Calcium carbonate-enriched cheese to improve nutrition, compliance and phosphorus control in patients on kidney replacement therapy.

BACKGROUND: Patients on renal replacement therapy face many dietary limitations, and cheese is often limited because of its high phosphate content; we have developed cheese with added calcium carbonate (CaCO3) to provide patients with a nutritional opportunity while improving their phosphate control. METHODS: The present double-blind crossover study was aimed to compare the new modified cheese with an equivalent standard product in 16 patients. The increase in inter-dialysis phosphorus (ΔP) and pre-dialysis calcium were used as the primary endpoints for efficacy and safety. RESULTS: The median ΔP (and IQR) was significantly lower with the modified cheese compared with the standard product: 2.5 (1.9-2.9) mg/dL vs. 2.7 (2.2-3.4) mg/dL, respectively (p < 0.02). No difference was observed in pre-dialysis serum calcium levels. CONCLUSIONS: The described modified cheese may represent an interesting means of overcoming some of the dietary limitations in patients on dialysis to help them achieve better nutrition and quality of life.

Catheter-related bloodstream infections in a nephrology unit: Analysis of patient- and catheter-associated risk factors.

BACKGROUND: Central venous catheter use is rising in chronic and acute hemodialysis. Catheter-related bloodstream infections are a major complication of central venous catheter use. This article examines clinical factors associated with catheter-related bloodstream infections incidence. METHODS: In this retrospective, single-center study, 413 patients undergoing extracorporeal treatments between 1 February 2014 and 31 January 2017 with 560 central venous catheters were recruited. Clinical parameters, such as gender, age, kidney disease status, diabetes, immunosuppression, and vintage dialysis, were collected at study entry. An incidence rate ratio (95% confidence interval) was calculated to assess the association between catheter-related bloodstream infections incidence rate and each clinical variable/central venous catheter type. Significant associations at the univariate analyses were investigated with multivariate Cox models. RESULTS: During a cumulative time of 66,686 catheter-days, 54 catheter-related bloodstream infections (incidence rate: 0.81) events occurred. Gram negative bacteria were more frequent in patients with age < 80 years (16 (36%) vs. 0, p = 0.02). At the univariate analyses, male sex (incidence rate ratio: 1.9 (1.1-3.5), p = 0.03), age < 80 years (incidence rate ratio: 2.4 (1.1-5.5), p = 0.016) and acute kidney injury (incidence rate ratio: 5.6 (3.1-10), p < 0.0001) were associated with higher catheter-related bloodstream infections incidence rate. Compared with tunneled jugular central venous catheter, higher catheter-related bloodstream infections incidence rate was associated with non-tunneled jugular (incidence rate ratio: 6.45 (2.99-13.56), p < 0.0001) and non-tunneled femoral (incidence rate ratio: 12.90 (5.87-27.61), p < 0.0001) central venous catheter use; tunneled femoral central venous catheter was associated with higher non-significant incidence rate (incidence rate ratio: 2.45 (0.93-5.85), p = 0.07). The multivariate analyses showed that acute kidney injury (hazard ratio: 3.03 (1.38-6.67), p = 0.006), non-tunneled (hazard ratio: 3.11 (1.30-7.41), p = 0.01) and femoral (hazard ratio: 2.63 (1.36-5.07), p = 0.004) central venous catheter were associated with higher catheter-related bloodstream infections incidence rate. CONCLUSION: Central venous catheter characteristics and acute kidney injury are independently associated with higher catheter-related bloodstream infections rate.

Cor triatriatum dexter associated with atrial septal defect: Management in a complex clinical case.

The coexistence of an atrial septal defect and a prominent eustachian valve is a rare congenital anomaly, rarely reported in literature. Differentiation between a giant eustachian valve and cor triatriatum dexter can be difficult. A case of a large atrial septal defect associated with cor triatriatum dexter diagnosed by echocardiography in an asymptomatic woman is reported. A watchful waiting strategy was adopted.

Methotrexate versus cyclophosphamide for remission maintenance in ANCA-associated vasculitis: A randomised trial.

OBJECTIVES: The treatment of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is based on remission-induction and remission-maintenance. Methotrexate is a widely used immunosuppressant but only a few studies explored its role for maintenance in AAV. This trial investigated the efficacy and safety of methotrexate as maintenance therapy for AAV. METHODS: In this single-centre, open-label, randomised trial we compared methotrexate and cyclophosphamide for maintenance in AAV. We enrolled patients with granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA), the latter with poor-prognosis factors and/or peripheral neuropathy. Remission was induced with cyclophosphamide. At remission, the patients were randomised to receive methotrexate or to continue with cyclophosphamide for 12 months; after treatment, they were followed for another 12 months. The primary end-point was relapse; secondary end-points included renal outcomes and treatment-related toxicity. RESULTS: Of the 94 enrolled patients, 23 were excluded during remission-induction or did not achieve remission; the remaining 71 were randomised to cyclophosphamide (n = 33) or methotrexate (n = 38). Relapse frequencies at months 12 and 24 after randomisation were not different between the two groups (p = 1.00 and 1.00). Relapse-free survival was also comparable (log-rank test p = 0.99). No differences in relapses were detected between the two treatments when GPA+MPA and EGPA were analysed separately. There were no differences in eGFR at months 12 and 24; proteinuria declined significantly (from diagnosis to month 24) only in the cyclophosphamide group (p = 0.0007). No significant differences in adverse event frequencies were observed. CONCLUSIONS: MTX may be effective and safe for remission-maintenance in AAV. TRIAL REGISTRATION: clinicaltrials.gov NCT00751517.

PTPN22 R620W polymorphism in the ANCA-associated vasculitides.

OBJECTIVES: PTPN22 is involved in T-cell activation and its R620W single-nucleotide polymorphism (SNP) has been shown to predispose to different autoimmune diseases. The aims of this study were to investigate the role of the PTPN22 R620W SNP in conferring susceptibility to the ANCA-associated vasculitides (AAVs), and to explore potential associations between the PTPN22 genotype and the disease manifestations. METHODS: PTPN22 R620W SNP was genotyped in a cohort of 344 AAV patients [143 with granulomatosis with polyangiitis (Wegener's) (GPA), 102 with microscopic polyangiitis (MPA) and 99 with Churg-Strauss syndrome (CSS)] and in 945 healthy controls. RESULTS: The frequency of the minor allele (620W) was significantly higher in GPA patients than in controls [P = 0.005, χ(2 )= 7.858, odds ratio (OR) = 1.91], while no statistically significant association was found with MPA or CSS. Among GPA patients, the 620W allele was particularly enriched in ANCA-positive patients as compared with controls (P = 0.00012, χ(2 )= 14.73, OR = 2.31); a particularly marked association was also found with ENT involvement (P = 0.0071, χ(2 )= 7.258, OR = 1.98), lung involvement (P = 0.0060, χ(2 )= 7.541, OR = 2.07) and skin manifestations of all kinds (P = 0.000047, χ(2 )= 16.567, OR = 3.73). CONCLUSION: The PTPN22 620W allele confers susceptibility to the development of GPA (but not of MPA or CSS), and particularly of its ANCA-positive subset.

Peripheral neuropathy in Wegener's granulomatosis, Churg-Strauss syndrome and microscopic polyangiitis.

OBJECTIVE: To compare the clinical aspects of peripheral neuropathy associated with Wegener's granulomatosis (WG), Churg-Strauss syndrome (CSS) and microscopic polyangiitis (MP). METHODS: Cohort study conducted in a single university hospital. Patients were included when a definite diagnosis of WG, CSS or MP was made according to the current classification criteria in our hospital, between 1999 and 2006. All patients underwent periodically clinical and electrophysiological screening for peripheral neuropathy, assessment of disability, and clinical and laboratory evaluation during a mean follow-up of 38 months. RESULTS: Sixty-four consecutive patients diagnosed with WG (26 patients), CSS (26 patients) and MP (12 patients) were recruited. Peripheral neuropathy occurred in 27/64 patients: six with WG, 15 with CSS and six with MP. Neuropathy occurred earlier in the disease history in CSS and MP compared with WG. Among patients with WG, those who developed peripheral neuropathy during follow-up were older than those without neuropathy both at the time of onset and of diagnosis of vasculitis. Distal symmetric polyneuropathy was present in 11 patients, and single or multiple mononeuropathy in 16. Patients with WG had a less severe form of mononeuritis multiplex than CSS or MPA patients. Disability and pain were greater in patients with mononeuropathy, although one-third of them were painless. Relapses of neuropathy were extremely infrequent. CONCLUSIONS: Peripheral neuropathy in WG occurs less frequently, later in the disease course and in a milder form than in CSS and MP. Single or multiple mononeuropathy associated with these subsets of vasculitis can often be painless.

Outcome and prognostic factors during the course of primary small-vessel vasculitides.

OBJECTIVE: To identify the prognostic factors of relapse and/or death during the course of primary small-vessel vasculitides (PSVV), and to differentiate their prognostic relevance by the type of vasculitis. METHODS: Seventy-five patients were retrospectively followed up after diagnosis: 36 with Wegener's granulomatosis (WG), 23 with Churg-Strauss syndrome (CSS), and 16 with microscopic polyangiitis. Cox regression analysis was used to identify the significant predictors of relapse and death. RESULTS: Gastrointestinal (GI) involvement was associated with an increased risk of relapse, mainly in the patients with CSS, whereas renal disease and perinuclear antineutrophil cytoplasmic antibody positivity were correlated with a lower risk of relapse. Presence of nasal Staphylococcus aureus tended to increase the risk of relapse in CSS [hazard ratio (HR) 4.45, p = 0.087], but to decrease it in WG (HR 0.12, p = 0.066). Older age, renal and hepatic involvement, erythrocyte sedimentation rate >or= 100 mm/h, and serum creatinine level >or= 1.5 mg/dl were all related to higher risk of death in univariate analysis; however, only cerebral (HR 8.52, p = 0.021) and hepatic involvement (HR 4.40, p = 0.028) and serum creatinine level >or= 1.5 mg/dl (HR 5.72, p = 0.044) were independently correlated with an unfavorable prognosis for survival. The risk of death associated with each of these indicators did not depend on the form of PSVV. CONCLUSION: GI involvement increases the risk of relapse in CSS, whereas the prognostic significance of nasal S. aureus in terms of relapse seems to be opposite in patients with CSS and those with WG. Patients with cerebral, hepatic, and renal involvement have the poorest prognosis for survival. Our data do not show that the prognostic relevance of these factors depends on the form of PSVV.

Cardiac involvement in the Churg-Strauss syndrome.

Churg-Strauss syndrome (CSS) is a rare systemic disease characterized by necrotizing vasculitis and peripheral eosinophilia. Cardiac involvement is considered common and is given a high rank among the causes of morbidity and mortality. The aim of this study was an update on the cardiac manifestations of this syndrome using a noninvasive approach. Sixteen patients with CSS were compared with a gender- and age-matched group of 20 healthy subjects. All patients but 1 were receiving treatment (steroids and/or immunosuppressive drugs). According to the Birmingham vasculitis activity score, 12 patients were in an active phase, and 4 were in drug-induced remission. All subjects underwent M-B-mode echocardiography and Doppler tissue echocardiography. Heart failure, life-threatening arrhythmias, and other prominent manifestations of heart disease were not observed. No differences were found in left ventricular diameter, volume, mass, or ejection fraction. The 2 groups did not differ in right ventricular diameter and pulmonary pressure. Few and nonspecific changes were detected by 2-dimensional echocardiography, including subclinical pericardial effusion and mitral regurgitation, in fewer than half the subjects. Subjects with CSS showed an impairment of ventricular relaxation. Changes were more prominent in the right ventricle. The peak velocity (PV) of early diastolic tricuspid inflow (E) was about 8% less than in controls, and the velocity of late diastolic inflow (A) was 35% greater. The E/A(PV) ratio was, on average, 33% less. In the left ventricle, E(PV) was 11% less and A(PV) 11% greater. The E/A ratio was decreased by 22%. Doppler analysis of tissue kinetics confirmed these indications. In the right ventricle, E(PV) was decreased by 10% and A(PV) was increased by 20% in the patient group. The E/A(PV) ratio was decreased by 29%. In the left ventricle, in which different sites were sampled, the average changes were -15%, +1%, and -23%, respectively. In the left ventricle, the velocity of systolic contraction was also decreased by 12%. Because of the small group size, only some of these differences were statistically significant. In conclusion, these moderate changes, devoid of clinical correlates, contrast with early reports emphasizing cardiac morbidity and poor prognosis in this syndrome.

Organic contamination in dialysis water: trichloroethylene as a model compound.

BACKGROUND: Routine water monitoring in a haemodialysis centre revealed high trichloroethylene (TCE) concentrations. The aim of this study is to describe the measures adopted after organic contamination of dialysis water in order to avoid the possibility of patient exposure. We also carried out in vitro experiments to evaluate the accumulation of TCE in various devices normally used in a dialysis water treatment system (DWTS). METHODS: In vivo and in vitro blood and water TCE levels were determined by means of solid phase microextraction-gas chromatography/mass spectrometer. RESULTS: High TCE concentrations were found throughout the DWTS; acceptably low levels were obtained only by replacing the activated charcoal, ionic-exchange resins, microfilters and PVC pipes. The adsorption and realising capacities of these devices were tested in vitro, and the elimination curves made it possible to calculate the total percentage of the previously absorbed TCE mass released into the water. Evidence of exposure was confirmed by the relatively high TCE levels in the patient blood samples taken 30 days after the last exposure even if the subjects were asymptomatic. In vivo experiments showed that the blood gain of TCE through the low flux membrane during the course of dialysis was about 77+/-10.4% of the amount carried by dialysis fluid as calculated on the basis of its partition coefficient value (K(b/w) 3.75). CONCLUSIONS: This study shows that, when present in dialysis water, the lipophilic TCE contaminant can accumulate in various devices, thus transforming them into possible sources of exposure. This highlights the importance of periodically monitoring dialysis water for organic substances that have a great affinity to the blood compartment, in order to prevent occasional or chronic patient exposure.

Prevalence and clinical significance of antineutrophil cytoplasmic antibodies in Churg-Strauss syndrome.

OBJECTIVE: Churg-Strauss syndrome (CSS) is classified among the so-called antineutrophil cytoplasmic antibody-associated systemic vasculitides (AASVs) because of its clinicopathologic features that overlap with the other AASVs. However, while antineutrophil cytoplasmic antibodies (ANCAs) are consistently found in 75-95% of patients with Wegener's granulomatosis or microscopic polyangiitis, their prevalence in CSS varies widely and their clinical significance remains uncertain. We undertook this study to examine the prevalence and antigen specificity of ANCAs in a large cohort of patients with CSS. Moreover, we evaluated the relationship between ANCA positivity and clinicopathologic features. METHODS: Immunofluorescence and enzyme-linked immunosorbent assay were used to determine the presence or absence of ANCAs in 93 consecutive patients at the time of diagnosis. The main clinical and pathologic data, obtained by retrospective analysis, were correlated with ANCA status. RESULTS: ANCAs were present by immunofluorescence in 35 of 93 patients (37.6%). A perinuclear ANCA (pANCA) pattern was found in 26 of 35 patients (74.3%), with specificity for myeloperoxidase (MPO) in 24 patients, while a cytoplasmic ANCA pattern, with specificity for proteinase 3, was found in 3 of 35 patients (8.6%). Atypical patterns were found in 6 of 30 patients with anti-MPO antibodies (20.0%). ANCA positivity was associated with higher prevalences of renal disease (51.4% versus 12.1%; P < 0.001) and pulmonary hemorrhage (20.0% versus 0.0%; P = 0.001) and, to a lesser extent, with other organ system manifestations (purpura and mononeuritis multiplex), but with lower frequencies of lung disease (34.3% versus 60.3%; P = 0.019) and heart disease (5.7% versus 22.4%; P = 0.042). CONCLUSION: ANCAs are present in approximately 40% of patients with CSS. A pANCA pattern with specificity for MPO is found in most ANCA-positive patients. ANCA positivity is mainly associated with glomerular and alveolar capillaritis.

Respiratory system involvement in ANCA-associated systemic vasculitides.

BACKGROUND AND AIM OF THE WORK: The respiratory system may be involved in all systemic vasculitides (SV), although with a variable frequency. Lung disease is a very common and important feature of the antineutrophil cytoplasmic antibodies (ANCA)-associated SV (AASV), such as Wegener's granulomatosis (WG), Churg-Strauss syndrome (CSS), and microscopic polyangiitis (MPA). The aim of the work is to review the clinical findings, as well as the radiological and pathological features of respiratory system involvement in AASV. METHODS: A detailed search via the PubMed index from the National Library of Medicine, covering the period from 1980 to December 2004, was accomplished. RESULTS: In WG, almost all patients have either upper airway or lower respiratory tract disease. Solitary or multiple nodules and masses are the most common findings on chest radiograph. Asthma is a main symptom of CSS, often preceded by allergic rhinitis, frequently complicated by nasal polyposis and sinusitis. Pulmonary transient and patchy alveolar infiltrates are the most common radiographic findings. In MPA, diffuse alveolar haemorrhage (DAH) due to alveolar capillaritis is the most frequent manifestation of the respiratory involvement, clinically expressing with haemoptysis, respiratory distress and anaemia. CONCLUSIONS: The involvement of the respiratory system is a very common and important feature of AASV. There is substantial overlap in many of the clinical pulmonary features of AASV. In some cases, distinguishing between these diseases on the basis of the clinical features alone is difficult and pathological assessment is needed.

"Late" regressions of metastases from renal cancer after a period of disease progression continuing the same intermittent low dose immunotherapy regimen.

We here describe two patients with metastatic renal cell cancer (mRCC) treated with immunotherapy in whom the metastases completely regressed after a period of progressive disease. The treatment schedule was based on repeated cycles of low-dose recombinant interleukin-2 and recombinant interferon-alpha, and was never changed during the course of the disease. The first patient received immunotherapy because of multiple bilateral lung metastases. Progressive disease, with mediastinal lymph node involvement and an increased number of lung metastases, was observed after 30 months of regularly repeated therapy; complete regression was achieved after 60 months of immunotherapy (after 16 immunotherapy cycles). The second patient began immunotherapy because of three small lung metastases. Disease progression was observed after three cycles, but complete regression was obtained about 16 months after the start of immunotherapy (after 5 immunotherapy cycles). Long-term low-dose immunotherapy may bring about an effective anti-tumour response even late in the course of the disease and after an initial disease progression.

Prognostic significance of albuminuria in patients with renal cell cancer.

PURPOSE: A relationship between the urinary albumin excretion rate (UAE) and different types of tumors has been previously described but little is known about UAE and renal cell cancer (RCC). We evaluated the prognostic significance of UAE and its correlation with tumor clinicopathological findings in patients with RCC treated with recombinant interleukin-2 (rIL-2) and recombinant interferon-alpha (rIFN-alpha). Because rIL-2 and rIFN-alpha increase glomerular permeability, we also determined whether the first immunotherapy cycle induced a significant increase in UAE and whether it was related to tumor parameters. MATERIALS AND METHODS: A total of 51 consecutive patients with RCC were enrolled. Inclusion criteria were patient age at diagnosis younger than 70 years and serum creatinine less than 1.8 mg/dl. Patients with central nervous system metastases and diabetes mellitus were excluded. Nephrectomy was followed by systemic treatment with 1-month cycles of low dose rIL-2 and rIFN-alpha, which were repeated every 4 months, UAE was determined before and after the first treatment cycle. RESULTS: Univariate analysis showed that pre-cycle and post-cycle UAE greater than 30 mg/24 hours significantly influenced survival (p = 0.006 and 0.007, respectively). A multivariate model adjusted for age at onset, performance status, post-cycle UAE, tumor stage and grade, and metastases showed that pre-cycle UAE greater than 30 mg/24 hours had an independent prognostic role (p = 0.011). The first treatment cycle increased UAE 81.8% vs baseline (p = 0.002). The post-cycle vs pre-cycle increase was significant in patients with stages III-IV (p = 0.003) and grades 3-4 (p = 0.028) tumors. Pre-cycle and post-cycle UAE were significantly higher in stages III-IV than in stages I-II cases (p = 0.030 and 0.007, respectively). CONCLUSIONS: UAE is an independent prognostic factor that is related to disease stage in patients with RCC.