[Optimization of enoxaparin dose in the prevention of coagulation in the circuits of hemodialysis: results of a multicenter study]. / Optimisation de la dose d'énoxaparine (Lovenox) dans la prévention de la coagulation des circuits d'hémodialyse: résultats d'une étude multicentrique.

In order to define the optimal dosage of a low molecular weight enoxaparine (Lovenox) in the prevention of clotting in extracorporeal circulation during hemodialysis, a multicentre trial was conducted in 72 patients dialysed in seven hemodialysis units. During three weeks, these patients received as antithrombic treatment a single injection of enoxaparine at the beginning of the session. The initial dose fixed by previous data concerning dialysis with high hemorrhagic risks patients was 0.5 mg/kg (50 U1 Anti-Xa/kg). According to the evaluation of thrombotic manifestations during a 4 hour dialysis, the dosage was progressively increased if necessary for each patient. For 41% patients, the initial dose of 0.5 mg/kg was maintained along the whole study; 59% patients needed higher dose, between 0.6 and 0.9 mg/kg. The mean dose for the whole patient population at the end of the study was 0.62 +/- 0.16 mg/kg. No complication nor side effect was noted. The influence of blood flow, nature of dialysis membrane, level of hematocrit was studied. In conclusion, 0.5 mg/kg of enoxaparine can prevent thrombotic manifestations in almost half of chronic hemodialysed patients with good results. Further studies could precise the place of personal or technical parameters in the choice of the optimal dose for each patient.

[Hyperphosphoremia and hypophosphoremia]. / Hyperphosphorémie et hypophosphorémie.

Disorders of phosphate metabolism are caused by a disrupted balance between intestinal absorption and renal excretion or by an altered distribution between intra- and extracellular pools. Hyperphosphatemia per se does not have any clinical effects except for ectopic calfifications. The most frequent cause is chronic renal disease. Other causes - increased tubular reabsorption as seen for instance un hypoparathyroïdism; increased intertinal absorption as seen with vitamin D excess; redistribution to the extracellular pool, as seen with the tumor lysis syndrome, are uncommon; and no one cause is outstanding in frequency. Hypophosphatemia is frequent caused by a redistribution of phosphate to the cellular pool, associated for instance with respiratory alkalosis or infusion of glucose and fructose. Hyperphosphaturia as a cause of hypophosphatemia is seen in primary and secondary hyperparathyroïdism as well as in familial hypophosphatemic rickets. Decreased intake of phosphate may be secondary to intravenous hyperalimentation, chronic ingestion of phosphate-binding antacids or vitamin D deficiency. Hypophosphatemia does not appear to produce any harmful effects. However acute hypophosphatemia, if it occurs in the presence of preexisting cellular injury and phosphate depletion, as in chronic alcoholic patients for instance, has been implicated as a cause of severe clinical syndromes. Chronic hypophosphatemia in children may induce rickets, and osteomalacia in adults.

Treatment of hypertension with lisinopril in end-stage renal failure.

Lisinopril (L), a novel angiotensin converting enzyme inhibitor, was studied as sole drug in the management of hypertensive, dialysis-treated, end-stage renal failure patients to assess its efficiency, tolerance, and removal by dialysis. High blood pressure (BP) was defined as sitting diastolic (D) BP greater than or equal to 95 mm Hg. Ten patients, two females and eight males, were treated for 12 weeks. Their features were age 49 +/- 14 years; dialysis duration 43 +/- 25 months; body weight 61 +/- 10 kg; and body mass index 21.7 +/- 3 (mean +/- SD). Serum L concentrations were measured regularly by radioimmunoassay, both before and after dialysis, which was performed with Cuprophane membranes three times per week. L, 2.5 mg orally, was given every 24 h initially; in six patients, dosage was decreased to an alternate or once-a-week schedule, because of a hypotensive effect during dialysis. At 12 weeks, BP--as compared to prestudy BP--was decreased in eight of nine patients (one patient had been withdrawn after kidney transplantation), and not changed in one patient (mean +/- SD): sitting DBP from 107 +/- 7 to 87 +/- 10 mm Hg, p less than 0.001; erect DBP from 105 +/- 5 to 86 +/- 10 mm Hg, p less than 0.001. L serum concentration was decreased by dialysis, the mean ratio of post-/predialysis serum L concentrations was 0.47 +/- 0.07 (n = 67). No side effects were disclosed, except for three patients, in whom hemoglobin decreased, while two of them also received quinine for a febrile illness of viral origin.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired C1 esterase-inhibitor deficiency: case report with emphasis on complement and kallikrein activation during two patterns of clinical manifestations.

A case of severe angioedema with several episodes of life-threatening attacks during a follow-up of 7 years is presented. Although the biologic profile is that of an acquired C1 INH deficiency, no lymphoproliferative malignancy or immune-complex disease could be proven until now. However, the patient has had a small monoclonal IgG lambda-gammopathy for 4 years. During the last 4 years, edematous manifestations have stopped. The patient now suffers at regular intervals of about a week from short-lasting attacks with digestive and vasomotor symptoms. This clinical evolution is accompanied by a worsening in the complement abnormalities. The digestive and vasomotor attacks were found to be correlated with sudden prekallikrein and high-molecular-weight kininogen consumption. These findings demonstrate that prekallikrein is activated during acquired C1 INH deficiency and that the products of this pathway such as bradykinin are probably responsible for a part of the clinical manifestations associated with this disorder.

Influence of parathyroid status of rats on renal tubular handling of adenosine 3'5'-monophosphate: a micropuncture study.

In order to correlate cyclic AMP handling by the nephron to the parathyroid status, clearance and micropuncture experiments were performed in rats with intact parathyroid glands, or immediately after parathyroidectomy, or six days after parathyroidectomy. In intact animals cyclic AMP urinary excretion was about twice the filtered load and the tubular addition of the nucleotide was achieved at the end of the accessible proximal tubule. In acutely parathyroidectomized rats cyclic AMP urinary excretion was not different from the filtered load and no proximal tubular addition was detected at the late accessible proximal tubule. In chronically parathyroidectomized animals urinary excretion of cyclic AMP was not different from the filtered load, nevertheless a proximal tubular addition of the nucleotide was observed, similar in magnitude to that of intact rats. The data afford a direct evidence that the convoluted proximal tubule is the major site of cyclic AMP tubular addition, confirm that this addition disappears immediately after parathyroidectomy, but indicate that it re-occurs in chronic parathyroidectomy.

Localization of parathyroid-hormone-independent sodium bicarbonate inhibition of tubular phosphate reabsorption.

We investigated phosphate transport along superficial nephrons in two groups of acutely parathyroidectomized (APTX) rats. Animals of group 1 were infused with 0.5 M sodium chloride; and those of group 2, with 0.5 M sodium bicarbonate at the same rates. Compared to the sodium chloride infusion, the sodium bicarbonate infusion was associated with a significant increase in urinary excretion of phosphate: the fractional phosphate excretion was 2.3 +/- (SD) 1.3% in the sodium chloride group and 14.4 +/- 3.2% in the sodium bicarbonate group, P less than 0.01, whereas the fractional sodium excretion was identical, 7.4 +/- 0.60% and 7.5 +/- 0.50%. Micropuncture studies performed at the late accessible proximal and early accessible distal sites of the same superficial nephrons indicate that the reabsorptive capacity for phosphate (absolute reabsorption/absolute delivered phosphate per nephron segment) is decreased during sodium bicarbonate infusion in the convoluted proximal tubule as well as in the loop (segment located between late proximal and early distal accessible convolutions) and the terminal nephron. Such an effect is independent of both parathyroid hormone secretion and extracellular fluid volume expansion.

Renal transplantation and immunological abnormalities in thrombotic microangiopathy of adults: report of 5 cases.

Renal transplantation was performed in five adult patients with thrombotic microangiopathy, three of whom had had a bilateral nephrectomy prior to transplantation. The graft remained functional in three patients 72, 18, and 12 months after transplantation. One patient developed a thrombosis of the renal artery and one patient died from infection. There was no clinical or histological evidence of recurrence of thrombotic microangiopathy in the five patients after transplantation. Immunological investigations were performed in four of five patients before transplantation: C3 and C1q levels were low in two patients; serum C3-splitting activity and circulating immune complexes were present in all four patients and remained unchanged on haemodialysis and/or after bilateral nephrectomy. Complement abnormalities and immune complexes were not detected in the three patients with successful renal transplantation.

Evidence for a parathyroid hormone-independent calcium modulation of phosphate transport along the nephron.

To disclose a parathyroid-independent calcium modulation of phosphate transport along the nephron, the effect of increasing plasma calcium concentration to subnormal levels in rats 6 days after parathyroidectomy (chronic PTX) was studied. Fractional phosphate reabsorption was significantly increased. The whole kidney response to calcium infusion was similar whether or not the thyroid gland was removed, which suggests that calcitonin is not involved. The micropuncture study indicated an increase in the reabsorptive capacity for phosphate (absolute reabsorption/absolute delivered phosphate per nephron segment) in the proximal tubule, the loop, and the terminal nephron when calcium was infused. Thus, the level of plasma calcium or some related factor affects the phosphate transport by the tubule independently of parathyroid hormone. With calcium infusion, the profile of phosphate reabsorption along the nephron became close to that of acutely parathyroidectomized rats, but with persisting differences. The level of plasma calcium concentration may partly account for the differences between the acute and the chronic steps of parathyroidectomy. The role of possible interferences between alterations of extracellular calcium concentration or some related factor and the adenylate cyclase-cyclic AMP system in such an action of calcium was evaluated. Cyclic AMP was infused so as to achieve a 10(-6) M plasma concentration. Combined infusions of calcium and cyclic AMP were also performed. The results are compatible with calcium inhibition of adenylate cyclase, although they do not rule out a direct action of calcium.

Cholangitis with acute renal failure: priorities in therapeutics.

Obstructive cholangitis with acute renal failure is a dramatic syndrome which merits individual definition. Twenty-one patients with acute suppurative cholangitis complicated by rapidly developing renal insufficiency were studied, and the severity of the renal failure, an acute interstitial tubulopathy, bore no significant relationship to the serum bilirubin level. The mechanism of renal damage was clearly related to episodes of septicemia. Increasing experience has modified the approach to treatment. The dominant septic problem can often be controlled by vigorous antibiotic and fluid therapy, allowing time for spontaneous improvements in renal function. All patients thus operated at a distance from the septic episode survived. If emergency operation is required because of persistent or recrudescnet sepsis, the necessity for dialysis should be considered first; the circumstances demanding dialysis are defined. The priorities in therapy are then: 1) treatment of the infection, 2) treatment of the renal failure, and finally 3) operation. The amount of the operation depends on the evolution of the sepsis, but should be preceded by dialysis when required.