Martin G. White

Hyperglucagonemia of Renal Failure

Elevation of plasma glucagon concentration has been observed in starvation and illnesses associated with increased catabolism such as diabetes mellitus and severe infections. Thus, we examined plasma glucose, immunoreactive insulin (IRI, microunits per milliliter) and glucagon (IRG, picograms per milliliter) responses to a beef meal (1 g/kg body wt) and intravenous glucose (1.5 g/min for 45 min) in patients with chronic renal failure (CRF). After the beef meal (n = 6), plasma glucose did not change, IRI rose from 10.1+/-1.2 to 16.3+/-1.1 (P < 0.01), and IRG rose from a fasting value of 225+/-26 to 321+/-40 (P < 0.01) by 90 min (mean+/-SEM). Intravenous infusion of glucose in CRF patients resulted in significant elevations and prolonged disappearance of plasma glucose and insulin when compared to control subjects (P < 0.01). Glucose infusion failed to suppress elevated plasma glucagon concentrations to normal levels.6 wk of chronic hemodialysis in five patients resulted in normal plasma glucose and insulin responses to the same intravenous glucose load. In contrast, plasma glucagon concentration remained unchanged after hemodialysis and there was no correlation of plasma glucagon levels with carbohydrate intolerance.

The effect of potassium and extracellular volume on renal bicarbonate reabsorption

Bicarbonate reabsorption was measured in dogs infused with either KCl or KHCO3. As has been previously reported, potassium loading depressed bicarbonate reabsorption. Similar studies in dogs with partial obstruction of the thoracic inferior vena cava failed to demonstrate an effect of potassium loading on bicarbonate reabsorption. Extracellular volume was expanded with isotonic saline in three groups of dogs: one with potassium depletion, a second with hyperkalemia, and a third normal group. Bicarbonate reabsorption varied inversely with fractional chloride excretion in all three groups. At any one level of fractional chloride excretion, however, bicarbonate reabsorption was higher in the potassium depleted animals than in the normal dogs, and higher in the normal dogs than in those subjected to potassium loading. This study demonstrates a significant regulatory role of potassium over renal bicarbonate reabsorption. This role can only clearly be defined, however, when the precise state of effective extracellular volume is delineated.

Relationship of Sodium Reabsorption and Glomerular Filtration Rate to Renal Glucose Reabsorption

Glucose reabsorption was measured in dogs in which sodium reabsorption was stimulated by obstruction of the thoracic inferior vena cava or inhibited by volume expansion with Ringers lactate. Glucose reabsorption was much higher during periods of enhanced sodium reabsorption than during sodium diuresis. The relationship of glucose reabsorption to glomerular filtration rate was examined using data from animals that had fractional sodium excretion rates of less than 1%. Under this condition the relationship of glucose reabsorption to glomerular filtration rate is highly linear. When points obtained during sodium diuresis (C(Na)/GFR>0.1) are plotted on the same graph, glucose reabsorption at any given glomerular filtration rate is much less than during antidiuresis. Glucose reabsorption divided by glomerular filtration rate varies inversely with fractional sodium excretion. This study demonstrates that glomerular tubular balance for glucose exists in the dog and that this balance is changed when sodium reabsorption changes.

Hyperglucagonemia in uremia: reversal by renal transplantation.

Chronic renal failure in man is associated with hyperglucagonemia that is not corrected by hemodialysis. Plasma glucagon concentrations were measured in nine patients before and after renal transplantation. Mean plasma glucagon concentration in eight patients with chronic renal failure before transplantation was 295 plus or minus 171 pg/ml (plus or minus SD). After successful transplantation, mean plasma glucagon concentration fell to 134 plus or minus 81 pg/ml (plus or minus SD) (P less than 0.001). Plasma glucagon concentration remained elevated in an additional patient who received a cadaveric graft that never functioned. Immunologic rejection of transplanted kidneys was associated with a dramatic increase of plasma glucagon concentration.