Vascular and valvular calcifications are highly prevalent in kidney transplant recipients 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 uremia-associated metabolic derangements, kidney transplant recipients 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 kidney transplant recipients, as well as novel therapeutic candidates to potentially prevent their long-term deleterious effects.
Calciphylaxis, also known as calcific uremic 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. Resumen: La calcifilaxis, también denominada arteriolopatía urémica calcificante, es un síndrome raro que causa típicamente necrosis cutánea y que afecta principalmente a los pacientes en diálisis. La patogénesis es multifactorial y depende de la suma de todos los factores que producen calcificaciones ectópicas en el paciente con enfermedad renal crónica, como las alteraciones del metabolismo calcio-fósforo, el hiper o el hipoparatiroidismo, la diabetes, la obesidad, la inflamación sistémica y el uso de inhibidores de vitamina K, entre otros. Desde un punto de vista clínico, la calcifilaxis puede evolucionar desde una púrpura dolorosa hasta extensas áreas de necrosis cutánea que pueden sobreinfectarse y llegar a causar el fallecimiento del paciente por sepsis. El tratamiento se basa fundamentalmente en el manejo de las heridas, la eliminación de todos los elementos que puedan precipitar la calcificación ectópica y el uso de agentes inhibidores del proceso de calcificación. Keywords: Calciphylaxis, Vascular calcifications, Hyperparathyroidism, Bisphosphonates, Palabras clave: Calcifilaxis, Calcificaciones vasculares, Hiperparatiroidismo, Bifosfonatos
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.
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. 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. 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. 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.
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.
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).
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.
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.
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).
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).
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 the national territory. The patients with better control of phosphataemia were patients with KT (93.3% had phosphorus values <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.
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.
El adecuado control de la fosfatemia es objeto de importante preocupación por los profesionales involucrados en el cuidado de los pacientes con enfermedad renal crónica (ERC), ya que los valores elevados de fósforo se encuentran directamente relacionados con un aumento de la mortalidad.
Con el objetivo de conocer la percepción e implicación que los nefrólogos españoles tienen de la necesidad de controlar el fósforo sérico, así como lograr una muestra lo más representativa posible de los valores séricos actuales, se organizó la denominada ‘Semana del Fósforo’ (13–17 de noviembre de 2017).
Se invitó a participar en una encuesta “on-line” a todos los socios de la Sociedad Española de Nefrología, que incluía preguntas sobre aspectos relacionados con el control del fósforo en pacientes con ERC avanzada (ERCA) (filtrado glomerular <30 ml/min/1.73 m2) y en las distintas modalidades de tratamiento renal sustitutivo diálisis peritoneal (DP), hemodiálisis (HD) y trasplante renal (TR).
Se obtuvieron 72 entradas de datos con 7463 pacientes incluidos, de los cuales el 35.4% de ellos estaban en HD, el 34.8% eran TR, el 24.2% tenían ERCA y el 5.5% estaban en DP. El objetivo de fósforo sérico para los cuatro grupos de pacientes fue de 4.5 mg/dl, con mínimas variaciones en función del área del territorio nacional. Los pacientes con mejor control de la fosfatemia fueron los pacientes con TR (el 93.3% presentaban valores de fósforo <4.5 mg/dL), seguidos por los pacientes en ERCA (65.6% con fósforo <4.5 mg/dL). Sólo un 53.6% de los pacientes en HD y el 39.4% de los que estaban en DP cumplieron el objetivo de fósforo <4.5 mg/dL. El grupo de pacientes en diálisis fue en el que más se prescribían captores de fósforo (73.5% y 75.6% en los pacientes en HD y DP, respectivamente), siendo menos frecuente en los pacientes en ERCA (39.9%) y sólo un 4.5% en los TR.
Los resultados nos indican que los objetivos de los profesionales españoles están en consonancia con lo que recomiendan las guías clínicas nacionales e internacionales; sin embargo, aún hay un amplio margen de mejora para lograr esos objetivos, especialmente en los pacientes en HD y DP.
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.
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.
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%)
< 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),
< 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,
< 0.001). In a multivariate logistic regression analysis, dialysis modality was the main determinant of the 1-84PTH/non-1-84PTH ratio.
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.
Introduction:
A case of dual corneal involvement due to Fuchs endothelial corneal dystrophy and epithelial basement membrane corneal dystrophy in a patient with Steinert’s myotonic dystrophy type 1 ...is described, and a literature review on the triple association is made.
Case description:
A 52-year-old male diagnosed with myotonic dystrophy type 1 presented due to progressive bilateral vision loss during the past year. A full ophthalmological evaluation was made, with biomicroscopy, funduscopy, anterior segment optical coherence tomography, and endothelial cell count using specular microscopy. Exploration revealed bilateral superior palpebral ptosis, visual acuity 0.5 in the right eye and 0.3 in the left eye, and with an intraocular pressure of 11 and 10 mmHg, respectively. Biomicroscopy revealed map-dot-fingerprint lesions characteristic of epithelial basement membrane corneal dystrophy in both eyes, as well as abundant endothelial guttae due to Fuchs endothelial corneal dystrophy (stage II) and bilateral nuclear and posterior subcapsular cataracts. Specular microscopy in turn showed cell loss and a destructured endothelial map. Finally, anterior segment optical coherence tomography revealed the accumulation of epithelial basement membrane and hyperreflective endothelial excrescences corresponding to guttae.
Conclusion:
The association of Fuchs endothelial corneal dystrophy with myotonic dystrophy has been described and explained by a common genetic basis in the expansion of a CTG trinucleotide repeat, though this is the first reported case of the triple association of Fuchs endothelial corneal dystrophy, epithelial basement membrane corneal dystrophy, and myotonic dystrophy type 1. New mutations or still unknown genetic alterations could possibly explain the triple association reported in our case.
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.
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.
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.
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.
Bisphosphonates could constitute an alternative to treat CUA in addition to standard therapy.
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