Augmented aldosterone and insulin responses to potassium infusion in dogs with renal failure

Abstract

The present study examines acute potassium-induced insulin and aldosterone responses in renal failure, and the role of chronic dietary potassium intake in modifying these acute responses. Plasma aldosterone (PA) and insulin (IRI) responses to acute KCl infusion were examined in control and remnant kidney dogs on two potassium intakes. Dogs (N = 8) received the KCl infusions after 10 days of a 60, and then 10 days of a 200, mEq daily potassium intake during control and after surgical-induced renal failure (CRF). A one hour intravenous infusion of KCl (2 mEq KCl/kg/hr) in dextrose and water was performed with blood samples for PA, IRI, creatinine and electrolytes, and urine for electrolytes and creatinine at 20 minute intervals one hour preceding, during, and after the infusion. Pre-infusion PA was higher (P < 0.05) in controls and CRF dogs on 200 mEq potassium intake compared to 60 mEq potassium intake. The peak incremental responses of PA to KCl infusion were increased (P < 0.01) in CRF compared to controls on 60 mEq (PA 36 ± 4.2 vs. 26 ± 3.0 ng/dl) and 200 mEq (Δ PA 49 ± 5.6 vs. 37 ± 2.8 ng/dl) potassium intakes. Differences in incremental PA responses in CRF were not due to altered aldosterone metabolic clearance rates, changes in renin, or ACTH activity. Pre-infusion IRI was higher (P < 0.05) in CRF than control dogs on both potassium diets. The peak incremental IRI responses to KCl infusion were also increased (P < 0.01) in CRF on the 200 mEq potassium diet (IRI 140 ± 16 μU/ml) compared to controls (39 ± 3 μU/ml). Responses were also greater (P < 0.05) in CRF than control dogs on the 60 mEq potassium intake (IRI 27 ± 3 μU/ml vs. 20 ± 1.4 μU/ml). Plasma potassium increased significantly during KCl infusion, but potassium increments showed no significant differences between the four study groups. The percent fractional excretion of potassium was augmented in CRF on both potassium diets during basal and infusion periods, but U(K)V was markedly blunted in CRF in response to the KCl infusion. Analysis of potassium distribution revealed a marked increase in potassium transfer from the extracellular to the intracellular compartment of CRF dogs. Thus, the sensitivity of adrenal PA and pancreatic IRI secretion to acute potassium loading is augmented in renal failure. The close temporal relationship between the high levels of PA and IRI and enhanced intracellular uptake of potassium indicate they could participate in the extrarenal disposal of potassium in renal failure. It could be postulated that the increased tissue uptake of potassium in CRF also occurs in the adrenal gland and pancreas and further activates hormonal secretion.