac index and total peripheral resistance. Erythrocyte Na-K pump activity was lower in hypertensive than in normotensive patients (P less than 0.02). Hypertensive patients had significantly higher peripheral resistance than normotensive patients (P less than 0.05), while the cardiac index was similar in both groups. Inverse correlations were found between the rate constant for ouabain-sensitive sodium efflux in erythrocytes and both systolic and diastolic pressure (r = -0.43 and r = -0.45, respectively; P less than 0.01) and total peripheral resistance (r = -0.76; P less than 0.0001). Our data suggest that reduced sodium transport by the Na-K pump plays a role in the pathogenesis of arterial hypertension in patients with chronic uraemia.

Peripheral T and B cell subpopulations in 41 CAPD patients and 30 healthy controls were identified using monoclonal anti-T cell antibodies and immunofluorescent staining. HLA typing was also studied. OKT8 reactive cells were significantly higher in patients who had had two or more episodes of peritonitis on follow-up, with no changes from normal in those who did not develop peritonitis. The HLA-B8, DR3 haptotype was more frequent in those who did not develop peritonitis, and since HLA-B8, DR3 is known to be associated with reduced suppressor T cells, such a haplotype may confer resistance to peritonitis.

Serum samples from 115 patients with various kidney diseases were studied by means of precipitation in 3.5% polyethylene-glycol (the PEG test), and by inhibition of the agglutination of IgG-coated polystyrene particles induced by C1q, two tests developed for the detection of circulating immune complexes. Positive results were found in acute glomerulonephritis, particularly in its early stages, and also in chronic forms of glomerulonephritis: membranous, focal sclerosing, mesangiocapillary and focal glomerulonephritis. High levels of circulating immune complexes were found inlupus nephritis. In most cases the test results showed a good correlation with the clinical course of the diseases.