Dialysis Subjects Research Articles

Evaluation of the Various Oral Candida Species among Patients on Hemodialysis: A Clinical Study.

Oral candidiasis develops as a result of an opportunistic infection. In patients on hemodialysis who may be immune-compromised, candida can change from a commensal to a pathogen. Identification and classification of Candida species are crucial for the treatment of these patients. To distinguish between distinct species of candida found in hemodialysis patients with chronic renal failure's oral cavity. A total of 100 people were investigated, including 50 patients with "Chronic Renal Failure (CRF)" on hemodialysis and 50 healthy controls. Using "Sabouraud's Dextrose Agar (SDA)" and "CHROM Agar Culture Media", salivary samples were incubated for 24, 48, or 72 hours at 37°C to develop candida species. Colony forming units/milliliter, a unit of measurement for colonies, were counted and calculated (CFU). On SDA and CHROM agar medium, positive candidal growth was seen in the CRF with HD and Control Groups. There was a significant variance in the growth and the subspecies distribution of the colonies among the groups. The most common species was c.albicans followed by c. cruzi and tropical. Other subspecies were negligible. The number of colonies was also greater than 400 CFU in the majority of the dialysis subjects, while it was only 200 CFU for the majority of the controls. Patients with chronic renal failure receiving hemodialysis showed significantly higher levels of candida isolation and differentiation than healthy individuals (P 0.05).

Postoperative mortality in peritoneal dialysis: analytic study in patients with peritonitis

The number of patients with end-stage renal disease (ESRD) who receive peritoneal dialysis (PD) therapy has been increasing worldwide because of the improvement in PD techniques and concomitant patient survival. PD-related peritonitis remains the leading cause of technique failure in PD therapy. The purpose of this study is to analysis the risk factors that lead to mortality in patients receiving PD who needs surgery. Retrospective study included 44 patients with peritoneal dialysis (PD) subjects to elective surgery for peritonitis. Collected data regarding demographic analysis, number of PD followed by peritonitis episodes, type of surgical operation and mortality due to peritonitis. The resulted data explained that PD with gastrointestinal surgery resulted with peritonitis were encountered in 10 patients and PD with cirrhosis patients increased mortality in old patients (p = 0.02). However, mortality increased with old age in patients with ischemic heart disease (p = 0.004). Furthermore, the results of binary logistic regression analysis for age (odds ratio [OR]= 1.09; 95% Cl [1.012-1.193]; p=0.012), ischemic heart diseases [OR] = 52.1; 95% Cl [5.192-433.631]; p=0.011. In conclusions surgical operations that performed in peritonitis patients due to PD needs experienced centers with professional staff.

Cardiorespiratory fitness in kidney transplant recipients compared to patients with kidney failure: a systematic review and meta-analysis.

Patients with kidney failure often present with reduced cardiovascular functional reserve and exercise tolerance. Previous studies on cardiorespiratory fitness examined with cardiopulmonary exercise testing (CPET) in kidney transplant recipients (KTR) had variable results. This is a systematic review and meta-analysis of studies examining cardiovascular functional reserve with CPET in KTR in comparison with patients with kidney failure (CKD-Stage-5 before dialysis, hemodialysis or peritoneal dialysis), as well as before and after kidney transplantation. Literature search involved PubMed, Web-of-Science and Scopus databases, manual search of article references and grey literature. From a total of 4,944 identified records, eight studies (with 461 participants) were included in quantitative analysis for the primary question. Across these studies, KTR had significantly higher oxygen consumption at peak/max exercise (VO2 peak/VO2 max) compared to patients with kidney failure (SMD=0.70, 95% CI [0.31, 1.10], I2 =70%, P=0.002). In subgroup analyses, similar differences were evident among seven studies comparing KTR and hemodialysis patients (SMD=0.64, 95% CI [0.16, 1.12], I2 =65%, P=0.009) and two studies comparing KTR with peritoneal dialysis subjects (SMD=1.14, 95% CI [0.19, 2.09], I2 =50%, P=0.16). Across four studies with relevant data, oxygen consumption during peak/max exercise showed significant improvement after kidney transplantation compared to pretransplantation values (WMD=2.43, 95% CI [0.01, 4.85], I2 =68%, P=0.02). In conclusion, KTR exhibit significantly higher cardiovascular functional reserve during CPET compared to patients with kidney failure. Cardiovascular reserve is significantly improved after kidney transplantation in relation to presurgery levels.

Polymorphism rs368234815 of interferon lambda 4 gene and spontaneous clearance of hepatitis C virus in haemodialysis patients: a case-control study

BackgroundIn non-uremic subjects, IFNL4 rs368234815 predicts HCV clearance. We investigated whether rs368234815 is associated with spontaneous HCV clearance in haemodialysis patients and whether it is a stronger predictor of HCV resolution than the IFNL polymorphisms already associated with HCV clearance in dialysis subjects. We also evaluated an association of rs368234815 with patients` survival and alterations in transcription factor binding sites (TFBS) caused by IFNL polymorphisms.MethodsAmong 161 haemodialysis patients with positive anti-HCV antibodies, 68 (42.2%) spontaneously resolved HCV infection, whereas 93 remained HCV RNA positive. Patients were tested for near IFNL3 rs12980275, IFNL3 rs4803217, IFNL4 rs12979860, IFNL4 rs368234815, and near IFNL4 rs8099917. IFNL4 rs368234815 polymorphism (TT/TT, ΔG/TT, ΔG/ΔG) was genotyped by restriction fragment length polymorphism analysis; other IFNL polymorphisms - by high resolution melting curve analysis. We used the Kaplan-Meier method with the log-rank test for survival analysis. In silico analysis included the use of ENCODE TFBS ChIP-seq data, HOCOMOCO, JASPAR CORE, and CIS-BP databases, and FIMO software.ResultsThe probability (OR, 95%CI, P) of spontaneous HCV clearance for rs368234815 TT/TT patients was higher than for the ΔG allele carriers (2.63, 1.38–5.04, 0.003). This probability for other major homozygotes varied between 2.80, 1.45–5.43, 0.002 for rs12980275 and 2.44, 1.27–4.69, 0.007 for rs12979860. In the additive model, rs368234815 TT/TT was the strongest predictor of HCV clearance (6.38, 1.69–24.2, 0.003). Survival analysis suggested an association of the ΔG allele with mortality due to neoplasms (log-rank P = 0.005). The rs368234815 ∆G allele caused TFBS removal for PLAGL1.ConclusionsIn haemodialysis patients, the association of rs368234815 with the spontaneous HCV clearance is better than that documented for other IFNL3/IFNL4 polymorphisms only in the additive mode of inheritance. However, identifying the homozygosity in the variant ∆G allele of rs368234815 means a more potent prediction of persistent HCV infection in haemodialysis subjects that we observe in the case of the variant homozygosity of other tested IFNL3/IFNL4 polymorphisms. Removal of PLAGL1 TFBS in subjects harbouring the rs368234815 ∆G allele may contribute to cancer susceptibility. The association of rs368234815 with cancer-related mortality needs further studies in HCV-exposed subjects.

A population‐based study of the association between hemodialysis and cognitive impairment

End-stage renal disease is a serious public health issue. The objective of this retrospective cohort study was to assess the association between hemodialysis and cognitive impairment, while controlling for age, sex, residence, and comorbidities. This study assesses the risk of cognitive impairment among a nationwide cohort of new hemodialysis patients derived from the NHIRD. A total of 4330 patients were assigned to the dialysis group and 17 320 patients were assigned to the control group. A total of 2103 of the patients developed cognitive impairment within 2 years after the date of dialysis initiation. Patients who developed cognitive impairment were older (69.85 ± 11.56) than their counterparts who did not develop cognitive impairment (58.58 ± 14.77; P < .001). The log-rank test of Kaplan-Meier analysis revealed a higher risk of cognitive impairment in the hemodialysis group than in the non-hemodialysis group (P < .001). The interval between dialysis initiation and the onset of cognitive impairment was 98.66 ± 46.39 months among non-dialysis subjects and 53.45 ± 41.90 months among dialysis subjects, and the between-group difference was significant (P < .001). The Cox Proportional Hazard Model revealed that after controlling for gender, age, residence, and comorbidities, hemodialysis was shown to have a significant impact on cognitive impairment (Hazard Ratio [HR]: 1.44; 95% confidence interval [CI]: 1.29-1.60). Furthermore, the risk of developing cognitive impairment increased with age (HR: 1.07; 95% CI: 1.06-1.08). Hemodialysis was associated with cognitive impairment. There was a significant association between age and cognitive impairment, regardless of the comorbidities prior to hemodialysis. There was no evidence of an association between comorbidities and cognitive impairment after beginning hemodialysis.

P1199THE IMPORTANCE OF DETERMINING ALPHA-2-MACROGLOBULIN CONCENTRATITON IN PATIENTS ON PERITONEAL DIALYSIS

Abstract Background and Aims To determine the concentration of Alpha-2-macroglobulin (α2M) and its activity in patients treated with peritoneal dialysis (PD) and healthy subjects (H). Method a cross-sectional study included 50 PD and 30 H, in which the concentration of active α2M molecules was determined. The measurement is based on covalent binding of α2M and trypsin and zymography with gelatin incorporated into the electrophoretic gel. Results The intensity of proteolytic bands seen with native α2M was analyzed in relation to the concentration of α2M in patients with PD with less and / or more than three peritonitis. Linear dependence was only visible in the case of the upper range, which originates from the intact α2M-trypsin complex. The highest coefficient of variation is calculated for the smallest α2M concentration (4.2%). The signal intensities originating from α2M (H) were higher compared to PD, with the PD group being lower in patients with higher peritonitis, and the difference was more pronounced as concentration increased, resulting in a lower slope of dependence. The proposed method can reliably measure the amount of α2M originating in a group H, while the quantification of α2M in PD groups that may have structurally altered α2M can be seen more for condition estimation than for accurate measurements. The zymographic test in this experiment allows us to investigate the relationship of the concentration, structure and function of α2M in different pathological conditions, as well as in the presence of modifying agents that can accompany them. Conclusion A simple method for the determination of α2M concentration and function by zymography has been developed, which can be used to examine residual α2M activity after partial denaturation or structural modification due to disease.

Pharmacokinetics and Immunogenicity of ASP0113 in CMV-Seronegative Dialysis Patients and CMV-Seronegative and -Seropositive Healthy Subjects.

Cytomegalovirus (CMV) infection causes significant morbidity and mortality in immunocompromised transplant patients. ASP0113, a first-in-class DNA vaccine containing plasmids encoding CMV phosphoprotein 65 and glycoprotein B (gB), was evaluated in a phase 1b, subject-blinded study in CMV-seropositive (n=13) and CMV-seronegative (n=12) healthy and CMV-seronegative dialysis subjects (n=12) randomized to ASP0113 or placebo. End points included pharmacokinetics, anti-gB antibody levels, phosphoprotein 65-specific T-cell responses measured by ex vivo enzyme-linked immune absorbent spot (ELISpot) assay and 10-day cultured ELISpot and Stat T-cell activation assays, and safety. ASP0113 concentrations peaked at 2-10 and 24-48 hours; the pharmacokinetics were similar across groups. No group demonstrated significant anti-gB antibody responses. T-cell responder rates in the cultured ELISpot assay were 8/12 (66.7%, 95%CI 35% to 90%) and 4/12 (33.3%, 95%CI 10% to 65%) in CMV-seronegative healthy subjects and dialysis patients, respectively, whereas ex vivo ELISpot assay response rates were 4/11 (36.4%, 95%CI 11% to 69%) and 0/12, respectively. Responses peaked at week 27, with lower magnitude observed in CMV-seronegative dialysis patients versus CMV-seronegative healthy subjects. No serious adverse events occurred; the most common adverse event in ASP0113-vaccinated patients was injection-site pain (64.9%). Some CMV-seronegative healthy subjects and dialysis patients had T-cell responses; no humoral responses were detected.

Evaluation of Antibody Responses in Hemodialysis Patients, Peritoneal Dialysis, Kidney Transplant Recipients and Normal Subjects after Administration of 23-Valent Pneumococcal Polysaccharide Vaccine

Background: Pneumococcal vaccines are recommended in patients with immune deficiencies such as kidney transplant recipients and dialysis subjects. Streptococcus pneumoniae is an agent of pneumonia, meningitis, important morbidities and mortality in such patients. The purpose of this study was to evaluate and compare the antibody responses in hemodialysis patients, peritoneal dialysis, kidney transplant recipients and normal subjects after administration of 23-valent pneumococcal polysaccharide vaccine (PPV23). Materials and Methods: The present randomized clinical trial was conducted on 162 subjects including 57 hemodialysis patients, 29 peritoneal dialysis patients, 48 kidney transplant recipients, and 28 healthy controls. The participants received a single-dose pneumococcal vaccine (Pneumovax 23) of 0.5 ml in the upper limb muscle. The efficacy of vaccination was evaluated by measuring the antibody response to the entire vaccine. Serum samples were collected before, one and six months after vaccination. Results: The levels of IgG pneumococcal antibodies at pre-vaccination periods, one and six months after vaccination were 11.6±1.52 IU/ml, 14.98±1.98 IU/ml and 14.87±0.66 IU/ml in kidney transplant recipients, 12.03±1.93 IU/ml, 15.26±0.49 IU/ml and 14.3±0.72 IU/ml in hemodialysis patients, and 11.5±1.55 IU/ml, 15.2±1.81 IU/ml, and 14.2±1.7 IU/ml, respectively. The serum antibody level was significantly higher in kidney transplant recipients than in both dialysis groups after six months of vaccination (p=0.029). Conclusion: We found that patients with renal failure respond to pneumococcal vaccination in hemodialysis and kidney transplantation. However, they lost their serum antibodies within six months of vaccination. Determining the protective level for serum IGG and IGG2 in these patients helps us to follow up on these patients more precisely in order to re-vaccinate when the protective level of serum antibody is broken.

Accuracy of the estimation of V and the implications this has when applying Kt/Vurea for measuring dialysis dose in peritoneal dialysis.

Current guidelines for the prescription of peritoneal dialysis dose rely on a single cut-off 'minimal' value of Kt/V. To apply this in the clinic, this requires an accurate estimation of V, the volume of urea distribution that equates to the total body water (TBW). This analysis sought to determine the accuracy to which V can be estimated. A literature search was undertaken of studies comparing TBW estimation using two or three of the following methods: isotopic dilution (gold standard), anthropometric equations (e.g. Watson formula) and bioimpedance analysis. Studies of healthy and dialysis populations of all ages were included. Mean differences and 95% limits of agreement (LOA) were extracted and pooled. In 44 studies (31 including dialysis subjects), the between-method population means were typically within 1-1.5 L of each other, although larger bias was seen when applying anthropometric equations to different racial groups. However, the 95% LOA for all comparisons were consistently wide, typically ranging ±12-18% of the TBW. For a typical individual whose TBW is 35 L with a measured Kt/V of 1.7, this translates into a range of Kt/V 1.4-2.05. There are limitations to the accuracy of estimation of V which call into question the validity of applying a single threshold Kt/V value as indicative of adequate dialysis. This should be taken into account in guideline development such that if a target Kt/V was deemed appropriate that this should be expressed as a range; alternatively single targets should be avoided and dialysis dose should be determined according to patient need.

Some parting words.

Some parting words.

Evaluate the Efficacy and Safety of Multiple Roxadustat Dosing Regimens for the Treatment of Anemia in Dialysis Subjects With Chronic Kidney Disease

Evaluate the Efficacy and Safety of Multiple Roxadustat Dosing Regimens for the Treatment of Anemia in Dialysis Subjects With Chronic Kidney Disease

A Novel Heterozygous Deletion Variant in KLOTHO Gene Leading to Haploinsufficiency and Impairment of Fibroblast Growth Factor 23 Signaling Pathway.

Hyperphosphatemia is commonly present in end-stage renal disease. Klotho (KL) is implicated in phosphate homeostasis since it acts as obligate co-receptor for the fibroblast growth factor 23 (FGF23), a major phosphaturic hormone. We hypothesized that genetic variation in the KL gene might be associated with alterations in phosphate homeostasis resulting in hyperphosphatemia. We performed sequencing for determining KL gene variants in a group of resistant hyperphosphatemic dialysis patients. In a 67-year-old female, blood DNA sequencing revealed a heterozygous deletion of a T at position 1041 (c.1041delT) in exon 2. This variation caused a frameshift with substitution of isoleucine for phenylalanine and introduction of a premature termination codon (p.Ile348Phefs*28). cDNA sequencing showed absence of deletion-carrier transcripts in peripheral blood mononuclear cells suggesting degradation of these through a nonsense-mediated RNA decay pathway. Experiments in vitro showed that p.Ile348Phefs*28 variant impaired FGF23 signaling pathway, indicating a functional inactivation of the gene. In the patient, serum levels of KL were 2.9-fold lower than the mean level of a group of matched dialysis subjects, suggesting a compromise in the circulating protein concentration due to haploinsufficiency. These findings provide a new loss-of-function variant in the human KL gene, suggesting that genetic determinants might be associated to clinical resistant hyperphosphatemia.

A randomized controlled trial of different serum phosphate ranges in subjects on hemodialysis

BackgroundHyperphosphataemia in dialysis subjects is associated with increased mortality. However cause and effect has not been proven, and the ideal phosphate target range is unknown despite KDOQI’s call for studies over 12 years ago. The design and conduct of a randomized controlled trial is challenging because maintaining two groups within differing target ranges of serum phosphate has not been achieved over a long follow-up of 1 year, in a trial setting, before. The SPIRiT study examines the subject acceptance, recruitment and retention rates for such a study in which subjects were randomised to two distinct serum phosphate concentrations, then titrated and maintained over 12 months.MethodsA two center trial of 104 hemodialysis subjects randomized to lower range LRG 0.8–1.4 mmol/L or 2.5–4.3 mg/dL) and higher range (HRG 1.8–2.4 mmol/L or 5.6–7.4 mg/dL) serum phosphate groups. Two months’ titration and ten months’ maintenance phase. Interventions were non-calcium phosphate binders, self-help questionnaires, with blood tests at specified time intervals.ResultsThirteen percent of the eligible dialysis population were successfully recruited. A mean separation by serum phosphate of 1.1 mg/dL was achieved and maintained between the groups over 10 months. Drop-out rate was 27% with mortality 10%. Nine subjects in the HRG (17.6%) and two subjects in the LRG (3.8%) died during the study, however the study was not powered to detect significant differences in outcomes.ConclusionRandomizing dialysis subjects to separate treatment targets for serum phosphate can achieve a clinically significant sustained separation over 12 months. A large scale longer term study is required to examine outcomes including mortality.Trial registrationThe trial registration number is ISRCTN24741445 – Date of registration 16th January, retrospectively registered.

Determinants of Left Ventricular Characteristics Assessed by Cardiac Magnetic Resonance Imaging and Cardiovascular Biomarkers Related to Kidney Transplantation.

Background:Cardiac magnetic resonance (CMR) imaging accurately and precisely measures left ventricular (LV) mass and function. Identifying mechanisms by which LV mass change and functional improvement occur in some end-stage kidney disease (ESKD) patients may help to appropriately target kidney transplant (KT) recipients for further investigation and intervention. The concentration of serum adiponectin, a cardiovascular biomarker, increases in cardiac failure, its production being enhanced by B-type natriuretic peptide (BNP), and both serum adiponectin and BNP concentrations decline posttransplantation.Objective:We tested the hypothesis that kidney transplantation alters LV characteristics that relate to serum adiponectin concentrations.Design:Prospective and observational cohort study.Setting:The study was performed at 3 adult kidney transplant and dialysis centers in Ontario, Canada.Patients:A total of 82 KT candidate subjects were recruited (39 to the KT group and 43 to the dialysis group). Predialysis patients were excluded.Measurements:Subjects underwent CMR with a 1.5-tesla whole-body magnetic resonance scanner using a phased-array cardiac coil and retrospective vectorographic gating. LV mass, LV ejection fraction (LVEF), LV end-systolic volume (LVESV), and LV end-diastolic volume (LVEDV) were measured by CMR pre-KT and again 12 months post-KT (N = 39), or 12 months later if still receiving dialysis (N = 43). LV mass, LVESV, and LVEDV were indexed for height (m2.7) to calculate left ventricular mass index (LVMI), left ventricular end-systolic volume index (LVESVI), and left ventricular end-diastolic volume index (LVEDVI), respectively. Serum total adiponectin and N-terminal proBNP (NT-proBNP) concentrations were measured at baseline, 3 months, and 12 months.Methods:We performed a prospective 1:1 observational study comparing KT candidates with ESKD either receiving a living donor organ (KT group) or waiting for a deceased donor organ (dialysis group).Results:Left ventricular mass index change was −1.98 ± 5.5 and −0.36 ± 5.7 g/m2.7 for KT versus dialysis subjects (P = .44). Left ventricular mass change was associated with systolic blood pressure (SBP) (P = .0008) and average LV mass (P = .0001). Left ventricular ejection fraction did not improve (2.9 ± 6.6 vs 0.7 ± 4.9 %, P = .09), while LVESVI and LVEDVI decreased more post-KT than with continued dialysis (−3.36 ± 5.6 vs −0.22 ± 4.4 mL/m2.7, P < .01 and −4.9 ± 8.5 vs −0.3 ± 9.2 mL/m2.7, P = .02). Both adiponectin (−7.1 ± 11.3 vs −0.11 ± 7.9 µg/mL, P < .0001) and NT-proBNP (−3811 ± 8130 vs 1665 ± 20013 pg/mL, P < .0001) declined post-KT. Post-KT adiponectin correlated with NT-proBNP (P = .001), but not estimated glomerular filtration rate (eGFR) (P = .13). Change in adiponectin did not correlate with change in LVEF in the KT group (Spearman ρ = 0.16, P = .31) or dialysis group (Spearman ρ = 0.19, P = .21).Limitations:Few biomarkers of cardiac function were measured to fully contextualize their role during changing kidney function. Limited intrapatient biomarker sampling and CMR measurements precluded constructing dose-response curves of biomarkers to LV mass and function. The CMR timing in relation to dialysis was not standardized.Conclusions:The LVESVI and LVEDVI but not LVMI or LVEF improve post-KT. LVMI and LVEF change is independent of renal function and adiponectin. As adiponectin correlates with NT-proBNP post-KT, improved renal function through KT restores the normal heart-endocrine axis.

DASS21: A Useful Tool in the Psychological Profile Evaluation of Dialysis Patients

BackgroundThe effect of dialysis treatment is complex, with both clinical and socio-psychological effects. In this study, we aimed to assess the psychological status of this growing population of end-stage renal disease. MethodsUsing the Short Form of Depression, Anxiety and Stress Scale (DASS21) questionnaire, we aimed (1) to measure the psychological states of hemodialysis (HD) or peritoneal dialysis (PD) subjects from 15 sites, (2) to compare DASS21 scores between HD and PD, and (3) to identify the associated demographic and medical factors of better psychological states. ResultsA total of 1,332 were eligible for analysis. Stress (48%) recorded the highest negative emotional states, followed by depression (37%) and anxiety (20%). By multivariate analysis, normal body mass index weight status, religion and absence of coronary artery disease were associated with lower score for depression, anxiety and stress, respectively. Tertiary education was associated with the lowest score in depression and anxiety, whereas HD had a lower score in stress than PD. A younger age was associated with worse DASS21 score of anxiety and stress. ConclusionsObesity, religion and coronary artery disease were significantly associated with all 3 symptoms of depression, anxiety and stress. Older age has a protective effect on anxiety and stress. Further study is needed to evaluate the relationship between these significant factors and each psychological state.

PP-13 An analysis of the applications for a paediatric investigation plan (pip) for indications in uro-nephrology

Introduction In order to assess the requirements of the European Medical Agency (EMA) for paediatric clinical trials in nephrology we assessed the decisions on Paediatric Investigation Plans (PIPs), which are required to get approval for new drugs. Paediatric nephrology comprises rare indications, but also frequent paediatric conditions. Clinical trials are needed in order to base therapy on ev-idence, but the relevant population can be very small in paediatric nephrology. Methods All 20 decisions on PIPs published by the EMA on the EMA website under ‘uro-nephrology’ were includ-ed. Data are presented as proportions (categorical data) and median (range) (numerical data). Results Full and partial waivers: 7 of the published decisions granted a full waiver (i.e., no paediatric studies required). For the remaining 13, a PIP was agreed. For 6 of those 13 PIPs, a partial waiver was granted for certain ages (0–6 months (2x), 0–5, 0–6, 0–8, 12–18 years.Agreed PIPs: The PIPs require the conduct of 0–3 (median 1) quality studies, 0–2 (median 0) non-clinical studies, and 1–6 (median 3) clinical studies. As there are ca. 9 paediatric dialysis subjects per million of all paediatric subjects, an estimate of the number of paediatric dialysis patients in EU is roughly ca. 400 patients. At least 4 PIPs require in-clusion of paediatric dialysis subjects, requiring 14 clinical studies, i.e., ca. 14 subjects are available for each of those studies. There are no concessions in powering the studies, and therefore, the required numbers will be much higher than the available number of subjects in EU. Time for decision and time for completion of PIP: The time between start of the procedure and the decision of the PdCo/EMA was 103 days (35–468 days). The time between the date of decision of the PdCO/EMA and the date of the required completion of the PIP ranged from 0.03 years – 13.47 years (median 4.84 years). Conclusion All partial waivers affected the lowest age groups. Although the youngest age groups need an eval-uation of new substances most urgently, the number of granted partial waivers indicates how difficult it is to con-duct clinical trials in this subpopulation. However, only 4 of the 13 agreed PIPs are concerned with frequent indi-cations, while 9 of those aim at rare indications. For those 9, a median of 3 clinical studies is required. It is unlikely that the required number of subjects can realistically be recruited. Further, the required studies make the timely conduct (median time 4.84 years) and completion at the same time as the studies in adults questionable. This could delay approval in adults. In summary, we show some im-balances: a) studies are most difficult in infants, but they need them most, b) the number of subjects required does not fit the indication epidemiology, c) timelinies for com-pleting paediatric studies are difficult to meet.

De novo weekly and biweekly darbepoetin alfa dosing in pediatric patients with chronic kidney disease.

Darbepoetin alfa is a commonly prescribed erythropoiesis-stimulating agent (ESA) for correcting anemia in pediatric chronic kidney disease (CKD) patients. However, little information exists on its use in ESA-naïve patients. This study evaluated the efficacy and safety of darbepoetin alfa in pediatric patients initiating ESA therapy. One-hundred sixteen pediatric ESA-naïve subjects (aged 1-18years) with CKD stages 3-5D and hemoglobin (Hb) <10g/dl from 43 centers in the US, Europe, and Mexico were randomized by age (three groups) and dialysis status (yes vs. no) to receive darbepoetin alfa once weekly (QW) or every 2weeks (Q2W) subcutaneously (not on dialysis and peritoneal dialysis subjects) and intravenously (hemodialysis subjects). The drug was titrated to achieve Hb levels of 10.0-12.0g/dl over 25weeks. Patient- and parent-reported health-related outcomes were measured by the Pediatric Quality of Life Inventory (PedsQL™) in children ≥2years. In both groups, mean Hb concentrations increased to ≥11.0g/dl over the first 3months of treatment and remained stable within the 10.0-12.0g/dl target range. The median time to achieve hemoglobin ≥10g/dl was slightly longer for subjects <12years (QW and Q2W, both 28days) vs. those ≥12years (23 and 22days, respectively). Adverse event profiles were similar between groups, with QW, four (7%) and Q2W, five (9%). PedsQL™ scores showed modest increases. Darbepoetin alfa can be safely administered either QW or Q2W to ESA-naïve pediatric patients with CKD-related anemia to achieve Hb targets of 10.0-12.0g/dl.

Health care providers' support of patients' autonomy, phosphate medication adherence, race and gender in end stage renal disease.

This study was designed to assess dialysis subjects' perceived autonomy support association with phosphate binder medication adherence, race and gender. A multi-site cross-sectional study was conducted among 377 dialysis subjects. The Health Care Climate (HCC) Questionnaire assessed subjects' perception of their providers' autonomy support for phosphate binder use, and adherence was assessed by the self-reported Morisky Medication Adherence Scale. Serum phosphorus was obtained from the medical record. Regression models were used to examine independent factors of medication adherence, serum phosphorus, and differences by race and gender. Non-white HCC scores were consistently lower compared with white subjects' scores. No differences were observed by gender. Reported phosphate binder adherence was associated with HCC score, and also with phosphorus control. No significant association was found between HCC score and serum phosphorus. Autonomy support, especially in non-white end stage renal disease subjects, may be an appropriate target for culturally informed strategies to optimize mineral bone health.

A Study on Bacteriological Profile of Blood Culture Sample from Dialysis Patients

Hemodialysis and peritoneal dialysis are reasons for chronic glomerulonephritis, diabetic nephropathy, polycystic kidney disease, chronic interstitial nephritis, and vasculitis. Dialysis is lifesaving for kidney malfunctioned patients, and in the absence of this intervention, kidneys no longer function resulting in the death of the patients due to electrolyte abnormalities and build up of toxins in the blood stream. Coinfection with other bacterial or fungal organisms is observed more frequently in dialysis failure patients. The study population had a total of 144 adult dialysis subjects comprising 78 male (55%) and 66 female (45%). Among them, blood samples of 32 patients (22% of total study population) were found to be infected with pathogenic bacteria as these samples were positive to culture. All these isolates were distinguished at the species level. Finally, it is concluded that the dialysis patients have to be often screened and diagnosed for bacterial infections. Broad spectrum of antibiotics may be prescribed if symptoms of bacterial infections suspected before diagnosis. Earlier diagnosis with prescription of appropriate dose of drugs will not only enable to avoid the morbidity of bacterial infections but also prevent the infection associated complications and thereby reduce the mortality.

Lipoprotein profile, lipoprotein-associated phospholipase A2 and cardiovascular risk in hemodialysis patients.

Cardiovascular disease is the leading cause of morbidity and mortality in hemodialysis patients; the increased risk of cardiovascular disease is due to accelerated atherosclerosis, inflammation and impaired lipoprotein metabolism. We aimed to evaluate lipoprotein-associated phospholipase A2 (Lp-PLA2) and some pro-inflammatory aspects of the lipoprotein profile in dialyzed patients in order to evaluate the relationship with the accelerated atherosclerosis and vascular accidents. In 102 dialysis patients and 40 non-uremic controls, we investigated the lipoprotein plasma profile, high sensitivity C-reactive protein (CRP), ceruloplasmin and serum amyloid A protein (SAA), and followed patients for 1year to analyze the risk of acute cardiovascular events. Total cholesterol, low-density lipoprotein and high-density lipoprotein plasma levels were significantly lower in uremic patients than controls, whereas CRP, SAA, ceruloplasmin, Lp-PLA2 and their ratio with apolipoprotein A1 were significantly higher. Patients with Lp-PLA2 levels >194nmol/min/ml had more acute cardiovascular events than patients with lower values. Our results show that in dialysis subjects: (1) low-density lipoproteins show a more atherogenic phenotype than in the general population; (2) high-density lipoproteins are less anti-inflammatory; (3) Lp-PLA2 could potentially be used to evaluate cardiovascular risk.