Albuminuria and cardiovascular risk.

Cardiovascular risk (CVR) estimation is a fundamental tool for guiding therapy. Albuminuria indicates target organ damage in an accessible, economic and non-invasive manner. Improves high-risk patient identification, especially in chronic kidney disease (CKD) and diabetes mellitus (DM). In addition, anti-albuminuric treatments may improve CVR. This would position albuminuria as a guide and therapeutic objective. Although the capacity of albuminuria as an epidemiological CVR marker in specific populations (hypertension, CKD, DM) is accepted, its profile as a risk marker in the general population and as a therapeutic target is controversial. There is ambiguous evidence regarding its predictive capacity, added to the fact that treatments such as SLGT2 blockers reduce CVR events regardless of albuminuria presence or magnitude. This review analyzes the available evidence on albuminuria as a CVR marker, a treatment goal and therapeutic guide.

Albuminuria and cardiovascular risk / Albuminuria y riesgo cardiovascular

Cardiovascular risk (CVR) estimation is a fundamental tool for guiding therapy. Albuminuria indicates target organ damage in an accessible, economic and non-invasive manner. Improves high-risk patient identification, especially in chronic kidney disease (CKD) and diabetes mellitus (DM). In addition, anti-albuminuric treatments may improve CVR. This would position albuminuria as a guide and therapeutic objective. Although the capacity of albuminuria as an epidemiological CVR marker in specific populations (hypertension, CKD, DM) is accepted, its profile as a risk marker in the general population and as a therapeutic target is controversial. There is ambiguous evidence regarding its predictive capacity, added to the fact that treatments such as SLGT2 blockers reduce CVR events regardless of albuminuria presence or magnitude. This review analyzes the available evidence on albuminuria as a CVR marker, a treatment goal and therapeutic guide. (AU)

La estimación de riesgo cardiovascular (RCV) es una herramienta fundamental para dirigir la terapéutica. Albuminuria indica daño en órgano blanco de manera accesible, económica y no invasiva. Mejora la identificación de pacientes de alto riesgo, especialmente en enfermedad renal crónica (ERC) y diabetes mellitus (DM). Además, tratamientos antialbuminúricos mejorarían el RCV y la ocurrencia de eventos. Esto posicionaría a la albuminuria como guía y objetivo terapéutico. Si bien la capacidad de albuminuria como marcador epidemiológico de RCV en poblaciones específicas es aceptado, su perfil de marcador de riesgo en población general y como objetivo terapéutico es controvertido. Existe evidencia contrapuesta respecto a su capacidad de predicción, sumado a que tratamientos como los bloqueadores SGLT2 reducen eventos CV independientemente de la presencia y/o magnitud de albuminuria. En esta revisión se analiza la evidencia disponible sobre albuminuria como marcador de RCV, como objetivo de tratamiento y como guía terapéutica. (AU)

[Epilepsy in children with congenital hemiparesis secondary to perinatal ictus]. / Epilepsia en niños con hemiparesia congénita secundaria a infartos cerebrales vasculares perinatales.

The objective was to describe the frequency, mode of presentation and characteristics of epilepsy in children with congenital hemiparesis (CH). It is a etrospective, descriptive and multicenter study, based on the collection of data from the clinical records of patients from 0 to 19 years with CH secondary to perinatal infarction in different centers of the community of Catalonia. A total of 310 children were included (55% males and 45% females), from a total of 13 centers in Catalonia. Average age of onset of the crises was 2 ± 1 year. Epilepsy was present in 29.5% (n = 76), among which the most frequent vascular subtype was arterial presumed perinatal ischemic stroke (51.3%), followed by neonatal arterial ischemic stroke (18.4%), periventricular venous infarction (15.8%), neonatal hemorrhagic stroke (10.5%) and neonatal cerebral sinovenous thrombosis (3.9%). Semiology of the most frequent seizures was motor focal in 82%, followed by focal motor with secondary bilateralization in 23%, focal discognitive in 13.5%, generalized by 2% and spasms in 6.5%. The 67.3% were controlled with monotherapy and the drugs used were valproate, levetiracetam or carbamazepine. The antecedent of electrical status during sleep was identified in 3 patients, all associated with extensive lesions that included the thalamus. Of the total number of children with epilepsy, 35% began with neonatal seizu res in the first 3 days of life. The 30% of children with perinatal stroke and CH present a risk of epilepsy during childhood. Children with ischemic strock have the highest risk, so they will require a follow-up aimed at detecting prematurely the epilepsy and start a treatment.

El objetivo fue describir la frecuencia, modo de presentación y características de la epilepsia en niños con hemiparesia congénita (HC). Estudio retrospectivo, descriptivo y multicéntrico, basado en la recolección de datos de las historias clínicas de pacientes de 0 a 19 años con HC secundaria a infarto perinatal en diferentes centros de la comunidad de Cataluña. Se incluyeron 310 niños (55% varones y 45% mujeres) de un total de 13 centros de Cataluña. Edad media del debut de las crisis fue de 2 ± 1 año. Presentaron epilepsia el 29.5% (n = 76), el subtipo vascular más frecuente fue el infarto presumiblemente perinatal (51.3%), seguido del accidente isquémico arterial neonatal (18.4%), infarto hemorrágico venoso periventricular (15.8%), infarto hemorrágico neonatal (10.5%) y trombosis venosa neonatal (3.9%). La semiología de las crisis más frecuente fue la focal motora en un 82%, seguida de las focales motoras con bilateralización secundaria en el 23%, focales discognitivas en 13.5%, generalizadas 2% y espasmos 6.5%. El 67.3% se controló con monoterapia y los fármacos empleados fueron el valproato, levetiracetam o carbamacepina. Se identificó el antecedente de estatus eléctrico durante el sueño en 3 pacientes, todos asociados a lesiones extensas que incluían al tálamo. Del total con epilepsia, el 35% debutaron con convulsiones neonatales en los primeros 3 días de vida. El 30% con accidente cerebrovascular perinatal y HC presentan riesgo de padecer epilepsia durante la infancia. Aquellos con infartos isquémicos tienen el riesgo más alto, por lo que requerirán un seguimiento dirigido a detectar precozmente la epilepsia e iniciar tratamiento.

Epilepsia en niños con hemiparesia congénita secundaria a infartos cerebrales vasculares perinatales / Epilepsy in children with congenital hemiparesis secondary to perinatal ictus

El objetivo fue describir la frecuencia, modo de presentación y características de la epilepsia en niños con hemiparesia congénita (HC). Estudio retrospectivo, descriptivo y multicéntrico, basado en la recolección de datos de las historias clínicas de pacientes de 0 a 19 años con HC secundaria a infarto perinatal en diferentes centros de la comunidad de Cataluña. Se incluyeron 310 niños (55% varones y 45% mujeres) de un total de 13 centros de Cataluña. Edad media del debut de las crisis fue de 2 ± 1 año. Presentaron epilepsia el 29.5% (n = 76), el subtipo vascular más frecuente fue el infarto presumiblemente perinatal (51.3%), seguido del accidente isquémico arterial neonatal (18.4%), infarto hemorrágico venoso periventricular (15.8%), infarto hemorrágico neonatal (10.5%) y trombosis venosa neonatal (3.9%). La semiología de las crisis más frecuente fue la focal motora en un 82%, seguida de las focales motoras con bilateralización secundaria en el 23%, focales discognitivas en 13.5%, generalizadas 2% y espasmos 6.5%. El 67.3% se controló con monoterapia y los fármacos empleados fueron el valproato, levetiracetam o carbamacepina. Se identificó el antecedente de estatus eléctrico durante el sueño en 3 pacientes, todos asociados a lesiones extensas que incluían al tálamo. Del total con epilepsia, el 35% debutaron con convulsiones neonatales en los primeros 3 días de vida. El 30% con accidente cerebrovascular perinatal y HC presentan riesgo de padecer epilepsia durante la infancia. Aquellos con infartos isquémicos tienen el riesgo más alto, por lo que requerirán un seguimiento dirigido a detectar precozmente la epilepsia e iniciar tratamiento.

The objective was to describe the frequency, mode of presentation and characteristics of epilepsy in children with congenital hemiparesis (CH). It is a etrospective, descriptive and multicenter study, based on the collection of data from the clinical records of patients from 0 to 19 years with CH secondary to perinatal infarction in different centers of the community of Catalonia. A total of 310 children were included (55% males and 45% females), from a total of 13 centers in Catalonia. Average age of onset of the crises was 2 ± 1 year. Epilepsy was present in 29.5% (n = 76), among which the most frequent vascular subtype was arterial presumed perinatal ischemic stroke (51.3%), followed by neonatal arterial ischemic stroke (18.4%), periventricular venous infarction (15.8%), neonatal hemorrhagic stroke (10.5%) and neonatal cerebral sinovenous thrombosis (3.9%). Semiology of the most frequent seizures was motor focal in 82%, followed by focal motor with secondary bilateralization in 23%, focal discognitive in 13.5%, generalized by 2% and spasms in 6.5%. The 67.3% were controlled with monotherapy and the drugs used were valproate, levetiracetam or carbamazepine. The antecedent of electrical status during sleep was identified in 3 patients, all associated with extensive lesions that included the thalamus. Of the total number of children with epilepsy, 35% began with neonatal seizu res in the first 3 days of life. The 30% of children with perinatal stroke and CH present a risk of epilepsy during childhood. Children with ischemic strock have the highest risk, so they will require a follow-up aimed at detecting prematurely the epilepsy and start a treatment.

Electron microscopy contribution to diagnosing transplant glomerulopathy: a single-center experience.

BACKGROUND: Transplant glomerulopathy (TG) may occur early after transplantation, and electron microscopy may contribute to diagnose it. METHODS: We analyzed kidney transplant biopsies from September 2009 to September 2012 to identify the presence of histologic changes associated with TG. RESULTS: Forty-eight biopsies from 65 patients, met the study criteria and were evaluated. The average evolution time of transplantation was 13.6 months. Sixty percent of patients received deceased-donor renal transplants, and biopsies were performed per protocol in most cases. Electron microscopy diagnosed the presence of changes associated with TG in 23% of patients. Light microscopy was not useful in the diagnosis of such graft pathology. The average transplantation time was significantly higher in patients with TG compared to patients without TG (20.6 mo vs 11.5 mo; P = .03). Light microscopy diagnosed mild interstitial fibrosis/tubular atrophy in 27 patients, of which 6 had early changes of TG according to the analysis by electron microscopy. CONCLUSIONS: Electron microscopy improves accurate diagnosis of TG, in patients both with and without graft dysfunction. It also allows diagnosis of early TG and thereby identification of patients who may have lower graft survival.

Preemptive kidney transplantation: experience in two centers.

INTRODUCTION: End-stage renal disease (ESRD) is a prevalent, important cause of death. Transplantation increases survival and improves the quality of life of patients with ESRD while long-term dialysis is related to poor outcomes even among patients who undergo subsequent transplantations. OBJECTIVES: To compare the advantages of preemptive procedures with kidney transplants among patients on renal replacement therapy. METHODS: This retrospective study was performed in two Córdoba city transplantation centers. Patients were divided into three groups: preemptive kidney transplant (PKT), patients on hemodialysis who received living donor kidney transplants (LDT), and subjects who received grafts from deceased donors (DDT). Serum creatinine, delayed graft function (DGF), subclinical rejection, and interstitial fibrosis/tubular atrophy (IF/TA) were evaluated at 6 months. RESULTS: Eighty patients were included: PKT (n = 28), LDT (n = 27), DDT (n = 25) mean age 29, 30, and 35 years, respectively. Women predominated among PKT and men in the other groups. In all groups, cyclosporine was the calcineurin inhibitor mostly used. Creatinine at 6 months was lower in the living donor groups (1.26 mg/dL PKT and 1.32 mg/dL LDT; P = NS) in relation to the deceased donor group (1.96 mg/dL; P < .05). DDT had the highest rate of DGF: 44% DDT versus 11.5% LDT vs 0% PKT (P < .05). Subclinical rejection was significantly lower among preemptive transplantations: PKT 7.6% versus LDT 18.5% versus DDT 24% (P < .05). IF/TA was higher in transplants from deceased donors: PKT 11.1%; LDT 11.5%; DDT 32%. CONCLUSIONS: Preemptive kidney transplantation offered the advantages of a lower creatinine, no DGF, as well as a reduced incidence of subclinical rejection and chronic allograft nephropathy at 6 months posttransplantation.

Renoprotective effect of high periprocedural doses of oral N-acetylcysteine in patients scheduled to undergo a same-day angiography

BACKGROUND: Few studies that have assessed the effect of abbreviated oral N-acetylcysteine (NAC) regimens in radiocontrast-induced nephropathy (RCIN) yield mixed results. OBJECTIVE: To evaluate the renoprotective effect of high periprocedural oral doses (HPOD) of NAC in patients with chronic renal impairment undergoing a same-day angiography. METHODS: Sixty one patients with renal impaired function scheduled to undergo a same-day angiography were randomly assigned to NAC 1200 mg orally 3 hours before and 3 after the procedure, or a placebo. All patients received 0.9% saline intravenous. RCIN was defined as an increase in SCC > 0.5 mg/dl 48 hours after the procedure. RESULTS: The mean baseline SCC for all patients was 1.44 +/- 0.42 mg/dl. A significant difference in SCC change at 48 hours after the angiography was found (-0.07 mg/dl NAC, 0.09 mg/dl placebo, P = 0.04). RCIN occurred in 1 (3%) patient of NAC group and in 2 (7.1%) patients of placebo group (P = 0.59). Adverse effects were similar in both groups. CONCLUSIONS: In patients with mild renal impairment patients undergoing angiographic procedures, HPOD of NAC were more effective than placebo in preventing SCC change 48 hours. A non significant benefit in RCIN incidence was found.

Los escasos estudios que han evaluados los efectos de regimenes abreviados de Nacetilcisteína (NAC) oral en la nefropatía por contraste (NC) han encontrado resultados contrapuestos. OBJETIVO: Evaluar el efecto renoprotector de altas dosis orales periprocedimiento (ADOP) de NAC en pacientes con insuficiencia renal con angiografía programada el mismo día. MATERIAL y METODOS: Sesenta y un pacientes con insuficiencia renal y angiografía programada para el mismo día fueron asignados aleatoriamente a 1200 mg de NAC 3 horas previas y 3 horas posteriores al cateterismo o un placebo. Todos los pacientes recibieron hidratación endovenosa con solución salina al 0.9%. La NC se definió como el aumento en la creatinina sérica (CS) > 0.5 mg/dl a las 48 horas del procedimiento. RESULTADOS: La CS media en todos los pacientes fue 1.44: t 0.42 mg/dl. Se encontró una diferencia significativa entre ambos grupos en el cambio de CS a las 48 horas de la angiografía (-0.07 mg/dl NAC, 0.09 mg/dl placebo, P=0.04). La NC se presentó en 1 (3%) paciente del grupo NAC y en 2 (7.1 %) pacientes del grupo placebo (P=0.59). Los efectos adversos fueron similares en ambos grupos. CONCLUSION: En pacientes con insuficiencia renal leve sometidos a angiografía en el mismo día, las ADOP de NAC fueron más efectivas que el placebo en la prevención del cambio de CS a las 48 horas del procedimiento. Se encontró un beneficio no significativo en la incidencia de NC.

Renoprotective effect of high periprocedural doses of oral N-acetylcysteine in patients scheduled to undergo a same-day angiography

BACKGROUND: Few studies that have assessed the effect of abbreviated oral N-acetylcysteine (NAC) regimens in radiocontrast-induced nephropathy (RCIN) yield mixed results. OBJECTIVE: To evaluate the renoprotective effect of high periprocedural oral doses (HPOD) of NAC in patients with chronic renal impairment undergoing a same-day angiography. METHODS: Sixty one patients with renal impaired function scheduled to undergo a same-day angiography were randomly assigned to NAC 1200 mg orally 3 hours before and 3 after the procedure, or a placebo. All patients received 0.9% saline intravenous. RCIN was defined as an increase in SCC > 0.5 mg/dl 48 hours after the procedure. RESULTS: The mean baseline SCC for all patients was 1.44 +/- 0.42 mg/dl. A significant difference in SCC change at 48 hours after the angiography was found (-0.07 mg/dl NAC, 0.09 mg/dl placebo, P = 0.04). RCIN occurred in 1 (3%) patient of NAC group and in 2 (7.1%) patients of placebo group (P = 0.59). Adverse effects were similar in both groups. CONCLUSIONS: In patients with mild renal impairment patients undergoing angiographic procedures, HPOD of NAC were more effective than placebo in preventing SCC change 48 hours. A non significant benefit in RCIN incidence was found.(AU)

Los escasos estudios que han evaluados los efectos de regimenes abreviados de Nacetilcisteína (NAC) oral en la nefropatía por contraste (NC) han encontrado resultados contrapuestos. OBJETIVO: Evaluar el efecto renoprotector de altas dosis orales periprocedimiento (ADOP) de NAC en pacientes con insuficiencia renal con angiografía programada el mismo día. MATERIAL y METODOS: Sesenta y un pacientes con insuficiencia renal y angiografía programada para el mismo día fueron asignados aleatoriamente a 1200 mg de NAC 3 horas previas y 3 horas posteriores al cateterismo o un placebo. Todos los pacientes recibieron hidratación endovenosa con solución salina al 0.9%. La NC se definió como el aumento en la creatinina sérica (CS) > 0.5 mg/dl a las 48 horas del procedimiento. RESULTADOS: La CS media en todos los pacientes fue 1.44: t 0.42 mg/dl. Se encontró una diferencia significativa entre ambos grupos en el cambio de CS a las 48 horas de la angiografía (-0.07 mg/dl NAC, 0.09 mg/dl placebo, P=0.04). La NC se presentó en 1 (3%) paciente del grupo NAC y en 2 (7.1 %) pacientes del grupo placebo (P=0.59). Los efectos adversos fueron similares en ambos grupos. CONCLUSION: En pacientes con insuficiencia renal leve sometidos a angiografía en el mismo día, las ADOP de NAC fueron más efectivas que el placebo en la prevención del cambio de CS a las 48 horas del procedimiento. Se encontró un beneficio no significativo en la incidencia de NC.(AU)

Reproducibility of ambulatory blood pressure monitoring in hemodialysis patients.

Ambulatory blood pressure monitoring (ABPM) has been increasingly used in hemodialysis (HD) practice and research; however, no study has evaluated the reproducibility of ABPM in this population. To address this question, we performed 48-hour interdialytic ABPM on 21 HD patients (mean age, 53 +/- 16 years; 7 women) on two different occasions 68 +/- 34 days (range, 30 to 154 days) apart. To qualify for the protocol, patients had to be at the same dry weight and on the same vasoactive drug regimen at both monitoring periods. BP was analyzed according to three different methods: isolated pre-HD and post-HD values, average pre-HD and post-HD values for the five HD sessions surrounding each monitoring period, and 48-hour interdialytic ABPM. Reproducibility was determined by analysis of the SD of the differences (SDD) between the two monitoring periods and the coefficient of variation of each method of BP determination. Our results show better reproducibility of ABPM (SDD, 10.6/6.6 mm Hg; coefficient of variation, 7.5%/8.1%) compared with isolated pre-HD BP (SDD, 24.4/11.3 mm Hg; coefficient of variation, 16.7%/14.1%) or post-HD BP (SDD, 16.8/14.5 mm Hg; coefficient of variation, 11.7%/17.8%), and averaged pre-HD BP (SDD, 14.7/7.2 mm Hg; coefficient of variation, 10.1%/9.1%) or post-HD BP (SDD, 12.4/8.7 mm Hg; coefficient of variation, 8.9%/11.1%). The reproducibility of the decrease in BP during sleep was poor, with up to 43% of the subjects changing dipping category within or between interdialytic periods. We conclude that ABPM is the most accurate method to study BP in HD patients over time. However, variability is significant, and there is poor reproducibility of the nocturnal decline in BP.

KCNA10: a novel ion channel functionally related to both voltage-gated potassium and CNG cation channels.

Our laboratory previously cloned a novel rabbit gene (Kcn1), expressed in kidney, heart, and aorta, and predicted to encode a protein with 58% amino acid identity with the K channel Shaker Kv1.3 (Yao X et al. Proc Natl Acad Sci USA 92: 11711-11715, 1995). Because Kcn1 did not express well (peak current in Xenopus laevis oocytes of 0.3 microA at +60 mV), the human homolog (KCNA10) was isolated, and its expression was optimized in oocytes. KCNA10 mediates voltage-gated K(+) currents that exhibit minimal steady-state inactivation. Ensemble currents of 5-10 microA at +40 mV were consistently recorded from injected oocytes. Channels are closed at the holding potential of -80 mV but are progressively activated by depolarizations more positive than -30 mV, with half-activation at +3.5 +/- 2.5 mV. The channel displays an unusual inhibitor profile because, in addition to being blocked by classical K channel blockers (barium tetraethylammonium and 4-aminopyridine), it is also sensitive to inhibitors of cyclic nucleotide-gated (CNG) cation channels (verapamil and pimozide). Tail-current analysis shows a reversal potential shift of 47 mV/decade change in K concentration, indicating a K-to-Na selectivity ratio of at least 15:1. The phorbol ester phorbol 12-myristate 13-acetate, an activator of protein kinase C, inhibited whole cell current by 42%. Analysis of single-channel currents reveals a conductance of approximately 11 pS. We conclude KCNA10 is a novel human voltage-gated K channel with features common to both K-selective and CNG cation channels. Given its distribution in renal blood vessels and heart, we speculate that KCNA10 may be involved in regulating the tone of renal vascular smooth muscle and may also participate in the cardiac action potential.

Extreme hyperphosphatemia and acute renal failure after a phosphorus-containing bowel regimen.

Phosphate intoxication, manifested by hypocalcemic tetany and acute renal failure, may complicate bowel-cleansing preparations which contain phosphate. These preparations are commonly used to prepare patients for various gastrointestinal procedures. Often, patients who receive these regimens are at increased risk of phosphate intoxication from diseases which slow gastrointestinal transit or decrease renal excretion (renal insufficiency). We present a patient who developed oliguric acute renal failure from severe phosphate intoxication associated with a phosphate-containing bowel-cleansing regimen.

[Blood pressure regulation by potassium channels]. / Regulación de la presión arterial a través de canales de potasio.

Potassium channels are transmembrane proteins that allow this ion to diffuse through the plasma membrane. By participating in the generation of membrane potential they regulate intracellular calcium levels and vascular smooth muscle contraction. Voltage-gated and ATP-gated potassium channels have been described in vessel smooth muscle. Minoxidil and diazoxide vasodilate by opening ATP-gated potassium channels. Soon other K-ATP channel openers will be available. It has been suggested that hypoxic vasodilatation and shock are due to excessive activation of potassium channels. Mutations in potassium channels have been implied in the pathogenesis of essential hypertension.

Cloning and localization of a double-pore K channel, KCNK1: exclusive expression in distal nephron segments.

The K-selective channel, TOK1, recently identified in yeast, displays the unusual structural feature of having two putative pore regions, in contrast to all previously cloned K channels. Using the TOK1 pore regions as probes, we identified a human kidney cDNA encoding a 337-amino acid protein (hKCNK1) with four transmembrane segments and two pore regions containing the signature sequence of K channels. Amino acid identity to TOK1 is only 15% overall but 40% at the pores. Northern analysis indicates high expression of a 1.9-kb message in brain > kidney >> heart. Nephron segment localization, carried out in rabbit by reverse transcription-polymerase chain reaction, reveals that KCNK1 is expressed in cortical thick ascending limb, connecting tubule, and cortical collecting duct. It was not detected in the proximal tubule, medullary thick ascending limb, distal convoluted tubule, and glomerulus. We conclude that KCNK1 is a unique, double-pore, mammalian K channel, distantly related to the yeast channel TOK1, that is expressed in distal tubule and is a candidate to participate in renal K homeostasis.

Genomic localization of the human gene for KCNA10, a cGMP-activated K channel.

Potassium (K) channels are important components of virtually all cells, and they play critical roles in many cellular functions. KCNA10 represents a new class of K channel specifically regulated by cGMP and postulated to mediate the effects of substances that increase intracellular cGMP. Since KCNA10 has the potential to be useful in candidate gene analysis of inherited diseases, the human gene for KCNA10 was characterized. Fluorescence in situ hybridization indicates that human KCNA10 maps to chromosome 1 at p13.1-->p22.1. Finer mapping of the gene was achieved by PCR of a set of CEPH YAC clones that spanned the region of interest. We found that YAC 818b9 contains human KCNA10. These data indicate human KCNA10 maps to 1p13.1 and resides within the genetic interval defined by microsatellite loci D1S2809 and D1S2726. That region of chromosome 1 contains another K channel gene, KCNA3.