International Conference on Nephrology November 19-21, 2018 Cape Town, South Africa

Tetsuhiro Tanaka is a currently working at the Division of Nephrology and Endocrinology, the University of Tokyo, School of Medicine. His major research interest is the role of chronic hypoxia and hypoxia-inducible gene transcription in the pathogenesis of CKD. He has completed his Graduation from the University of Tokyo, School of Medicine in 1997 and has obtained his Ph.D. degree at the University of Tokyo Graduate, School of Medicine in 2005. He has received the Young Investigator Award of the Japanese Society of Nephrology in 2014. He is currently serving as an editorial board member of Kidney International and Clinical and Experimental Nephrology.

Pathophysiology of Diabetic Kidney Disease (DKD) is complex. In addition to high glucose-induced inflammation, oxidative stress and activation of the renin-angiotensin system, the pathogenic role of chronic hypoxia in the tubulointerstitium is increasingly recognized. Beginning from the early stage of DKD, an increase in oxygen consumption secondary to mitochondrial uncoupling reduces local oxygenation, and together with loss of peritubular capillaries and impaired oxygen diffusion, negatively influences the balance of injury and repair in tubular epithelial cells and serves as a final common pathway leading to fibrosis. Studies on Erythropoietin (EPO) transcription led to the identification of Hypoxia Inducible Factors (HIFs) and their key regulators, Prolyl Hydroxylases (PHDs). Inhibition of Ph.D. leads to HIF stabilization irrespective of oxygen content and up-regulates EPO, as well as other 100-200 target genes involved in processes such as angiogenesis and anaerobic metabolism necessary for cellular hypoxic adaptation. Based on this, several small molecule PHD inhibitors are currently under human clinical trials for the treatment of anemia in CKD. Application of PHD inhibitors has several potential implications beyond anemia treatment. Because HIF drives the expression of genes essential to adaptation to hypoxia, there is a promising view that activation of HIF using PHD inhibitors might protect against DKD. Besides, animal and human clinical studies even suggest that PHD inhibitors may improve glucose and lipid metabolism, which may also orchestrate protection against DKD progression.

Margaret Williams is a Public Health/Primary Healthcare Specialist who coordinates, teaches and mentors post graduate students and supervises research students focusing on public health issues and participates in interfaculty and interprofessional research projects. Her passion is to improve healthcare for all communities, starting at primary healthcare level.

Chronic kidney disease is defined as a reduced glomerular filtration rate, increased urinary albumin excretion, or both, and is an increasing public health issue. It is a common disorder that is associated with raised risk of cardiovascular disease, kidney failure, and other complications. In developed countries, age, hypertension, diabetes, increased body-mass index and smoking are associated consistently with chronic kidney disease. In the developing world, infectious diseases are factors, such as bacterial and viral, particularly HIV. Prevalence is estimated at 8-16% worldwide. Complications include increased cardiovascular mortality, kidney-disease progression, acute kidney injury, cognitive decline, anemia, mineral and bone disorders and fractures. Worldwide, diabetes mellitus is the most common cause of chronic kidney disease together with other causes, such as herbal and environmental toxins. Awareness of the disorder remains low in developing countries therefore strategies to reduce burden and costs related to chronic kidney disease need to be included in national programmes for non-communicable diseases. Awareness of chronic kidney disease is low among patients and health-care providers. The number of patients with chronic kidney disease is expected to grow at the fastest rate in the poorest parts of the world, but a strong association is seen between low levels of economic development and reduced availability of renal replacement therapy, thus care for advanced chronic kidney disease is associated with catastrophic health expenditure in developing countries. Early detection of chronic kidney disease requires the development of cost-effective approaches relevant to the local level of economic development and resources. Integration of screening and management strategies for chronic kidney disease into national programmes for non-communicable diseases can reduce the burden and cost of care of chronic kidney disease, particularly in developing countries. Methods should suit local needs, and factors such as health awareness and availability of human and material resources should be considered.