[Vascular dysfunction in Cardiorenal Syndrome type 4].

The Cardiorenal Syndrome type 4 (CRS-4) defines a pathological condition in which a primary chronic kidney disease (CKD) leads to a chronic impairment of cardiac function. The pathophysiology of CRS-4 and the role of arterial stiffness remain only in part understood. Several uremic toxins, such as uric acid, phosphates, advanced glycation end-products, asymmetric dimethylarginine, and endothelin-1, are also vascular toxins. Their effect on the arterial wall may be direct or mediated by chronic inflammation and oxidative stress. Uremic toxins lead to endothelial dysfunction, intima-media thickening and arterial stiffening. In patients with CRS-4, the increased aortic stiffness results in an increase of cardiac workload and left ventricular hypertrophy whereas the loss of elasticity results in decreased coronary artery perfusion pressure during diastole and increased risk of myocardial infarction. Since the reduction of arterial stiffness is associated with an increased survival in patients with CKD, the understanding of the mechanisms that lead to arterial stiffening in patients with CRS4 may be useful to select potential approaches to improve their outcome. In this review we aim at discussing current understanding of the pathways that link uremic toxins, arterial stiffening and impaired cardiac function in patients with CRS-4.

Digoxin and Hypermagnesuria.

In a recent issue of Nephron, Abu-Amer et al.[1] reported the presence of hypermagnesuria in patients following acute intravenous administration of digoxin and suggested that the Na+/K+-ATPase γ-subunit, which is the pharmacological target of digoxin, can play a role in this process. Hypermagnesuria induced by digoxin may have important clinical consequences, particularly in the presence of inherited and acquired conditions associated with hypermagnesuria and hypomagnesemia. Moreover, the co-administration of digoxin with other drugs that reduce gastrointestinal absorption (i.e., proton pump inhibitors) or increase urinary excretion (i.e., loop diuretics) may increase the likelihood of developing hypomagnesemia. In this article, we reviewed the main causes of hypermagnesuria and discussed potential drug interactions that can enhance the magnesuric effect of digoxin. We suggest that during the administration of digoxin, clinicians should consider the presence of other causes of hypomagnesemia and hypermagnesuria that could enhance the magnesuric effect of digoxin, monitor the urinary and serum levels of magnesium and prescribe an oral supplementation of magnesium.

[Magnesium, calcium and potassium: "no one was born alone"]. / Magnesio, calcio e potassio: "Nessuno nasce solo o è nato per sé solo".

In contrast to other ions, magnesium is treated as an orphan by the body: there are no hormones that have a substantial role in regulating urinary magnesium excretion, and bone, the principal reservoir of magnesium, does not readily exchange with circulating magnesium.The Mg ++ is often overlooked by physicians in the differential diagnosis because it is considered insignificant, but its role is crucial for cells function, first of all neurons and cardiomyocytes. A condition of hypocalcemia associated with hypokalemia, especially in the presence of chronic renal failure, should raise suspicion of a lack of Mg ++.We report the case of an old man of 77 year with kidney transplant for 13 years, treated with cyclosporine, and sodium mycophenolate and steroid who, for about a month, accused impaired balance and walking instability, who fell accidentally down with wrist fracture.Blood tests showed hypocalcemia and hypokalemia, and so we required dosage of serum and urinary magnesium. A significant reduction in the ion plasma concentration was seen, associated to a fraction of excretion inappropriately high in relation to the degree of hypomagnesemia.The cause of this important renal loss is likely attributable to cyclosporine, a drug that has as a side effect the inhibition of the reabsorption of Mg ++ in the distal convoluted tubule. then, oral supplementation was started (244 mg of Mg ++ ion / day), with subsequent normalization, after a few days, not only of magnesiemia, but also in serum calcium and potassium levels, and improvement of neurological symptoms.Hypomagnesaemia is common in patients with renal transplantation in therapy with calcineurin inhibitors ICN, due to the effects of such drugs on the TRPM6 transporter present in the kidney distal convoluted tubule. To prevent complications caused by chronic and severe depletion of magnesium in this particular population, we recommend periodic monitoring of magnesium plasma levels.