Effect of short-term rHuEPO treatment on insulin resistance in haemodialysis patients.

BACKGROUND/AIM: Decreased sensitivity to the hypoglycaemic action of insulin is an almost universal phenomenon in uraemic patients, and it is attributed either to uraemic toxins or to anaemia or even to secondary hyperparathyroidism. Considering the conflicting data of few existing studies, we examined the influence of erythropoietin (EPO) treatment on insulin resistance and tested the probable correlation of this influence with sympathetic nervous system (SNS) activity. METHODS: We studied 8 non-obese, non-diabetic, stable dialysis patients using the euglycaemic insulin clamp technique before administration of EPO (phase A), 10 days after (phase B), and after the correction of the haematocrit level, at least 8 weeks later (phase C). We estimated the indices (glucose infusion rate, mg/kg/min), M/G (glucose clearance), and M/I (tissue sensitivity to insulin), and we measured haematocrit, haemoglobin, triglyceride, ferritin, EPO, and fasting insulin levels in each phase. During each phase, we tested the SNS activity using the response of blood pressure to persistent handgrip and the response of blood pressure to the standing position. RESULTS: Our patients appeared to have an increased insulin resistance in phase A (M(A) = 6.24 +/- 1.01) which was significantly improved 10 days after the beginning of EPO treatment and before the rise of haematocrit (M(B) = 7.71 +/- 1.54, p < 0.05). There was no further improvement in phase C. Indices M/G and M/I behaved similarly. The serum triglyceride levels decreased in response to the increased insulin sensitivity. The patients studied did not demonstrate fasting hyperinsulinaemia, while the SNS activity was abnormal and remained unchanged throughout the study period in spite of some individual improvement. CONCLUSIONS: Our study proves the beneficial effect of EPO treatment on insulin resistance in dialysis patients which could be attributed to the EPO itself and not to the correction of anaemia and is accompanied by improvement in triglyceride levels. Amelioration of insulin resistance did not influence the SNS activity, making the association between EPO treatment and SNS-derived changes in blood pressure quite improbable.

The effect of spironolactone in hypertensive patients on regular haemodialysis and after renal allotransplantation.

To determine the role of the renin-angiotensin-aldosterone system in the maintenance of hypertension in patients with end stage renal disease, twenty four hypertensive patients were studied on regular haemodialysis treatment (RDT) and after successful kidney transplantation. The first group consisted of nine patients on RDT with their own kidneys in situ, and the second group consisted of nine kidney transplants. All 18 patients were given spironolactone 300 mg daily for three weeks following a control period of the same duration. In addition, three anephric patients on RDT were studied with the above protocol and three other patients on RDT were given the same dose for only six days. Blood pressure (BP), body weight, plasma K-Na, aldosterone and renin activity in all patients, and Na and aldosterone in urine in the second group were measured. In the first group of patients on RDT plasma potassium and renin activity increased significantly but BP remained unchanged. In the second group of transplanted patients plasma potassium, renin activity, and aldosterone were increased and BP diminished significantly. In the group of three anephric patients plasma potassium increased but plasma renin activity remained very low. Finally, in the patients on dialysis who received spironolactone for only six days there was a parallel increase of serum potassium and plasma renin activity. These findings suggest that in patients on RDT spironolactone stimulates renin secretion and potassium retention possibly by an effect on the remaining nephrons and/or the intestinal wall. On the contrary, in the transplanted patients the effect of spironolactone on the renal tubule is capable of producing sodium depletion and fall in BP.

Effect of furosemide on acut ischaemic renal failure in the dog.

The effect of furosemide on the development of the acute ischaemic renal failure in the dog was studied. 11 canine kidneys were used as controls (group I) and 12 as a group where furosemide (6-8 mg/kg of body weight) was given (group II) immediately after releasing the clamps. Urine volume and sodium clearance were found significantly higher in the second group of kidneys during a period of 60 min after restoration of the blood flow to the kidney. Urea clearances remained low with no noted difference between the 2 groups. By the end of the first hour osmolar and potassium clearances were found to be significantly higher in the second group. The above findings suggest that furosemide given after an induction of acute ischaemic renal failure in the dog provides, up to the 1st hour after recirculation, some benefit in water and solute excretion but no benefit in urea clearance.