No abstract

The mechanism of proteinuria at high altitude is unclear. Renal function and urinary excretion rate of albumin (Ualb) at rest and during submaximal exercise and transcapillary escape rate of 125I-labeled albumin (TERalb) were investigated in 12 normal volunteers at sea level and after rapid and passive ascent to 4,350 m. The calcium antagonist isradipine (5 mg/day; n = 6) or placebo (n = 6) was administered to abolish hypoxia-induced rises in blood pressure. Lithium clearance and urinary excretion of beta 2-microglobulin were used to evaluate renal tubular function. High altitude increased Ualb from 2.8 to > 5.0 micrograms/min in both groups (P < 0.05). In the placebo group, high altitude significantly increased filtration fraction (P < 0.05), but this response was abolished by isradipine. Lithium clearance and urinary excretion of beta 2-microglobulin remained unchanged by hypoxia in both groups. Exercise did not reveal any further renal dysfunction. In both groups, high altitude increased TERalb from 4.8 to > 6.7%/h (P < 0.05). In conclusion, acute altitude hypoxia increases Ualb despite unchanged tubular function and independent of effects of isradipine on filtration fraction. The elevated TERalb suggests an overall increase in capillary permeability, including the glomerular endothelium, as the critical factor in high-altitude induced albuminuria.

We have tested whether our previous finding in normal subjects that the disappearance of insulin from plasma obeys saturation kinetics alone also applies to type I diabetic patients. In six long-term diabetic patients steady state plasma insulin concentrations resulting from constant insulin infusion at different rates were compared with the predictions of three models for the kinetics of insulin in plasma. The models allowed the existence of non-saturable (first order equation) or saturable (Michaëlis-Menten equation) mechanisms, or both. The minimal acceptable model included saturation kinetics alone in four subjects and first order kinetics alone in two subjects. The clearance of insulin in diabetic patients, calculated from the best fitting model, was 18.0 (median, range 10.0-23.7) ml X kg-1 X min.-1 versus 25.0 (18.6-47.1) ml X kg-1 X min.-1 in six normal subjects (2p = 0.008). Insulin thus disappears from plasma at a lower rate in diabetic patients than in normal subjects at physiological plasma concentrations.