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Daily hemodialysis (DHD) is a promising option; however, logistic obstacles and clinical perplexities limit its dissemination. Understanding the mechanisms of, and the time until, the onset of improved well-being may help to quantify clinical advantages and to define the minimum length of a "trial" of daily dialysis. By following 30 patients treated in 4 centers, this study aimed to determine how long a period of time is needed until a patient experiences subjective improvement. From November 1998 to November 2000, 30 patients tried at least 2 weeks of short daily dialysis in four Northern Italian centers of Piemonte and Valle d'Aosta. The DHD (2 - 3 hours; blood flow 270 - 350 mL/min; individual HCO3 , Na, K) was performed at home or in a center. Motivations to try DHD, fears and concerns regarding DHD, and changes in perceived well-being were assessed by semi-structured interview. The main clinical indications for a trial of DHD were poor tolerance of conventional treatment, cardiovascular disease, and hypertension or hypotension; only 6 patients had no comorbidity at start. The patients' main reasons for choosing DHD were related to job problems and the search for a better treatment. Most of the patients continued DHD because of improved well-being; logistic reasons accounted for the drop-outs (5 patients). The main fears were related to logistic aspects, vascular access problems, and excessive involvement of the partner on home dialysis. Improved well-being was reported by 28 of 30 patients; 2 patients reported no difference. Subjective improvement was perceived within 2 weeks in 22 of 30 patients, and within 1 month in 28 of 30 patients. An offer of a 2 - 4 week trial of DHD may help patients and caregivers to determine whether subjective and objective benefits outweigh logistic problems and whether a permanent transfer to DHD is worthwhile.

INTRODUCTION Demographic analysis shows the ageing of the global population and the consequent increase in the age of hospitalized subjects and of patients starting dialysis. Hence, interest in the feasibility, safety, and usefulness of renal biopsy in elderly patients is growing. We examined the data of 131 patients over the age of 75 who underwent renal biopsy. We analyzed the safety of the procedure, treatment, and outcomes. RESULTS Histological diagnoses included: membranous glomerulonephritis (GN) 20.6%, crescentic GN 12.9%, IgAGN 10.6%, focal segmental glomerulosclerosis 9.1%, acute GN 4.5%, amyloidosis 9.1%, and acute tubular necrosis 3.8%. Mean glomerular obsolescence was 28.9 Â ± 27.9%. Mean age of the patients was 78.7 Â ± 5.73 years. At the time of biopsy, serum creatinine (SCr) was 4.47 Â ± 2.56 mg/dL and proteinuria was 4.82 Â ± 6.78 g/day. Targeted treatment was given to 51.9% of patients, 52.9% of whom had a good clinical response. Eight patients had clinically non-relevant side effects (11.7%). A positive response (defined as a more than 50% reduction of SCr, or by partial or complete remission of proteinuria) was observed in 36 patients (52.9%). 76 patients were monitored for 57 Â ± 9.89 months: 18 patients were on dialysis (follow-up 2.56 Â ± 3.61 months), 15 died (follow-up 58.5 Â ± 13.43 months), and 52 remained under nephrologic observation for 36 Â ± 31 months (SCr was 2.56 Â ± 0.75 mg/dL and proteinuria was 4.82 Â ± 6.78 g/day). CONCLUSION In our experience, renal biopsy is safe even in very elderly patients; it allowed targeted treatment in 51.9% of patients, 52.9% of whom had a good clinical response, possibly contributing to prolonged patient survival and improved quality of life.

Volume overload is typical of haemodialysis patients; correct volume status evaluation is crucial in achieving blood pressure homeostasis, hypertension management and good treatment planning. This study evaluates the effect of acute volume depletion on ultrasonographic parameters and suggests two of them as able to predict patients volume overload.27 patients with end stage renal disease treated with haemodialysis underwent a complete echocardiographic exam before, after 90 min and at the end of the dialysis.Blood pressure levels significantly drop during the first 90 min of dialysis (139 ± 20 vs 126 ± 18; p0.0001), reaching a steady state with significantly lower values compared to baseline (130 ± 28; p = 0.02). LV and left atrial volume significantly decreased (baseline vs end dialysis 98 ± 32 vs 82 ± 31 p = 0.003 and 28 ± 10 vs. 21 ± 9 cc/m(2) p0.001). A significant reduction of systolic function (EF 61.6 % ± 9 vs 58.7 % ± 9 p = 0.04), of diastolic flow velocities (E/A 1.13 ± 0.37 vs. 0.87 ± 0.38 p0.001) and mitral annulus TDI tissue velocity (i.e. E' lat 10.6 ± 3 vs. 9.4 ± 3 cm/s; p 0.0001) were observed. Stroke work (SW) and LV end-diastolic diameter (LVEDd) indexed to height 2.7(LVEDdi) were able to predict volume overload: cut off values of respectively 13.5 mm/m(2.7) for LVEDdi and 173 cJ for SW were able to predict with a specificity of 100 % the presence of a volemic overload of at least 4 %.Blood pressure, cardiac morphology and function are significantly modified by acute volume depletion and such variations are strictly interrelated. SW and LVEDd/height(2.7) may identify ESRD patients carrying an higher volume load.

BackgroundIntradialytic hypotension (IDH) is still a major clinical problem for haemodialysis (HD) patients. Haemodiafiltration (HDF) has been shown to be able to reduce the incidence of IDH.MethodsFifty patients were enrolled in a prospective, randomized, crossover international study focussed on a variant of traditional HDF, haemofiltration with endogenous reinfusion (HFR). After a 1-month run-in period on HFR, the patients were randomized to two treatments of 2 months duration: HFR (Period A) or HFR-Aequilibrium (Period B), followed by a 1-month HFR wash-out period and then switched to the other treatment. HFR-Aequilibrium (HFR-Aeq) is an evolution of the haemofiltration with endogenous reinfusion (HFR) dialysis therapy, with dialysate sodium concentration and ultrafiltration rate profiles elaborated by an automated procedure. The primary end point was the frequency of IDH.ResultsSymptomatic hypotension episodes were significantly lower on HFR-Aeq versus HFR (23 ± 3 versus 31 ± 4 of sessions, respectively, P l l0.03), as was the per cent of clinical interventions (17 ± 3 of sessions with almost one intervention on HFR-Aeq versus 22 ± 2 on HFR, P, SCOPUS: ar.j, info:eu-repo/semantics/published

The kidneys are a major target of PAPS. The histologic lesions of PAPS nephropathy are vascular; among them thrombotic microangiopathy (TMA) is the most characteristic. It is still not clear in the literature whether the nephropathy can be the unique manifestation of PAPS in the absence of other thrombotic processes; that is: do the renal microthrombotic lesions allow to make the diagnosis of PAPS in presence of anti-phospholipid antibodies (APA)? With this purpose we present three clinical cases. The first patient had severe hypertension C4 hypocomplementemia, thrombocytopenia, and mitralic valve insufficiency. LAC and anti-cardiolipin antibodies at high titre were positive. The histologic picture was characterized by basement membrane reduplication and arteriolar mucoid degeneration, which are features of early phase of TMA. The second patient had severe hypertension. The detection of anti-cardiolipin antibodies was performed several times and resulted positive three times, four months after the diagnosis as well. The renal histologic features were consistent with late lesions of TMA. The third patient had severe hypertension, rapidly progressive renal failure, tricuspidal valve insufficiency and two positive anti-phospholipid antibodies determinations three weeks apart (in two occasions anti-cardiolipin and in one occasion LAC as well were found). The renal lesions were characteristic for TMA. In conclusion we think that patients with TMA and antiphospholipid antibodies can be considered affected by PAPS, as the thrombotic process is represented by thrombosis in preglomerular arterioles, which leads to TMA.

Among currently available vascular access options for hemodialysis, central venous catheters show the poorest reliability, with frequent complications of thrombosis and stenosis impairing patency. The most serious problem, however, is catheter-related bloodstream infection (CRBI), which is typically a cause for removal of the catheter and protracted systemic antibiotic therapy. In our experience, a totally implanted device (Dialock®, Biolink Corp.) seems to confer a better global protection against catheter-related infections than standard tunneled catheters, accounting for 0.97 vs. 4.75 infection episodes/1,000 catheter-days, respectively (p < 0.001). Bloodstream infection rates, however, are not statistically different in the two groups (0.85 vs. 0.81 per 1,000 catheter-days; p = n.s.), indicating that the improvement is mainly related to local cutaneous infections. On the other hand, in the Sodemann experience, a new taurolidine-based lock solution (Neutrolin®, Biolink Corp.) greatly reduced CRBI rates with both subcutaneous ports and tunneled catheters to 0.29 and 0.20 episodes/1,000 catheter-days, respectively. These promising results await further confirmation from ongoing clinical trials.

Retroperitoneal fibrosis (RPF) is characterized by replacement of the normal tissue of the retroperitoneum with fibrosis and/or chronic inflammation. About two-thirds of cases of RPF are idiopathic and one-third is secondary to drugs, infections (tuberculosis, syphilis, actinomycosis, fungal infections), retroperitoneal hemorrhage, or malignancy. We report the case of a patient who was diagnosed as having RPF and schistosomiasis caused by Schistosoma haematobium with histological documentation. He was treated with praziquantel and afterwards with corticosteroids with remission of RPF. To our knowledge, the association between schistosomiasis and RPF has not been described in the literature. We postulate that there is a causal relationship between these two conditions.

The increase in the incidence of elderly patients starting dialysis has been as sharp, during the 1980s-1990s, as an epidemic (+70%, +150% in different settings). According to this study, performed in Piemonte, northern Italy, the process is still ongoing. During the period 1981-93, according to the Regional Registry of Dialysis and Transplantation (RPDT: data on 100% of centres and patients), the cohort on treatment increased by 79.5% and the annual incidence by 48.3%; the increase is limited to older people and is greater in males. Nephroangiosclerosis/ischaemic renal disease and diabetes mellitus are the main diagnoses. Since the increase of elderly patients is still ongoing, forecasts are difficult; according to a computer simulation, a plateau of patients on treatment is reached only if incidence is stabilized, While it is impossible to exclude a decrease in hidden selection or an increase in referral, complex modifications at the overall population level are presumably at the basis or the increase of elderly patients on dialysis. Despite the increase in average age, however, survival improved throughout the period; this confirms the interest towards the open dialysis system adopted in Piemonte, which is characterized by easy shifts among treatments and by the widespread use of high tolerance techniques.

The aim of this study was the detection of HCV viremia in both anti-HCV antibody positive and negative hemodialysis patients. Sera from 75 patients on extracorporeal blood purification in the same dialysis unit were analyzed. Anti-HCV antibodies were detected using a 2nd-generation ELISA assay and in all positive cases a RIBA 3rd-generation test was performed. HCV-RNA was tested by a reverse transcription-nested polymerase chain reaction (RT-PCR) assay with primers located in the 5' region. PCR products were analyzed by a nonradioactive hybridation assay. The presence of anti-HCV antibodies was detected in 30 (40%) patients by means of ELISA II test; 28 of them were RIBA III positive and two indeterminate. Twenty-four of the 30 HCV Ab ELISA II positive patients (80%) were HCV-RNA positive (23 RIBA III positive and 1 indeterminate). Six anti-HCV Ab ELISA II positive patients tested negative for HCV-RNA (20%); 5 of these patients were also positive for anti-HCV antibodies with a RIBA III test and 1 was indeterminate. None of the anti-HCV negative patients was HCR-RNA positive. In two cases we documented the disappearance of viremia after an acute HCV infection, with the persistence of antibody reactivity. In conclusion, anti-HCV antibody positive hemodialysis patients should be considered as potentially infectious.

Analysis of long-term dialysis results is the cornerstone of renal replacement therapy evaluation. Elderly patients may be considered a crucial cohort, since subtle differences may be enhanced in a population of lower life expectancy. The aim of the study was an analysis, from the Piedmont Registry of Dialysis and Transplantation, of the results obtained in 1981-1992 (northern Italy, about 4,400,000 inhabitants, 21 dialysis centres, open acceptance since mid-1970s) in patients aged > or = 65 years (475 patients started treatment in 1981-1985, 1026 in 1986-1992). As a first treatment, during the 12 years considered acetate haemodialysis decreased sharply; bicarbonate haemodialysis is currently the standard treatment (68%). Peritoneal dialysis is stable (21%), and haemodiafiltration is increasing (8%). Shifts between treatments are frequent: 15% of elderly patients changed treatment at least once in 1991-1992. Nephroangiosclerosis/ischaemic renal disease, undefined causes and diabetes mellitus are the major causes of end-stage renal disease; 57.3% of patients have high risk conditions in addition to age. In this cohort of patients, mean age of new cases starting dialysis significantly increased in 1986-1992 (72.7 +/- 5.4 years) versus 1981-1985 (71.3 +/- 4.5; P < 0.001). Despite this, survival at 2 years increased significantly from 54.6% in the period 1981-1985 to 59% in the period 1986-1992 (P < 0.05). Even in an ageing dialysis population, therefore, choice of an open dialysis system with easy changes among treatments allowed improvement of survival results; further technical advances may help in maintaining present trends.

Acute kidney injury (AKI) occurs in 5-45% of critically ill patients, and renal replacement therapy (RRT) is required in 4-10% of patients with AKI. AKI has long been considered to be hemodynamic damage from low blood flow resulting in shock, and efforts have been made to prevent and cure it by increasing the renal blood flow and improving the cardiac output and perfusion pressure. In recent years, new experimental studies on patients with septic AKI have shown that the renal blood flow remains unaltered or even increases in septic shock. An important mechanism in the pathophysiology of sepsis and septic shock appears to be apoptosis rather than ischemic necrosis. The type of treatment as well as the dose and timing of initiation of RRT seem to have strategic importance in the recovery of AKI in patients admitted to the ICU. In critically ill (often postsurgical and septic) patients with acute renal failure the use of new anticoagulation strategies has permitted to perform treatments for a sufficient number of hours to achieve the correct level of purification by minimizing the downtime and the bleeding risk. In our center the use of protocols for different methods and different types of anticoagulants has simplified the treatment of all patients with AKI and septic shock admitted to the ICU.

Acute pyelonephritis (APN) is a frequent pathological condition. Its etiology is prevalently due to E. coli and risk factors include sexual activity, genetic predisposition, old age and urinary instrumentation. No correlation between APN and vesicoureteral reflux has been established in adults. The diagnosis of APN is usually clinical, but computed tomography (CT) and magnetic resonance imaging (MRI) allow a more precise definition and can document evidence of abscesses. Severe cases should be treated with a fluoroquinolone or an extended-spectrum cephalosporin. Treatment should last 10-14 days. The long-term evolution of APN is prevalently favorable in adults, even though formation of cortical scars and development of macroalbuminuria and renal failure have been described. The formation of renal abscesses is underestimated and must be evaluated by CT or MRI. Abscesses need to be drained only when they are large, and medical treatment is successful in the majority of cases.

The evolution of home dialysis marked the main steps in the progress of renal replacement therapy. From the origins when home hemodialysis was often the only alternative to death, to the advent and widespread use of peritoneal dialysis, the dream of kidney transplant as a solution to all problems (at least in the young), and ultimately the profound social and organizational changes that have led to a drastic reduction of home hemodialysis, we arrive at the present with the rediscovery of the clinical, rehabilitative and economic advantages of home dialysis. Seven experts from five different centers with different expertise in home dialysis report their opinions on the future of home dialysis in a ''noncontroversial controversy''. Beyond the sterile competition between peritoneal dialysis and home hemodialysis, the shared opinion is that the two methods may complement each other, allowing a tailored treatment for each patient and a tailored organization in each setting. The organizational solutions are many; the authors underline the importance of longer survival and better rehabilitation, and the ethical need of offering each patient a choice among all available treatments. Add to this the importance of dedicated educational programs targeted to physicians, nurses and patients alike and focused on self-care and patient empowerment. A new generation of dialysis machines, easier technical solutions, and financial incentives may strengthen motivations and simplify problems; all these elements may in the near future be combined in a joint effort to increase peritoneal dialysis and revive home hemodialysis in Italy.

Background Acute pyelonephritis (APN) is a common disease which rarely evolves into abscesses. Methods We prospectively collected clinical, biochemical and radiological data of patients hospitalized with a diagnosis of APN from 2000 to 2008. Results Urinary culture was positive in 64/208 patients (30.7%) and blood cultures in 39/182 cases (21.4%). Two hundred and thirteen patients were submitted to computed tomography (CT) or nuclear magnetic resonance (NMR): confirmation of APN was obtained in 196 patients (92%). Among these, 46 (23.5%) had positive urine culture, 31 (15.8%) had positive blood culture and 15 (7.6%) had positive cultures of both urine and blood. In 98 patients, either urine or blood cultures were negative, but CT/NMR were positive for APN. Fifty of the 213 patients submitted to CT/NMR (23.5%) had intrarenal abscesses: only 2 were evidenced by ultrasound examination. No differences were found between patients with positive or negative CT with regards to fever, leucocytosis, C-reactive protein, pyuria, urine cultures and duration of symptoms before hospitalization. No differences were found between patients with or without abscesses with regards to these parameters and risk factors. Patients with abscesses had a longer duration of treatment and hospitalization. Conclusions Our data suggest that in APN it is not always possible to routinely document urinary infection in a clinical setting. This finding could be explained by previous antibiotic treatment, low bacterial growth or atypical pathogens. Systematic CT or NMR is necessary to exclude evolution into abscesses, which cannot be suspected on clinical grounds or by ultrasound examination and may also develop in the absence of risk factors.

The characteristics of patients hospitalized in nephrology wards in Italy have changed in recent years due to the aging Italian population and the increased immigration. We analyzed the demographic and clinical characteristics of patients hospitalized in our nephrology ward (17 beds) from 15 November 2008 to 15 November 2009. In this period there were 507 hospitalizations including 448 patients. The mean age was 64.4+/-18 years (range 16-96 years). Foreigners accounted for 10% of the total; their mean age was significantly lower than that of Italian patients (38.2+/-13.4 vs 67.4+/-15.9 years, p0.01). 36.3% of patients were on dialysis, 10% were transplant recipients: the reasons for admission in these cases were internal medicine related; 18.15% were hospitalized because of emergency unit crowding without indications for admission to a nephrology ward. Hospitalization lasted a mean of 13+/-13 days. The most frequent diagnosis at discharge was acute renal failure (ARF) (28.9%) (prerenal 42.1%, obstructive 12.2%, drug induced 6.8%, other causes of ARF 38.7%). Patients with ARF were older than patients with other kidney conditions (67.05+/-16.98 vs 56.03+/-18.65 years, p0.01). ARF resolved or improved in 86 patients (63.7%). Other diagnoses were cardiovascular disease 25.1%, glomerular disease 18.7%, acute pyelonephritis 10.6%, other 16.7%. Foreign patients presented infectionrelated diseases more often than Italian patients (39.2% vs 20.4%, p=0.02). 392 patients were discharged to their homes, 40 (7.9%) found a place in a long-term care facility or home for the elderly, 25 (4.9%) in other hospital units, and 50 patients died (9.8%). In conclusion, patients hospitalized in nephrology wards in 2009 were mostly elderly with a high frequency of cardiovascular disease and diabetes. The most frequent diagnosis was prerenal ARF. These data suggest the necessity of improving the prevention of this type of kidney disease. Moreover, the length of hospitalization, which is increasing because of difficult clinical and social situations, could be shortened if more nursing homes, convalescent homes and homes for the elderly were available in Italy.

Vesicoureteral reflux (VUR) may be congenital or acquired. The most frequent form of congenital VUR is primary VUR. Its prevalence in adults is not exactly known, but it is higher in women, whose greater propensity for urinary tract infections increases the likelihood of an instrumental examination leading to the diagnosis of less severe cases. In men, even severe VUR may go undiagnosed for a long time. Primary VUR is due to a defect in the valve mechanism of the ureterovesical junction. In physiological conditions, the terminal ureter enters the bladder wall obliquely and bladder contraction leads to compression of this intravesical portion. Abnormal length of the intravesical portion of the ureter due to a genetic mutation (whose location is yet to be established) leads to VUR. In its less severe forms VUR may be asymptomatic, but in 50-70% of cases it manifests with recurrent cystitis or pyelonephritis. The manifestations leading to a diagnosis of VUR in adults, besides urinary tract infections, are proteinuria, renal failure and hypertension. The gold-standard diagnostic examination is a micturating cystourethrogram. Reflux nephropathy develops as a result of a pathogenetic mechanism unrelated to high cavity pressure or urinary tract infections but due to reduced formation of the normal renal parenchyma (hypoplasia or dysplasia). Abnormal renal parenchyma development is attributable to the same genes that control the development of the ureters and ureterovesical junction. VUR is considered only a marker of this abnormal development, playing no role in scar formation. There is no conclusive evidence regarding the indications for VUR correction. However, the risk that VUR leads to recurrent pyelonephritis and reflux nephropathy must be kept in mind. VUR certainly has to be corrected in women who contemplate pregnancy.

The number of immigrants has been rapidly increasing in Italy in the last decade, with potentially profound effects on the national health care system. Yet, few data are available on the clinical and demographic features of these subjects, or on their need for nephrological care and dialysis treatment. A survey was conducted in 19 dialysis facilities of Piedmont (a northwestern Italian region) about immigrants on chronic dialysis treatment. Data on native country, administrative position, clinical and dialysis aspects were anonymously collected. Overall, 93 immigrant dialysis patients coming from 24 foreign countries were registered. Most of them were young (mean age 46∓14 years) and on extracorporeal treatment (87%); late referral (38%) or starting dialysis in emergency (17%) were common modalities of presentation. Glomerular (33%) or unknown (31%) nephropathies were the most representative causes of end stage renal disease. No difference in incidence of HCV, HBV and HIV compared with native Italian patients was observed. Notably, more than 50% of the immigrant patients had low-level knowledge of Italian. As regards administrative position, 69% were regular foreign citizens, 19% were temporary foreign workers, and 9% had a residence permit. Our survey confirms the existence of a young immigrant population on dialysis in Piedmont, whose social and relational problems are more challenging than clinical aspects and call for new organizational models to manage this growing population on dialysis.

In March 2009 a clinical audit was held in Turin on peritoneal dialysis in order to analyze the problems that still hinder the effective deployment of the technique in Piedmont-Aosta Valley. Various data about epidemiological and clinical management were collected by means of a questionnaire that all 26 nephrology centers of the two regions responded to. The two major critical issues highlighted were the role of the outpatient facility dedicated to uremic patients and why the peritoneal technique was not chosen for new dialysis patients. With regard to the first issue, the presence of a well structured outpatient facility dedicated to chronic renal failure seems to direct more uremic patients to peritoneal dialysis, at the same time decreasing the rate of late referrals. Regarding the second issue, patient choice was the leading cause followed by problems related to the partner, while traditional clinical contraindications interfered to a lesser extent with the choice of dialysis technique. We therefore believe that it will be possible to increase the use of peritoneal dialysis by improving organizational aspects of the dialysis center and trying to remedy the lack of social support. Accurate information and early care of uremic patients by dedicated outpatient facilities are in fact able to lead more patients to choose peritoneal dialysis. The implementation of measures of support, such as financial incentives to dialysis patients following a recent decision of the Piedmont region, could help to overcome problems related to the lack or unhelpfulness of a partner.

BACKGROUND: Hemodialysis is complicated by a high incidence of intradialytic hypotension and disequilibrium symptoms caused by hypovolemia and a decrease in extracellular osmolarity. Automatic adaptive system dialysis (AASD) is a proprietary dialysis system that provides automated elaboration of dialysate and ultrafiltration profiles based on the prescribed decrease in body weight and sodium content. STUDY DESIGN: A noncontrolled (single arm), multicenter, prospective, clinical trial. SETTING & PARTICIPANTS: 55 patients with intradialytic hypotension or disequilibrium syndrome in 15 dialysis units were studied over a 1-month interval using standard treatment (642 sessions) followed by 6 months using AASD (2,376 sessions). INTERVENTION: AASD (bicarbonate dialysis with dialysate sodium concentration and ultrafiltration rate profiles determined by the automated procedure). OUTCOMES: Primary and major secondary outcomes were the frequency of intradialytic hypotension and symptoms (hypotensive events, headache, nausea, vomiting, and cramps), respectively. RESULTS: More stable intradialytic systolic and diastolic blood pressures with lower heart rate were found using AASD compared with standard treatment. Sessions complicated by hypotension decreased from 58.7% ± 7.3% to 0.9% ± 0.6% (P < 0.001). The incidence of other disequilibrium syndrome symptoms was lower in patients receiving AASD. There were no differences in end-session body weight, interdialytic weight gain, or presession natremia between the standard and AASD treatment periods. LIMITATIONS: A noncontrolled (single arm) study, no crossover from AASD to standard treatment. CONCLUSIONS: This study shows the long-term clinical efficacy of AASD for intradialytic hypotension and disequilibrium symptoms in a large number of patients and dialysis sessions.

The purpose of this study was to evaluate the In vltro and in vivo efficacy of a new connection system for continuous ambulatory peritoneal dialysis (CAPO), called the T-set. With this system the patient wears a 27–cm extension line filled with Amuchina during the dwell time; the bag is made of a fill container linked to a drainage tube with a Y-shaped set. For bag exchange, only one connection is needed and this is subsequently flushed with the entire drainage volume. The in vitro efficacy of the system was tested with 20 sets filled with 10 mL of Amuchina and inoculated in the distallumen with 2.1x103 colony-forming units (cfu) of S. aureus. After an Incubation of 4–6 hours at 35–37°C, three dialysate samples per set were collected, respectively, at the beginning of drainage and filling. Al1120 samples were negative, whereas two control sets, filled with a phosphate-buffered saline, had positive drainage samples, and at least one positive Infusion sample, Indicating the efficacy of Amuchina in sterilizing the system under conditions simulating touch contamination. To evaluate the in vivo efficacy, safety, and acceptability of the T-system, a prospective randomized controlled trial was performed In seven centers: a control group (CG) of 56 patients (follow-up: 952.3 months, mean±SO: 17.0±7.8) was treated with a long branch (21 patients) or short branch (35 patients) Y-set and a test group (TG) of 66 patients (follow-up: 898.1 months, mean±SO: 13.6±7.8) with the T-set. The two groups were comparable for patient and dialysis characteristics. The incidence of peritonitis was 1143.3 months in the CG and 1129.0 months In the TG (p=NS). The percentage of patients without peritonitis was 67.8% In the CG and 68.2% In the TG (p=NS); the probability of remaining free from peritonitis was, respectively, 76% and 75% In the CG and in the TG at 1 year, and 66% and 60% at 2 years (p=NS). In the CG 26 patients and In the TG 21 patients were already on CAPO before the trial; among these 21 patients, 10 of 10 with the long Y-set and 4 of 11 with the short Y-set who transferred to the T-set preferred the latter for better handling (52.4%) or for less encumbrance (14.3%).

The nephrotoxicity of some cancer drugs is well known. Given the rapid development of cancer research, careful assessment of patients treated with new drugs, which may have new toxicity profiles, is mandatory. The nephrotoxicity of cisplatin is likely due to inhibition of autophagy priming, while that of methotrexate is related to direct tubular toxicity and intratubular precipitation. Both can be prevented by adequate hydration. The mechanism of radiation nephropathy development is unclear, but chronic oxidative stress and inflammation seem to play a key role. Mesangiolysis is a characteristic feature, followed by vascular alterations, atrophy, fibrosis, and necrosis. Inhibitors of vascular endothelial growth factor (VEGF), such as bevacizumab, sunitinib, and sorafenib, interfere with angiogenesis. Bevacizumab is a humanized monoclonal antibody which binds to circulating VEGF. Sunitinib and sorafenib are small molecules inhibiting tyrosine kinase of the intracellular domain of the VEGF receptor. Treatment with anti-VEGF drugs is frequently complicated by proteinuria, acute renal failure, and hypertension. The most frequent histological lesion is thrombotic microangiopathy. Inhibitors of the BCR-Abl tyrosine kinase domain on the Philadelphia chromosome (imatinib, nilotinib and dasatinib) may cause acute renal failure.

Isolated asymptomatic hematuria is frequently encountered in clinical practice but there are no established recommendations for its evaluation and management. There is controversy regarding which tests are necessary and whether renal biopsy is indicated. In the pediatric population, renal biopsy should be considered if there is evidence of progressive renal disease or when parents are worried about their child's diagnosis or prognosis. In adults, examinations for isolated microhematuria should include exclusion of pharmacological causes, journeys to endemic areas for S. haematobium or tuberculosis, sickle-cell disease, endometriosis and, in patients older than 40 years, kidney, ureteral or bladder cancer. Examination of urinary sediment may help in identifying the origin of microhematuria. If it is decided to perform a renal biopsy, the patient should be carefully informed of the possible complications of renal biopsy, including the possibility of finding normal renal tissue.

Patch tests were carried out to evaluate the presence of a sensitization to some components of dialytic circuits in 17 uremic patients complaining of pruritus of unknown origin. Fragments of different dialyzer membranes, of tubing sets, of dialyzer membranes recently resterilized with ethylene oxide and the International Contact Dermatitis Research Group standard series substances were tested. Neither patients nor healthy subjects reacted positively to patch tests, which leads us to question the role of contact allergy in the determination of uremic pruritus.

Central venous accesses have become an integral component of vascular access procedures for hemodialysis. Although the DOQI guidelines recommend that less than 10% of chronic hemodialysis patients should be maintained on catheters, in some countries higher prevalences are reported, as in the United States and the United Kingdom (18% and 24%, respectively, according to the DOPPS). The native arteriovenous fistulas are still the best suited accesses for hemodialysis. However, this option is impractical in many situations, so that several justifiable reasons exist for protracted dialysis catheter use; these include the catheter as a bridge angioaccess device, while the patient is awaiting living-related kidney donor transplantation or maturation of an autologous fistula or graft or, increasingly, as the permanent vascular access for patients with unsuitable vascular anatomy who have exhausted all other options. Moreover, the surgical creation of an AVF is felt to be impossible or at least seems to entail significant risks in situations of high output cardiac failure, myocardial ischaemic events and steal syndrome. In these cases, the dialysis access catheter brings considerable advantages, but it also carries tremendous drawbacks. In addition to the increased risk of luminal thrombosis, infection, unreliable blood flows, central venous stenosis, shorter use life and patient cosmetic concern, tunneled catheters are associated with an increased risk of death. Tunnellization, exit site protection, antibiotic-coated or antiseptic-impregnated hemodialysis catheters, antibiotic lock solutions could be helpful in preventing and treating catheter-related bacteremias. Moreover, the development of a subcutaneous port, that is durable, offers a high blood flow and is fully implantable subcutaneously, may become an alternative for chronic use. In our 10-year experience we implanted in our center over 450 central venous catheters with a satisfactory survival (86% at 1 year and 79% at 2 years for the subcutaneous port). In a matched comparison between Tesio twin catheters and Dialock ports (37 vs. 35, respectively), followed for a 2 year period, no significant differences emerged as regards bacteremia incidence, 0.58/1,000 catheter-days in the Tesio catheter group vs. 0.9/1000 catheter-days in the subcutaneous port group, p=0.12; thrombolytic agents needed, 4.5% vs 4.3% of dialysis sessions; or access failure with removal of the device, 8.1% vs 14.2%, p=0.4. The longer duration of antibiotic therapy in the Tesio group (24.6 vs 14.3 days, p=0.006) was due to the higher incidence of cutaneous infectious episodes (3.8 vs 0.16/1,000 catheter-days). In conclusion, although central venous catheter is the vascular access of last choice, in particular cases it can be a useful alternative, provided that strict protocols for nursing care and proper catheter management are implemented in every center.

Clinical and therapeutic characteristics of chronic dialysis patients vary widely at national and/or regional levels. Their increased cardiovascular (CV) mortality is not explained by traditional cardiovascular disease (CVD) risk factors only. Therefore, this study aimed to investigate and compare the characteristics of patients starting dialysis in a homogeneous Alpin region and possibly to identify new biological parameters (phenotypes or genotypes), which eould be responsible for the increased CVD seen in end-stage renal disease (ESRD) patients.A cohort of 279 non-selected consecutive patients entering a dialysis program was prospectively investigated in eight centers of three adjacent regions in France, Italy and Switzerland. In addition to the usual demographic, clinical and biological data, we analyzed at study entry the blood levels of homocysteine, lipoprotein(a) (Lp(a)) and antioxidized low density lipoprotein (LDL) antibodies, vitamin B12 status, Lp(a) and haptoglobin phenotypes, methylenetetrahydrofolate reductase (MTHFR), angiotensin-converting enzyme (ACE), allele epsilon E4 of apolipoprotein (ApoE4) and plasminogen activator inhibitor-1 (PAI-1) genetic polymorphism.At entry, 90.3% of patients were hypertensive, 30% had type 2 diabetes mellitus and 17.6% were current smokers; 42% of patients had already experienced at least one CV event: peripheral artery disease (26% of the cohort), coronary artery disease (22%) or ischemic cerebro-vascular disease (16%). Forty-two patients had hador =2 CV events or documented atherosclerotic localizations. Anemia was not optimally treated: mean hemoglobin (Hb) was at 97.7 g/L and, while overall 62% of patients received erythropoietin (EPO) prior to dialysis, large national differences were observed. Compared to the reference population, ESRD patients exhibited increased homocysteinemia, Lp(a) levels and ApoE4 allele prevalence. Conversely, the distribution of Lp(a) phenotype, MTHFR TT, ACE DD and PAI-1 4G/4G was equivalent to that of the reference population. In addition, none of the analyzed phenotypical or genotypical parameters, except for the haptoglobin 2.2 phenotype, could be associated with the existence of a previous adverse CV event.(1) The clinical characteristics of the ESRD patients entering dialysis in our region were comparable to the currently observed dialysis populations in most European countries with the deleterious role of advancing age, diabetes, previous CVD, smoking and hypertension evident (2). Except for anemia therapy, there were no regional or national differences observed at dialysis start. (3) An analysis of the phenotypic and genotypic CV risk factors demonstrated differences with the reference population only for hyperhomocysteinemia, Lp(a) and ApoE4 allele prevalence, with no notable differences among the participating centers.

Background: We tested whether the combination of verapamil (V) or amlodipine (A) with trandolapril (T) affected proteinuria differently from T alone in patients with nondiabetic nephropathies. Methods: After T, 2 mg, in open conditions for 1 month, 69 patients were randomly assigned to be administered T, 2 mg, combined with V, 180 mg, plus a placebo or T, 2 mg, plus A, 5 mg, once a day in a double-blind fashion. Patients were followed up for 8 months. Results: Proteinuria diminished significantly after T treatment from mean protein excretion of 3,078 ± 244 (SEM) to 2,537 ± 204 mg/24 h ( P = 0.018). In the randomized phase, there was a slight reduction in proteinuria in both groups without significant differences within and between treatments (T + V, protein from 2,335 ± 233 to 2,124 ± 247 mg/24 h; T + A, protein from 2,715 ± 325 to 2,671 ± 469 mg/24 h). The selectivity index (SI; calculated as the ratio of immunoglobulin G to albumin clearance) was slightly and not significantly reduced in patients treated with T plus V from a median of 0.20 (interquartile range, 0.13) to 0.16 (interquartile range, 0.15; P = not significant), whereas it significantly increased from 0.20 (interquartile range, 0.14) to 0.30 (interquartile range, 0.14; P = 0.0001) in patients treated with T plus A. Modifications in SI and serum creatinine levels at the end of the study from randomization were significantly directly correlated ( r = 0.45; P = 0.001). The number of patients reporting adverse effects was significantly higher in the T plus A than T plus V group (63.8% versus 33.3%; P = 0.016). Conclusion: In patients with nondiabetic proteinuric nephropathies treated with T, the combination of V or A does not significantly increase its antiproteinuric effect.

The effectiveness of percutaneous revascularisation (PTRA) in the treatment of atherosclerothic renovascular nephropathy (ARN), a leading cause of progressive renal failure, is still a matter of debate.we reviewed 52 patients submitted to selective stenting from 1991 to 2000 because of ARN, followed for a mean of 22.3 months before and 24.6 after the procedure, looking for complications, re-stenosis rates, blood pressure, renal function and survival.Arterial patency was achieved in 97.1% of procedures (71.6% by stent deployment); complications occurred in 42% of patients, and re-stenoses in 17.3% of vessels, most often in those without a stent (31.6% vs 8.3%). No effect was detectable on hypertension and renal failure in the whole group, but in the subgroup without technical failure or early dialysis start PTRA reduced the creatinine clearance (BCRC) decline from 0.9 to 0.19 mL/min/month. At univariate analysis, BCRC outcome was better in bilateral or single kidney stenoses, proteinuria1 g/day, serum creatinine4 mg/dL and resistance index0.8. Survival was 68.9% at five years, with a mortality rate of 4.5/100 person-years.Renal outcome of successful PTRA differs from case to case, but efficacy is substantial. Primary stenting in ostial stenosis and selection of patients based on prognostic factors seem likely to improve the effectiveness.

Cardiovascular disease accounts for almost half of the total mortality in patients with end stage renal disease (ESRD). It has recently been debated whether coronary revascularization has the same rate of risks and successes in this cohort of patients compared to patients without renal disease. Since 1991, 17 dialysis patients were submitted to coronary revascularization in our center. Seven patients were following peritoneal, 10 hemodialytic treatment. Four patients were submitted to percutaneous transluminal coronary angioplasty (PTCA) and 13 to surgical revascularization (CABG). In 2 patients the coronary lesion was unique, in the others stenosis of multiple vessels were found. Six patients were diabetic. The mean age at the onset of the coronary artery disease (CAD) was 57.17 +/- 11.6 years. The mean time elapsed from the onset of the CAD and the performance of the PTCA or CABG was 30.1 +/- 35.4 months. The mean time from beginning of dialysis treatment to revascularization was 48.2 +/- 39.6 months. Mean hemoglobin values were 9.7 +/- 1 g/dL, mean phosphorus values were 5.2 +/- 8.7 mg/dL, mean cholesterol values were 211 +/- 49.5 mg/dL. The procedure was technically successful in all patients. Mean survival was 25.09 +/- 28.12 months. Twelve patients died, 5 of whom within one month. Survival at one month was 70.5%, at 6 months 58.8%, at one year 52.9%, at 2 years 47%. There was neither significant difference patients submitted to PTCA and those submitted to CABG, nor between diabetic and non-diabetic patients. In conclusion, coronary revascularization in our experience is a high risk procedure in dialysis patients. The reasons for this could be the severe general conditions of these patients affected with diffuse vasculopathy and the long time elapsed since the onset of the ischemic cardiopathy. Thus, our results could suggest the opportunity of performing earlier screening of coronary situation and revascularization treatment in CAD dialysis patients.

Vecuronium is a curaric agent, largely used in anesthesia. Indications as to its employ in uremic patients appear to be debated because of partial renal elimination of the drug. A 52-year-old hemodialyzed woman required transplantectomy for rejection. At awakeness after general anesthesia (induced with fentanyl, propofol, and 6 mg of vecuronium, repeated with a single 2 mg dose 30 min later), she presented diafragmatic and muscular limb weakeness that lasted 180 min in spite of prostigmine administration. A 2 h 30 min predilutional hemofiltration was then performed, which induced rapid disappearance of neuromuscular blockade. Even if vecuronium can be used in dialysis patients, one should remember its possible side effects, especially with repeated doses, in determining prolonged neuromuscular blockade. Cautious use of this drug in renal failure is mandatory. Low dosage must be employed and repeated administration avoided. Neuromuscular blockade seems to be rapidly reversible with dialytic treatment.

The prolactin (PRL) receptor (R), a member of the cytokine hemopoietin receptor superfamily, has been shown to activate early differentiation steps along the erythroid pathway. In particular PRL, a product of bone marrow stroma, induces functional erythropoietin (EPO)-R on CD34+ hemopoietic progenitors. In this study, expression of EPO-R mRNA and responsiveness to EPO were assessed on enriched hemopoietic progenitor cells (HPC) from seven hyperprolactinemic and three normoprolactinemic patients and two normal subjects. Expression of EPO-R mRNA by semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) was found in HPC of four out of seven hyperprolactinemic patients but not in normoprolactinemic patients or normal donors. Development of EPO-dependent Colony Forming Unit-Erythroid (CFU-E) colonies in semi-solid medium was observed only in hyperprolactinemic patients (six out of seven). A much higher number of CFU-E colonies was observed in the four patients with a positive EPO-R message. We conclude from these data that abnormally high levels of PRL may increase the number of EPO-responsive hemopoietic precursors in vivo as they do in vitro. Since hyperprolactinemia associates in these patients with depressed EPO production, it may be regarded as a compensatory mechanism for the reduced availability of the hemopoietic factor.

dialysis strategies and pharmacological management of hypertension. Background. The tenet that peritoneal dialysis is capable of either normalizing or improving blood pressure Key words: ambulatory blood pressure monitoring; control in uraemic patients is based on outdated or antihypertensive therapy; prevalence of hypertension; monocentric experiences. Therefore, we assessed the peritoneal dialysis; white-coat hypertension prevalence of hypertension and the eYcacy of antihypertensive therapy in a large, multicentric cohort of patients on peritoneal dialysis. Methods. Twenty seven out of the 50 centres belonging Introduction to the Italian Co-operative Peritoneal Dialysis Study Group took part in the study. The main patient Cardio- and cerebrovascular events are the main causes selection criteria were: peritoneal dialysis therapy for of morbidity and mortality of patients on peritoneal at least 3 months and no peritonitis or changes in dialysis [1]. Although high blood pressure (BP) is the dialysis technique for at least 1 month. Clinical blood leading factor causing cardiovascular mortality in the pressure was measured according to WHO/ISH general population, scant attention is paid to arterial guidelines. Ambulatory blood pressure monitoring hypertension in recent peritoneal dialysis studies. This was carried out using a SpaceLabs 90207 recorder. might be due to the general belief that end-stage renal Hypertension was defined according to WHO/ISH disease (ESRD)-related hypertension is easily concriteria and staged according to the criteria of the Joint trolled by peritoneal dialysis. Unfortunately, this asserNational Committee on Detection, Evaluation and tion is at least in part based on outdated reports [2]. Treatment of High Blood Pressure (JNC ), 5th Report. In recent years, ambulatory blood pressure monitoring Ambulatory blood pressure monitoring recordings has been applied in peritoneal dialysis patients. This were used to evaluate white-coat hypertension, blood evaluation technique oVers some advantages over trapressure load and the dipping phenomenon. ditional oYce measurement as it avoids ‘observer bias’, Results. Five hundred and four subjects were evalu- ‘digit preference’ of the operator and the stress reaction ated. Hypertension was prevalent in 88.1% of the of the patient, and provides mean BP levels represpopulation, and 362 out of 444 hypertensive patients enting the average of >90 measurements per day. were on antihypertensive therapy. JNC staging Nonetheless, only a few small studies have been carried revealed that 188 patients had moderate to severe out using ambulatory blood pressure monitoring in hypertension. Blood pressure load was pathological in peritoneal dialysis patients [3]. 77.3% of the patients receiving antihypertensive treat- We were thus prompted to conduct a large multicenment. White-coat hypertension was identified in 9.1% tre study to evaluate the prevalence of hypertension of the hypertensive patients not on antihypertensive and the eYcacy of antihypertensive therapy in peritontherapy, and 53.1% of the patients were non-dippers. eal dialysis patients using traditional clinical sphygmoConclusions. The study demonstrates that hyper- manometric measurements and 24 h ambulatory blood tension is a dramatic, unsolved problem in uraemic pressure monitoring recordings. patients treated with peritoneal dialysis, and casts doubts on the eVectiveness of our current peritoneal Subjects and methods

In this paper we report some results of our studies on patients with immunoglobulin (Ig)A nephropathy regarding (1) the familiar aggregation of erythrocyte sodium-lithium (Na,Li) countertransport; (2) the association of Na,Li countertransport with the presence of arterial hypertension and lipid abnormalities; (3) the correlation between Na,Li countertransport activity and renal functional reserve; and (4) the preliminary results of a longitudinal study. In 13 families of patients with IgA nephropathy, selected because both parents were available, we found a significant correlation between midparent and offspring Na,Li countertransport activity (Spearman's rank correlation = 0.65; P = 0.023), but no husband-wife relationship. In 49 patients, the activity of Na,Li countertransport was significantly higher in erythrocytes from 20 hypertensive patients than from either 29 normotensive patients or from 36 healthy age- and sex-matched normal subjects. Hyperlipidemic patients had an erythrocyte Na,Li countertransport activity significantly higher than normolipidemic patients and controls. In 17 patients a significant inverse correlation was found between the peak variation of creatinine clearance over baseline value after an oral protein load and the erythrocyte Na,Li countertransport activity (Spearman r = 0.54; P = 0.03). In a longitudinal study of 36 patients followed from 12 to 36 months, those showing a progression toward renal failure had an erythrocyte Na,Li countertransport activity higher than median value. The results of our studies show that in patients with IgA nephropathy a high erythrocyte Na,Li countertransport rate, genetically determined, is associated with the presence of arterial hypertension and lipid abnormalities, and perhaps with a less favorable disease outcome.

Increased sodium-lithium countertransport activity in red cells of IgA nephropathy patients. The aim of this work was to analyze Na,Li countertransport activity in the erythrocytes from patients with IgA nephropathy, in relationship with their blood pressure status and lipid profile Forty-nine patients (32 males, 17 females) with biopsy-proven IgA nephropathy and without significant impairment of renal function (serum creatinine ≤ 1.4 mg/dl) and 36 normal subjects (21 males, 15 females) were evaluated Twenty-nine patients with IgA nephropathy were normotensive and 20 hypertensive (diastolic pressure ≥ 95 mm Hg or treated by antihypertensive drugs). Na,Li countertransport was significantly higher in red cells from hypertensive than from normotensive patients (P = 0.002) and normal subjects (P = 0.0001), (values respectively 309 ± 17; 241 ± 12 and 211 ± 11 µmol/liter RBC/hr); normotensive patients with IgA nephropathy did not differ from controls regarding the Na,Li countertransport rate. A multiple stepwise logistic regression analysis with blood pressure status as the dependent variable and Na,Li countertransport activity, age, serum creatinine, proteinuria, cholesterol, triglycerides, plasma potassium and time from onset as independent variables, indicated an independent significant association for Na,Li countertransport (P = 0.002) proteinuria (P = 0.006), plasma potassium (P = 0.006) and age (P = 0.029). Other tested variables were not independently related to blood pressure status. Hyperlipidemic patients (plasma total cholesterol concentration >200 mg/dl and/or plasma triglycerides >172 mg/dl) had an erythrocyte Na,Li countertransport activity significantly higher than normolipidemic (P = 0.005) and controls (P = 0.001) (values respectively 295 ± 14; 226 ± 12 and 211 ± 11 µmol/liter RBC/hr). A high erythrocyte Na,Li counter-transport rate may be a marker of an increased risk of developing arterial hypertension, lipid abnormalities, and perhaps a more severe renal disease in IgA nephropathy.

Renal failure due to diabetic nephropathy accounts for approximately 28% of all new hemodialysis patients in the United States (1), where an acceptance rate of about 130 per million population (p.m.p.) has been reported.