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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.

Citrate is an organic compound involved in tricarboxylic acid cycle, regulation of acid-base balance, lipid metabolism and bone formation. The 90% of body citrate is deposited in bone tissue and is released with calcium ions during bone resorption; therefore, bone resorption contributes to maintain normal plasma levels of citrate together with kidney excretion. The parallel release of citrate and calcium from bones decreases the possibility of calcium-phosphate precipitation in soft tissues, as citrate can bind calcium ions in organic fluids. Citrate may also take part to the bone formation as it sustains the correct mineralization of bone organic matrix: its molecule binds calcium ions at the surface of hydroxyapatite nanocrystals and maintains the correct spatial disposition of nanocrystals, thus, stabilizing the structure of bone lamellae and sustaining biomechanical characteristics of bone tissue. Multiple studies observed that citrate administration significantly increased areal and volumetric bone mineral density at different locations of 1-2% per year and improved bone resorption markers as well. Therefore, it has been hypothesised a therapeutic role of citrate in osteoporosis; however, this role has to be better clarified to understand its real anti-fracture effect.

Indoxyl sulfate (IS) and p-cresyl sulfate (PCS) are uremic toxins associated with cardiovascular outcome in CKD patients. The present work is an analysis of the association of serum free, total IS and PCS with cardiovascular events and calcium-phosphate metabolism variables in hemodialysis patients.Serum levels of total and free IS and PCS were measured in 139 hemodialysis patients. Their relationship with calcium-phosphate metabolism variables were tested in an observational cohort study. In addition, their association with cardiovascular events was investigated during a 4-year follow-up.Patients in the highest tertile (T3) of serum free IS showed lower serum 1,25(OH)Serum free IS may be associated with PTH and 1,25(OH)

The correct management of energy intake is crucial in CKD (chronic kidney disease) patients to limit the risk of protein energy wasting especially during low-protein regimes, but also to prevent overweight/obesity. The aim of this study was to assess the energy requirement of older CKD patients using objective measurements. This cross-sectional study enrolled 67 patients (aged 60–86 years) with CKD stages 3–5 not on dialysis, all of whom were metabolically and nutritionally stable. All patients underwent indirect calorimetry and measurement of daily physical activity level expressed by the average daily Metabolic Equivalent Task, using an accelerometer, in order to measure total energy expenditure (mTEE). Estimated TEE (eTEE) was derived from predictive equations for resting energy expenditure and physical activity levels coefficients. The mTEE were lower than eTEE-based on Harris–Benedict or Schofield or Mifflin equations (1689 ± 523 vs. 2320 ± 434 or 2357 ± 410 or 2237 ± 375 Kcal, p &lt, 0.001, respectively). On average mTEE was 36.5% lower than eTEE. When eTEE was recalculated using ideal body weight the gap between mTEE and eTEE was reduced to 26.3%. A high prevalence of a sedentary lifestyle and reduced physical capabilities were also detected. In conclusion, our data support the energy intake of 25–35 Kcal/Kg/d recently proposed by the NKF-KDOQI (National Kidney Foundation-Kidney Disease Improving Quality Initiative) guidelines on nutritional treatment of CKD, which seem to be more adequate and applicable than that of previous guidelines (30–35 Kcal/Kg/d) in elderly stable CKD patients with a sedentary lifestyle. According to our findings we believe that an energy intake even lower than 25 Kcal/Kg/d may be adequate in metabolically stable, elderly CKD patients with a sedentary lifestyle.

Background In February 2020 the corona virus disease 2019 (COVID-19) infection started spreading throughout Italy, hitting the Lombardy region very hard. Despite the high diffusion, only a subset of patients developed severe COVID-19: around 25% of them developed acute kidney injury (AKI) and one-third of them died. Elderly patients and patients with high comorbidities were identified as being at higher risk of severe COVID-19. Methods Our prospective observational cohort study includes 392 consecutive patients hospitalized for COVID-19 in Milan (median age 67 years, 75% male). We evaluated the relationship between blood pressure at presentation, presence of AKI at Emergency Department admission and during hospitalization, and total in-hospital mortality (24%). Results Although 58% of our study patients reported a history of hypertension (HYP) (86% on treatment), 30% presented with low blood pressure levels. Only 5.5% were diagnosed with AKI on admission; 75% of hypertensive patients discontinued therapy during hospitalization (only 20% were on treatment at discharge). Gender and hypertension were strongly associated with AKI at admission (odds ratio 11). Blood pressure was inversely correlated with increased risk of AKI upon admission, regardless of the severity of respiratory distress. Age over 65, history of hypertension, and severity of respiratory distress were the main predictors of AKI, which developed in 34.7% of cases during hospitalization. AKI was associated with increased in-hospital mortality. Hypertension and low blood pressure at presentation were the main predictors of in-hospital mortality, together with age over 65, baseline pulmonary involvement, and severity of illness. Conclusions In patients hospitalized for COVID-19, hypertension and low blood pressure at presentation are important risk factors for AKI and mortality. Early reduction of antihypertensive therapy may improve outcomes in patients with SARS-CoV-2 infection.