Renin-angiotensin-aldosterone system blockers effect in chronic kidney disease progression in hypertensive elderly patients without proteinuria: PROERCAN trial.

INTRODUCTION: Evidence about nefroprotective effect with RAAS blockers in elderly patients with chronic kidney disease (CKD) without proteinuria is lacking. The primary outcome of our study is to evaluate the impact of RAAS blockers in CKD progression in elderly patients without proteinuria. MATERIALS AND METHODS: Multicenter open-label, randomized controlled clinical trial including patients over 65 year-old with hypertension and CKD stages 3-4 without proteinuria. Patients were randomized in a 1:1 ratio to either receive RAAS blockers or other antihypertensive drugs and were followed up for three years. Primary outcome is estimated glomerular filtration rate (eGFR) decline at 3 years. Secondary outcome measures include BP control, renal and cardiovascular events and mortality. RESULTS: 88 patients were included with a mean age of 77.9±6.1 years and a follow up period of 3 years: 40 were randomized to RAAS group and 48 to standard treatment. Ethiology of CKD was: 53 vascular, 16 interstitial and 19 of unknown ethiology. In the RAAS group eGFR slope during follow up was -4.3±1.1ml/min, whereas in the standard treatment group an increase on eGFR was observed after 3 years (+4.6±0.4ml/min), p=0.024. We found no differences in blood pressure control, number of antihypertensive drugs, albuminuria, potassium serum levels, incidence of cardiovascular events nor mortality during the follow up period. CONCLUSIONS: In elderly patients without diabetes nor cardiopathy and with non proteinuric CKD the use of RAAS blockers does not show a reduction in CKD progression. The PROERCAN (PROgresión de Enfermedad Renal Crónica en ANcianos) trial (trial registration: NCT03195023).

Mis-splicing of Tau exon 10 in myotonic dystrophy type 1 is reproduced by overexpression of CELF2 but not by MBNL1 silencing.

Tau is the proteinaceous component of intraneuronal aggregates common to neurodegenerative diseases called Tauopathies, including myotonic dystrophy type 1. In myotonic dystrophy type 1, the presence of microtubule-associated protein Tau aggregates is associated with a mis-splicing of Tau. A toxic gain-of-function at the ribonucleic acid level is a major etiological factor responsible for the mis-splicing of several transcripts in myotonic dystrophy type 1. These are probably the consequence of a loss of muscleblind-like 1 (MBNL1) function or gain of CUGBP1 and ETR3-like factor 1 (CELF1) splicing function. Whether these two dysfunctions occur together or separately and whether all mis-splicing events in myotonic dystrophy type 1 brain result from one or both of these dysfunctions remains unknown. Here, we analyzed the splicing of Tau exons 2 and 10 in the brain of myotonic dystrophy type 1 patients. Two myotonic dystrophy type 1 patients showed a mis-splicing of exon 10 whereas exon 2-inclusion was reduced in all myotonic dystrophy type 1 patients. In order to determine the potential factors responsible for exon 10 mis-splicing, we studied the effect of the splicing factors muscleblind-like 1 (MBNL1), CUGBP1 and ETR3-like factor 1 (CELF1), CUGBP1 and ETR3-like factor 2 (CELF2), and CUGBP1 and ETR3-like factor 4 (CELF4) or a dominant-negative CUGBP1 and ETR-3 like factor (CELF) factor on Tau exon 10 splicing by ectopic expression or siRNA. Interestingly, the inclusion of Tau exon 10 is reduced by CUGBP1 and ETR3-like factor 2 (CELF2) whereas it is insensitive to the loss-of-function of muscleblind-like 1 (MBNL1), CUGBP1 and ETR3-like factor 1 (CELF1) gain-of-function, or a dominant-negative of CUGBP1 and ETR-3 like factor (CELF) factor. Moreover, we observed an increased expression of CUGBP1 and ETR3-like factor 2 (CELF2) only in the brain of myotonic dystrophy type 1 patients with a mis-splicing of exon 10. Taken together, our results indicate the occurrence of a mis-splicing event in myotonic dystrophy type 1 that is induced neither by a loss of muscleblind-like 1 (MBNL1) function nor by a gain of CUGBP1 and ETR3-like factor 1 (CELF1) function but is rather associated to CUGBP1 and ETR3-like factor 2 (CELF2) gain-of-function.

[Anaemia prevalence in pregnant population]. / Prevalencia de anemia en población gestante.

INTRODUCTION: Gestational anaemia, which has specific haemoglobin (Hb) reference values in each trimester of gestation, increases the risk of maternal mortality and complications both in pregnancy and in the first months of the newborn's life. The objective of this study is to evaluate haemoglobin levels in pregnant women in our population, to determine the prevalence of gestational anaemia and to propose reference values specific to them. MATERIAL AND METHODS: Retrospective study of all blood counts requested in pregnancy and postpartum controls during 2019. RESULTS: 9995 gestation haemograms corresponding to 5507 pregnant women were reviewed. Of these, 1134 patients underwent complete follow-up in 2019. The prevalence data for anaemia were 1.8%, 11.8% and 13.2% in each trimester respectively, and the global prevalence in pregnancy was 22.6%. Regarding postpartum anaemia, its prevalence with respect to all pregnant women was 2.99%, increasing to 38.2% in those patients with complications during delivery. CONCLUSIONS: The prevalence of gestational anaemia in our population is somewhat higher than in countries like ours. Therefore, there is room for improvement in our current clinical protocols. It is important to assess updating analytical controls with other more adequate parameters to determine iron reserves, as this is the main cause of anaemia.

COVID-19 vaccination among Spanish nephrologists: Acceptance and side effects.

INTRODUCTION: Four vaccines against Covid-19 have been approved to date. Their acceptance and safety have not been addressed on healthcare workers. The aim of the present study is to evaluate vaccination rates and side effects among Spanish nephrologists. METHODS: All the Spanish nephrologists were invited to participate in this survey. Data on demographics, Covid-19 infection status, received vaccine doses and side effects were collected. Acceptance and side effects were analyzed for Covid-19 vaccination. Factors associated to vaccination were assessed and a multivariate adjusted model was constructed to determine independent predictors for Covid-19 vaccine side effects. RESULTS: A total of 708 nephrologists answered the survey (460 [65%] women, mean age 44±11 years). Six-hundred and eight (86%) had received the first dose and 513 (72%) were fully vaccinated. Most of the subjects (565, 93%) received BNT162b2 (Pfizer-BioNTech®) vaccine. Among vaccinated nephrologists, 453 (75%) presented any side effect; the most frequent was local reaction (68%), followed by myalgia (44%), tiredness (39%) and headache (34%). Age (OR 0.97, 95%CI [0.95-0.99], p<0.0001) and prior Covid-19 infection (OR 2.37, 95%CI [1.27-4.42], p=0.007) were independent predictors for developing side effects with Covid-19 vaccine. Overall side effects were similar with both vaccines, being myalgia (p=0.006) and tiredness (p=0.032) more frequent with the Pfizer-BioNTech® one. CONCLUSION: Age and prior Covid-19 infection were predictors of vaccination side effects among Spanish nephrologists.

Patient-specific iPSC-derived cellular models of LGMDR1.

Limb-girdle muscular dystrophy recessive 1 (LGMDR1) represents one of the most common types of LGMD in the population, where patients develop a progressive muscle degeneration. The disease is caused by mutations in calpain 3 gene, with over 500 mutations reported to date. However, the molecular events that lead to muscle wasting are not clear, nor the reasons for the great clinical variability among patients, and this has so far hindered the development of effective therapies. Here we generate human induced pluripotent stem cells (iPSCs) from skin fibroblasts of 2 healthy controls and 4 LGMDR1 patients with different mutations. The generated lines were able to differentiate into myogenic progenitors and myotubes in vitro and in vivo, upon a transient PAX7 overexpressing protocol. Thus, we have generated myogenic cellular models of LGMDR1 that harbor different CAPN3 mutations within a human genetic background, and which do not derive from muscular biopsies. These models will allow us to investigate disease mechanisms and test therapies. Despite the variability found among iPSC lines that was unrelated to CAPN3 mutations, we found that patient-derived myogenic progenitors and myotubes express lower levels of DMD, which codes a key protein in satellite cell regulation and myotube maturation.

Obesity related risk for chronic kidney disease progression and cardiovascular disease after propensity score matching.

INTRODUCTION: Obesity is a major health problem worldwide. It carries a markedly increased risk for multiple diseases such as type 2 diabetes mellitus, hypertension, cardiovascular disease (CVD) and chronic kidney disease (CKD). To complicate an already difficult topic a new subtype of obesity has been defined lately, the metabolically healthy obese. Our study aimed to clarify the association between obesity, metabolic syndrome and kidney disease progression. METHODS: Observational retrospective single centre study including 212 patients with stage 3-4 CKD with no previous history of rapid kidney disease progression. Patients were divided according to BMI status and presence of metabolic syndrome. Anthropometric, clinical and laboratory data were collected to follow-up. Propensity score matching was performed for age, albuminuria and baseline renal function. During follow-up renal and cardiovascular events were recorded. RESULTS: After a mean follow-up of 88.44±36.07 months a total of 18 patients reached the renal outcome in the non-obese group and 21 in the obese group. Differences were not statistically significant (log rank=0.21: p=0.64). Multiple Cox regression analysis showed that obesity was not predictor for worse renal outcomes [HR 1.01, 95% CI 0.45-2.24; p=0.97]. When stratifying the sample according to baseline metabolic syndrome and obesity presence there was no difference in renal survival (log rank=0.852; p=0.35) A total of 48 cardiovascular events were registered: seventeen in the non-obese group and thirty-one in the obese group. Differences in event-free time between both groups were statistically significant (log rank=4.44;p=0.035), especially after four years of follow-up. After stratifying for MS and obesity presence at baseline the event-free time differences where again statistically significant (log rank=16.86;p=0.001), specially for the obese patients with metabolic syndrome. CONCLUSIONS: Obesity has little impact on chronic kidney disease progression despite the presence or absence of metabolic syndrome in a cohort matched for age, baseline renal function and albuminuria. Obesity conferred greater cardiovascular risk when combined with metabolic syndrome.

Chronic kidney disease progression in patients with resistant hypertension subject to 2 therapeutic strategies: Intensification with loop diuretics vs aldosterone antagonists. / Progresión de la enfermedad renal crónica en pacientes con hipertensión resistente sometidos a 2 estrategias terapéuticas: intensificación con diuréticos de asa vs. antagonistas de la aldosterona.

INTRODUCTION: Actualy, there are few data about glomerular filtration rate (eGFR) drop in patients with resistant hypertension and how diferent therapies can modify chronic kidney disease progression (CKD). OBJECTIVE: To evaluate CKD progression in patients with resistant hypertension undergoing 2diferent therapies: treatment with spironolactone or furosemide. METHODS: We included 30 patients (21M, 9W) with a mean age of 66.3±9.1 years, eGFR 55.8±16.5ml/min/1.73 m2, SBP 162.8±8.2 and DBP 90.2±6.2mmHg: 15 patients received spironolactone and 15 furosemide and we followed up them a median of 32 months (28-41). RESULTS: The mean annual eGFR decrease was -2.8±5.4ml/min/1.73 m2. In spironolactone group was -2.1±4.8ml/min/1.73 m2 and in furosemide group was -3.2±5.6ml/min/1.73 m2, P<0.01. In patients received spironolactone, SBP decreased 23±9mmHg and in furosemide group decreased 16±3mmHg, P<.01. DBP decreased 10±8mmHg and 6±2mmHg, respectively (P<.01). Treatment with spironolactone reduced albuminuria from a serum albumin/creatine ratio of 210 (121-385) mg/g to 65 (45-120) mg/g at the end of follow-up, P<.01. There were no significant changes in the albumin/creatinine ratio in the furosemide group. The slower drop in kidney function was associated with lower SBP (P=.04), higher GFR (P=.01), lower albuminuria (P=.01), not diabetes mellitus (P=.01) and treatment with spironolactone (P=.02). Treatment with spironolactone (OR 2.13, IC 1.89-2.29) and lower albuminuria (OR 0.98, CI 0.97-0.99) maintain their independent predictive power in a multivariate model. CONCLUSION: Treatment with spironolactone is more effective reducing BP and albuminuria in patients with resistant hypertension compared with furosemide and it is associated with a slower progression of CKD in the long term follow up.

The effect of renin-angiotensin-aldosterone system blockers on the progression of chronic kidney disease in hypertensive elderly patients without proteinuria: PROERCAN study. Rationale and design.

INTRODUCTION: Blood pressure (BP) control is fundamental to the care of patients with chronic kidney disease (CKD), and is relevant at all stages of CKD. Renin-angiotensin-aldosterone system (RAAS) blockers have shown to be effective, not only in BP control but also in reducing proteinuria and slowing CKD progression. However, there is a lack of evidence for recommending RAAS blockers in elderly patients with CKD without proteinuria. The primary outcome of the present study is to evaluate the impact of RAAS blockers on CKD progression in elderly patients without proteinuria. MATERIALS AND METHODS: The PROERCAN trial (trial registration, NCT03195023) is a multicentre open-label, randomized controlled clinical trial with 110 participants over 65 years-old with hypertension and CKD stages 3-4 without proteinuria. Patients will be randomized in a 1:1 ratio to either receive RAAS blockers or other antihypertensive drugs, and will be followed up for three years. Primary outcome is the estimated glomerular filtration rate (eGFR) decline at 3 years. Secondary outcomes include BP control, renal and cardiovascular events, and mortality. RESULTS AND CONCLUSIONS: The design of this trial is presented here. The results will show if antihypertensive treatment with RAAS blockers has an impact on CKD progression in elderly patients without proteinuria. Any differences in BP control, cardiovascular events, and mortality with each antihypertensive treatment will be also clarified.

Characterization of novel CAPN3 isoforms in white blood cells: an alternative approach for limb-girdle muscular dystrophy 2A diagnosis.

Limb-girdle muscular dystrophy type 2A (LGMD2A) is an autosomal recessive disorder caused by mutations in the CAPN3 gene. Its definitive diagnosis is laborious, since the clinical phenotype is often similar to other types of muscular dystrophy and since the CAPN3 gene encompasses a large genomic region with more than 300 pathogenic mutations described to date. In fact, it is estimated that nearly 25% of the cases with a phenotype suggestive of LGMD2A do not have mutations in the CAPN3 gene and that, in up to 22% of the cases, only one mutation is identified. In the present work, we have characterised CAPN3 messenger RNA (mRNA) expression in peripheral blood, and we have performed a retrospective diagnostic study with 26 LGMD2A patients, sequencing a transcript of CAPN3 present in white blood cells (WBCs). The 25% of the mutations presented in this paper (7/28) act modifying pre-mRNA splicing of the CAPN3 transcript, including the first deep-intronic mutation described to date in the CAPN3 gene. Our results determine that the sequencing of CAPN3 transcripts present in WBCs could be applied as a new approach for LGMD2A diagnosis. This method improves and simplifies diagnosis, since it combines the advantages of mRNA analysis in a more accessible and rapidly regenerated tissue. However, the lack of exon 15 in the CAPN3 isoforms present in blood, and the presence of mRNA degradation make it necessary to combine mRNA and DNA analyses in some specific cases.

Early steroid treatment improves the recovery of renal function in patients with drug-induced acute interstitial nephritis.

The role of steroid treatment in drug-induced acute interstitial nephritis (DI-AIN) is controversial. We performed a multicenter retrospective study to determine the influence of steroids in 61 patients with biopsy-proven DI-AIN, 52 of whom were treated with steroids. The responsible drugs were antibiotics (56%), non-steroidal anti-inflammatory drugs (37%) or other drugs. The final serum creatinine was significantly lower in treated patients while almost half of untreated patients remained on chronic dialysis. Among treated patients, over half showed a complete recovery of baseline renal function, whereas the rest remained in renal failure. There were no significant initial differences between these two subgroups in terms of duration or dosage of steroids. After withdrawal of the presumed causative drug, we found that when steroid treatment was delayed (by an average of 34 days) renal function did not return to baseline levels compared to those who received steroid treatment within the first 2 weeks after withdrawal of the offending agent. We found a significant correlation between the delay in steroid treatment and the final serum creatinine. Renal biopsies, including three patients who underwent a second biopsy, showed a progression of interstitial fibrosis related to the delay in steroid treatment. Our study shows that steroids should be started promptly after diagnosis of DI-AIN to avoid subsequent interstitial fibrosis and an incomplete recovery of renal function.

Molecular characterization of putative modulatory factors in two Spanish families with A1555G deafness.

The aim of this work is to characterize possible modifying factors in 2 large families carrying the A1555G mitochondrial mutation. The heteroplasmy of the mutation, the presence of aminoglycosides, the cosegregation with other mitochondrial mutations, the proposed linkage in chromosome 8 and the association with TRMU and MTO1 genes were studied. None of the mentioned modifying factors were related with the phenotype presentation of A1555G mutation. However, TRMU G28T single nucleotide polymorphism is present in 1 of the studied families.

Minimizing creatine kinase variability in rats for neuromuscular research purposes.

Rat serum or plasma creatine kinase (CK) activity is widely used to evaluate myopathic processes, to test the myotoxicity of different drugs, or to analyse the benefits of emerging gene therapies in some neuromuscular disorders. However, great variability is found in this determination. The aim of this study has been to control some factors of variation in order to reduce variability and increase the reproducibility of analytical data. 8-10-week-old Wistar-Han rats were used. The study consisted of four sequential phases. Phase I aimed to analyse the effect of ether and isoflurane as anaesthetic drugs. The objective of Phase II was to evaluate bleeding rats via retro-orbital sinus vs. tail vein. Phases III and IV were designed as two separate, repeated measure experiments on two factors: habituation to laboratory handling procedures in Phase III and gender in Phase IV. The repeated factor was the storage temperature of blood sample prior to centrifugation. Ether did not significantly increased the CK value. Using isoflurane, getting rats accustomed to laboratory handling procedures and whole blood refrigeration prior to centrifugation and serum separation resulted in statistically significant reduction in CK value and variability. Male rats showed significantly higher values than female rats. In the light of our findings, CK value and variability in rats may be minimized by choosing tail vein as site of bleeding, getting rats accustomed to laboratory handling procedures and maintaining whole blood refrigerated until centrifugation and serum separation.

[Calciphylaxis: fatal complication of cardiometabolic syndrome in patients with end stage kidney disease]. / Calcifilaxis: complicación grave del síndrome cardio-metabólico en pacientes con enfermedad renal crónica terminal (ERCT).

UNLABELLED: Calciphylaxis characterized by schemic skin ulceration due to subcutaneous small arterioles calcification, is a rare disease but usually fatal. Disorders of calcium metabolism and vascular calcifications are common in dialysis patients but calciphylaxis prevalence is low in patients with end stage renal disease. So we proposed other emergent factors implicated in calciphylaxis development. METHODS: We studied retrospective 8 patients who developed calciphylaxis in our service from january 2001 to december 2006. RESULTS: All patients were female with mean age at diagnosis 68.5+/-6.7 years. All patients were receiving hemodialysis therapy and 6 patients had been receiving hemodialysis less than four months. Six patients had diabetes mellitus type II and all patients were obese (BMI >25 kg/m2). All patients had metabolic syndrome (APTIII) with bad control hypertension and 6 (75%) were receiving anticoagulation therapy with warfarin. Patients didn t have severe alterations of calcium metabolism, all had product calcium-phosphorus <55. All patients developed low blood pressure at the beginning of dialysis treatment (98.3+/-22.7/60+/-18,29 mmHg). 7 patients present proximal lesions in fatty regions like abdomen and thighs. Histopathologic examination reveals calcium deposits in arteriole-sized and small vessels with vascular thrombosis. Prognosis was poor, seven patients died secondary to a sepsis originated in infected cutaneous ulcers. CONCLUSIONS: calciphylaxis is a disease with poor prognosis and high mortality, without specific treatment actually. Female gender, obesity associated with diabetes mellitus and cardiometabolic syndrome, anticoagulant therapy with warfarin and low blood pressure associated with hemodialysis therapy, are risk factors to develop calciphylaxis, in absence of severe disorders of calcium metabolism. In these patients is important to avoid hypotension episodes during dialysis, dialysis hypotension appears to be an important risk factor who promotes ischemia of subcutaneous adipose tissue.

[Therapeutic guidelines fulfillment in clinical practice in patients with chronic kidney disease (CKD)]. / Evaluación del cumplimiento de las guías terapéuticas en la práctica clínica en pacientes con enfermedad renal crónica (ERC).

OBJECTIVE: The present study was designed to determine the degree of fulfillment of the therapeutic objectives recommended in the clinical guidelines in patients with chronic kidney disease (CKD) in a nephrology outpatient clinic and the treatment that the patients were receiving to control these objectives. METHODS: A descriptive, cross-sectional study was performed in unselected patients with CKD (stages 1-5) who attended the nephrology outpatient clinic of the Hospital General Universitario Gregorio Marañón for follow up between 1st January and 1st April 2006. RESULTS: Data from 600 patients with a mean age of 62.8 years (56.5% male) were collected. The distribution of patients according to the stage (S) of CKD was as follows: S1: 11.5%, S2: 18%, S3: 36.7%, S4: 27.5% and S5: 6.3%. The target blood pressure (BP) < 130/80 mmHg was reached in 35.5%. The target diastolic blood pressure was controlled in 70%. However, systolic blood pressure increasing significantly with age and the degree of renal failure was controlled only in 42%. Total cholesterol was or=50 mg/l in 64.1% of patients. Triglyceride level was related to renal function (p=0.04). Most of the patients (94%) had hemoglobin (Hb) levels >or=11 g/dl, because of a significant increase in the percentage of patients treated with erythropoiesis-stimulating agents as the degree of renal function is reduced. Target levels of calcium-phosphorus (CaXP) product (<55 mg2/dl 2) were maintained in all the stages at the expense of decreased Ca and increased P in relation to the decrease in glomerular filtrate (p=0.001). Target Ca (8.4-9.5 mg/dl) was reached in 85% of cases (2% of patients in S3, 37% of patients in S4 and 54% in S5 were receiving calcitriol). Phosphorus levels were adequate in 80% of patients, but target levels of parathyroid hormone (PTH) were maintained only in 28.6% of patients in S3 (35-70 pg/ml), 14% of patients in S4 (70-110 pg/ml) and 28% in S-5 (115-300 pg/ml). CONCLUSIONS: Anemia is the best controlled factor of all the factors related to renal function. The degree of control of blood pressure (BP) has improved in recent years. However, it is still poor, particularly the control of systolic blood pressure getting worse with renal failure and age. It is difficult to reach the target PTH, despite adequate levels of Ca and P. Cholesterol levels, unlike triglyceride levels, do not depend on renal function and require an increase in the use and/or doses of cholesterol-lowering drugs.

LGMD2A: genotype-phenotype correlations based on a large mutational survey on the calpain 3 gene.

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%.

[Prolonged acute renal failure and severe polyradiculopathy in ethylene glycol intoxication]. / Fracaso renal agudo prolongado y polirradiculopatía severa en paciente intoxicado con etilenglicol.

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.

[Evaluation of efficacy of darbepoetin alfa administered once monthly as treatment of anemia in predialysis patients with chronic kidney disease]. / Evaluación de la eficacia de la darbepoetina alfa subcutánea administrada en dosis única mensual en el tratamiento de la anemia en pacientes con insuficiencia renal crónica prediálisis.

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.

Antiplatelet therapy alters iron requirements in hemodialysis patients.

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.

[Susceptibility of non-typhi Salmonella spp. at the Galdakao Hospital (1992-1998)]. / Estudio de sensibilidad de Salmonella spp. no typhi en el Hospital de Galdakao (1992 a 1998).

Non-typhi Salmonella spp. are a common cause of gastroenteritis. In patients with a greater risk of bacteremia (those with immunosuppression, cardiovascular abnormalities, prostheses, those older than 50, especially those with atherosclerosis, and neonates) the need for antibiotic treatment may be affected by the presence of resistance. We retrospectively studied the evolution of antibiotic resistance of 917 strains isolated from feces, during the period between January 1992 and May 1998. Resistances of 32.1% to ampicillin, 14.6% to amoxicillin- clavulanic acid, 14.8% to chloramphenicol, 3.5% to trimethoprim-sulfamethoxazole and 1.8% to gentamicin were found. All the strains were susceptible to cefotaxime and ciprofloxacin. There was a distinct increase in the ampicillin resistance (12.9% in 1992 to 52.5% in 1998), amoxicillin-clavulanic acid (8.3% in 1992 to 23% in 1998), chloramphenicol (8.3% in 1994 to 23% in 1998) and trimethoprim-sulfamethoxazole (0% in 1992 to 6.6% in 1998). The typhimurium serotype showed higher resistance levels than the enteritidis serotype. Ciprofloxacin and trimethoprim-sulfamethoxazole (in children), used as first-choice antibiotics in patients with intestinal infections caused by non-typhi Salmonella spp., show excellent activity in our area.