G. Mecca

Prognosis of Untreated Patients with Idiopathic Membranous Nephropathy

Background Defining the most appropriate treatment for patients with idiopathic membranous nephropathy is a matter of controversy. The course of the disorder is often benign, and the immunosuppressive regimens used in some patients have uncertain benefits and substantial risks. We studied the natural history of idiopathic membranous nephropathy in patients who received only symptomatic therapy. Methods We prospectively studied 100 consecutive patients (68 men and 32 women; mean [±SD] age, 51 ±17 years) with biopsy-proved idiopathic membranous nephropathy. The patients received diuretic or antihypertensive drugs as needed, but no glucocorticoid or immunosuppressive drugs. We examined the patients and measured their urinary protein excretion and serum creatinine concentrations every 6 months for a mean of 52 months. Results Twenty-four (65 percent) of the 37 patients followed for at least five years had complete or partial remission of proteinuria; in 6 others (16 percent), end-stage renal disease developed...

HÆMOLYTIC-URÆMIC SYNDROME: DEFICIENCY OF PLASMA FACTOR(S) REGULATING PROSTACYCLIN ACTIVITY?

It is suggested that patients with the haemolytic-uraemic syndrome and related disorders (such as thrombotic thrombocytopenic purpura) lack a plasma factor which stimulates prostacyclin (P.G.I2) activity. Normal plasma would supply the missing factor and is a rational treatment for some life-threatening symptoms (thrombocytopenia, haemolytic anaemia, hypertension) of this syndrome.

Reduced umbilical and placental vascular prostacyclin in severe pre-eclampsia

Prostacyclin production was significantly depressed in foetal and placental vascular tissues from five patients with severe pre-eclampsia in comparison to vascular tissues from women with uncomplicated pregnancy. Such an abnormality may be responsible for a reduced blood flow and defective fetal nutrition thus playing a major role in the pathogenesis of this syndrome.

Bleeding in renal failure: altered platelet function in chronic uraemia only partially corrected by haemodialysis

Bleeding time, blood loss and platelet retention by glass beads, measured by standardized techniques, were significantly altered in a group of 30 non-thrombocytopenic patients with chronic renal failure undergoing maintenance haemodialysis. Bleeding time or blood loss did not correlate with platelet retention either before or after haemodialysis. No correlation could be found between the above tests and a number of biochemical parameters characterizing the uraemic condition. Haemodialysis only partially corrected the abnormal bleeding time, blood loss and platelet retention. These tests were still significantly different after haemodialysis from those of 30 normal subjects. It is suggested that some non-dialyzable material could play an important role in the aetiology of uraemic bleeding.

PROSTACYCLIN-LIKE ACTIVITY AND BLEEDING IN RENAL FAILURE

Specimens of venous tissue from three normal subjects and three patients with renal failure and very prolonged bleeding-times showed prostacyclin-like activity (inhibition of platelet aggregation) during incubation at room temperature. The specimens from all three uraemic patients showed more prostacyclin-like activity than those from the controls. After repeated washings, when this activity could hardly be detected in the controls, pronounced inhibitory activity was still evident in samples containing venous tissue from the three uraemic patients. These findings may be relevant to the pathogenesis of bleeding in renal failure.

Prostacyclin and human foetal circulation.

Tissues from human umbilical cord arteries and placental veins generated much greater prostacyclin activity than vessels from normal adults. High prostacyclin generation could contribute to maintaining the low peripheral vascular resistance typical of foetal circulation in which blood pressure is low despite very high cardiac output.

Moderate doses of aspirin and risk of bleeding in renal failure

Uraemic patients have a bleeding tendency thought to be due to platelet functional abnormalities, but haemodialysis paradoxically exposes patients to the thrombotic complications of arteriovenous shunts. Possible treatments of the latter have been debated. The effect of 100 mg/m2 aspirin on haemostatic function was studied in 29 uraemic patients on chronic haemodialysis who had normal or only slightly prolonged bleeding times. Aspirin did not significantly affect bleeding time in healthy controls but prolonged it in uraemic patients. In 12 of the 29 uraemic patients, the bleeding time after aspirin was longer than 15 min. Aspirin completely abolished thromboxane A2 generation by both control and uraemic platelets, indicating that its effect in uraemic patients is not due to differential inhibition of platelet cyclo-oxygenase. Products of lipoxygenase enzyme and factor VIII von Willebrand factor did not seem to have a role. A careful risk-benefit evaluation is necessary before giving aspirin to uraemic patients on haemodialysis to prevent thrombosis of the arteriovenous shunt.

Altered platelet and vascular prostaglandin-generation in patients with renal failure and prolonged bleeding times.

Abstract Venous tissues from 15 patients with renal failure (five acute and 10 chronic) generated significantly higher PGI2-like (platelet aggregation inhibitory) activity than venous tissues from 10 normal subjects. The longer the bleeding times, the higher the values for PGI2-like activity found in these patients. Both bleeding times and PGI2-like activity values returned to normal in three acute uraemic patients on restoration of their renal function. Two additional patients with acute renal failure and greatly prolonged bleeding times were under aspirin treatment at the moment of this study: venous specimens from neither of them generated measurable amounts of PGI2-like material. Malondialdehyde formation in platelets from 12 patients with chronic renal failure and prolonged bleeding times was significantly lower than in platelets from 11 controls. The defect was evident with each of the three stimuli used, i.e., collagen, arachidonic acid and thrombin. It is concluded that prostaglandin metabolism in platelets and in the vessel wall from uraemic patients is impaired in different ways, both contributing to the impaired primary haemostasis in these patients.

Haemolytic uraemic syndrome: therapeutic effect of plasma infusion

The therapeutic effect of plasma infusion was evaluated in 10 children and seven adults with haemolytic uraemic syndrome. All but one patient responded to this treatment with rapid disappearance of haematological abnormalities. The patient who apparently failed to respond to plasma infusion obtained complete remission of the disease after plasmapheresis. Although 15 of the 17 patients were anuric or oliguric on admission, renal function recovered completely in eight children and two adults. Seven patients showed residual chronic renal failure and two required long-term maintenance haemodialysis. Treatment with plasma was also successful in patients with relapses or recurrent episodes. Plasma infusion is a promising therapeutic approach for the haemolytic uraemic syndrome and deserves further study in clinical trials.

Plasmatic regulation of vascular prostacyclin in pregnancy.

Activity of prostacyclin-stimulating factor was measured in six normal, non-pregnant women, six women in early normal pregnancy, six in late normal pregnancy, and six in late pregnancy complicated by severe pre-eclampsia. The activity was lower in the women in late pregnancy than in those in early pregnancy and the controls but was about normal in those with severe pre-eclampsia. These results may be relevant to the physiology of pregnancy and the pathogenesis of pre-eclampsia.