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Vascular and valvular calcifications are highly prevalent in kidney transplant recipients (KTRs) and are associated with an increased risk of cardiovascular events, which represent the leading cause of long-term mortality in these patients. However, cardiovascular calcification has been traditionally considered as a condition mostly associated with advanced chronic kidney disease stages and dialysis, and comparatively fewer studies have assessed its impact after kidney transplantation. Despite partial or complete resolution of uraemia-associated metabolic derangements, KTRs are still exposed to several pro-calcifying stimuli that favour the progression of pre-existing vascular calcifications or their de novo development. Traditional risk factors, bone mineral disorders, inflammation, immunosuppressive drugs and deficiency of calcification inhibitors may all play a role, and strategies to correct or minimize their effects are urgently needed. The aim of this work is to provide an overview of established and putative mediators involved in the pathogenesis of cardiovascular calcification in kidney transplantation, and to describe the clinical and radiological features of these forms. We also discuss current evidence on preventive strategies to delay the progression of cardiovascular calcifications in KTRs, as well as novel therapeutic candidates to potentially prevent their long-term deleterious effects.
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Enfermedades Cardiovasculares , Trasplante de Riñón , Calcificación Vascular , Humanos , Enfermedades Cardiovasculares/etiología , Trasplante de Riñón/efectos adversos , Diálisis Renal/efectos adversos , Factores de Riesgo , Receptores de Trasplantes , Calcificación Vascular/complicacionesRESUMEN
The dialysis-based definition of Delayed Graft Function (dDGF) is not necessarily objective as it depends on the individual physician's decision. The functional definition of DGF (fDGF, the failure of serum creatinine to decrease by at least 10% daily on 3 consecutive days during the first week post-transplant), may be more sensitive to reflect recovery after the ischemia-reperfusion injury. We retrospectively analyzed both definitions in 253 deceased donor kidney transplant recipients for predicting death-censored graft failure as primary outcome, using eGFR < 25 ml/min/1.73 m2 as a surrogate end-point for graft failure. Secondary outcome was a composite outcome that included graft failure as above and also patient's death. Median follow-up was 3.22 [2.38-4.21] years. Seventy-nine patients developed dDGF (31.2%) and 127 developed fDGF (50.2%). Sixty-three patients fulfilled criteria for both definitions (24.9%). At multivariable analysis, the two definitions were significantly associated with the primary [HR (95%CI) 2.07 (1.09-3.94), P = 0.026 for fDGF and HR (95%CI) 2.41 (1.33-4.37), P = 0.004 for dDGF] and the secondary composite outcome [HR (95%CI) 1.58 (1.01-2.51), P = 0.047 for fDGF and HR (95%CI) 1.67 (1.05-2.66), P = 0.028 for dDGF]. Patients who met criteria for both definitions had the worst prognosis, with a three-year estimates (95%CI) of survival from the primary and secondary outcomes of 2.31 (2.02-2.59) and 2.20 (1.91-2.49) years for fDGF+/dDGF+, in comparison with the other groups (P < 0.01 for trend). fDGF provides supplementary information about graft outcomes on top of the dDGF definition in a modern series of kidney transplantation.
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Trasplante de Riñón , Funcionamiento Retardado del Injerto , Rechazo de Injerto , Supervivencia de Injerto , Humanos , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Donantes de TejidosAsunto(s)
COVID-19/prevención & control , Inmunosupresores/administración & dosificación , Enfermedades Renales/complicaciones , Trasplante de Riñón , SARS-CoV-2/aislamiento & purificación , Receptores de Trasplantes/estadística & datos numéricos , Adulto , Anciano , COVID-19/epidemiología , COVID-19/inmunología , COVID-19/virología , Femenino , Humanos , Enfermedades Renales/cirugía , Masculino , Persona de Mediana Edad , España/epidemiologíaRESUMEN
Donor after cardiac death (DCD) grafts have excellent survival despite the high incidence of delayed graft function (DGF). We assessed the feasibility of a mammalian target of rapamycin inhibitor (mTOR-I) protocol in uncontrolled DCD kidney transplantation and compared it with brain-dead donor (DBD) transplantation under calcineurin inhibitor (CNI) treatment. This retrospective study (2002-2011) included 109 Maastricht category II DCD patients and 218 standard-criteria DBD as controls. Immunosuppression consisted of polyclonal antibody induction, mycophenolate mofetil, prednisone, and mTOR-I (starting on day 6) in the DCD group and tacrolimus in the DBD group. DGF occurred in 72.5% of the DCD group vs. 26.1% of the DBD group (P = 0.001). Patient survival at 1 year was 99.1% vs. 95.9% (P = 0.112), and graft survival was 89% vs. 92.2% (P = 0.253). Patient survival at 5 years was 85.3% vs. 90.1% (P = 0.340) and graft survival was 85.5% vs. 78.8% (P = 0.166). During the first year, 46.8% (n = 51) of DCD patients were converted to CNI therapy. Serum creatinine at 1 year was 1.5(1.26-2) mg/dl vs. 1.4(1.16-1.8) mg/dl (P = 0.078). At 1 year, the acute rejection rate was 7.3% vs. 12.5% (P = 0.766). mTOR-I-based therapy was not associated with inferior graft function or higher rejection rates than standard CNI therapy. DCD kidney transplantation with an mTOR-I-based protocol is feasible but is associated with a high conversion rate to CNI-based therapy.
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Everolimus/uso terapéutico , Rechazo de Injerto/prevención & control , Inmunosupresores/uso terapéutico , Trasplante de Riñón/mortalidad , Serina-Treonina Quinasas TOR/antagonistas & inhibidores , Adulto , Anciano , Inhibidores de la Calcineurina/uso terapéutico , Funcionamiento Retardado del Injerto , Everolimus/farmacología , Estudios de Factibilidad , Femenino , Rechazo de Injerto/epidemiología , Humanos , Terapia de Inmunosupresión/estadística & datos numéricos , Inmunosupresores/farmacología , Pruebas de Función Renal , Masculino , Persona de Mediana Edad , Proteinuria/epidemiología , Estudios Retrospectivos , España/epidemiología , Adulto JovenRESUMEN
BACKGROUND AND OBJECTIVES: Calcific uremic arteriolopathy (CUA) is a life-threatening condition almost exclusively affecting patients with end-stage renal failure. Several therapies have been employed to treat this disease with irregular results. METHODS: Comparison of a prospective case series with a historical cohort. Group I: 12 patients with CUA diagnosed before 2002 (5 men, 6 on dialysis and 6 with functioning allografts) treated with standard treatment. Group II: 11 patients with CUA diagnosed between 2002 and 2010 (4 men, 6 on dialysis and 5 with functioning allografts) treated with standard treatment and bisphosphonates for 6 months. The diagnosis was made by clinical suspicion and a confirmatory biopsy in both groups. Ten patients had a previous history of high calcium-phosphorus product, 9 had a history of high parathyroid hormone (> 800 pg/ml) levels, 13 had a history of high cumulative steroids and 9 patients were under dicoumarin treatment. Two patients were obese and 5 had diabetes mellitus. RESULTS: In Group I, 58.7% required amputation of the affected limb, 3 patients recovered and 2 died. In all patients of Group II the progression of the skin lesions decreased between 2 and 4 weeks after the start of bisphosphonate therapy with no changes in blood levels of calcium and phosphate. The improvement in pain and lesions was faster in the patients receiving endovenous bisphosphonates. Renal function remained stable in transplant recipients. No adverse effects were observed. CONCLUSIONS: Bisphosphonates could constitute an alternative to treat CUA in addition to standard therapy.
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Difosfonatos/uso terapéutico , Fallo Renal Crónico/complicaciones , Calcificación Vascular/terapia , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
AIMS: Our aim was to evaluate the long-term effect of cinacalcet in patients with hypercalcaemic secondary hyperparathyroidism (SHPT) after renal transplantation (RT) in order to expand real-world data in this population. METHODS: We performed a multicentre, observational, retrospective study in 17 renal transplant units from Spain. We collected data from renal recipients with hypercalcaemic (calcium >10.2 mg/dL) SHPT (intact parathyroid hormone (iPTH) > 120 pg/mL) who initiated cinacalcet in the clinical practice. RESULTS: We included 193 patients with a mean (standard deviation (SD)) age of 52 (12) years, 58% men. Cinacalcet treatment was initiated at a median of 20 months after RT (median dose 30 mg/day). Mean calcium levels decreased from a mean (SD) of 11.1 (0.6) at baseline to 10.1 (0.8) at 6 months (9.0% reduction, P < 0.0001). Median iPTH was reduced by 23.0% at 6 months (P = 0.0005) and mean phosphorus levels increased by 11.1% (P < 0.0001). The effects were maintained up to 3-years. No changes were observed in renal function or anticalcineurin drug levels. Only 4.1% of patients discontinued cinacalcet due to intolerance and 1.0% due to lack of efficacy. CONCLUSIONS: In renal transplant patients with hypercalcaemic SHPT, cinacalcet controlled serum calcium, iPTH and phosphorus levels up to 3 years. Tolerability was good.
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Hipercalcemia/tratamiento farmacológico , Hiperparatiroidismo Secundario/tratamiento farmacológico , Trasplante de Riñón/efectos adversos , Naftalenos/uso terapéutico , Adulto , Anciano , Calcio/sangre , Cinacalcet , Femenino , Humanos , Hipercalcemia/sangre , Hiperparatiroidismo Secundario/sangre , Masculino , Persona de Mediana Edad , Hormona Paratiroidea/sangre , Fósforo/sangre , Estudios RetrospectivosRESUMEN
BACKGROUND: The adequate control of phosphorus levels is a major concern for professionals involved in the care of patients with chronic kidney disease (CKD), since high phosphorus levels are directly related to an increase in mortality. OBJECTIVES: To know the perception and involvement of Spanish nephrologists on the control of phosphorus levels, the so-called 'Phosphorus Week' was organized (November 13-17, 2017). METHODS: All members of the Spanish Society of Nephrology were invited to participate in an online survey, which included questions on aspects related to phosphorus control in patients with advanced CKD (aCKD) (glomerular filtration rate <30 ml/min/1, 73 m2) and in the different modalities of renal replacement therapies [peritoneal dialysis (PD), hemodialysis (HD) and renal transplantation (KT)]. RESULTS: 72 data entries were obtained in the survey with an inclusion of 7463 patients. Of them, 35.4% were on HD, 34.8% were KT, 24.2% had aCKD and 5.5% were on PD. The serum phosphorus level target for the four groups of patients was 4.5 mg/dl, with minimal variations depending on the area of ââthe national territory. The patients with better control of phosphataemia were patients with KT (93.3% had phosphorus values ââ<4.5 mg/dl), followed by patients with aCKD (65.6% with phosphorus <4.5 mg/dl). Only 53.6% of the patients on HD and 39.4% of those on PD reached the phosphorus goal <4.5 mg/dl. The group of patients on dialysis was the one in whom phosphorus binders prescribed the most (73.5% and 75.6% in HD and PD, respectively), being less frequent in patients with patients with aCKD (39.9%) and only 4.5 % in KT. CONCLUSIONS: The objectives of the Spanish nephrologists are in line with those recommended by the national and international clinical guidelines; however, there is still a wide room for improvement to achieve these goals, especially in HD and PD patients.
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Diálisis Peritoneal , Insuficiencia Renal Crónica , Humanos , Fósforo , Nefrólogos , Diálisis Renal , Insuficiencia Renal Crónica/terapiaRESUMEN
BACKGROUND: Fabry disease (FD) is an X-linked condition caused by variants in the GLA gene. Since females have two X chromosomes, they were historically thought to be carriers. Although increased knowledge has shown that females often develop the disease, data from Spain and other countries reported that females were undertreated. The aim of this study was to provide a wider and more recent description of the disease characteristics and associated management of females with a GLA variant in a Spanish cohort. RESULTS: Ninety-seven females from 12 hospitals were included in this retrospective study. Mean age was 50.1 ± 17.2 years. Median follow-up time from GLA variant identification was 36.1 months, and most (70.1%) were identified through family screening. Variants associated with classic/non-classic phenotypes were similarly distributed (40.2%/53.6%). Missense variants were the most prevalent (n = 84, 86.6%). In the overall group, 70.4% had major organ involvement (i.e., cardiac, renal, cerebrovascular, peripheral nervous system or gastrointestinal), and 47.3% also had typical Fabry signs (angiokeratoma, cornea verticillata or increased plasma lyso-Gb3). Cardiac involvement was the most prevalent (49.5%) and the main reason for treatment initiation. A total of 33 (34%) patients received disease-specific therapy, 55% of whom were diagnosed by family screening. Females carrying variants associated with a classic phenotype had higher frequencies of clinical manifestations (92.3%) and were predominant in the treated subgroup (69.7%). Despite this, there were 34 untreated females (56.7% of total untreated), with both phenotypes represented, who had major organ involvement, with 27 of cardiac, renal or cerebrovascular nature. Age or comorbidities in this subgroup were comparable to the treated subgroup (P = 0.8 and P = 0.8, respectively). CONCLUSIONS: Efforts have been made in recent years to diagnose and treat timely Fabry females in Spain. A high percentage of females with pathogenic variants, regardless of their associated phenotype, will likely develop disease. A proportion of females with severe disease in this cohort received specific treatment. Still a significant number of females, even with same profile as the treated ones, who may be eligible for treatment according to European recommendations, remained untreated. Reasons for this merit further investigation.
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Distrofias Hereditarias de la Córnea , Enfermedad de Fabry , Femenino , Humanos , Estudios Retrospectivos , Cognición , Enfermedad de Fabry/epidemiología , Enfermedad de Fabry/genética , FenotipoRESUMEN
As in 2011, when the Spanish Society of Nephrology (SEN) published the Spanish adaptation to the Kidney Disease: Improving Global Outcomes (KDIGO) universal Guideline on Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD), this document contains an update and an adaptation of the 2017 KDIGO guidelines to our setting. In this field, as in many other areas of nephrology, it has been impossible to irrefutably answer many questions, which remain pending. However, there is no doubt that the close relationship between the CKD-MBD/cardiovascular disease/morbidity and mortality complex and new randomised clinical trials in some areas and the development of new drugs have yielded significant advances in this field and created the need for this update. We would therefore highlight the slight divergences that we propose in the ideal objectives for biochemical abnormalities in the CKD-MBD complex compared to the KDIGO suggestions (for example, in relation to parathyroid hormone or phosphate), the role of native vitamin D and analogues in the control of secondary hyperparathyroidism and the contribution of new phosphate binders and calcimimetics. Attention should also be drawn to the adoption of important new developments in the diagnosis of bone abnormalities in patients with kidney disease and to the need to be more proactive in treating them. In any event, the current speed at which innovations are taking place, while perhaps slower than we might like, globally drives the need for more frequent updates (for example, through Nefrología al día).
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Enfermedades Óseas Metabólicas , Trastorno Mineral y Óseo Asociado a la Enfermedad Renal Crónica , Nefrología , Insuficiencia Renal Crónica , Humanos , Trastorno Mineral y Óseo Asociado a la Enfermedad Renal Crónica/terapia , Trastorno Mineral y Óseo Asociado a la Enfermedad Renal Crónica/complicaciones , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/terapia , Insuficiencia Renal Crónica/diagnóstico , Enfermedades Óseas Metabólicas/tratamiento farmacológico , Enfermedades Óseas Metabólicas/etiología , Enfermedades Óseas Metabólicas/diagnóstico , Minerales/uso terapéutico , FosfatosRESUMEN
BACKGROUND: There are currently no models for the transition of patients with metabolic bone diseases (MBDs) from paediatric to adult care. The aim of this project was to analyse information on the experience of physicians in the transition of these patients in Spain, and to draw up consensus recommendations with the specialists involved in their treatment and follow-up. METHODS: The project was carried out by a group of experts in MBDs and included a systematic review of the literature for the identification of critical points in the transition process. This was used to develop a questionnaire with a total of 48 questions that would determine the degree of consensus on: (a) the rationale for a transition programme and the optimal time for the patient to start the transition process; (b) transition models and plans; (c) the information that should be specified in the transition plan; and (d) the documentation to be created and the training required. Recommendations and a practical algorithm were developed using the findings. The project was endorsed by eight scientific societies. RESULTS: A total of 86 physicians from 53 Spanish hospitals participated. Consensus was reached on 45 of the 48 statements. There was no agreement that the age of 12 years was an appropriate and feasible point at which to initiate the transition in patients with MBD, nor that a gradual transition model could reasonably be implemented in their own hospital. According to the participants, the main barriers for successful transition in Spain today are lack of resources and lack of coordination between paediatric and adult units. CONCLUSIONS: The TEAM Project gives an overview of the transition of paediatric MBD patients to adult care in Spain and provides practical recommendations for its implementation.
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Enfermedades Óseas Metabólicas , Transición a la Atención de Adultos , Humanos , Adulto , Niño , Algoritmos , Consenso , Atención a la SaludRESUMEN
Background: Calciphylaxis is not uniquely observed in uraemic patients, as some cases have also been reported in patients with normal renal function or moderate chronic kidney disease (CKD), in association with severe vasculopathy or systemic inflammation. A particular subset worthy of studying is represented by those patients who develop calciphylaxis after kidney transplantation (KT). Methods: Analysis of the local series of calciphylaxis after KT (n = 14) along with all the other cases reported in the literature from 1969 to 2019 (n = 31), for a total population of 45 patients, is presented. Demographic data, CKD history, risk factors, immunosuppression, clinical presentation and management have been analysed both as a whole and according to the time period (before or after the year 2000). Results: Calciphylaxis developed during the first year after KT in 43.2% of patients and median (interquartile range) creatinine at diagnosis was 2.4 (1.25-4.64) mg/dL. The most frequent presentation included distal purpura or ulcers in one-third of cases and 39.1% of patients were receiving vitamin K antagonists. PTH values were above 500 pg/mL and below 100 pg/mL in 50.0% and 25.0% of cases, respectively. Whole population mortality was 55.6%. As expected, clinical presentation, immunosuppression and management varied depending on the time period. Patients diagnosed after 2000 were older, with longer dialysis vintage, and treatment was usually multimodal; on the contrary, in patients diagnosed before 2000, parathyroidectomy was the treatment of choice in 61.9% of cases. Conclusions: Calciphylaxis can still occur after KT, in many cases during the first year and in patients with a good renal function. Risk factors and management varied according to the time period studied.
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In the original article, third author name has been published incorrectly.
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X-linked hypophosphataemia (XLH) rickets is a rare disease frequently misdiagnosed and mismanaged. Despite having clinical guidelines that offers some therapeutic recommendations based on the clinical experience of experts, physicians still have questions about some important aspects of the diagnosis and treatment of XLH, such as when the disease should be suspected, who should be in charge of the diagnosis, what should be done once the disease is diagnosed, or what therapeutic options are currently available. The objective of this paper is to answer some of the more frequent questions related to the management of patients with XLH by a group of experts participating in a scientific conference on XLH held in Madrid.
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Anticuerpos Monoclonales/uso terapéutico , Quimioterapia/normas , Raquitismo Hipofosfatémico Familiar/diagnóstico , Raquitismo Hipofosfatémico Familiar/tratamiento farmacológico , Guías de Práctica Clínica como Asunto , Adolescente , Niño , Preescolar , Cálculo de Dosificación de Drogas , Femenino , Factor-23 de Crecimiento de Fibroblastos , Humanos , MasculinoRESUMEN
In the original article, there is an error in age related reference.
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INTRODUCTION: The TRANSFORM study demonstrated that an immunosuppression based on a combination of calcineurin inhibitors and de-novo mTOR inhibitors (mTORi) is safe and effective in kidney transplant recipients. However, data that validate this approach in clinical practice are currently missing. MATERIALS AND METHODS: Analysis of 401 kidney transplant recipients transplanted from June 2013 to December 2016. All patients received tacrolimus with prednisone in combination with either mycophenolate (n = 186) or mTORi (either everolimus or sirolimus, n = 215). A propensity score to receive mTORi was calculated based on the inverse probability of treatment weighting (IPTW) from the following parameters: age and sex of donor and recipient, BMI, previous transplants, diabetes, cPRA, dialysis before transplantation, dialysis vintage, type of donor, ABO-incompatibility, HLA-mismatches, induction and ischemia time. Median follow-up was 2.6 [1.9; 3.7] years. RESULTS: Cox-regression analysis suggests good results for mTORi versus MPA in terms of 1-year biopsy-proven acute rejection (BPAR, P = 0.063), 1-year graft loss (P = 0.025) and patient survival (P < 0.001). Results observed for BPAR and graft failure were largely attributed to those patients that would have been excluded by the TRANSFORM because of some exclusion criteria (52.9% of the population, P = 0.003 for 1-year BPAR and P = 0.040 for graft loss). In patients who met selection criteria for TRANSFORM, no effect of treatment for BPAR or graft failure was observed, while the beneficial effect on overall survival persisted. CONCLUSIONS: In a real-life setting, a protocol based on de-novo mTORi with tacrolimus and prednisone could be employed as a standard immunosuppressive regimen and was associated with good outcomes.
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Trasplante de Riñón , Calcineurina , Inhibidores de la Calcineurina/efectos adversos , Rechazo de Injerto/prevención & control , Supervivencia de Injerto , Humanos , Inmunosupresores/efectos adversos , Trasplante de Riñón/efectos adversos , Ácido Micofenólico/efectos adversos , Puntaje de Propensión , Serina-Treonina Quinasas TOR , Tacrolimus/efectos adversosRESUMEN
BACKGROUND: It is commonly believed that mTOR inhibitors (mTORi) should not be used in high-immunological risk kidney transplant recipients due to a perceived increased risk of rejection. However, almost all trials that examined the association of optimal-dose mTORi with calcineurin inhibitor (CNI) have excluded hypersensitized recipients from enrollment. METHODS: To shed light on this issue, we examined 71 consecutive patients with a baseline calculated panel reactive antibody (cPRA) ≥50% that underwent kidney transplantation from June 2013 to December 2016 in our unit. Immunosuppression was based on CNI (tacrolimus), steroids and alternatively mycophenolic acid (MPA; n = 38), or mTORi (either everolimus or sirolimus, n = 33, target trough levels 3-8 ng/mL). RESULTS: Demographic and immunological risk profiles were similar, and almost 90% of patients in both groups received induction with lymphocyte-depleting agents. Cox-regression analysis of rejection-free survival revealed better results for mTORi versus MPA in terms of biopsy-proven acute rejection (hazard ratio [confidence interval], 0.32 [0.11-0.90], P = 0.031 at univariable analysis and 0.34 [0.11-0.95], P = 0.040 at multivariable analysis). There were no differences in 1-year renal function, Banff chronicity score at 3- and 12-month protocol biopsy and development of de novo donor-specific antibodies. Tacrolimus trough levels along the first year were not different between groups (12-mo levels were 8.72 ± 2.93 and 7.85 ± 3.07 ng/mL for MPA and mTORi group respectively, P = 0.277). CONCLUSIONS: This single-center retrospective cohort analysis suggests that in hypersensitized kidney transplant recipients receiving tacrolimus-based immunosuppressive therapy similar clinical outcomes may be obtained using mTOR inhibitors compared to mycophenolate.
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Desensibilización Inmunológica/métodos , Rechazo de Injerto/prevención & control , Inmunosupresores/administración & dosificación , Trasplante de Riñón/efectos adversos , Serina-Treonina Quinasas TOR/antagonistas & inhibidores , Adulto , Anciano , Inhibidores de la Calcineurina/administración & dosificación , Inhibidores de la Calcineurina/efectos adversos , Desensibilización Inmunológica/efectos adversos , Quimioterapia Combinada/efectos adversos , Quimioterapia Combinada/métodos , Everolimus/administración & dosificación , Everolimus/efectos adversos , Femenino , Glucocorticoides/administración & dosificación , Glucocorticoides/efectos adversos , Rechazo de Injerto/inmunología , Antígenos HLA/inmunología , Humanos , Inmunosupresores/efectos adversos , Isoanticuerpos/inmunología , Masculino , Persona de Mediana Edad , Ácido Micofenólico/administración & dosificación , Ácido Micofenólico/efectos adversos , Estudios Retrospectivos , Sirolimus/administración & dosificación , Sirolimus/efectos adversos , Serina-Treonina Quinasas TOR/inmunología , Tacrolimus/administración & dosificación , Tacrolimus/efectos adversos , Resultado del TratamientoRESUMEN
BACKGROUND: Calciphylaxis in end-stage renal disease is characterized by painful necrotic skin ulcers and high mortality. There are no approved therapies. SNF472, an intravenous formulation of myo-inositol hexaphosphate, inhibits the formation and growth of hydroxyapatite crystals, the final common pathway in the pathogenesis of vascular calcification. METHODS: In this open-label, single-arm study, calciphylaxis patients on thrice-weekly hemodialysis and standard care, received intravenous SNF472 3 times per week for 12 weeks. The primary endpoint was wound healing assessed using the quantitative Bates-Jensen Wound Assessment Tool (BWAT). Pain visual analog scale (VAS), quality of life (wound-QoL), and qualitative wound image review were secondary endpoints. Quantitative changes from baseline were analyzed by paired t-tests using multiple imputation to account for missing observations. RESULTS: Fourteen patients received SNF472. Improvements from baseline to week 12 were observed for mean BWAT score (- 8.1; P < 0.001), pain VAS (- 23.6 mm; P = 0.015) and wound-QoL global score (- 0.90; P = 0.003). Of the 9 patients with ulcerated lesions at baseline who completed treatment, wound image review showed improvement for 7. SNF472 was well tolerated with no serious treatment-related adverse events. The most common adverse events were infections which occur frequently in patients on hemodialysis. None of these were considered as treatment-related. CONCLUSIONS: SNF472 was well-tolerated and improvements from baseline to week 12 in wound healing, pain, and quality of life were observed. A randomized, double-blind, placebo-controlled trial is planned to evaluate SNF472 in patients with calciphylaxis.
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Calcifilaxia/tratamiento farmacológico , Dolor/tratamiento farmacológico , Ácido Fítico/administración & dosificación , Calidad de Vida , Cicatrización de Heridas/efectos de los fármacos , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Ácido Fítico/farmacología , Estudios Prospectivos , Factores de TiempoRESUMEN
BACKGROUND: Persistent secondary hyperparathyroidism (SHP) is the most frequent cause of hypercalcemia observed in approximately 10% of renal transplanted (RT) patients 1 year after surgery. Persistent SHP with hypercalcemia is an important factor of bone loss after renal transplantation. This study prospectively evaluates the effects of cinacalcet therapy on serum calcium (SCa) and parathyroid hormone (PTH) blood levels, and basically on bone mineral density (BMD) in RT patients with persistent hyperparathyroidism. METHODS: Nine RT patients (eight women, one man) with allograft function more than 6 months were included based on total SCa more than 10.5 mg/dL and intact parathyroid hormone (iPTH) concentration more than 65 pg/mL. After inclusion, patients started on a single daily oral dose of 30 mg of cinacalcet. At inclusion and every study visit blood levels of creatinine, Ca, P, alkaline phosphatase, iPTH 1,25- dihydroxyvitamin D3, and 25-hydroxyvitamin D3 were assessed. Baseline and at the end of study radial BMD were measured. Study follow-up was 12 months. RESULTS: During the study period, SCa decreased from 11.72+/-0.39 to 10.03+/-0.54 mg/dL (P<0.001). iPTH decreased from 308.85+/-120.12 to 214.66+/-53.75 mg/dL (P<0.05). The mean serum creatinine decreased from 1.58+/-0.34 to 1.25+/-0.27 mg/dL (P=0.03) and the mean radial BMD increased from 0.881+/-0.155 to 0.965+/-0.123 gr/cm2 (P<0.05). There were no significant changes in the other parameters assessed. One patient was excluded for gastrointestinal intolerance. CONCLUSIONS: In RT patients with hypercalcemia secondary to persistent SHP, cinacalcet corrects hypercalcemia and PTH, simultaneously improving BMD.
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Densidad Ósea/efectos de los fármacos , Hipercalcemia/tratamiento farmacológico , Hiperparatiroidismo Secundario/tratamiento farmacológico , Trasplante de Riñón/efectos adversos , Naftalenos/uso terapéutico , Administración Oral , Anciano , Fosfatasa Alcalina/sangre , Calcifediol/sangre , Calcitriol/sangre , Calcio/sangre , Cinacalcet , Creatinina/sangre , Femenino , Humanos , Hipercalcemia/etiología , Hipercalcemia/fisiopatología , Hiperparatiroidismo Secundario/etiología , Hiperparatiroidismo Secundario/fisiopatología , Masculino , Persona de Mediana Edad , Naftalenos/administración & dosificación , Naftalenos/efectos adversos , Hormona Paratiroidea/sangre , Fosfatos/sangre , Estudios Prospectivos , Factores de Tiempo , Resultado del TratamientoRESUMEN
Calciphylaxis, also known as calcific uraemic arteriolopathy, is a rare syndrome that typically causes skin necrosis and usually affects dialysis patients. Its pathogenesis is multifactorial and is the consequence of many factors causing ectopic calcifications in patients with chronic kidney disease, such as calcium-phosphate metabolism disorders, hyper- or hypo-parathyroidism, diabetes, obesity, systemic inflammation and the use of vitamin K antagonists, among others. From a clinical point of view, calciphylaxis may progress from painful purpura to extensive areas of skin necrosis that can potentially lead to superinfection and the death of the patient due to sepsis. Treatment is primarily based on managing the wounds, eliminating all the possible precipitating factors of ectopic calcification and administering agents which are capable of inhibiting the process of calcification.
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Calcifilaxia/etiología , Insuficiencia Renal Crónica/complicaciones , Calcifilaxia/diagnóstico , Calcifilaxia/terapia , Humanos , Diálisis Renal , Insuficiencia Renal Crónica/terapia , Factores de RiesgoRESUMEN
Background: The prevalence of low- turnover bone disease (LTBD) in peritoneal dialysis (PD) patients is higher than in hemodialysis (HD) patients. LTBD patients may be at risk for vascular calcification, and cardiovascular disease. Current therapy for chronic kidney disease metabolic bone disorders (CKD-MBD) is guided by biochemical parameters, as bone biopsy is not used in routine clinical care. Methods: We assessed intact PTH (iPTH: 1-84PTH plus non-1-84PTH), 1-84PTH, and the 1-84PTH/non-1-84PTH ratio in 129 hemodialysis and 73 PD prevalent patients dialyzed with solutions containing 1.75 mmol/L calcium. Results: Hemodialysis and PD patients presented similar iPTH and tCa values and prevalence of putative LTBD as defined according to KDOQI iPTH cut-off levels or 1-84 PTH levels. However, iCa accounted for a higher percentage of tCa in PD (53%) than in hemodialysis (39%) p < 0.001, and the 1-84PTH/non-1-84PTH ratio was lower in PD than in hemodialysis patients (0.44 ± 0.12) vs. (0.60 ± 0.10), p < 0.001. The prevalence of putative LTBD when using the coexistence of 1-84PTH/non-1-84PTH ratio < 1.0 and iPTH < 420 pg/m, was higher in PD than in hemodialysis patients (73 vs. 16% respectively, p < 0.001). In a multivariate logistic regression analysis, dialysis modality was the main determinant of the 1-84PTH/non-1-84PTH ratio. Conclusion: Solutions containing 1.75 mmol/L calciums are associated to a higher proportion of non-1-84PTH fragments in PD than in HD patients. Different analytical criteria result in widely different estimates of LTBD prevalence, thus impairing the ability of clinicians to optimize therapy for CKD-MBD.