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Journal of Nephrology Mar 2024Ultraprocessed food (UPF) is defined as industrialized, packaged and ready-to-eat food produced on a large scale, using sophisticated industrial machinery. Examples of...
Ultraprocessed food (UPF) is defined as industrialized, packaged and ready-to-eat food produced on a large scale, using sophisticated industrial machinery. Examples of UPFs include salty and sweet snacks, industrialized biscuits and packaged meals, processed meats and sugary drinks. Ultraprocessed food has a long-shelf life, is highly palatable, microbiologically safe, affordable and most of all, easy to consume. For these reasons, its consumption has been increasing worldwide, and is replacing healthy homemade meals. The main concern of this dietary shift is that UPFs come with the addition of salt, sugar, unhealthy fats, and several additives and taste enhancers that contain, among other substances, relevant quantities of potassium, phosphate and sodium. A large proportion of UPF in the diet may carry risks for patients with chronic kidney disease (CKD) since it can worsen blood pressure and glycemic control, and lead to constipation, hyperkalemia and hyperphosphatemia. Acknowledging the importance of UPF in kidney health implies integrating nutritional counseling with information on UPFs, and specific educational material can be helpful for patients, caregivers, and also for health care providers. We developed a set of 3 infographics dedicated to CKD patients, with information on how to identify UPFs, reasons for decreasing consumption, how to compose a healthy CKD plate and tips for reading food labels in supermarkets and grocery shops. We hope that this material can be useful in CKD outpatient clinics and dialysis centers as well as in general practitioners' offices, caring for early stage CKD.
Topics: Humans; Renal Insufficiency, Chronic; Diet, Healthy; Fast Foods; Food Handling; Patient Education as Topic; Nutritive Value; Food, Processed
PubMed: 37995043
DOI: 10.1007/s40620-023-01817-3 -
CPT: Pharmacometrics & Systems... Nov 2023Pemigatinib is a selective, potent, oral inhibitor of fibroblast growth factor receptor (FGFR)1-3 with efficacy in patients with previously treated, advanced/metastatic...
Pemigatinib is a selective, potent, oral inhibitor of fibroblast growth factor receptor (FGFR)1-3 with efficacy in patients with previously treated, advanced/metastatic cholangiocarcinoma (CCA) with FGFR2 alterations. A previously developed population pharmacokinetic (PK) model of pemigatinib was refined using an updated dataset with 467 participants from seven clinical studies, including patients with CCA. Updated PK model parameters were used to evaluate the association between pemigatinib exposure and efficacy and safety. Pemigatinib PK was adequately described by a two-compartment model with linear elimination and sequential zero- and first-order absorption. The final model successfully minimized, had a successful covariance step, and showed unbiased goodness-of-fit. Estimated first-order absorption rate constant and apparent clearance were 3.7/h and 10.7 L/h, respectively. Sex, baseline body weight, and concomitant use of phosphate binders, proton pump inhibitors, or histamine-2 antagonists significantly impacted PK parameters; however, the impact of covariates on PK exposure was not clinically significant. Steady-state pemigatinib exposure and mean change from baseline in serum phosphate concentration were associated with objective response rate in a bell-shaped relationship and were significantly associated with increased hyperphosphatemia. Pemigatinib exposure was associated with treatment-emergent adverse events, such as decreased appetite, nausea, and stomatitis, although the relationships were shallow. Overall, analyses indicate that 13.5 mg pemigatinib once daily in 21-day cycles (2 weeks on, 1 week off) offers a favorable benefit-risk profile in patients with advanced/metastatic or surgically unresectable CCA and is the optimal dose for clinical development.
Topics: Humans; Cholangiocarcinoma; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Phosphates
PubMed: 37969064
DOI: 10.1002/psp4.13064 -
The Journal of International Medical... Jan 2024This study aimed to examine the mechanism of hyperphosphatemia-induced vascular calcification (HPVC).
OBJECTIVE
This study aimed to examine the mechanism of hyperphosphatemia-induced vascular calcification (HPVC).
METHODS
Primary human aortic smooth muscle cells and rat aortic rings were cultured in Dulbecco's modified Eagle's medium supplemented with 0.9 mM or 2.5 mM phosphorus concentrations. Type III sodium-dependent phosphate cotransporter-1 (Pit-1) small interfering RNA and phosphonoformic acid (PFA), a Pit-1 inhibitor, were used to investigate the effects and mechanisms of Pit-1 on HPVC. Calcium content shown by Alizarin red staining, expression levels of Pit-1, and characteristic molecules for phenotypic transition of vascular smooth muscle cells were examined.
RESULTS
Hyperphosphatemia induced the upregulation of Pit-1 expression, facilitated phenotypic transition of vascular smooth muscle cells, and led to HPVC in cellular and organ models. Treatment with Pit-1 small interfering RNA or PFA significantly inhibited Pit-1 expression, suppressed phenotypic transition, and attenuated HPVC.
CONCLUSIONS
Our findings suggest that Pit-1 plays a pivotal role in the development of HPVC. The use of PFA as a Pit-1 inhibitor has the potential for therapeutic intervention in patients with HPVC. However, further rigorous clinical investigations are required to ensure the safety and efficacy of PFA before it can be considered for widespread implementation in clinical practice.
Topics: Animals; Humans; Rats; Aorta; Foscarnet; Hyperphosphatemia; RNA, Small Interfering; Transcription Factors; Vascular Calcification; Sodium-Phosphate Cotransporter Proteins, Type III
PubMed: 38180904
DOI: 10.1177/03000605231222156 -
European Journal of Cancer (Oxford,... Mar 2024Pemigatinib is approved for patients with pretreated, locally advanced or metastatic CCA harboring FGFR2 rearrangements or fusions. We aim to assess the effectiveness...
Pemigatinib for patients with previously treated, locally advanced or metastatic cholangiocarcinoma harboring FGFR2 fusions or rearrangements: A joint analysis of the French PEMI-BIL and Italian PEMI-REAL cohort studies.
BACKGROUND
Pemigatinib is approved for patients with pretreated, locally advanced or metastatic CCA harboring FGFR2 rearrangements or fusions. We aim to assess the effectiveness and safety of pemigatinib in real-world setting.
MATERIAL AND METHODS
A joint analysis of two multicentre observational retrospective cohort studies independently conducted in France and Italy was performed. All consecutive FGFR2-positive patients affected by CCA and treated with pemigatinib as second- or further line of systemic treatment in clinical practice, within or outside the European Expanded Access Program, were included.
RESULTS
Between July 2020 and September 2022, 72 patients were treated with pemigatinib in 14 Italian and 25 French Centres. Patients had a median age of 57 years, 76% were female, 81% had ECOG-PS 0-1, 99% had intrahepatic CCA, 74% had ≥ 2 metastatic sites, 67% had metastatic disease at diagnosis, while 38.8% received ≥ 2 previous lines of systemic treatment. At data cut-off analysis (April 2023), ORR and DCR were 45.8% and 84.7%, respectively. Median DoR was 7 months (IQR: 5.8-9.3). Over a median follow-up time of 19.5 months, median PFS and 1-year PFS rate were 8.7 months and 32.8%. Median OS and 1-year OS rate were 17.1 months and 60.6%. Fatigue (69.4%), ocular toxicity (68%), nail toxicities (61.1%), dermatologic toxicity (41.6%) hyperphosphataemia (55.6%), stomatitis (48.6%), and diarrhea (36.1%) were the most frequent, mainly G1-G2 AEs. Overall incidence of G3 AEs was 22.2%, while no patient experienced G4 AE. Dose reduction and temporary discontinuation were needed in 33.3% and 40.3% of cases, with 1 permanent discontinuation due to AEs.
CONCLUSIONS
These results confirm the effectiveness and safety of pemigatinib in a real-world setting.
Topics: Humans; Female; Middle Aged; Male; Retrospective Studies; Cholangiocarcinoma; Cohort Studies; Bile Ducts, Intrahepatic; Bile Duct Neoplasms; Receptor, Fibroblast Growth Factor, Type 2; Morpholines; Pyrimidines; Pyrroles
PubMed: 38340384
DOI: 10.1016/j.ejca.2024.113587 -
Clinical Kidney Journal Jan 2024The efficacy and safety of tenapanor has not been confirmed in Chinese end-stage renal disease (ESRD) patients with hyperphosphatemia on haemodialysis (HD).
BACKGROUND
The efficacy and safety of tenapanor has not been confirmed in Chinese end-stage renal disease (ESRD) patients with hyperphosphatemia on haemodialysis (HD).
METHODS
This was a randomised, double blind, phase 3 trial conducted at 26 dialysis facilities in China (https://www.chictr.org.cn/index.aspx; CTR20202588). After a 3-week washout, adults with ESRD on HD with hyperphosphatemia were randomised (1:1) using an interactive web response system to oral tenapanor 30 mg twice a day or placebo for 4 weeks. The primary endpoint was the change in mean serum phosphorous level from baseline to the endpoint visit (day 29 or last serum phosphorus measurement). Efficacy was analysed in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of the study drug.
RESULTS
Between 5 March 2021 and 8 June 2022, 77 patients received tenapanor and 73 received placebo. Tenapanor treatment ( = 75) resulted in a significantly greater least squares (LS) mean reduction in serum phosphate at the endpoint visit versus placebo ( = 72): LS mean difference -1.17 mg/dl (95% CI -1.694 to -0.654, < .001). More patients receiving tenapanor achieved a serum phosphorous level <5.5 mg/dl at the endpoint visit (44.6% versus 10.1%). The most common treatment-related adverse event was diarrhoea [tenapanor 28.6% (22/77), placebo 2.7% (2/73)], which was mostly mild and led to treatment discontinuation in two patients receiving tenapanor.
CONCLUSIONS
Tenapanor significantly reduced the serum phosphorous level versus placebo in Chinese ESRD patients on HD and was generally well tolerated.
PubMed: 38186905
DOI: 10.1093/ckj/sfad216 -
Scientific Reports Oct 2023Vascular calcification, an ectopic calcification exacerbated by aging and renal dysfunction, is closely associated with cardiovascular disease. However, early detection...
Vascular calcification, an ectopic calcification exacerbated by aging and renal dysfunction, is closely associated with cardiovascular disease. However, early detection indicators are limited. This study focused on dental pulp stones, ectopic calcifications found in oral tissues that are easily identifiable on dental radiographs. Our investigation explored the frequency and timing of these calcifications in different locations and their relationship to aortic calcification. In cadavers, we examined the association between the frequency of dental pulp stones and aortic calcification, revealing a significant association. Notably, dental pulp stones appeared prior to aortic calcification. Using a rat model of hyperphosphatemia, we confirmed that dental pulp stones formed earlier than calcification in the aortic arch. Interestingly, there were very few instances of aortic calcification without dental pulp stones. Additionally, we conducted cell culture experiments with vascular smooth muscle cells (SMCs) and dental pulp cells (DPCs) to explore the regulatory mechanism underlying high phosphate-mediated calcification. We found that DPCs produced calcification deposits more rapidly and exhibited a stronger augmentation of osteoblast differentiation markers compared with SMCs. In conclusion, the observation of dental pulp stones through X-ray examination during dental checkups could be a valuable method for early diagnosis of aortic calcification risk.
Topics: Rats; Animals; X-Rays; Dental Pulp Calcification; Radiography; Vascular Calcification; Early Diagnosis; Dental Pulp
PubMed: 37903847
DOI: 10.1038/s41598-023-45902-w -
Journal of Multidisciplinary Healthcare 2024Patients on maintenance hemodialysis have an increased risk of fracture. However, the relationship between fracture and poor prognosis is not clear.
BACKGROUND
Patients on maintenance hemodialysis have an increased risk of fracture. However, the relationship between fracture and poor prognosis is not clear.
METHODS
A total of 182 maintenance hemodialysis patients were enrolled in the study. The relationship between fracture and poor prognosis (cardiovascular events, stroke, malignancy and 5-year all-cause mortality) were analyzed.
RESULTS
21 of 182 patients had a history of fracture at the time of enrollment. 26 patients had a new fracture after enrollment. A total of 57 fractures occurred in 47 patients, the most common fracture site was the rib. Patients with fracture group had a higher proportion of elderly and female, higher serum phosphorus and B-type natriuretic peptide and lower hemoglobin, albumin, and potassium compared with those without fracture. Age (), hemoglobin (), and serum phosphorus () were the independent risk factors of new fractures in MHD patients. The incidence of malignancy and 5-year all-cause mortality in patients with fracture was higher than those without fracture (). But there was no significant difference in the incidence of acute myocardial infarction or stroke.
CONCLUSION
25.8% of maintenance hemodialysis patients had at least one fracture, with rib fractures accounting for the highest proportion. Age, hemoglobin and serum phosphorus were the independent risk factors of new fractures. The incidence of malignancy and 5-year all-cause mortality in patients with fracture was higher than those without fracture, but there was no significant difference in the incidence of acute myocardial infarction and stroke.
PubMed: 38706503
DOI: 10.2147/JMDH.S457193 -
Journal of Clinical Biochemistry and... Nov 2023Hyperphosphatemia is an independent and non-classical risk factor of cardiovascular disease and mortality in patients with chronic kidney disease (CKD). Increased levels...
Hyperphosphatemia is an independent and non-classical risk factor of cardiovascular disease and mortality in patients with chronic kidney disease (CKD). Increased levels of extracellular inorganic phosphate (Pi) are known to directly induce vascular calcification, but the detailed underlying mechanism has not been clarified. Although serum Pi levels during the growth period are as high as those observed in hyperphosphatemia in adult CKD, vascular calcification does not usually occur during growth. Here, we have examined whether the defence system against Pi-induced vascular calcification can exist during the growth period using mice model. We found that calcification propensity of young serum (aged 3 weeks) was significantly lower than that of adult serum (10 months), possibly due to high fetuin-A levels. In addition, when the aorta was cultured in high Pi medium , obvious calcification was observed in the adult aorta but not in the young aorta. Furthermore, culture in high Pi medium increased the mRNA level of tissue-nonspecific alkaline phosphatase (TNAP), which degrades pyrophosphate, only in the adult aorta. Collectively, our findings indicate that the aorta in growing mouse may be resistant to Pi-induced vascular calcification via a mechanism in which high serum fetuin-A levels and suppressed TNAP expression.
PubMed: 37970550
DOI: 10.3164/jcbn.23-11 -
International Urology and Nephrology Dec 2023Endothelial dysfunction is the primary step for the development of CKD-related cardiovascular disease. Early prediction and management can influence patient survival....
BACKGROUND
Endothelial dysfunction is the primary step for the development of CKD-related cardiovascular disease. Early prediction and management can influence patient survival. Serum testing of FGF 23 hormone and urinary phosphate excretion were studied as predictors of all-cause cardiovascular morbidity in CKD patients; however, their relation to endothelial dysfunction is controversial. A combination of both in one index is hypothesized to increase their sensitivity in detecting endothelial dysfunction, especially in the early stages of CKD before the dominance of hyperphosphatemia, the original risk.
METHODS
A cross-sectional comparative analysis between thirty CKD stage 3 patients and sixty stage 4-5 CKD patients was conducted. All patients were tested for markers of mineral bone disorders including serum FGF 23 and 24-h urinary phosphate excretion. A combination of both in one index (nephron index) is calculated and hypothesized to correlate with nephron number. Endothelial dysfunction was assessed by measuring the post-occlusion brachial flow-mediated dilatation (FMD).
RESULTS
In univariate and multivariate regression analyses, the nephron index was the only predictor of endothelial dysfunction in individuals with stage 3 CKD (r = 0.74, P 0.01). This was not applied to stage 4-5 CKD patients where serum phosphorus (r = - 0.53, P 0.001), intact PTH (r = - 0.53, P 0.001), uric acid (r = - 0.5, P 0.001), and measured GFR (r = 0.59, P 0.001) were the highest correlates to FMD; the Nephron index had the weakest correlation (r = 0.28, P = 0.02) and is not predictive of endothelial dysfunction.
CONCLUSION
Nephron index calculation showed better correlation with endothelial dysfunction than using any of its determinants alone in early stages of CKD when FGF 23 levels are just beginning to rise. In advanced CKD patients, hyperphosphatemia, hyperparathyroidism, hyperuricemia, and measured GFR are more reliable than nephron index.
Topics: Humans; Cross-Sectional Studies; Fibroblast Growth Factors; Hyperphosphatemia; Phosphates; Renal Insufficiency, Chronic
PubMed: 37043155
DOI: 10.1007/s11255-023-03589-y -
Clinical Cancer Research : An Official... Apr 2024Futibatinib, a covalently-binding inhibitor of fibroblast growth factor receptor (FGFR)1-4 gained approval for the treatment of refractory, advanced intrahepatic...
PURPOSE
Futibatinib, a covalently-binding inhibitor of fibroblast growth factor receptor (FGFR)1-4 gained approval for the treatment of refractory, advanced intrahepatic cholangiocarcinoma (iCCA) harboring an FGFR2 fusion/other rearrangement. An integrated analysis was performed to evaluate safety and provide guidance on the management of futibatinib-associated adverse events (AEs) in patients with unresectable/metastatic tumors, including iCCA.
PATIENTS AND METHODS
Data from three global phase I or II studies of futibatinib (NCT02052778; JapicCTI-142552) were pooled. AEs were graded per NCI CTCAE v4.03, where applicable. Safety was analyzed for patients receiving any futibatinib starting dose (overall population) and in those receiving the approved starting dose of 20 mg once every day.
RESULTS
In total, 469 patients with one of 33 known tumor types were analyzed, including 318 patients who received futibatinib 20 mg every day. AEs of clinical interest (AECI; any grade/grade ≥3) in the overall population included hyperphosphatemia (82%/19%), nail disorders (27%/1%), hepatic AEs (27%/11%), stomatitis (19%/3%), palmar-plantar erythrodysesthesia syndrome (PPES; 13%/3%), rash (9%/0%), retinal disorders (8%/0%), and cataract (4%/1%). Median time to onset of grade ≥3 AECIs ranged from 9 days (hyperphosphatemia) to 125 days (cataract). Grade ≥3 hyperphosphatemia, hepatic AEs, PPES, and nail disorders resolved to grade ≤2 within a median of 7, 7, 8, and 28 days, respectively. Discontinuations due to treatment-related AEs were rare (2%), and no treatment-related deaths occurred. AE management included phosphate-lowering medication and dose adjustments.
CONCLUSIONS
Futibatinib showed a consistent and manageable safety profile across patients with various tumor types. AECIs were mostly reversible with appropriate clinical management.
Topics: Humans; Hyperphosphatemia; Cholangiocarcinoma; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Cataract; Receptor, Fibroblast Growth Factor, Type 1; Pyrazoles; Pyrimidines; Pyrroles
PubMed: 38329716
DOI: 10.1158/1078-0432.CCR-23-2646