Clock gene expression in mouse kidney and testis: analysis of periodical and dynamical patterns.

Molecular clocks drive circadian rhythmicity of cellular functions in peripheral tissues and organs, kidney included, whereas in the testis this clockwork seems constitutively active. We have evaluated the periodicity and the dynamics of expression of the clock genes BMAL1, CLOCK, PER1, PER2, CRY1, CRY2 and REV ERBalpha over 24 h in the kidney and testis using a mouse model. The periodicity was explored by single cosinor, and dynamics were explored by calculation of fractional variations of gene expression related to time intervals. Kidney and testis were harvested at 4-h intervals over a 24-h period from eight-week-old C57BL/6 male mice housed individually on a 12 h light (L)-dark (D) cycle (lights on at 08:00 h; lights off at 20:00 h) and mRNA was extracted and analyzed by Quantitative Real-time Reverse Transcription PCR. A statistically significant difference was evidenced between kidney and testis for the original values of expression level of BMAL1, PER1, PER2 CRY1, CRY2 and REV ERBα. A statistically significant difference was evidenced between kidney and testis for the fractional variation of BMAL1, PER2, CRY1, CRY2 and REV ERBα. A significant 24-h rhythmic component was found for BMAL1, CLOCK, PER1, PER2, CRY1, CRY2 and REV ERBα in the kidney, whereas no core clock gene showed circadian rhythmicity in the testis. Fractional variations provided significant circadian rhythms for BMAL1, PER2, CRY, CRY2 and REV ERBα in the kidney, whereas in the testis the fractional variation calculations showed no circadian rhythmicity, but quantitative comparison showed statistically significant differences in only 16.7 percent of the time points studied. In conclusion, in the kidney the clock gene machinery shows circadian oscillation of mRNA levels and time-related variations in the rate of change of clock gene expression. In the testis the clock genes do not show circadian rhythmicity of expression and the dynamics of variation are not characterized by a periodical pattern, but are quantitatively similar to those observed in the kidney. These data suggest that in the testis the clock gene machinery shows a tissue-specific pattern of function and clock genes may play a different role in the testis with regard to other peripheral tissues, maybe in relation to the presence of developmental and differentiation phenomena.

Reduced glomerular filtration rate and prior cardiovascular event entail similar risk for coronary atherosclerotic burden.

OBJECTIVE: Prior cardiovascular event and kidney dysfunction are both strong risk factors for coronary artery disease. The aim of this study is to assess coronary atherosclerotic burden in a large population of patients undergoing coronary angiography, according to prior cardiovascular event or chronic kidney disease. PATIENTS AND METHODS: We evaluated 700 consecutive patients who underwent coronary angiography (CA). Serum creatinine to estimate glomerular filtration rate (eGFR) was measured. Clinically significant coronary artery disease (CAD) was defined by the presence of a coronary lesion resulting in a luminal stenosis >50%. For the purpose of the study, the whole population was divided into 4 subgroups according to the presence/absence of eGFR <60 ml/min/1.73 m2 or prior cardiovascular event: eGFR≥60/no event (Group A), eGFR≥60/yes event (Group B), eGFR<60/no event (Group C), eGFR<60/yes event (Group D). PATIENTS: As expected, patients in group D had the worst clinical and biochemical profile. These patients also presented the highest values of urinary albumin creatinine ratio (ACR, p<0.001) and the lowest values of eGFR (p<0.01). One-hundred-ninety-six patients had three-vessel disease. Patients who had undergone PCI procedure showed a lower eGFR as compared to patients who had not (p=0.009). Considering group A as reference, the risk of having three-vessel disease was increased in group B (OR= 2.09; 95% CI 1.37-3.19), in group C, (OR= 1.80; 95% CI 1.04-3.14), and finally in group D (OR= 3.35; 95% CI 2.01-5.58). The risk carried by group C was not significantly different from that carried by Group B: OR= 0.86; 95% CI 0.5-1.5. CONCLUSIONS: In our study, low eGFR seems to have the same excess risk of prior CV event.

Proteinuria in the prognosis of IgA nephropathy.

IgA Nephropathy (IgAN) is the most common lesion causing primary glomerulonephritis in the world. The main clinical predictors of progression are: elevated blood pressure, high histological score and proteinuria. Although elevated serum creatinine concentration at diagnosis, increased excretion of cytochines, age at onset, obesity and genetic factors may all influence clinical outcome, it is quite clear that proteinuria is the hallmark of renal damage in IgAN. Patients with IgAN and little or no proteinuria (<500 mg/day) have low risk of progression in the short term, while the rate of decline in renal function is 25-fold faster in those with sustained proteinuria >3 g/day. The product of duration (years) and urinary protein excretion (g/day) at the time of renal biopsy is more significantly correlated with progression. So, this so called proteinuria index may be a useful predictor for glomerular and interstitial histopathological changes and the fate of renal function in IgAN. The progression of IgAN may be slowed by antihypertensive and antiproteinuric therapy, such as angiotensin converting enzyme inhibitors and/or angiotensin II receptor blockers, that can minimize secondary glomerular injury. Proteinuria has been shown to be an adverse prognostic factor in IgAN, with a strong relationship between proteinuria and prognosis and established importance of remission. Consequently, targeting proteinuria may be a valid surrogate for individualized kidney protective therapy.

[Uremic pruritus: an unresolved challenge]. / Lettera del Presidente.

Pruritus is a common and unpleasant symptom in the dialysis setting, affecting about half of all hemodialysis and peritoneal dialysis patients. It has a great impact on patients' quality of life and is also associated with increased mortality. The pathogenesis of uremic pruritus (UP) is clearly multifactorial and still poorly understood. At least four main hypotheses have been put forward: dermatological abnormalities, an immune-system derangement that results in a proinflammatory state, an imbalance of the endogenous opioidergic system, and a neuropathic mechanism. The neurophysiology of itch has been shown to be quite similar to that of pain, supporting the hypothesis that the two phenomena may be closely related in dialysis patients, who often also experience uremic neuropathy. Moreover, an array of other triggering factors may include uremic toxins, systemic inflammation, cutaneous xerosis, and common comorbidities such as diabetes mellitus, endocrinopathies and viral hepatitis. The first step in the treatment of UP focuses on some general strategies that include the optimization of the dialysis schedule using biocompatible membranes such as polymethyl methacrylate, and the control of the divalent ion metabolism. The second step may be local therapy with skin emollients and capsaicin creams. More specific treatments that appear promising but have not been proven to be definitively efficacious include UVB light, gabapentin and the novel k-opioid-agonist nalfurafine. Nephrologists, who still tend to neglect this disabling symptom, need to be aware that UP is associated with poorer patient outcomes and that a stepwise therapeutic approach is now available.

[Why does a patient on hemodialysis have radiopaque material in his abdomen?]. / Perchè questo paziente emodializzato ha materiale radiopaco in addome?

Lanthanum is a third-generation, non-calcium and non-aluminium-based phosphate binder indicated for the treatment of hyperphosphatemia in stage 5 chronic kidney disease. The drug is well tolerated, with gastrointestinal complications as its main side effect. Recently, some case reports have described the typical X-ray features of this compound. We report another case of the radiopaque appearance of lanthanum carbonate, which underlines that clinicians need to be aware that its ingestion may cause opacifications in the colon.

[Color-Doppler ultrasound in renal artery stenosis and cardiovascular risk: case report]. / Eco-color-Doppler delle arterie renali nel rischio cardiovascolare: case report.

Renal artery stenosis (RAS) is a common manifestation of generalized atherosclerosis, frequently involving other vascular districts, particularly the coronary tree. Duplex ultrasonography is the diagnostic procedure of choice for screening outpatients for RAS. We report a case of metabolic syndrome in a 63-year-old obese man with atherosclerosis and low-grade RAS that was an important sign of cardiovascular risk. In fact, cardioscintigraphy and coronary arteriography showed severe coronary artery disease. RAS is an independent predictor of adverse cardiovascular events such as myocardial infarction, stroke, and cardiovascular death. In this case, duplex ultrasonography demonstrated the importance of screening for RAS as the expression of coronary artery disease.

Kinetics of hepatitis B virus load and haemodialysis: a prospective study.

The control of the spread of hepatitis B virus (HBV) infection within dialysis units has been an important goal in the management of patients on regular dialysis but infected patients continue to enter the dialysis system. It is evident that HBV viraemia in hepatitis B surface antigen (HBsAg)-positive patients on dialysis is low but it remains unclear whether haemodialysis per se can contribute to viral load reduction in such patients. HBV DNA was determined in 40 HBsAg-positive patients on maintenance haemodialysis immediately before and at the end of a 4-h haemodialysis session. The same measurements were repeated 48 and 72 h later. Twenty (50%) of 40 HBsAg-positive patients had detectable HBV DNA in serum. Detectable HBV DNA in serum was not predicted by demographic, clinical or biochemical parameters. HBV load decreased in the majority of patients after haemodialysis, although the difference was not significant (29 390 +/- 48 820 vs 23 862.8 +/- 4 350 copies/mL, NS). There was a strong relationship between mean HBV DNA levels before dialysis and absolute reduction of HBV DNA during haemodialysis sessions (r = 0.75, P = 0.0001). No difference occurred in the magnitude of change in HBV DNA titre when comparing cellulosic to synthetic membranes. Haemodialysis per se leads to a reduction in HBV load in HBsAg-chronic carriers on maintenance dialysis. This phenomenon could explain the low viral loads in these patients. Prospective studies are in progress to identify the mechanisms responsible for reduction in HBV load during haemodialysis.

[Health-related quality of life in patients with chronic kidney disease]. / Qualita' della vita nei nefropatici.

Assessment of quality of life in patients with different degrees of chronic kidney disease is an important issue because of its impact on clinical decisions and financial resource management in the health-care system. The aim of this study was to assess whether a generic instrument like the SF-36 questionnaire is able to discriminate three different populations of patients with different degrees of renal disease (pre-ESRD, ESRD, TxR). Five hundred sixty-three patients from 12 Italian nephrology units completed the SF-36 scales by themselves. The results from these samples were compared with those from the general population. Univariate analysis and multivariate regression were used. The generic SF-36 questionnaire proved to be a powerful instrument to discriminate populations with different degrees of chronic renal failure. The quality of life of patients on dialysis is significantly worse than that of the normal population and other patients with less severe renal function impairment.

Gamma glutamyltranspeptidase activity and viral hepatitis in dialysis population.

BACKGROUND: Numerous investigations have reported that viral hepatitis is associated with significant hepatocellular damage, as expressed by raised aminotransferases in serum, in dialysis population. However, scarce information exists on the activity of gamma glutamyltranspeptidase (GGTP) in dialysis patients with infection by hepatotropic viruses. OBJECTIVES: We measured serum GGTP values in a large cohort (n=757) of patients receiving long-term dialysis; healthy controls were also included. The relationship between GGTP values and a series of demographic, clinical, and biochemical parameters was analyzed. METHODS: Serum GGTP levels were tested by spectrophotometry. A subset (n=333) of dialysis patients was tested by molecular technology (branched-chain DNA (bDNA) assay) to evaluate the relationship between serum GGTP and HCV viremia. A subgroup (n=78) of dialysis patients was analyzed by an ultrasound scan of gallbladder and biliary tract to assess the presence of gallstone disease. Multivariate analyses were made using regression models; serum GGTP values were included as a dependent variable. The usefulness of serum GGTP levels in detecting HBsAg and anti-HCV positivity was evaluated using receiver operating characteristics (ROC) curve analysis. RESULTS: Univariate analysis showed that serum GGTP levels were significantly higher in HBsAg positive and/or anti-HCV positive patients than in HBsAg negative/anti-HCV negative patients on dialysis; 85.1+/-184.1 versus 25.86+/-23.9 IU/l (P=0.0001). The frequency of raised GGTP levels was 22.2% (41/184) among dialysis patients with chronic viral hepatitis. Multivariate analysis showed a significant and independent association between serum GGTP values and positive HBsAg (P=0.005) and anti-HCV antibody (P=0.0001) status. Mean GGTP values were significantly higher in study patients than controls, 32.32+/-60.02 versus 23.5+/-16.92 IU/L (P=0.01); however, no significant difference with regard to GGTP between study and healthy cohorts persisted after correction for age, gender, race, and viral markers. No relationship between gallstone disease and serum GGTP was found (NS). An independent and significant association (P=0.0291) between raised GGTP levels and detectable HCV RNA in serum was noted among patients tested by biology molecular techniques. ROC technology demonstrated that GGTP was equally useful for detecting HBV (P=0.0004) and HCV (P=0.0005) among dialysis patients. CONCLUSIONS: We found an independent and significant association between serum GGTP values and HBsAg and/or anti-HCV antibody in dialysis population. Twenty-two percent of dialysis patients with chronic viral hepatitis had elevated GGTP. No difference in GGTP between HBsAg- negative/anti-HCV- negative dialysis patients and healthy individuals was found. Routine testing for serum GGTP levels to assess liver disease induced by hepatotropic viruses or other agents in dialysis population is suggested.

[Health technology assessment]. / La valutazione delle tecnologie in sanità.

Health technology assessment (HTA) provides information about the effectiveness, costs and broader impact of health technologies to those who plan, administer or receive care in the national health system. ''Technology'' includes all interventions used to promote health, prevent and treat disease, and improve rehabilitation and long-term care. An HTA program addresses the questions to which patients and the national health systems need answers, by investigating four main factors: whether the technology (intervention) works, for whom and at what cost, and how it compares with alternatives. Health technology assessment is not simply another kind of research. It has a number of key features that are critical to its ongoing impact and distinguish it from research: it is policy oriented, it is interdisciplinary in its content and procedures, it summarizes information from databases/reviews and sometimes produces original data; moreover, those engaged in health technology assessment recognize the importance of disseminating and communicating the information acquired. Health technology assessment constitutes a bridge between the world of research and the world of decision-making, particularly policy-making, in health care.

Intra-dialytic blood oxygen saturation (SO2): association with dialysis hypotension (the SOGLIA Study).

BACKGROUND: Intradialytic hypotension (IDH) has a dramatic impact on the main outcomes of dialysis patients. Early warning of hemodynamic worsening during dialysis would enable preventive measures to be taken. Blood oxygen saturation (SO2) is used for hemodynamic monitoring in the critical care setting and may provide useful information about IDH onset. AIM: To evaluate whether short- and medium-term variations in the SO2 signal (ST-SO2var, MT-SO2var,) during dialysis are a predictor of IDH. METHODS: In this 3-month observational cohort study, 51 hypotension-prone chronic hemodialysis (HD) patients, with vascular access by arteriovenous fistula (AVF) or central venous catheter (CVC), were enrolled. Continuous non-invasive blood SO2 was monitored (fc = 0.2 Hz) by an optical sensor on the arterial line of the extracorporeal circulation; blood pressure (every 30 min), symptoms and their time of appearance were noted. Predictive power of IDH was expressed by the area under curve (AUC) sensitivity and specificity based on intradialytic variations in SO2. RESULTS: A total of 1290 HD sessions were analyzed. Overall, off-line ST-SO2var analysis proved able to correctly predict IDH in 67 % of the sessions where IDH occurred. The best predictive performance was found in the presence of highly arterialized AVF (SO2 > 95 %) (75 % sensitivity; AUC 0.825; p < 0.05). On the contrary, in sessions with CVC, IDH prediction proved more efficient by MT-SO2var (AUC 0.575; p = 0.01). CONCLUSIONS: Intradialytic SO2 variability could be a valid parameter to detect in advance the hemodynamic worsening that precedes IDH. Appropriate timely intervention could help prevent IDH onset.

Quantitative ultrasound technique at the phalanges in discriminating between uremic and osteoporotic patients.

This study was conducted to test the ability of quantitative ultrasound technique (QUS) at the phalanges to discriminate between uremic and osteoporotic patients. Three groups of subjects (38 dialytic women, 16 osteoporotic women with vertebral fractures, 19 non-dialytic and non-fractured women) were recruited at the Department of Radiology at "Casa Sollievo della Sofferenza" Hospital, San Giovanni Rotondo, Italy. The groups were matched for age and body mass index (BMI). On all subjects the following measurements were performed: spinal BMD by QCT and by DXA, Femoral BMD by DXA, phalangeal QUS. For QUS measurements, the DBM Sonic (IGEA, Carpi, Italy) was applied to the metaphysis of the proximal phalanges of the last four fingers of the hand. Osteoporotic women with vertebral fractures showed significantly lower values of spinal BMD by QCT and DXA and Ward's Triangle BMD with respect to hemodialytic patients (p<0.005). All QUS values, except for BTT and SoS, showed lower values in osteoporotic women with respect to hemodialytic patients (p<0.05). Control group showed higher values of AD-SoS, BTT and SoS than hemodialytic patients (p<0.005) while the two groups did not differ for BMD values measured with both QCT and DXA. UBPI and FWA data showed a similar behaviour to DXA and QCT results, whereas BTT and SoS showed a completely different behaviour. AD-SoS was the only parameter that could effectively discriminate among the three groups (ANOVA, p<0.0001). We conclude that phalangeal QUS can discriminate between hemodialysed patients and controls with similar bone mineral density, and can also discriminate between hemodialysed and osteoporotic subjects with vertebral fractures. Different characteristics of ultrasound signal can be ascribed to each bone tissue condition, enabling a clear differentiation of bone tissue changes occurring in menopause, osteoporosis and renal osteodystrophy.

Hepatitis C virus infection and diabetes mellitus in end-stage renal disease: evidence of a negative association.

Epidemiological studies have implicated hepatitis C virus (HCV) infection in the pathogenesis of diabetes mellitus (DM) both in the population as a whole and after solid organ transplantation. Whether this association exists in patients with end-stage renal disease (ESRD) undergoing dialysis is unclear. The aim of this study is to investigate the relationship between HCV and DM in a large group (n=742) of patients with ESRD from Europe and North America. The presence of diabetes was ascertained by using American Diabetes Association guidelines based on fasting glucose measurement and medication history. Presence of HCV infection was assessed by serum testing for anti-HCV antibodies. The prevalence of anti-HCV antibody positive patients was 15% (112/742); the frequency of DM was higher among anti-HCV positive than -HCV negative patients but the difference did not approach statistical significance, 32% (36/112) vs 29.5% (186/630). The frequency of patients with diabetic nephropathy was not higher in anti-HCV positive than -negative patients; 21.4% (24/112) vs 23.3% (147/630), NS. Logistic regression model showed an independent and significant link between anti-HCV seropositive status and raised GPT (P=0.032), male gender (P = 0.0462), positive history of prior renal transplant (P=0.0006), and longer time on dialysis (P=0.00001). In summary, no link between anti-HCV antibody and DM occurred in this ESRD population; there was no association between rate of anti-HCV antibody and diabetic nephropathy.

Review article: hepatitis C virus infection and type-2 diabetes mellitus in renal diseases and transplantation.

A link between hepatitis C virus infection and development of diabetes mellitus has been suggested by many investigators; however, this remains controversial. The mechanisms underlying the association between hepatitis C virus and diabetes mellitus are unclear but a great majority of clinical surveys have found a significant and independent relationship between hepatitis C virus and diabetes mellitus after renal transplantation and orthotopic liver transplantation. We have systematically reviewed the scientific literature to explore the association between hepatitis C virus and diabetes mellitus in end-stage renal disease; in addition, data on patients undergoing orthotopic liver transplantation were also analysed. The unadjusted odds ratio for developing post-transplant diabetes mellitus in hepatitis C virus-infected renal transplant recipients ranged between 1.58 and 16.5 across the published studies. The rate of anti-hepatitis C virus antibody in serum was higher among dialysis patients having diabetes mellitus (odds ratio 9.9; 95% confidence interval 2.663-32.924). Patients with type-2 diabetes-related glomerulonephritis had the highest anti-hepatitis C virus prevalence [19.5% (24/123) vs. 3.2% (73/2247); P < 0.001] in a large cohort of Japanese patients who underwent renal biopsy. The link between hepatitis C virus and diabetes mellitus may explain, in part, the detrimental role of hepatitis C virus on patient and graft survival after orthotopic liver transplantation and/or renal transplantation. Preliminary evidence suggests that anti-viral therapies prior to renal transplantation and novel immunosuppressive regimens may lower the occurrence of diabetes mellitus in hepatitis C virus-infected patients after renal transplantation. Clinical trials are under way to assess if the hepatitis C virus-linked predisposition to new onset diabetes mellitus after renal transplantation may be reduced by newer immunosuppressive medications.

Occult hepatitis B virus infection in dialysis patients: a multicentre survey.

BACKGROUND: The epidemiology and clinical significance of occult hepatitis B virus infection (serum hepatitis B surface antigen-negative patients with detectable hepatitis B virus viraemia in serum) remains controversial with only limited information about its prevalence in patients on long-term dialysis. AIM: To address the epidemiology of occult HBV infection in a large cohort of dialysis patients. METHODS: We screened a large cohort (n = 585) of Italian chronic dialysis patients; from this population, a group of hepatitis B virus surface antigen seronegative patients (n = 213) was tested by Amplicor hepatitis B virus Monitor Test to detect hepatitis B virus viraemia (hepatitis B virus-DNA) in serum. RESULTS: Occult hepatitis B virus infection was absent (zero of 213 = 0%). Persistent hepatitis B virus surface antigen carriage was less frequent than anti-hepatitis B virus core antibody (anti-hepatitis B core antigen) seropositive status in this study group [1.88% (11 of 585) vs. 36% (216 of 585), P = 0.0001]. No dialysis patients seropositive for anti-hepatitis B core antibody in serum (zero of 123 = 0%) had detectable hepatitis B virus-DNA by polymerase chain reaction technology. No significant association between abnormal biochemical liver tests and serum anti-hepatitis B core antibody was noted in our population. Nominal logistic regression analysis demonstrated an independent and significant relationship between anti-HCV antibody and anti-hepatitis B virus core antibody in serum (Wald chi-square 16.06, P = 0.0001). The rate of seropositive patients for anti-hepatitis B virus core antibody was higher among study patients than controls with normal renal function [36.9% (216 of 585) vs. 21.4% (59 of 275), P = 0.0001]; this difference partially persisted after correction for demographic parameters, and viral markers. CONCLUSION: In conclusion, occult hepatitis B virus was absent in our study group. Anti-hepatitis B core antibody was significantly related to presence of anti-HCV antibody supporting shared modes of transmission. Clinical studies based on molecular biology techniques provided with higher sensitivity are planned.

New horizon in dialysis depuration: Characterization of a polysulfone membrane able to break the 'albumin wall'.

The uremic syndrome is attributed to the progressive retention of a large number of toxins, which under normal conditions are excreted by the healthy kidneys. Standard dialytic membranes do not purify middle-high molecular weight toxins. Haemodiafiltration with endogenous reinfusion coupled with a highly permeable membrane could break the limit of the 'albumin wall' improving the dialytic depuration without loss of important nutrients. The aim of this study was to evaluate the performance of a new polysulfone membrane, Synclear 0.2, to remove uremic molecules. Surface Enhanced Laser Desorption Ionization-Time of Flight was employed to evaluate the proteomic profile of ultrafiltrate and Electrospray Ionization-Quadruple-ToF coupled with on-chip elution was used for proteins identification. A high and specific permeability for middle-high molecular weight molecules was revealed by mass spectrometry for the investigated membrane. The identified proteins are mostly uremic toxins: their relative abundance, estimated in the ultrafiltrate by exponentially modified protein abundance index, showed a high purification efficiency of the new membrane when compared with conventional ones. In conclusion, Synclear 0.2, used as convective membrane in hemodiafiltration with endogenous reinfusion treatment, permits to break the 'albumin wall', clearing middle-high molecular weight uremic toxins, improving the dialytic treatment purification efficiency.

Reduction of mononuclear cytokine production in hemodialysis patients treated with steam-sterilized low-flux polysulphone membranes.

An increased cytokine production, correlated with long term complications of uremic disease, has been described during hemodialysis. To identify possible differences in the cytokine release of differently sterilized membranes, we enrolled six uremic patients on chronic hemodialysis. The patients underwent dialysis with ETO-sterilized low-flux polysulphone membranes (F6, Fresenius AG) for at least three months (A1), they were then switched to steam-sterilized polysulphone membranes (F6-HPS Fresenius AG) and further evaluations after one (B1) and two months (B2) were carried out. A final evaluation (A2) was made one month after switching back to F6 dialyzers. At each time period, samples were drawn to measure IL-1beta released by cultured mononuclear cells (MN). Moreover, dialysate samples were collected to test endotoxin levels. C3a and C5a levels were assessed at 0, 5, 15 and 60 min from starting hemodialysis. Anti-ETO IgE levels were also assayed at A1, B1 and A2. The LAL test revealed a good quality dialysate. The mean pre-dialysis IL-1beta levels were 215 pg/million cells at A1; falling to 49 at B1, and 54 at B2 (p<0.01); there was then a sharp rebound at A2: 284, p<0.01. Post-dialysis levels followed the same pattern. No correlation between the dialysate endotoxin level and cytokine release was found. Complement activation did not change and in all the phases of the study no anti-ETO IgE was detected in any of the subjects. Our data suggest that the steam sterilized polysulphone membrane induces a lower cytokine release than the ETO sterilized membrane, although the mechanism by which it does so remains to be clarified.

Is steam sterilization really making any difference in dialysis-induced cytokine release?

Ethylene oxide (ETO) is presently the most commonly used sterilization method for medical devices. Although alternative sterilization modes such as steam sterilization have been suggested, the effect of steam on dialysis-induced cytokine release is unknown. We enrolled 9 patients on chronic hemodialysis and evaluated at different intervals IL-1beta production while treated with ETO (NC 1785-Bellco) and steam sterilized NC 1785S-Bellco) Synthetically Modified Cellulose (SMC). A basal test during treatment with NC 1785 was performed (A); the same test was set up 4 weeks after treatment with NC 1785S (B) and, lastly, 4 weeks after returning to NC 1785 (C). Peripheral blood mononuclear cells (PBMC) were purified before and after the dialysis session, were isolated on a Ficoll/Hypaque gradient and incubated for 24 h. Spontaneous IL-1beta release was evaluated in the supernatant and in the lysate. In A, IL-1beta levels were (in pg/ml/10(6) cells, in supematant and lysate, respectively): 5.8 +/- 4.8 and 7.6+/-5.2 in pre-HD and 4.68 +/- 3.6 and 9.7 +/- 6.65 in post-HD. These levels showed a clear reduction in B: 2.5 +/- 2.2 and 4.4 +/- 3.1 in pre-HD, and 4.35+/- 6.6 and 7.52 +/- 7.22 in post-HD. In the C test, 4 weeks after the return to the ETO membrane, IL-1beta levels remained unchanged: 2.9 +/- 1.8 and 4.5 +/- 3.1 in pre-HD; and 2.6 +/- 3 and 5.7 +/- 6.6 in post-HD. Statistical analysis showed significant changes in the pre-HD levels both in supematant (p < 0.04) and in lysate (p < 0.04). Steam sterilization of SMC induced a lower spontaneous IL-1beta release, but this effect was not statistically significant due to the large inter-individual variation. Hence, contrary to claims of better biocompatibility, steam sterilization does not result in a reduced production of pro-inflammatory IL-1beta.

Ethylene-oxide and steam-sterilised polysulfone membrane in dialysis patients with eosinophilia.

Eosinophilia and some acute dialysis side-effects, such as itching, flushing and bronchospasm, are often associated with the presence of ethylene oxide (ETO) as dialyzer sterilizing agent. This study evaluated the effects of two different polysulfone (PS) hollow-fiber dialysers sterilized with ETO and steam in 31 chronic dialysis patients with eosinophilia. Clinical symptoms, metabolic and biochemical parameters, complement (C3a and C5a) activation and production were evaluated in each patient dialysed for two months at a time with Cuprophan dialyser, ETO-PS dialyser and steam-PS dialyser. The steam-sterilizer agent does not alter the purifying capacity of the PS membrane which maintains its superiority over Cuprophan in terms of biocompatibility. Using steam-PS, intradialytic eosinophil kinetics seems to improve. In some patients with high serum levels of ETO-specific IgE these levels tend to diminish. Generic intradialytic symptoms do not differ between the two sterilization methods, although some hypersensitivity symptoms during the first dialysis hour are considerably lower in some patients when steam-sterilized PS is used.

Epidemiology and clinical significance of hepatotropic infections in dialysis patients. Recent evidence.

Hepatitis C virus (HCV) infection is frequent among patients receiving long-term dialysis in developed and developing countries. It is difficult to assess the natural history of HCV in the dialysis population; however, recent studies have demonstrated that positive anti-HCV status is a significant and independent risk factor for mortality among dialysis patients. Recent meta-analyses have shown that interferon (IFN) initial monotherapy is effective in the treatment of chronic hepatitis C among dialysis patients, but tolerance to IFN mono-therapy was rather poor. Large, multicenter and prospective trials based on pegylated IFN for the treatment of chronic hepatitis C are planned. The frequency of HBV infection in patients undergoing maintenance dialysis in the industrialized world is low but not negligible; persistent HBsAg seropositivity is much higher in less-developed countries. Recent surveys have shown that detectable HBsAg/ HBV DNA status in serum is an independent and significant predictive factor for hepatocellular dysfunction in dialysis patients. No significant difference in morbidity and mortality between dialysis patients according to hepatitis B surface antigen status has been consistently shown. Preliminary reports suggest that lamivudine appears to be safe and effective in patients receiving long-term dialysis.