[Consensus document for the detection and management of chronic kidney disease]. / Documento de consenso para la detección y manejo de la enfermedad renal crónica.

Chronic kidney disease (CKD) is an important global health problem, involving to 10% of the Spanish population, promoting high morbidity and mortality for the patient and an elevate consumption of the total health resources for the National Health System. This is a summary of an executive consensus document of ten scientific societies involved in the care of the renal patient, that actualizes the consensus document published in 2007. The central extended document can be consulted in the web page of each society. The aspects included in the document are: Concept, epidemiology and risk factors for CKD. Diagnostic criteria, evaluation and stages of CKD, albuminuria and glomerular filtration rate estimation. Progression factors for renal damage. Patient remission criteria. Follow-up and objectives of each speciality control. Nephrotoxicity prevention. Cardio-vascular damage detection. Diet, life-style and treatment attitudes: hypertension, dyslipidaemia, hyperglycemia, smoking, obesity, hyperuricemia, anemia, mineral and bone disorders. Multidisciplinary management for Primary Care, other specialities and Nephrology. Integrated management of CKD patient in haemodialysis, peritoneal dialysis and renal transplant patients. Management of the uremic patient in palliative care. We hope that this document may be of help for the multidisciplinary management of CKD patients by summarizing the most updated recommendations.

Drug utilization and off-label drug use among Spanish emergency room paediatric patients.

OBJECTIVE: To describe the use of medicines and to determine the frequency of off-label use in emergency room paediatric patients. PATIENTS AND METHODS: A prospective, observational and descriptive study was carried out in the setting of the paediatric emergency room of a Spanish general hospital. Medicines used by children <14 years prior to their emergency room visit were analysed based on information collected from parents/guardians and relatives for each drug prescription. Off-label use was defined as the utilization of a drug at an indication, dosage, frequency or route of administration that differed from the specifications in the Summary of Product Characteristics or by children outside the authorized age group. RESULTS: The patient cohort comprised 462 children, among whom 336 children had been prescribed 667 prescriptions. Of the medicines prescribed, 90% fell into only five 5 Anatomical Therapeutic Chemical Classification System groups. The most frequent active principles were ibuprofen and paracetamol. Of a total of 152 different formulations recorded, no paediatric information was provided for 40 formulations, and one formulation was contraindicated in children. Based on the established criteria, 338 prescriptions were off-label: no paediatric information or contraindication in children were available (82 prescriptions); the drug was used for an indication different from the authorized one (111 prescriptions); drug use was inconsistent with age recommendations (16 prescriptions); drug use was inconsistent with dose/frequency (129 prescriptions). Of the 152 formulations, 107 were occasionally used in an off-label manner. CONCLUSIONS: Although the mean number of drugs used in children is small, off-label use is frequent. Research efforts should target paediatric studies that allow a rational drug use in children.

Solifenacin pharmacology.

Antimuscarinics are the drugs of choice for the treatment of overactive bladder syndrome, and their benefit/risk ratio depends largely on selectivity for the different subtypes of muscarinic receptors. Solifenacin is the antimuscarinic that presents greatest selectivity for M3 bladder receptors, which may translate into a lower incidence of undesirable effects related to other receptor subtypes. Metabolic pathways of the antimuscarinics may impact efficacy and appearance of interactions. Solifenacin is metabolized only by the CYP3A4, giving three inactive metabolites and one with a similar activity to the original compound. However, other drugs in the group are also a substrate for the CYP 2D6 which presents polymorphisms, whereby their pharmacokinetics may be modified in slow metabolizers. The risk of interactions of solifenacin is low, and it is lower than that of the antimuscarinics which are also metabolized by the CYP 2D6. The unaltered fraction of solifenacin which is eliminated in urine, together with the active metabolite, can contribute to the therapeutic effect by acting on the urothelium receptors. It is not necessary to adjust doses of solifenacin in elderly patients or those with moderate liver or kidney impairment.

Number of drugs used in secondary cardiovascular prevention and late survival in the population of Valencia Community, Spain.

BACKGROUND: Drug treatment for secondary prevention of cardiovascular disease is recommended by guidelines, but it is not always followed in real life. This study wanted to assess the size of this gap and its impact on mortality in subjects after a cardiovascular event (MACE). METHODS: Patients with any of MACE in the period from January 1st 2011 to December 31st 2013, and more than one year of follow-up were selected from population of the Valencian Community. Drugs for secondary prevention were antiplatelets, renin-angiotensin system blockers and statins. Assessment of treatment was performed one year after the initial event. Mortality risk was assessed using Cox by the number of drug classes (G0 no medication, G1 one, G2 two and G3 three drugs) adjusted by confounders. RESULTS: A total of 92,436 patients (62% men, mean age 72 years) of whom 60.5% presented with stroke, 30.6% with myocardial infarction and 8.9% with revascularization were included. Among them, 4.1% were G0, 20.2% G1, 32.9% G2 and 42.7% G3. A progressive decrease in mortality was observed in G1 (HR 0.83, CI 95% 0.73-0.95), G2 (HR 0.70, CI 95% 0.60-0.82) and G3 (HR 0.61, CI95% 0.51-0.74) vs. G0. In diabetic subgroup, significant reduction of risk was observed in the G2 (0.79, CI 95% 0.63-0.98) and G3 (0.72, CI9 5% 0.56-0.95), but not in G1 (0.97, CI 95% 0.80-1.17). CONCLUSION: A gap between guidelines and reality in the use of cardiovascular protecting drugs one year after the initial event still exists and it is largely related with all-cause late mortality.

[Drug-drug interactions. An update]. / Interacciones medicamentosas. Nuevos aspectos.

A drug interaction is the quantitative or qualitative modification of the effect of a drug by the simultaneous or successive administration of a different one. The simultaneous administration of several medicines to the same patient can facilitates their appearance. It is difficult to determine their incidence, but it is related to the number of drugs administered simultaneously. Although it is impossible to remember all the clinical relevant interactions, to bare in mind their existence and the possible mechanisms of production can help to identify them and to contribute to their prevention. The most frequent interactions related with clinical problems are the pharmacokinetic ones, mainly those related to the metabolism through the cytochrome P450 system or the presystemic clearance by means of the P-glycoprotein and other drug transporters. Interactions between drugs and grapefruit juice or St John's wort are frequent and it is important to bear in mind in clinical practice.

Clinical relevance of the selectivity of sodium-glucose cotransporter-2 inhibitors. / Relevancia clínica de la selectividad de los inhibidores del cotransportador sodio-glucosa tipo 2.

Selectivity is the property of a drug to preferentially bind to a biological structure. Most drugs can bind and stimulate or inhibit more than one system. Therefore, it is important that they are selective for the intended site and that the doses used do not have effects on other sites, which could provoke adverse reactions. Selectivity is assessed through in vitro experiments on organs or isolated cells. If the aim is to compare drugs, the experiment should be conducted in the same tissue and with the same design. Even so, the results cannot be directly extrapolated to clinical practice due to the influence of pharmacokinetic properties, which allow an adequate dose of the drug to reach the target site. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are able to inhibit renal SGLT2 without modifying intestinal SGLT1, whose inhibition could produce gastrointestinal adverse reactions. The concentration needed to inhibit each of the transporters is calculated, as well as the ratio between the concentration that inhibits SGLT1 and the concentration needed to inhibit SGLT2. The higher the ratio, the greater the selectivity and the lower the risk of gastrointestinal adverse reactions. The three SGLT2i recently introduced in the therapeutic arsenal are sufficiently selective for SGLT2 to make effects on intestinal SGLT1 unlikely. To differentiate the components of this therapeutic class, its pharmacokinetic properties should be analysed rather than its pharmacodynamic characteristics, such as selectivity.

[Antihypertensive drug-drug interactions]. / Interacciones farmacológicas de los fármacos antihipertensivos.

A drug interaction is the quantitative or qualitative modification of the effect of a drug by the simultaneous or successive administration of a different one. Hypertensive patients, mainly the more elderly ones, frequently present concomitant diseases that require the administration of several medicines which facilitates the appearance of interactions. The lack of effectiveness of the antihypertensive treatment is a relatively frequent fact that sometimes is due to interactions of antihypertensive drugs with other treatments. It is difficult to determine the incidence of interactions, but it is related to the number of drugs administered simultaneously. Between 37 and 60% of hospital-admissions are treated with potentially dangerous drug associations and up to a 6% of fatal events are due to this circumstance. Among antihypertensive drugs, diuretics and angiotensin converting enzyme inhibitors are less affected by drug-interactions. Lipophilic beta-blockers agents may present some clinical relevant interactions, whereas calcium channel blockers, especially the non-dihydropiridinic ones, are implied in clinically relevant pharmacokinetic interactions. Among the angiotensin receptor blockers there are differences that would have to be considered when they are used in patients who receive other drugs. Although it is impossible for the doctor to remember all the clinical relevant interactions, it is important to bear in mind their existence and the possible mechanisms of production which can help to identify them and to contribute to their prevention. The most frequent interactions related with clinical problems are the pharmacokinetic ones, mainly those related to the metabolism through the cytochrome P450 system or the presystemic clearance by means of the P-glycoprotein. Enzymes of the cytochrome P450 system may present polymorphisms that can explain the individual differences in the response to drugs or the appearance of drug-interactions.

The KARTAN study: a postmarketing assessment of Irbesartan in patients with hypertension.

BACKGROUND: An important purpose of postmarketing surveillance of drugs is to better characterize the safety profile of drug therapy in the clinical setting. Another goal is to confirm the effectiveness of these drugs in patients who are candidates for antihypertensive therapy and who may have been excluded from Phase III studies. Irbesartan is a long-acting angiotensin II-receptor blocker specific for the angiotensin 1-receptor subtype that, in clinical trials in patients with hypertension, reduces blood pressure. OBJECTIVES: The KARTAN (this word was derived from the first and last syllables of Karvea [trademark of Bristol-Myers Squibb Group, Madrid, Spain] and irbesartan) study was designed to confirm and extend the findings from previous clinical trials using data from a large number of patients with hypertension treated with irbesartan in routine clinical practice. The primary goal was to assess the types and incidences of adverse drug reactions (ADRs) occurring at a low frequency (<0.05%) with irbesartan. The secondary objectives were to study the effect of irbesartan as an antihypertensive agent, to assess the types and incidences of the most frequent ADRs (>/=0.05%) occurring in routine clinical practice, and to detect possible interactions between irbesartan and other drugs frequently used in the primary care setting. METHODS: This 6-month, observational, open-label, uncontrolled, national, longitudinal, prospective study was conducted by 852 primary care physicians across Spain. Men and women aged >/=18 years with mild to moderate hypertension who, in their physicians' opinion, should have been treated with irbesartan were included. Each patient was followed up for 6 months, attending visits at baseline (ie, the start of treatment) and 1, 3, and 6 months after the start of treatment. A sample size of 3219 patients was calculated for the detection of >/=1 low-incidence (<0.05%) ADR. After the baseline visit, therapy typically was begun with irbesartan 150 mg/d. The initial dose was titrated up, at 300-mg increments based on the patient's response, at each visit as needed to achieve the treatment goals (systolic blood pressure, <140 mm Hg; diastolic blood pressure, <90 mm Hg). Information regarding ADRs was collected on case-report forms designed for each visit and analyzed by the scientific committee of the study. All recruited patients were included in the tolerability analysis. RESULTS: A total of 4887 patients were enrolled (2165 men, 2 772 women; mean [SD] age, 61.1 [11.0] years [range, 19-94 years]; 23.3% of patients were aged >70 years); 4612 were assessable for efficacy. One hundred eight patients (2.2%) experienced ADRs over the 6-month treatment period; 3 of these patients (0.1%) experienced >1 ADR. Of the total number of clinical manifestations of ADRs, 24 occurred at an incidence <0.05%. Irbesartan produced reductions in blood pressure that were statistically significant from the first visit (all p < 0.001), and 39.9% of the patients achieved the treatment goal at the end of the follow-up period. CONCLUSION: In this postmarketing surveillance study of patients with hypertension treated in routine clinical practice, irbesartan showed a satisfactory tolerability profile that was consistent with that seen in randomized, controlled trials.

[Risk of pharmacological interactions due to the co-administration of statins and cytochrome P450 isoenzyme 3A4-metabolized drugs: multicentre, crossover study]. / Riesgo de interacciones farmacológicas por la coadministración de estatinas con fármacos metabolizados por la isoenzima 3A4 del citocromo P450: estudio epidemiológico, transversal y multicéntrico.

BACKGROUND AND OBJECTIVES: Statins are safe but have a significant potential for pharmacological interactions. The objective of the study was to evaluate the prevalence of potential interactions throughout the cytochrome P450 isoenzyme 3A4 (CYP3A4) system in a large sample of statin-treated subjects and to determine which factors, from the patient and the physician, were associated with a higher risk of interactions. PATIENTS AND METHODS: This is an observational, cross-over, population study that included 7,880 subjects treated with statins. Both data from patients and from the1,681 participating physicians were recorded and analyzed. RESULTS: Fifty-nine percent of the participants were receiving a statin metabolized by the CYP3A4, and 21.5% of all participants received a drug, different from a statin, metabolized by the CYP3A4. There were no differences in the frequency of utilization of statins metabolized or not by the CYP3A4 in relation to the simultaneous prescription of drugs metabolized by the same pathway (22 vs. 21%, respectively). Globally, 12.9% of all participants were at risk of an interaction. These patients were older, received a higher number of drugs and had more comorbidity. Sixty percent of the physicians mentioned that the possibility of an interaction greatly conditioned their selection of a particular statin. Likewise, 56% of them had software that alerted of possible interactions. These aspects, however, did not influence the number of patients at risk of interactions. CONCLUSION: The proportion of statin-treated patients at risk of interaction is elevated. Physicians do not usually pay attention to this possibility despite having available alert software and therapeutic alternatives.

[Consensus document for the detection and management of chronic kidney disease]. / Documento de consenso para la detección y manejo de la enfermedad renal crónica.

Chronic kidney disease (CKD) is an important global health problem, involving to 10% of the Spanish population, promoting high morbidity and mortality for the patient and an elevate consumption of the total health resources for the National Health System. This is a summary of an executive consensus document of ten scientific societies involved in the care of the renal patient, that actualizes the consensus document published in 2007. The central extended document can be consulted in the web page of each society. The aspects included in the document are: Concept, epidemiology and risk factors for CKD. Diagnostic criteria, evaluation and stages of CKD, albuminuria and glomerular filtration rate estimation. Progression factors for renal damage. Patient remission criteria. Follow-up and objectives of each speciality control. Nephrotoxicity prevention. Cardio-vascular damage detection. Diet, life-style and treatment attitudes: hypertension, dyslipidaemia, hyperglycemia, smoking, obesity, hyperuricemia, anemia, mineral and bone disorders. Multidisciplinary management for Primary Care, other specialities and Nephrology. Integrated management of CKD patient in haemodialysis, peritoneal dialysis and renal transplant patients. Management of the uremic patient in palliative care. We hope that this document may be of help for the multidisciplinary management of CKD patients by summarizing the most updated recommendations.

Consensus document for the detection and management of chronic kidney disease.

Chronic kidney disease (CKD) is a major public health problem that, in its different stages, may affect up to 10% of the Spanish population and results in high morbidity and mortality, as well as high consumption of National Health System resources. Ten scientific societies involved in the management of kidney patients agreed to update the 2007 CKD consensus document. The current version is an abridged edition of the detailed general document, which can be consulted on the webpages of each signatory society. It includes the following aspects: CKD definition, epidemiology and risk factors and criteria on diagnosis, assessment and staging of CKD, albuminuria and glomerular filtration estimation. Progression factors and concept. Criteria for referral to Nephrology. Patient follow-up, attitudes and objectives by specialty. Prevention of nephrotoxicity. Detection of cardiovascular damage. Attitudes, lifestyle and treatment: management of high blood pressure, dyslipidaemia, hyperglycaemia, smoking, obesity, hyperuricaemia, anaemia and mineral and bone metabolism disorders. Coordinated follow-up by Primary Care – other specialties – Nephrology. Management of renal replacement therapy, haemodialysis, peritoneal dialysis and renal transplantation patients. Palliative treatment of terminal uraemia. We hope that this document will be very useful in the multidisciplinary management of CKD patients, in view of the updated recommendations.

[Consensus document for the detection and management of chronic kidney disease]. / Documento de consenso para la detección y manejo de la enfermedad renal crónica.

Chronic kidney disease (CKD) is an important global health problem, involving to 10% of the Spanish population, promoting high morbidity and mortality for the patient and an elevate consumption of the total health resources for the National Health System. This is a summary of an executive consensus document of ten scientific societies involved in the care of the renal patient, that actualizes the consensus document published in 2007. The central extended document can be consulted in the web page of each society. The aspects included in the document are: Concept, epidemiology and risk factors for CKD. Diagnostic criteria, evaluation and stages of CKD, albuminuria and glomerular filtration rate estimation. Progression factors for renal damage. Patient remission criteria. Follow-up and objectives of each speciality control. Nephrotoxicity prevention. Cardio-vascular damage detection. Diet, life-style and treatment attitudes: hypertension, dyslipidaemia, hyperglycemia, smoking, obesity, hyperuricemia, anemia, mineral and bone disorders. Multidisciplinary management for Primary Care, other specialities and Nephrology. Integrated management of CKD patient in haemodialysis, peritoneal dialysis and renal transplant patients. Management of the uremic patient in palliative care. We hope that this document may be of help for the multidisciplinary management of CKD patients by summarizing the most updated recommendations.

Management of high blood pressure in children and adolescents: recommendations of the European Society of Hypertension.

Hypertension in children and adolescents has gained ground in cardiovascular medicine, thanks to the progress made in several areas of pathophysiological and clinical research. These guidelines represent a consensus among specialists involved in the detection and control of high blood pressure in children and adolescents. The guidelines synthesize a considerable amount of scientific data and clinical experience and represent best clinical wisdom upon which physicians, nurses and families should base their decisions. They call attention to the burden of hypertension in children and adolescents, and its contribution to the current epidemic of cardiovascular disease, these guidelines should encourage public policy makers, to develop a global effort to improve identification and treatment of high blood pressure among children and adolescents.

Cold medication containing oral phenylephrine as a cause of hypertension in children.

A 5-year-old girl presented hypertension [24-h blood pressure (BP) average 135/80 mmHg, above the 99th BP percentile], as confirmed by ambulatory BP monitoring, following the use of a cold preparation (2.5 ml every 8 h for 4 days) containing phenyephrine (1 mg/ml). There was a clear relationship between the administration of the medication and hypertension, and between normalized BP values (24-h BP average 109/66 mmHg, 90th percentile) and the withdrawal of the medication. Alternative causes of hypertension could not be found. This is the first reported case of children's hypertension related with oral administration of phenylephrine. The potential risk of medicines containing sympathomimetic drugs should not be underestimated, and cold preparations should be included in the differential diagnosis of the etiology of hypertension in children.

Prevalence of abnormal urinary albumin excretion rate in hypertensive patients with impaired fasting glucose and its association with cardiovascular disease.

The prevalence and significance of microalbuminuria in hypertensive patients with impaired fasting glucose (IFG) has received very little attention. A total of 10,320 hypertensive patients who attended primary care centers were enrolled in this study, and the final analysis was done in 7625 patients: 1459 without IFG (plasma glucose <100 mg/dl), 3010 with IFG (plasma glucose > or =100 mg/dl and <126 mg/dl), and 3156 with type 2 diabetes (plasma glucose >126 mg/dl). Microalbuminuria was determined using the Micro Albustix reactive strip from Bayer (high urinary albumin excretion [UAE]: Albumin/creatinine ratio > or =3.4 mg/mmol). The proportion of patients with high UAE was 39.4, 48.3, and 65.6%, respectively, in the three groups (P < 0.01 for the trend). The differences in UAE between the group with IFG and the group with normal fasting glucose persisted after adjustment for age, gender, systolic BP, fasting plasma glucose, and cardiovascular comorbidity (odds ratio 1.74; 95% confidence interval 1.08 to 2.80). Hypertensive patients with IFG and high UAE showed a higher prevalence of ischemic heart disease, cardiac insufficiency, left ventricular hypertrophy, atrial fibrillation, and renal insufficiency than the group with normal UAE. Global prevalence of cardiovascular conditions was 30.4% in the group with high UAE compared with 21.4% in the group with normal UAE (odds ratio 1.60; 95% confidence interval 1.31 to 1.95). It is concluded that almost half of hypertensive patients with IFG have high UAE and a higher prevalence of associated cardiovascular involvement and renal insufficiency.

Urinary albumin excretion and glomerular filtration rate across the spectrum of glucose abnormalities in essential hypertension.

The objective of this study was to assess the relationship between urinary albumin excretion (UAE) and GF across the spectrum of the glucose metabolism abnormalities in a large population of patients with hypertension. The Microaluminuria en Pacientes con Glucemia Basal Alterada (MAGAL) is a multicenter, cross-sectional study that was carried out by 1723 primary care physicians. A total of 6227 patients with essential hypertension (in three groups: [1] normal fasting glucose <100 mg/dl, [2] impaired fasting glucose > or =100 to 126 mg/dl, and [3] type 2 diabetes) were analyzed in this substudy. GFR was estimated by using the Modification of Diet in Renal Disease (MDRD) abbreviated equation. A single first-morning urine albumin/creatinine ratio was measured using Bayer reagent strip Microalbustix, a semiquantitative method. Abnormal UAE was defined as an albumin/creatinine ratio > or =3.4 mg/mmol (equivalent to > or =30 mg/g). The prevalence of abnormal UAE, > or =3.4 mg/mmol, increased across the spectrum of glucose abnormalities: 39.7, 46.2, 48.6, and 65.6% for normoglycemic, low-range, and high-range impaired fasting glucose and diabetes, respectively. UAE was positively related to SBP (P = 0.003) and inversely to GFR (P < 0.001). Renal insufficiency (GFR <60 ml/min per 1.73 m2) was present in 21.8% of the patients, more frequently older patients, women, and those with diabetes. The factors that were related to renal insufficiency were UAE > or =3.4 mg/mmol (odds ratio 1.86; 95% confidence interval 1.60 to 2.17) and diabetes (odds ratio 1.62; 95% confidence interval 1.29 to 2.04). There is a close relationship between abnormal UAE and renal insufficiency in essential hypertension. This is more marked in patients with diabetes and moderate in patients with high-range impaired fasting glucose.