The Dissociation of Renin and Aldosterone during Critical Illness*

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Abstract
A syndrome of elevated PRA accompanied by inappropriately low plasma aldosterone (ALDO) levels has been identified in some critically ill patients. To determine whether this phenomenon is due to a disturbance in factors that stimulate ALDO, we measured PRA, angiotensin II (All), potassium (K+), and ACTH levels in 83 patients admitted to an intensive care unit. In 59 patients, PRA was greater than 2.0 ng/ml·h. Of these, 24 had an ALDO to PRA ratio (ALDO/PRA) below 2 (group I), and 35 had an ALDO/PRA ratio of 2 or more (group II). An ALDO/PRA ratio below 2 was deemed inappropriately low. Despite markedly elevated PRA [34 ± 12 (±se) ng/ml·h], the group I patients had inappropriately low ALDO levels (19 ± 5 ng/dL). Patients in group II had significantly higher ALDO levels (48 ± 6 ng/dL) despite lower PRA (9 ± 1 ng/ml·h). All levels were appropriately elevated in group I (89 ± 26 pg/mL) and significantly greater (P < 0.5) than those in group II. PRA correlated well with AH in both groups. There were no differences in plasma ACTH or K+ in these 2 groups, and plasma cortisol levels were similarly elevated in both groups of patients. Of 66 consecutively studied patients, 14 (21%) had inappropriate ALDO (group I). Mortality was significantly greater in group I (75%) than in group II (46%; P < 0.001). In summary, a significant subset (21%) of seriously ill patients have inappropriately low ALDO levels despite elevated PRA. This dissociation is not due to an impairment of All production or changes in plasma ACTH or K+. This phenomenon is associated with a higher mortality during critical illness. In light of evidence of decreased adrenal androgen secretion during severe illness, this dissociation of renin and aldosterone may represent an additional adrenal adaptation designed to promote cortisol production in critically ill patients.