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BACKGROUND AND AIMS Irisin is a circulating myokine released by skeletal muscle after exercise. Its production decreases in chronic kidney disease (CKD) as a potential consequence of sarcopenia and physical inactivity. Irisin produces beneficial effects in glucose and lipid homeostasis: it promotes glucose tolerance and lipid metabolism and improves insulin resistance, stimulates browning of white adipose tissue and upregulates thermogenesis. Irisin may also produce a protective effect on the cardiovascular system as it promoted the proliferation of cardiomyocytes and suppressed myocardial fibrosis and hypertrophy. Low serum irisin was proposed as a predictor of cardiovascular mortality. We studied the relationship of serum irisin with cardiovascular risk in a sample of patients at different stages of CKD not undergoing dialysis and characterized for their artery calcification and mineral metabolism variables. METHOD Seventy-nine consecutive patients with stage 3–5 CKD were recruited from the patients of the nephrology outpatient clinic of our institute in Milan from 2010 to 2014. Serum irisin levels were measured at baseline in all recruited patients and in 20 healthy controls. Incident cardiovascular events were recorded during a 3-year follow-up. They included myocardial infarction, angina pectoris, coronary revascularization, congestive heart failure, stroke, TIA and cardiovascular death. RESULTS Serum irisin was significantly higher in controls than that in patients with CKD and in patients with CKD stage 3 than that in patients at stage 4 and 5 taken together. Taking controls and patients with CKD together eGFR was positively correlated with serum irisin. Patients with CKD were grouped according to tertiles of serum irisin. Patients in the lowest tertile had lower serum 1,25(OH)2D levels than patients in the middle and the highest tertile. Patients in the highest tertile had lower Kauppila aortic calcification score than patients in the middle and the lowest tertiles. Twenty patients suffered from cardiovascular events during a 3-year follow-up. Cox regression analysis confirmed the association of serum irisin with incident cardiovascular events during the follow-up, as patients in the highest tertile of serum irisin showed a lower cardiovascular risk than patients in the middle or the lowest tertile. Kaplan–Meier survival analysis showed that patients in the highest serum irisin tertile developed less cardiovascular events during the follow-up than patients in the other tertiles taken together (P = 0.049). CONCLUSION The present study suggests that irisin is a marker of cardiovascular risk in patients with CKD. It might contribute to the cardiovascular protection that physical exercise and active lifestyle produce in patients with CKD.

BACKGROUND AND AIMS Indoxyl sulphate (IS) and Cresyl sulphate (CS) are uremic toxins generated by the intestinal amino acid catabolism. Blood levels of these toxins increase in patients with CKD and are linked to cardiovascular events. Therefore, we studied the relationship between serum levels of free IS and CS and divalent ion metabolism variables and cardiovascular morbidity (stroke, heart failure, angor and myocardial infarction) in 139 haemodialysis patients (age 68 + 13 years, weight 65 + 13 kg, dialysis vintage 69 + 71 months). METHOD We divided patients according to tertiles of free serum IS and CS. RESULTS Patients in the highest tertile of serum free IS showed shorter dialysis vintage and higher body weight gain between dialysis sessions than patients in the other two tertiles. Patients in the highest tertile of IS showed lower body weight and serum concentrations of alkaline phosphatase, 1,25(OH)2D and PTH compared with the lowest tertile. Serum PTH was also measured during 2 years after the baseline; it was higher in patients in the lowest than those in the highest tertile of serum free IS. No relationships of serum free CS concentrations with phosphate and calcium metabolism variables were observed. Kaplan–Meier survival analysis shows an increased cardiovascular morbidity in patients in the CS highest tertile (blue line in the figure) compared with those in the lowest and middle tertiles taken together (red line; P = 0.01). This association was not found considering IS tertiles. CONCLUSION Our findings suggest that serum free IS may be associated with PTH and 1,25(OH)2D secretion, whereas free PCS may predict cardiovascular risk in haemodialysis patients. A point for future investigation could be the relationship between IS and adynamic bone disease.

BACKGROUND AND AIMS X-linked hypophosphoremic rickets (XLH) is a rare disease caused by mutations in the PHEX gene leading to an increase in the serum levels of FGF23, which inhibits the tubular reabsorption of phosphates and the production of 1,25(OH)2D. These alterations cause hypophosphatemia, rickets, bone deformities, growth retardation and muscle activity impairment. METHOD Burosumab (B) is a monoclonal antibody against FGF23, used for the treatment of XLH. In Italy B can be employed in adults only as compassionate use. In 2020, we treated four adult XLH patients with B (1 mg/kg sc every 4 weeks) for 24 weeks. These patients, V.M. (M, 32 years), S.T. (F, 47), E.R. (M, 46) and S.M. (F, 20) had legs deformities, musculoskeletal pain and severe disability. RESULTS In all patients, phosphorus levels were normalized by B 2 weeks after the B injection, but its levels decreased during the following 28 days; the effect of B on serum phosphate declined during the 24-week follow-up. Plasma values of 1,25(OH)2D and CTX (C-terminal telopeptide of type I collagen) increased after burosumab, but their increase was less marked after the first two injections. In contrast, PTH and bALP values did not change during B therapy. Scores of BPI test, chair test and walking test confirmed an improvement in the fatigue resistance and physical performance. Other tests showed the improvement of self-reported well-being and quality of life in all patients. These effects were not observed in adult patients on conventional therapy with phosphate salts and active vitamin D. CONCLUSION Therefore, markers of physical conditions and life quality may be more indicative for the necessity of burosumab treatment than serum phosphate, which may not be a significant marker to initiate burosumab treatment in adult patients. Burosumab treatment of XLH patients is well-tolerated and leads to prolonged beneficial effects on general conditions of patients although the inconstant improvement of serum phosphate.