Francesco Quarello

Prevention of Hemodialysis Catheter-Related Bloodstream Infection Using an Antimicrobial Lock

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.

The verapamil versus amlodipine in nondiabetic nephropathies treated with trandolapril (VVANNTT) study

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.

Acute Effects of Hemodialysis on Erythrocyte Sodium Fluxes in Uremic Patients

The acute effects of both acetate and bicarbonate hemodialysis on erythrocyte transmembrane sodium fluxes were investigated in 15 patients with chronic uremia. We observed a significance (p less than 0.01) stimulation of the Na+,K+ pump in both procedures, with a significant correlation to the amount of fluid removed during hemodialysis (r = 0.56, p less than 0.03). Outward Na+ cotransport fluxes significantly rose (p less than 0.05) after acetate hemodialysis and decreased (p less than 0.05) after bicarbonate hemodialysis. Minor and not significant pre- and posthemodialysis bidirectional changes were observed as regards the intraerythrocyte Na+ and K+ concentration, passive Na+ and K+ permeability, and Na+,Li+ countertransport. Hemodialysis may acutely affect the erythrocyte sodium pump and cotransport fluxes, possibly through the modulation of hormonal factors triggered by the extracellular volume changes.

Acute pyelonephritis in adults: a case series of 223 patients

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.

Continuous Ambulatory Peritoneal Dialysis Improves Immunodeficiency in Uremic Patients

F. Giacchino, MD, Nephrology and Dialysis Unit, San Giovanni Hospital, Largo Gottardo 143, I-10154 Turin (Italy) Dear Sir, The high incidence of infections and malignancies in uremic patients [1, 2] is a clear indication of the immuno-suppressive effect of uremia [3–5]. Numerous hypotheses have been put forward, including protein-calorie malnutrition [6], vitamin deficiency [7], and lowered blood zinc levels [8], but so far none of them has proved satisfactory. A more recent suggestion is that serum factors (medium molecular weight) may be responsible for this phenomenon in vitro [9], and in experimental animals [10]. There is still considerable debate however, as to whether middle molecules play a toxic role in cell-mediated immunity in man [11]. In order to evaluate the effect of different degrees of removal of middle molecules by dialysis treatment on cellular immunodeficiency, we analyzed the immunological state of 60 uremic patients treated by continuous ambulatory peritoneal dialysis (CAPD) and hemodialysis (HD) during a follow-up of 12 months. 30 healthy people were also studied as controls. DNCB and PPD skin tests, Eand active Erosettes, the E-rosette inhibition assay were investigated as markers of cellular immunity [12]. The results of our study are summarized in table I. CAPD patients showed an improvement in cellular immunity, with a significant increase in the E-rosette count (p < O.Ol), and improved delayed hypersensitivity reactions 3 months after treatment was started, while no difference was observed in HD patients. The most compelling evidence for a role of middle molecules in cellmediated deficiency has been provided by the E-rosette inhibition test. Serum from CAPD patients showed a significant reduction of the percentage of E-rosette inhibition (p < 0.02), even 1 month after treatment was started, and the results were confirmed at the following controls. In the HD patients the percentage of inhibition remained high throughout our study. Our results are in agreement with previous findings in vitro and in animals [9, 10]. Since CAPD removes middle molecules more satisfactory than hemodialysis [13], and Table I. Cellular immunity in CAPD and HD patients

Effect of a plasma sodium biofeedback system applied to HFR on the intradialytic cardiovascular stability. Results from a randomized controlled study

Background Intradialytic 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. Methods Fifty 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. Results Symptomatic 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 <0.01). In a post-hoc analysis, the effect of HFR-Aeq was greater on more unstable patients (35 ± 3% of sessions with hypotension on HFR-Aeq versus 71 ± 3% on HFR, P <0.001). No clinical or biochemical signs of Na/water overload were registered during the treatment with HFR-Aeq. Conclusions HFR-Aeq, a profiled dialysis supported by the Natrium sensor for the pre-dialysis Na+ measure, can significantly reduce the burden of IDH. This could have an important impact in every day dialysis practice.

ACUTE PYELONEPHRITIS: ANALYSIS OF 52 CASES

Acute pyelonephritis (APN) is a frequent disease, but diagnostic approach, evolution into abscesses, and indication to hospitalization are still open problems. We have made a retrospective analysis of APN cases observed in our hospital. We identified 58 patients (pt) and selected 52 of these who presented fever and loin pain at the onset (31 were hospitalized in Nephrology and 21 in other units). Urine culture was positive in 11/48 cases (22.9%), blood cultures in 3/26 cases (11.5%) (Escherichia coli). Renal sonography was normal in 20/48 cases (41.6%) and suggestive for APN in 23/48 cases (47.9%). CT with contrast medium was normal in 9/28 cases (32.1%) and positive in 19/28 cases (67.8%), with evidence of unique or multiple hypodense areas; abscesses were found in 8 patients (28.5%). No statistically significant differences were found between patients with positive or negative CT as regards fever, leukocytosis, ESR, CRP, CRP at 20 days, urinary leukocytes, urine culture, duration of symptoms before hospitalization. Moreover no differences were found between patients with and without abscesses. CT was performed more frequently among patients hospitalized in Nephrology than among patients hospitalized in other services (24/31—77.4%—vs. 4/21—19%—, p = 0.05). NMR was abnormal in 6/9 cases. A radiographic documentation of APN was obtained in 61.53% of patients with clinical diagnosis of APN. Of these, only 18.7% had positive urine culture. In conclusion, our data suggest that demonstration of urine infection is not necessary for APN diagnosis, when clinical and/or radiologic diagnosis of APN has been made. Evolution into abscesses is frequent and not easily susceptible on clinical ground; for this reason we think it is advisable to perform CT or NMR systematically. Differences in clinical behavior between different units suggest the need for diagnostic guidelines.

Association Between Elevated Prolactin Levels and Circulating Erythroid Precursors in Dialyzed Patients

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.

WHAT IS THE ROLE OF SENSITIZATION IN UREMIC PRURITUS ? : AN ALLERGOLOGIC STUDY

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.

Outcome of dialysis patients submitted to coronary revascularization

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 submited 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.