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Bone mineral abnormalities (defined as Chronic Kidney Disease Mineral Bone Disorder; CKD-MBD) are prevalent and associated with a substantial risk burden and poor prognosis in CKD population. Several lines of evidence support the notion that a large proportion of patients receiving maintenance dialysis experience a suboptimal biochemical control of CKD-MBD. Although no study has ever demonstrated conclusively that CKD-MBD control is associated with improved survival, an expanding therapeutic armamentarium is available to correct bone mineral abnormalities. In this position paper of Lombardy Nephrologists, a summary of the state of art of CKD-MBD as well as a summary of the unmet clinical needs will be provided. Furthermore, this position paper will focus on the potential and drawbacks of a new injectable calcimimetic, etelcalcetide, a drug available in Italy since few months ago.

In recent years, novel anticoagulant drugs have been introduced in the clinical armamentarium and have progressively gained momentum. Although their use is increasing among CKD patients, some skepticism about their risk–benefit ratio still persists. We sought to investigate the safety and effectiveness of rivaroxaban in a cohort of moderate-to-advanced CKD patients. This observational, retrospective, longitudinal study involved 347 consecutive CKD stage 3b–4 (according to NKF–KDOQI guidelines) patients enrolled from 8 cardiac outpatient clinics between March 2015 and October 2017. All patients received anticoagulation (100 warfarin vs. 247 rivaroxaban) as part of their non-valvular atrial fibrillation management at the attending physician’s discretion. Clinical effectiveness (defined as the occurrence of ischemic stroke, venous thromboembolism, or transient ischemic attack) and safety (intracranial hemorrhage, gastrointestinal or other bleeding) were assessed separately. Over a mean follow-up period of 16 ± 0.3 months, 25 stroke episodes (15 hemorrhagic, and 10 ischemic) occurred in 24 warfarin treated patients vs. none in the rivaroxaban arm. There were 5 vs. 0 episodes of deep venous thrombosis and 8 vs. 2 major episodes of bleeding in the warfarin and rivaroxaban groups, respectively. In contrast, the proportion of minor episodes of bleeding was similar between groups. Rivaroxaban seems a safe and effective therapeutic option in CKD stage 3b–4 patients. However, future randomized controlled trials are needed to definitively establish the role of rivaroxaban in CKD patients.

Background Metabolic acidosis is associated with accelerated progression of chronic kidney disease (CKD). Whether treatment of metabolic acidosis with sodium bicarbonate improves kidney and patient survival in CKD is unclear. Methods We conducted a randomized (ratio 1:1). open-label, controlled trial (NCT number: NCT01640119. www.clinicaltrials.gov) to determine the effect in patients with CKD stage 3–5 of treatment of metabolic acidosis with sodium bicarbonate (SB) on creatinine doubling (primary endpoint), all-cause mortality and time to renal replacement therapy compared to standard care (SC) over 36-months. Parametric, non-parametric tests and survival analyses were used to assess the effect of SB on these outcomes. Results A total of 376 and 364 individuals with mean (SD) age 67.8 (14.9) years, creatinine clearance 30 (12) ml/min, and serum bicarbonate 21.5 (2.4) mmol/l were enrolled in SB and SC, respectively. Mean (SD) follow-up was 29.6 (9.8) vs 30.3 (10.7) months in SC and SB. respectively. The mean (SD) daily doses of SB was 1.13 (0.10). 1.12 (0.11). and 1.09 (0.12) mmol/kg*bw/day in the first, second and third year of follow-up, respectively. A total of 87 participants reached the primary endpoint [62 (17.0%) in SC vs 25 (6.6%) in SB, p

CKD and HIV infection are two chronic diseases impacting heavily on the survival of the affected patients. The interplay between HIV infection and chronic kidney disease (CKD) is complex and interactions occur at multiple levels. Approach to the management of HIV-infected patients requires special attention to face the numerous therapeutic difficulties ranging from drug-drug interactions to drug-toxicity. The most effective strategy is targeted to suppression of HIV viral load, as it dramatically changes the prognosis of the patients as well as prevents the development of HIV-associated kidney disease. As shown in this review, the approach to the therapeutic management of CKD in the setting of HIV infection varies in relation to the degree of renal impairment.

In the general population and in hemodialysis patients epicardial adipose tissue (EAT) has been associated with increased mortality and cardiovascular events. Weight loss and lipid lowering therapies reduced EAT in the general population. It is unknown whether sevelamer, a phosphate (Pi) binder that lowers cholesterol and reduces inflammation in dialysis patients also affects EAT progression. Post-hoc analysis of a randomized trial of sevelamer (SVL) versus calcium-based Pi binders (CPiB) in incident hemodialysis patients. EAT was measured on cardiac computed tomography scans performed at enrollment, 6, 12 and 18 months from baseline. Of 109 patients, 54 received SVL and 55 CPiB; the median LDL change was −16.4 % (IQR: −67.5, 142.3 %) and 12.1 % (IQR: −51.9, 193.8 %) with SVL and CPiB respectively (p

Background Phosphorus is associated with mortality in patients with chronic kidney disease (CKD) not on dialysis, possibly through phosphorus-dependent vascular calcification. Although a phosphorus-restricted diet reduces serum phosphorus, it is unlikely that it reduces vascular calcification progression in CKD. This study evaluated whether a combined strategy of phosphorus-restricted diet and phosphate-binding therapy can reduce the risk of allcause mortality and/or dialysis initiation by attenuating coronary artery calcification (CAC) progression in nondialysis CKD patients. Methods This was a post hoc analysis of a subgroup of patients from a study that evaluated the impact of two phosphorus binder regimens on hard outcomes in CKD. Patients (n = 113) with stage 3–4 CKD and evidence of CAC on a phosphorus-restricted diet were randomized to receive either calcium carbonate or sevelamer added to their phosphorus-restricted diet. End-points were death for any cause and initiation of dialysis. Patients were monitored to the first event or to conclusion of the 36-month follow-up. Results Overall, treatment with calcium carbonate was associated with increased CAC progression and occurrence of all-cause mortality, dialysis initiation, and the composite end-point. After adjustment for confounders, sevelamer use was the only independent predictive factor of reduced risk of each endpoint but only if CAC progression was either absent or moderate. Accelerated progression (annual CAC increase[75th percentile of the study cohort) increased the risk of all-cause mortality and composite end-point (p = 0.01) independently of the use of sevelamer. Conclusions A significant reduction in all-cause mortality, dialysis initiation, and composite end-point risk was achieved by combining phosphorus-restricted diet and sevelamer in non-dialysis CKD patients with absent or moderate but not accelerated CAC progression. Future studies should investigate the role of serum phosphorus, the usefulness of a phosphorus- restricted diet, and the appropriateness of current normal ranges of serum phosphorus concentration in relation to events in non-dialyzed CKD patients.

Although less frequent than vascular calcification, cardiac valve calcification (CVC) is a relevant clinical problem affecting about 2%-10% of adults from the general population aged 75 years and older, and is 5- to 10-fold more prevalent in individuals with impaired kidney function. An expanding body of evidence suggests that mineral metabolism abnormalities aside from traditional cardiovascular risk factors are involved in CVC pathogenesis. Nonetheless, very few studies have investigated whether mineral metabolism manipulation impacts CVC. In this issue of the Journal of Nephrology, it is reported that a combination of low-phosphate diet and sevelamer may reduce CVC. Though the observational nature of that study and the lack of a control group significantly limit the generalizability of these results, they fit in with the ongoing debate on the role of chronic kidney disease mineral bone metabolism (CKD-MBD) in the pathogenesis of vascular disease and suggest the importance of mineral metabolism control in patients with CKD.

Vascular and valvular calcifications are a common finding in chronic kidney disease (CKD) patients and are associated with increased morbidity and mortality. We investigated the hypothesis that calcification of the cardiac valves is a marker of coronary artery calcification (CAC) and thoracic aorta calcification (AoC) in hemodialysis (CKD-5) patients.This was a cross-sectional study of 145 maintenance CKD stage 5 (CKD-5) patients. All patients underwent electron beam tomography for quantification of CAC and AoC score via the Agatston score. The presence of calcification of the cardiac valves was assessed by standard bi-dimensional echocardiography.Eighty-four of the study patients (58%) had echocardiographic evidence of valvular calcification. A significant and graded association between valvular calcification and CAC as well as AoC was detected. Patients with 1 or 2 calcified valves had a significantly greater likelihood of having a CAC score1,000 (odds ratio [OR] = 5.94; 95% confidence interval [95% CI], 1.91-18.44; p=0.002; and OR=3.27; 95%CI, 1.36-7.88; p=0.007, respectively). Similarly, the presence of 1 or 2 calcified valves was associated with an eightfold and threefold increased probability of an AoC score greater than the third quartile, respectively.This cross-sectional analysis shows that calcification of the cardiac valves is closely associated with vascular calcification, an established marker of risk in prevalent hemodialysis patients.

In chronic kidney disease patients, vascular calcification (VC) is a marker of advanced vasculopathy, suggesting both atherosclerotic and medial calcification. Detection and quantification of VC provide physicians with useful prognostic information independent of traditional cardiovascular risk factors. In addition, this knowledge may help guide appropriate therapeutic choices. A number of noninvasive imaging techniques are available to screen for the presence of VC, some with merely qualitative, and others with both qualitative and quantitative, capabilities. We review the strengths and limitations of the most common noninvasive techniques employed to image VC and the prognostic implications of VC.

Coronary artery calcification (CAC) is common in patients with advanced chronic kidney disease on dialysis. A sizeable proportion of patients has no or minimal CAC at the inception of dialysis, but it is unclear how long they remain free of it.For the purpose of this study, 36 incident hemodialysis patients were submitted to sequential chest computed tomography to quantify CAC at baseline, 6, 12, 18 and 30 months.Among them, 15 had absent or minimal CAC score (CACS 0 to 30) and 21 had a CACS30 at baseline. Overall, the median baseline CACS was 129 (interquartile range [IQR]=0-709) and it increased to 364 (IQR=8.3-1683) at study completion (182% increase). Among the 15 patients with minimal CACS, only 3 progressed and the median CACS increase was 20, as opposed to 15 of 21 patients with a baseline CACS30 whose median progression was 431 (p0.02). The 18 patients who had CACS progression were older (68.5 vs. 57.3 years, p=0.0081) and exhibited a poorer control of mineral metabolism (phosphorus 5.2 vs. 4.9 mg/ dL, p=0.048; corrected calcium x phosphorus product [CaxP] 49.3 vs. 46.2 mg2/dL2, p=0.001) than the patients without progression. On multivariable analysis, independent predictors of progression were baseline CACS (p=0.038) and time-averaged Cax;P (p=0.077).These data suggest that absent or low CAC at baseline is associated with minimal progression even up to 30 months. Careful management of mineral metabolism appears to be one of the main factors that limit progression of CAC.