Hypertension-misattributed kidney disease in African Americans

Lipkowitz et al. extend the African American Study of Kidney Disease and Hypertension to the level of genetic epidemiology, in a case–control study design. Analysis of genotypes at the APOL1 kidney disease risk region supports a paradigm shift in which genetic risk is proximate to both kidney disease and hypertension. The findings mandate urgency in clarifying mechanisms whereby APOL1 region risk variants interact with environmental triggers to cause progressive kidney disease accompanied by dangerous hypertension

The Diagnostic Value of the Pleural Fluid C-Reactive Protein in Parapneumonic Effusions

properly cited. Purpose. The aim of this study was to evaluate the sensitivity of pleural C-reactive protein (CRP) biomarker levels in identifying parapneumonic effusions. Methods. A single-center, retrospective review of 244 patients diagnosed with pleural effusions was initiated among patients at the Rabin Medical Center, Petah Tikva, Israel, between January 2011 and December 2013. The patients were categorized into 4 groups according to their type of pleural effusion as follows: heart failure, malignant, postlung transplantation, and parapneumonic effusion. Results. The pleural CRP levels significantly differentiated the four groups ( < 0.001) with the following means: parapneumonic effusion, 5.38 ± 4.85 mg/dL; lung transplant, 2.77 ± 2.66 mg/dL; malignancy, 1.19±1.51 mg/dL; and heart failure, 0.57±0.81 mg/dL. The pleural fluid CRP cut-off value for differentiating among parapneumonic effusions and the other 3 groups was 1.38 mg/dL. The sensitivity, specificity, positive predictive value, and negative predictive value were 84.2%, 71.5%, 37%, and 95%, respectively. A backward logistic regression model selected CRP as the single predictor of parapneumonic effusion (OR = 1.59, 95% CI = 1.37-1.89). Conclusions. Pleural fluid CRP levels can be used to distinguish between parapneumonic effusions and other types of exudative effusions. CRP levels < 0.64 mg/dL are likely to indicate a pleural effusion from congestive heart failure, whereas levels ≥ 1.38 mg/dL are suggestive of an infectious etiology

Preliminary Report: Missense mutations in the APOL gene family are associated with end stage kidney disease risk previously attributed to the MYH9 gene

MYH9 has been proposed as a major genetic risk locus for a spectrum of non-diabetic end stage kidney disease (ESKD). We use recently released sequences from the 1000 Genomes Project to identify two western African specific missense mutations (S342G and I384M) in the neighbouring APOL1 gene, and demonstrate that these are more strongly associated with ESKD than previously reported MYH9 variants. We also show that the distribution of these risk variants in African populations is consistent with the pattern of African ancestry ESKD risk previously attributed to the MYH9 gene. Additional associations were also found among other members of the APOL gene family, and we propose that ESKD risk is caused by western African variants in members of the APOL gene family, which evolved to confer protection against pathogens, such as Trypanosoma.Comment: 25 pages, 6 figure

African ancestry allelic variation at the MYH9 gene contributes to increased susceptibility to non-diabetic end-stage kidney disease in Hispanic Americans

Recent studies identified MYH9 as a major susceptibility gene for common forms of non-diabetic end-stage kidney disease (ESKD). A set of African ancestry DNA sequence variants comprising the E-1 haplotype, was significantly associated with ESKD. In order to determine whether African ancestry variants are also associated with disease susceptibility in admixed populations with differing genomic backgrounds, we genotyped a total of 1425 African and Hispanic American subjects comprising dialysis patients with diabetic and non-diabetic ESKD and controls, using 42 single nucleotide polymorphisms (SNPs) within the MYH9 gene and 40 genome-wide and 38 chromosome 22 ancestry informative markers. Following ancestry correction, logistic regression demonstrated that three of the E-1 SNPs are also associated with non-diabetic ESKD in the new sample sets of both African and Hispanic Americans, with a stronger association in Hispanic Americans. We also identified MYH9 SNPs that are even more powerfully associated with the disease phenotype than the E-1 SNPs. These newly associated SNPs, could be divided into those comprising a haplotype termed S-1 whose association was significant under a recessive or additive inheritance mode (rs5750248, OR 4.21, P < 0.01, Hispanic Americans, recessive), and those comprising a haplotype termed F-1 whose association was significant under a dominant or additive inheritance mode (rs11912763, OR 4.59, P < 0.01, Hispanic Americans, dominant). These findings strengthen the contention that a sequence variant of MYH9, common in populations with varying degrees of African ancestry admixture, and in strong linkage disequilibrium with the associated SNPs and haplotypes reported herein, strongly predisposes to non-diabetic ESKD

The Envy of Scholars: Applying the Lessons of the Framingham Heart Study to the Prevention of Chronic Kidney Disease

During the past 50 years, a dramatic reduction in the mortality rate associated with cardiovascular disease has occurred in the US and other countries. Statistical modeling has revealed that approximately half of this reduction is the result of risk factor mitigation. The successful identification of such risk factors was pioneered and has continued with the Framingham Heart Study, which began in 1949 as a project of the US National Heart Institute (now part of the National Heart, Lung, and Blood Institute). Decreases in total cholesterol, blood pressure, smoking, and physical inactivity account for 24%, 20%, 12%, and 5% reductions in the mortality rate, respectively. Nephrology was designated as a recognized medical professional specialty a few years later. Hemodialysis was first performed in 1943. The US Medicare End-Stage Renal Disease (ESRD) Program was established in 1972. The number of patients in the program increased from 5,000 in the first year to more than 500,000 in recent years. Only recently have efforts for risk factor identification, early diagnosis, and prevention of chronic kidney disease (CKD) been undertaken. By applying the approach of the Framingham Heart Study to address CKD risk factors, we hope to mirror the success of cardiology; we aim to prevent progression to ESRD and to avoid the cardiovascular complications associated with CKD. In this paper, we present conceptual examples of risk factor modification for CKD, in the setting of this historical framework

Linkage disequilibrium analysis reveals an albuminuria risk haplotype containing three missense mutations in the cubilin gene with striking differences among European and African ancestry populations

Abstract Background A recent meta-analysis described a variant (p.Ile2984Val) in the cubilin gene (CUBN) that is associated with levels of albuminuria in the general population and in diabetics. Methods We implemented a Linkage Disequilibrium (LD) search with data from the 1000 Genomes Project, on African and European population genomic sequences. Results We found that the p.Ile2984Val variation is part of a larger haplotype in European populations and it is almost absent in west Africans. This haplotype contains 19 single nucleotide polymorphisms (SNPs) in very high LD, three of which are missense mutations (p.Leu2153Phe, p.Ile2984Val, p.Glu3002Gly), and two have not been previously reported. Notably, this European haplotype is absent in west African populations, and the frequency of each individual polymorphism differs significantly in Africans. Conclusions Genotyping of these variants in existing African origin sample sets coupled to measurements of urine albumin excretion levels should reveal which is the most likely functional candidate for albuminuria risk. The unique haplotypic structure of CUBN in different populations may leverage the effort to identify the functional variant and to shed light on evolution of the CUBN gene locus.</p

Emergence of an Israel faith-based community organization facilitating live donor kidney transplantation

Abstract Background The 2014 Consensus Conference on Best Practices in Living Kidney Donations recognized live donor kidney transplantation as the best treatment for late-stage kidney disease, yielding superior graft and patient survival, improved quality of life, fewer requirements for dialysis and increased cost-effectiveness compared to deceased donor kidney transplantation. Yet in spite of the excellent results of living kidney donation, the annual number of living kidney donors is declining in many countries, including the United States. In Israel, a non-profit organization, Matnat Chaim (“Gift of Life” in Hebrew), a faith-based initiative, has emerged as a major force for arranging living donor kidney transplantation mainly by facilitating altruistic living unrelated donor transplantation. Methods A retrospective review of the records of live kidney donations facilitated by the Matnat Chaim organization and referred to Israel transplant centers, since the organization’s inception in 2009, was performed and compared to published data from the Israel Ministry of Health. Results Matnat Chaim has facilitated 494 live kidney donations since its founding in February 2009 until the end of 2017. Of the 124 live kidney transplants performed in 2016, 111 (90%) were shown to be altruistic and unrelated. This large number of donations was associated with a doubling of the total number of kidney transplantations, performed in Israel (data published by the Israel Ministry of Health). Conclusions The success of an Israel community organization in the promotion of kidney transplantation may serve as a model for other religious and non-religious communities worldwide

Erratum to “Endobronchial Enigma: A Clinically Rare Presentation of Nocardia beijingensis in an Immunocompetent Patient”

Lan istripuek eraginiko heriotzen trataera, euskal prentsaren aldetik, aztergai dugu artikulu honetan. Horretarako 2001. eta 2009. urteetan Bizkaian izandako heriotzak aintzat hartu dira. Abiapuntuko hipotesia zera da: beste heriotza bortitz batzuetan ez bezala "esate baterako ETAk burututako atentatuetan edo Genero Indarkeriagaitik sortutakoetan, non hedabideen jarreretan izandako bilakaera azken urteotan nabarmena den" lan istripuen kasuan gertaerako kazetaritzatik oso hurbil dagoen beste ikuspegi bat mantentzen da. Gure azterketa osatzeko hainbat elkarrizketa egin zaie Euskal Herriko sindikatu nagusietako ordezkariei. Testu hau Zientzi eta Berrikuntzarako Ministerioak fintzatutako Ikerkerta Proiektu batean oinarrituta dago (CSO2010-19866, erreferiantziaduana, hain zuzen).; This article explores the evolution of the Basque print media"s approach to reporting labour fatalities, beginning with an analysis of press coverage of workplacerelated deaths in the Province of Biscay during the period 2001-2009. Our initial hypothesis held that the regional press policy of treating certain types of violent death (such as deaths related to violence perpetrated by Basque separatists and gender violence) as key social issues has been in sharp contrast to its perception and handling of labour-related fatalities, which have generally been treated as undifferentiated local news events and lumped together with items such as traffic accidents. This paper is part of a wider research project financed by the Ministry of Science and Innovation titled "The evolution of newspaper coverage of violent deaths in the Basque Country" (reference CSO2010-19866).; En este artículo se analiza la evolución en el tratamiento de los accidentes laborales mortales por parte de la prensa vasca, tomando como referencia los fallecimientos ocurridos en Bizkaia en los años 2001 y 2009. Como hipótesis de partida se considera que, al contrario de lo que ha ocurrido con otras muertes violentas, como las provocadas por los atentados de ETA o por la violencia de género, en donde se puede observar una toma de postura por parte de los medios en los últimos años, en el caso de la siniestralidad laboral nos encontramos con un enfoque mucho más cercano al periodismo de sucesos, en el que los fallecimientos en el puesto de trabajo se equiparan a los accidentes de tráfico. Este texto forma parte de un proyecto de investigación más amplio sobre "La evolución en el tratamiento de las muertes violentas en la prensa del País Vasco", financiado por el Ministerio de Ciencia e Innovación (referencia CSO2010-19866)