Serum potassium and acid-base parameters in severe dialysis-associated hyperglycemia treated with insulin therapy.

We analyzed the changes in serum potassium concentration ([K]) and acid-base parameters in 43 episodes of dialysis-associated hyperglycemia (serum glucose level > 33.3 mmol/L), 22 of which were characterized as diabetic ketoacidosis (DKA) and the remaining 21 as nonketotic hyperglycemia (NKH). All episodes were treated with insulin therapy only. Age, gender, initial and final serum values of glucose, sodium, chloride, tonicity and osmolality did not differ between DKA and NKH. At presentation, serum values of [K] (DKA 6.2 +/- 1.3 mmol/L; NKH 5.2 +/- 1.5 mmol/L) and anion gap [AG] (DKA 27.2 +/- 6.4 mEq/L; NKH 15.4 +/- 3.5 mEq/L) were higher in DKA, whereas serum total carbon dioxide content [TCO2 ] (DKA 12.0 +/- 4.6 mmol/L; NKH 22.5 +/- 3.1 mmol/L), arterial blood pH (DKA 7.15 +/- 0.09; NKH 7.43 +/- 0.07) and arterial blood PaCO2 (DKA 26.2 +/- 12.3 mm Hg; NKH 34.5 +/- 6.7 mm Hg) were higher in NKH. At the end of insulin treatment, serum values of [K] (DKA 4.0 +/- 0.7 mmol/L, NKH 4.0 +/- 0.5 mmol/L), [AG] (DKA 16.3 +/- 5.4 mEq/L, NKH 14.9 +/- 3.0 mEq/L), [TCO2 ] (DKA 23.5 +/- 5.0 mmol/L, NKH 24.1 +/- 4.2 mmol/L), arterial blood pH (DKA 7.42 +/- 0.09, NKH 7.51 +/- 0.14) and arterial blood PaCO2 (DKA 31.8 +/- 6.7 mm Hg, NKH 34.2 +/- 8.3 mm Hg) did not differ between the two groups. Linear regression of the decrease in serum [K] value during treatment, (Delta[K]), on the presenting serum [K] concentration,([K]2 ), was: DKA, Delta[K] = 2.78 - 0.81 x [K]2 , r = -0.85, p < 0.001; NKH, Delta[K] = 2.44 - 0.71 x [K]2 , r = -0.90, p < 0.001. The slopes of the regressions were not significantly different. Stepwise logistic regression including both DKA and NKH cases identified the presenting serum [K] level and the change in serum [TCO2 ] value during treatment as the predictors of Delta[K] (R2 = 0.81). Hyperkalemia is a feature of severe hyperglycemia (DKA or NKH) occurring in patients on dialysis. Insulin administration brings about correction of DKA and return of serum [K] concentration to the normal range in the majority of the hyperglycemic episodes without the need for other measures. The initial serum [K] value and the change in serum [TCO2 ] level during treatment influence the decrease in serum [K] value during treatment of dialysis-associated hyperglycemia with insulin.

Serum tonicity, extracellular volume and clinical manifestations in symptomatic dialysis-associated hyperglycemia treated only with insulin.

The absence of osmotic diuresis modifies the effects of hyperglycemia on body fluids in patients with advanced renal failure. To determine the relationship between clinical manifestations and abnormalities in tonicity and extracellular volume in such patients, we analyzed 43 episodes of severe dialysis-associated hyperglycemia (serum glucose exceeding 600 mg/dL) treated only with insulin. The main manifestations were dyspnea in 22 cases (pulmonary edema in 19), nausea and vomiting in 15, coma in 13 and seizures in 3, while 5 patients had no symptoms. Treatment with insulin resulted in a decrease in serum glucose value from 913 +/- 197 mg/dL to 170 +/- 78 mg/dL, an increase in serum sodium level from 125 +/- 5 to 136 +/- 5 mmol/L, and a fall in calculated serum tonicity value from 300 +/- 13 to 282 +/- 11 mmol/kg (all at p < 0.001). The ratio of the change in serum sodium level over change in serum glucose concentration was -1.50 +/- 0.22 mmol/L per 100 mg/dL. The percent increase in extracellular volume secondary to hyperglycemia developing from the prior euglycemic state and calculated from changes in serum sodium and chloride concentrations, was 10.9% +/- 4.6% (1.5% +/- 0.6% per 100 mg/dL increase in serum glucose level). All clinical manifestations dissipated after correction of hyperglycemia in 42 patients. One woman developed during treatment a fatal myocardial infarction. Dialysis patients with severe hyperglycemia may develop symptoms as a result of hypertonicity and extracellular expansion. Insulin alone may be sufficient treatment for these symptoms. The changes in serum tonicity and electrolytes during treatment are consistent with theoretical predictions.

Dialysance of adrenocorticoids during continuous ambulatory peritoneal dialysis.

We postulated that significant quantities of both protein-bound and unbound adrenocorticoids are lost during continuous ambulatory peritoneal dialysis (CAPD). To test this hypothesis we measured the dialysate removal rates (DRR) of adrenocorticoids in six CAPD patients. The distribution of the adrenocorticoids among unbound, albumin-bound, and transcortin-bound fractions in dialysate effluent was determined. The distribution of cortisol among unbound, albumin-bound, and transcortin-bound fractions in plasma was determined in six other CAPD patients. The mean DRR of cortisol was 193.8 +/- 20.3 (+/- SE) nmol/day. Smaller quantities of 11-deoxycorticosterone, corticosterone, aldosterone, 18-hydroxy-11-deoxycorticosterone, and 18-hydroxycorticosterone were removed during CAPD. The mean DRR values for total protein, albumin, and transcortin were 11.2 +/- 2.1, 6.0 +/- 2.2, and 0.087 +/- 0.018 g/day, respectively. The distribution of cortisol among unbound, albumin-bound, and transcortin-bound fractions was normal in plasma from CAPD patients. Plasma transcortin had a normal affinity (2 x 10(7) mol/L-1) and a normal binding capacity (559 nmol/L) for cortisol. In contrast, dialysate transcortin had a low affinity (1.4 x 10(7) mol/L-1) for cortisol and a low cortisol-binding capacity (11.5 nmol/L). The fractional occupancy rates of high affinity cortisol-binding sites on transcortin were 52.0 +/- 3.3% and 3.3 +/- 0.6% in plasma and dialysate effluent, respectively (P less than 0.001). The transcortin to cortisol molar concentration ratio in dialysate (6.3 +/- 0.6) was significantly higher than that in plasma (1.6 +/- 0.2; P less than 0.001). These results demonstrate that cortisol is the major adrenocorticoid lost during CAPD. However, the amount of cortisol removed in the dialysate is less than 1% of the normal daily secretion rate. Significant quantities of other adrenocorticoids are also lost during CAPD. The adrenocorticoids present in dialysate effluent are principally unbound, in contrast to their state in plasma. However, small fractions of the respective steroids are bound to transcortin and albumin.

Corticosterone methyloxidase II activity during hemodialysis.

Plasma levels of aldosterone decrease during hypokalemic hemodialysis. Our study was performed to determine whether the changes in plasma aldosterone level observed during hemodialysis are modulated by changes in corticosterone methyloxidase II activity. We measured plasma levels of adrenal zona glomerulosa steroids, for example, aldosterone and 18-hydroxycorticosterone (18-OH-B), immediately before and after 4 hours of hemodialysis (n = 8). Plasma levels of steroids originating from the adrenal zona fasciculata, for example, cortisol, corticosterone, 18-hydroxy-11-deoxycorticosterone, and 11-deoxycorticosterone, were also measured. Dialysance rates of 18-OH-B, aldosterone, and cortisol were calculated (n = 8). Plasma levels of both aldosterone (P less than 0.05) and 18-OH-B (p less than 0.01) decreased during hemodialysis. The 18-OH-B/aldosterone plasma concentration ratios did not change significantly during hemodialysis. No significant changes in plasma levels of fasciculata steroids were observed during hemodialysis. Dialysance rates for aldosterone and 18-OH-B were similar (P not significant). The dialysance of cortisol was 10-fold lower than that of aldosterone (P less than 0.01) and 18-OH-B (P less than 0.01). The relative constancy of the 18-OH-B/aldosterone plasma concentration ratios indicates that corticosterone methyloxidase II activity is normal in patients with end-stage renal disease who are maintained by hemodialysis.

Distribution of 18-hydroxycorticosterone between red blood cells and plasma.

Plasma 18-hydroxycorticosterone (18-OH-B) to aldosterone (aldo) concentration ratios reflect adrenal corticosterone methyloxidase type II activity. This ratio is determined not only by the relative secretion rates of the two steroids but also by differences in binding, distribution, and metabolism. Plasma cortisol alters the distribution of aldo between red blood cells (RBC) and plasma. We postulated that the distribution of 18-OH-B, like that of aldo, is determined by the availability of high affinity binding sites on plasma transcortin. Double equilibrium dialyses demonstrated that 18-OH-B, aldo, and cortisol compete for binding sites on transcortin. Increasing amounts of each of the three unlabeled steroids produced progressive decrements in the binding of all three labeled steroids to transcortin. The affinity of 18-OH-B (2 X 10(6) M-1) for transcortin was intermediate between those of cortisol (3 X 10(7) M-1) and aldo (0.9 X 10(6) M-1). Heat treatment of plasma decreased the binding of 18-OH-B and cortisol to transcortin by 82% and 75%, respectively. Gel filtration of plasma revealed that protein-bound [3H]18-OH-B and [14C]cortisol eluted in the same fractions. The addition of increasing quantities of unlabeled cortisol to whole blood in vitro produced similar increments in RBC to plasma concentration ratios of [3H]18-OH-B and [14C]aldo. The ratio of the percentage of circulating 18-OH-B in plasma to the percentage of circulating aldo in plasma was constant in blood containing low and high cortisol concentrations. Therefore, changes in plasma cortisol have similar effects on the distribution of 18-OH-B and aldo between RBC and plasma.

Low dose adrenocorticotropin infusion in continuous ambulatory peritoneal dialysis patients.

The adrenocorticoid responses to low doses of ACTH (0.03-10 ng/min) in sodium-deplete normal subjects and end-stage renal disease patients maintained on continuous ambulator peritoneal dialysis (CAPD) were compared. All subjects were pretreated with dexamethasone. ACTH was administered by graded iv infusions in doses of 0.03, 0.3, 1.0, 3.0, and 10 ng ACTH/min. Each rate of infusion was maintained for 30 min. Plasma aldosterone, 18-hydroxycorticosterone, corticosterone, 18-hydroxy-11-deoxycorticosterone, and cortisol were measured in plasma sampled at the end of each rate of infusion in both groups. Plasma 11-deoxycorticosterone was measured in CAPD patients. The plasma steroid levels in the CAPD patients after each infusion rate were equal to or greater than the levels in normal subjects. The slopes of the cumulative increases above baseline in plasma steroid levels in the CAPD patients were equal to or greater than those in the normal subjects. In both groups, plasma corticosterone increased the most and aldosterone the least. Kinetic analyses indicated that the adrenal responses to low dose ACTH were not linear. A distinct threshold for ACTH-stimulated increase in plasma adrenocorticoid levels, if present, is very low. The responses of plasma adrenocorticoids to low dose ACTH are normal in CAPD patients.