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BACKGROUND AND PURPOSE: Alterations of the Basilar Artery (BA) anatomy have been suggested as a possible Magnetic Resonance Angiography (MRA) feature of Fabry Disease (FD). Nonetheless, no information about their clinical or pathophysiological correlates is available, limiting our comprehension of the real impact of vessel remodeling in FD. MATERIALS AND METHODS: Brain MRIs of 53 FD subjects (40.7±12.4 years, M/F=23/30) were collected in this single center study. Mean BA diameter and its Tortuosity Index (TI) were calculated on MRA. Possible correlations between these metrics and clinical, laboratory and advanced imaging variables of the posterior circulation were tested. In a subgroup of 20 subjects, a two-year clinical and imaging follow-up was available, with possible longitudinal changes of these metrics and their ability in predicting clinical scores that were also probed. RESULTS: No significant association was found between MRA metrics and any clinical, laboratory or advanced imaging variable (ρ values ranging from -0.006 to 0.32). At the follow-up examination, no changes were observed over time for mean BA diameter (p = 0.84) and TI (p = 0.70). Finally, baseline MRA variables failed to predict the clinical status of FD patients at follow-up (p=0.42 and 0.66, respectively). CONCLUSIONS: Alterations of BA in FD lack of any significant association with clinical, laboratory or advanced imaging findings collected in this study. Furthermore, this lack of correlation seems constant over time, suggesting their stability over time. Taken together, all these results suggest that the role of BA dolichoectasia in FD should be reconsidered. ABBREVIATIONS: CNS = Central Nervous System; FASTEX = FAbry STabilization indEX; FD = Fabry Disease; Gb3 = Globotriaosylceramide; LysoGb3 = globotriaosylsphingosine; MSSI = Mainz Severity Score Index.
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Orexin-A is a neuropeptide product of the lateral hypothalamus that acts on two receptors, OX1R and OX2R. The orexinergic system is involved in feeding, sleep, and pressure regulation. Recently, orexin-A levels have been found to be negatively correlated with renal function. Here, we analyzed orexin-A levels as well as the incidence of SNPs in the hypocretin neuropeptide precursor (HCRT) and its receptors, HCRTR1 and HCRTR2, in 64 patients affected by autosomal dominant polycystic kidney disease (ADPKD) bearing truncating mutations in the PKD1 or PKD2 genes. Twenty-four healthy volunteers constituted the control group. Serum orexin-A was assessed by ELISA, while the SNPs were investigated through Sanger sequencing. Correlations with the main clinical features of PKD patients were assessed. PKD patients showed impaired renal function (mean eGFR 67.8 ± 34.53) and a statistically higher systolic blood pressure compared with the control group (p < 0.001). Additionally, orexin-A levels in PKD patients were statistically higher than those in healthy controls (477.07 ± 69.42 pg/mL vs. 321.49 ± 78.01 pg/mL; p < 0.001). Furthermore, orexin-A inversely correlated with blood pressure (p = 0.0085), while a direct correlation with eGFR in PKD patients was found. None of the analyzed SNPs showed any association with orexin-A levels in PKD. In conclusion, our data highlights the emerging role of orexin-A in renal physiology and its potential relevance to PKD. Further research is essential to elucidate the intricate mechanisms underlying orexin-A signaling in renal function and its therapeutic implications for PKD and associated cardiovascular complications.
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Receptores de Orexina , Orexinas , Polimorfismo de Nucleótido Simple , Humanos , Orexinas/metabolismo , Orexinas/genética , Masculino , Femenino , Persona de Mediana Edad , Receptores de Orexina/metabolismo , Receptores de Orexina/genética , Adulto , Canales Catiónicos TRPP/genética , Canales Catiónicos TRPP/metabolismo , Riñón Poliquístico Autosómico Dominante/metabolismo , Riñón Poliquístico Autosómico Dominante/genética , Riñón Poliquístico Autosómico Dominante/sangre , Estudios de Casos y Controles , Anciano , Presión Sanguínea , Enfermedades Renales Poliquísticas/genética , Enfermedades Renales Poliquísticas/metabolismo , Enfermedades Renales Poliquísticas/sangreRESUMEN
PURPOSE: How to measure brain globotriaosylceramide (Gb3) accumulation in Fabry Disease (FD) patients in-vivo is still an open challenge. The objective of this study is to provide a quantitative, non-invasive demonstration of this phenomenon using quantitative MRI (qMRI). METHODS: In this retrospective, monocentric cross-sectional study conducted from November 2015 to July 2018, FD patients and healthy controls (HC) underwent an MRI scan with a relaxometry protocol to compute longitudinal relaxation rate (R1) maps to evaluate gray (GM) and white matter (WM) lipid accumulation. In a subgroup of 22 FD patients, clinical (FAbry STabilization indEX -FASTEX- score) and biochemical (residual α-galactosidase activity) variables were correlated with MRI data. Quantitative maps were analyzed at both global ("bulk" analysis) and regional ("voxel-wise" analysis) levels. RESULTS: Data were obtained from 42 FD patients (mean age = 42.4 ± 12.9, M/F = 16/26) and 49 HC (mean age = 42.3 ± 16.3, M/F = 28/21). Compared to HC, FD patients showed a widespread increase in R1 values encompassing both GM (pFWE = 0.02) and WM (pFWE = 0.02) structures. While no correlations were found between increased R1 values and FASTEX score, a significant negative correlation emerged between residual enzymatic activity levels and R1 values in GM (r = -0.57, p = 0.008) and WM (r = -0.49, p = 0.03). CONCLUSIONS: We demonstrated the feasibility and clinical relevance of non-invasively assessing cerebral Gb3 accumulation in FD using MRI. R1 mapping might be used as an in-vivo quantitative neuroimaging biomarker in FD patients.
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Enfermedad de Fabry , Imagen por Resonancia Magnética , Trihexosilceramidas , Humanos , Enfermedad de Fabry/diagnóstico por imagen , Enfermedad de Fabry/metabolismo , Masculino , Femenino , Adulto , Imagen por Resonancia Magnética/métodos , Trihexosilceramidas/metabolismo , Estudios Transversales , Estudios Retrospectivos , Estudios de Casos y Controles , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Persona de Mediana Edad , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/metabolismoRESUMEN
Fabry disease (FD), also known as Anderson-Fabry disease, is a hereditary disorder of glycosphingolipid metabolism, caused by a deficiency of the lysosomal alpha-galactosidase A enzyme. This causes a progressive accumulation of glycosphingolipids in tissues and organs which represents the main pathogenetic mechanism of FD. The disease is progressive and multisystemic and is characterized by early symptoms and late complications (renal, cardiac and neurological dysfunction). Fatigue and exercise intolerance are early common symptoms in FD patients but the specific causes are still to be defined. In this narrative review, we deal with the contribution of cardiac and pulmonary dysfunctions in determining fatigue and exercise intolerance in FD patients.
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Fabry disease (FD) is caused by mutations in the galactosidase alpha (GLA) gene which lead to the accumulation of globotriaosylceramide (Gb-3). Enzyme replacement therapy (ERT) and oral chaperone therapy are the current pharmacological treatments for this condition. However, in the literature, there is a growing emphasis on exploring non-pharmacological therapeutic strategies to improve the quality of life of patients with FD. In particular, the nutritional approach to FD has been marginally addressed in the scientific literature, although specific dietary interventions may be useful for the management of nephropathy and gastrointestinal complications, which are often present in patients with FD. Especially in cases of confirmed diagnosis of irritable bowel syndrome (IBS), a low-FODMAP diet can represent an effective approach to improving intestinal manifestations. Furthermore, it is known that some food components, such as polyphenols, may be able to modulate some pathogenetic mechanisms underlying the disease, such as inflammation and oxidative stress. Therefore, the use of healthy dietary patterns should be encouraged in this patient group. Sports practice can be useful for patients with multi-organ involvement, particularly in cardiovascular, renal, and neurological aspects. Therefore, the aim of this review is to summarize current knowledge on the role of nutrition and physical activity in FD patients.
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Enfermedad de Fabry , Humanos , Enfermedad de Fabry/terapia , Calidad de Vida , Dieta , Ejercicio Físico , Estado NutricionalRESUMEN
INTRODUCTION: Hyperkalemia, one of the most important electrolyte abnormalities of chronic kidney disease (CKD), often limits the use of renin-angiotensin-aldosterone system inhibitors and can increase in the postprandial period. In this study we report a real-world experience with the new non-adsorbed potassium binder patiromer in stage 3b-4 CKD patients. Moreover, we performed a cross-sectional analysis to evaluate, for the first time, the efficacy of patiromer in the control of postprandial potassium concentrations. METHODS: We retrospectively collected data of 40 patients at the time of patiromer initiation (T0), and after 2 (T2), 6 (T6) and 12 (T12) months of treatment. For cross sectional analysis, a blood sample was collected 2 h after the main meal for the evaluation of postprandial potassium concentrations. RESULTS: Eighty-two point five percent of patients (33/40) reached normal potassium concentrations at T2. Serum potassium significantly decreased at T2 compared to T0 (5.13 ± 0.48 vs 5.77 ± 0.41 mmol/L, respectively; p < 0.001) and the reduction remained significant during the follow-up (5.06 ± 0.36 at T6 and 5.77 ± 0.41 at T12; p < 0.001 vs T0). Renin-angiotensin-aldosterone system inhibitors were continued by 93% of patients (27/29). Adverse events were reported in 27.5% of patients and were all mild-to-moderate. Postprandial potassium concentrations did not significantly change compared to fasting state potassium measured at T12 (4.53 ± 0.33 vs 5.06 ± 0.36 mmol/L; p = 0.15). CONCLUSIONS: In a real-world setting of advanced CKD patients, patiromer is a useful treatment for hyperkalemia, since it significantly reduces serum potassium levels over the long term and is able to maintain potassium concentrations in the normal range even in the post-prandial period.
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Hiperpotasemia , Polímeros , Periodo Posprandial , Potasio , Insuficiencia Renal Crónica , Humanos , Hiperpotasemia/sangre , Hiperpotasemia/tratamiento farmacológico , Hiperpotasemia/etiología , Estudios Retrospectivos , Masculino , Femenino , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/sangre , Anciano , Potasio/sangre , Persona de Mediana Edad , Estudios Transversales , Polímeros/uso terapéutico , Resultado del Tratamiento , Factores de Tiempo , Anciano de 80 o más AñosRESUMEN
Hyperprolinemia is a rare genetic condition due to mutations in proline metabolic pathway. Type I Hyperprolinemia (HPI) typically causes neuropsychiatric disorders, and diagnosis is usually confirmed in pediatric population with suggestive neuropsychiatric involvement by elevated serum proline levels and elevated urinary proline, hydroxyproline, and glycine levels. The possible coexistence of nephropathy in patients with HPI, often specified as malformative urinary disease, is often mentioned. However, reports of HPI diagnosis due to kidney impairment do not exist in scientific literature yet. Here we present the case of a patient presenting with chronic kidney disease secondary to obstructive nephropathy who received a HPI diagnosis in adulthood. Interestingly, the family study showed the same 22q11.21 deletion and elevated blood proline levels in the father, who had no clinical anomalies. We therefore suggest, in light of the high frequency of mutations involving 22q11 and PRODH in the general population, to consider these rare alterations in patients with congenital urinary malformations, even in the presence of nuanced neurological symptoms and negative family history.
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Acidosis , Errores Innatos del Metabolismo de los Aminoácidos , Humanos , Niño , Prolina Oxidasa/genética , Mutación , Prolina/genética , Prolina/metabolismo , Errores Innatos del Metabolismo de los Aminoácidos/genética , Riñón/metabolismoRESUMEN
Autosomal dominant polycystic kidney disease (ADPKD) is the most common heritable multifocal cystic disease encountered in clinical practice, and it is usually diagnosed in patients with family history by the evidence of markedly enlarged kidneys with multiple bilateral cysts at ultrasound (U.S.), computed tomography (CT) scan, or magnetic resonance imaging (MRI). In most cases, genetic testing is not required. Though ADPKD diagnosis is often straightforward, misdiagnosis is possible. Here we present a case of ADPKD misdiagnosis, followed by a review of the most important kidney heritable multifocal cystic diseases. Our case report demonstrates that ADPKD can be erroneously diagnosed when other kidney heritable multifocal cystic diseases occur without their distinguishing manifestations and when there is no genetic characterization among the relatives. A proper diagnosis of heritable diseases is crucial, as it allows an appropriate management of family members who carry disease allele, apart from patient management. Therefore, we suggest a careful differential diagnosis with possible molecular genetic analysis in presentations with familial cystic kidneys and suspicious clinical and radiological features.
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Riñón Poliquístico Autosómico Dominante , Humanos , Riñón Poliquístico Autosómico Dominante/diagnóstico , Ultrasonografía , Tomografía Computarizada por Rayos X , Imagen por Resonancia Magnética , Diagnóstico DiferencialRESUMEN
Inhibition of the renin-angiotensin-aldosterone system (RAAS) is broadly recommended in many nephrological guidelines to prevent chronic kidney disease (CKD) progression. This work aimed to analyze the robustness of randomized controlled trials (RCTs) investigating the renal and cardiovascular outcomes in CKD stages 3-5 patients treated with RAAS inhibitors (RAASi). We searched for RCTs in MEDLINE (PubMed), EMBASE databases, and the Cochrane register. Fragility indexes (FIs) for every primary and secondary outcome were calculated according to Walsh et al., who first described this novel metric, suggesting 8 as the cut-off to consider a study robust. Spearman coefficient was calculated to correlate FI to p value and sample size of statistically significant primary and secondary outcomes. Twenty-two studies met the inclusion criteria, including 80,455 patients. Sample size considerably varied among the studies (median: 1693.5, range: 73-17,276). The median follow-up was 38 months (range 24-58). The overall median of both primary and secondary outcomes was 0 (range 0-117 and range 0-55, respectively). The median of FI for primary and secondary outcomes with a p value lower than 0.05 was 6 (range: 1-117) and 7.5 (range: 1-55), respectively. The medians of the FI for primary outcomes with a p value lower than 0.05 in CKD and no CKD patients were 5.5 (range 1-117) and 22 (range 1-80), respectively. Only a few RCTs have been shown to be robust. Our analysis underlined the need for further research with appropriate sample sizes and study design to explore the real potentialities of RAASi in the progression of CKD.
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Simple renal cysts are a common finding during abdominal imaging assessment. The incidence increases with age and it is higher in male gender. Parapelvic cysts are a subset of simple cysts that arise within the renal parenchyma, adjacent to the renal sinus, characterized by being generally single, larger, and incompletely surrounded by renal parenchyma. Noteworthy, parapelvic cysts are a rare and understudied condition which, although considered clinically insignificant due to the absence of influence on renal function, still have a controversial aetiopathogenesis. On the other hand, urological management and differential diagnosis have been thoroughly investigated. The aim of our review is to provide an overall vision on this rare condition, usually misdiagnosed and underestimated, on the basis of more recent data. An accurate differential diagnosis of parapelvic cysts can lead to the identification of treatable conditions such as Fabry disease, autosomal dominant polycystic kidney disease, polycystic liver disease and tuberous sclerosis complex disease.
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Quistes , Neoplasias Renales , Hepatopatías , Riñón Poliquístico Autosómico Dominante , Humanos , Masculino , Riñón Poliquístico Autosómico Dominante/complicaciones , Riñón Poliquístico Autosómico Dominante/diagnóstico por imagen , Riñón Poliquístico Autosómico Dominante/genética , Quistes/diagnóstico por imagen , Quistes/terapia , Riñón/patología , Hepatopatías/diagnóstico , Hepatopatías/patología , Neoplasias Renales/patología , Biomarcadores , Enfermedades Raras/patologíaRESUMEN
In order to fight the SARS-CoV-2 pandemic, mass-vaccination programs have been launched globally starting December 2020. The pace of COVID-19 vaccines development was impressive and although data from clinical trials and post-authorization studies showed acceptable safety profile, additional studies and long-term population-level surveillance are needed. A possible link between all type of vaccination and immunological diseases is perhaps one of the hottest topics in literature; correspondingly, there is growing concern over the small but growing number of case reports linking COVID-19 vaccines with the development of glomerular disease. Our group conducted a systematic review of such cases. Results showed that IgA nephropathy (IgAN) and Minimal Change Disease (MCD) are the most frequently associated glomerulopathies. Interestingly, IgAN cases are mostly flares occurring few hours after the second dose of RNA vaccines and have a good clinical outcome, while both de novo and recurring MCD can occur up to 28 days after the first or second dose of vaccines. RNA vaccines are the most common vaccine type to be associated with glomerulopathy. Of course, this may simply reflect the more widespread use of these vaccines. However, compared to traditional vaccines, they do seem produce a higher antibody response and a stronger CD8+ T- and CD4+ T-cell response, including higher production of chemokines and cytokines.
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COVID-19 , Glomerulonefritis por IGA , Nefrosis Lipoidea , COVID-19/prevención & control , Vacunas contra la COVID-19/efectos adversos , Femenino , Humanos , Masculino , Nefrólogos , SARS-CoV-2 , VacunaciónRESUMEN
Hyperkalemia is common in patients treated with renin-angiotensin-aldosterone system inhibitors (RAASis), and it represents the main cause of the large gap reported between guideline recommendations and real-world practice in chronic kidney disease (CKD). We conducted a CKD-population-based restrospective study to determine the prevalence of patients with CKD treated with RAASis, incidence of hyperkalemia in patients with CKD treated with RAASis, and proportion of patients with RAASi medication change after experiencing incident hyperkalemia. Among 809 patients with CKD analyzed, 556 (68.7%) were treated with RAASis, and RAASi prescription was greater in stages 2-4 of CKD. Hyperkalemia occurred in 9.2% of RAASi-treated patients, and the adjusted rate of hyperkalemia among patients with stage 4-5 CKD was 3-fold higher compared with patients with eGFR > 60 ml/min/1.73 m2. RAASi treatment was discontinued in 55.3% of the patients after hyperkalemia event (74.2% discontinued therapy, 3.2% received a reduced dose, and 22.6% reduced the number of RAASi drugs). This study shows that the incidence of hyperkalemia is frequently observed in patients with CKD patients with RAASis, and that rates increase with deteriorating levels of kidney function from stages 1 to 3. RAASi medication change following an episode of hyperkalemia occurred in almost half of the patients after experiencing hyperkalemia.
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Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic disorder with an estimated prevalence between 1 : 1,000 and 1 : 2,500. Until a few decades ago, ADPKD was considered an untreatable disease, relentlessly progressing towards end-stage renal disease because of the lack of specific interventions. In the last decade, some aberrant molecular pathways involved in ADPKD development have been identified, and controlled clinical trials have been conducted to investigate the potential role of active drugs on these pathophysiological mechanisms such somatostatin and tolvaptan. Somatostatin analogues have been shown to be effective not only in ADPKD, but also in polycystic liver disease (PLD) with beneficial effect on cardiac function and a better cost/benefit profile; the only somatostatin analogue currently available for clinical use is octreotide long-acting release (octreotide-LAR), and it is approved only in Italy. On the contrary, tolvaptan is authorized worldwide and has received more attention in the last years, even if its clinical use is widely limited by aquaresis tolerability. The aim of this review is to investigate the advantages and drawbacks of somatostatin analogues and tolvaptan in the treatment of ADPKD.
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Riñón Poliquístico Autosómico Dominante , Antagonistas de los Receptores de Hormonas Antidiuréticas/uso terapéutico , Tasa de Filtración Glomerular , Humanos , Octreótido/uso terapéutico , Riñón Poliquístico Autosómico Dominante/tratamiento farmacológico , Somatostatina/uso terapéutico , Tolvaptán/uso terapéuticoRESUMEN
Autosomal dominant polycystic kidney disease (ADPKD) is a heterogeneous genetic disorder included in ciliopathies, representing the fourth cause of end stage renal disease (ESRD), with an estimated prevalence between 1:1000 and 1:2500. It is mainly caused by mutations in the PKD1 and PKD2 genes encoding for polycystin 1 (PC1) and polycystin 2 (PC2), which regulate differentiation, proliferation, survival, apoptosis, and autophagy. The advances in the knowledge of multiple molecular pathways involved in the pathophysiology of ADPKD led to the development of several treatments which are currently under investigation. Recently, the widespread approval of tolvaptan and, in Italy, of long-acting release octreotide (octreotide-LAR), represents but the beginning of the new therapeutic management of ADPKD patients. Encouraging results are expected from ongoing randomized controlled trials (RCTs), which are investigating not only drugs acting on the calcium/cyclic adenosin monoposphate (cAMP) pathway, the most studied target so far, but also molecules targeting specific pathophysiological pathways (e.g. epidermal growth factor (EGF) receptor, AMP-activated protein kinase (AMPK) and KEAP1-Nrf2) and sphingolipids. Moreover, studies on animal models and cultured cells have also provided further promising therapeutic strategies based on the role of intracellular calcium, cell cycle regulation, MAPK pathway, epigenetic DNA, interstitial inflammation, and cell therapy. Thus, in a near future, tailored therapy could be the key to changing the natural history of ADPKD thanks to the vigorous efforts that are being made to implement clinical and preclinical studies in this field. Our review aimed to summarize the spectrum of drugs that are available in the clinical practice and the most promising molecules undergoing clinical, animal, and cultured cell studies.
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Fallo Renal Crónico , Riñón Poliquístico Autosómico Dominante , Animales , Apoptosis , Calcio/metabolismo , Humanos , Fallo Renal Crónico/etiología , Riñón Poliquístico Autosómico Dominante/tratamiento farmacológico , Riñón Poliquístico Autosómico Dominante/genética , Canales Catiónicos TRPP/genética , Tolvaptán/uso terapéuticoRESUMEN
A clear evidence on the benefits of somatostatin analogues (SA) on liver outcome in patients affected by polycystic liver disease is still lacking. We performed a meta-analysis of RCTs and a trial sequential analysis (TSA) evaluating the effects of SA in adult patients with polycystic liver disease on change in liver volume. As secondary outcome, we evaluated the effects on quality of life as measured by SF36-questionnaire. Six RCTs were selected with an overall sample size of 332 adult patients with polycystic liver disease (mean age: 46 years). Mean liver volume at baseline was 3289 ml in SA group and 3089 ml in placebo group. Overall, unstandardized mean difference in liver volume was - 176 ml (95%CI, - 406, 54; p < 0.133). Heterogeneity was low (I2:0%, p < 0.992). However, we performed a moderator analysis and we found that a higher eGFR significantly correlates to a more pronounced effect of SA on liver volume reduction (p = 0.036). Cumulative Z-curve in TSA did not reach either significance and futility boundaries or required information size. Three RCTs have evaluated Quality of life parameters measured by SF36-QOL questionnaire for a total of 124 patients; no significant difference was found on the effect of SA on QOL parameters when compared with placebo. The present meta-analysis revealed a potential effect of SA on reduction of liver volume and quality of life parameters, but results did not reach a statistical significance. These data could be explained by the need of further studies, as demonstrated through TSA, to reach an adequate sample size to confirm the beneficial outcomes of SAs treatment.
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Quistes/tratamiento farmacológico , Hepatopatías/tratamiento farmacológico , Hígado/efectos de los fármacos , Tamaño de los Órganos/efectos de los fármacos , Somatostatina/análogos & derivados , Somatostatina/uso terapéutico , Humanos , Persona de Mediana Edad , Riñón Poliquístico Autosómico Dominante/tratamiento farmacológico , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND: Although enzyme replacement therapy with agalsidase beta resulted in a variety of clinical benefits, life-long biweekly intravenous infusion may impact on patients' quality of life. Moreover, regular infusions are time-consuming: although a stepwise shortening of infusion duration is allowed up to a minimum of 1.5 hr, in most centers it remains ≥3 hr, and no data exists about the safety and tolerability of agalsidase beta administration at maximum tolerated infusion rate. METHODS: In this study, we reported our experience with a stepwise infusion rate escalation protocol developed in our center in a cohort of 53 Fabry patients (both already receiving and treatment-naΪve), and explored factors predictive for the infusion rate increase tolerability. RESULTS: Fifty-two patients (98%) reduced infusion duration ≤3 hr; of these, 38 (72%) even reached a duration ≤2 hr. We found a significant difference between the mean duration reached by already treated and naΪve patients (p < .01). More severely affected patients (male patients and those with lower enzyme activity) received longer infusions for higher risk of infusion-associated reactions (IARs). A significant correlation between anti-agalsidase antibodies and IARs was found. CONCLUSION: Our infusion rate escalation protocol is safe and could improve patient compliance, satisfaction and quality of life.
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Terapia de Reemplazo Enzimático/métodos , Enfermedad de Fabry/tratamiento farmacológico , Isoenzimas/administración & dosificación , alfa-Galactosidasa/administración & dosificación , Adulto , Anciano , Esquema de Medicación , Enfermedad de Fabry/patología , Femenino , Humanos , Infusiones Intravenosas/métodos , Isoenzimas/uso terapéutico , Masculino , Persona de Mediana Edad , alfa-Galactosidasa/uso terapéuticoRESUMEN
The treatment options for Fabry disease (FD) are enzyme replacement therapy (ERT) with agalsidase alfa or beta, and the oral pharmacological chaperone migalastat. Since few data are available on the effects of switching from ERT to migalastat, we performed a single-center observational study on seven male Fabry patients (18-66 years) to assess the effects of the switch on renal, cardiac, and neurologic function, health status, pain, lyso-Gb3, α-Gal A activity and adverse effects. Data were retrospectively collected at time of diagnosis of FD (baseline, T0), and after 12 months of ERT (T1), and prospectively after 1 year of therapy with migalastat (T2). No patient died or reported renal, cardiac, or cerebrovascular events during the study period. The predefined measures for cardiac, renal and neurologic function, and FD-related symptoms and questionnaires were stable between baseline and the switch, and remained unchanged with migalastat. However, a significant improvement was observed in left ventricular mass index from baseline to T2 (p = 0.016), with a significative difference between the treatments (p = 0.028), and in median proteinuria from T2 vs T1 (p = 0.048). Moreover, scores of the BPI improved from baseline to T1, and remained stable with migalastat. Plasma lyso-Gb3 levels significantly decreased from baseline to T1 (P = 0.007) and T2 (P = 0.003), while did not significantly differ between the two treatments. α-Gal A activity increased from T0 to T2 (p < 0.0001). The frequency of adverse effects under migalastat and ERT was comparable (28% for both drugs). In conclusion, switching from ERT to migalastat is valid, safe and well tolerated.
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1-Desoxinojirimicina/análogos & derivados , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Enfermedad de Fabry/tratamiento farmacológico , 1-Desoxinojirimicina/administración & dosificación , 1-Desoxinojirimicina/efectos adversos , 1-Desoxinojirimicina/uso terapéutico , Administración Oral , Adolescente , Adulto , Anciano , Esquema de Medicación , Tolerancia a Medicamentos , Terapia de Reemplazo Enzimático , Humanos , Isoenzimas/administración & dosificación , Isoenzimas/efectos adversos , Isoenzimas/uso terapéutico , Masculino , Persona de Mediana Edad , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/efectos adversos , Proteínas Recombinantes/uso terapéutico , alfa-Galactosidasa/administración & dosificación , alfa-Galactosidasa/efectos adversos , alfa-Galactosidasa/uso terapéuticoAsunto(s)
Lesión Renal Aguda , Angiotensinas , Infecciones por Coronavirus , Pandemias , Neumonía Viral , Betacoronavirus , COVID-19 , Humanos , Nefrólogos , SARS-CoV-2RESUMEN
BACKGROUND: Oral iron is recommended as first line treatment of anemia in non-dialysis chronic kidney disease (ND-CKD) patients. Sucrosomial® iron, a new generation oral iron with high absorption and bioavailability and a low incidence of side effects, has shown to be not inferior to intravenous (IV) iron in the replacement of iron deficiency anemia in patients with ND-CKD. Besides the clinical benefit, it is also important to determine the comparative total costs of oral versus IV iron administrations. The aim of this study was to perform a cost-minimization analysis of oral Sucrosomial iron, compared with IV iron gluconate from an Italian societal perspective. METHODS: Cost analysis was performed on the 99 patients with ND-CKD and iron-deficiency anemia of the randomized trial by Pisani et al. Human and material resources utilization was recorded during each iron administration. According to study perspective, direct and indirect costs were considered. Costs for each resource unit were taken from official Italian sources. Probabilistic sensitivity analyses were carried out to test the robustness of the results. RESULTS: The base case analysis showed an average cost/cycle per patient of 111 for oral iron and 1302 for IV iron. Thus, the potential saving was equal to 1191 per patient/cycle. The sensitivity analysis showed that the most sensitive driver is the time loss by patient and caregivers for the therapy and related-care, followed by the minutes of nursing care and the number of kilometres travelled to reach the referral centre. DISCUSSION: This study showed that oral Sucrosomial® iron could offer specific advantages in terms of potential savings, and allowed identifying some implications for future research. Such advantages still persist with the new single dose IV iron formulation available in the market, although to a lesser extent.