The oxygen cascade in patients treated with hemodialysis and native high-altitude dwellers: lessons from extreme physiology to benefit patients with end-stage renal disease

Patients treated with hemodialysis (HD) repeatedly undergo intradialytic low arterial oxygen saturation and central venous saturation, reflecting an imbalance between upper body systemic supply demand, which are associated increased mortality. Abnormalities along the entire cascade, impaired diffusive convective transport, contribute to reduced tissue supply. HD treatment impairs pulmonary gas exchange reduces ventilatory drive, whereas ultrafiltration can reduce perfusion due a decline in cardiac output. In addition these factors, capillary rarefaction mitochondrial efficacy further affect balance cellular demand. Whereas it has been convincingly demonstrated that of heart brain during contributes organ damage, significance hypoxia remains uncertain, although may oxidative stress, inflammation, accelerated senescence. These abnormalities cascade patients appear be diametrically opposite situation Tibetan highlanders Sherpa, whose physiology adapted inescapable hypobaric their living environment over many generations. Their adaptation includes pulmonary, vascular, metabolic alterations enhanced density, nitric oxide production, without stress. Improving depends primarily on preventing hemodynamic instability by increasing dialysis time/frequency or prescribing cool dialysis. Whether dietary pharmacological interventions, such as administration L-arginine, fermented food, nitrate, nuclear factor erythroid 2-related 2 agonists, prolyl hydroxylase inhibitors, improve clinical outcome warrants future research.