Kidney hemodynamics after ketone body and amino acid infusion in normal and IDDM subjects

Abstract

Little information is available on the hemodynamic response (renal reserve) of the diabetic kidney during an acute amino acid infusion, which has been shown to increase glomerular filtration rate (GFR) in normal humans. We recently found that the infusion of ketone bodies is able to raise GFR in both normal subjects and insulin-dependent diabetes mellitus (IDDM) patients. The aim of this study was to evaluate the renal reserve in 15 IDDM patients with a duration of diabetes of >9 yr [8 with albumin excretion rate <15 μg/min (group 1) and 7 with albumin excretion rate >100 μg/min (group 2)] and in 8 normal subjects during amino acid infusion (33 μmol · kg−1 · min−1 , Travasol 10% wt/vol solution containing 0.154 mM sodium chloride concentration; Travenol, Savage, MD) and during acetoacetic sodium salt (25 μmol · kg−1 · min−1) infusion. Blood glucose was clamped at euglycemic levels. The infusion of sodium acetoacetate resulted in a 10- to 15-fold increase in circulating concentrations of ketone bodies, which were similar in magnitude in normal subjects and diabetic patients. The GFR peak increase above baseline after sodium acetoacetate infusion was 28% in normal subjects and 27% in group 1 and 19% in group 2 diabetic patients. The infusion of amino acid solution produced a three- to fivefold increase in plasma concentrations of amino acids in both normal subjects and diabetic patients. The GFR peak increase above baseline after amino acid infusion was significantly lower in diabetic patients (IDDM group 1: 5%, P < .01; IDDM group 2: 6%, P < .01) than in normal subjects (38%). During sodium acetoacetate infusion, proximal sodium reabsorption increased as well as distal sodium delivery in normal subjects and group 1 and group 2 IDDM patients. During amino acid infusion, only normal subjects showed a significant increase in proximal sodium reabsorption and distal sodium delivery, whereas no change was found in group 1 and group 2 IDDM patients. Amino acid infusion resulted in a marked increase in the albumin fractional clearance rate in both normal subjects and diabetic patients. On the contrary, ketone body infusion slightly increased the albumin fractional clearance rate in group 2 diabetic patients but not in group 1 diabetic patients and normal subjects. This study demonstrates that long-standing diabetic patients, irrespective of the presence of impaired renal function, show a peculiar defect in the kidney hemodynamic response to amino acid but not to ketone body infusion. These results question the use of an amino acid load to test for glomerular filtration reserve in diabetic patients, because a lack of response may simply be related to an altered response of the kidney to amino acids. A macula densa feedback mechanism could not account for the increase in GFR after both amino acid and ketone body infusion, because these compounds increase the sodium distal delivery. Amino acids increase albumin excretion rate with a mechanism independent of GFR and renal plasma flow changes, in that this effect occurs even in diabetic patients who showed no changes in these variables.