Biomedical subjects
Publications and source records attributed to M Goicoechea.
The allele C in the CD24 gene has been related to multiple sclerosis (MS). In this work we check this single nucleotide polymorphism (SNP) in a population of 135 patients and 285 controls. Our results confirm the association between the V/V genotype at aa 57 of this gene and MS and highlight the importance of taking into account the origin of the subjects to avoid a population bias.
Ethylene glycol intoxication involves acute renal failure and severe metabolic acidosis. Prolonged renal insufficiency can occur but terminal chronic renal failure has been reported in very few cases. We describe a patient who after ingestion of 920 ml of ethylene glycol developed prolonged acute renal failure needing hemodialysis for 37 days and then he partly recovered renal function. The patient developed a severe sensitive-motor and autonomic polyradiculopathy.
We present here the clinical, molecular and biochemical findings from 238 limb-girdle muscular dystrophy type 2A (LGMD2A) patients, representing approximately 50% (238 out of 484) of the suspected calpainopathy cases referred for the molecular study of the calpain 3 (CAPN3) gene. The mean age at onset of LGMD2A patients was approximately 14 years, and the first symptoms occurred between 6 and 18 years of age in 71% of patients. The mean age at which the patients became wheelchair bound was 32.2 years, with 84% requiring the use of a wheelchair between the age of 21 and 40 years. There was no correlation between the age at onset and the time at which the patient became wheelchair bound, nor between the sex of the patient and the risk of becoming wheelchair bound. Of the cases where the CAPN3 gene was not affected, approximately 20% were diagnosed as LGMD2I muscular dystrophy, while facioscapulohumeral muscular dystrophy (FSHD) was uncommon in this sample. We identified 105 different mutations in the CAPN3 gene of which 50 have not been described previously. These were distributed throughout the coding region of the gene, although some exons remained free of mutations. The most frequent mutation was 2362AG-->TCATCT (exon 22), which was present in 30.7% of the chromosomes analysed (146 chromosomes). Other recurrent mutations described were N50S, 550DeltaA, G222R, IVS6-1G-->A, A483D, IVS17+1G-->T, 2069-2070DeltaAC, R748Q and R748X, each of which was found in >5 chromosomes. The type of mutation in the CAPN3 gene does not appear to be a risk factor for becoming dependent on a wheelchair at a determined age. However, in the cases with two null mutations, there were significantly fewer patients that were able to walk than in the group of patients with at least one missense mutation. Despite the fact that the results of phenotyping and western blot might be biased due to multiple referral centres, producing a diagnosis on the basis of the classical phenotype is neither sufficiently sensitive (86.7%) nor specific (69.3%), although western blot proved to be even less sensitive (52.5%) yet more specific (87.8%). In this case LGMD2I was a relevant cause of false-positive diagnoses. Considering both the clinical phenotype and the biochemical information together, the probability of correctly diagnosing a calpainopathy is very high (90.8%). However, if one of the analyses is lacking, the probability varies from 78.3 to 73.7% depending on the information available. When both tests are negative, the probability that the sample comes from a patient with LGMD2A was 12.2%.
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BACKGROUND: Darbepoetin alfa has demonstrated its efficacy when is administered subcutaneously once-weekly and once every 2 weeks as treatment of anemia in patients with chronic kidney disease (CKD). The aim of this study is to assess the efficacy of subcutaneus darbepoetin alfa administered once monthly in patients with progressive CKD who maintained stable levels of Hb treated on once every other week dosing. METHODS: Patients included in the study maintained hemoglobin (Hb) > 11 g/dl and were receiving darbepoetin alfa once every other week during at least 4 months. We studied a frequency interval dose change: once every other week frequency was converted to once monthly at equivalent dose. The study completers were 12 patients over the third month and 7 at the end of one year evaluation period. RESULTS: A statistic significant decrease in Hb and hematocrit (Hto) was observed over the third month, although all patients maintain Hb levels higher than 11 g/dl. At the same time it was appreciated a statistic significant increased on creatinine (Cr) and parathyroid hormone levels (PTH). At the end of one year evaluation period no differences were observed in any of variables. CONCLUSION: Darbepoetin alfa administered once monthly is an efficacious option as treatment of anemia for patientes with CKD. With a dose of 1 mcg/kg/month, all patientes maintain Hb > 11 g/dl.
BACKGROUND: Recent data have suggested the existence of a relationship between the use of synthetic vascular accesses and increased erythropoietin (Epo) requirements. The present study aimed to evaluate the possible role of the type of vascular access in both Epo and intravenous (i.v.) iron requirements. METHODS: One-hundred-and-seven individuals without recognized causes of Epo resistance, 62 of them undergoing chronic haemodialysis through native arteriovenous fistulae (AVF) and 45 through PTFE grafts, were retrospectively studied (one-year follow-up). Sixty-nine patients, i.e. all but three with a PTFE graft and 27 with native AVF, were taking anti-platelet agents. Doses of i.v. iron and Epo and laboratory parameters were recorded. RESULTS: Erythropoietin and i.v. iron requirements were higher in the patients dialysed through PTFE grafts compared with those with native AVF (Epo: 103.8+/-58.4 vs 81.0+/-44.5 U/kg/week, P=0.025; i.v. iron: 178.9+/-111 vs. 125.9+/-96 mg/month, P=0.01). On a yearly basis, the difference in Epo dose represented a total of 94582+/-16789 U Epo/patient/year. Moreover, the patients with PTFE grafts received more red blood cell transfusions than patients with native AVF (P=0.021). No differences between laboratory, dialysis kinetics, demographic or comorbidity parameters were found. The type of vascular access was the best predictor of the requirement of > or =150 U/kg/week Epo (P=0.03). Even though the patients who received anti-platelet therapy required more i.v. iron (167.5+/-103.6 vs. 114.5+/-101.4 mg/month, P=0.008) but not more Epo (P=NS), the possibility of an accessory role of anti-platelet agents in the increased Epo requirements with PTFE grafts cannot be ruled out. CONCLUSIONS: The use of a PTFE graft and anti-platelet drugs represents a previously undescribed association related to higher Epo and i.v. iron requirements. The association described herein adds new arguments to the debate concerning the choice of vascular access in chronic haemodialysis patients.
Cases of porphyria cutanea tarda (PCT) are occasionally reported in hemodialysis patients. Recently, hepatitis C virus has been recognized as a precipitating factor of PCT. The activity of the liver disease may be critical for the appearance of PCT. In this regard, liver disease reactivation after treatment with interferon alpha (IFN-alpha) is a well-known phenomenon. We report the case of a hemodialysis patient who developed PCT coincidentally with reactivation of liver disease, immediately after treatment with IFN-alpha. Therefore, in the present case, reactivation of hepatitis after IFN-alpha withdrawal could be the triggering factor. The occurrence of a bout of PCT should be considered as a possible complication at the end of IFN-alpha therapy, if reactivation of the disease exists.
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Hemodialysis (HD) patients are prone to develop iron deficiency because of consumption of iron stores during erythropoietin (EPO) therapy. Data are needed to establish the factors involved in the different iron needs among these patients. Sixty-five HD patients were prospectively studied during a year. The subjects were dialyzed through polytetrafluoroethylene (PTFE) grafts (n = 23), arteriovenous native fistulae (n = 41), and a Permcath (n = 1). Twenty-four patients were administered aspirin; 23 patients, ticlopidine; 1 patient, dipyridamole; and 4 patients, anticoagulation with acenocoumarol. Iron supplementation (oral or parenteral) and laboratory parameters were recorded monthly. Significant differences in iron requirements, depending on the use of antiplatelet and/or anticoagulation agents, were found. Total parenteral iron supplements were greater in patients on antiplatelet therapy with either native or graft vascular accesses compared with the rest (2,406 +/- 1,445 versus 1,562 +/- 858 mg; P = 0.0081). Twelve of 52 patients on antiplatelet therapy required oral iron and only 1 of 13 patients not on antiplatelet therapy was administered oral iron supplements (P < 0.05). Patients on antiplatelet therapy were administered more transfusions (1.9 +/- 3.8 transfusions/y) than individuals not on antiplatelet therapy (0.15 +/- 0.3 transfusions/y; P = 0.0015). However, only patients with PTFE grafts on antiplatelet therapy had a post-HD bleeding time longer than patients not on antiplatelet therapy (9.1 +/- 3.6 versus 5.7 +/- 3.9 minutes; P < 0.0001). Multiple logistic regression analysis showed that the use of antiplatelet agents (P < 0.05) is an independent factor that increased the probability of requiring greater parenteral iron supplements (>2.5 g/y). Patients with PTFE grafts required more EPO than those with autologous fistulae (160 +/- 93 versus 100 +/- 63 U/kg/wk; P = 0.012). No differences between groups were found that could explain this finding. Antiplatelet and/or anticoagulation therapy implied the use of greater amounts of iron supplements in HD patients. Although these greater requirements of iron occurred in parallel with bleeding from the vascular access, additional data favor the existence of other factors, eg, interdialytic blood losses. The present study suggests that antiplatelet therapy may be an important factor in determining iron requirements in HD patients. Moreover, our data relate for the first time the use of prosthetic grafts with increased EPO requirements, an issue of great potential importance in the debate about vascular access policy in dialysis units.
The role of vitamin D receptor (VDR) gene polymorphisms in the pathogenesis of hyperparathyroidism is uncertain. Controversial results have been reported. The aim of this study was to explore the relevance of BsmI VDR gene polymorphism in patients with primary hyperparathyroidism (PHPT) due to adenomas. For this purpose, 36 postmenopausal patients with PHPT, mean age 64 years, were compared with a normal age-matched female population (n = 81). BsmI polymorphism distribution in PHPT group was as follows: Bb 50% (18/36); BB 22% (8/36); bb 28% (10/36). In the control group, the distribution was Bb 49% (40/81); BB 16% (13/81); bb 35% (28/81). No statistical differences were found between the two groups. In the PHPT group, no statistical associations were found between different allelic distribution and age, creatinine, hematocrit, phosphorus, alkaline phosphatase (ALP), total calcium, serum parathyroid hormone (PTH), or gland weight. By contrast, levels of serum calcium and iPTH values positively correlated with the PT weight (r = 0.421 and 0.599, respectively, P = 0.0001). Our data suggest that at least in this group, BsmI VDR gene polymorphism appears to be of minor relevance in clinical presentation and possibly, tumorigenesis in PHPT due to adenomas.
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BACKGROUND: Cytokines are regulatory factors of erythropoiesis, especially in pathologic conditions. Even though a relevant role for a deranged cytokine production in the pathogenesis of dialysis anemia has been suggested, no data are available that analyze the role of cytokines in the key therapeutic issue of the needs of erythropoietin. The aim of the present study in hemodialysis patients was, therefore, to examine the relationship between the dose of recombinant human erythropoietin (EPO) and the production of cytokines by peripheral blood mononuclear cells (PBMC). METHODS: After the exclusion of subjects with major active causes of EPO resistance, data from 34 hemodialysis patients were available for analysis. Cytokine levels were measured in the supernatants of stimulated [with bacterial lipopolysaccharide and interferon gamma (IFN-gamma)] and unstimulated PBMC. Mean yearly values of hematocrit, hemoglobin, transferrin saturation, ferritin, parathormone (PTH) and aluminum levels and EPO doses (U/kg/week) were calculated. For analysis, the 34 patients were divided according to their cutoff requirements for EPO: patients with requirements of EPO > or = 60 U/kg/week (group A1, 26 subjects) versus EPO < 60 U/kg/week (group B1, 8 subjects) and patients with requirements of EPO > or = 100 U/kg/week (group A2, 18 subjects) versus <100 U/kg/week (group B2, 16 subjects). RESULTS: A significant direct correlation between interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-a) production values and EPO doses was found (P = 0.039 and P = 0.02 respectively). On the other hand, there was a significantly negative correlation between interleukin-12 (IL-12) production values and EPO doses (P = 0.029). Patients of groups A1 and A2 had spontaneously higher tumor necrosis factor-alpha (TNF-alpha) and lower IL-12 and IFNgamma production compared to patients from groups B1 and B2. CONCLUSIONS: Our data disclose a previously undescribed pattern of cytokine alteration that is relevant to determine increased needs of EPO in hemodialysis patients. The present results have potential applicability in designing strategies to improve EPO resistance.
In cases with severe hyperparathyroidism, anaemia improves after parathyroidectomy. The objective of this study was to investigate the influence of treatment with intravenous calcitriol on anaemia in 28 haemodialysis patients. The patients showed moderate to severe hyperparathyroidism (mean parathyroid hormone level 811.6 +/- 327 pg/ml) and were treated with calcitriol (2 microg i.v.) after haemodialysis. The follow-up period was 12 months. 21 out of the 28 patients had been receiving erythropoietin (EPO) prior to calcitriol administration; the remaining 7 did not receive EPO. 24 patients received oral or intravenous iron. The doses of EPO and iron were modified throughout the study period to maintain a haematocrit equal to or higher than 30% and ferritin levels above 150 ng/ml, respectively. EPO needs were evaluated according to the relation EPO dose/haematocrit. We found a significant rise in haematocrit and haemoglobin at 3 and 12 months on calcitriol therapy, with no modification of the EPO dose nor ferritin levels. This improvement in anaemia was observed both in those patients who received EPO initially (p < 0.01) and in those who did not (p < 0.05). Upon dividing the patients according to the response of hyperparathyroidism to the intravenous calcitriol treatment, we observed in the responding patients (n = 19) significant increases in haematocrit (from 31.7 +/- 4.2 to 36.3 +/- 4.9%) and haemoglobin(from 10.6 +/- 1.5 to 12.2 +/- 1.5 g/dl; p < 0.001) at 12 months on intravenous calcitriol therapy, while this was not true of the non-responding patients. The EPO needs diminished in the group of responding patients and increased in the non-responders, although these changes were not statistically significant. We found no direct correlation between the decrease of parathyroid hormone and EPO needs in the group of responding patients. However, an inverse correlation between parathyroid hormone levels and EPO needs (r = -0.799, p < 0.05) was seen in the group of non-responding patients. Treatment with intravenous calcitriol in patients on haemodialysis controls secondary hyperparathyroidism, improves anaemia, and decreases the need for EPO. Studies including a larger number of patients are necessary to clarify the mechanisms underlying the improvement of anaemia upon control of secondary hyperparathyroidism with intravenous calcitriol treatment and to confirm our findings.
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Secondary hyperparathyroidism is still one of the main problems affecting the dialysis population. The use of aluminium hydroxide as a phosphate binder is limited by significant long-term toxicity. Therefore, actually, most patients on haemodialysis receive treatment with calcium containing phosphate binders to avoid hyperphosphataemia.