[Recent advances in the prevention of cardiovascular morbidity and mortality in end-stage renal disease: role of anemia, hyperparathyroidism and calcifications]. / Recenti progressi nella prevenzione di morbilità e mortalità cardiovascolari nell'uremico: ruolo dell'anemia, iperparatiroidismo e calcificazioni.

The mortality rate in patients with end-stage renal disease (ESRD) is extremely high, mainly because of the high prevalence of cardiovascular disease. In addition to traditional cardiovascular risk factors, other factors peculiar to chronic kidney disease play a role. Anemia and calcium-phosphate disorders are of particular interest, not only because they have been related to an increased risk of death but, more importantly, because they can be reversed by treatment, thereby providing the opportunity to prevent or delay the onset of cardiovascular disease. Despite a clear association between higher hemoglobin levels and better survival, data from interventional trials do not seem to show a significant positive effect of hemoglobin normalization with erythropoiesis-stimulating agents on survival and left ventricular mass in ESRD patients. Nevertheless, partial correction of anemia is still an important goal to be reached, as is also suggested by international guidelines. Disorders of calcium-phosphate metabolism have also been clearly related to increased mortality. Unlike anemia, which can be easily corrected by treatment in most cases, mineral metabolism is much less effectively treated. New agents, such as phosphate binders not containing calcium and aluminum, vitamin D analogs with lower calcemic activity, and calcimimetics, are becoming increasingly available in everyday clinical practice and are likely to allow a higher percentage of patients to achieve the recommended targets for calcium-phosphate and parathyroid hormone. Given that these molecules have only been introduced recently, clear data from interventional studies showing improved survival after adequate correction of mineral metabolism parameters are still lacking.

Simultaneous measurement of peritoneal glucose and free water osmotic conductances.

Ultrafiltration (UF) failure is one of the most important causes of long-term peritoneal dialysis (PD) failure in patients. Osmotic forces acting across small and ultra-small pores generate a UF with solutes through the small pore and free water transport (FWT) through the ultra-small pore. The ability of glucose to exert an osmotic pressure sufficient to cause UF is the so-called 'osmotic conductance to glucose' (OCG) of the peritoneal membrane. Our study proposes a simple method to determine both the OCG and FWT. In 50 patients on PD, a Double Mini-Peritoneal Equilibration Test (Double Mini-PET), consisting of two Mini-PET, was performed consecutively. A solution of 1.36% glucose was used for the first test, whereas a solution of 3.86% glucose was used for the second test. The sodium removal values and the differences in UF between the two tests were used to calculate FWT and the OCG. Patients with UF failure showed significant reductions not only in the OCG and the FWT but also of UF of small pores. The Double Mini-PET is simple, fast, and could become useful to evaluate patients on PD in everyday clinical practice.

Constitutive expression of insulin-like growth factor 1 and insulin-like growth factor 1 receptor abrogates all requirements for exogenous growth factors.

BALB/c3T3 cells are exquisitely growth regulated and require both platelet-derived growth factor and insulin-like growth factor-1 (IGF-1) for optimal proliferation. BALB/c3T3 cells that constitutively express IGF-1 and elevated levels of IGF-1 receptor (IGF-1R) are capable of growth in serum-free medium without the addition of any exogenous growth factors. BALB/c3T3 cells overexpressing only the IGF-1R plasmid required IGF-1 or insulin for serum-free growth. Antisense oligodeoxynucleotides complementary to IGF-1R mRNA inhibited IGF-1-mediated cell growth. Under these conditions, neither the epidermal growth factor receptor nor phospholipase C gamma 1 was autophosphorylated. These findings indicate that constitutive expression of IGF-1 and IGF-1R allows 3T3 cells to grow in serum-free medium without addition of those exogenous growth factors that are required by the parent cell line.