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

Obesity induced alterations in redox homeostasis and oxidative stress are present from an early age.

OBJECTIVES:Oxidative stress and inflammation have been postulated as underlying mechanisms for the development of obesity-related insulin resistance. This association however, remains elusive especially in childhood. We sought to investigate this relation by measuring oxidative stress and antioxidant response biomarkers, before and during an oral glucose tolerance test (OGTT), in different biological samples from obese children. SUBJECTS:24 children were recruited for the study, (18 obese and 6 controls). After OGTT, the obese group was subdivided in two, according to whether or not carbohydrate metabolic impairment (Ob.IR+, Ob.IR-; respectively) was found. Different biomarkers were analyzed after fasting (T = 0) and during an OGTT (T = 60 and 120 min). Lipoperoxides were measured in plasma, erythrocytes, and urine; while advanced glycation end products were determined in plasma, and redox status (GSH/GSSG ratio) in erythrocytes. RESULTS:We found marked differences in the characterization of the oxidative status in urine and erythrocytes, and in the dynamics of the antioxidant response during OGTT. Specifically, Ob.IR+ children show increased oxidative stress, deficient antioxidant response and a significant imbalance in redox status, in comparison to controls and Ob.IR- children. CONCLUSION:Obese children with insulin resistance show increased levels of oxidative stress biomarkers, and a stunted antioxidant response to an OGTT leading to increased oxidative stress after a single glucose load, as detected in erythrocytes, but not in plasma. We propose erythrocytes as sensors of early and acute changes in oxidative stress associated with insulin resistance in childhood obesity. This is a pilot study, performed with a limited sample size, so data should be interpreted with caution until reproduced

Redox status in RBC of healthy and obese children before and along an OGTT.

<p>(A) Total glutathione concentration (sum of all glutathione equivalents or tGSH, and (B) Reduced glutathione/oxidized glutathione rate, as measured in RBCs, at baseline and along the OGTT. White bars represent the control group, grey bars represent Ob.IR- group, and black bars represent Ob.IR+ group. Data are represented as mean ± SEM. P<0.05 was considered for statistical significance. (a) show significant differences relative to control at baseline, (b) shows significant differences relative to Ob.IR-, and (#) intragroup differences along the OGTT compared to baseline values.</p

Characteristics of study population.

<p>Characteristics of study population.</p

Total antoxiodant capacity (TAC) in venous blood in control and obese children.

<p>(A) Plasmatic TAC and, (B) RBC’s TAC at baseline and along 75 g. OGTT. White bars represent the control group, grey bars represent Ob.IR- group, and black bars represent Ob.IR+ group. Data are represented as mean ± SEM. P<0.05 was considered for statistical significance. (a) show significant differences relative to control at baseline, (b) shows significant differences relative to Ob.IR-, and (#) intragroup differences along the OGTT compared to baseline values.</p

Catalase activity in RBC of healthy and obese children.

<p>At baseline and along the OGTT. Data is expressed in nmol H₂O₂ x min^-1 x mg^-1 of protein. White bars represent the control group, grey bars represent Ob.IR- group, and black bars represent Ob.IR+ group. Data are represented as mean ± SEM. P<0.05 was considered for statistical significance. (a) show significant differences relative to control at baseline, (b) shows significant differences relative to Ob.IR-, and (#) intragroup differences along the OGTT compared to baseline values.</p

Plasmatic Advanced Glycation End Products (AGEs) in control and obese children.

<p>Measured at baseline and along the OGTT. Data is expressed in μg of CML/ml. White bars represent the control group, grey bars represent Ob.IR- group, and black bars represent Ob.IR+ group. Data are represented as mean ± SEM. P<0.05 was considered for statistical significance. (a) show significant differences relative to control at baseline, (b) shows significant differences relative to Ob.IR-, and (#) intragroup differences along the OGTT respect to baseline values.</p