Polymethylmethacrylate membrane and serum free light chain removal: enhancing adsorption properties.

INTRODUCTION: Polymethylmethacrylate (PMMA) membranes can adsorb a wide variety of uremic toxins including serum free light chains (sFLC). However, limited data are available regarding the clinical use of PMMA in multiple myeloma patients and its maximum adsorption capacity in this setting. AIM: This study aimed to measure the capacity of PMMA to adsorb sFLC and identify strategies to improve its efficiency in clinical practice. METHODS: Ten patients with dialysis-dependent renal failure and high levels of sFLC were included in the study. Five patients received standard PMMA hemodialysis (HD; n = 18), while in the other 5 patients a new technique called enhanced adsorption dialysis (EAD) was used, which involves PMMA dialyzer replacement after 2 h (n = 19). In all patients, sFLC were measured at the beginning and at the end of each dialysis session to calculate the difference between start and end of treatment and the percentage removal. RESULTS: PMMA membranes reduced sFLC in both the PMMA HD and EAD groups. PMMA HD showed similar efficiency on κ and λ percentage removal (22.3 and 21.0%, respectively, n.s.) but, in contrast, had a significantly greater effect on the delta of sFLC in κ [1,555 mg/l (-511 to +6,027)] versus λ [390 mg/l (120-650)] treatments (p = 0.007). EAD treatments only partially increased percentage removal of κ sFLC (22.3-31.0%, p = 0.38), while they had a significantly great effect on λ (21.0-53.1%, p = 0.003). A positive linear correlation was found between delta sFLC and pre-HD sFLC concentrations in PMMA HD κ treatments (r = 0.68, p < 0.02) but not for λ treatments (r = 0.54, p = 0.21), while the analysis of patients receiving EAD demonstrated a strong positive correlation for both κ and λ subtypes (r = 0.81 and r = 0.85, respectively, p < 0.008). In EAD sessions, a positive linear correlation was shown between blood flow during treatment and percentage removal of sFLC (r = 0.58, p = 0.02); however, with PMMA HD such a correlation was not observed (r = 0.28, p = 0.25). CONCLUSIONS: PMMA membranes can efficiently adsorb sFLC, but the process is limited by membrane saturation and is different between κ and λ sFLC. The new EAD technique can greatly improve λ removal but only partially act on κ sFLC. Therefore, EAD should be considered a valid economic treatment option without side effects in particular subsets of patients for the removal of sFLC.

Natural course of temporomandibular disorders with low pain-related impairment: a 2-to-3-year follow-up study.

To describe the natural course of temporomandibular disorders (TMD) in patients with low levels of pain-related impairment, independently by the physical diagnoses they received. Amongst all patients who attended the TMD Clinic, University of Padova, Italy, during the year 2009, those who: (i) had Research Diagnostic Criteria for TMD (RDC/TMD) axis II Graded Chronic Pain Scale (GCPS) grade 0 or 1 scores, (ii) received counselling on their signs and symptoms at the time of their first visit and suggestions on how to self-manage their symptoms, (iii) did not attend the Clinic since the time of their last visit and (iv) were visited by the same resident, were recalled for a follow-up assessment during the period from September to December 2011. Sixty-nine patients (79% females; mean age 47.4 ± 11.3 years; range 26-77) of 86 who were potentially eligible accepted to enter the study. The time span since the first visit ranged from 23 to 36 months. At the follow-up assessment, the percentage of patients with muscle disorders decreased from 68.1% to 23.1%; disc displacement with reduction remained unchanged (52.1%), whilst the 5.7% of patients who had disc displacement without reduction with limited opening then showed absence of limitation; diagnoses related to other joint disorders decreased from 30.4% to 14.4% for arthralgia and from 27.5% to 24.6% for osteoarthritis/osteoarthrosis. In a sample of patients TMD with low pain-related impairment followed up with a single recall assessment at 2-to-3 years, the natural course of disease was generally favourable.

Changes in proteinase 3 anti-neutrophil cytoplasm autoantibody levels in early systemic granulomatosis with polyangiitis (Wegener's) may reflect treatment rather than disease activity.

OBJECTIVES: To investigate the nature of the relationship between proteinase 3 anti-neutrophil cytoplasm autoantibody (PR3-ANCA) and relapse in patients with early systemic granulomatosis with polyangiitis (Wegener's) (GPA). METHODS: Clinical data from 16 relapsing and 12 non-relapsing patients with early systemic GPA from a randomised clinical trial were correlated to monthly PR3-ANCA values over 18 months. Each sample was examined using 9 different enzyme-linked immunosorbent assays (ELISAs) to ensure reliability of ANCA results. PR3-ANCA peaks were identified by the highest sum of logarithmic transformation values from all assays in samples after remission. RESULTS: A PR3-ANCA peak was identified in all relapsing and non-relapsing patients and coincided with relapse in all 14 evaluable relapsing patients. The monthly increment before the peak, however, was similar in relapsing and non-relapsing patients in all assays. Increments from remission to peak were higher in relapsing patients in 2/9 assays. PR3-ANCA values at entry and peak PR3-ANCA values were higher in relapsing patients in 3/9 and 2/9 assays, respectively. However, large overlaps of PR3-ANCA values prevented a distinction between relapsing and non-relapsing patients. The median time to reach peak values was 14 months in relapsing and 12 months in non-relapsing patients with scheduled termination of treatment at 12 months. CONCLUSIONS: The predictive value for relapses of PR3-ANCA determinations confirm and extend previous reports. Although all relapses were related to PR3-ANCA increases, reduction or withdrawal of immunosuppression without relapse was also related to increases and may explain the lack of predictive value of sequential PR3-ANCA determinations.

[Heparin-induced thrombocytopenia syndrome and thrombosis in patients undergoing periodic haemodialysis]. / La sindrome di trombocitopenia e trombosi indotte dall eparina (HIT) in emodialisi.

Heparin-induced thrombocytopenia (HIT) is the most important immunological drug reaction that patients face today. Being unfractionated heparin the standard anticoagulation used in haemodialysis, acute or chronic uremic patients starting haemodialysis are at risk of developing HIT. Through the accurate description of two patients, one with chronic and the other with acute uraemia, who developed this complication at the start of haemodialysis, we compare the distinct clinical problems of haemodialysis-related HIT with the general clinical features of HIT. We report the occurrence of repeated clotting of both dialysers and catheters, as well as thrombosis of the central veins where the catheters are placed and of the fistulas. We also report an accurate review of the literature on haemodialysis-related HIT. We have observed that HIT seems to be particularly rare in haemodialysis patients. Since newly treated haemodialysis patients are at risk of developing HIT, and most of the studies were made on long-term chronic haemodialysis patients, we assume that the syndrome is poorly documented. Our own experience on 37 haemodialysis patients who developed HIT is reported by focusing on both the clinical presentation of HIT as well as the long-term follow up of the patients. We present some considerations on the treatment options of acute HIT in uremic patients as well as on the problem of heparin re-exposure subsequent to the HIT episode, a very prominent problem in chronic haemodialysis patient.

alpha 1-Antitrypsin (AAT) deficiency and ANCA-positive systemic vasculitis: genetic and clinical implications.

A high incidence of alpha 1-antitrypsin (AAT) deficiency has been reported in patients with C-ANCA systemic vasculitis in association with antibodies against proteinase-3 (PR3). To clarify the role of AAT deficiency in the acute vasculitic process as well as in progression of the disease, we studied 84 patients with either C-ANCA or P-ANCA vasculitis with special reference to: (a) the AAT gene, (b) the phenotypic (Pi) variants and (c) the serum levels during both acute illness and remission. The PiZ gene was found in six patients (8% vs. 1.5% controls) irrespective of the type of autoantibodies (C-ANCA vs. P-ANCA). All PiZ patients displayed the ability to raise their AAT serum levels up to the normal range during acute illness. In contrast, 24 patients with the PiM phenotype presented low AAT serum levels during acute illness. In all these patients, the AAT levels returned to normal values during the remission. Low AAT levels were associated with low levels of C-reactive protein (PCR) (P < 0.001), with a less severe renal involvement or a minor risk of death, and, in one tested patient, with a novel point mutation (TCGA-->TCAA) at the enhancer-promoter region of the AAT gene. Low AAT serum levels did not correlate with either type/titre of autoantibody or distribution/severity of the vasculitis process. In the case-control study, high AAT levels emerged as a major determinant of progression towards end-stage renal failure [odds ratio 3 (95% CI 1.1-8.4)]. These results indicate: (a) a high incidence of the PiZ gene of AAT in systemic vasculitis irrespective of the type of autoantibodies; (b) a novel form of AAT deficiency associated with the normal PiM phenotype becoming manifest only during acute illness; (c) dysregulation of the acute-phase response affecting selectively AAT or both AAT and PCR; (d) correlation between low plasma levels of AAT and less severe renal involvement or risk of death.

Lack of IgA antineutrophil cytoplasmic antibodies in Henoch-Schönlein purpura and IgA nephropathy.

To verify whether IgA antineutrophil cytoplasmic antibody (ANCA) represents a serologic marker in Henoch-Schönlein purpura (HPS), we examined sera from 41 patients with the disease. Control sera from 28 patients with primary IgA nephropathy (IgA-N), 26 IgG-ANCA-positive vasculitis, and 28 normal controls were also studied. An increased IgA binding to neutrophil cytoplasmic extracts but not to purified ANCA antigens was found in 12.2-14.6% of HSP patients and in 14.3-21.4% of IgA-N patients versus 3.5% of normal controls. IgA binding to neutrophil cytoplasmic extracts correlated with serum IgA levels, IgA-rheumatoid factor, and IgA-fibronectin binding capacity. Moreover, low amounts of IgG and fibronectin were detected as contaminants in neutrophil cytoplasmic extracts and fibronectin could partly inhibit the binding of IgA to "crude" extracts. We conclude that IgA-ANCA are neither diagnostically nor immunologically specific in HSP and IgA-N. Several factors present in the sera of patients with IgA-related nephropathies seem to contribute to the "false-positive" IgA-ANCA demonstrable in these patients.

Association between silica exposure and necrotizing crescentic glomerulonephritis with p-ANCA and anti-MPO antibodies: a hospital-based case-control study.

A hospital-based case-control study was carried out to investigate the association between ANCA positive rapidly progressive glomerulonephritis (RPGN) and occupational exposure to silica dust. All ANCA positive male patients admitted to the Department of Nephrology of the University of Brescia between 1987 and 1992 were enrolled in the study as cases. The controls were pts of the same age, admitted at the Department immediately before or after the cases, affected by other renal diseases. Seven of the 16 cases and one of the 32 controls, had a positive history for jobs exposing to silica dust (relative risk 14; 95% C.I.: 1.7-113.8, p < 0.001). ANCA pattern was p-ANCA with anti-MPO antibodies in 6/7 of exposed pts. The review of renal histology showed a distinctive glomerular lesion consisting in peripheral nodular areas of glomerular sclerosis, in addition to the crescentic necrotizing glomerulonephritis, in 3/6 silica exposed pts, but in none of the unexposed pts.

Clinical manifestations in patients on chronic dialysis with high titres of ANCA.

Eight untreated patients with an apparent renal-limited disease continued to maintain high titres of ANCA long after the onset of the disease and the start of dialysis. In spite of the high ANCA titres, three of them remained for a long time free of symptoms related to the disease. Three pts developed, at various times from the beginning of the disease, fatal pulmonary hemorrhages.

Renal function at hospital admission as a prognostic factor in adult hemolytic uremic syndrome. The Italian Registry of Haemolytic Uremic Syndrome.

The clinical records of adult patients with a diagnosis of hemolytic uremic syndrome were retrospectively reviewed with the aim of evaluating the long-term outcome of renal function. The setting is the Italian Registry of Haemolytic Uraemic Syndrome, with which 13 Nephrology Centers have participated. Clinical and laboratory data of 43 patients with hemolytic uremic syndrome were evaluated. The mean age at onset was 34.3 +/- 18.3 yr. Men and women were equally affected. No seasonal trend in presentation was observed. In 20 patients, hemolytic uremic syndrome was primitive, whereas in 23, it was associated with another disease (cancer, preeclampsia, malignant hypertension, vasculitides). Gastrointestinal symptoms were the most frequently observed prodromes. Thirty (70%) patients required dialysis during the acute phase of the disease. Six patients died during the acute phase of the disease, and one died later after discharge (overall mortality, 16%). After 1 yr of follow-up, 11 (26%) patients had recovered a normal renal function, 14 (33%) had hypertension and/or renal insufficiency, and 11 (26%) were on regular dialysis. When prognostic factors of survival and recovery of renal function were considered, it was found that older age was associated with higher mortality in the acute phase, whereas severe renal involvement at the onset of the disease (as expressed by elevated serum creatinine) was associated with a long-term unfavorable prognosis.

[The heterotopic autograft of spleen fragments following splenectomy for trauma in the healthy subject]. / L'autotrapianto eterotopico di frammenti di milza dopo splenectomia per trauma, nel soggetto sano.

Authors report their experience on self-grafting of the spleen on 3 patients, among which a 9-year-old child. The surgical method is easy and quick and in their opinion it has given satisfactory results. In fact, basing themselves on the computation of the platelets values close to normality have been observed.

Anti-endothelial cell antibodies in patients with Wegener's granulomatosis and micropolyarteritis.

Anti-endothelial cell antibodies (AECA) have been detected by cell surface radioimmunoassay in nine out of 15 patients with micropolyarteritis (MPA) and in two out of five patients with Wegener's granulomatosis. AECA mostly belonged to the IgG isotype and were present in the active phase of the diseases. These antibodies were not detectable in 10 sera from patients with essential mixed cryoglobulinaemia, suggesting that they were not a mere epiphenomenon consequent to the inflammatory vascular injury. The binding activity was not related to ABH antigens or to HLA class I antigens displayed by resting human endothelial cells in culture and was not influenced by removing immune complexes. Absorption of the anti-neutrophil cytoplasmic antibodies (ANCA), present in MPA and Wegener's granulomatosis sera, did not affect the endothelial binding. AECA-positive sera did not display lytic activity against endothelial cells, neither alone nor after addition of fresh complement or normal human peripheral blood mononuclear cells. Although AECA are not cytolytic for endothelial cell monolayers in vitro, the reactivity against intact endothelial cells suggests their possible involvement in in vivo pathological processes affecting vascular structures in small vessel primary vasculitides.