A systematic review of patient and health system characteristics associated with late referral in chronic kidney disease

<p>Abstract</p> <p>Background</p> <p>To identify patient and health system characteristics associated with late referral of patients with chronic kidney disease to nephrologists.</p> <p>Methods</p> <p>MEDLINE, CENTRAL, and CINAHL were searched using the appropriate MESH terms in March 2007. Two reviewers individually and in duplicate reviewed the abstracts of 256 articles and selected 18 observational studies for inclusion. The reasons for late referral were categorized into patient or health system characteristics. Data extraction and content appraisal were done using a prespecified protocol.</p> <p>Results</p> <p>Older age, the existence of multiple comorbidities, race other than Caucasian, lack of insurance, lower socioeconomic status and educational levels were patient characteristics associated with late referral of patients with chronic kidney disease. Lack of referring physician knowledge about the appropriate timing of referral, absence of communication between referring physicians and nephrologists, and dialysis care delivered at tertiary medical centers were health system characteristics associated with late referral of patients with chronic kidney disease. Most studies identified multiple factors associated with late referral, although the relative importance and the combined effect of these factors were not systematically evaluated.</p> <p>Conclusion</p> <p>A combination of patient and health system characteristics is associated with late referral of patients with chronic kidney disease. Overall, being older, belonging to a minority group, being less educated, being uninsured, suffering from multiple comorbidities, and the lack of communication between primary care physicians and nephrologists contribute to late referral of patients with chronic kidney disease. Both primary care physicians and nephrologists need to engage in multisectoral collaborative efforts that ensure patient education and enhance physician awareness to improve the care of patients with chronic kidney disease.</p

Maintaining over time Clinical Performance targets on Anaemia correction in unselected population on chronic dialysis at 20 Italian Centres. Data from a retrospective study for a Clinical Audit

<p>Abstract</p> <p>Background</p> <p>The Italian and European Best Practice Guidelines (EBPG) recommend a target haemoglobin value greater than 11 g/dl in most patients with Chronic Kidney Diseases. However, it is still difficult to maintain these values at a steady rate. Thus, the main aim of the study was to evaluate, throughout 2005, how many patients steadily maintained the performance targets related to anaemia treatment.</p> <p>Methods</p> <p>The survey was conducted on 3283 patients on haemodialysis (HD) and peritoneal dialysis (PD) at 20 Italian dialysis centres. 540 patients were randomly selected; each centre provided a statistically significant sample proportional to its total number of patients. Maintenance of the following target levels was assessed over time: Haemoglobin (HB) 11-12 gr/dl; Iron: 60-160 mcg/dl; Ferritin: 30-400 mcg/l; Transferrin: 200-360 mg/dl; Transferrin saturation percentage (TSAT %):> 25 <50; Dialysis doses (KT/V): >1.2 <2.0 for non-diabetic HD patients; >1.5 <2.2 for diabetic HD patients; DP: >1.8 <2.5.</p> <p>Outcome included:</p> <p indent="1">1- Percentage of target maintenance for each parameter.</p> <p indent="1">2- Erythropoietin dose in relation to dialysis techniques, presence of cancer or myeloma, diabetic status, Vitamin B therapy.</p> <p indent="1">3- Erythropoietin dose (International Units/kg/week) (IU/kg/wk) depending on: haemoglobin values, hospitalization of more than 3 days.</p> <p>Results</p> <p>Mean age was 65.1; mean haemoglobin concentration over the whole population was 11.3 gr/dl (Standard Deviation (SD): 0.91). The clinical performance targets were maintained over time as follows: HB: 4.3% (Mean 11.43 gr/dl) (SD: 0.42); Ferritin: 71.1% (Mean: 250.23 mcg/L (SD:104.07); Iron: 95.0% (Mean 59.79 mcg/dl)(SD:16.76); Transferrin: 44.8% (Mean 216.83 mg/dl) (SD: 19,50); TSAT %: in 8.4% (Mean: 34.33% (SD: 6.56); HD KT/V: 61.0% (Mean:1.46) (SD: 0.7); PD KT/V:31.4% (Mean: 2.10) (SD: 0.02). The average weekly dose of Erythropoietin (IU/Kg/Wk) was significantly lower for the peritoneal dialysis technique; the higher haemoglobin values, the lower the Erythropoietin dose (IU/Kg/Wk).</p> <p>Conclusion</p> <p>A very low percentage of patients maintained haemoglobin target values over time. We need to identify precise criteria to evaluate the stability over time of clinical performance targets proposed by the guidelines.</p

Duplication of 7q34 is specific to juvenile pilocytic astrocytomas and a hallmark of cerebellar and optic pathway tumours

BACKGROUND: Juvenile pilocytic astrocytomas (JPA), a subgroup of low-grade astrocytomas (LGA), are common, heterogeneous and poorly understood subset of brain tumours in children. Chromosomal 7q34 duplication leading to fusion genes formed between KIAA1549 and BRAF and subsequent constitutive activation of BRAF was recently identified in a proportion of LGA, and may be involved in their pathogenesis. Our aim was to investigate additional chromosomal unbalances in LGA and whether incidence of 7q34 duplication is associated with tumour type or location. METHODS AND RESULTS: Using Illumina-Human-Hap300-Duo and 610-Quad high-resolution-SNP-based arrays and quantitative PCR on genes of interest, we investigated 84 paediatric LGA. We demonstrate that 7q34 duplication is specific to sporadic JPA (35 of 53-66%) and does not occur in other LGA subtypes (0 of 27) or NFI-associated-JPA (0 of 4). We also establish that it is site specific as it occurs in the majority of cerebellar JPA (24 of 30-80%) followed by brainstem, hypothalamic/optic pathway JPA (10 of 16-62.5%) and is rare in hemispheric JPA (1 of 7-14%). The MAP-kinase pathway, assessed through ERK phosphorylation, was active in all tumours regardless of 7q34 duplication. Gain of function studies performed on hTERT-immortalised astrocytes show that overexpression of wild-type BRAF does not increase cell proliferation or baseline MAPK signalling even if it sensitises cells to EGFR stimulation. CONCLUSIONS AND INTERPRETATION: Our results suggest that variants of JPA might arise from a unique site-restricted progenitor cell where 7q34 duplication, a hallmark of this tumour-type in association to MAPK-kinase pathway activation, potentially plays a site-specific role in their pathogenesis. Importantly, gain of function abnormalities in components of MAP-Kinase signalling are potentially present in all JPA making this tumour amenable to therapeutic targeting of this pathway. British Journal of Cancer (2009) 101, 722-733. doi: 10.1038/sj.bjc.6605179 www.bjcancer.com Published online 14 July 2009 (C) 2009 Cancer Research U

The importance of iron in long-term survival of maintenance hemodialysis patients treated with epoetin-alfa and intravenous iron: analysis of 9.5 years of prospectively collected data

<p>Abstract</p> <p>Background</p> <p>In patients treated by maintenance hemodialysis the relationship to survival of hemoglobin level and administered epoetin-alfa and intravenous iron is controversial. The study aim was to determine effects on patient survival of administered epoetin-alfa and intravenous iron, and of hemoglobin and variables related to iron status.</p> <p>Methods</p> <p>The patients were 1774 treated by maintenance hemodialysis in 3 dialysis units in New York, NY from January 1998 to June, 2007. A patient-centered, coded, electronic patient record used in patient care enabled retrospective analysis of data collected prospectively. For survival analysis, patients were censored when transplanted, transferred to hemodialysis at home or elsewhere, peritoneal dialysis. Univariate Kaplan-Meier analysis was followed by multivariate analysis with Cox's regression, using as variables age, race, gender, major co-morbid conditions, epoetin-alfa and intravenous iron administered, and 15 laboratory tests.</p> <p>Results</p> <p>Median age was 59 years, epoetin-alfa (interquartile range) 18,162 (12,099, 27,741) units/week, intravenous iron 301 (202, 455) mg/month, survival 789 (354, 1489) days. Median hemoglobin was 116 (110, 120)g/L, transferrin saturation 29.7 (24.9, 35.1)%, serum ferritin 526 (247, 833) μg/L, serum albumin 39.0 (36.3, 41.5) g/L. Survival was better the higher the hemoglobin, best with > 120 g/L. Epoetin-alfa effect on survival was weak but had statistically significant interaction with intravenous iron. For intravenous iron, survival was best with 1–202 mg/month, slightly worse with 202–455 mg/month; it was worst with no intravenous iron, only slightly better with > 455 mg/month. Survival was worst with transferrin saturation ≤ 16%, serum ferritin ≤ 100 μg/L, best with transferrin saturation > 25%, serum ferritin > 600 μg/L The effects of each of hemoglobin, intravenous iron, transferrin saturation, and serum ferritin on survival were independently significant and not mediated by other predictors in the model.</p> <p>Conclusion</p> <p>Long term survival of maintenance hemodialysis patients was favorably affected by a relatively high hemoglobin level, by moderate intravenous iron administration, and by indicators of iron sufficiency. It was unfavorably influenced by a low hemoglobin level, and by indicators of iron deficiency.</p

Inhibitory effect on expression of angiogenic factors by antiangiogenic agents in renal cell carcinoma

Since it has been widely recognised that renal cell carcinoma is refractory to standard therapies such as chemotherapy and radiotherapy, a new modality of treatment is needed. One of the potential alternative therapies for renal cell carcinoma may be inhibition of angiogenesis. In this study, we analysed the inhibitory effects of several potential agents on expression of angiogenic factors such as vascular endothelial growth factor and basic fibroblast growth factor, which are the main mediators in angiogenesis of renal cell carcinoma. We used medroxyprogesterone acetate, interferon-alpha, interferon-gamma, minocycline hydrochrolide and genistein, which are known to be antiangiogeneic. Northern blot analyses revealed that, among the five agents examined, genistein had a strong inhibitory effect on expression of vascular endothelial growth factor mRNA and basic fibroblast growth factor mRNA. Medroxyprogesterone acetate and interferon-alpha did not significantly decrease the level of either vascular endothelial growth factor mRNA or basic fibroblast growth factor mRNA. Interferon-gamma and minocycline had mild inhibitory effects on vascular endothelial growth factor mRNA and basic fibroblast growth factor mRNA expression. Genistein also inhibited both vascular endothelial growth factor mRNA and basic fibroblast growth factor mRNA expression after treatment with epidermal growth factor and hypoxia. These findings suggest that one of the mechanisms of the inhibition of angiogenesis by genistein is suppression of the expression of the angiogenic factors vascular endothelial growth factor and basic fibroblast growth factor in renal cell carcinoma

Prevalence of chronic kidney disease in population-based studies: Systematic review

which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background: Chronic kidney disease (CKD) is becoming a major public health problem worldwide. This article reviews the published evidence of prevalence of CKD in population-based study samples that used the standardized definition from the Kidney Disease Outcomes Quality Initiative of the National Kidney Foundation (K/DOQI) practice guideline, and particularly focus on performance of serum-creatinine based equations for GFR estimation. We provide a summary of available data about the burden of CKD in various populations. Methods: We performed a systematic review of available published data in MEDLINE. A combination of various keywords relevant to CKD was used in this research. Related data of included studies were extracted in a systematic way. Results: A total of 26 studies were included in this review. The studies were conducted in different populations, and the number of study participants ranged from 237 to 65181. The median prevalence of CKD was 7.2 % in persons aged 30 years or older. In persons aged 64 years or older prevalence of CKD varied from 23.4 % to 35.8%. Importantly, the prevalence of CKD strongl

End-stage renal disease in young black males in a black-white population: longitudinal analysis of the Bogalusa Heart Study

<p>Abstract</p> <p>Background</p> <p>Risk factors in childhood create a life-long burden important in the development of cardiovascular (CV) disease in adulthood. Many risk factors for CV disease (e.g., hypertension) also increase the risk of renal disease. However, the importance of childhood risk factors on the development of chronic kidney disease and end-stage renal disease (ESRD) is not well characterized.</p> <p>Methods</p> <p>The current observations include data from Bogalusa Heart Study participants who were examined multiple times as children between 1973 and 1988.</p> <p>Results</p> <p>Through 2006, fifteen study participants subsequently developed ESRD in adulthood; seven with no known overt cause. Although the Bogalusa Heart Study population is 63% white and 37% black and 51% male and 49% female, all seven ESRD cases with no known overt cause were black males (p < 0.001). Mean age-adjusted systolic and diastolic blood pressure in childhood was higher among the ESRD cases (114.5 mmHg and 70.1 mmHg, respectively) compared to black (103.0 mmHg and 62.3 mmHg, respectively) and white (mean = 103.3 mmHg and 62.3 mmHg, respectively) boys who didn't develop ESRD. The mean age-adjusted body mass index in childhood was 23.5 kg/m²among ESRD cases and 18.6 kg/m²and 18.9 kg/m²among black and white boys who didn't develop ESRD, respectively. Plasma glucose in childhood was not significantly associated with ESRD.</p> <p>Conclusion</p> <p>These data suggest black males have an increased risk of ESRD in young adulthood. Elevated body mass index and blood pressure in childhood may increase the risk for developing ESRD as young adults.</p

Turtle Carapace Anomalies: The Roles of Genetic Diversity and Environment

Background: Phenotypic anomalies are common in wild populations and multiple genetic, biotic and abiotic factors might contribute to their formation. Turtles are excellent models for the study of developmental instability because anomalies are easily detected in the form of malformations, additions, or reductions in the number of scutes or scales. Methodology/Principal Findings: In this study, we integrated field observations, manipulative experiments, and climatic and genetic approaches to investigate the origin of carapace scute anomalies across Iberian populations of the European pond turtle, Emys orbicularis. The proportion of anomalous individuals varied from 3 % to 69 % in local populations, with increasing frequency of anomalies in northern regions. We found no significant effect of climatic and soil moisture, or climatic temperature on the occurrence of anomalies. However, lower genetic diversity and inbreeding were good predictors of the prevalence of scute anomalies among populations. Both decreasing genetic diversity and increasing proportion of anomalous individuals in northern parts of the Iberian distribution may be linked to recolonization events from the Southern Pleistocene refugium. Conclusions/Significance: Overall, our results suggest that developmental instability in turtle carapace formation might be caused, at least in part, by genetic factors, although the influence of environmental factors affecting the developmental stability of turtle carapace cannot be ruled out. Further studies of the effects of environmental factors, pollutants an

TNFα Cooperates with IFN-γ to Repress Bcl-xL Expression to Sensitize Metastatic Colon Carcinoma Cells to TRAIL-mediated Apoptosis

BACKGROUND: TNF-related apoptosis-inducing ligand (TRAIL) is an immune effector molecule that functions as a selective anti-tumor agent. However, tumor cells, especially metastatic tumor cells often exhibit a TRAIL-resistant phenotype, which is currently a major impediment in TRAIL therapy. The aim of this study is to investigate the synergistic effect of TNFα and IFN-γ in sensitizing metastatic colon carcinoma cells to TRAIL-mediated apoptosis. METHODOLOGY/PRINCIPAL FINDINGS: The efficacy and underlying molecular mechanism of cooperation between TNFα and IFN-γ in sensitizing metastatic colon carcinoma cells to TRAIL-mediated apoptosis were examined. The functional significance of TNFα- and IFN-γ-producing T lymphocyte immunotherapy in combination with TRAIL therapy in suppression of colon carcinoma metastasis was determined in an experimental metastasis mouse model. We observed that TNFα or IFN-γ alone exhibits minimal sensitization effects, but effectively sensitized metastatic colon carcinoma cells to TRAIL-induced apoptosis when used in combination. TNFα and IFN-γ cooperate to repress Bcl-xL expression, whereas TNFα represses Survivin expression in the metastatic colon carcinoma cells. Silencing Bcl-xL expression significantly increased the metastatic colon carcinoma cell sensitivity to TRAIL-induced apoptosis. Conversely, overexpression of Bcl-xL significantly decreased the tumor cell sensitivity to TRAIL-induced apoptosis. Furthermore, TNFα and IFN-γ also synergistically enhanced TRAIL-induced caspase-8 activation. TNFα and IFN-γ was up-regulated in activated primary and tumor-specific T cells. TRAIL was expressed in tumor-infiltrating immune cells in vivo, and in tumor-specific cytotoxic T lymphocytes (CTL) ex vivo. Consequently, TRAIL therapy in combination with TNFα/IFN-γ-producing CTL adoptive transfer immunotherapy effectively suppressed colon carcinoma metastasis in vivo. CONCLUSIONS/SIGNIFICANCE: TNFα and IFN-γ cooperate to overcome TRAIL resistance at least partially through enhancing caspase 8 activation and repressing Bcl-xL expression. Combined CTL immunotherapy and TRAIL therapy hold great promise for further development for the treatment of metastatic colorectal cancer