Regarding the report by Baber et al, it was stressed that the pathophysiologic mechanisms responsible for the increased risk for peripheral vascular disease and chronic kidney disease remain poorly understood. Lessons learned from space flight (SF) can be applicable to studies on Earth as well. Oxidative stress, inflammation, and endothelial dysfunction triggered by a magnesium deficit can be one underlying link responsible for (SF)–peripheral vascular dysfunction as well as renal dysfunction. I have emphasized that Apollo 15 astronauts James Irwin and David Scott might have had underlying endothelial dysfunction, even before dust inhalation in the lunar habitat, to account for the severe fingertip pain both experienced while on their first lunar excursion.

This is supported by the development of nail bed cyanosis, which Irwin showed by the 18th minute during a stress test on the day of return from his 12-day mission, supporting my hypothesis that the pain was secondary to peripheral vasospasm of the arterial and venous vessels. I postulated that a magnesium deficit secondary to invariable SF malabsorption and a loss of skeletal muscle storage sites for magnesium, even on this brief 12-day mission, could have been responsible. In support of my hypothesis is the decrease of calf blood flow of 40% during SF, relative to supine conditions preflight; measurements taken 4 to 12 SF days showed that calf vascular resistance doubled but returned to preflight levels after SF.

Furthermore, SF proteinuria (more pronounced after prolonged missions but disappearing after SF), elevations of serum creatinine, and an impairment of kidney concentrating ability have been shown.

It is noteworthy that studies in rats after SF of <3 weeks invariably demonstrated elevated activity of the juxtaglomerular apparatus. Seelig emphasized that experimental magnesium deficiency has been shown to cause hypertrophy of the juxtaglomerular apparatus, resulting in aldosterone secretion, which in turn increases magnesium loss and vicious cycles. Also, vicious cycles can develop from magnesium ion deficits with resultant catecholamine elevations and an increased angiotensin effect. The latter can contribute to an upregulated intrarenal renin-angiotensin system with hypertension.