Phosphate levels in patients treated with low-flux haemodialysis, pre-dilution haemofiltration and haemodiafiltration: post hoc analysis of a multicentre, randomized and controlled trial.

BACKGROUND: Whether convective therapies allow better control of serum phosphate (P) is still undefined, and no data are available concerning on-line haemofiltration (HF). The objectives of the study are to evaluate the effect of convective treatments (CTs) on P levels in comparison with low-flux haemodialysis (HD) and to evaluate the correlates of serum phosphate in a post hoc analysis of a randomized clinical trial. METHODS: This analysis was performed in the database of a multicentre, open label and randomized controlled study in which 146 chronic HD patients from 27 Italian centres were randomly assigned to HD (70 patients) or CTs: on-line pre-dilution HF (36 patients) or on-line pre-dilution haemodiafiltration (40 patients). RESULTS: CTs did not affect P (P = 0.526), calcium (Ca) (P = 0.849) and parathyroid hormone levels (P = 0.622). P levels were associated with the use of phosphate binders including aluminium-based phosphate binders (P < 0.001) and sevelamer (P < 0.001), pre-dialysis bicarbonate levels (P < 0.001) and pre-dialysis blood K levels (P < 0.001). On multivariate analysis (generalized linear model), serum P was again largely unassociated with CTs (P = 0.631). Notably, participating centres were by far the strongest independent correlate of serum P, explaining 45.3% of the variance of serum P over the trial and this association was confirmed at multivariate analysis. Bicarbonate (P < 0.001) and, to a weaker extent, serum K (P = 0.032) were independently related to serum P. CONCLUSIONS: In comparison with low-flux HD, CTs did not significantly affect serum P levels. Participating centres were the main source of P variability during the trial followed by treatment with phosphate binders, serum bicarbonate and, to a weak extent, serum potassium levels (ClinicalTrials.gov Identifier: NCT011583309).

Imaging of the peritoneum evaluated by 99mTc-icodextrin scintigraphy in peritoneal dialysis patients: preliminary data.

AIM: In this study, we proposed a peritoneal scintigraphy with a different marker, the 99mTechnetium-Icodextrin, to evaluate the distribution of the dialysate within the peritoneal cavity in peritoneal dialysis (PD) patients. METHODS: 99mTc-Icodextrin scintigraphy was performed in 16 PD patients. 0.5 ml of 7.5% Icodextrin solution was labeled with 74 megabecquerel (MBq) of 99mTc and then added to 2,000 ml of dialysate solution (2.5% dextrose). The peritoneum scintigraphy was performed by a SPECT gamma camera with the peritoneal cavity filled and after the complete drainage of the radio compound-dialysate mixture. The images were reviewed for evidence of peritoneal leaks, hernias, loculated fluid collections, and peritoneal membrane adhesions. RESULTS: Abnormal findings were detected by 99mTc-Icodextrin scintigraphy in 4 (25%) out of 16 patients and included retroperitoneal (n = 1), diaphragmatic (n = 1) and inguinal (n = 1) leakages and peritoneal membrane adhesions (n = 1). CONCLUSIONS: Peritoneum scintigraphy with 99mTc-Icodextrin is a useful method to detect some complications occurring during peritoneal dialysis; it offers excellent imaging to assess these complications.

Effects of a diet rich in N-3 polyunsaturated fatty acids on systemic inflammation in renal transplant recipients.

OBJECTIVE: n-3 Polyunsaturated fatty acids (PUFAs) supplementation reduces systemic inflammation and improves renal and cardiovascular prognosis in kidney transplant recipients. However, patient compliance is poor because bad-tasting fish oils are used as an n-3 PUFA source. Therefore, we explored whether the beneficial effects of n-3 can be obtained by administering a diet based on n-3-rich foods. METHODS: Sixty kidney transplant recipients were assigned to 2 different groups: the CON group (n = 28), which continued with their usual diet, and the DIET group (n = 32), which followed an n-3-rich diet for 6 months. Twenty-six patients in the DIET group and 24 in the CON group completed the study. End points of the study were changes in n-3 PUFAs intake, n-6:n-3 PUFAs ratio, systemic inflammation markers, and renal function during the 6 months of the dietary treatment. RESULTS: Three and 6 months after the beginning of the study, n-3 PUFA intake was significantly higher and the n-6:n-3 PUFA ratio was markedly lower than baseline in the DIET group. Plasma total cholesterol, triglycerides, C-reactive protein, and interleukin (IL)-6 decreased as well. IL-6 mRNA levels in peripheral blood mononuclear cells were also lower than at the beginning of the study. Proteinuria and microalbuminuria were reduced by 50% with respect to the baseline, whereas glomerular filtration rate (GFR) was unchanged. No change in the aforementioned parameters was observed in the CON group throughout the study. CONCLUSION: In long-term kidney transplant recipients a naturally n-3 PUFA-rich dietary plan causes an increase in n-3 PUFA intake, decreases systemic inflammation and proteinuria, and improves plasma lipid pattern.

Evidence on the prevalence and geographic distribution of major cardiovascular risk factors in Italy.

OBJECTIVE: To assess the prevalence and geographic distribution of major cardiovascular risk factors in a large community-wide sample of the Italian population. DESIGN: A cross-sectional survey. Standardized methods were used to collect and measure cardiovascular risk factors. Data were adjusted for survey weightings. Qualitative and quantitative variables were compared with parametric and non-parametric tests, as appropriate. SETTING: Towns (n 193) across different Italian regions. SUBJECTS: Unselected adults (n 24 213; 12 626 men; 11 587 women) aged 18-98 years (mean age 56·9 (sd 15·3) years), who volunteered to participate in a community-wide screening programme over a 2 d period in 2007. RESULTS: Overall, the prevalence of major cardiovascular risk factors was: obesity, 22·7 % (women 18·9 %, men 26·1 %); overweight, 44·7 % (women 31·6 %, men 56·7 %); hypertension, 59·6 % (women 48·3 %, men 70·0 %); dyslipidaemia, 59·1 % (women 57·7 %, men 60·3 %); diabetes, 15·3 % (women 11·2 %, men 19·0 %) and smoking, 19·8 % (women 14·0 %, men 25·2 %). We found a high prevalence of unhealthy eating habits; fruit and vegetable consumption was below the recommended range in 60 % of the study population. Ninety per cent of the study population had more than one cardiovascular risk factor and 84 % had between two and five cardiovascular risk factors. There were differences among Italian macro-areas mainly for obesity, hypertension, dyslipidaemia and diabetes. CONCLUSIONS: The study provides alarming evidence on current prevalence data for major cardiovascular risk factors in a large sample of the Italian population. Particularly, obesity and hypertension represent a relevant public health problem. There is a pressing need for effective preventive health measures which must also take into account the differences among Italian macro-areas.

Human mature adipocytes express albumin and this expression is not regulated by inflammation.

AIMS: Our group investigated albumin gene expression in human adipocytes, its regulation by inflammation and the possible contribution of adipose tissue to albumin circulating levels. METHODS: Both inflamed and healthy subjects provided adipose tissue samples. RT-PCR, Real-Time PCR, and Western Blot analysis on homogenates of adipocytes and pre-adipocytes were performed. In sixty-three healthy subjects and fifty-four micro-inflamed end stage renal disease (ESRD) patients circulating levels of albumin were measured by nephelometry; all subjects were also evaluated for body composition, calculated from bioelectrical measurements and an thropometric data. RESULTS: A clear gene expression of albumin was showed in pre-adipocytes and, for the first time, in mature adipocytes. Albumin gene expression resulted significantly higher in pre-adipocytes than in adipocytes. No significant difference in albumin gene expression was showed between healthy controls and inflamed patients. A significant negative correlation was observed between albumin levels and fat mass in both healthy subjects and inflamed ESRD patients. CONCLUSIONS: In the present study we found first time evidence that human adipocytes express albumin. Our results also showed that systemic inflammation does not modulate albumin gene expression. The negative correlation between albumin and fat mass seems to exclude a significant contributing role of adipocyte in plasma albumin.

Proteomic analysis of peritoneal fluid of patients treated by peritoneal dialysis: effect of glucose concentration.

BACKGROUND: Depending on both membrane composition and solute transport rate across the membrane, protein composition of the dialysate of patients receiving peritoneal dialysis (PD) has recently become of great interest. Unfortunately, thus far few studies have focused on dialysate characterization, and further investigations are required to better understand the biological mechanisms influencing PD efficiency. METHODS: Different classical proteomic approaches were combined with advanced mass spectrometric (MS) techniques to analyse peritoneal fluid (PF) protein composition of adult patients receiving PD. Characterization was performed by using 1D gel electrophoresis combined with nano-RP-HPLC-ESI-MS/MS and shotgun proteomics, while comparative analyses were performed coupling 2D gel electrophoresis with MALDI-TOF MS. RESULTS: The study allowed the identification of 151 different proteins from PF, which are mainly of plasmatic origin. Comparison of PD effluents characterized by different glucose concentrations demonstrated four proteins (apolipoprotein A-IV, fibrinogen beta chain, transthyretin and alpha-1-antitrypsin) to be under-expressed in the highest osmolar solution having 4.25% compared to others having 1.5% and 2.5% glucose. All of them were found to be involved in the inflammatory processes. CONCLUSIONS: This study provides a possible platform for future diagnostic and therapeutic applications in the field of PD and allowed the identification of potential targets to be used in preventing inflammatory processes induced by the exposure to dialysis solutions.

Hemofiltration and hemodiafiltration reduce intradialytic hypotension in ESRD.

Symptomatic intradialytic hypotension is a common complication of hemodialysis (HD). The application of convective therapies to the outpatient setting may improve outcomes, including intradialytic hypotension. In this multicenter, open-label, randomized controlled study, we randomly assigned 146 long-term dialysis patients to HD (n = 70), online predilution hemofiltration (HF; n = 36), or online predilution hemodiafiltration (HDF; n = 40). The primary end point was the frequency of intradialytic symptomatic hypotension (ISH). Compared with the run-in period, the frequency of sessions with ISH during the evaluation period increased for HD (7.1 to 7.9%) and decreased for both HF (9.8 to 8.0%) and HDF (10.6 to 5.2%) (P < 0.001). Mean predialysis systolic BP increased by 4.2 mmHg among those who were assigned to HDF compared with decreases of 0.6 and 1.8 mmHg among those who were assigned to HD and HF, respectively (P = 0.038). Multivariate logistic regression demonstrated significant risk reductions in ISH for both HF (odds ratio 0.69; 95% confidence interval 0.51 to 0.92) and HDF (odds ratio 0.46, 95% confidence interval 0.33 to 0.63). There was a trend toward higher dropout for those who were assigned to HF (P = 0.107). In conclusion, compared with conventional HD, convective therapies (HDF and HF) reduce ISH in long-term dialysis patients.

A translational approach to micro-inflammation in end-stage renal disease: molecular effects of low levels of interleukin-6.

Inflammation plays a key role in the progression of cardiovascular disease, the leading cause of mortality in ESRD (end-stage renal disease). Over recent years, inflammation has been greatly reduced with treatment, but mortality remains high. The aim of the present study was to assess whether low (<2 pg/ml) circulating levels of IL-6 (interleukin-6) are necessary and sufficient to activate the transcription factor STAT3 (signal transducer and activator of transcription 3) in human hepatocytes, and if this micro-inflammatory state was associated with changes in gene expression of some acute-phase proteins involved in cardiovascular mortality in ESRD. Human hepatocytes were treated for 24 h in the presence and absence of serum fractions from ESRD patients and healthy subjects with different concentrations of IL-6. The specific role of the cytokine was also evaluated by cell experiments with serum containing blocked IL-6. Furthermore, a comparison of the effects of IL-6 from patient serum and rIL-6 (recombinant IL-6) at increasing concentrations was performed. Confocal microscopy and Western blotting demonstrated that STAT3 activation was associated with IL-6 cell-membrane-bound receptor overexpression only in hepatocytes cultured with 1.8 pg/ml serum IL-6. A linear activation of STAT3 and IL-6 receptor expression was also observed after incubation with rIL-6. Treatment of hepatocytes with 1.8 pg/ml serum IL-6 was also associated with a 31.6-fold up-regulation of hepcidin gene expression and a 8.9-fold down-regulation of fetuin-A gene expression. In conclusion, these results demonstrated that low (<2 pg/ml) circulating levels of IL-6, as present in non-inflamed ESRD patients, are sufficient to activate some inflammatory pathways and can differentially regulate hepcidin and fetuin-A gene expression.

Myocardial fibrosis and diastolic dysfunction in patients on chronic haemodialysis.

BACKGROUND: Left ventricular (LV) diastolic dysfunction is linked to myocardial collagen content in many cardiac diseases. There are no data regarding such relationship in patients with end-stage renal disease (ESRD) undergoing haemodialysis. METHODS: Twenty-five patients with ESRD undergoing haemodialysis were studied by echocardiography. LV diastolic function was investigated by Doppler echocardiography, by analysing LV filling velocities at rest and during loading manoeuvres, which represent an estimate of LV filling pressure. According to the Doppler pattern, LV filling pressure in a given patient was judged to be normal or slightly increased or to be moderately or severely increased. The presence of myocardial fibrosis was estimated by ultrasound tissue characterization with integrated backscatter, which in diastole correlates with the collagen content of the myocardium. RESULTS: Integrated backscatter was higher in patients with moderate or severely increased than in patients with normal or slightly increased LV filling pressure (integrated backscatter: 51.0 +/- 9.8 vs 41.6 +/- 5.6%; P = 0.008). Integrated backscatter was a strong and independent determinant of diastolic dysfunction (odds ratio = 1.212; P = 0.040). CONCLUSION: Our data support the hypothesis that, in a selected population of patients with ESRD undergoing haemodialysis, myocardial fibrosis is associated with LV diastolic myocardial properties.

Serum fetuin a in hemodialysis: a link between derangement of calcium-phosphorus homeostasis and progression of atherosclerosis?

BACKGROUND: Fetuin A, a circulating inhibitor of ectopic calcification, is downregulated in hemodialysis and has been shown to predict cardiovascular mortality in this setting. The association of altered calcium-phosphorus with serum fetuin A levels is still a matter of debate. Although carotid intima-media thickness (cIMT) is a strong predictor of major cardiovascular events, its association with serum fetuin A levels is poorly defined. STUDY DESIGN: Cohort study. PARTICIPANTS & SETTINGS: 174 uremic patients on long-term hemodialysis therapy enrolled in 4 university hospitals. PREDICTORS: Serum fetuin A levels at the beginning of the study (T0) and after 12 months (T12). OUTCOMES: Progression of atherosclerosis assessed by means of cIMT measurements at 24 months (T24); cardiovascular morbidity and mortality at 36 months. RESULTS: Serum fetuin A concentrations at T0 and T12 were 282.3 +/- 79.4 and 290.0 +/- 92.2 microg/mL, respectively. Mean T0 and T24 cIMT values were 1.02 +/- 0.2 and 1.06 +/- 0.2 mm, respectively (P < 0.001). Fatal and nonfatal cardiovascular disease occurred in 36 and 86 patients by 36 months, respectively. In multivariate logistic regression, higher calcium-phosphorus product was associated with lower serum fetuin A level (odds ratio, 0.96; 95% confidence interval [CI], 0.93 to 1.00; P = 0.02). Multiple regression analysis showed that T0 serum fetuin A level was associated with T24 cIMT (P = 0.01) after adjustments for age, cholesterol level, high-sensitivity C-reactive protein level, previous cardiovascular events, and T0 cIMT. In a multivariate Cox regression analysis, cardiovascular mortality was independently associated with a 1-tertile lower T0 serum fetuin A level, and a 1-tertile higher T0 cIMT value was independently associated with greater cardiovascular mortality (hazard ratio, 0.45; 95% CI, 0.15 to 0.65; P = 0.007 and hazard ratio, 10.00; 95% CI, 3.16 to 31.73; P < 0.001, respectively) after adjustment for age and previous cardiovascular events. LIMITATION: Length of follow-up. CONCLUSION: Calcium-phosphorus product in hemodialysis patients inversely correlated with serum fetuin A level, which, in turn, was associated inversely with progression of atherosclerotic lesions and cardiovascular mortality in this study population.

Beneficial effects of better control of secondary hyperparathyroidism with paricalcitol in chronic dialysis patients.

BACKGROUND: Treatment of secondary hyperparathyroidism (SHPT) with calcitriol is often limited by the occurrence of hypercalcemia, hyperphosphatemia and risk of vascular calcifications. Paricalcitol, a vitamin D analogue with lower calcemic and phosphatemic effects, is successfully utilized in dialysis patients, although some uncertainty remains about the optimal dosage. Amelioration of survival in hemodialysis patients has been correlated to the use of calcitriol and, even better, paricalcitol. METHODS: We evaluated 1-year treatment with paricalcitol in 12 chronic hemodialysis patients with moderate-severe SHPT previously treated with intravenous calcitriol. Starting dose of paricalcitol was calculated according to the severity of the disease by the formula: intact parathyroid hormone (iPTH)/80, and successive titration performed according to the NKF-DOQI guidelines. RESULTS: Paricalcitol caused a rapid decrease in serum levels of iPTH with a consistent percentage of values falling below 150 pg/mL in the first months of treatment. Although the occurrence of hypercalcemia was not significantly different between treatment with calcitriol and paricalcitol, a slight but significant increase in mean calcium levels was observed during paricalcitol treatment. A significant amelioration of erythropoiesis and acid-base balance was observed during paricalcitol treatment. CONCLUSIONS: Paricalcitol efficiently suppresses PTH secretion in dialysis patients with SHPT, with a moderate calcemic, but not a phosphatemic, effect. The dose of paricalcitol calculated as iPTH/80 may cause acute lowering of bone turnover. The improvement of anemia control and the amelioration of acid-base balance are 2 important additive effects of the better control of SHPT that may improve survival of hemodialysis patients.

Local activation of interleukin 6 signaling is associated with arteriovenous fistula stenosis in hemodialysis patients.

BACKGROUND: Vascular access failure is the main cause of morbidity in hemodialysis patients. Stenosis of the arteriovenous fistula (AVF) is similar histologically to atherosclerosis. Recent studies showed that interleukin 6 (IL-6) has a key role in the pathogenesis of atherosclerosis by binding 2 specific receptors, gp80 and gp130. When activated, gp130 interacts with a tyrosine kinase, Janus kinase (JAK2), which then activates a transcription factor, signal transducers and activators of transcription (STAT3), directly turning on several proinflammatory genes. The aim of this study is to evaluate gp130 expression and JAK2/STAT3 activation within stenotic AVFs. METHODS: 44 patients undergoing surgery for AVF creation were enrolled; 10 of them had AVF failure with histologically proven AVF stenosis (wall-lumen ratio > 1). A venous fragment of the AVFs was collected during creation and revision of the vascular access. gp130 and gp80 expression, as well as JAK/STAT activation, were evaluated by means of confocal microscopy. Peripheral-blood mononuclear cells were isolated at the time of AVF creation and revision. RESULTS: gp130 protein expression, barely detectable in native AVFs, was strikingly increased within the venous branch of stenotic AVFs. The signaling subunit of the IL-6 receptor broadly colocalized with gp80, the IL-6-binding subunit. gp130-expressing cells were mainly CD34(+), suggesting that this receptor is expressed primarily by neovasculature endothelial cells. At the same time, a significant increase in phosphorylation of JAK2/STAT3 was observed in endothelial cells of stenotic AVFs. Interestingly, peripheral-blood mononuclear cells isolated at the time of AVF failure presented strikingly greater IL-6 expression compared with dialysis age-matched controls. CONCLUSION: IL-6 receptor activation may have a role in the pathogenesis of AVF failure in hemodialysis patients and may represent a potential therapeutic target in this setting.

Fetuin-A gene expression, synthesis and release in primary human hepatocytes cultured in a galactosylated membrane bioreactor.

This paper reports on human hepatocytes cultured in a galactosylated membrane bioreactor in order to explore the modulation of the effects of a pro-inflammatory cytokine, Interleukin-6 (IL-6) on the liver cells at molecular level. In particular the role of IL-6 on gene expression and production of a glycoprotein, fetuin-A produced by hepatocytes, was investigated by culturing hepatocytes in the membrane bioreactor, both in the absence and presence of IL-6 (300 pg/ml). IL-6 modulated the fetuin-A gene expression, synthesis and release by primary human hepatocytes cultured in the bioreactor. A 75% IL-6-induced reduction of fetuin-A concentration in the medium was associated with a 60% increase of C-reactive protein in the same samples. Real-time-PCR demonstrated an 8-fold IL-6-induced reduction of fetuin-A gene expression. These results demonstrate that the hepatocyte galactosylated membrane bioreactor is a valuable tool to study IL-6 effects and gave evidence, for the first time, that IL-6 down-regulates the gene expression and synthesis of fetuin-A by primary human hepatocytes. The human hepatocyte bioreactor behaves like the in vivo liver, reproducing the same hepatic acute-phase response that occurs during the inflammatory process.

Stop Flow in abdominal and pelvic cancer relapses.

To determinate MTD, DLT and safe doses for phase II study, a dose finding study with Mitomycin and Adriamycin Stop-Flow administration was carried out. A phase II study focused on resectability of pelvic colorectal relapses is in progress. From November 1995, 84 pts, 52 male and 32 female (94 treatments), with advanced not resectable abdominal (14 pts) or pelvic (70 pts) relapses, and resistant to previous systemic chemotherapy, were enrolled in the study. 46 pts entered the phase I-early phase II study, while subsequently 38 pts were recruited in ongoing phase II study. Safe dose were: MMC 20 mg/mq and ADM 75 mg/mq. The phase II study focused on colorectal relapses registered very promising responses: 90% pain control, 1 pCR and 26 PR / 63 (OR 43%), 8 NC (13%) 9/27 responder patients (33%) obtained a complete resectability of colorectal relapses. Stop-Flow is a safe and feasible technique very useful as a palliation treatment.

Radiocontrast media cause dephosphorylation of Akt and downstream signaling targets in human renal proximal tubular cells.

Radiocontrast medium induced nephrotoxicity is a major clinical problem. There is considerable interest in reducing the incidence of acute renal failure due to the use of radiocontrast media (RCM). Reduction of renal blood flow and direct toxic effect on renal tubular epithelial cells have been postulated as major causes of RCM nephropathy. Understanding the molecular mechanisms by which RCM cause cell damage may allow the development of pharmacological therapy to prevent their nephrotoxicity. In this work we have investigated the signaling pathways that may be affected by RCM. The incubation of human renal tubular proximal cells with sodium diatrizoate, iopromide and iomeprol caused a marked dephosphorylation of the kinase Akt on Ser473 within 5min of incubation. RCM also caused a decrease in cell viability, which was substantially alleviated by transfecting the cells with a constitutively active form of Akt. Further downstream targets of Akt, including the Forkhead family of transcription factors FKHR and FKHRL1, were also dephosphorylated by RCM at Thr24 and Thr32, respectively. The P70S6 kinase was also dephosphorylated at Thr389 and Ser371 by RCM. However there was a more dramatic decrease in phosphorylation of the phosphorylated form of mammalian target of rapamycin (mTOR) and of the extracellular-signal regulated kinases (ERK) 1/2 caused by sodium diatrizoate than by iopromide. These results demonstrate the effect of RCM on some intracellular signaling pathways that may allow understanding of the mechanism of their toxicity and may allow the development of strategies to overcome their adverse effects.

Long-term maintenance of human hepatocytes in oxygen-permeable membrane bioreactor.

An oxygen-permeable membrane bioreactor utilizing human hepatocytes has been tested in this study. In the bioreactor, human hepatocytes were cultured between flat-sheet gas-permeable polymeric membranes, which ensure the diffusion of O(2) and CO(2) providing a support for cell anchorage and growth and permit the online observation of the cells with an inverse microscope. This bioreactor allows a direct oxygenation of cells adhered on membranes and of the medium overlaying cells simulating in vivo sinusoidal organization. Human hepatocytes were cultured in the presence of some therapeutic molecules to assess the temporal liver-specific functions of the cells. Interleukin 6 (IL-6), which is a multifactorial proinflammatory cytokine involved in a variety of host defences and pathological processes, and diclofenac, an arylacetic non-steroidal anti-inflammatory drug, were used as therapeutic molecules. The aim of this study was to evaluate the in vitro performance of the small oxygen-permeable membrane bioreactor in the long-term maintenance and differentiation of human hepatocytes under in-vivo-like conditions. The fluid dynamics of the bioreactor were characterized before using it for human cell culture. The functional response to a step challenge in the medium of IL-6 (120 pg/ml), diclofenac (80 microm) and IL-6 and diclofenac together was investigated. The ability of hepatocytes to perform liver-specific functions in terms of urea and albumin synthesis, as well as secretion of total proteins, was maintained for 32 days. Also, the diclofenac biotransformation functions were sustained as the formation of the metabolites 4'-OH-diclofenac and 5-OH-diclofenac lactam demonstrated. This study attested the feasibility of the membrane bioreactor as an in vitro simple model system that allows human hepatocytes to be maintained in a differentiated state similar to that in vivo.

[The use of Cinacalcet in chronic kidney disease: a case report]. / Utilizzo del calcio-mimetico in terapia conservativa: un caso clinico.

Secondary Hyperparathyroidism is an important concurrent cause of cardiovascular and osteo-articular events, as well as, high morbidity and mortality for patients suffering from chronic kidney disease in conservative therapy and dialysis. The usual therapies, such as the vitamin D active metabolites and the phosphate binders did not always demonstrate effective in SHP control. New drugs, such as the calcimimetics, are available, resulting beneficial in highly reducing PTH levels. The only calcimimetic drug clinically used is cinacalcet, whose use is planned only in patients undergoing dialysis (peritoneal and extracorporeal). We describe the clinical case of a caucasian woman of 82 yrs old, with chronic kidney disease and secondary hyperparathyroidism resistant to usual therapies, in conservative treatment, which is prescribed cinacalcet (off-label). At first we found a worsening of the indices of renal function secondary to the effects of the drug on the hydrosaline balance. Increasing the hydrosaline intake we have seen the reduction and the subsequent stability of exams. Cinacalcet was effective in controlling the levels of parathyroid hormone and has contributed significantly to the achievement of optimal calcium-phosphorus balance. In view of these data, there is no doubt in taking in consideration the use of this drug also in the earliest stages of IRC.

Changes of serum albumin and C-reactive protein are related to changes of interleukin-6 release by peripheral blood mononuclear cells in hemodialysis patients treated with different membranes.

Protein malnutrition, a condition associated with an albumin concentration less than 3.5 g/dL, has been shown to be a major risk factor for increased mortality in hemodialysis patients. The aim of this cross-over study was to evaluate the relationship between the type of membrane adopted and serum albumin changes by measuring peripheral blood mononuclear cells (PBMC) interleukin-6 (IL-6) release, serum albumin, and plasma concentrations of C-reactive protein (CRP) in 18 patients dialyzed with different membranes. During the study, all patients were dialyzed with cuprophan (CU), synthetically modified cellulosic (SMC) membrane (a new cellulosic membrane with lesser complement activation), and cellulose diacetate (CD) membrane, and have served as their own controls. IL-6 spontaneous release by PBMC resulted after 3 months of SMC (436.2 +/- 47.4 pg/mL) significantly (P < 0.05) reduced as compared with CU (569.3 +/- 24.5 pg/mL). This effect was more evident after 6 months of dialysis with SMC (220 +/- 35.3 pg/mL, P < 0.01 versus CU and versus 3 months of SMC). The passage to CD membrane was followed by a progressive new increase in the IL-6 PBMC release (332.3 +/- 30.7 after 3 months, and 351.2 +/- 35.8 pg/mL after 6 months, respectively) that, however, remained significantly (P < 0.05) lower than CU. The behavior of CRP plasma levels resembled that of IL-6 PBMC release (23.3 +/- 4.7 in CU, 11.0 +/- 2.1 after 3 months in SMC, and 7.9 +/- 1.5 after 6 months in SMC, respectively). IL-6 release values were positively correlated with circulating levels of CRP (r = 0.3264, P < 0.002). Serum albumin increased after 6 months of dialysis with SMC membranes (3.25 +/- 0.09 g/dL in CU and 3.64 +/- 0.07 g/dL in SMC, P < 0.05). When the patients were switched to CD, serum albumin showed a slight, though not statistically significant, decrease. Serum albumin concentrations negatively correlated with both IL-6 release values (r = -0.247, P < 0.05) and CRP plasma levels (r = -0.433, P < 0.001). In conclusion, our data clearly show that a significant relationship exists between biocompatibility of the membranes and serum albumin changes; serum albumin levels, in fact, are negatively correlated with the PBMC spontaneous IL-6 release values and CRP circulating levels.