Background: Pro-inflammatory cytokines play a key role in bone remodeling. Inflammation is highly prevalent in CKD-5D patients, but the relationship between pro-inflammatory cytokines and fractures in CKD-5D patients is unclear. We studied the relationship between inflammatory cytokines and incident bone fractures in a cohort of CKD-5D patients. Methods: In 100 CKD-5D patients (66 on HD, 34 on CAPD; males:63, females:37; mean age: 61 ± 15; median dialysis vintage: 43 months) belonging to a single renal Unit, we measured at enrolment bone metabolic parameters (intact PTH, bone and total alkaline phosphatase, calcium, phosphate) and inflammatory cytokines (TNF-α, IL-6, CRP). Patients were followed-up until the first non traumatic fracture. Results: During follow-up (median: 74 months; range 0.5 -84.0) 18 patients experienced fractures. On categorical analysis these patients compared to those without fractures had significantly higher intact PTH (median: 319 pg/ml IQ range: 95–741 vs 135 pg/ml IQ: 53–346; p = 0.04) and TNF-α levels (median: 12 pg/ml IQ: 6.4-13.4 vs 7.8 pg/ml IQ: 4.6-11; p = 0.02). Both TNF-α (HR for 5 pg/ml increase in TNF-α: 1.62 95% CI: 1.05-2.50; p = 0.03) and intact PTH (HR for 100 pg/ml increase in PTH: 1.15 95% CI: 1.04-1.27; p = 0.005) predicted bone fractures on univariate Cox’s regression analysis. In restricted (bivariate) models adjusting for previous fractures, age, sex and other risk factors both PTH and TNF-α maintained an independent association with incident fractures. Conclusions: In our bivariate analyses TNF-α was significantly associated with incident fractures. Analyses in larger cohorts and with adequate number of events are needed to firmly establish the TNF α -fracture link emerged in the present study.
Etelcalcetide is a new calcimimetic indicated for the treatment of secondary hyperparathyroidism (SHPT) in dialysis patients. Etelcalcetide efficacy in SHPT has been ascertained only in randomized controlled trials. This multicenter study was carried out in “real world” setting that is different from randomized controlled trials (RCTs) to (1) evaluate the effectiveness of etelcalcetide in SHPT, (2) to assess calcium, phosphorus, alkaline phosphatase changes, (3) to register gastrointestinal side effects. Data were collected from twenty-three dialysis units with n = 1190 patients on the charge. From this cohort, n = 168 (14%) patients were on treatment with etelcalcetide, and they were evaluated for statistics. A median weekly dose of etelcalcetide was 15 mg (7.5–45 mg). Patients were either naïve (33%) or switched from cinacalcet to obtain better control of SHPT with reduced side effects or pills burden. Serum parathyroid hormone (PTH) declined over time from a median value of 636 pg/mL to 357 pg/mL. The median time for responders (intact PTH (iPTH) range: two to nine times the upper normal limit) was 53 days; the percentage of responders increased (from baseline 27% to 63%) being similar in switched-patients and naïve-patients. Few patients had symptomatic hypocalcemia requiring etelcalcetide withdrawal (four cases (3%) at 30-day control, two cases (2%) at 60-day, one case (1%) at 90-day control). Side effects with etelcalcetide were lower (3–4%) than that registered during cinacalcet treatment (53%). Etelcalcetide is a new therapeutic option for SHPT with low side effects and pills burden. Etelcalcetide may improve adherence to therapy, avoiding unremitting SHP. It remains to be assessed whether etelcalcetide may reduce parathyroidectomy, vascular calcification, or mortality. Being etelcalcetide very potent in suppressing PTH levels, even in severe SHPT, future studies should evaluate the potential risk of more adynamic bone disease during long-term therapy.
DNDialysis And Transplantation On Behalf Of The Sicilian Registry Of Nephrology
Dialysis And Transplantation On Behalf Of The Sicilian Registry Of Nephrology
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Background/Objectives: Phosphate is a macro-element involved in all cellular energetic processes. As about 90% of the phosphate filtered by the glomerulus is excreted by kidneys, the impairment of renal function and the consequent over-secretion of parathyroid hormone and fibroblast growth factor 23 results in the increase in the serum phosphate levels. The association between phosphate and hemoglobin is controversial, as both direct and indirect relationships have been reported. The present study aims to investigate the relationship between phosphate and hemoglobin in a large prospective, longitudinal cohort including dialysis patients from the Sicilian Registry of Nephrology, Dialysis, and Transplantation. Methods: In this prospective cohort study, we included 6263 hemodialysis patients to achieve a total of 120,462 repeated measurements of serum phosphate and hemoglobin over time. The longitudinal association between phosphate and hemoglobin was analyzed by univariate and multivariate Linear Mixed Models. Results: The mean age was 66 ± 16 years and the median dialysis vintage was 5 months [IQR: 2–16]. Mean and median values of hemoglobin and phosphate were 10.7 g/dL (SD 1.3 g/dL) and 4.6 mg/dL [IQR 3.9–5.5 mg/dL], respectively. The multivariate model, adjusted for potential confounders, confirmed the positive association between serum phosphate and hemoglobin [adjβ = 0.13, 95%CI 0.03–0.23, p = 0.01)]. These results were confirmed in analyses stratified for the use of phosphate binders. Conclusions: In our large cohort of dialysis patients, we found a linear, direct relationship between phosphate and hemoglobin levels. As a reduction in phosphate is associated with a parallel reduction in hemoglobin levels, hypophosphatemia can accentuate anemia in dialysis patients. Our results generate the hypothesis that monitoring serum phosphate in clinical practice might provide a better management of anemia.
The management of end-stage kidney disease (ESKD) has been constantly evolving over the last decade with the development of targeted approaches. In this field, telemedicine and remote monitoring are based on the availability of new cyclers that allow for bidirectional communication (between patient and physician) and for the application of the Sharesource cloud-based platform. These technologies allow patients with ESKD to undergo automated peritoneal dialysis (APD) at home. However, these approaches are not well standardized and largely applied yet. Therefore, this study aimed to elaborate a protocol for the utilization of the Sharesource platform to facilitate the practical management of patients treated with APD. A series of expert meetings were held between September 2022 and January 2023 in Italy. The participants (ten nephrologists and five nurses) from nine Italian public dialysis centers shared their opinions, examined the current scientific literature in the field, and reviewed the key characteristics of the Sharesource system to achieve a common position on this topic. A detailed and practical document containing experts’ opinions and suggestions on the use of the Sharesource platform for the management of patients treated with APD was produced. This expert opinion might represent a new useful instrument in clinical practice for managing patients undergoing home-based peritoneal dialysis (PD) through the Sharesource platform, which is valid not only for Italy. These recommendations pave the way to novel patient-centered and personalized therapeutic approaches for ESKD and highlight the advantages of telemedicine and remote monitoring in the management of patients with ESKD undergoing PD and its positive impact on their quality of life.
29 May 2020 in Frontiers in Cell and Developmental Biology
Paget bone disease (PDB) is often asymptomatic and incidentally diagnosed. It is a cause of osteoporosis and bone fragility and exposes patients to a high incidence of bone fractures. In Europe the prevalence varies according to the geographical area of origin, and increases with age. In patients with chronic renal disease, the prevalence is unknown and only few cases with PDB have been reported. We present a challenging case in an elderly patient with chronic kidney disease on peritoneal dialysis treatment. Our patients presented extremely high levels of alkaline phosphatase, suggesting a Paget bone disease. Secondary hyperparathyroidism was confirmed by the bone histological examination. The surprising biochemical and clinical response to active vitamin D confirms the well-known role on hyperparathyroidism and may indicate an additional role in the pathogenesis of Paget’s disease.
Introduction: Acute pulmonary edema (APE) due to fluid overload is considered the most feared complication in hemodialysis patients. Various diagnostic tests have been proposed to assess the fluid status in patients with end-stage kidney failure (ESKF); among these, lung ultrasound (measuring the number of B-lines) is emerging as a promising tool to identify pulmonary congestion in this patient population. Methods: We compared the incidence of APE before and after the implementation of lung ultrasound as a routine practice in our unit. The pre (from 1 January 2007 to 31 December 2008)- and post (from 1 January 2017 to 31 December 2018)-B-line implementation periods included 98 and 108 hemodialysis patients, respectively. By accurately reviewing their electronic medical records, all episodes of APE were collected. The 10-year interval between the two periods was specifically chosen to ensure no overlap between patients of the two cohorts whereas the single-center design was adopted to minimize the influence of center effect on the study results. Results: APE episodes occurred more frequently in patients from the pre-B-line implementation group (18/98, i.e., 18.4%) compared with those from the post B-line implementation group (6/108, i.e., 5.5%) (p = 0.004). An analysis based on repeated APE events showed that the incidence rate of APE was significantly higher during the pre-implementation period (2.0 APE episodes per 100 person-months, 95% CI: 1.4–2.7) than during the post-implementation period (0.3 APE episodes per 100 person-months, 95% CI: 0.1–0.7), with an incidence rate ratio (post- versus pre-) of 0.17 (95% CI: 0.07–0.40; p < 0.001). The odds of experiencing APE episodes were 74% lower (odds ratio: 0.26, 95% CI: 0.10–0.69) in patients from the post B-line implementation period compared with those from the pre-implementation period. Notably, adjusting for potential confounders did not affect the strength of this association, which remained statistically significant (p ≤ 0.030). Finally, dominance analysis indicated that the implementation of B-lines was the primary factor explaining the difference in APE episodes between the two periods, followed by dialysis duration and intra-dialysis weight gain. Conclusions: The systematic use of lung ultrasound (a simple, easy-to-learn, rapid and non-invasive method, easily performed at the patient’s bed) in everyday clinical practice was associated with a drastic reduction in episodes of APE in hemodialysis patients. Further observational and interventional studies are needed to confirm these results.