Dialysis and Renal Transplantation in HIV-Infected Patients: a European Survey

OBJECTIVES:: To determine prevalence and characteristics of end-stage renal diseases (ESRD) [dialysis and renal transplantation (RT)] among European HIV-infected patients. METHODS:: Cross-sectional multicenter survey of EuroSIDA clinics during 2008. RESULTS:: Prevalence of ESRD was 0.5%. Of 122 patients with ESRD 96 were on dialysis and 26 had received a RT. Median age was 47 years, 73% were males and 43% were black. Median duration of HIV infection was 11 years. Thirty-three percent had prior AIDS; 91% were receiving antiretrovirals; and 88% had undetectable viral load. Median CD4T-cell count was 341 cells per cubic millimetre; 20.5% had hepatitis C coinfection. Most frequent causes of ESRD were HIV-associated nephropathy (46%) and other glomerulonephritis (28%). Hemodialysis (93%) was the most common dialysis modality; 34% of patients were on the RT waiting list. A poor HIV control was the reason for exclusion from RT waiting list in 22.4% of cases. All the RT recipients were all alive at the time of the survey. Acute rejection was reported in 8 patients (30%). Functioning graft was present in 21 (80%). CONCLUSIONS:: This is the first multinational cross-sectional study of ESRD among European HIV population. Low prevalence of ESRD was found. Two-thirds of patients were excluded from RT for non-HIV/AIDS-related pathologies. Most patients had a functioning graft despite a high acute rejection rate.

Demographics of blood pressure and hypertension in children on renal replacement therapy in Europe

Hypertension is a well-known complication in children on renal replacement therapy and an important risk factor for cardiovascular disease in later life. In order to define the prevalence of and risk factors for hypertension among children, we enrolled 3337 pediatric patients from 15 countries in the ESPN/ERA-EDTA Registry of whom 464 were on hemodialysis, 851 on peritoneal dialysis, and 2023 had received a renal allograft. Hypertension was defined as either systolic or diastolic blood pressures in the 95th percentile or greater for age, height, and gender or use of antihypertensive medication. Analyses were adjusted for age, gender, duration, and modality of renal replacement therapy. In 10 countries in which information on the use of antihypertensive medication was available, hypertension was present in over two-thirds of hemodialysis, peritoneal dialysis, or transplant patients. Blood pressure values above the 95th percentile were significantly more prevalent in very young patients (under 3 years) compared to 13- to 17-year olds (odds ratio 2.47), during the first year compared to over 5 years of renal replacement therapy (odds ratio 1.80), and in patients on hemodialysis compared to transplant recipients or those on peritoneal dialysis (odds ratios of 2.48 and 1.59, respectively). Over time, mean blood pressures decreased in both hemodialysis and transplant patients, but not in peritoneal dialysis patients. Hence, our findings highlight the extent of the problem of hypertension in children with end-stage renal disease in Europe.

Nanoparticle-based test measures overall propensity for calcification in serum

Vascular and soft tissue calcification contributes to cardiovascular morbidity and mortality in both the general population and CKD. Because calcium and phosphate serum concentrations are near supersaturation, the balance of inhibitors and promoters critically influences the development of calcification. An assay that measures the overall propensity for calcification to occur in serum may have clinical use. Here, we describe a nanoparticle-based assay that detects, in the presence of artificially elevated calcium and phosphate concentrations, the spontaneous transformation of spherical colloidal primary calciprotein particles (CPPs) to elongate crystalline secondary CPPs. We used characteristics of this transition to describe the intrinsic capacity of serum to inhibit the precipitation of calcium and phosphate. Using this assay, we found that both the sera of mice deficient in fetuin-A, a serum protein that inhibits calcification, and the sera of patients on hemodialysis have reduced intrinsic properties to inhibit calcification. In summary, we developed a nanoparticle-based test that measures the overall propensity for calcification in serum. The clinical use of the test requires evaluation in a prospective study.

Perilipin-1 in hemodialyzed patients: association with history of coronary heart disease and lipid profile

Perilipin-1 surrounds lipid droplets in both adipocytes and in atheroma plaque foam cells and controls access of lipases to the lipid core. In hemodialysis (HD) patients, dyslipidemia, malnutrition, inflammation and atherosclerosis are common. Thirty-six HD patients and 28 healthy volunteers were enrolled into the study. Ten HD patients suffered from coronary heart disease (CHD). Perilipin-1, triglycerides, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-C), body mass index, albumin, geriatric nutritional risk index, normalized protein catabolic rate, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were measured. Perilipin-1 did not differ between HD patients and healthy volunteers. IL-6 and TNF-α were higher in HD patients. The evaluated nutritional markers and the markers of inflammation did not differ between HD patients with high perilipin-1 levels and HD patients with low perilipin-1 levels. Regarding the lipid profile, only HDL-C differed between HD patients with high perilipin-1 levels and HD patients with low perilipin-1 levels, and it was higher in the first subgroup. Perilipin-1 was significantly higher in HD patients without CHD. Perilipin-1 is detectable in the serum of HD patients and it is associated with increased HDL-C and decreased incidence of CHD.

The Validation of a New Visual Anaemia Evaluation Tool HemoHue HH1 in Patients with End-Stage Renal Disease

In chronic haemodialysis patients, anaemia is a frequent finding associated with high therapeutic costs and further expenses resulting from serial laboratory measurements. HemoHue HH1, HemoHue Ltd, is a novel tool consisting of a visual scale for the noninvasive assessment of anaemia by matching the coloration of the conjunctiva with a calibrated hue scale. The aim of the study was to investigate the usefulness of HemoHue in estimating individual haemoglobin concentrations and binary treatment outcomes in haemodialysis patients. A prospective blinded study with 80 hemodialysis patients comparing the visual haemoglobin assessment with the standard laboratory measurement was performed. Each patient's haemoglobin concentration was estimated by seven different medical and nonmedical observers with variable degrees of clinical experience on two different occasions. The estimated population mean was close to the measured one (11.06 ± 1.67 versus 11.32 ± 1.23 g/dL, P < 0.0005). A learning effect could be detected. Relative errors in individual estimates reached, however, up to 50%. Insufficient performance in predicting binary outcomes (ROC AUC: 0.72 to 0.78) and poor interrater reliability (Kappa < 0.6) further characterised this method.

Arterial stiffness depends on serum ionized calcium levels during dialysis with regional citrate anticoagulation

Hemodynamic effects related to changes in serum ionized calcium (iCa) are difficult to determine during conventional hemodialysis (HD) using a fixed dialysate concentration of calcium. Regional citrate anticoagulation (RCA) allows the study of the effects of predefined iCa changes on arterial stiffness and blood pressure (BP) during a single dialysis session. In a crossover study, 15 patients with end-stage renal disease underwent two HD sessions with RCA. Each session was divided into two study phases in which iCa was titrated either to 0.8-1.0 mm or to 1.1-1.4 mm. The sequence of phases was randomly chosen and alternated for the second session. After reaching a stable iCa level, pulse wave velocity (PWV), arterial BP, and heart rate were measured. iCa levels were modified during sequence 1 (iCa low-high) from a predialysis baseline value of 1.15 ± 0.09 mm, first to 0.92 ± 0.05 mm (time point 1; P < 0.001 vs. baseline) and then to 1.18 ± 0.05 (time point 2; ns). During sequence 2 (iCa high-low), iCa levels were modified from 1.15 ± 0.12 mm first to 1.20 ± 0.05 mm (time point 1; ns vs. baseline) and then to 0.93 ± 0.03 (time point 2; P < 0.001). Assuming a basic linear repeated measures model, PWV was positively related to iCa levels (P < 0.03) independent of systolic or diastolic BP, heart rate, or ultrafiltration rate. PWV is closely related to acute changes in serum iCa levels in HD patients using RCA. RCA provides an interesting opportunity to study the effects of acute iCa changes during one dialysis procedure.

Duration of methicillin-resistant Staphylococcus aureus carriage, according to risk factors for acquisition

OBJECTIVE: To examine the duration of methicillin-resistant Staphylococcus aureus (MRSA) carriage and its determinants and the influence of eradication regimens. DESIGN: Retrospective cohort study. SETTING: A 1,033-bed tertiary care university hospital in Bern, Switzerland, in which the prevalence of methicillin resistance among S. aureus isolates is less than 5%. PATIENTS: A total of 116 patients with first-time MRSA detection identified at University Hospital Bern between January 1, 2000, and December 31, 2003, were followed up for a mean duration of 16.2 months. RESULTS: Sixty-eight patients (58.6%) cleared colonization, with a median time to clearance of 7.4 months. Independent determinants for shorter carriage duration were the absence of any modifiable risk factor (receipt of antibiotics, use of an indwelling device, or presence of a skin lesion) (hazard ratio [HR], 0.20 [95% confidence interval {CI}, 0.09-0.42]), absence of immunosuppressive therapy (HR, 0.49 [95% CI, 0.23-1.02]), and hemodialysis (HR, 0.08 [95% CI, 0.01-0.66]) at the time MRSA was first MRSA detected and the administration of decolonization regimen in the absence of a modifiable risk factor (HR, 2.22 [95% CI, 1.36-3.64]). Failure of decolonization treatment was associated with the presence of risk factors at the time of treatment (P=.01). Intermittent screenings that were negative for MRSA were frequent (26% of patients), occurred early after first detection of MRSA (median, 31.5 days), and were associated with a lower probability of clearing colonization (HR, 0.34 [95% CI, 0.17-0.67]) and an increased risk of MRSA infection during follow-up. CONCLUSIONS: Risk factors for MRSA acquisition should be carefully assessed in all MRSA carriers and should be included in infection control policies, such as the timing of decolonization treatment, the definition of MRSA clearance, and the decision of when to suspend isolation measures.

Arterial stiffness assessed by digital volume pulse correlates with comorbidity in patients with ESRD

BACKGROUND: Digital volume pulse (DVP), a noninvasive method for indirect assessment of arterial stiffness, was not tested previously in patients with end-stage renal disease (ESRD). Therefore, we compared the DVP-derived stiffness index (SI(DVP)) with aortic pulse wave velocity (PWV) determined by means of Doppler ultrasonography in 2 groups of patients with ESRD and analyzed the correlation between SI(DVP) and comorbidity. METHODS: Photoplethysmography was performed on the index finger of the dominant hand or the hand from the nonfistula arm in 49 renal transplant (TX) recipients and 48 hemodialysis (HD) patients. Pulse curves were analyzed with computer assistance. Comorbidity was assessed by using an established index. RESULTS: The intrasubject variability of SI(DVP) was 5.7%. SI(DVP) and aortic PWV values correlated significantly (r = 0.66; P = 0.001) in patients with ESRD. SI(DVP) could not be assessed reliably in 25% and 6% of HD patients and TX recipients, respectively. Multivariate regression analyses showed that SI(DVP) increased with age in both HD patients and TX recipients (r = 0.61; P < 0.001) and with systolic blood pressure (r = 0.53; P < 0.025), mean arterial pressure (r = 0.47; P < 0.05), and pulse pressure (r = 0.52; P = 0.02) in TX recipients. Severity of comorbid status was associated highly with individual residuals of age-adjusted SI(DVP) in HD patients and TX recipients (P < 0.001). CONCLUSION: DVP allows the measurement of arterial stiffness in most, but not all, patients with ESRD. SI(DVP) values correlate with comorbidity in HD patients and TX recipients.

Percutaneous endoscopic gastrostomy in children on peritoneal dialysis

OBJECTIVE: Insertion of percutaneous endoscopic gastrostomies (PEG) in patients on chronic peritoneal dialysis (PD) has been reported to be contraindicated due to an increased risk of morbidity and mortality. However, no systematic survey on this topic has yet been published. DESIGN: Retrospective multicenter study. SETTING: 23 pediatric dialysis units associated with the working group Arbeitsgemeinschaft für Pädiatrische Nephrologie (APN). DATA SOURCE: A structured questionnaire on clinical details of PD patients who had undergone PEG insertion or open gastrostomy (OG) since 1994 was distributed to all pediatric dialysis units of the APN. RESULTS: 27 PD patients (20 males) from 12 centers in whom PEG insertion was performed after Tenckhoff catheter introduction were evaluated. Age at intervention ranged from 0.25 to 10.9 years (median 1.3 years). Most patients were malnourished, with standard deviation score (SDS) for body weight between -4.2 and -0.6 (median -2.2). Major complications were early peritonitis < 7 days after PEG in 10/27 (37%) patients, episodes of fungal peritonitis in 7/27 (26%) patients, 4 cessations of PD and change to hemodialysis, and 2 associated deaths. However, in 14 patients, no such problems were encountered and, in 4 patients, early peritonitis effectively treated with intraperitoneal antibiotics was the only major complication. Thus, in 18/27 (67%) patients, PD was successfully reinitiated shortly after PEG insertion. Among all participating centers, only two OG procedures were reported during the study period, illustrating a clear preference for the PEG over the OG procedure among members of the APN. CONCLUSION: PEG insertion following PD initiation carries a high risk for fungal peritonitis and potential PD failure; however, complication rates in this largest reported series were lower than previously described. Antibiotic and antifungal prophylaxis, withholding PD for 2 - 3 days, and gastrostomy placement by an experienced endoscopy team are suggested precautions for lowering the risk of associated complications. When gastrostomy placement does not occur prior to or at the time of initiating PD, the risks and benefits of percutaneous versus open placement must be carefully weighed.

Pitfall in pediatric dialysis: malposition of a dialysis catheter mimicking azygos continuation syndrome

Central venous catheters are established as vascular access in hemodialysis therapy. Vascular catheter misdirection may occur and is a well known problem. We present a rare catheter malposition in a young dialysis patient with consequent dilatation of the azygos vein system, simulating the appearance of an azygos continuation syndrome.

Randomized, double-blind comparative trial of subunit and virosomal influenza vaccines for immunocompromised patients

BACKGROUND: To our knowledge, no study to date has compared the effects of a subunit influenza vaccine with those of a virosomal influenza vaccine on immunocompromised patients. METHODS: A prospective, double-blind, randomized study was conducted to compare the immunogenicity and reactogenicity of subunit and virosomal influenza vaccines for adult patients who had an immunosuppressive disease or who were immunocompromised as a result of treatment. RESULTS: There were 304 patients enrolled in our study: 131 with human immunodeficiency virus (HIV) infection, 47 with a chronic rheumatologic disease, 74 who underwent a renal transplant, 47 who received long-term hemodialysis, and 5 who had some other nephrologic disease. There were 151 patients who received the subunit vaccine and 153 patients who received the virosomal vaccine. A slightly higher percentage of patients from the subunit vaccine group were protected against all 3 influenza vaccine strains after being vaccinated, compared with patients from the virosomal vaccine group (41% vs. 30% of patients; P = .03). Among HIV-infected patients, the level of HIV RNA, but not the CD4 cell count, was an independent predictor of vaccine response. Among renal transplant patients, treatment with mycophenolate significantly reduced the immune response to vaccination. The 2 vaccines were comparable with regard to the frequency and severity of local and systemic reactions within 7 days after vaccination. Disease-specific scores for the activity of rheumatologic diseases did not indicate flare-ups 4-6 weeks after vaccination. CONCLUSIONS: For immunosuppressed patients, the subunit vaccine was slightly more immunogenic than the virosomal vaccine. The 2 vaccines were comparable with regard to reactogenicity. Vaccine response decreased with increasing degree of immune suppression. Among HIV-infected patients, the viral load, rather than the CD4 cell count, predicted the protective immune response to the vaccine. CLINICAL TRIALS REGISTRATION: NCT00783380 .

Treatment of acute renal failure in the intensive care unit: lower costs by intermittent dialysis than continuous venovenous hemodiafiltration

Intermittent and continuous renal replacement therapies (RRTs) are available for the treatment of acute renal failure (ARF) in the intensive care unit (ICU). Although at present there are no adequately powered survival studies, available data suggest that both methods are equal with respect to patient outcome. Therefore, cost comparison between techniques is important for selecting the modality. Expenditures were prospectively assessed as a secondary end point during a controlled, randomized trial comparing intermittent hemodialysis (IHD) with continuous venovenous hemodiafiltration (CVVHDF). The outcome of the primary end points of this trial, that is, ICU and in-hospital mortality, has been previously published. One hundred twenty-five patients from a Swiss university hospital ICU were randomized either to CVVHDF or IHD. Out of these, 42 (CVVHDF) and 34 (IHD) were available for cost analysis. Patients' characteristics, delivered dialysis dose, duration of stay in the ICU or hospital, mortality rates, and recovery of renal function were not different between the two groups. Detailed 24-h time and material consumption protocols were available for 369 (CVVHDF) and 195 (IHD) treatment days. The mean daily duration of CVVHDF was 19.5 +/- 3.2 h/day, resulting in total expenditures of Euro 436 +/- 21 (21% for human resources and 79% for technical devices). For IHD (mean 3.0 +/- 0.4 h/treatment), the costs were lower (Euro 268 +/- 26), with a larger proportion for human resources (45%). Nursing time spent for CVVHDF was 113 +/- 50 min, and 198 +/- 63 min per IHD treatment. Total costs for RRT in ICU patients with ARF were lower when treated with IHD than with CVVHDF, and have to be taken into account for the selection of the method of RRT in ARF on the ICU.

The prevalence of anemia in chronic heart failure.

OBJECTIVES To assess prevalence of anemia and its correlation with NYHA-class in patients with congestive heart failure. BACKGROUND Recently, it was reported that anemia in congestive heart failure patients is common and correlated with the severity of disease. In these patients with anemia, treatment with erythropoietin and intravenous iron improved cardiac function significantly. METHODS 193 patients from a tertiary heart failure outpatient clinic (mean age 54 years) were included in a retrospective analysis. Fourteen patients were in NYHA-class I, 69 class II, 79 class III, and 31 class IV. All patients had clinical and laboratory evaluation, echocardiography and coronary angiography. Patients with secondary anemia or on hemodialysis were excluded. Etiology of heart failure was ischemic in 41%. RESULTS Anemia (hemoglobin<120 g/l) was present in 28 of 193 patients (15%). There was an inverse relationship between NYHA-class and left ventricular ejection fraction (NYHA-class I 45%, class II 32%, class III 25%, class IV 25%). Serum creatinine increased with NYHA-class. Hemoglobin levels were similar in all four NYHA-classes but there were significantly more patients with anemia in NYHA-class III and IV (19%) compared with class I and II (8%, P<0.05). Hemoglobin was similar in surviving patients (mean 140 g/l) and those who died or were transplanted (mean 136 g/l, ns). CONCLUSIONS The prevalence of anemia in our heart failure service is 15% (compared with 56% in the literature) and is correlated to NYHA-class.

Pharmacokinetics of meprobamate in overdose treated with continuous venovenous hemodiafiltration (CVVHDF)

We report a case of massive suicidal overdose of meprobamate leading to cardiovascular collapse, respiratory failure, and severe central nervous system depression. We observed first-order elimination kinetics despite significant overdose, and demonstrated effectiveness of continuous venovenous hemodiafiltration (CVVHDF) for extracorporeal removal of meprobamate in this patient. Total body clearance was calculated to be 87 mL/minute, with 64 mL/minute (74%) due to CVVHDF. CVVHDF was stopped after 36 hours, and the patient made an uneventful recovery.

Inoculum effect with cefazolin among clinical isolates of methicillin-susceptible Staphylococcus aureus: frequency and possible cause of cefazolin treatment failure.

Methicillin (meticillin)-susceptible Staphylococcus aureus (MSSA) strains producing large amounts of type A beta-lactamase (Bla) have been associated with cefazolin failures, but the frequency and impact of these strains have not been well studied. Here we examined 98 MSSA clinical isolates and found that 26% produced type A Bla, 15% type B, 46% type C, and none type D and that 13% lacked blaZ. The cefazolin MIC(90) was 2 microg/ml for a standard inoculum and 32 microg/ml for a high inoculum, with 19% of isolates displaying a pronounced inoculum effect (MICs of >or=16 microg/ml with 10(7) CFU/ml) (9 type A and 10 type C Bla producers). At the high inoculum, type A producers displayed higher cefazolin MICs than type B or C producers, while type B and C producers displayed higher cefamandole MICs. Among isolates from hemodialysis patients with MSSA bacteremia, three from the six patients who experienced cefazolin failure showed a cefazolin inoculum effect, while none from the six patients successfully treated with cefazolin showed an inoculum effect, suggesting an association between these strains and cefazolin failure (P = 0.09 by Fisher's exact test). In summary, 19% of MSSA clinical isolates showed a pronounced inoculum effect with cefazolin, a phenomenon that could explain the cases of cefazolin failure previously reported for hemodialysis patients with MSSA bacteremia. These results suggest that for serious MSSA infections, the presence of a significant inoculum effect with cefazolin could be associated with clinical failure in patients treated with this cephalosporin, particularly when it is used at low doses.