The differential effect of intravenous iron in patients with non-dialysis chronic kidney disease in terms of fibroblast growth factor 23, phosphate, bone metabolism, functional status and quality of life and cardiovascular variables

Background: Modern intravenous iron preparations (e.g. ferric derisomaltose (FDI), ferric carboxymaltose (FCM)) are commonly used in non-dialysis-dependent chronic kidney disease (CKD) patients. Despite similar efficacy and safety in terms of previously described side-effect profile, a differential effect in hypophosphatemia has been noted with FCM. This appears to be related to fibroblast growth factor 23 (FGF23). Fibroblast growth factor 23 is an important phosphatonin with intertwined effects to phosphate metabolism, relevant to vitamin D and parathyroid hormone, leading to enhanced phosphaturia. In addition such alterations may lead to changes in bone turnover, and may be responsible for subtle differences in clinical and patient reported outcome measures. No previous randomised study evaluated this phenomenon in patients with non-dialysis dependent CKD. Moreover, no prior study adopting such a methodology evaluated any differential effect in terms of clinical and patient reported outcome measures, alongside potential cardiovascular implications. The primary hypothesis under study was whether any differential effect could arise secondary to the use of various modern intravenous iron compounds. This study primarily examined the comparative effects of FDI and FCM on FGF23, phosphate and other bone metabolism markers. In addition, it secondarily evaluated the impact of intravenous iron on functional status and cardiovascular variables, and assessed for any difference between the two compounds.Methods: This single-center double-blind randomised controlled trial primarily assessed the effects of FCM and FDI on intact FGF23 and phosphate, whilst also studying the impact on vitamin D, parathyroid hormone and phosphaturia. Bone turnover markers (alkaline phosphatase, bone-specific alkaline phosphatase, cross-linked C-telopeptide of type I collagen, N-terminal propeptides of Type I collagen), functional status (fatigue severity scale, 36-Item Short Form Health Survey, Duke Activity Status Index and 1-minute-sit-to-stand test) and cardiovascular variables (NT-pro-BNP, troponin T and pulse wave velocity) were monitored. Non-dialysis-dependent CKD patients with iron deficiency with/without anemia (serum ferritin <200μg/L or transferrin saturation ≤20% and serum ferritin 200-299μg/L) were randomised to receive FDI or FCM (1:1). At baseline 1000mg of intravenous iron was administered followed by 500-1000mg at one month. Measurements were performed at baseline, 1-2 days following iron administration, 14 days, 1 month, 1-2 days following second administration, 2 months and 3 months following initial infusion. Safety was assessed throughout the study.Results: Twenty-six patients were randomized to FDI (n=14) and FCM (n=12). Intact FGF23 increased following iron administration, which was significantly higher with FCM compared to FDI (Baseline to 1-2 days following 1st administration: FDI: 3.0 (IQR: - 15.1 - 13.8) % vs. FCM: 146.1 (IQR: 108.1-203.1) %; p < 0.001 and Baseline to 1-2 days following 2nd administration: FDI: 3.2 (IQR: - 3.5 - 25.4) % vs. FCM: 235.1 (138.5-434.6) %; p = 0.001). Phosphate levels decreased in the FCM group, causing a significant difference versus FDI at 14 days (FDI: 1.26 (IQR: 1.05–1.66) mmol/L vs. FCM: 1.09 (IQR: 0.94–1.23) mmol/L; p = 0.049). No clinically significant hypophosphataemia was detected ad either group. A significantly greater decrease in 1,25 (OH)2 Vitamin D was noted with FCM. A trend for increased phosphaturia was noted with FDI, albeit not statistically significant. Several bone turnover markers significantly changed following FCM administration but not FDI, both in terms of resorption and formation. Functional status improved in the total cohort and more specifically FDI in certain domains. This was particularly evident in those pertinent to fatigue and physical function as indicated both by the 36-Item Short Form Health Survey questionnaire and the Fatigue Severity Scale. No cardiovascular detriment was identified. Clinical efficacy and safety were similar between the two groups.Conclusions: The study suggests a differential effect in FGF23 following FCM administration in non-dialysis-dependent CKD patients. This may lead to changes consistent with hypovitaminosis D and alterations in bone turnover with potential clinical consequences. A common complication of non-dialysis-dependent CKD is mineral bone disease, characterised by impact on quality of life, strength and succeptibility to fractures. This is fueled by changes in the metabolism of both vitamin D and parathyroid hormone. It is hence possible that any further detriment to the already fragile kidney-bone axis secondary to such differential effect can have a significant clinical impact on patients with reduced kidney function. This becomes increasingly important, as the cumulative effect of repeated intravenous iron infusions is yet to be established. The positive effect of iron on patient reported outcome measures and functional status, alongside the similar efficacy and safety displayed, complement evidence relevant to intravenous iron, and can increase the confidence of clinicians in the use of such compounds. Nonetheless, as this study was small in nature with certain inherent limitations, further definitive studies are required to understand these differences and provide further insights, both clinical and mechanistic, into any arising differences

The differential effect of intravenous iron in patients with non-dialysis chronic kidney disease in terms of fibroblast growth factor 23, phosphate, bone metabolism, functional status and quality of life and cardiovascular variables “Iron and Phosphaturia in CKD”

Background: Modern intravenous iron preparations (e.g. ferric derisomaltose (FDI), ferric carboxymaltose (FCM)) are commonly used in non-dialysis-dependent chronic kidney disease (CKD) patients. Despite similar efficacy and safety in terms of previously described side-effect profile, a differential effect in hypophosphatemia has been noted with FCM. This appears to be related to fibroblast growth factor 23 (FGF23). Fibroblast growth factor 23 is an important phosphatonin with intertwined effects to phosphate metabolism, relevant to vitamin D and parathyroid hormone, leading to enhanced phosphaturia. In addition such alterations may lead to changes in bone turnover, and may be responsible for subtle differences in clinical and patient reported outcome measures. No previous randomised study evaluated this phenomenon in patients with non-dialysis dependent CKD. Moreover, no prior study adopting such a methodology evaluated any differential effect in terms of clinical and patient reported outcome measures, alongside potential cardiovascular implications. The primary hypothesis under study was whether any differential effect could arise secondary to the use of various modern intravenous iron compounds. This study primarily examined the comparative effects of FDI and FCM on FGF23, phosphate and other bone metabolism markers. In addition, it secondarily evaluated the impact of intravenous iron on functional status and cardiovascular variables, and assessed for any difference between the two compounds. Methods: This single-center double-blind randomised controlled trial primarily assessed the effects of FCM and FDI on intact FGF23 and phosphate, whilst also studying the impact on vitamin D, parathyroid hormone and phosphaturia. Bone turnover markers (alkaline phosphatase, bone-specific alkaline phosphatase, cross-linked C-telopeptide of type I collagen, N-terminal propeptides of Type I collagen), functional status (fatigue severity scale, 36-Item Short Form Health Survey, Duke Activity Status Index and 1-minute-sit-to-stand test) and cardiovascular variables (NT-pro-BNP, troponin T and pulse wave velocity) were monitored. Non-dialysis-dependent CKD patients with iron deficiency with/without anemia (serum ferritin <200µg/L or transferrin saturation ≤20% and serum ferritin 200-299µg/L) were randomised to receive FDI or FCM (1:1). At baseline 1000mg of intravenous iron was administered followed by 500-1000mg at one month. Measurements were performed at baseline, 1-2 days following iron administration, 14 days, 1 month, 1-2 days following second administration, 2 months and 3 months following initial infusion. Safety was assessed throughout the study. Results: Twenty-six patients were randomized to FDI (n=14) and FCM (n=12). Intact FGF23 increased following iron administration, which was significantly higher with FCM compared to FDI (Baseline to 1-2 days following 1st administration: FDI: 3.0 (IQR: - 15.1 - 13.8) % vs. FCM: 146.1 (IQR: 108.1-203.1) %; p < 0.001 and Baseline to 1-2 days following 2nd administration: FDI: 3.2 (IQR: - 3.5 - 25.4) % vs. FCM: 235.1 (138.5-434.6) %; p = 0.001). Phosphate levels decreased in the FCM group, causing a significant difference versus FDI at 14 days (FDI: 1.26 (IQR: 1.05–1.66) mmol/L vs. FCM: 1.09 (IQR: 0.94–1.23) mmol/L; p = 0.049). No clinically significant hypophosphataemia was detected ad either group. A significantly greater decrease in 1,25 (OH)2 Vitamin D was noted with FCM. A trend for increased phosphaturia was noted with FDI, albeit not statistically significant. Several bone turnover markers significantly changed following FCM administration but not FDI, both in terms of resorption and formation. Functional status improved in the total cohort and more specifically FDI in certain domains. This was particularly evident in those pertinent to fatigue and physical function as indicated both by the 36-Item Short Form Health Survey questionnaire and the Fatigue Severity Scale. No cardiovascular detriment was identified. Clinical efficacy and safety were similar between the two groups. Conclusions: The study suggests a differential effect in FGF23 following FCM administration in non-dialysis-dependent CKD patients. This may lead to changes consistent with hypovitaminosis D and alterations in bone turnover with potential clinical consequences. A common complication of non-dialysis-dependent CKD is mineral bone disease, characterised by impact on quality of life, strength and succeptibility to fractures. This is fueled by changes in the metabolism of both vitamin D and parathyroid hormone. It is hence possible that any further detriment to the already fragile kidney-bone axis secondary to such differential effect can have a significant clinical impact on patients with reduced kidney function. This becomes increasingly important, as the cumulative effect of repeated intravenous iron infusions is yet to be established. The positive effect of iron on patient reported outcome measures and functional status, alongside the similar efficacy and safety displayed, complement evidence relevant to intravenous iron, and can increase the confidence of clinicians in the use of such compounds. Nonetheless, as this study was small in nature with certain inherent limitations, further definitive studies are required to understand these differences and provide further insights, both clinical and mechanistic, into any arising differences

Epidemiology of inflammatory bowel disease in sub-Saharan Africa: A review of the current status

While inflammatory bowel disease (IBD) has been well characterised in the West and other parts of the world, there are little data from sub-Saharan Africa (SSA). To throw light on the current status of IBD in SSA, we performed a systematic review of the literature, extracting relevant publications. We found only 210 documented IBD cases in SSA (excluding South Africa (SA)), which were reported in 34 publications until August 2019. The majority were cases of ulcerative colitis. Only three reports, all from SA, attempted to determine IBD incidence rates. The rest were mostly case reports or small case series; the largest from Nigeria comprised 32 patients. The paucity of documented cases possibly reflects under-diagnosis and under-reporting. Major deficiencies in diagnostic and clinical capacity were noted, which need to be addressed going forward

Treatment of advanced hepatocellular carcinoma with very low levels of amplitude-modulated electromagnetic fields

BACKGROUND: Therapeutic options for patients with advanced hepatocellular carcinoma (HCC) are limited. There is emerging evidence that the growth of cancer cells may be altered by very low levels of electromagnetic fields modulated at specific frequencies. METHODS: A single-group, open-label, phase I/II study was performed to assess the safety and effectiveness of the intrabuccal administration of very low levels of electromagnetic fields amplitude modulated at HCC-specific frequencies in 41 patients with advanced HCC and limited therapeutic options. Three-daily 60-min outpatient treatments were administered until disease progression or death. Imaging studies were performed every 8 weeks. The primary efficacy end point was progression-free survival >= 6 months. Secondary efficacy end points were progression-free survival and overall survival. RESULTS: Treatment was well tolerated and there were no NCI grade 2, 3 or 4 toxicities. In all, 14 patients (34.1%) had stable disease for more than 6 months. Median progression-free survival was 4.4 months (95% CI 2.1-5.3) and median overall survival was 6.7 months (95% CI 3.0-10.2). There were three partial and one near complete responses. CONCLUSION: Treatment with intrabuccally administered amplitude-modulated electromagnetic fields is safe, well tolerated, and shows evidence of antitumour effects in patients with advanced HCC. British Journal of Cancer (2011) 105, 640-648. doi:10.1038/bjc.2011.292 www.bjcancer.com Published online 9 August 2011 (C) 2011 Cancer Research U

Patient blood management: A solution for South Africa

For more than 70 years the default therapy for anaemia and blood loss was mostly transfusion. Accumulating evidence demonstrates a significant dose-dependent relationship between transfusion and adverse outcomes. This and other transfusion-related challenges led the way to a new paradigm. Patient blood management (PBM) is the application of evidence-based practices to optimise patient outcomes by managing and preserving the patient’s own blood. ‘Real-world’ studies have shown that PBM improves patient outcomes and saves money. The prevalence of anaemia in adult South Africans is 31% in females and 17% in males. Improving the management of anaemia will firstly improve public health, secondly relieve the pressure on the blood supply, and thirdly improve the productivity of the nation’s workforce. While high-income countries are increasingly implementing PBM, many middle- and low-income countries are still trying to upscale their transfusion services. The implementation of PBM will improve South Africa’s health status while saving costs

An integrated system for computer based training of process operators

Imperial Users onl

A study of the effects of scintillation on digital satellite communication systems

Available from British Library Document Supply Centre-DSC:DXN053164 / BLDSC - British Library Document Supply CentreSIGLEGBUnited Kingdo

Asymptomatic Abnormal Liver Chemistry - it’s all NAFLD

No Abstract