Pasquale Coratelli

Acute Renal Failure During Intermittent Rifampicin Therapy

A case of acute renal failure during intermittent rifampicin therapy (600 mg once a week) is reported. The anuria persisted for 6 days and was followed by prompt recovery. A renal biopsy showed tubula

LDL-Apheresis Accelerates the Recovery of Nonarteritic Acute Anterior Ischemic Optic Neuropathy

Abstract:  Nonarteritic acute anterior ischemic optic neuropathy (NAION) is a disabling disease which impairs visual function. It is presumed to result from disturbances of microcirculation in the anterior portion of the optic nerve head due to hemodynamic factors derived from excessive blood viscosity, or restriction of the vasal lumen in hypertensive, hypercholesterolemic, diabetic patients. We aimed to determine whether acute reduction of plasma fibrinogen and serum low‐density lipoprotein (LDL) cholesterol is effective for treatment of NAION. We recruited 11 patients (7 females, 4 males) with a mean age of 57.2 ± 19.6 years. All except one of them presented risk factors for atherosclerosis. The mean values of LDL‐cholesterol and fibrinogen before treatment were 144 ± 32 mg/dL and 341 ± 80 mg/dL, respectively. All were treated with standard therapy (prednisone, salicylate, pentoxiphyllin) and underwent three sessions of LDL‐apheresis (HELP system—B Braun) that can reduce plasma LDL‐cholesterol and fibrinogen by more than 50% in a very short time. In all patients we observed a drastic reduction of LDL cholesterol and fibrinogen and a clear improvement in the visual functional data. In fact, mean values of corrected vision increased from 3.7/10 ± 3/10 to 7.9/10 ± 2.2/10 (P = 0.002) after the third session, while the scotomatous portion of the visual field regressed after the first session, and in 5 patients further regressed after the third session. This improvement had remained stable after 3 months. Thanks to its effect of antagonizing hemorheologic disorders of the ocular microcirculation, fibrinogen/LDL‐apheresis seems to be an efficacious treatment of NAION.

Effect of Low-Density Lipoprotein Apheresis on Circulating Endothelial Progenitor Cells in Familial Hypercholesterolemia

Background: Long-term treatment with low-density lipoprotein (LDL) apheresis (LA) has been shown to reduce the incidence of cardiovascular events in patients affected by familial hypercholesterolemia (FH). Data from experimental studies suggest that circulating endothelial progenitor cells (EPCs) can repair the vascular lesions caused by atherosclerosis. Since a reduction of these cells has been demonstrated to predict atherosclerosis progression, the aim of this study was to verify whether LA can increase the percentage of EPCs. Methods: In 15 patients affected by FH periodically treated with LA, the percentage of EPCs was determined before and after performing LA, and compared with the values of 15 control subjects and 15 hypercholesterolemic patients treated with statins. Results: Significant differences were found in FH patients between the pre-apheresis percentages of CD34+/KDR+, defined as EPCs by a wide consensus of opinion, and the values found 24 h after the procedures (0.00868 ± 0.003 vs. 0.01009 ± 0.002%, p < 0.005). Instead, the percentages of CD34+/KDR+/CD133+, considered as an immature subset of EPCs, remained substantially unchanged. However, a significant reduction in the percentage of EPCs was observed in both patient groups as compared to the controls, at all the assessment times. Conclusion: In the short-term LA seems to stimulate mobilization of CD34+/KDR+ cells. Hypercholesterolemic patients show a lower percentage of EPCs than controls. There were no differences in the EPCs percentages between the 2 patients groups, despite the fact that LDL cholesterol levels were higher in the group undergoing LA.

Fibrinogen Apheresis in the Treatment of Peripheral Arterial Disease

Background: Fibrinogen is mainly responsible for determining the viscosity of whole blood. In peripheral arterial disease (PAD) the fibrinogen concentration seems to affect the microcirculation flow. Aim: To study the effects of an abrupt reduction of fibrinogen on the hemodynamics of the lower extremities and the clinical picture of patients with PAD. Methods: Ten patients affected by various stages of PAD underwent 1 session of fibrinogen apheresis (TheraSorb, Miltenyi Biotec, Germany). Laboratory parameters of endothelial activation were assessed before and after the session, as well as walking distance (WD), the ankle-brachial index and laser Doppler flowmetry. Results: A significant reduction in the laboratory parameters was observed: fibrinogen (50%), total cholesterol (18%), LDL cholesterol (24%), sE-selectin (23%), sICAM-1 (19%) and sVCAM-1 (10%). The procoagulant factors, factor VIII and von Willebrand factor, did not vary significantly. Both pain-free and total WD were significantly improved (p < 0.003 and p <0.006, respectively), the ankle-brachial index remained unchanged, and laser Doppler flowmetry showed a modest but not significant increase. Conclusions: Fibrinogen apheresis allowed us to study the effects of an acute modification of fibrinogen in PAD, on both some aspects of the endothelial function and on the hemodynamics, demonstrating an improvement of WD and a minimal increase in the skin microcirculation.

A Case Report of Double Filtration Plasmapheresis in an Acute Episode of Multiple Sclerosis

Abstract:  Plasma exchange has been proposed as support therapy in both acute and chronic forms of multiple sclerosis (MS). For the first time, we aimed to assess whether double filtration plasmapheresis (DFPP) could be clinically efficacious. We describe the case of a patient affected by MS who developed a severe crisis refractory to conventional steroids, and immunosuppressive and immunomodulating therapy. The patient underwent 12 sessions of DFPP. In each session 3000 mL of plasma was treated. Before and immediately after each session the routine laboratory parameters were assessed. Before the apheresis cycle and one month after the end of treatment, encephalic magnetic resonance imaging (MRI) was performed. A neurological examination and assessment of the extended disability status scale (EDSS) were made once each week from the beginning of treatment until one month after the end of the cycle. No therapy was administered during the course of the apheresis cycle, with the exception of a scaled dose of steroids, that was completely withdrawn half‐way through the cycle. The immunoglobulin (Ig) G, IgA and IgM values declined from 465 ± 104 mg/dL, 69 ± 18 mg/dL, 34 ± 16 mg/dL, respectively, pre‐apheresis to 331 ± 76 mg/dL, 42 ± 5 mg/dL, 15 ± 6 mg/dL, respectively, post‐apheresis; C3 and C4 decreased from 105 ± 27 mg/dL and 21 ± 5 mg/dL to 75 ± 9 mg/dL and 15 ± 4 mg/dL, respectively; fibrinogen went from 228 ± 72 mg/dL to 128 ± 28 mg/dL. The EDSS dropped from a value of 6 before the cycle to 5.5 one month after the end of the treatment. As compared with the pretreatment conditions, post‐apheresis MRI showed stabilization of the lesions already present, the reduction of one lesion and a complete absence of enhancement of all lesions. DFPP, adopted for the first time in MS, seems to foster a short‐term improvement in both the clinical and magnetic resonance images during an acute MS episode.

Endotoxemia in Hemolytic Uremic Syndrome

Hemolytic uremic syndrome (HUS) was diagnosed and confirmed by renal biopsy in an 18-year-old primigravida at the 13th week of pregnancy. Circulating endotoxin was detected and the endotoxemia was progressively reduced by hemodialysis (HD) performed daily from the 3rd to the 9th day of disease. Complete normalization of the renal function was observed on day 34. The authors emphasize the importance of detecting endotoxemia in HUS in order to initiate dialysis early; at the same time they also discuss the pathogenetic role of endotoxin in this disease.

Cutaneous Microcirculation Is Impaired in Early Autosomal Dominant Polycystic Kidney Disease

Background/Aims: An endothelial dysfunction has been described in autosomal dominant polycystic kidney disease (ADPKD) before the development of hypertension and renal impairment. The aim of this work was to verify the existence of a microvascular reactivity in the early stages of ADPKD. Methods: Fifteen ADPKD normotensive patients with normal renal function underwent laser Doppler examination of the cutaneous microcirculation in basal conditions and after the warm test, as well as evaluation of plasma concentrations of some endothelial activation parameters [total cholesterol and fractions, fibrinogen, von Willebrand factor, Lp(a)]. The results were compared with those in 15 healthy subjects, 15 essential hypertensive patients and 15 hypertensive ADPKD patients with normal renal function. Results: Both basal and post-warm-test values were significantly lower in normotensive ADPKD subjects than controls (3.2 ± 1 vs. 5.8 ± 1.3 AU, p = 0.0001; 35.2 ± 10.9 vs. 50.5 ± 10.8 AU, p = 0.005, respectively). All evaluated parameters were within normal limits and comparable between normotensive ADPKD subjects and controls, except for LDL cholesterol (125 ± 18 vs. 101 ± 22 mg/dl, p = 0.01) and Lp(a), which was significantly higher in the ADPKD subjects (52.2 ± 36 vs. 6.0 ±4 mg/dl, p = 0.0006). Conclusion: Our study confirms the existence of a systemic microcirculation defect in ADPKD. The presence of high levels of Lp(a) could contribute to causing the high incidence of cardiovascular events in ADPKD.

Prognosis in Acute Renal Failure Accompanied by Jaundice

The mortality rate of 67 sequential cases of acute renal failure (ARF) accompanied by jaundice was compared with the mortality rate of 168 patients without jaundice. The mortality rate in the group of jaundiced patients was 57%, significantly greater (p less than 0.05) than the 42% mortality in patients without jaundice. The mortality rate correlated with serum bilirubin levels; patients with serum bilirubin greater than 20 mg% had a mortality rate of 85%, whereas patients with levels lower than 10 mg% had a mortality rate of only 33%. Average blood pressures were significantly lower (p less than 0.01) in patients with jaundice than in those without. The data indicate that: (1) ARF accompanied by jaundice carries a worse prognosis; (2) reduced blood pressure which accompanies this condition may be an aggravating factor, and (3) serum bilirubin levels may be used as a prognostic index.

Acute renal failure after septic shock.

The problem of sepsis and acute renal failure(ARF)remains to date a major unsolved challenge to nephrologists. Despite the regular use of dialysis and other major improvements in the management of patients (pts) with ARF,mortality continues to be distressingly high(1,2).

Role of Endotoxin in Hepatorenal Syndrome

It is known that patients affected by liver cirrhosis may develop functional renal failure induced by circulatory disorder of the kidney, likely due to active vasoconstriction with reduction of cortical perfusion (1), and characterized by reduced glomerular filtration rate with intact tubular function. In fact the urine sodium concentration in these patients is extremely low, usualy less than 10 milliequivalent per liter, and urine sediment is relatively unremarkable. This type of renal failure is called hepatorenal syndrome (HRS) and many factors have been considered in its pathogenesis, including activation of the renin — angiotensin system due to reduced “effective” blood volume (2,3,4), increase in sympathetic nervous system activity (5,6,7,8), alterations in the endogenous release of renal prostaglandins (9,10,11,12,13,14,15) and changes in the kallikrein-kinin system (16).