[Use of cinacalcet in clinical practice for the treatment of secondary hyperparathyroidism: analysis of the Italian data of the ECHO study]. / Utilizzo del cinacalcet nella pratica clinica per il trattamento dell'iperparatiroidismo secondario: analisi dei dati italiani dello studio osservazionale ECHO.

Several studies have shown that, compared with standard therapy, cinacalcet reduces parathyroid hormone (PTH) as well as calcium and phosphorus levels in dialysis patients with secondary hyperparathyroidism (SHPT). The ECHO study evaluated cinacalcet use in actual clinical practice. ECHO enrolled 1865 patients treated with cinacalcet at 187 sites in 12 European countries. In Italy 263 patients were enrolled at 20 sites. The primary objective of the study was to evaluate K/DOQI target achievement in SHPT dialysis patients after the introduction of cinacalcet. Patients on cinacalcet treatment between July 2005 and October 2006 were enrolled and data were collected from 6 months prior to starting cinacalcet up to 12 months after. No treatment algorithm was provided to the investigators. Italian patients had suboptimally controlled SHPT at baseline according to K/DOQI targets (median PTH 760 pg/mL, P 5.4 mg/dL, Ca 9.7 mg/dL). After 1 year of cinacalcet treatment a reduction of PTH (-53.4%), Ca (-7.3%), P (-4.6%) and Ca x P (-14.4%) was observed. The proportion of patients that reached the K/DOQI targets after 1 year of cinacalcet treatment was higher compared to baseline for all parameters (PTH 32% vs 5%; Ca 48% vs 35%; P 59% vs 55%, Ca x P 82% vs 64%). The Italian ECHO data show that cinacalcet treatment increases the proportion of patients achieving the K/DOQI targets for PTH, Ca, P and Ca x P, confirming the effectiveness of cinacalcet in clinical practice in Italy. These findings are consistent with the phase III study results on cinacalcet use in dialysis patients in Europe.

Proteomic analysis of urine from proteinuric patients shows a proteolitic activity directed against albumin.

BACKGROUND: Nephrotic syndrome is a condition that is clinically associated with poor outcome. In this study, we compared different techniques of urine sample preparation in order to develop a robust analytical protocol to define the differential urinary proteome of urinary abnormalities compared to nephrotic proteinuria. METHODS: We recruited 5 normal control subjects, 16 patients with urinary abnormalities and 16 patients with nephrotic syndrome. Proteins from normal urine were processed using three different protocols [acetone, ultrafiltration and trichloroacetic acid (TCA) precipitation], depletion of albumin and IgGs and then analysed by two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) gels and mass spectrometry. RESULTS: Comparing the three extraction methods by visual inspection of gels after 2D gel electrophoresis, the acetone precipitation and TCA methods yielded the best quality of protein extraction, while the acetone precipitation method was the most efficient. Furthermore, we tested three commercial kits for albumin and IgG depletion. We applied the optimized acetone extraction protocol to compare urinary samples from nephrotic patients (NP) to urinary samples obtained from patients presenting with urinary abnormalities (UAP). We observed a proteolytic activity directed against albumin. This observation was more prevalent in urinary samples from NP than from UAP. Within both groups, there was some inter-individual variability in the observed proteolytic activity. An increased concentration of alpha1 antitrypsin was also observed in urine of NP. We analysed albumin fragmentation by 1D and 2D western blots in the same samples skipping the albumin and IgG depletion steps to avoid the possible confound of albumin fragment removal. The analysis confirmed a stronger proteolytic activity in the nephrotic group. CONCLUSIONS: The proteolytic activity against albumin and the anti-proteolytic activity of alpha1 antitrypsin are likely linked and could play an important role in the nephrotic process. If replicated in larger samples, this methodology may lead to a better understanding of the underlying pathophysiological process of nephrotic syndrome.

Primary IgA nephropathy is more severe in TGF-beta1 high secretor patients.

BACKGROUND: IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide and is characterized by extremely variable clinical and morphological features and outcome. TGF-beta1 has a key role in fibrogenesis and the progression of renal damage. Its production is under genetic control. METHODS: We recruited 105 Italian biopsy-proven IgAN patients for genotyping for the TGF-beta1 C-509T, T869C (COD 10) and G915C (COD 25) polymorphisms; 200 healthy blood donors were used as normal controls. Glomerular and interstitial mRNA levels of TGF-beta1 were assessed by real-time PCR in 34 patients to seek relationships with clinical, renal histopathological features and outcome. RESULTS: The genotype distributions in the IgAN population were not statistically different from the controls. The COD 10 TT genotype was associated with more severe histological damage as assessed by Lee's classification (CC 50%, CT 39.6% and TT 17.2% were graded as mild; CC 35.7%, CT 43.7% and TT 44.8% as moderate, and CC 14.3%, CT 16.7% and TT 37.9% as severe [p=0.0049]) and with severe interstitial infiltrates (CC 10.4%, CT 35.2% and TT 54.2% [p=0.03]). A higher interstitial immunodeposition was observed for TGF-beta1, collagen IV and alpha-SMA in patients with the COD 10 T allele (p=0.045, p=0.049, p=0.032, respectively). The T allele was associated with significantly higher TGF-beta1 mRNA levels in the interstitium (TT+CT vs. CC: 0.52 +/- 0.16 vs. 0.18 +/- 0.10 copies/mL, respectively; p=0.000). The T allele was also associated with higher mRNA levels in glomeruli, though the difference was not statistically significant. Finally, the T allele was significantly associated with a worse prognosis, the end points being reached by 40% of TT+CT and 32% of CC patients (p=0.009). CONCLUSIONS: In primary IgA nephropathy, the T allele of the TGF-beta1 COD 10 C/T polymorphism seems to be associated with more severe histological lesions, higher renal TGF-beta1 mRNA levels and a worse prognosis. This polymorphism seems to be functionally relevant and to have a prognostic impact.

Plasma exchange in acute and chronic hyperviscosity syndrome: a rheological approach and guidelines study.

Therapeutic plasma exchange is an extra-corporeal technique able to remove from blood macromolecules and/or replace deficient plasma factors. It is the treatment of choice in hyperviscosity syndrome, due to the presence of quantitatively or qualitatively abnormal plasma proteins such as paraproteins. In spite of a general consensus on the indications to therapeutic plasma exchange in hyperviscosity syndrome, data or guide lines about the criteria to plan the treatment are still lacking. We studied the rheological effect of plasma exchange in 20 patients with plasma hyperviscosity aiming to give data useful for a rational planning of the treatment. Moreover, we verified the clinical applicability of the estimation of plasma viscosity by means of Kawai's equation. Plasma exchange decreases plasma viscosity about 20-30% for session. Only one session is required to normalize plasma viscosity when it is < 2.2 mPas, whereas a maximum of 3 session are required when it is > 2.2 till to 6 mPas. A fourth session is useless, especially if the inter-session interval is < 15 days. By means of a polynomial equation, knowing basal-plasma viscosity and the disease of a patient, we can calculate the decrease of viscosity obtainable by each session of plasma exchange then the number of session required to normalize the viscosity. Kawai's equation is able to evaluate plasma viscosity in healthy volunteers, but it is not clinically reliable in paraproteinemias.

Screening for silent ischemia with coronary artery calcium and nuclear stress testing in nondiabetic patients prior to kidney transplant.

Whether coronary artery calcium (CAC) screening in pretransplant patients may help predict silent myocardial ischemia is unknown. Accordingly, we performed CAC imaging on 46 nondiabetic patients awaiting kidneytransplant. All patients underwent multidetector computed tomography imaging for CAC quantification, and a vasodilator myocardial perfusion stress (MPS) test was performed only in patients with a total CAC score>300 or>100 in a single coronary artery. The mean patient's age was 46+/-14 years and the median dialysis vintage was 33 months (interquartile range 19-53). The median CAC score was 82 (interquartile range 0-700) and correlated with patients' age (p=0.006) and dialysis vintage (p=0.02). Nineteen patients qualified for MPS, but 5 refused the test. Of the remaining 14 patients, 7 patients had normal scans and 7 showed a minimal perfusion defect in the inferoposterior segment of the left ventricle. At the time of writing, 12 patients have undergone successful kidney transplantation without untoward complications. CAC screening does not appear to be associated with silent ischemia in pretransplant patients. Though CAC is extensive in dialysis patients, calcium may be associated with nonobstructive atherosclerotic lesions or calcification of the media layer of the vessel wall.

A validated model of disease progression in IgA nephropathy.

BACKGROUND: IgA nephropathy (IgAN) is the most common primary glomerulonephritis in the general population. There is accumulating evidence that immunosuppressive treatment is efficacious in IgAN. However, it is critical to define appropriate indicators for this therapy especially in the wake of potentially deleterious side effects to immunosuppressives. METHODS: This study retrospectively reviewed IgAN cases collected since 1981 to identify clinical and/or histological parameters for disease progression; 310 patients with biopsy proven IgAN, diagnosed from January 1981 to March 2004, were included. RESULTS: We defined a clinical prognostic index (CPI) using multivariate analysis, which incorporated these clinical/ histological parameters. Semiquantitative scores were assigned as follows: 2 points if creatinine (Cr) was >1.4 mg/dL, 1 point if proteinuria was >1 g/24 hr, 1 point if a patient was affected by hypertension, and 1 point if a patient was older than 30 yrs. Dividing our population into two groups (scores 0-2 = low CPI group; scores 3-5 = high CPI group), we demonstrated a significantly different 10-yr renal survival rate; in the low CPI group, renal survival since time of biopsy at 10 yrs was 91.7%; in the high CPI group the renal survival at 10 yrs was 35%. We validated the CPI in an independent sample from Verona (validation group) and demonstrated similar results for the CPI. CONCLUSIONS: The CPI is convenient to use for defining the risk of disease progression.

Water treatment and monitor disinfection.

Water treatment system and dialysis monitors are susceptible to microbial contaminations and periodical disinfection procedures are mandatory to obtain results requested from international standards and guidelines. Several chemical germicides or some physical treatments are on the market validated by device manufacturer according to medical device directives. With time, interfering substances from dialysis device or water are able to modify disinfection efficiency. Simulating-use testing is not a common procedure to validate disinfectants and recent data document as biofilm represents the most important cause of disinfection inefficacy. Some international standards include tests in the presence of various interfering substances but their use is not widespread. When using a disinfectant, residue toxicity, material compatibility and potential risks for the staff also have to be considered. A quality assurance program has to be implemented to obtain adequate performances and to improve results on patients.

The role of blood volume reduction in the genesis of intradialytic hypotension.

BACKGROUND: The aim of this multicenter prospective study was to investigate the role of relative blood volume (RBV) reduction on intradialytic hypotension. METHODS: One hundred twenty-three patients on chronic hemodialysis therapy were considered a priori normotensive (reference group A), intradialytic hypotension prone (group B), and hypertensive (group C). RBV was continuously monitored, and diastolic and systolic blood pressure (SBP) and heart rate (HR) were measured at 20-minute intervals during three dialysis sessions. RESULTS: Intradialytic RBV reduction was -13.8% +/- 7.0% and similar in the three groups (P = 0.841). SBP and RBV decreased during dialysis, with a sharp initial decrease (in the first 20 minutes for SBP and the first 40 minutes for RBV), followed by a slower decrease. The lying bradycardic response before dialysis was less in group B than group A (a decrease of 3 +/- 7 versus 9 +/- 9 beats/min; P < 0.001). When symptomatic hypotension occurred, RBV reduction was not significantly different from that recorded at the same time during hypotension-free sessions (-13.9% +/- 6.4% versus -12.7% +/- 5.2%; P = 0.149). Group, baseline plasma-dialysate sodium gradient, RBV line irregularity, and early RBV and HR reduction during dialysis influenced the relative risk for symptomatic hypotension with a sensitivity of 80% versus 30% for RBV alone. CONCLUSION: We found no difference in reduction in RBV in the three groups and no critical RBV level for the appearance of symptomatic hypotension. With variables easily available within 40 minutes of dialysis, RBV monitoring increases the prediction of symptomatic hypotension.

Epidermal growth factor receptor polymorphism and autosomal dominant polycystic kidney disease.

BACKGROUND: The clinical variability in the rate of progression of autosomal dominant polycystic kidney disease (ADPKD) has been attributed to genetic heterogeneity, though environmental factors and modifying genes very likely play an important role as well. We examined the association between clinical outcome, defined by age at onset of end-stage renal disease (ESRD) in 46 ADPKD patients, and a polymorphism in the epidermal growth factor receptor (EGFR) gene, a candidate modifying gene. EGFR is a key element in renal tubular proliferation. METHODS: This study comprised 46 unrelated patients with ADPKD and ESRD, and 58 healthy controls. The patients had prevalently PKD 1 mutations. The EGFR microsatellite polymorphism was genotyped according to Gebhardt et al (11). RESULTS: The allele frequencies of the EGFR polymorphism were different in the ADPKD sample and the control population (G2=17.19; P=0.009). In particular, the frequencies of the 122 and 118bp length alleles had a different distribution (P=0.010 and P=0.047 respectively). Patients with the 122bp length polymorphism had ESRD at an earlier age,but this finding was not statistically significant. CONCLUSIONS: These findings suggest an association between the EGFR microsatellite polymorphism and ADPKD. However, it is difficult to establish which alleles are protective and which harmful. A larger, multicenter study may help clarify these results and is also required to replicate our preliminary finding of an association between ADPKD and the EGFR polymorphism.

Identification and characterization of a new autoimmune protein in membranous nephropathy by immunoscreening of a renal cDNA library.

Membranous Nephropathy (MN) represents a large amount of Nephrotic Syndromes in the adult population and its definitive diagnosis is currently carried out through biopsy. An autoimmune condition has been demonstrated in idiopathic MN (iMN) in which some kidney structures are targeted by patient autoantibodies. Some candidate antigens have been described and other likely involved target proteins responsible for the disease are not known yet. In this work our aim is to identify these proteins by screening a lambda-phage library with patients' sera. We enrolled four groups of patients: two MN groups of 12 full iMN patients; one control group of 15 patients suffering from other renal diseases; one control group of 15 healthy individuals. A commercial cDNA phagemide library was screened using the above described sera, in order to detect positive signals due to antigen-antibody bond. We detected one phagemide clone expressing a protein which was shown to be targeted by the antibodies of the iMN sera only. Control sera were negative. The sequence analysis of cDNA matched the Synaptonemal Complex protein 65 (SC65) coding sequence. Further proteomic analyses were carried out to validate our results. We provide evidence of an involvement of SC65 protein as an autoimmune target in iMN. Considering the invasiveness and the resulting risk coming from renal biopsy, our ongoing aim is to set a procedure able to diagnose affected patients through a little- or non-invasive method such as blood sampling rather than biopsy.

Interstitial fluid obtained from kidney biopsy as new source of renal biomarkers.

INTRODUCTION: Development of renal biomarkers is required to improve on diagnostic accuracy, prognosis and prediction of response to therapy in renal disease. We describe a new method of obtaining from renal specimens a biologic fluid potentially enriched in secreted proteins. METHODS: A renal biopsy specimen was centrifuged, and the interstitial fluid (IF) obtained was evaluated by SELDI-ToF, 1D and 2D gel electrophoresis. Twelve spots were extracted from the 2D gel and characterized by MALDI-TOF-MS. RESULTS: The SELDI diagrams demonstrated abundant peptide peaks. One-dimensional gel electrophoresis demonstrated the presence of many bands indicating a diversity of proteins in the sample. Comparison of serum to IF demonstrated a number of bands that were not shared, suggesting that the IF is not a simple "replica" of plasma fluid. Employing 2D-PAGE, 418 spots were identified in the IF sample; 12 spots were selected and analyzed by mass spectrometry. CONCLUSIONS: We have described a novel technique to obtain a biologic fluid that contains a significant quantity and diversity of proteins from renal tissue. The procedure to obtain the fluid is simple and easily applicable to standard renal biopsy procedures. This fluid has the potential to identify informative proteins that are more concentrated than in any other renal biologic fluid previously analyzed and strictly related to renal pathophysiology. Future work includes the development of a clinical protocol to identify and validate informative biomarkers that have diagnostic and prognostic value.

Lipoprotein glomerulopathy treated with LDL-apheresis (Heparin-induced Extracorporeal Lipoprotein Precipitation system): a case report.

INTRODUCTION: Lipoprotein glomerulopathy is a glomerulonephritis which was described for the first time by Saito in 1989 and is currently acknowledged as a separate nosological entity. It is histologically characterized by a marked dilatation of the glomerular capillaries and the presence of lipoprotein thrombi in the glomerular lumens. The dyslipidemic profile is similar to that of type III dyslipoproteinemia with Apolipoprotein E values that are often high; proteinuria and renal dysfunction are present. Proteinuria often does not respond to steroid and cytostatic treatments. The phenotypic expression of lipoprotein glomerulopathy is most probably correlated to a genetic alteration of the lipoprotein metabolism (mutation of the Apolipoprotein E coding gene). In literature, lipoprotein glomerulopathies have mainly been reported in Japanese and Chinese subjects, except for three cases in the Caucasian race, reported in France and the USA. CASE PRESENTATION: We describe the case of a 60-year-old female, Caucasian patient suffering from lipoprotein glomerulopathy, carrier of a new mutation on the Apolipoprotein E gene (Apolipoprotein E(MODENA)), and treated successfully with low density lipoprotein-apheresis with the Heparin induced extracorporeal lipoprotein precipitation system. After a first phase of therapeutic protocol with statins, the patient was admitted for nephrotic syndrome, renal failure and hypertension. Since conventional treatment alone was not able to control dyslipidemia, aphaeretic treatment with heparin-induced Extracorporeal Lipoprotein Precipitation - apheresis (HELP-apheresis) was started to maintain angiotensin converting enzyme inhibitor therapy for the treatment of hypertension. Treatment with HELP-apheresis led to a complete remission of the proteinuria in a very short time (four months), as well as control of hypercholesterolemia and renal function recovery. CONCLUSION: According to this case of lipoprotein glomerulopathy, we believe that renal damage expressed by proteinuria correlates to the levels of lipids and, furthermore, the treatment with HELP-apheresis, by lowering low-density lipoprotein cholesterol and triglycerides, may be considered as a therapeutic option in synergy with pharmacological treatment in the treatment of lipoprotein glomerulopathy.

Everolimus with very low-exposure cyclosporine a in de novo kidney transplantation: a multicenter, randomized, controlled trial.

BACKGROUND: In combination with everolimus (EVL), cyclosporine A (CsA) may be used at low exposure, so reducing the risk of renal dysfunction in renal transplant recipients (RTR). We evaluated whether higher exposure of EVL could allow a further reduction of CsA. METHODS: De novo RTR were randomized to standard exposure EVL (C0 3-8 ng/mL) with low-concentration CsA (C2 maintenance levels 350-500 ng/mL, group A) or higher EVL exposure (C0 8-12 ng/mL) with very low-concentration CsA (C2 maintenance levels 150-300 ng/mL, group B). The primary endpoints were 6-month creatinine clearance (CrCl) and biopsy-proven acute rejection (BPAR) rate. After 6 months, patients were followed up (observational extension) to 12 months. RESULTS: Two hundred eighty-five RTR (97% from deceased donors) were enrolled. Two patients per group died (1.4%). The 6-month death-censored graft survival was 90.2% in group A and 97.9% in group B and was unchanged at 12 months (P=0.007). There was no significant difference between groups at 6 months in CrCl (59.9 vs. 57.8 mL/min) and BPAR rates (14.7% vs. 11.9%) and also at 12 months (CrCl 62.5+/-20.7 vs. 61.3+/-22.0 mL/min, BPAR 14.7% vs. 14.1%). No significant differences were seen in treated acute rejections, steroid-resistant acute rejections, treatment failures, or delayed graft function, although there was a trend to better results in group B. CONCLUSIONS: EVL given at higher exposure for 6 months plus very low CsA concentration may obtain low acute rejection rate and good graft survival in De novo renal transplantation. However, there was no difference between groups in CrCl.

Proteomic analysis of early urinary biomarkers of renal changes in type 2 diabetic patients.

Diabetic nephropathy (DN) is a complication associated with diabetes, leading to end-stage renal disease (ESRD). Despite significant progress in understanding DN, the cellular mechanisms leading to the renal damage are incompletely defined. In this study, with the aim to identify urine biomarkers for the early renal alterations in type 2 diabetes mellitus (T2D), we performed urinary proteomic analysis of 10 normoalbuminuric patients with T2D, 12 patients with type 2 DN (T2DN), and 12 healthy subjects. Proteins were separated by 2-DE and identified with ESI-Q-TOF MS/MS. Comparing the patients proteomic profiles with those of normal subjects, we identified 11 gradually differently changed proteins. The decreased proteins were the prostatic acid phosphatase precursor, the ribonuclease and the kallikrein-3. Eight proteins were progressively increased in both patients groups: transthyretin precursor, Ig κ chain C region, Ig κ chain V-II region Cum, Ig κ-chain V-III region SIE, carbonic anhydrase 1, plasma retinol-binding protein, ß-2-microglobulin precursor, ß-2-glycoprotein 1. The proteomic analysis allowed us to identify several increased urinary proteins, not only in T2DN but also in T2D patients in which the microalbuminuria was in the normal range. These patterns of urinary proteins might represent a potential tool for a better understanding of diabetic renal damage.

Psychological factors associated with medication adherence following renal transplantation.

BACKGROUND: A relationship exists between non-adherence and clinical outcomes in health care, including renal transplantation. The aim of this study was to identify the psychological variables associated with non-adherence to medication after renal transplantation. METHODS: This cross-sectional study involved 34 patients, 38% male, with a mean age of 49 yr (range 26-70) and a mean of six yr post-transplantation. Adherence to medication was measured by two items: (i) the frequency of not taking medications and (ii) the frequency of not taking medications exactly as prescribed. The psychological variables were: dispositional coping style (COPE) and five items measuring barriers and perceived characteristics of the medication regimen. Descriptive and multivariate analyses were utilized to examine the data. RESULTS: Twenty-four per cent of patients reported less than perfect adherence. Individuals who were younger, who perceived less autonomy in the management of treatment and who were characterized by an active coping style were less likely to adhere to medication. Individuals who perceived less autonomy and a higher level of interference of treatment with their life patterns were less likely to take medication exactly as prescribed. CONCLUSIONS: The finding of this study suggests that adherence to medications after renal transplant is associated with psychological variables, such as coping style and perceived autonomy in the management of treatment. Understanding of the patient's perspective may help to develop effective interventions to increase the levels of adherence to medications that may result in better clinical outcomes.

Effect of a continuous erythropoietin receptor activator (C.E.R.A.) on stable haemoglobin in patients with CKD on dialysis: once monthly administration.

AIMS: This Phase II study aimed to determine the optimal dose and administration schedule of continuous erythropoietin receptor activator (C.E.R.A.) given subcutaneously (s.c.) in patients receiving dialysis converting directly from s.c. epoetin therapy 1-3 times/week. An extension phase examined long-term safety and efficacy. METHODS: Patients were assigned to one of three C.E.R.A. dose groups determined by multiplying the previous weekly dose of epoetin by one of three ratios (0.4/150, 0.8/150, 1.2/150 for groups A, B and C, respectively). Within each group, patients were randomized to once weekly (QW), once every 3 weeks (Q3W) and once monthly (Q4W) schedules. Dose adjustments were not permitted for the first 6 weeks. The core study period was 19 weeks (21 weeks in the Q4W cohorts). Patients could enter a 12-month extension period at the same schedule, aiming to maintain haemoglobin (Hb) at 11-12 g/dL. RESULTS: 137 patients entered the core period, and 62 continued into the extension period. A dose-dependent relationship was seen in the primary efficacy variable, change in Hb standardized to a 6 week period (p < 0.0001), but effect was independent of schedule. Hb levels were maintained throughout the study, with few dose changes. C.E.R.A. was generally well tolerated and the most frequent adverse event was hypotension. CONCLUSION: The results suggest that s.c. C.E.R.A. at up to once monthly intervals provides stable maintenance of Hb levels in dialysis patients converting directly from epoetin 1-3 times/week. Achieving tight Hb control with few dose adjustments at extended administration intervals may offer health benefits and improvements in resource management.

Influence of ACE I/D gene polymorphism in the progression of renal failure in autosomal dominant polycystic kidney disease: a meta-analysis.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is a renal disease characterized by an important variability in clinical course, which cannot be fully explained by the genetic heterogeneity of the disease. Although the role for the angiotensin I-converting enzyme (ACE) insertion/deletion (I/D) polymorphism as a modifier factor in ADPKD renal deterioration has been suggested, direct evidence from genetic association studies remain inconclusive. To provide a more robust estimate of the putative effect of the ACE I/D polymorphism on the renal progression in ADPKD, we performed a meta-analysis pooling data from all relevant studies in which the role of the ACE I/D variant in ADPKD clinical features was evaluated. METHODS: We applied a random-effects model to combine odds ratio and 95% confidence intervals. Q-statistic was used to evaluate the homogeneity, and both Egger's and Begg-Mazumdar tests were used to assess publication bias. RESULTS: Altogether, three distinct meta-analyses were generated using data from 13 studies. Despite the absence of publication bias and the presence of homogeneity among study results, the DD genotype failed to show an influence on risk of end-stage renal disease (ESRD), mean age at ESRD or risk of hypertension in ADPKD patients when compared with I-allele carriers (DD vs ID+II). Likewise, meta-analyses carried out separately for Caucasian and Asian studies showed no indication of an association between the DD genotype and a faster renal deterioration in ADPKD. CONCLUSION: These findings do not support the hypothesis that the enhanced ACE activity associated with the D allele might promote a significantly worse prognosis in patients with ADPKD.

Activation of coagulation during hemodialysis: effect of blood lines alone and whole extracorporeal circuit.

Activation of coagulation during hemodialysis (HD) is a relevant clinical problem, especially when patients at risk of bleeding are treated. However, little is known about the relative contribution of the various components of the circuit to the thrombotic process. Thus, an experimental model was developed that is aimed at evaluating biochemical markers of coagulation activation at different times and sites throughout the HD circuit. A HD blood-tubing set with integrated arterial and venous chambers (cartridge-line set) was used, which was added with the following sampling points: at the beginning of the arterial line (P1), before the blood pump (P2), after the blood pump (P3), and at the end of the venous line (P4). A bypass system allowed us to circulate the blood only into the blood lines for the first 20 min of the extracorporeal circulation. The extracorporeal circuit was rinsed with 1.7 L of heparinized saline (2,500 IU/L) that was completely discarded before patient connection. A continuous administration of unfractionated heparin (500-800 IU/h) without a starting bolus was adopted as a low heparin extracorporeal treatment. Samples were collected before the start of the extracorporeal circulation from the fistula needle (T0P0), after 5 (T1), 10 (T2), and 20 min (T3) from P1, P2, P3, and P4. After 20 min, the blood was returned to the patient using only saline and HD was then started, circulating the blood through the dialyzer. Further samples were obtained from P1 and P4 after 5 (T4) and 210 min (T5). Plasma levels of coagulation activation markers-thrombin-antithrombin complex (TAT) and prothrombin fragment 1 + 2 (F1 + 2)-were evaluated in all the samples in 12 stable HD patients. In each patient, the activated partial thromboplastin time (APTT) was measured at T0P0 and T1-T5 from P1. No significant changes were found at any time as far as F1 + 2 is concerned. However, TAT levels increased over time only after the start of HD, suggesting that the latter test could be more useful in order to detect coagulation activation during HD. The same experiments performed with nonheparin-primed extracorporeal circuit showed similar results. The blood lines used did not significantly activate coagulation during the first 20 min, whereas only 5 min of blood circulation throughout the whole circuit increased TAT values, which still remained lower than previous reports, even after 210 min of treatment.

Water treatment for hemodialysis: a 2005 update.

Water for dialysis represents an additive risk factors to the chronic inflammatory state documented in patients on ESRD. The possibility of sustaining proinflammatory cytokines through microbial derived products, coming from dialysate or infused solutions, is enhanced by biofilm presence on piping and on water treatment system or monitor components. Spread use of reverse osmosis, loop distribution system and pre-treatment components tailored to local raw water characteristics have greatly contributed to a general improvement in final water quality. Notwithstanding these contributions literature still reports fatal accidents or significant percentage of dialysis units not complying to the water quality standards. Technological improvement lowers chemical contamination but microbial quality relays more on quality assurance programs than on technology. Optimal water quality represents part of the anti-inflammatory strategies we need to assure to our dialysis patients to improve outcome.