RICORS2040 : The need for collaborative research in chronic kidney disease

Chronic kidney disease (CKD) is a silent and poorly known killer. The current concept of CKD is relatively young and uptake by the public, physicians and health authorities is not widespread. Physicians still confuse CKD with chronic kidney insufficiency or failure. For the wider public and health authorities, CKD evokes kidney replacement therapy (KRT). In Spain, the prevalence of KRT is 0.13%. Thus health authorities may consider CKD a non-issue: very few persons eventually need KRT and, for those in whom kidneys fail, the problem is 'solved' by dialysis or kidney transplantation. However, KRT is the tip of the iceberg in the burden of CKD. The main burden of CKD is accelerated ageing and premature death. The cut-off points for kidney function and kidney damage indexes that define CKD also mark an increased risk for all-cause premature death. CKD is the most prevalent risk factor for lethal coronavirus disease 2019 (COVID-19) and the factor that most increases the risk of death in COVID-19, after old age. Men and women undergoing KRT still have an annual mortality that is 10- to 100-fold higher than similar-age peers, and life expectancy is shortened by ~40 years for young persons on dialysis and by 15 years for young persons with a functioning kidney graft. CKD is expected to become the fifth greatest global cause of death by 2040 and the second greatest cause of death in Spain before the end of the century, a time when one in four Spaniards will have CKD. However, by 2022, CKD will become the only top-15 global predicted cause of death that is not supported by a dedicated well-funded Centres for Biomedical Research (CIBER) network structure in Spain. Realizing the underestimation of the CKD burden of disease by health authorities, the Decade of the Kidney initiative for 2020-2030 was launched by the American Association of Kidney Patients and the European Kidney Health Alliance. Leading Spanish kidney researchers grouped in the kidney collaborative research network Red de Investigación Renal have now applied for the Redes de Investigación Cooperativa Orientadas a Resultados en Salud (RICORS) call for collaborative research in Spain with the support of the Spanish Society of Nephrology, Federación Nacional de Asociaciones para la Lucha Contra las Enfermedades del Riñón and ONT: RICORS2040 aims to prevent the dire predictions for the global 2040 burden of CKD from becoming true

Lanthanum Carbonate Modulates Inflammatory Profile in Hemodialysis Patients: Relationship with Fibroblast Growth Factor-23

Elevated fibroblast growth factor 23 (FGF-23) is independently associated with increased inflammatory markers in chronic kidney disease. Lanthanum carbonate (LaCa) reduces FGF-23. We studied the effects of LaCa on inflammatory profile of hemodialysis patients, and the relationship with changes in FGF-23. This prospective study was performed under habitual clinical practice conditions. Twenty-six hemodialysis patients with serum phosphate > 5 mg/dl receiving calcium-based phosphate binders were switched to LaCa. Ten patients with phosphate ≤ 5 mg/dl under calcium-based phosphate binders were enrolled as a control group for comparison. Serum calcium, phosphorus, calcium-phosphate product (CaxP), intact parathyroid hormone and the inflammatory profile [including serum high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α), interleukin (IL)-6 and IL-10, as well as mRNA expression levels of TNF-α and IL-6 in peripheral blood mononuclear cells] were analyzed. Serum FGF-23 significantly decreased in patients switched to LaCa (P< 0.01), with a concomitant reduction in serum hsCRP (-10.9%, P < 0.01), TNF-α (-6.7%, P < 0.05) and IL-6 (-8.1%, P < 0.01). mRNA expression levels of TNF-α and IL-6 in PBMC also decreased by 7.8% (P< 0.05) and 10.3% (P< 0.01), respectively. Multivariate regression analysis demonstrated that variations in FGF-23 were the only independent determinant of the changes in serum and mRNA expression levels of inflammatory parameters. In conclusion, LaCa posses anti-inflammatory actions, which are significant and independently associated with the reduction of FGF-23. FGF-23 may regulate inflammatory cytokine gene expression at the transcriptional level. Whether these effects have influence on clinical outcomes warrants consideration

Selective Vitamin D Receptor Activation as Anti-Inflammatory Target in Chronic Kidney Disease

Paricalcitol, a selective vitamin D receptor (VDR) activator used for treatment of secondary hyperparathyroidism in chronic kidney disease (CKD), has been associated with survival advantages, suggesting that this drug, beyond its ability to suppress parathyroid hormone, may have additional beneficial actions. In this prospective, nonrandomised, open-label, proof-of-concept study, we evaluated the hypothesis that selective vitamin D receptor activation with paricalcitol is an effective target to modulate inflammation in CKD patients. Eight patients with an estimated glomerular filtration rate between 15 and 44 mL/min/1.73 m2 and an intact parathyroid hormone (PTH) level higher than 110 pg/mL received oral paricalcitol (1 μg/48 hours) as therapy for secondary hyperparathyroidism. Nine patients matched by age, sex, and stage of CKD, but a PTH level <110 pg/mL, were enrolled as a control group. Our results show that five months of paricalcitol administration were associated with a reduction in serum concentrations of hs-CRP (13.9%, P<0.01), TNF-α (11.9%, P=0.01), and IL-6 (7%, P<0.05), with a nonsignificant increase of IL-10 by 16%. In addition, mRNA expression levels of the TNFα and IL-6 genes in peripheral blood mononuclear cells decreased significantly by 30.8% (P=0.01) and 35.4% (P=0.01), respectively. In conclusion, selective VDR activation is an effective target to modulate inflammation in CKD

The impact of social violence on HIV risk for women in Colombia: A concurrent mixed methods study.

Gender, violence, and migration structurally impact health. The Venezuelan humanitarian crisis comprises the largest transnational migration in the history of the Americas. Colombia, a post-conflict country, is the primary recipient of Venezuelans. The Colombian context imposes high levels of violence on women across migration phases. There is little information on the relationship between violence and HIV risk in the region and how it impacts these groups. Evidence on how to approach the HIV response related to Venezuela's humanitarian crisis is lacking. Our study seeks to 1) understand how violence is associated with newly reported HIV/AIDS case rates for women in Colombian municipalities; and 2) describe how social violence impacts HIV risk, treatment, and prevention for Venezuelan migrant and refugee women undergoing transnational migration and resettlement in Colombia. We conducted a concurrent mixed-methods design. We used negative binomial models to explore associations between social violence proxied by Homicide Rates (HR) at the municipality level (n = 84). The also conducted 54 semi-structured interviews with Venezuelan migrant and refugee women and key informants in two Colombian cities to expand and describe contextual vulnerabilities to HIV risk, prevention and care related to violence. We found that newly reported HIV cases in women were 25% higher for every increase of 18 homicides per 100,000, after adjusting for covariates. Upon resettlement, participants cited armed actors' control, lack of government accountability, gender-based violence and stigmatization of HIV as sources of increased HIV risk for VMRW. These factors impose barriers to testing, treatment and care. Social violence in Colombian municipalities is associated with an increase in newly reported HIV/AIDS case rates in women. Violence hinders Venezuelan migrant and refugee women's access and engagement in available HIV prevention and treatment interventions

Clinical Study Selective Vitamin D Receptor Activation as Anti-Inflammatory Target in Chronic Kidney Disease

Paricalcitol, a selective vitamin D receptor (VDR) activator used for treatment of secondary hyperparathyroidism in chronic kidney disease (CKD), has been associated with survival advantages, suggesting that this drug, beyond its ability to suppress parathyroid hormone, may have additional beneficial actions. In this prospective, nonrandomised, open-label, proof-of-concept study, we evaluated the hypothesis that selective vitamin D receptor activation with paricalcitol is an effective target to modulate inflammation in CKD patients. Eight patients with an estimated glomerular filtration rate between 15 and 44 mL/min/1.73 m 2 and an intact parathyroid hormone (PTH) level higher than 110 pg/mL received oral paricalcitol (1 g/48 hours) as therapy for secondary hyperparathyroidism. Nine patients matched by age, sex, and stage of CKD, but a PTH level &lt;110 pg/mL, were enrolled as a control group. Our results show that five months of paricalcitol administration were associated with a reduction in serum concentrations of hs-CRP (13.9%, &lt; 0.01), TNF-(11.9%, = 0.01), and IL-6 (7%, &lt; 0.05), with a nonsignificant increase of IL-10 by 16%. In addition, mRNA expression levels of the TNF and IL-6 genes in peripheral blood mononuclear cells decreased significantly by 30.8% ( = 0.01) and 35.4% ( = 0.01), respectively. In conclusion, selective VDR activation is an effective target to modulate inflammation in CKD