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.
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.
Primary aldosteronism (PA) is the most frequent cause of secondary hypertension (HT), and is associated with a higher cardiometabolic risk than essential HT. However, PA remains underdiagnosed, ...probably due to several difficulties clinicians usually find in performing its diagnosis and subtype classification. The aim of this consensus is to provide practical recommendations focused on the prevalence and the diagnosis of PA and the clinical implications of aldosterone excess, from a multidisciplinary perspective, in a nominal group consensus approach by experts from the Spanish Society of Endocrinology and Nutrition (SEEN), Spanish Society of Cardiology (SEC), Spanish Society of Nephrology (SEN), Spanish Society of Internal Medicine (SEMI), Spanish Radiology Society (SERAM), Spanish Society of Vascular and Interventional Radiology (SERVEI), Spanish Society of Laboratory Medicine (SEQC(ML)), Spanish Society of Anatomic-Pathology, Spanish Association of Surgeons (AEC).
Highlights
Following a positive screening test, no further studies are needed for diagnosis of PA if a plasma aldosterone concentration (PAC) > 20 ng/dL and a low circulating direct renin or plasma renin activity (PRA) are detected in a patient with spontaneous hypokalemia.
In all other patients, one (or more) of four different tests is (are) currently recommended: the fludrocortisone suppression test, the oral salt loading test, the intravenous saline test, and/or the captopril challenge test.
In all cases, hypokalemia must be corrected prior to testing.
Interfering medication must be progressively withdrawn before testing, while introducing alpha-1 adrenergic blockers, long-acting non-dihydropyridine calcium antagonists, and/or hydralazine as needed for control of hypertension.
All but the captopril challenge test run the risk of inducing hypokalemia, fluid overload, and a worsening of hypertension.
In the case of borderline results, the initial test employed can be repeated, or a second test performed. Patients with both a negative saline infusion and captopril challenge test appear to be at a low risk for harboring unilateral disease, whereas those positive for both are more likely to exhibit unilateral aldosterone secretion than when tests render conflicting results.
Patients showing a positive screening aldosterone to renin ratio (ARR) with normal/high PAC and a low renin/PRA, yet with negative diagnostic testing, presenting mild hyperaldosteronism, can benefit from targeted therapy of hypertension with mineralocorticoid receptor antagonists.
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.
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.
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.
Treatment with oral risedronate to prevent bone mineral density (BMD) loss in renal transplant recipients has been shown to be effective. There is no agreement on the optimum moment of introduction ...or how long it should be continued. The aim was to evaluate the effectiveness of risedronate at doses of 35 mg/week in renal transplant recipients who underwent treatment immediately after transplant.
A randomized clinical trial was performed on 101 renal transplant patients. The study group (52 patients) received 35 mg risedronate weekly, vitamin D, and calcium, whereas the control group (49 patients) received only vitamin D and calcium. At baseline, 3, 6, and 12 months, basic biochemistry and mineral bone metabolic parameters were determined. Vertebra and hip fracture assessment was performed by means of x-ray and DEXA; an intention-to-treat analysis was performed.
Patients in control group showed a significant worsening of BMD (P<0.05) 12 months into the study. At all follow-up points, lumbar BMD of the study group was significantly greater (P<0.05), whereas femoral BMD of those treated with risedronate was only significant at 6-month follow-up (P<0.05). There was a trend of more vascular calcifications and fractures in the control group, but this was not statistically significant.
Weekly oral administration of risedronate immediately after renal transplantation contributes to an improved BMD, particularly in the femoral neck at 6-month follow-up, without major side effects. Long-term follow-up is needed to establish whether oral risedronate has an influence on vascular calcifications and bone fractures.
Primary aldosteronism (PA) is the most frequent cause of secondary hypertension and is associated with a higher cardiometabolic risk than essential hypertension. The aim of this consensus is to ...provide practical clinical recommendations for its surgical and medical treatment, pathology study and biochemical and clinical follow-up, as well as for the approach in special situations like advanced age, pregnancy and chronic kidney disease, from a multidisciplinary perspective, in a nominal group consensus approach of experts from the Spanish Society of Endocrinology and Nutrition (SEEN), Spanish Society of Cardiology (SEC), Spanish Society of Nephrology (SEN), Spanish Society of Internal Medicine (SEMI), Spanish Radiology Society (SERAM), Spanish Society of Vascular and Interventional Radiology (SERVEI), Spanish Society of Laboratory Medicine (SEQC(ML)), Spanish Society of Anatomic-Pathology and Spanish Association of Surgeons (AEC).
Keypoints
The treatment of choice for PA is medical therapy with mineralocorticoid receptor blockade for bilateral cases and unilateral adrenalectomy for unilateral PA.
The goals of PA treatment are to normalize blood pressure (BP) and excessive aldosterone production, with the final aim of improving associated comorbidities and reducing mortality.
Spironolactone is usually the mineralocorticoid receptor antagonist (MRA) of choice for medical treatment of PA. However, eplerenone has a similar efficacy to that of spironolactone when used in doses 2–3 times higher than the latter and administered 2–3 times a day.
Eplerenone has the advantage of not inducing the anti-androgenic side effects commonly seen with spironolactone.
Adrenalectomy is the gold standard procedure used to remove the aldosterone-hypersecreting adrenal tissue.
The Primary Aldosteronism Outcome (PASO) group criteria are recommended for defining the control objectives of biochemical and clinical response to treatment.
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.
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.
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.
In RT patients with hypercalcemia secondary to persistent SHP, cinacalcet corrects hypercalcemia and PTH, simultaneously improving BMD.
PDF
