Progress in pharmacotherapy for the treatment of hyperphosphatemia in renal failure.

INTRODUCTION: Among the clinical and metabolic complications of progressive chronic kidney disease (CKD), CKD-mineral bone disorder (CKD-MBD) significantly contributes to morbidity and mortality. While overt and persistent hyperphosphatemia is typical of advanced CKD and requires treatment, other abnormalities of calcium/phosphate metabolism begin to occur since the early stages of the disease. AREAS COVERED: We searched on the PubMed database, without restrictions for language or time range, for randomized clinical trials and meta-analyses investigating phosphate-lowering therapies. The various phosphate binders show different safety profiles and diverse effects on calcium/phosphate metabolism and vascular calcification. The in-depth knowledge of the characteristics of these drugs is crucial to ensure adequate treatment to CKD patients. EXPERT OPINION: A proper control of serum phosphate can be achieved using phosphate binders. These medications may induce side effects. Moreover, data on their impact on clinical outcomes are partly controversial or scarce, especially for the new generation drugs. Hyperphosphatemia favors cardiovascular disease and increases the risk for CKD progression. These effects are partially mediated by fibroblast growth factor 23 (FGF23), a phosphaturic hormone that raises to maintain normal serum phosphate. Since there are no data supporting the use of phosphate-lowering agents when phosphataemia is normal, a key role is played by reducing dietary phosphate intake with the aim to control serum phosphate and the compensatory FGF23 and parathyroid hormone (PTH) increase.

PLAIN LANGUAGE SUMMARY: The progressive reduction in renal function, a condition known as chronic kidney disease (CKD), is characterized by several clinical and metabolic complications. Among them are the alterations of calcium and phosphorous metabolism that are part of the so-called CKD-MBD (chronic kidney disease-mineral bone disorder) and contribute to increase morbidity and mortality, especially due to vascular calcification. Persistent hyperphosphatemia is typical of advanced CKD but other abnormalities occur earlier to maintain normal serum calcium and phosphorus levels. These compensatory mechanisms are also involved in the pathophysiology of CKD-MBD and should be counteracted to improve clinical outcomes of CKD patients. Given the crucial role of hyperphosphatemia, numerous therapeutic strategies have been developed over time to help maintain phosphate serum levels within the normal range and prevent or treat CKD-MBD and its consequences. Phosphate binders act by binding dietary phosphate in the gastrointestinal lumen to prevent its absorption. According to their molecular structure, these drugs can be classified into calcium-based (calcium carbonate, calcium acetate), non-calcium-containing (sevelamer carbonate, sevelamer hydrochloride, lanthanum carbonate), aluminum-containing (aluminum hydroxide), and iron-based (sucroferric oxyhydroxide, ferric citrate) compounds. The various phosphate binders show different safety profiles and diverse effects on calcium/phosphate metabolism and vascular calcification. Despite the ability of hyperphosphatemia to favor CKD-MBD development and cardiovascular risk, there are no data supporting the use of phosphate-lowering agents when serum phosphate is normal also due to the potential adverse effects of long-term therapies. Accordingly, a key role is played by reducing dietary phosphate overload since the first stages of CKD.

Lung Dysfunction and Chronic Kidney Disease: A Complex Network of Multiple Interactions.

Chronic kidney disease (CKD) is a progressive disease that affects > 10% of the total population worldwide or >800 million people. CKD poses a particularly heavy burden in low- and middle-income countries, which are least able to cope with its consequences. It has become one of the leading causes of death worldwide and is one of the few non-communicable diseases where the number of related deaths has increased over the last two decades. The high number of people affected, and the significant negative impact of CKD should be a reason to increase efforts to improve prevention and treatment. The interaction of lung and kidney leads to highly complex and difficult clinical scenarios. CKD significantly affects the physiology of the lung by altering fluid homeostasis, acid-base balance and vascular tone. In the lung, haemodynamic disturbances lead to the development of alterations in ventilatory control, pulmonary congestion, capillary stress failure and pulmonary vascular disease. In the kidney, haemodynamic disturbances lead to sodium and water retention and the deterioration of renal function. In this article, we would like to draw attention to the importance of harmonising the definitions of clinical events in pneumology and renal medicine. We would also like to highlight the need for pulmonary function tests in routine clinical practise for the management of patients with CKD, in order to find new concepts for pathophysiological based disease-specific management strategies.

Potential Role of Copper in Diabetes and Diabetic Kidney Disease.

Copper is a fundamental element for the homeostasis of the body. It is the third most abundant essential transition metal in humans. Changes in the concentration of copper in the blood are responsible for numerous diseases affecting various organs, including the heart, brain, kidneys, and liver. Even small copper deficiencies can lead to the development and progression of several pathologies. On the other hand, excessive exposure to copper can cause toxicity in many human organs, leading to various systemic alterations. In the kidney, increased copper concentration in the blood can cause deposition of this element in the kidneys, leading to nephrotoxicity. One of the most interesting aspects of copper balance is its influence on diabetes and the progression of its complications, such as Diabetic Kidney Disease (DKD). Several studies have shown a close relationship between copper serum levels and altered glycemic control. An imbalance of copper can lead to the progression of diabetes-related complications and impaired antioxidant homeostasis. A high Zinc/Copper (Zn/Cu) ratio is associated with improved renal function and reduced risk of poor glycemic control in patients with type two diabetes mellitus (T2DM). Furthermore, the progression of DKD appears to be related to the extent of urinary copper excretion, while regulation of adequate serum copper concentration appears to prevent and treat DKD. The aim of this review is to evaluate the possible role of copper in DKD patients.