Double-filtration plasmapheresis in the treatment of leg ulcers in cryoglobulinemia.

Hepatitis C virus (HCV) is the major cause of cryoglobulinemia. Skin lesions are frequent and can be cured from the removal of cryoglobulins by therapeutic apheresis. We describe a case of HCV-positive type I cryoglobulinemia with severe leg ulcers, not responsive to antiviral and immunosuppressive treatment. Thirty sessions of double filtration plasmapheresis were performed, over a period of 6 months, with no other associated treatment. Before and after each session an assessment of immunoglobulins, complement, cryocrit, and fibrinogen was made. HCV RNA levels were determined in serum cryoprecipitate, supernatant before and after each session, and in the collection bag. No differences in pre and postapheresis values were observed in the serum concentrations and the supernatant, whereas the postapheresis cryoprecipitate showed a significantly reduced viral load (P < 0.02) as compared with the preapheresis values. There was improvement in the condition of ulcers in the leg during apheresis and had completely regressed by the end of the cycle.

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.

Kidney disease associated with primary antiphospholipid syndrome: clinical signs and histopathological features in an case experience of five cases.

BACKGROUND: The primary antiphospholipid syndrome (PAPS) is characterized by the presence of circulating antiphospholipid antibodies, clinically associated with blood hypercoagulability. Renal involvement in course of PAPS is very frequent, although the true prevalence of PAPS-correlated kidney disease is difficult to estimate. MATERIALS AND METHODS: We reviewed 270 consecutive renal biopsies examined in our Nephrology Division of Bari University Hospital between 1998 and 2004 to identify those performed in patients with PAPS. RESULTS: We identified five biopsies performed in patients with PAPS. In three patients the diagnosis of PAPS was made at onset of the kidney disorder, while in the other two cases the initial diagnosis was primary focal segmental glomerulosclerosis (FSGS). In these cases the subsequent finding of positive antiphospholipid antibodies reoriented the diagnosis toward PAPS-correlated nephropathy. The clinical onset of kidney disease consisted of acute renal failure in three patients and urinary abnormalities in the other two. Histological examination of renal biopsies showed vascular lesions (intimal fibrous hyperplasia, arteriolar hyalinosis, double outline of the capillary walls) in four patients. Focal segmental glomerulosclerosis was present in four patients, two of whom showed double outline of the capillary walls. All patients had tubulo-interstitial lesions, while immunofluorescence was positive in only two patients. All patients preserved stable renal function throughout follow-up (mean value: 10.6 years, range 4 months-24 years). The prevalence of PAPS-correlated nephropathy in our population was 1.85% CONCLUSION: Our data confirm that PAPS-associated nephropathy has slow progression and rarely leads to end-stage renal failure. The prevalence of PAPS-correlated nephropathy is likely underestimated because some patients with a diagnosis of primary focal sclerosis may actually be affected by PAPS.

Nitrendipine and amlodipine mimic the acute effects of enalapril on renal haemodynamics and reduce glomerular hyperfiltration in patients with chronic kidney disease.

Antihypertensive drugs may have an important effect on glomerular haemodynamics. In chronic nephropathy patients, we compared the effect on glomerular haemodynamics of two second-generation dihydropyridinic agents, nitrendipine and amlodipine, with a first generation dihydropyridinic agent and an ACE-inhibitor, enalapril. In all, 32 patients (pts), divided into four groups, received the different drugs: ENA (enalapril, eight pts), NIF (nifedipine, eight pts), NIT (nitrendipine, eight pts) AML (amlodipine, eight pts). The study assessed the effect on glomerular haemodynamics of a single administration of the test drug in baseline conditions and in glomerular hyperfiltration experimentally induced by amino-acid infusion. The glomerular filtration rate (GFR, measured by inulin clearance), effective renal plasma flow (ERPF, measured by p-aminohippurate clearance), renal vascular resistances (RVR) and filtration fraction (FF) were assessed. Administration of AML and NIT test dose reduced FF, as did ENA, but not NIF, in both baseline (AML: P=0.005; NIT: P=0.02; ENA: P=0.007) and glomerular hyperfiltration conditions (AML: P=0.0003; NIT: P=0.03; ENA: P=0.00006). In baseline conditions, only ENA resulted in a significant drop in the GFR (P=0.008), while NIF, NIT and AML induced a significant increase (P=0.003, 0.03, 0.0001, respectively). However, in hyperfiltration conditions, NIT (0.08) and AML (0.00003) caused a decrease in the GFR, as did ENA (0.0003) but not NIF. In all the experimental conditions, a RVR reduction and an ERPF increase were observed. Single dose of NIT and AML were effective in attenuating the effect of amino-acid infusion on glomerular filtration, similar to ENA; this effect of NIT and AML on the glomerular filtration rate is not observed under basal conditions.

A rare case of central post-gravid diabetes insipidus.

Central diabetes insipidus (CDI) arising in the puerperal period has been attributed mainly to Sheehan's syndrome or to lymphocytic infundibulo-neurohypophysitis. We report the case of a 24-year-old woman who came to our observation for the appearance, 3 weeks after a normal delivery, of a polyuric-polydipsic syndrome. Measurements of urinary volumes, plasma osmolality and urinary osmolality, in conditions of free water intake, water deprivation and a water deprivation-vasopressin administration test, demonstrated CDI. Brain magnetic resonance imaging showed a normal morphology of the adenohypophysis and total absence of the neurohypophysis. Assays of the pituitary hormones were found to be within normal limits. These results, incompatible with a diagnosis of Sheehan's syndrome and lymphocytic infundibulo-neurohypophysis, excluded all the other known causes of acquired CDI. Our diagnosis was therefore of post-gravid idiopathic CDI. Thus, it is possible that in the puerperal period other diseases of the posterior hypophysis may develop, of unknown etiopathogenesis but equally responsible for CDI.

A simple method for correcting overestimated glomerular filtration rate in obese subjects evaluated by the Cockcroft and Gault formula: a comparison with 51Cr EDTA clearance.

AIM: The Cockcroft and Gault formula is a quick and reliable method for calculating creatinine clearance without a 24-hour urine collection (CG-cl). In obese subjects an excess of fat mass provokes a reduction in daily creatinine urine excretion per body kilo weight and is responsible for overestimated renal function when calculated by CG-cl. The aim of this study was to devise a simple correction method which could also make use of CG-cl in obese subjects. PATIENTS AND METHODS: In 52 subjects with a body mass index (BMI) > 25, renal function was assessed by simultaneously determining creatinine clearance using 24-hour urine collection (Cr-cl) and the CG-cl. The percentage difference between the 2 clearances (delta %) was correlated with BMI for each patient using simple linear regression analysis. The estimated regression model (delta% = 1.217 BMI-- 24.81) provided the following CG-cl correction formula for obese subjects: Corrected CG-cl = CG-cl (1.25 - 0.012 BMI). Its validity was evaluated in another group of 20 subjects with BMI > 25 by comparing the results obtained with Corrected CG-cl to those obtained by CG-cl and MDRD formula (MDRD-cl) using the clearance of 51Cr-EDTA (5 Cr-EDTA-cl) as the GFR measurement gold standard. RESULTS AND CONCLUSION: Linear regression analysis of CG-cl, MDRD-cl and Corrected CG-cl compared to 5tCr-EDTA-cl (considered as the independent variable) resulted in the following determination coefficients (R2): 0.687; 0.818; 0.947, respectively. In conclusion, this formula can be considered a quick and reliable method for CG-cl correction in obese subjects.

Effectiveness of long-term heparin-induced extracorporeal LDL precipitation (HELP) in improving coronary calcifications.

There is clear clinical evidence that a drastic lowering of plasma LDL-Cholesterol (LDL) concentrations significantly reduces the rate of total and coronary mortality as well as the incidence of cardiovascular events in high risk hypercholesterolemic patients. We describe the case of a 51-year-old woman with coronary heart disease (CHD) who presented with increasing angina on exertion in 1995, at the age of 45. She suffered from a heterozygous familial hypercholesterolemia and in 1985 her total cholesterol (TCHO) was 328 +/- 62 mg/dl (mean value of ten analysis). After ten years of statins her mean values (20 analysis, 2 per year) were: TCHO 259 +/- 71, LDL 209 +/- 47, HDL 35 +/- 7 mg/dl. Coronary angiography (CA) performed in 1995 disclosed three vessel coronary heart disease with significant stenoses of the distal right coronary artery, multiple calcifications of the interventricularis artery and multiple plaques with significant stenoses in the ramus circumflexus. The woman underwent coronary by-pass surgery. Thereafter the patient was treated for six years with HELP in biweekly intervals, in combination with statins. TCHO, LDL, HDL and fibrinogen (fb) levels were measured before and after each treatment. Their mean values for an amount of 120 sessions were: TCHO pre 216 +/- 23, post 111 +/- 18 LDL pre 152 +/- 16 post 67 +/- 18, HDL pre 42 +/- 5 post 35 +/- 4 fb pre 306 +/- 48 post 125 +/- 31. In 2001 a new CA was performed. Calcifications disappeared and stenoses were identical to the previous CA or reduced. There were no further clinical manifestations of CHD. We trust that the clinical benefit of the HELP procedure will be substantial for those patients who have problems in clearing LDL from their plasma pool and who are at the same time sensitive to elevated LDL levels by the development of premature coronary sclerosis.

LDL-apheresis in acute anterior ischemic optic neuropathy.

Acute anterior ischemic optic neuropathy (AION) is a disabling disease which impairs visual function. Standard treatment is unable to affect the outcome and the visual damage persists. We describe the case of a 64-year-old patient affected by AION, whose only known risk factor was hypercholesterolemia. After a first onset of involvement of the right eye (RE), the patient presented four weeks later with an analogous episode affecting the left eye (LE). Since standard treatment, started at involvement of the RE, had not yielded any beneficial effect, the patient underwent three sessions of LDL apheresis. The scotomatous portion of the visual field reduced even after the first session, there was further improvement after the third, and after six months the condition remained stable. Corrected vision improved from 2/10 to 6/10 after the third session. LDL cholesterol and fibrinogen decresade after the third session from 239 mg/dL to 31 mg/dL and from 289 mg/dL to 92 mg/dL, respectively. In conclusion, thanks to its effect of antagonizing hemorheologic disorders of the ocular microcirculation, LDL apheresis seems to be an efficacious treatment of AION, especially in patients suffering from hypercholesterolemia.

LDL apheresis in the treatment of non-arteritic ischaemic optic neuropathy: a 6-month follow-up study.

PURPOSE: Verify the recovery of visual capacity after the administration of a combination of LDL apheresis (LA) and conventional therapy (CT). Design, prospective and interventional case series. METHODS: 20 patients affected by NAION were randomly subdivided into two groups of 10 patients (Group 1 and Group 2). Group 1 underwent three sessions of LA associated with CT, whereas group 2 received only CT. At discharge and at the 6 months follow-up visit, assessment in both groups was made of the best corrected visual acuity (BCVA) and the computerised visual field (CVF), comparing the findings with those at admission in each patient. RESULTS: Only the mean deviation (MD) at CVF was statistically improved in group 1 as compared with group 2 at discharge, judged against the values at admission (-11.08+/-6.51 vs -16.53+/-10.03, P=0.039; -17+/-5.24 vs -14.14+/-9.42, respectively). However, this increase was not confirmed at 6 months (-16.83+/- -10.72, group 1; -13.56+/-3.60 group 2). CONCLUSION: In NAION, LA induced a short term improvement in the MD, but by 6 months this had disappeared.

Is the efficacy of LDL apheresis in ischemic optic neuropathy linked to a reduction in endothelial activation markers?

Endothelial dysfunction of the optic microcirculation is considered to be the main pathogenetic mechanism in nonarteritic ischemic optic neuropathy. The aim of the present work was to assess whether a clinical improvement is correlated with a reduction in the endothelial activation markers by means of LDL apheresis (LDLA). Three weekly sessions of LDLA were administered in 23 patients affected by nonarteritic ischemic optic neuropathy. Statistically significant reductions were achieved in all parameters: total cholesterol (44.6%), LDL cholesterol (54.6%), fibrinogen (60.9%), von Willebrand factor (38.6%), sE-Selectin (22.6%), sICAM-1 (14%) and sVCAM-1 (15.5%), each of which was correlated with an improvement in the mean deviation of the visual field, although statistical significance for the single parameters was not reached. However, analysis of variance between the mean deviation improvement and the set of parameters taken together yielded highly significant results (p < 0.0001). LDLA was effective in reducing the values of all evaluated endothelial activation markers, and this trend was correlated with an improvement in the visual field.