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SummarySerum β2 microglobulin (β2m) levels were determined together with serum creatinine and inulin clearance in 500 patients with various degrees of renal insufficiency, excluding patients with connective tissue disorders or lymphoproliferative disorders. The logarithmic relationship observed between S β2m and inulin clearance, was best fitted to experimental data when β2m values below and above 245 mg/l were treated separately. The plasma turnover of 125I β2m was studied in two healthy adults, two anuric patients (one of them without kidneys) and eight patients with various degrees of renal insufficiency. Results were analyzed according to a bicompartmental model. The fractional metabolic rate was positively correlated with inulin clearance and little (< 3.5 %) extrarenal catabolism was demonstrated. The half-life of β2m in intravascular compartment varied from 107 min. in normals to more than 39 hrs in the anephric patient.

A retrospective study made of 114 cases of renovascular hypertension was undertaken to compare the effectiveness of different types of treatment. In this series, with a follow-up of 18 months to 9 years, a favourable result with regard to blood pressure was obtained in 45% of cases with surgery, in 63% of cases with medical treatment and in 88% of cases if treatment included beta-blockers. Medical treatment represents a valid alternative to surgery in hypertension of this type, regardless of the amount of renin secretion and whatever the criteria of ischaemia. The choice of surgery as a method of treatment thus depends above all upon the age of patient, the type of stenosis and the anatomical risk represented by the vascular malformation. Despite the very spectacular results of medical treatment, it remains essential to seek a renal cause for hypertension, since many renal conditions which require specific treatment present with hypertension alone.

The kinetics of piretanide was studied in patients with renal failure. After oral administration of a high dose of piretanide (96 mg), the pharmacokinetic parameters were: elimination rate constant 0.346 +/- 0.072 h-1, half life 2.00 +/- 0.35 h, and total plasma clearance 119.55 +/- 35.90 ml x min-1. Compared to the values obtained in adults with normal renal function, these results show a decrease in total plasma clearance, but conservation of the metabolic clearance which amounts to 45% of the total clearance in the healthy adult.

The frequency of measures of prevention of stone recurrence was evaluated in 250 patients treated in one center by extra corporeal shock wave lithotripsy (ESWL). Half were recurrent stone formers (RSF). Only two thirds admitted a previous 24 h urinary analysis and less than 30% knew the result as abnormal while hypercalciuria and or hyperuricuria was later evidenced in 63%. These figures were similar in first stone and recurrent stones formers. Dietary or drug based regimen were followed by only 27.5% of RSF irrespective of the activity of the disease. This percentage was the highest (40%) in RSF known as having abnormal urinary values and the lowest (13%) in those without previous analysis. Only 17% of RSF admitted having received dietary advise after ESWL.

The inhibitory effect of magnesium on the first stages of renal calcium stone formation is modest in vitro and more pronounced in experimental in vivo studies. Magnesium deficiency has not yet been convincingly demonstrated in man. However, urinary magnesium concentrations are abnormally low in relation to urinary calcium concentrations in more than 25% of patients with kidney stones. A supplementary magnesium intake corrects this abnormality and prevents the recurrence of stones. Magnesium seems to be as effective against stone formation as diuretics. The modalities of magnesium therapy still have to be determined and its results to be confirmed. Magnesium, possibly added to drinking water, may well play a role in the primary prevention of renal calcium stones.

A pharmacokinetic study of sachets containing nalidixic acid (0.66 g) associated with sodium citrate (3.75 g)--NSC--was carried out in 10 healthy volunteers in order to determine the influence of the urine alcalinization due to sodium citrate on the elimination of nalidixic acid (NA) and its 7-hydroxy (HNA) and 7-carboxy (CNA) derivatives. Urine alcalinization enhanced markedly the urinary excretion of HNA, but not of NA and CNA. The urinary concentrations of bacteriologically active compounds--NA + HNA--remained above five times their minimum inhibitory concentration for 10 h following each dose. After a 3-day treatment using NSC three times daily there was no significant accumulation of NA and derivatives in the plasma and no significant change in their kinetics. Finally, from a pharmacokinetic viewpoint, the daily administration of 3 sachets of NSC each containing 0.66 g of NA seems valuable in the treatment of urinary tract infections.

The disappearance of the anticoagulant activities of a standard commercial heparin and of a low molecular weight (LMW) heparin (PK 10169), administered as single intravenous injections, was studied in patients with chronic renal failure. Heparin and LMW heparin anticoagulant activities were determined by activated partial thromboplastin time (APTT) and chromogenic assays of anti-Xa and anti-IIa activities. Following heparin injection, a fast initial decay of anticoagulant activities preceded a slow convex disappearance curve, in semilogarithmic plots. These experimental data are in agreement with a model based on a predominant saturable mechanism of elimination of heparin in patients with renal failure. The disappearance of LMW heparin anti-Xa activity was obviously different, with linear or concave elimination curves, and longer apparent half-life. Taken together, our kinetic data and those previously reported in normal subjects strongly suggest that the mechanism of elimination of the LMW heparin studied is not saturable (at least for the tested dosages), and that the kidneys play a minimal role in the elimination.

The plasma turnover of 125I beta 2 microglobulin (B2m) was studied in two healthy adults, two anuric patients (one of them without kidneys) and eight patients with various degrees of renal insufficiency. Results were analyzed according to a bicompartmental model. The fractional metabolic rate was positively correlated with inulin clearance, and little (less than 3.5%) extrarenal catabolism was demonstrated. The half-life of B2m in intravascular compartment varied from 107 min in normals to more than 39 hrs in the anephric patient.

Four beta-blockers: atenolol 15 mg i.v., metoprolol 25 mg i.v., acebutolol 45 mg i.v. and labetalol 50 mg i.v. were administered to 106 patients suffering from hypertension and with normal or disturbed renal function. During an identical test protocol, measurements of clearance of inulin, of PAH, urine sodium and the fraction of sodium excreted were recorded one hour before and four or five hours after administration of the antihypertensive. Mean blood pressure and heart rate were also recorded. The three pure beta-blockers reduced inulin and PAH clearance and lowered urine sodium. These modifications were the same for all three drugs. Labetalol, which also possesses alpha-blocking properties, did not reduce renal function values or urine sodium. While a slight fall in blood pressure occurred with all the antihypertensives, heart rate was reduced only by the three pure beta-blockers. The action of the four drugs was very similar whatever the state of the subject's renal function. The study of the renal effects of the beta 1-selective atenolol and metoprolol, and acebutolol which has a higher intrinsic sympathomimetic activity does not demonstrate any significantly different renal action among these three drugs, but the effects of labetalol on renal function values and urine sodium are slighter. The renal action of the beta-blockers cannot be fully explained. Though the fall in the renal plasma flow and in the glomerular filtration rate can be related partly to the decrease in the cardiac output consequent to induced bradycardia, stimulation of renal alpha-receptors must be considered.(ABSTRACT TRUNCATED AT 250 WORDS)

The nephrotoxicity of contrast media in common use today may be regarded as almost negligible. However, several reports on contrast medium-induced renal failure have been published and several risk factors have been identified as, for instance, pre-existing renal insufficiency and diabetes mellitus [1]. The relative nephrotoxicity of various contrast media has not been clearly assessed as yet.

One hundred and eight patients suffering from hypertension due to a unilateral parenchymatous neophropathy were studied over a period of one to eight years after treatment was starded. The aetiologies were diverse: harmonious hypoplasia, segmental hypoplasia, pyelonephritis, reflux nephropathy, hydronephrosis and tuberculosis. Thirty nine patients were treated surgically, with 50% good results. In 82 cases medical treatment was continued for at least a year with a 52% success rate. Such success was recorded in 94% of cases in which beta-blockers were used (38 cases). Surgical success was not dependent upon the period for which hypertension had been present. The best results were seen in cases of hydronephrosis and pyelonephritis and the worst in tuberculosis. Thirteen patients underwent surgery event though there was no unilateral increase in plasma renin levels. Seven were improved or cured. Ten patients underwent surgery with a renin activity 50% greater than on the healthy side, 9 being improved or cured. Treatment with beta-blockers, alone or in association with diuretics, controlled blood pressure in 90% of cases, regardless of the renin activity. Plasma renin activity in the renal veins is of good prognostic value in terms of the effectiveness of nephrectomy against hypertension. In Call cases, beta-blockers were more effective than surgery.

Forty patients suffering from idiopathic oedema were studied. The disturbance in water excretion is characterised by a delay in excretion of a water load (20 ml/kg body weight), an inability to decrease urinary osmolarity below 137 mOsm/1 standing (normal: 60 mOsm +/- 25) and an inability to increase free water clearance: 2.36 +/- 2 ml/mn/1. 73 m2 (normal value: 6.8 ml/mn/1.73 m2) in the upright position. This problem of water excretion related to orthostasis defines and characterises the syndrome, the clinical picture of which is well known. The disturbance suggest a fault in the regulation of anti-diuretic hormone whilst the aldosteronism often described would seem to be inconstant and secondary to diuretic therapy too often prescribed without supervision.

The influence of 2 diuretics (D) on renal handling of uric acid (UA) was evaluated. 8 normal male volunteers (age : 32.5 ± 4.6, BW : 68 ± 8 kg, H : 175 ± 6 cm) received in random order placebo (P), methyclothiazide (MCT, 2 mg) alone or with triamterene (75 mg, MCT + T) for 4 days. Urine (u) was collected every 12 hours and blood (b) was drawn at days 1 and 5, for measurement of : b UA (micromol/1), excreted (u UA) and filtered (f UA) UA (micromol/min) and fractional clearance (f Cl UA) D increased (p

Spontaneous variations in renal handling of uric acid (UA) were studied in 8 normal male volunteers (age : 32.5 ± 4.6, BW : 68 ± 8 kg, H : 175 ± 6 cm). Over 10 weeks, urine was collected every 12 hours for 6 consecutive days, then once every 2 weeks and blood (b) was drawn at day 1, 5 then every 2 weeks for measurement of night (n) and daytime (d) UA excretion (UA e micromol/min), blood concentration (b UA, micromol/1), fractionnal clearance (f Cl : cl UA/GFR) and intraindividual coefficient of variation (ICV = sd/m) Over the range of observed b UA, UA e was positively correlated with filtered UA (= 1.88 + .04 f UA, r = .60, p < .001), f Cl was correlated negatively with b UA (= .007 + 30.27/b UA, r = .69, p < .001) and positively with f Cl for sodium (p < .05), suggesting that spontaneous variations of b UA are partly due to changes in net renal transport of UA and dependent on sodium status. Conclusion : These variations should be taken in account when evaluating the effect of drugs interfering with UA metabolism.