Intravenous 1,25 dihydroxycholecalciferol corrects glucose intolerance in hemodialysis patients.

The effects of intravenous 1,25 dihydroxycholecalciferol [(OH)2D3] on glucose tolerance and insulin secretion were studied in eleven uremic patients on regular hemodialysis and compared with eleven healthy controls. Intravenous glucose tolerance tests (IVGTT) were used to assess glucose tolerance, and the hyperglycemic clamp technique was used to quantitate endogenous insulin secretion. Three days after they had discontinued oral 1,25(OH)2D3, the dialysis patients were then studied with (+D) and without (-D) a single intravenous dose of 1,25(OH)2D3 at 2 micrograms/m2, given two hours before the IVGTT or clamp studies. During the -D studies, the uremic patients were glucose intolerant but not hyperinsulinemic. Intravenous 1,25(OH)2D3 in dialysis patients increased glucose uptake (K values) during IVGTT by 38% (P less than 0.02) and increased early component of insulin secretion during hyperglycemic clamps by 48% (P less than 0.01) and the late component by 32% (P less than 0.01). After intravenous 1,25(OH)2D3, the dialysis patients became hyperinsulinemic and regained glucose tolerance. Intravenous 1,25(OH)2D3 did not change the K values during IVGTT nor the insulin secretion during hyperglycemic clamps in the control subjects. During the -D studies, serum concentrations of 1,25(OH)2D3 were significantly lower in uremic patients compared with controls. Serum 1,25(OH)2D3 during the +D studies increased to supraphysiological levels in both uremic patients and controls. Serum concentrations of intact parathyroid hormone, total and ionized calcium, magnesium, potassium, urea nitrogen and creatinine were not different between the +D and -D studies in neither the uremic patients nor the controls. These results suggest that 1,25(OH)2D3 deficiency, independent of parathyroid hormone and calcium, may contribute to the abnormalities in glucose tolerance and insulin secretion in dialysis patients.     

Acetate metabolism and bicarbonate generation during hemodialysis: 10 years of observation

The capacity of chronically hemodialyzed patients to metabolize acetate during conventional hemodialysis was evaluated using a retrospective study in 219 patients dialyzed for up to ten years under similar dialysis conditions. For each patient, and using all available data, a regression line relating the changes of plasma total CO2 during dialysis as a function of the pre-dialysis value was calculated. The intercept of this function indicates the plasma concentration where the losses of bicarbonate in the dialysate is matched by the generation of bicarbonate arising from the metabolism of acetate. This value therefore represents an individual index of the capacity of each patient to metabolize acetate. A value for this index smaller than 18.0 mM was considered abnormal. It was shown that around 10% of chronically hemodialyzed patients are clearly unable to metabolize acetate optimally. This defect is not related to the duration of dialysis, body weight or quality of hemodialysis treatments but is strongly related to sex, 19 of the 22 "acetate intolerant" patients being women. In a prospective study, all the 60 patients of the same population undergoing active dialysis were studied, and this index identified 12 abnormal (11 women, 1 man) patients and 48 normal patients. Plasma acetate measured at the end their dialysis treatments were significantly higher in abnormal than in normal patients. It is concluded: that this index is useful to identify the patients unable to metabolize acetate optimally; that only around 10% of hemodialyzed patients present a severe problem when dialyzed against acetate and should be dialyzed against bicarbonate; that dialysis against acetate does not fully correct the metabolic acidosis even in "normal" patients.     

Hemodynamic monitoring during hemodialysis.

Intradialytic monitoring of hemodynamic parameters is an active area of research; future developments in this field will decrease intradialytic morbidity and the mortality of end-stage renal disease patients treated by hemodialysis. Recent investigations have been assisted by the development of devices that can continuously and noninvasively measure hematocrit and plasma protein concentration during the treatment. Intradialytic morbidity, fluid overload, and hypertension in chronic hemodialysis patients have been shown to be associated with either large or small intradialytic decreases in blood or plasma volume that can be routinely measured by these devices. The use of intradialytic changes in blood volume as a feedback control parameter to vary the ultrafiltration rate and dialysate sodium concentration, so called profiling, is now possible, but further research in this area is necessary to show how to optimize the control algorithms. Other, more preliminary studies suggest that monitoring of central blood volume, extracellular volume, and cardiac output during hemodialysis may permit improved hemodynamic stability during treatment and better control of blood pressure. Although optimal application of these techniques and devices remains to be shown, their routine use during maintenance hemodialysis therapy will likely be the standard of care in the near future.     

Acetate versus bicarbonate hemodialysis in critically ill patients

The hemodynamic state, acid-base balance and blood gases were studied in 9 acute renal failure patients during recirculation acetate- and bicarbonate dialysis. A significant hemodynamic instability, due to a decreased cardiac performance, was observed during acetate dialysis, whereas during bicarbonate dialysis, there was a stable hemodynamic state. During acetate dialysis, pO2 dropped significantly, due to a decreasing ventilatory drive as a consequence of the significantly lower pCO2 in acetate dialysis. From these findings, we conclude that bicarbonate dialysis should be the first choice in the treatment of acute renal failure patients.     

Muscle protein metabolism during hemodialysis.

Despite improvement in many aspects of the care of maintenance hemodialysis (HD) patients, protein-calorie malnutrition, which is characterized by an insidious loss of somatic protein, is common and is a major risk factor for increased morbidity and mortality. We present here an overview of the current knowledge on protein metabolism in uremic patients with the expectation of providing insights into the mechanisms involved in HD-associated catabolism and outlining the rationale underlying intradialytic nutrition. We concentrate on the discussion of muscle protein metabolism because muscle is the predominant site of protein storage, and its integrity is mandatory for the maintenance of a good quality of life.     

Oxygen consumption during maintenance hemodialysis.

The influence of hemodialysis on oxygen consumption was studied in 15 patients on maintenance dialysis. Red cell 2,3-DPG, P50, an inverse measure of oxygen affinity of hemoglobin, arterial and central venous blood gases and cardiac index were measured. 2,3-DPG remained unchanged, whereas in vivo P50 fell significantly during dialysis due to a rise of pH (Bohr effect). Arterial PO2 was lower after than before dialysis, but arterial and central venous oxygen saturations did not change significantly. Cardiac index increased from 3.66 to 4.0k liter/min/m2. Oxygen consumption rose from 120.5 to 131.7 ml/min/m2 (p less than 0.05), the rise being accounted for by an increase in cardiac index and by a slight post-dialysis hemoconcentration. However, even correcting for these parameters did not reveal a decrease in oxygen consumption. It is concluded that, contrary to previous assumptions, the hemodialysis-induced rise in pH with its consequent increase of oxygen hemoglobin affinity did not impair oxygen delivery in this group of patients on maintenance dialysis.     

Minimal intermittent heparinization during hemodialysis.

Minimal dose heparinization inhibiting clotting factor IXa, Xa, XIa, as monitored by the activated partial thromboplastin time, was compared with conventional intermittent, continuous and regional heparinization during hemodialysis treatment. Blood loss in coil dialyzers was the same. Heparin dosage was reduced markedly. Protamine sulfate and infusion equipment were not required. No bleeding problems were encountered in high-risk patients.     

Computer analysis of hypoxemia during hemodialysis.

Arterial oxygen partial pressure decreases during hemodialysis if acetate as buffer is used or if certain types of bioincompatible dialyzer membranes are used. Several hypotheses considering the main cause of this hypoxemia have been proposed. To gain more insight into the mechanisms leading to this hypoxemia, a mathematical model for the computerized simulation of exchange processes during hemodialysis has been used. To simulate the ventilation-perfusion ratio (VA/Q), a simplified two-compartment model of the lung has been applied. The simulation results reveal that hypoxemia during hemodialysis has two reasons. In acetate hemodialysis, the main cause is a shift of the CO2-bicarbonate equilibrium caused by "consumption" of hydrogen ions during acetate metabolization resulting in hypoventilation due to a decrease in CO2 partial pressure. During hemodialysis with bioincompatible dialyzer membranes, the hypoxemia may be explained by an increase in inhomogeneity of the VA/Q ratio in the lung. The loss of CO2 and bicarbonate into the dialysate during acetate hemodialysis has only a minor effect on arterial PO2 and cannot explain the observed hypoxemia. The decrease of O2 diffusing capacity during hemodialysis with bioincompatible membranes has only a negligible effect on the arterial PO2. The simulation results show also that the venous PO2 in the brain may fall below a critical level of less than 25 mm Hg, thereby possibly causing oxygen deficiency in the cortex.     

Changes in oxygen delivery during hemodialysis.

The effect of hemodialysis on oxygen delivery has been assessed in nine patients. During hemodialysis the arterial PO2 decreased from 76.89 mm Hg to 69.03 mm Hg. There was also an increase in pH from 7.39 to 7.49 which resulted in an increase in the affinity of the blood for oxygen. In the absence of compensatory changes this could result in a 17.9% decrease in oxygen delivery. This could be hazardous in patients who are already anemic particularly in the presence of cardiac or respiratory insufficiency.     

Exercise during hemodialysis

In patients with end-stage renal failure physical exercise has beneficial effects on functional capacity, anemia, cardiovascular risks factors and on psychosocial problems. However, only few patients are able or willing to participate in an exercise training which is organised on an outpatient basis. As a consequence, an exercise program was developed which can be performed during hemodialysis. This program consists of a low intensity endurance training with a bed bicycle ergometer, gymnastics to increase muscular strength, flexibility and co-ordination and of relaxation techniques. An increasing number of studies show that this type of exercise training has comparable beneficial effects as an outpatient exercise rehabilitation program. In addition, exercise during hemodialysis increases the solute removal and thereby the efficiency of dialysis probably by an increased perfusion of skeletal muscles. Since 1995 this type of exercise training was implemented in about 200 German dialysis centers. The participation rate is much higher than in supervised outpatient rehabilitation programs as also elderly patients and patients with severe additional medical problems participate. Even in very old patients functional capacity is improved by exercise during dialysis. As a consequence, some patients do not need any longer professional help for the activity of daily living. Up to now no serious adverse effects or complications were induced by exercise during dialysis. This could be achieved as the patients are instructed and supervised by physiotherapists who have special knowledge and skills in renal exercise rehabilitation. Almost all patients can do some exercise during dialysis and therefore this is the most favourable type of exercise training for hemodialysis patients today.     

Glucose intolerance during prolonged sevoflurane anaesthesia

Purpose

The effects of prolonged sevoflurane anaesthesia on insulin sensitivity were investigated by two successive intravenous glucose tolerance tests (IVGTT) in eight patients who underwent prolonged surgery.

Methods

The first IVGTT was administered (25 g glucose as 20% dextrose in water iv) over two minutes 35 min after initiation of surgery. Arterial blood samples were obtained at 0, 5, 10, 30, 60, and 120 min after glucose administration for blood glucose and plasma insulin determination. A second IVGTT was performed six hours following the initiation of surgery.

Results

The disappearance rate of glucose (k-value) for the first IVGTT was 0.887 ± 0.436 (mean ± SD) % · min^?1, and 0.784 ± 0.289 for the second IVGTT. Both k-values are lower than the normal value. The maximum insulin response to glucose (ΔIRI · ΔBS^?1) of the second IVGTT was lower than the first IVGTT (0.124 ± 0.092 vs 0.071 ± 0.056, P < 0.05). The total insulin output of the first IVGTT was higher than the second IVGTT (1,161 ± 830 vs 568 ± 389 μU · min · ml^?1, P < 0.05).

Conclusion

Glucose intolerance is enhanced by diminished insulin output in response to blood glucose elevation during prolonged anaesthesia and surgery.     

Calcium balance during hemodialysis

Calcium balance during hemodialysis (HD) is important in determining short-term cardiovascular function, this influences the hemodynamic tolerability of dialysis. In the longer term, calcium flux during HD is an important determinant of overall calcium balance in a patient and may also influence the development and progression of vascular calcification, with its attendant consequences. This article aims to review the assessment and mechanisms of calcium flux during HD, choice of dialysate calcium concentration, influence of HD modality, and potential consequences of therapy choices (cardiovascular and skeletal) resulting from an inappropriate intradialytic calcium balance.     

Sodium fluxes during hemodialysis

Three sets of experiments were performed to determine the effect of the dialysate sodium concentration on the sodium balance of patients undergoing maintenance hemodialysis. First, patients were treated with three different dialysate bath sodium concentrations: 125-132 mEq/l (n = 7), 135-140 mEq/l (n = 11) and 145-150 mEq/l (n = 6). We demonstrated that the pretreatment plasma sodium concentration was independent of the sodium concentration of the dialysate used. Second, the plasma sodium concentration available for diffusion during the treatment was calculated from the plasma sodium concentration and the plasma proteins. The accuracy of this calculation was demonstrated by comparing the predicted value with the concentration of sodium measured in an ultrafiltrate obtained at minimal filtration fraction. Third, the sodium fluxes using a hypernatremic or hyponatremic dialysate were calculated for 100 ml of plasma going through the dialyzer. At steady state, no significant differences in net sodium fluxes were demonstrated between hyper- and hyponatremic dialysis.