Margherita Dogliani

Vitamin E supplementation in preeclampsia.

An oxidant/antioxidant imbalance has been suggested among the pathogenetic factors involved in preeclampsia. As vitamin E is one of the most important antioxidant body components, a nonrandomized controlled trial was undertaken in 36 preeclamptic patients in order to evaluate the effect of vitamin E supplementation (100-300 mg/day per os) on fetal and maternal outcome. Fetal mortality was similar in 14 patients treated with conventional therapy plus oral vitamin E supplementation (35%) and in 22 patients treated with conventional therapy only (36%). Furthermore, in both groups of patients proteinuria increased, and increased dosages of antihypertensive drugs were called for in order to control blood pressure. We conclude that, with these dosages and in case of an already established disease, vitamin E does not improve fetal outcome in severe preeclampsia. Furthermore, it does not show favorable effects on maternal hypertension and proteinuria.

Hemolytic—Uremic Syndrome during Recombinant α-Interferon Treatment for Hairy Cell Leukemia

We report a case of hemolytic uremic syndrome in a patient suffering from hairy cell leukemia during recombinant α-interferon treatment. We believe that this is the first report of the occurrence of this peculiar kind of acute renal failure following α-interferon therapy. This association may suggest possible speculations regarding side effects of interferon treatment and pathogenesis of hemolytic uremic syndrome.

Acute renal failure in preeclampsia-eclampsia

Acute renal failure (ARF) is regarded as relatively uncommon in preeclampsia-eclampsia (PE-E) and, in any event, of moderate degree or reversible. Cortical necrosis is reported as rare, even in fatal cases. Little light has as yet been shed on the mechanisms responsible for ARF in PE-E. This paper describes 17 cases observed over the last 15 years, in which cortical necrosis (3 histological and 2 clinical diagnoses) was relatively frequent (29.4%). The severity of renal impairment did not appear to be related to chronological age, parity, period of pregnancy in which PE-E commenced and its duration prior to delivery, presence of frank eclamptic crises or the concomitance of earlier vascular or renal disease (p greater than 0.05). The superimposition of abruptio placentae (AP) was the only clinical factor significantly correlated with cortical necrosis (p greater than 0.05). The association PE-E + AP seems to be a particularly unfavorable prognostic sign for the kidney owing to the contribution of additional damage mechanisms (vasospasm, disseminated intravascular coagulation, hemorrhagic shock) furnished by AP, while PE-E itself prepares the ground for AP. The fact that PE-E is difficult to diagnose when AP is the onset symptom may be responsible for the underestimation of its contribution towards the induction of severe renal damage.

Oxygen Free Radicals Are Not the Main Factor in Experimental Gentamicin Nephrotoxicity

As a role for oxygen free radicals has been suggested in gentamicin (G) nephrotoxicity, we tested the hypothesis that exogenously administered glutathione (GSH), able to restore intracellular antioxidant potential, could be useful in reducing damage. Adult Sprague-Dawley rats were injected with saline (n = 30), subcutaneous (s.c.) G 100 (n = 23) and 150 mg/kg/day (n = 14), or s.c. G at the same dosages plus intraperitoneal (i.p.) GSH 1200 mg/kg/day (n = 24 and 14, respectively) for 7 days. In the G-100-day protocol, GSH-treated rats showed significantly lower renal G content (2.79 +/- 0.8 vs. 3.61 +/- 1.4 micrograms/mg prot) coupled with lower plasma urea (153 +/- 79 vs. 188 +/- 61 mg/dL) and creatinine levels (1.63 +/- 1 vs. 2.45 +/- 1 mg/dL). As to renal oxidant/antioxidant balance, local GSH was increased (0.32 +/- 0.01 vs. 0.19 +/- 0.01 microgram/mg prot) while lipid peroxidation, determined by production of thiobarbituric acid reactive substances (TBARS), was decreased (0.35 +/- 0.02 vs. 0.52 +/- 0.02 nmol/mg prot). In the G-150-mg protocol, GSH-treated rats showed no differences in renal gentamicin content or in blood urea and creatinine levels, in spite of a significantly lower renal TBARS production and a significantly higher GSH content. Urine enzyme excretion did not significantly change in GSH-treated vs. not-GSH-treated rats in both protocols. We conclude that: (a) GSH interferes with G nephrotoxicity mainly via a reduction in G uptake; (b) the oxidative renal stress is not crucial in inducing renal damage. In fact, when increased G dosages blunt the ability of GSH in reducing G uptake, no substantial protection is demonstrated.

Concomitant Iron and Aluminum Mass Transfer Following Deferoxamine Infusion During Hemofiltration

Variable tissue overloading can alter the removal rate of iron and aluminum from uremics. Owing to its higher affinity to deferoxamine (DFO) and higher plasma concentrations, Fe could impair Al removal in cases of simultaneous body burden. Fe and Al plasma kinetics and mass transfer were therefore studied in 12 uremic patients with different Fe and Al status: six with normal ferritin levels (less than 400 micrograms/L [ng/mL]), and Al 1.4 to 4.7 mumol/L (40 to 131 micrograms/L) (group A); six with increased ferritin (greater than 2,000 micrograms/L), and Al 1.7 to 17 mumol/L (47 to 476 micrograms/L) (group B). DFO (40 and 80 mg/kg in a random sequence) was administered once a week during the first hour of the first hemofiltration (HF). The results show that in both groups and with both DFO doses, maximum Fe and Al mass transfer was achieved in the first and second HF, respectively. The 80-mg/kg dose of DFO significantly raised Al mass transfer in both groups, whereas Fe mass transfer was only slightly affected. Even though plasma Fe levels were almost always higher than Al, Al mass transfer eventually exceeded that of Fe, in both Fe-normal and Fe-overload patients. The bias towards Al in mass transfer was enhanced in both groups in the second HF, and at the higher DFO doses. Thus, DFO once a week reduced Fe loss to less than 30 mumol/wk in patients with normal ferritin levels. In both Fe and Al overloaded patients, Al can be removed, and Al mass transfer may often exceed Fe mass transfer, depending on the degree of tissue burden, the time from DFO infusion, and the DFO dose.

The role of intravascular coagulation in pregnancy related acute renal failure.

SummaryPregnancy-related acute renal failure (ARF) can include reversible tubular necrosis as well as irreversible cortical necrosis. Though pathogenetic mechanism are not fully understood, disseminated intravascular coagulation (DIC) probably plays a primary role. We report 25 cases of pregnancy-related ARF: 13 were associated with preeclampsia or eclampsia and 12 with obstetric complications. The following parameters were studied: partial thromboplastin, prothrombin and thrombin time, fibrinogen, antithrombin III and FDP levels, platelet count, whole blood clot lysis time and area, fragmented red cells (schistocytes) in the blood smear, hemoglobin, aptoglobin and LDH concentrations. DIC was scored in arbitrary units ranging from 12 to 36 and related to the clinical picture, renal outcome and the treatment employed. Five patients had irreversible renal damage, while 19 recovered fully; one patient died and no renal histology was available. The DIC score did not seem to have a significant relation to the severity of renal damage.

Postpartum acute renal failure in a drug addict

Renal diseases occur in intravenous drug abusers, especially heroin addicts, in the form of interstitial nephritis, nephrotic syndrome or acute renal failure due to rhabdomyolysis. We report a case of acute renal failure not ascribable to rhabdomyolysis nor to the main pathogenetic mechanisms of pregnancy-related acute renal failure in a pregnant heroin addict woman after vaginal delivery following uncomplicated pregnancy. Drug-related immunological abnormalities and microcirculatory distress may be involved.

Intravascular Volume Expansion as Therapeutic Approach to the Underfill State of Preeclampsia

Plasma volume expansion is a central physiological adjustment of normal pregnancy, and inadequate plasma volume expansion has been associated with specific complications of pregnancy, in particular preeclampsia (PE). In view of the important role of atrial natriuretic peptide (ANP) in volume homeostasis, ANP kinetics might help to understand plasma volume changes in different conditions (1). Nevertheless a direct relationship between ANP and plasma volume is evident only in physiological conditions, while in some pathological conditions such as PE, it is possible to observe a dissociation between plasma volume contraction and high ANP level (2–5).

Premises for an Antioxidant Therapy in Pregnancy Induced Nephropathy

Different experimental and clinical observations support an imbalance between oxidant and anti oxidant factors in preeclampsia (PE): a) an increased concentration of lipid peroxides, and byproducts of peroxidation due to free-radicals (1); b) a reduced ability to produce Prostacyclin by the fetal and maternal endothelial cells (2); c) the preeclamptic-like syndrome induced in pregnant rat by a vitamin E deficient diet (3); d) the directly reduced placental Prostacyclin production due to a deficit of Vitamin E (4).