Higher rates of acute rejection early in treatment were seen with the steroid-free regimens, but this did not translate into poorer long-term outcomes, such as graft and patient survival and renal function. A trend for a more favorable cardiovascular risk profile was observed for steroid-free immunosuppression with Tac/Bas.

Basal levels of [Ca2+]i are elevated in diabetes mellitus. Such an abnormality is most likely due to both increased calcium influx into cells and decreased efflux of this ion out of the cells. The present study examined the cellular pathways that are responsible for hyperglycemia-induced acute rise in polymorphonuclear leukocytes (PMNL), and explored whether such a rise is due to increased calcium entry into PMNL and/or to calcium release from their intracellular stores. There were dose dependent and time dependent rises in the [Ca2+]i of PMNL exposed to high concentrations of glucose. Similar effects were observed when the PMNL were exposed to high concentrations of choline chloride or mannitol. A substantial part of the rise in [Ca2+]i was inhibited when the media contained verapamil or nifedipine or when the PMNL were placed in calcium free media, and the rise in [Ca2+]i was completely abolished when the PMNL were placed in calcium free media containing ryanodine. GDP beta S or pertussis toxin almost completely prevented the glucose-induced rise in [Ca2+]i of PMNL. Rp-cAMP, H-89 or staurosporine produced significant inhibition of the rise in [Ca2+]i. High concentrations of glucose produced a dose dependent shrinkage of PMNL volume over a period of two hours. The volume of PMNL, however, was normal after 24 hours in vitro incubation studies as well as after 1, 2 and 12 days of streptozotocin-induced hyperglycemia in rats. The results are consistent with the formulation that the osmotic activity (cell shrinkage) of the high glucose concentrations activates G protein(s) which then stimulates the adenylate-cAMP-protein kinase A pathway, phospholipase C system and calcium channels. The stimulation of these cellular pathways permits both calcium influx into the PMNL as well as mobilization of calcium from their intracellular stores. Both of these events contribute to the acute rise in their [Ca2+]i. It is possible that the rise in [Ca2+]i is critical for the stimulation of the events that lead to the generation and accumulation of inorganic osmolytes to restore cell volume to normal.

Endocrine abnormalities in patients with chronic renal failure are well documented. The present study aimed to assess the influence of long-term erythropoietin (EPO) therapy on endocrine abnormalities in hemodialyzed patients. Two groups of hemodialyzed patients, each of which comprised 17 subjects, were examined. The first group was treated by EPO (EPO group) while the second one did not receive this hormone (No-EPO group). A complete biochemical and hormonal check-up was performed before and at the 3, 6, 9, and 12 month points of the study period. Normal values for the estimated parameters were obtained in appropriately selected sex- and age-matched healthy subjects. After EPO therapy, an increase of the hematocrit value from 21.8 +/- 0.9 to 32.6 +/- 0.9% was observed, which was accompanied by a significant decline of plasma ferritin and saturation of transferrin. In patients of the No-EPO group, a significant although less marked rise of the hematocrit value (21.4 +/- 0.4 to 24.2 +/- 0.6%) was also noticed. EPO therapy did not change plasma levels of electrolytes (Na, K, Ca, inorganic phosphate), osteocalcin, creatinine, glucose, and alkaline phosphatase as well as plasma concentrations of calcium-related hormones (PTH, calcitonin, 1,25[OH]2D3), vasopressin, and triiodothyronine. EPO treatment induced a significant decrease in somatotropin, prolactin, follitropin, lutropin, ACTH, cortisol, plasma renin activity, aldosterone, noradrenaline, adrenaline, dopamine, glucagon, pancreatic polypeptide, and gastrin plasma levels and an increase in plasma insulin, estradiol, testosterone, atrial natriuretic peptide, thyrotropin, and thyroxine.(ABSTRACT TRUNCATED AT 250 WORDS)

The results are consistent with the formulation that the osmotic activity (cell shrinkage) of the high glucose concentration may activate a stretch receptor with subsequent stimulation of various cellular pathways including G protein(s), cAMP-protein kinase A and phospholipase C systems and calcium channels. Activation of these cellular pathways permits both calcium influx into renal tubular cells and mobilization of calcium from their intracellular stores. Further, a decrease in calcium efflux secondary to the reduction in the Vmax of Ca2+ ATPase may occur. It is possible that the rise in [Ca2+]i is critical for the stimulation of the events that lead to restoration of cell volume to normal.

An elevation in intracellular calcium ([Ca2+]i) in rats with chronic renal failure and elevated blood levels of PTH is associated with down-regulation of the mRNA of many proteins. Similarly, in phosphate depleted animals that have normal renal function and low blood levels of PTH, [Ca2+]i is elevated and the mRNA of PTH-PTHrP receptor is down-regulated. The effect of elevation in [Ca2+]i on molecular machinery of many proteins may represent a generalized phenomenon. Diabetes mellitus may also be associated with a rise in [Ca2+]i and therefore down-regulation of the mRNA of proteins may also occur. The present study examined the effect of streptozotocin-induced diabetes mellitus in rats on the [Ca2+]i of the renal proximal tubular cells and on their mRNAs of the PTH-PTHrP, V1a and AT1 receptors. The basal levels of [Ca2+]i of these cells increased significantly (P < 0.01) after one day of diabetes and remained elevated thereafter. There was a significant (r = 0.67, P < 0.01) direct correlation between the [Ca2+]i of the cells and blood levels of glucose up to 350 mg/dl, and the value of [Ca2+]i plateaued with higher concentrations of glucose. Three days of amlodipine therapy prevented and reversed the elevated levels of [Ca2+]i despite marked hyperglycemia. The mRNA of all three receptors in the kidney were down-regulated and this defect was prevented by amlodipine which normalized the [Ca2+]i of the cells. The results show that: (1) the hyperglycemia of IDDM in rats causes a significant elevation in the basal levels of [Ca2+]i of the renal proximal tubular cells and down-regulation of their mRNA of PTH-PTHrP, V1a and AT1 receptors; (2) normalization of the [Ca2+]i of these cells by treatment of the diabetic rats with amlodipine prevented the elevation of [Ca2+]i and the down-regulation of the mRNA of these receptors; (3) these effects occurred in the presence of normal renal function and normal blood of PTH and phosphorus.