Abstract
In high-altitude climbers, the kidneys play a crucial role in acclimatization and in mountain sickness syndromes [acute mountain sickness (AMS), high-altitude cerebral edema, high-altitude pulmonary edema] through their roles in regulating body fluids, electrolyte and acid-base homeostasis. Here, we discuss renal responses to several high-altitude-related stresses, including changes in systemic volume status, renal plasma flow and clearance, and altered acid-base and electrolyte status. Volume regulation is considered central both to high-altitude adaptation and to maladaptive development of mountain sickness. The rapid and powerful diuretic response to the hypobaric hypoxic stimulus of altitude integrates decreased circulating concentrations of antidiuretic hormone, renin and aldosterone, increased levels of natriuretic hormones, plasma and urinary epinephrine, norepinephrine, endothelin and urinary adrenomedullin, with increased insensible fluid losses and reduced fluid intake. The ventilatory and hormonal responses to hypoxia may predict susceptibility to AMS, also likely influenced by multiple genetic factors. The timing of altitude increases and adaptation also modifies the body's physiologic responses to altitude. While hypovolemia develops as part of the diuretic response to altitude, coincident vascular leak and extravascular fluid accumulation lead to syndromes of high-altitude sickness. Pharmacological interventions, such as diuretics, calcium blockers, steroids, phosphodiesterase inhibitors and β-agonists, may potentially be helpful in preventing or attenuating these syndromes.