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Objective: The aim of this study was to evaluate the economic consequences of the introduction of roxadustat on the market as treatment for chronic kidney disease (CKD)-related anaemia in Italy. Method: A budget impact model was developed to assess the economic impact of the introduction of roxadustat for the management of patient with CKD-related anaemia. The analysis was conducted considering National Health Service (NHS) perspective and three years' time horizon. Eligible population for the treatment with roxadustat was estimated through published literature and clinicians' support. Direct healthcare costs included drug acquisition (list prices for base case) and administration costs, monitoring costs, cost per blood transfusion, costs related to the management of adverse events and dialysis costs. Results: The model estimated a three years expenditure associated with the management of patients with CKDrelated incident anaemia in Italy of about € 260 and € 44.6 million for non-dialysis dependent (NDD) and dialysisdependent (DD) patients respectively. The introduction of roxadustat on the market could generate a reduction in the expenditure related to the iron supplementation both for NDD and for DD patients (-€ 397,305 and -€ 50,135 over three years of the analysis, respectively) and a reduction in the pharmaceutical expenditure for NDD patients (-€ 2.3 million, -€ 7.5 million and -€ 13 million at first, second and third year of the analysis). Overall, the introduction of roxadustat could generate a saving for NHS approximately equal to € 2.3, € 7.5 and € 13 million at first, second and third year of the analysis. Conclusion: The introduction of roxadustat could generate a reduction in the expenditure for the management of patients with CKD anaemia. A scenario analysis which used tender prices for ESAs and hypothesis of confidential discount for roxadustat showed that the saving for NHS will be kept if roxadustat's discount is greater than 60.3%. [ABSTRACT FROM AUTHOR]

Anaemia is a frequent complication of chronic kidney disease; if severe and untreated, it leads to a worsening of quality of life and an increased risk of resorting to haemotransfusions. Beginning with studies in physio-pathology that began in the late 19th century and continued into the 20th century, the first step was the identification of erythropoietin, then its purification, identification of the gene involved and finally the synthesis of recombinant human erythropoietin and its 'long-acting' analogues. Today, therapy with erythropoiesis-stimulating agents (ESAs), often in combination with martial therapy, is the standard of care for patients with chronic kidney disease and anaemia. Recently, ESAs have been joined by HIF-PHD inhibitors. Unfortunately, both categories of drugs, although effective and well-tolerated in most cases, may be associated with a possible increased cardiovascular and thrombotic risk, especially in particular categories of patients. For this reason, the choice of therapy with ESA and HIF-PHD must be customised in terms of haemoglobin target, molecule type and dosage to be used., (Copyright by Società Italiana di Nefrologia SIN, Rome, Italy.)

We report the case of a 75-year-old man who developed acute myocardial infarction 12 hours after the first dose of ChAdOx1 nCov-19 vaccine. The event was associated with a transient decrease of platelet count and the detection of anti-PF4 antibodies approximately 45 days after the event. Vaccine-induced thrombotic thrombocytopenia (VITT) is characterized by the onset of venous or arterial thrombosis in temporal relationship to the administration of anti-Sars-Cov-2 viral vector vaccines (ChAdOx1 nCov-19 and Ad26.COV2.S), thrombocytopenia and the production of anti-PF4 antibodies. It occurs mainly at a young age, even if the median age is 54 years; it is often associated with thrombosis in atypical sites, such as the cerebral sinus. Our reported case does not present all the diagnostic criteria of VITT. However, the close temporal relationship between ChAdOx1 nCov-19 vaccine administration, thrombosis, and concomitant anti-PF4 antibodies positivity makes the case suggestive of a possible slight form of VITT., (Copyright by Società Italiana di Nefrologia SIN, Rome, Italy.)

Erythropoiesis Stimulating Agents (ESAs) are well-tolerated and effective drugs for the treatment of anaemia in patients with chronic kidney disease. In the past, scientific research and clinical practice around ESAs have mainly focused on the haemoglobin target to reach, and to moving towards the normality range; more cautious approach has been taken more recently. However, little attention has been paid to possible differences among ESA molecules. Although they present a common mechanism of action on the erythropoietin receptor, their peculiar pharmacodynamic characteristics could give different signals of activation of the receptor, with possible clinical differences. Some studies and metanalyses did not show significant differences among ESAs. More recently, an observational study of the Japanese Registry of dialysis showed a 20% higher risk of mortality from any cause in the patients treated with long-acting ESAs in comparison to those treated with short-acting ESAs; the difference increased in those treated with higher doses. These results were not confirmed by a recent, post-registration, randomised, clinical trial, which did not show any significant difference in the risk of death from any cause or cardiovascular events between short-acting ESAs and darbepoetin alfa or methoxy polyethylene glycol-epoetin beta. Finally, data from an Italian observational study, which was carried out in non-dialysis CKD patients, showed an association between the use of high doses of ESA and an increased risk of terminal CKD, limited only to the use of short-acting ESAs. In conclusion, one randomised clinical trial supports a similar safety profile for long- versus short-acting ESAs. Observational studies should always be considered with some caution: they are hypothesis generating, but they may suffer from bias by indication., (Copyright by Società Italiana di Nefrologia SIN, Rome, Italy.)

Renal function reduction rises difficulties in dealing with many drugs. These problems are mainly due to the need of decreasing progressively the doses of the drugs that are cleared by the kidneys, in parallel with the progressive reduction in renal function. The degree of renal impairment should be better measured as the estimated glomerular filtration rate, avoiding to simply rely on plasma creatinine. Physicians should also be aware of the important potential side effects of some very effective and safe drugs, when they are used in patients with relevant reduction in renal function, independently of their possible plasma accumulation. As paradigmatic, we will discuss here the case of azathioprine, metformin and denosumab use, when renal function is heavily decreased.

The number of patients with chronic kidney disease (CKD) is increasing worldwide like an unstoppable tsunami. This causes considerable suffering for patients and families and places a severe economic burden also on society, especially when the patient reaches the stage of being in need of renal replacement therapy. Accordingly, a program of prevention and treatment of CKD at its earlier stages is of great importance, also in view of the fact that the general population is getting older and older and is more frequently affected by comorbidities such as hypertension, diabetes, obesity and cardiovascular disease. All these factors increase the likelihood of the development and worsening of CKD. In the meantime, nephrologists have developed new and better strategies to halt or at least slow the progression of CKD. These are based on the prescription to quit smoking and on dietary interventions guaranteeing an adequate calorie, protein, phosphate and sodium intake together with the correction of metabolic acidosis through either the supplementation of sodium bicarbonate or the choice of basic proteins. The treatment of hypertension and proteinuria (when detectable) by means of RAS inhibitors is another important strategy, where partial correction of anemia and statin use may be of help. Other treatments have not proven to be effective or their introduction into clinical practice is still far away.

Angiotensin-converting enzyme inhibitors (ACE-i) and angiotensin II receptor blockers (ARBs) are of paramount importance in everyday clinical practice. Developed as antihypertensive drugs, they soon acquired another important indication as a result of their antiproteinuric activity and capacity to delay the progression of chronic kidney disease. ACE-i and ARBs started out being used as single drugs and were subsequently combined to obtain more complete blocking of the renin-angiotensin-aldosterone system (RAAS). The most evident advantages derived from the administration of these drugs - alone or in combination - have been obtained in proteinuric nephropathies, such as chronic glomerulonephritis and diabetic nephropathy, where they have become the treatment choice. Dual RAAS blockade has been recently evaluated in a large trial of high-risk cardiovascular patients, in whom no related benefits were shown. To the contrary, a higher risk of worsening renal function emerged. It is now quite clear that patients with high proteinuria levels are the ones that benefit most from RAAS inhibition, also with combined ACE-i and ARB. It is very important to pay the utmost attention when these drugs are used in patients in whom no benefit is obtained by RAAS inhibition, such as patients with chronic kidney disease and atherosclerosis, elderly patients, and those without any significant proteinuria.

The development of recombinant human erythropoietin and its introduction into the market in the late 1980s has significantly improved the quality of life of patients with chronic kidney disease (CKD) and reduced the need for blood transfusions. Starting from a cautious target, a progressive increase in the recommended hemoglobin levels has been observed over the years, in parallel with an increase in the obtained levels. This trend has gone together with the publication of findings of observational studies showing a relationship between the increase in hemoglobin levels and a reduction in the mortality risk, with the conduction of clinical trials testing the effects of complete anemia correction, and with the compilation of guidelines on anemia control in CKD patients by scientific societies and organizations. In the last two years, evidence of a possible increase in the mortality risk in those patients who were randomized to high hemoglobin levels has resulted in a decrease in the upper limit of the recommended Hb target to be obtained with erythropoietin stimulating agents (ESA), and consequently in a narrowing of the target range. Comparison of guidelines on anemia control in CKD patients is an interesting starting point to discuss single recommendations, strengthen their importance, or suggest new topics of research to fill up important gaps in knowledge.