[Effects of dose of erythropoiesis stimulating agents on cardiovascular outcomes, quality of life and costs of haemodialysis. the clinical evaluation of the DOSe of erythropoietins (C.E. DOSE) Trial]. / Effetti della dose degli agenti stimolanti l'eritropoiesi su esiti cardio-cerebrovascolari, qualità di vita e costi in emodialisi.

BACKGROUND: Anaemia is a risk factor for death, adverse cardiovascular outcomes and poor quality of life in patients with chronic kidney disease (CKD). Erythropoietin Stimulating Agents (ESA) are the most used treatment option. In observational studies, higher haemoglobin (Hb) levels (around 11-13 g/dL) are associated with improved survival and quality of life compared to Hb levels around 9-10 g/dL. Randomized studies found that targeting higher Hb levels with ESA causes an increased risk of death, mainly due to adverse cardiovascular outcomes. It is possible that this is mediated by ESA dose rather than haemoglobin concentration, although this hypothesis has never been formally tested. METHODS: We present the protocol of the Clinical Evaluation of the Dose of Erythropoietins (C.E. DOSE) trial, which will assess the benefits and harms of a high versus a low ESA dose therapeutic strategy for the management of anaemia of end stage kidney disease (ESKD). This is a randomized, prospective open label blinded end-point (PROBE) design trial due to enroll 900 haemodialysis patients. Patients will be randomized 1:1 to 4000 UI/week i. v. versus 18000 UI/week i. v. of epoetin alfa, beta or any other epoetin in equivalent doses. The primary outcome of the trial is a composite of cardiovascular events. In addition, quality of life and costs of these two strategies will be assessed. The study has been approved and funded by the Italian Agency of Drugs (Agenzia Italiana del Farmaco (AIFA)) within the 2006 funding plan for independent research on drugs (registered at www.clinicaltrials.gov (NCT00827021)).

Exercise training and endothelial progenitor cells in haemodialysis patients.

Haemodialysis patients have few endothelial progenitor cells (EPCs) and an unfavourable cardiovascular outcome. The effects on peripheral blood CD34(+) cells and EPCs of a 6-month walking exercise programme were studied. Thirty dialysis patients (20 males, age 67 +/- 12 years) were prescribed exercise (two daily 10-min home walking sessions at moderate intensity, group E, n = 16) or not prescribed exercise (control, group C, n = 14). On entry and after 6 months peripheral blood CD34(+) cells, EPCs (assessed as CD34(+) cells co-expressing AC133 and vascular endothelial growth factor receptor 2 [VEGFR2], and as endothelial colony-forming units [e-CFU]) and exercise capacity (6-min walking distance, 6MWD) were evaluated. In group E, 6MWD and e-CFU increased significantly during the study period, with no significant changes in CD34(+) or CD34(+) AC133(+) VEGFR2(+) cell numbers. The change in e-CFU was directly and significantly correlated to patient-reported training load. Group C showed no significant change in any variable. In haemodialysis patients, moderate-intensity exercise selectively increased the number of e-CFU.

[Unexpected cause of acute renal failure in an 85-year-old woman]. / Una inaspettata causa di insufficienza renale acuta in una 85-enne.

Acute postinfectious glomerulonephritis (APIGN) is usually diagnosed in young people, while in elderly people rapidly progressive forms appear to be the most important glomerular disease causing acute renal failure. We report on a 85-year-old woman with acute renal failure due to APIGN. An 85-year-old woman with a history of hypertension and cerebrovascular disease was hospitalized because of diarrhea and syncope associated with atrial fibrillation. She was found to have left lower lobe pneumonia. Serum creatinine was over 2 mg/dL. Fluids were given, without improvement in renal function but leading to volume overload instead. Within a few days serum creatinine reached a level of 5.4 mg/dL with reduction of urine output despite administration of diuretics. The patient developed hematuria and purpura of the feet. Serum IgA was high and the urine sediment showed casts. Methylprednisolone 125 mg i.v. was given for three days followed by prednisone 50 mg daily. The patient's clinical condition gradually improved and serum creatinine decreased to 1.9 mg/dL. Renal biopsy showed APIGN. During hospitalization, three major complications occurred: hemodynamic instability due to atrial fibrillation, Clostridium difficile colitis and urinary tract infections due to Enterococcus faecalis and Candida tropicans, all successfully treated. APIGN should be taken into account as a cause of acute renal failure in hospitalized elderly patients with many comorbidities.

Pseudostenosis of axillary vein due to adduction of the upper limb.

Axillary vein stenosis is a well-documented complication in hemodialysis (HD) patients, but in adipose or athletic subjects, pseudostenosis of the axillary vein can be detected. We report a case of pseudostenosis in a fit dialysis patient who underwent phlebography of the right upper limb, performed to create a new vascular access (VA). The investigation demonstrated that the axillary vein appeared sharpened with a reduced lumen. Based on this exam, angioplasty of the right axillary vein was planned. The new phlebographic study, performed abducting the arm, demonstrated that the previously marked stenosis of the axillary vein disappeared. Our case illustrates how the reduction of the axillary vein lumen was secondary to ""muscular print"" and was present only if the arm was adducted. In uremic patients, the squeezing of the vascular nervous bundle of the upper limb is possible in fit patients at the time of phlebography, an examination that should be performed with the arm both in adduction and abduction.

Displacement of the inferior vena cava as a factor limiting catheter performance in long-term hemodialysis patients.

We report a case of a lady affected by autosomal dominant polycystic kidney disease who had been on hemodialyis for 24 years. She has exhausted all options for arterious-venous fistula. The presence of an acquired anatomical abnormality was an obstacle in order to get appropriate blood flow from standard tunnelled femoral catheters. The enlarged right kidney was pushing the inferior vena cava to the left side of the abdomen, and the abnormality was demonstrated by phlebography. Only after placing a cuffed catheter 53 cm long in her left femoral vein we could dialyze efficiently. Venography is mandatory before placing a cuffed catheter especially in uremic patients with long history of access failure, because it saves costs.

The relationship between carotid and coronary atherosclerotic damage in dialysis patients.

BACKGROUND: Data relating carotid ultrasound (CU) to atherosclerotic damage evaluated by coronary angiography in hemodialysis patients are scarce. METHODS: We carried out a cross-sectional study in 33 uremic subjects (age 55 +/- 12 years, 22 male, 7 diabetic), who have been on dialysis for 41 +/- 48 months (range 2-192). Twenty-two underwent a coronary angiography in order to complete clinical evaluation for inclusion on the kidney transplantation waiting list, and 11 because of coronary artery disease (CAD); Gensini's score was calculated. Intima-media thickness (IMT) and presence of plaques were related to the degree of coronary stenosis and to cardiovascular risk factors. Patients were divided into two groups depending on mean IMT (group 1 IM 0.9 mm, n=15). RESULTS: Group 2 was older (60 +/- 8 vs 50 +/- 12 year, p=0.01), had higher frequency of CAD (53 vs 16%, p=0.02) and had higher prevalence of coronary artery stenosis >or= 75% in the right (60 vs 22%, p=0.02), left anterior descending (46 vs 16%, p=0.06) and left circumflex coronary arteriers (60 vs 11%, p=0.05) than group 1. IMT was not related to the degree of CAD evaluated by Gensini's score. IMT sensibility and specificity in detecting the presence of hemodynamically significant coronary stenosis were 64% and 68%, respectively. Coronary narrowing was correlated with the degree of stenosis of common, internal and external carotid arteries (Spearman's rank correlation coefficient). During two years of follow-up, six major cardiac events were recorded and they were related to Gensini's score. CONCLUSIONS: In uremic patients, ultrasonographic evaluation of carotid arteries is a simple, noninvasive examination that could be a helpful tool in detecting coronary atherosclerotic damage, but IMT does not appear to add more information regarding risk stratification of CAD.

[MEN type 1 and chronic renal failure: a rarely reported association]. / MEN tipo 1 ed insufficienza renale: una associazione poco conosciuta.

BACKGROUND: Multiple endocrine neoplasia type 1 (MEN 1), or Wermer's syndrome, is a rare autosomal dominant genetic syndrome characterized by tumors or hyperplasia involving the pituitary, parathyroid, and pancreatic islet cells. Association between MEN 1 and nephrocalcinosis is well known, though data published in medical literature regarding Wermer's syndrome and chronic renal failure relation are still rare. CASE: A 70-year-old Caucasian female patient had a history of primitive hyperparathyroidism, prolactinoma, glucagonoma, adrenal adenoma and pulmonary neuroendocrine neoplasia. She presented at our clinic first when she was 62 years old because of hypertension, nephrolithiasis (calcium oxalate) and diabetes mellitus treated with oral agents. During the eight-year follow-up she developed chronic renal failure (serum creatinine 1.8 mg/dL, glomerular clearance 35 mL/min) and partial thrombosis of abdominal aortic wall. CONCLUSIONS: Although the association between renal failure and MEN 1 is rarely reported, patients affected by Wermer's syndrome have several risk factors of decreasing renal function such as hypertension, nephrolithiasis and diabetes mellitus. Moreover, hyperparathyroidism in MEN 1 is clinically similar to the kidney failure condition; indeed, diffuse hyper-plasia of more than one gland is common. Vitamin D should not be administered to these patients. Nephrologists should be involved in MEN 1 follow-up, with the aim to prevent kidney failure development by correcting risk factors.

Exercise capacity and circulating endothelial progenitor cells in hemodialysis patients.

Mobilization of circulating endothelial progenitor cells (EPCs) is increased after acute exercise and training. This study aims to evaluate whether, in a low performance population, EPC levels may be related to exercise capacity in steady state conditions. Study population consisted of sixteen hemodialysis patients. The distance walked in the 6-minute walking test (6 MWD) and the maximal speed attained in an incremental treadmill test were used to assess the exercise capacity. Physical functioning was measured by the scale on the SF36 questionnaire. Quantification of peripheral blood CD34(+) cells and enumeration of EPCs, assessed as CD34(+) cells coexpressing AC 133 and vascular endothelial growth factor receptor-2, were performed. Hemoglobin concentration, white blood cells, high-sensitivity C-reactive protein, total cholesterol, and triglycerides were measured. Statistical analysis examined the relationship between blood progenitors cells versus performance parameters, laboratory parameters, age, body mass index, hemodialysis duration, and erythropoietin therapy. Univariate analysis revealed a significant association between percentage values of EPC and performance parameters only: 6 MWD (r=0.720; p=0.0017), maximal treadmill speed (r=0.721; p=0.0016), and physical functioning score (r=0.506; p=0.0453). A similar statistical association between EPC absolute values and performance parameters was found. No correlation between CD34 (+) and any parameter under study was observed. Multivariate analysis indicated 6 MWD as the most significant independent factor associated with EPC level. EPC percentage value was significantly lower (p=0.0087) in the worse (6 MWD < 300 m, n=8) than in the better performing group (6 MWD > 300 m, n=8). In a group of renal patients, mobilization of EPCs was related to the degree of exercise capacity, suggesting a possible connection with the cardiovascular risk in low performance populations limited by chronic diseases.

Role of B-type natriuretic peptide in cardiovascular state monitoring in a hemodialysis patient with primary amyloidosis.

BACKGROUND: Cardiac involvement occurs in up to 50% of patients with primary or A amyloidosis (ALA) and is associated with very poor prognosis. B-type natriuretic peptide (BNP) has been proposed as a guide for treatment of heart failure patients and as an index of myocardial dysfunction in patients with ALA. Data about BNP dosage for cardiovascular monitoring of patients with ALA on renal replacement therapy are lacking. CASE: A 64 year old Caucasian man was admitted because of nephrotic syndrome in July 2003. Renal diagnosis was ALA. Melphalan and prednisolone were given but renal function worsened and in April 2004 standard bicarbonate hemodialysis was started. In March 2004 thalidomide was added to his therapy. During the follow-up ejection fraction was stable and was 65% on the contrary E/A ratio gradually increased and overtook 1. BNP plasma levels were increased and the values recorded during the follow-up were: 2505 pg/mL in October 2003 (normal reference values<100), 1827 in April 2004, 4006 in June 2004, 5000 in September 2004, 3750 in January 2005 and 1920 in April 2005. In September 2005 BNP was 3380 pg/mL. The patient was still alive after a follow-up longer than two years. CONCLUSION: In ALA patients a powerful prognostic role of BNP has been reported whose expression is increased in ventricular myocytes of patients with cardiac involvement. BNP level monitoring does not appear to be superior to standard echocardiography in evaluating cardiovascular status of uremic patients with ALA.

Prevalence of hyperlipidemia in a cohort of CAPD patients. Italian Cooperative Peritoneal Dialysis Study Group (ICPDSG).

An association between hyperlipidemia and cardiovascular disease is well described in the literature. We conducted an observational study in order to evaluate the lipid profile, the prevalence of hyperlipidemia and its relationship with age, sex, duration of CAPD, peritoneal glucose load (PGL), serum albumin (ALB), serum glucose (GLU), and BMI in a large cohort of uremics undergoing long-term treatment with CAPD. 457 nondiabetic patients (245 males, 212 females; mean age 63.8 +/- 11.9 years; mean duration of CAPD: 41.8 +/- 26.9 months) treated during 1992 in 25 centers participating in the Italian Cooperative Peritoneal Dialysis Study Group (ICPDSG) were studied. The serum lipid parameters evaluated were triglycerides (TG), total cholesterol (CHO), HDL-cholesterol (HDL). Indications given in the New England Journal of Medicine, SI Unit Conversion Guide, 1992, were adopted for normal ranges. In the whole population the evaluation of lipid parameters showed: TG 227.4 +/- 123.3 mg/dl, CHO 232.8 +/- 56.0 mg/dl, HDL 40.7 +/- 12.0 mg/dl. No differences were found between the two sexes with regard to age, BMI, duration of CAPD, distribution of renal diseases, TG, ALB, and GLU; whereas CHO and HDL were significantly lower in males than in females (CHO: 222.2 +/- 53.5 vs. 245.0 +/- 56.5 mg/dl, p < 0.001; HDL: 39.3 +/- 11.4 vs. 42.6 +/- 12.6 mg/dl, p < 0.05). The prevalence of hypercholesterolemia was significantly lower in males than in females (19.7 vs. 35.4%; p < 0.001). The multiple regression analysis indicated that TG were directly correlated to PGL (p < 0.05), and HDL was inversely correlated with TG (p < 0.001). The coexistence of the two variables (TG and HDL) may increase the risk of cardiovascular events. Further strategies should therefore be developed to select and manage CAPD patients to reduce the incidence of hyperlipidemia.

Two years of experience with a new device system: a multicenter study.

Peritonitis is a crucial complication of peritoneal dialysis. Over the last few years, new device systems have been developed to reduce episodes of peritonitis caused by exogenous contamination. Remarkable improvement has been obtained by modifying the original connection between the catheter and the bag with the introduction of the Y-set. The aims of this study were to test the reliability and simple use of a double-bag system without disinfectant in-line (Gemini, Gambro) and to evaluate the incidence of peritonitis in a 2-year period of follow-up. In a group of 167 patients, enrolled in 14 dialysis units in Italy, with a follow-up of 2433 patient-months, we observed 82 episodes of peritonitis in 52 patients, with a cumulative incidence of 1 episode every 29.7 patient-months. At 12 months the percentage of patients peritonitis-free was 69.7%, and at 24 months it was 62.8%. The training to complete the bag exchange, assessed by patient and nursing staff, was defined as "easy" in 61% of the cases and "difficult" in only 12% of the cases. The percentage of patients requiring a partner was 23%. For patients this device system presents easy handling in terms of the bag exchange, and it may prevent peritonitis.

Dialysis-related amyloidosis in a large CAPD population.

We studied 212 patients from 13 Italian dialysis centers to evaluate the clinical aspects of dialysis-related amyloidosis in continuous ambulatory peritoneal dialysis (CAPD). The mean age was 64.2 +/- 12.3 years and mean time on dialysis was 36.9 +/- 25.1 months. Residual diuresis was 615.7 +/- 554.0 mL/day and plasma beta 2-microglobulin (beta 2M) level was 27.0 +/- 12.8 mg/L. Radiological skeletal examination, neurological problems related to beta 2M, and urinary and dialytic balance of beta 2M were evaluated. Correlations between age, time on dialysis, residual diuresis, beta 2M plasma levels, beta 2M peritoneal and renal removal, carpal tunnel syndrome, and bone disease were studied. Only the number of bone lesions had a significant positive correlation with patient age and negative correlation with residual diuresis. The latter had an inverse relation with beta 2M plasma levels. Dialytic age did not correlate with any of the parameters. No other correlation was observed. Hand lesions were found in 85% of patients with bone dialysis-related amyloidosis. In conclusion, residual diuresis in our patients played a positive role in the number of bone localizations. Only age, but not time on dialysis, had a positive impact on the bone lesions. The high percentage of hand lesions suggests that the observation of this skeletal segment is a simple, safe, and effective modality of bone follow-up for dialysis-related amyloidosis.

Long-term outcome in continuous ambulatory peritoneal dialysis: a 10-year-survey by the Italian Cooperative Peritoneal Dialysis Study Group.

Over a 10-year period, 1,990 end-stage renal disease patients in 30 centers were treated with continuous ambulatory peritoneal dialysis by the Italian Cooperative Peritoneal Dialysis Study Group. At the start of treatment, patients had an average age of 58.4 years, with a 66% prevalence of one or more clinical risk factors for premature death. Patient survival was 51% and 33% at 4 and 8 years on continuous ambulatory peritoneal dialysis, respectively, and technique survival was 62% and 48%, respectively. Occurrences of peritonitis progressively reduced until they reached an incidence of 0.50 episodes/yr in the last 5 years (1985 to 1989). Hernias and catheter-related problems did not influence the dropout rates. These Italian Cooperative Peritoneal Dialysis Study Group results demonstrate that continuous ambulatory peritoneal dialysis is a viable dialysis technique for long-term treatment of chronic renal failure and that it is an effective alternative to hemodialysis, especially for older and high-risk patients.

Well being in patients on CAPD and hemodialysis.

In the present multicenter study, 120 pts who had been treated by both hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD) for at least 6 months each, were invited to answer questions on 34 matters, to compare symptoms and their well-being while on the two treatments. Patients were invited to choose HD or CAPD and indicate the reasons for their choice. For 28 patients the first treatment was HD and for 92 CAPD. The mean time between the change of therapy and the study was 46 +/- 35 months. Their final choices were found to be strictly related to the present treatment (p < 0.001). The reasons for choice of CAPD were: more free time (21%), more freedom (67%), better well-being (44%), less worry (5%); for HD they were: more free time (53%), better well-being (39%), less worry (13%), no need for a peritoneal catheter and fewer clinical complications (19%). The catheter was considered more cumbersome than the A.V. fistula, the time involved was considered to be shorter on HD by 52 patients and on CAPD by 39, thirst and cramps were considered to be more frequent and severe on CAPD by half of the patients. The prevalence and severity of problems and symptoms and choice of treatment were not related to sex, job, education or age.

Ten years experience of CAPD in diabetics: comparison of results with non-diabetics. Italian Cooperative Peritoneal Dialysis Study Group.

CAPD outcomes were compared between a group of 301 diabetic patients (mean age +/- SD, 58.9 +/- 12.7 years, 55.8% males) and a group of 1689 non-diabetic patients (mean age +/- SD 57.8 +/- 14.8 years, 55.9% males) treated in 30 centres participating in the Italian Cooperative Peritoneal Dialysis Study Group from 1980 to 1989, with follow-up observation periods of 444 years (mean +/- SD, 1.48 +/- 1.24) and of 3502 years (mean +/- SD, 2.07 +/- 1.91) respectively. CAPD was the first modality for 87.2% of diabetics and 78.1% of non-diabetics (P < 0.001). The percentage of patients who needed a partner for CAPD was 45.9% in diabetics and 30.2% in non-diabetics (P < 0.001). In diabetics compared with non-diabetics, cardiovascular diseases and cachexia were nearly twice and infections other than peritonitis more than three times as frequent in causing death. In diabetics, survival was significantly worse (P < 0.0001) and the relative risk of death 2.13 times higher (P < 0.001). The technique survival and the relative risk of drop-out were not significantly different in the two groups. Clinical problems were the most important cause of drop-out among diabetics. The probability and relative risk of drop-out due to peritonitis, as well as of the first peritonitis episode, were not significantly different between the two groups and between diabetics using or not using intraperitoneal insulin. Days per patient year of hospitalization, excluding the first, were 18.4 in diabetics and 14.3 in non-diabetics. CAPD-related problems caused hospitalization in a similar way in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

[Bone cysts and continuous ambulatory peritoneal dialysis]. / Cisti ossee e dialisi peritoneale ambulatoriale continua.

The clinical and radiologic patterns of amyloid osteoarthropathy in long-term hemodialysis patients are well known. However, few studies about the incidence of dialysis-associated amyloidosis in continuous ambulatory peritoneal dialysis (CAPD) patients have been published to date. In a series of 27 CAPD patients, the authors found bone cysts in 63.6% of cases, at the beginning of their dialysis treatment. After a mean follow-up period of 20.9 +/- 13.8 months, carpal bone cysts were seen in 70.4% of cases and clinical patterns worsened in 26.3% of patients. Therefore, CAPD does not prevent the development of dialysis-associated amyloidosis; prolonged uremic state and decreased diuresis seem to be the main pathogenetic factors of osteoarthropathy. The incidence and the evolution of bone lesions were related to the clinical data of this series and then compared with those of a group of hemodialysis patients. This study confirms that plain wrist films are a simple and useful method in the early detection and in the follow-up of amyloidosis-related disease.

In vitro and in vivo efficacy of a new connector device for continuous ambulatory peritoneal dialysis.

The purpose of this study was to evaluate the in vitro and in vivo efficacy of a new connection system for continuous ambulatory peritoneal dialysis (CAPD), 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 distal lumen with 2.1 x 10(3) colony-forming units (cfu) of S. aureus. After an incubation of 4-6 hours at 35-37 degrees C, three dialysate samples per set were collected, respectively, at the beginning of drainage and filling. All 120 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 +/- SD: 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 +/- SD: 13.6 +/- 7.8) with the T-set.(ABSTRACT TRUNCATED AT 250 WORDS)

Ten years of continuous ambulatory peritoneal dialysis: analysis of patient and technique survival.

The patient survival (PS) and technique survival (TS) were evaluated in 1990 patients on continuous ambulatory peritoneal dialysis (CAPD) (males: 55.9%, mean age +/- SD: 58.4 +/- 14.8 years), treated in 30 centers participating in the Italian PD Study Group, from 1980 to 1989 (follow-up: 3953 years; mean +/- SD: 2.02 +/- 1.86 years). The total PS was 50.7% at 4 years, compared to 73.3% of patients without clinical high-risk condition (HRC) at the beginning of CAPD. In this group (34.0%) PS was significantly higher (p < 0.001) compared, respectively, to patients with cardiovascular disease (30.5%), diabetes (13.1%), and age > or = 70 years (11.2%). The percentage of death reached the mean value of 11.3% per year without any statistically significant tendency to variation during the follow-up, despite the increased number of patients > or = 65 years old and those with HRC (p < 0.001). Cardiovascular diseases (47.3%) and cachexia (17.8%) were the most frequent causes of death, whereas the mortality due to peritonitis showed a progressive increase in patients with peritonitis incidence 1 ep/year (G4) compared to those with < 0.5 ep/year (G2). Peritonitis (0.68 ep/year) was the most frequent cause of technique failure (30.0%), with clinical complications (18.2%) and peritoneal membrane failure (16.4%) as the second and third causes. The dropout percentage was 8.3% per year with a significant decrease over time (p = 0.012) and a positive correlation with the reduction of peritonitis incidence (p = 0.035). The total TS was 50.1% at 7 years, and it was significantly worse in G4 compared to G2.(ABSTRACT TRUNCATED AT 250 WORDS)