The church and paediatric HIV care in rural South Africa

Religion has substantial – positive and negative – influence on South Africa’s HIV context. This qualitative study explored possibilities for positive church engagement in paediatric HIV care in a rural district in Limpopo Province, South Africa. Opinions, attitudes and experiences of various stakeholders including religious leaders, healthcare workers and people infected/affected with/by HIV were investigated through participant observation, semi-structured interviews and focus group discussions. During the research the original focus on paediatric HIV care shifted to HIV care in general in reaction to participant responses. Participants identified three main barriers to positive church engagement in HIV care: (a) stigma and disclosure; (b) sexual associations with HIV and (c) religious beliefs and practices. All participant groups appreciated the opportunity and relevance of strengthening church involvement in HIV care. Opportunities for positive church engagement in HIV care that participants identified included: (a) comprehensive and holistic HIV care when churches and clinics collaborate; (b) the wide social reach of churches and (c) the safety and acceptance in churches. Findings indicate that despite barriers great potential exists for increased positive church engagement in HIV care in rural South Africa. Recommendations include increased medical knowledge and dialogue on HIV/AIDS within church settings, and increased collaboration between churches and the medical sector

Blood pressure in chronic kidney disease: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) controversies conference

In September 2017, KDIGO (Kidney Disease: Improving Global Outcomes) convened a Controversies Conference titled Blood Pressure in Chronic Kidney Disease (CKD). The purpose of the meeting was to consider which recommendations from the 2012 KDIGO Clinical Practice Guideline for the Management of Blood Pressure in CKD should be reevaluated based on new evidence from clinical trials. Participants included a multidisciplinary panel of clinical and scientific experts. Discussions focused on the optimal means for measuring blood pressure (BP) as well as managing BP in CKD patients. Consistent with the 2012 Guideline, the conference did not address BP management in patients on maintenance dialysis

Disclosure of human immunodeficiency virus status to children in South Africa: A comprehensive analysis

Background: The extent of disclosure of HIV status to children and adolescents and the context facilitating their disclosure process have received little attention. Objectives: To assess disclosure and provide a comprehensive analysis of characteristics associated with disclosure to children (3–14 years) receiving antiretroviral treatment in a South African semi-urban clinic. Methods: This cross-sectional study used structured interview administered questionnaires which were supplemented with medical record data. Predictors included child, caregiver, clinical and socio-economic characteristics, viral suppression, immune response, adherence, health-related quality of life and family functioning. Results: We included 190 children of whom 45 (23.7%) received disclosure about their HIV status, of whom 28 (14.7%) were partially disclosed and 17

APOL1-Associated glomerular disease among African-American children: A collaboration of the chronic kidney disease in children (CKiD) and nephrotic syndrome study network (NEPTUNE) cohorts

Background: Individuals of African ancestry harboring two variant alleles within apolipoprotein L1 (APOL1) are classified with a high-risk (HR) genotype. Adults with an HR genotype have increased risk of focal segmental glomerulosclerosis and chronic kidney disease compared with those with a low-risk (LR) genotype (0 or 1 variants). The role of APOL1 risk genotypes in children with glomerular disease is less well known. Methods: This study characterized 104 African-American children with a glomerular disease by APOL1 genotype in two cohorts: The Chronic Kidney Disease in Children (CKiD) and Nephrotic Syndrome Study Network (NEPTUNE). Results: Among these subjects, 46% had an HR genotype with a similar age at cohort enrollment. For APOL1 HR children, the median age of disease onset was older (CKiD: 4.5 versus 11.5 years for LR versus HR; NEPTUNE: 11 versus 14 years for LR versus HR, respectively) and preterm birth was more common [CKiD: 27 versus 4%; NEPTUNE: 26 versus 12%; combined odds ratio 4.6 (95% confidence interval: 1.4, 15.5)].Within studies, HR children had lower initial estimated glomerular filtration rate (EGFR) (CKiD: 53 versus 69 mL/min/1.73 m2; NEPTUNE: 74 versus 94 mL/min/1.73 m2). Longitudinal EGFR decline was faster among HR children versus LR (CKiD: -18 versus -8% per year; NEPTUNE: -13 versus-3% per year). Conclusions: Children with an HR genotype in CKiD and NEPTUNE seem to have a more aggressive form of glomerular disease, in part due to a higher prevalence of focal segmental glomerulosclerosis. These consistent findings across independent cohorts suggest a common natural history for children with APOL1-Associated glomerular disease. Further study is needed to determine the generalizability of these findings

Genetic drivers of kidney defects in the digeorge syndrome

BACKGROUND The DiGeorge syndrome, the most common of the microdeletion syndromes, affects multiple organs, including the heart, the nervous system, and the kidney. It is caused by deletions on chromosome 22q11.2; the genetic driver of the kidney defects is unknown. METHODS We conducted a genomewide search for structural variants in two cohorts: 2080 patients with congenital kidney and urinary tract anomalies and 22,094 controls. We performed exome and targeted resequencing in samples obtained from 586 additional patients with congenital kidney anomalies. We also carried out functional studies using zebrafish and mice. RESULTS We identified heterozygous deletions of 22q11.2 in 1.1% of the patients with congenital kidney anomalies and in 0.01% of population controls (odds ratio, 81.5; P = 4.5×1014). We localized the main drivers of renal disease in the DiGeorge syndrome to a 370-kb region containing nine genes. In zebrafish embryos, an induced loss of function in snap29, aifm3, and crkl resulted in renal defects; the loss of crkl alone was sufficient to induce defects. Five of 586 patients with congenital urinary anomalies had newly identified, heterozygous protein-Altering variants, including a premature termination codon, in CRKL. The inactivation of Crkl in the mouse model induced developmental defects similar to those observed in patients with congenital urinary anomalies. CONCLUSIONS We identified a recurrent 370-kb deletion at the 22q11.2 locus as a driver of kidney defects in the DiGeorge syndrome and in sporadic congenital kidney and urinary tract anomalies. Of the nine genes at this locus, SNAP29, AIFM3, and CRKL appear to be critical to the phenotype, with haploinsufficiency of CRKL emerging as the main genetic driver

Obesity and kidney disease: hidden consequences of the epidemic

Obesity has become a worldwide epidemic and its prevalence has been projected to grow by 40% in the next decade. This increasing prevalence has implications for the risk of diabetes, cardiovascular disease and also for chronic kidney disease (CKD). A high body mass index is one of the strongest risk factors for new-onset CKD. In individuals affected by obesity, a compensatory hyperfiltration occurs to meet the heightened metabolic demands of the increased body weight. The increase in intraglomerular pressure can damage the kidneys and raise the risk of developing CKD in the long-term. The incidence of obesity-related glomerulopathy has increased ten-fold in recent years. Obesity has also been shown to be a risk factor for nephrolithiasis, and for a number of malignancies including kidney cancer. This year, the World Kidney Day will promote education on the harmful consequences of obesity and its association with kidney disease, advocating healthy lifestyle and health policy measures that make preventive behaviors an affordable option

Time-lapse imaging of primary preneoplastic mammary epithelial cells derived from genetically engineered mouse models of breast cancer.

Time-lapse imaging can be used to compare behavior of cultured primary preneoplastic mammary epithelial cells derived from different genetically engineered mouse models of breast cancer. For example, time between cell divisions (cell lifetimes), apoptotic cell numbers, evolution of morphological changes, and mechanism of colony formation can be quantified and compared in cells carrying specific genetic lesions. Primary mammary epithelial cell cultures are generated from mammary glands without palpable tumor. Glands are carefully resected with clear separation from adjacent muscle, lymph nodes are removed, and single-cell suspensions of enriched mammary epithelial cells are generated by mincing mammary tissue followed by enzymatic dissociation and filtration. Single-cell suspensions are plated and placed directly under a microscope within an incubator chamber for live-cell imaging. Sixteen 650 μm x 700 μm fields in a 4x4 configuration from each well of a 6-well plate are imaged every 15 min for 5 days. Time-lapse images are examined directly to measure cellular behaviors that can include mechanism and frequency of cell colony formation within the first 24 hr of plating the cells (aggregation versus cell proliferation), incidence of apoptosis, and phasing of morphological changes. Single-cell tracking is used to generate cell fate maps for measurement of individual cell lifetimes and investigation of cell division patterns. Quantitative data are statistically analyzed to assess for significant differences in behavior correlated with specific genetic lesions