Robot-assisted implantation of a microelectrode array in the occipital lobe as a visual prosthesis: technical note.

The prospect of direct interaction between the brain and computers has been investigated in recent decades, revealing several potential applications. One of these is sight restoration in profoundly blind people, which is based on the ability to elicit visual perceptions while directly stimulating the occipital cortex. Technological innovation has led to the development of microelectrodes implantable on the brain surface. The feasibility of implanting a microelectrode on the visual cortex has already been shown in animals, with promising results. Current research has focused on the implantation of microelectrodes into the occipital brain of blind volunteers. The technique raises several technical challenges. In this technical note, the authors suggest a safe and effective approach for robot-assisted implantation of microelectrodes in the occipital lobe for sight restoration.

Body Fat Distribution, Adipocytokines Levels and Variability in Associated Genes and Kidney Transplant Outcomes.

Introduction: Body fat distribution is known to contribute to a variety of pathologies. Research Questions: We aimed to assess whether this distribution is associated with clinical outcomes in renal transplant recipients (RTR) and to examine its relationship with leptin and adiponectin gene variants and plasma concentrations. Design: Bioelectrical impedance analyses were performed in 236 RTR. Leptin/adiponectin levels were measured by immunoassay and relevant polymorphisms in the leptin receptor (LEPR) and adiponectin (ADIPOQ) genes were identified. Associations were assessed by logistic regression modeling. Results: The waist-to-height ratio (WHr) displayed a significant association with delayed graft function, acute rejection and post-transplant diabetes mellitus, with OR values of 2.04 (1.02-4.08) p = 0.045; 3.08 (1.22-7.79) p = 0.017 and 2.79 (1.16-6.74) p = 0.022, respectively. Waist circumference was linked to delayed graft function [OR = 1.03 (1.01-1.05), p = 0.025] and AR [OR = 1.041 (1.01-1.07), p = 0.009]. Leptin levels were significantly higher in patients who experienced rejection [19.91 ± 23.72 versus 11.22 ± 16.42 ng/ml; OR = 1.021 (1.01-1.04), p = 0.017]. The ADIPOQ rs1501299TT genotype showed a significant association with higher WHr (0.63 ± 0.11 vs 0.59 ± 0.87 for GG/GT genotypes; p = 0.015) and WC values (102.3 ± 14.12 vs 96.38 ± 14.65 for GG/GT genotypes; p = 0.021). Conclusion: WC, and especially WHr, are associated with adverse outcomes in renal transplantation and are affected by variability in the ADIPOQ gene.

[Genogram and genealogical tree]. / Genograma y árbol genealógico.

A genogram and a genealogical tree are graphic representations of families that share similarities but have different functionality and meanings. While the first basic objective is to represent the family structure and the relationships between its members, the second seeks to identify the inheritance pattern and inheritable traits, although its use and applications go much further. Graphic representation is normalized with similar symbols, although some of them have different meanings. Both are used by family doctors, and they must have the necessary skills for their effective management. This work aims to improve these skills by defining the main differences between the two tools, establishing the basic elements for the construction and interpretation of a genealogical tree, and pointing out its clinical utility and its most frequent uses.

How I do it: paramedian supracerebellar transtentorial approach for a temporomesial glioma.

BACKGROUND: Classical approaches to the temporomesial region (TMR) include transtemporal, transylvian, or subtemporal. The supracerebellar infratentorial, initially developed to access dorsolateral cavernomas, has of late shown its versatility to access areas around the central core. The TMR is one such area that can be accessed through this approach with the addition of a tentorial incision. METHOD: The paramedian supracerebellar transtentorial approach (PSCTA) is described along with its advantages and limits compared to other approaches to treat TMR gliomas. CONCLUSION: The PSCTA offers a basal panoramic view of the TMR without the need of retraction, cortical incision, and white matter transgression.

Results of the fecal immunochemical test in a colorectal cancer screening program in Mexico.

BACKGROUND: Colorectal cancer (CRC) is one of the main five causes of morbidity and mortality by oncologic diseases in our country and worldwide. Recently, fecal immunochemical test (FIT) has proven to be a noninvasive screening test that allows to select patients most likely to have a pre-malign lesion in order to perform a colonoscopy. OBJECTIVE: To report the findings of a CRC screening program using FIT in our country population. METHOD: A multicentric study was performed, by inviting open population older than 50 years to participate in a CRC screening. Quantitative FIT specific for human hemoglobin was used, with a cut point of 100 ng/ml or higher to consider as positive. Those patients with positive results were asked to undergo a colonoscopy. In the cases where polypoid lesions were found, biopsies were performed. RESULTS: In total, 751 FIT were processed, and 51 (6.8) of those were positive, with a rate of 15.9 premalign lesions for 1,000 individuals, and 1.3 patients with CRC for every 1,000. CONCLUSIONS: The present study matches worldwide reports, supporting the initiative of establishing a formal and standardized CRC screening program in the public health sector.

ANTECEDENTES: El cáncer colorrectal (CCR) es una de las cinco primeras causas de morbimortalidad por cáncer en nuestro país y en todo el mundo. La prueba inmunoquímica fecal (FIT, fecal immunochemical test) es una herramienta de tamizaje no invasiva que permite seleccionar a los sujetos con mayor probabilidad de lesión premaligna en la colonoscopia. OBJETIVO: Reportar los resultados del programa de escrutinio para CCR mediante FIT en población abierta en México. MÉTODO: Estudio multicéntrico nacional en población abierta mayor de 50 años a través de medios de difusión masiva para participar en un programa de escrutinio de CCR. Se utilizó FIT cuantitativa específica para detectar hemoglobina humana con un punto de corte de 100 ng/ml (prueba positiva). Se realizó colonoscopia a los positivos. Se tomaron biopsias dirigidas de las lesiones premalignas/cáncer para análisis histopatológico. RESULTADOS: Se procesaron 751 FIT, de las cuales 51 (6.8%) fueron positivas, con una tasa de 15.9 lesiones premalignas por cada 1,000 sujetos evaluados, y 1.3 pacientes con CCR por cada 1,000 pacientes. CONCLUSIONES: Nuestro estudio concuerda con lo reportado en la literatura mundial, apoyando así la iniciativa de fomentar el establecimiento de un tamizaje formal y estandarizado dentro del sector de salud pública.

Combined donor-recipient genotypes of leptin receptor and adiponectin gene polymorphisms affect the incidence of complications after renal transplantation.

BACKGROUND: We aimed to examine whether combined donor/recipient variants in the leptin receptor (LEPR) and adiponectin (ADIPOQ) genes may affect outcomes in renal transplantation. METHODS: A total of 233 donors and their corresponding 307 recipients were genotyped for LEPR rs1805094, rs1137100 and rs1137101, and ADIPOQ rs1501299 and rs224176. Combined donor/recipient genetic scores were created to investigate associations with delayed graft function (DGF), graft loss and estimated glomerular filtration rate (eGFR). RESULTS: Recipients whose donors carried variant alleles of LEPR rs1137100 and rs1137101 had lower risk of DGF [OR = 0.48 (0.24-0.97), p = 0.040] and [OR = 0.47 (0.23-0.95), p = 0.035], respectively. In addition, rs1137101 also showed an inverse association with lower incidence of graft loss [OR = 0.44 (0.31-0.97), p = 0.040]. The analysis of genetic scores of donor/recipients showed that again rs1137101 was inversely associated with both outcomes: OR = 0.46 (0.23-0.92), p = 0.029 and OR = 0.45 (0.11-0.81), p = 0.009, respectively. With regard to graft function, the T-allele of ADIPOQ rs1501299 in the donor was related to higher eGFR values (75.26 ± 29.01 vs. 67.34 ± 25.39 ml/min for wild-type grafts, p = 0.012). Higher combined genetic scores in this same polymorphism were also associated with better function (78.33 ± 31.87 vs. 68.25 ± 24.32 ml/min, p = 0.018). Finally, eGFR values were similar between paired kidneys but they were different when comparing grafts with or without the rs1501299 T-variant (77.87 ± 26.50 vs. 69.27 ± 26.73 ml/min, p = 0.016). CONCLUSIONS: Our study has shown for the first time to our knowledge that variants in LEPR and ADIPOQ genes of the donors and/or their combination with those in the recipients may affect the outcome of renal transplantation.

Acidosis metabólica en la enfermedad renal crónica: dificultades para una corrección adecuada / Successful correction of metabolic acidosis is difficult to achieve in chronic kidney disease

INTRODUCCIÓN: La acidosis metabólica (AM) es una alteración frecuente en la enfermedad renal crónica (ERC) que se asocia a numerosas complicaciones, por lo que su corrección es recomendable. El bicarbonato sódico oral es actualmente el tratamiento de elección. OBJETIVOS: Describir la prevalencia de AM en la ERC avanzada, y determinar cuáles son las características clínicas y bioquímicas que se asocian a una corrección adecuada. MATERIAL Y MÉTODOS: Estudio retrospectivo de observación en una cohorte de pacientes adultos con ERC estadio 4-5. Los criterios de inclusión fueron: no estar siendo tratado con alcalinos en el momento de la inclusión y tener al menos 3 medidas consecutivas de filtrado glomerular (FG) y parámetros bioquímicos durante un periodo > 3 meses. Los pacientes con un bicarbonato sérico < 22 mEq/l se incluyeron en el estudio de seguimiento, siendo tratados con bicarbonato sódico oral. Se consideró que la corrección fue adecuada cuando más de la mitad de las muestras y la media de los niveles de bicarbonato durante el seguimiento individual fueron ≥ 22 mEq/l. RESULTADOS: Se incluyeron 969 pacientes (edad 65± 14 años, 507 hombres) con FG medio 14,8± 4,5 ml/min/1,73 m2. Basalmente 530 pacientes (55%) que mostraron un bicarbonato sérico < 22 mEq/l fueron tratados con bicarbonato sódico y seguidos durante 15 meses. En tan solo 133 pacientes (25%) se alcanzó una corrección satisfactoria de la AM. Por regresión logística multivariable las principales características en los que se logró el control adecuado de la AM fueron: edad (OR = 1,03; IC. 95%1,01-1,05), FG basal (OR = 1,07; 1,02-1,12) y tratamiento con inhibidores de bomba protones (OR = 1,61; IC 95%: 1,06-2,44). En aquellos en los que se logró corrección de AM tuvieron progresión más lenta de ERC (-1,67± 3,71 vs. -4,36± 4,56 ml/min/1,73 m2/año, p < 0,0001) y menor concentración de potasio sérico promedio (5,1± 0,5 vs. 5,3± 0,5, p < 0,0001) que los del resto de pacientes, aunque no se observaron diferencias en la tasa de ingresos hospitalarios y ni en la mortalidad. CONCLUSIÓN: La AM es una alteración frecuente en la ERC avanzada, pero de difícil corrección con los tratamientos actuales. Debido al importante beneficio que puede suponer el control de la AM se deberían investigar nuevas terapias más efectivas

INTRODUCTION: Metabolic acidosis (MA) is a common complication of chronic kidney disease (CKD) and is associated with numerous adverse effects, which is why its correction is highly recommended. Oral sodium bicarbonate is the current treatment of choice. OBJECTIVES: To describe the prevalence of MA in advanced CKD patients and to determine the clinical and biochemical characteristics associated with its successful correction. MATERIAL AND METHODS: Retrospective, observational cohort study in adult patients with CKD stage 4-5. The inclusion criteria were: not being treated with alkali therapy at the time of inclusion, and to have at least three consecutive glomerular filtration rate (GFR) measurements and biochemical parameters during a minimum follow-up period of 3 months. Incident patients with serum bicarbonate < 22 mEq/l were included in the follow-up study and treated with oral sodium bicarbonate. Correction was considered successful when more than half of the samples and the mean bicarbonate levels during individual follow-up were ≥ 22 mEq/l. RESULTS: The study group consisted of 969 patients (age 65±14 years, 507 males) with a mean GFR of 14.8 ± 4.5 ml/min/1.73 m2. At baseline, 530 patients (55%) had serum bicarbonate < 22 mEq/l. They were treated with sodium bicarbonate and followed for 15 months. Satisfactory correction of MA was only achieved in 133 patients (25%). By multivariate logistic regression analysis, the main characteristics of patients with adequate control of MA were: age (OR = 1.03; 95% CI 1.01 - 1.05), baseline GFR (OR = 1.07; 1.02 - 1.12), and treatment with proton-pump inhibitors (OR = 1.61; 95% CI 1.06 - 2.44). Patients who achieved successful correction of MA showed slower CKD progression (-1.67 ± 3.71 vs -4.36 ± 4.56 ml/min/1.73 m2/year, P < .0001), and lower average serum potassium concentration (5.1 ± 0.5 vs 5.3 ± 0.5, P < .0001) than those who did not. However, there were no differences in the hospitalisation or mortality rate. CONCLUSION: MA is a common complication of advanced CKD but difficult to manage with current therapies. Due to the significant potential benefit of controlling MA, new, more effective therapies should be further researched

Manejo renal del potasio en la enfermedad renal crónica avanzada: diferencias entre pacientes con o sin hipercaliemia / Renal potassium handling in chronic kidney disease: Differences between patients with or wihtout hyperkalemia

INTRODUCCIÓN: La hipercaliemia (HK) es un hallazgo frecuente en la enfermedad renal crónica (ERC), sobre todo en sus estadios más avanzados. El mecanismo patogénico más común de esta alteración es la ingesta-absorción de potasio que sobrepasa la capacidad excretora renal. La investigación sobre el papel relativo de cada uno de los elementos patogénicos en el desarrollo de HK podría ayudar a su tratamiento. OBJETIVO: Analizar el manejo renal de potasio en pacientes con ERC avanzada prediálisis, y establecer qué diferencias existen entre los que presentan o no HK. MATERIAL Y MÉTODOS: Estudio transversal de observación en pacientes adultos con ERC estadio 4-5 prediálisis. Entre los pacientes incidentes en la consulta ERCA se seleccionaron aquellos clínicamente estables con capacidad para recoger adecuadamente la orina de 24horas. Se midieron parámetros bioquímicos en sangre y orina que incluyeron las concentraciones de sodio y potasio (K). Se calculó la fracción de excreción de K (FEK) y la carga de K relativa al filtrado glomerular (Ko/FG). Se definió la HK como una concentración de K sérico ≥ 5,5 mmol/l. RESULTADOS: Se incluyeron 212 pacientes (edad 65 ± 14 años, 92 mujeres) con un FG 15,0 ± 4,2 ml/min/1,73 m2. Sesenta y tres pacientes (30%) presentaban HK. Los pacientes con HK tenían un bicarbonato sérico más bajo (20,3 ± 3,1 vs. 22,8 ± 3,2 mEq/l, p < 0,0001), y un menor filtrado glomerular (14,1 ± 3,3 vs. 15,4 ± 4,4 ml/min/1,73 m2, p = 0,028), pero no mostraban diferencias en la excreción urinaria total de sodio o K. La FEK era inferior en los pacientes con HK con respecto a los que presentaban normocaliemia (32,1 ± 12,1% vs. 36,4 ± 14,3%, p = 0,038), mientras que la Ko/FG fue mayor (4,2 ± 1,5 vs. 3,7 ± 1,4 mmol por cada ml/min, p = 0,049). Existía una fuerte correlación lineal entre Ko/FG y FEK (R2 = 0,74), y en regresiones parciales se observó que a igual carga de K, la FEK era inferior en los pacientes con HK. Mediante regresión lineal y regresión logística multivariable, tanto la FEK como la Ko/FG fueron los principales determinantes del K sérico y de la HK. CONCLUSIONES: Aunque la carga de K relativa a la función renal (Ko/FG) se asocia de forma relevante a la HK de la ERC, la principal característica asociada a esta alteración bioquímica es la incompleta excreción renal compensatoria de K, expresada como una menor FEK

INTRODUCTION: Hyperkalemia (HK) is a common electrolyte disorder in chronic kidney disease (CKD), mainly in the advanced stages. A positive potassium balance due to reduced renal excretory capacity is likely the main pathogenic mechanism of HK. Research into the relative role of each pathogenic element in the development of HK in CKD may help to implement more suitable therapies. OBJECTIVE: To investigate renal potassium handling in advanced CKD patients, and to determine the differences between patients with or without HK. MATERIAL AND METHODS: Cross-sectional observational study in adult patients with stage 4-5 CKD pre-dialysis. Selection criteria included clinically stable patients and the ability to collect a 24 hour urine sample correctly. Blood and urinary biochemical parameters were analysed including sodium and potassium (K). Fractional excretion of K (FEK) and K load relative to glomerular filtration (Ku/GFR) were calculated. HK was defined as a serum K concentration ≥ 5.5 mmol/l. RESULTS: The study group consisted of 212 patients (mean age 65 ± 14 years, 92 females) with a mean GFR of 15.0 ± 4.2 ml/min/1.73 m2. 63 patients (30%) had HK. Patients with HK had lower mean bicarbonate levels with respect to patients with normal K levels (NK) (20.3 ± 3.1 vs. 22.8 ± 3.2 mEq/l, P < .0001), but no differences were noted in total urinary sodium and K excretion. While mean FEK values were lower in patients with HK (32.1 ± 12.1% vs. 36.4 ± 14.3%, P = .038), Ku/GFR values were significantly greater with respect to the NK subgroup (4.2 ± 1.5 vs. 3.7 ± 1.4 mmol/ml/min, P = 0,049). FEK showed a strong linear correlation with Ku/GFR (R2 = 0.74), and partial linear regressions demonstrated that at a similar Ku/GFR level, the FEK of patients with HK was lower than that of NK patients. By multivariate linear and logistic regression analyses, both FEK and Ku/GFR were shown to be the main determinants of K serum levels and HK. CONCLUSIONS: Although the K load relative to glomerular filtration (Ku/GFR) is an important determinant of HK in advanced CKD, the most noteworthy characteristic associated with HK in these patients was the limitation of compensatory urinary K excretion, as indicated by lower FEK

Efecto negativo del bloqueo del sistema renina-angiotensina sobre la progresión de la enfermedad renal crónica avanzada: ¿una cuestión de ajuste de dosis? / Detrimental effect of renin-angiotensin blockade on progression of chronic kidney disease at later stages: A matter of dosage adjustment?

INTRODUCCIÓN: El efecto renoprotector de los fármacos inhibidores del sistema renina-angiotensina (ISRA) ha sido cuestionado en la enfermedad renal crónica (ERC) avanzada. La combinación de tratamiento ISRA (doble bloqueo) puede, además, acelerar el deterioro de la función renal en algunas poblaciones de riesgo. Sin embargo, se desconoce si este efecto adverso está relacionado con la dosis total prescrita de ISRA o más específicamente con una interacción farmacológica. OBJETIVO: Investigar si la tasa de reducción de función renal en la ERC avanzada se asocia a la dosis total de ISRA, y si el doble bloqueo SRA deteriora la función renal independientemente de los principales factores de confusión. MATERIAL Y MÉTODOS: Estudio retrospectivo de observación en una cohorte de pacientes adultos con ERC estadios 4-5 prediálisis, tratados con ISRA desde al menos 3 meses antes de la inclusión en el estudio. Otros criterios de inclusión fueron: tener al menos 3 medidas consecutivas de filtrado glomerular durante un periodo superior a 3 meses. Las dosis equipotentes de ISRA fueron normalizadas (DEN-ISRA) a un peso corporal de 70 kg o a una superficie corporal de 1,73 m2. La asociación de DEN-ISRA o doble bloqueo con la progresión de ERC fue analizada mediante modelos de regresión lineal uni- y multivariante, tomando en cuenta las principales variables de confusión. RESULTADOS: Se incluyeron 813 pacientes (edad media: 64 ± 14 años; 430 hombres) con un filtrado glomerular medio de 14,9 ± 4,2 ml/min/1,73 m2; 729 pacientes eran tratados con ISRA monoterapia y 84 pacientes con doble bloqueo. La mediana de la DEN-ISRA en el grupo total de estudio fue de 0,91 (rangos IQ: 0,69-1,20). Los pacientes con doble bloqueo tenían una DEN-ISRA significativamente mayor que el resto (1,52 ± 0,49 vs. 0,93 ± 0,44; p < 0,0001). Mediante regresión lineal univariable, DEN-ISRA se correlacionó significativamente con la tasa de progresión de la ERC (R = -0,149; p < 0,0001). Los pacientes con doble bloqueo mostraron un deterioro más acelerado de la función renal que el resto (-6,19 ± 5,57 vs. -3,04 ± 5,37 ml/min/1,73 m2/año, p < 0,0001). Mediante regresión lineal multivariante, el tratamiento con doble bloqueo SRA mantuvo la asociación significativa e independiente con el deterioro de la función renal (beta = -0,094; p = 0,005), mientras que la DEN-ISRA no alcanzó significación estadística. CONCLUSIÓN: La DEN-ISRA se asocia de forma significativa con la tasa de progresión en pacientes con ERC avanzada. Sin embargo, el efecto negativo del doble bloqueo SRA sobre la progresión de la ERC parece independiente de la DEN-ISRA y de otros factores relevantes de confusión

INTRODUCTION: The renoprotective effect of renin-angiotensin (RAS) blockers (angiotensin converting enzyme inhibitors and angiotensin receptor blockers) has been questioned in patients with advanced chronic kidney disease (CKD). Moreover, combination therapy (dual RAS blockade) can further accelerate renal function decline in some populations at risk. However, it is unknown whether this adverse outcome is due to a dose-dependent effect or if it can be attributed more specifically to a drug interaction. Aim This study aims to investigate if the rate of renal function decline in advanced CKD patients is associated to the doses of RAS blockers, and if dual RAS blockade worsens renal function independently of major confounding factors. MATERIAL AND METHODS: Retrospective, observational study in an incident cohort of adult patients with CKD stage 4 or 5 not on dialysis, treated with RAS blockers for at least 3 months prior to the study inclusion. Inclusion criteria were: having at least three consecutive measurements of estimated glomerular filtration rate (eGFR) in a follow-up period > 3 months. Decline in renal function was estimated as the slope of the individual linear regression line of eGFR over follow-up time. Equipotent doses of RAS blockers were normalised for a body weight of 70 kg or a body surface area of 1.73 m2 (END-RASI). Associations of END-RASI or dual RAS blockade with the rate of renal function decline were analysed by uni- or multivariate linear regression models, accounting for major confounding variables. RESULTS: The study group consisted of 813 patients (mean age 64 ± 14 years, 430 males) with a mean eGFR 14.9 ± 4.2 ml/min/1.73 m2; 729 patients were on RAS blockade monotherapy and 84 on dual RAS blockade. Median END-RASI in the whole group was 0.91 (I.Q. ranges: 0.69-1.20). Patients on dual RAS blockade had significantly higher END-RASI than the rest of study patients (1.52 ± 0.49 vs. 0.93 ± 0.44; p < 0.0001). In univariate linear regression, END-RASI were significantly correlated with eGFR decline (R = -0.149; p < 0.0001). Patients on dual RAS blockade showed a significantly faster decline of renal function than the rest of the study patients (-6.19 ± 5.57 vs. -3.04 ± 5.37 ml/min/1.73 m2/year, p < 0.0001). By multivariate linear regression, while dual RAS blockade remained independent and significantly associated with faster renal function decline (beta = -0.094; p = 0.005), END-RASI (normalised either for body weight or surface area) did not reach statistical significance. CONCLUSION: END-RASI are significantly associated with the rate of renal function decline in advanced CKD patients. However, the detrimental effect of dual RAS blockade on CKD progression seems to be independent of END-RASI and other major confounding factors

Renal potassium handling in chronic kidney disease: Differences between patients with or wihtout hyperkalemia. / Manejo renal del potasio en la enfermedad renal crónica avanzada: diferencias entre pacientes con o sin hipercaliemia.

INTRODUCTION: Hyperkalemia (HK) is a common electrolyte disorder in chronic kidney disease (CKD), mainly in the advanced stages. A positive potassium balance due to reduced renal excretory capacity is likely the main pathogenic mechanism of HK. Research into the relative role of each pathogenic element in the development of HK in CKD may help to implement more suitable therapies. OBJECTIVE: To investigate renal potassium handling in advanced CKD patients, and to determine the differences between patients with or without HK. MATERIAL AND METHODS: Cross-sectional observational study in adult patients with stage 4-5 CKD pre-dialysis. Selection criteria included clinically stable patients and the ability to collect a 24hour urine sample correctly. Blood and urinary biochemical parameters were analysed including sodium and potassium (K). Fractional excretion of K (FEK) and K load relative to glomerular filtration (Ku/GFR) were calculated. HK was defined as a serum K concentration ≥5.5mmol/l. RESULTS: The study group consisted of 212 patients (mean age 65±14 years, 92 females) with a mean GFR of 15.0±4.2ml/min/1.73m2. 63 patients (30%) had HK. Patients with HK had lower mean bicarbonate levels with respect to patients with normal K levels (NK) (20.3±3.1 vs. 22.8±3.2 mEq/l, P<.0001), but no differences were noted in total urinary sodium and K excretion. While mean FEK values were lower in patients with HK (32.1±12.1% vs. 36.4±14.3%, P=.038), Ku/GFR values were significantly greater with respect to the NK subgroup (4.2±1.5 vs. 3.7±1.4 mmol/ml/min, P=0,049). FEK showed a strong linear correlation with Ku/GFR (R2=0.74), and partial linear regressions demonstrated that at a similar Ku/GFR level, the FEK of patients with HK was lower than that of NK patients. By multivariate linear and logistic regression analyses, both FEK and Ku/GFR were shown to be the main determinants of K serum levels and HK. CONCLUSIONS: Although the K load relative to glomerular filtration (Ku/GFR) is an important determinant of HK in advanced CKD, the most noteworthy characteristic associated with HK in these patients was the limitation of compensatory urinary K excretion, as indicated by lower FEK.

Detrimental effect of renin-angiotensin blockade on progression of chronic kidney disease at later stages: A matter of dosage adjustment? / Efecto negativo del bloqueo del sistema renina-angiotensina sobre la progresión de la enfermedad renal crónica avanzada: ¿una cuestión de ajuste de dosis?

INTRODUCTION: The renoprotective effect of renin-angiotensin (RAS) blockers (angiotensin converting enzyme inhibitors and angiotensin receptor blockers) has been questioned in patients with advanced chronic kidney disease (CKD). Moreover, combination therapy (dual RAS blockade) can further accelerate renal function decline in some populations at risk. However, it is unknown whether this adverse outcome is due to a dose-dependent effect or if it can be attributed more specifically to a drug interaction. Aim This study aims to investigate if the rate of renal function decline in advanced CKD patients is associated to the doses of RAS blockers, and if dual RAS blockade worsens renal function independently of major confounding factors. MATERIAL AND METHODS: Retrospective, observational study in an incident cohort of adult patients with CKD stage 4 or 5 not on dialysis, treated with RAS blockers for at least 3 months prior to the study inclusion. Inclusion criteria were: having at least three consecutive measurements of estimated glomerular filtration rate (eGFR) in a follow-up period >3 months. Decline in renal function was estimated as the slope of the individual linear regression line of eGFR over follow-up time. Equipotent doses of RAS blockers were normalised for a body weight of 70kg or a body surface area of 1.73m2 (END-RASI). Associations of END-RASI or dual RAS blockade with the rate of renal function decline were analysed by uni- or multivariate linear regression models, accounting for major confounding variables. RESULTS: The study group consisted of 813 patients (mean age 64±14 years, 430 males) with a mean eGFR 14.9±4.2ml/min/1.73m2; 729 patients were on RAS blockade monotherapy and 84 on dual RAS blockade. Median END-RASI in the whole group was 0.91 (I.Q. ranges: 0.69-1.20). Patients on dual RAS blockade had significantly higher END-RASI than the rest of study patients (1.52±0.49 vs. 0.93±0.44; p<0.0001). In univariate linear regression, END-RASI were significantly correlated with eGFR decline (R=-0.149; p<0.0001). Patients on dual RAS blockade showed a significantly faster decline of renal function than the rest of the study patients (-6.19±5.57 vs. -3.04±5.37ml/min/1.73m2/year, p<0.0001). By multivariate linear regression, while dual RAS blockade remained independent and significantly associated with faster renal function decline (beta=-0.094; p=0.005), END-RASI (normalised either for body weight or surface area) did not reach statistical significance. CONCLUSION: END-RASI are significantly associated with the rate of renal function decline in advanced CKD patients. However, the detrimental effect of dual RAS blockade on CKD progression seems to be independent of END-RASI and other major confounding factors.

Successful correction of metabolic acidosis is difficult to achieve in chronic kidney disease. / Acidosis metabólica en la enfermedad renal crónica: dificultades para una corrección adecuada.

INTRODUCTION: Metabolic acidosis (MA) is a common complication of chronic kidney disease (CKD) and is associated with numerous adverse effects, which is why its correction is highly recommended. Oral sodium bicarbonate is the current treatment of choice. OBJECTIVES: To describe the prevalence of MA in advanced CKD patients and to determine the clinical and biochemical characteristics associated with its successful correction. MATERIAL AND METHODS: Retrospective, observational cohort study in adult patients with CKD stage 4-5. The inclusion criteria were: not being treated with alkali therapy at the time of inclusion, and to have at least three consecutive glomerular filtration rate (GFR) measurements and biochemical parameters during a minimum follow-up period of 3 months. Incident patients with serum bicarbonate<22 mEq/l were included in the follow-up study and treated with oral sodium bicarbonate. Correction was considered successful when more than half of the samples and the mean bicarbonate levels during individual follow-up were≥22 mEq/l. RESULTS: The study group consisted of 969 patients (age 65±14 years, 507 males) with a mean GFR of 14.8±4.5ml/min/1.73 m2. At baseline, 530 patients (55%) had serum bicarbonate<22mEq/l. They were treated with sodium bicarbonate and followed for 15 months. Satisfactory correction of MA was only achieved in 133 patients (25%). By multivariate logistic regression analysis, the main characteristics of patients with adequate control of MA were: age (OR=1.03; 95% CI 1.01 - 1.05), baseline GFR (OR=1.07; 1.02 - 1.12), and treatment with proton-pump inhibitors (OR=1.61; 95% CI 1.06 - 2.44). Patients who achieved successful correction of MA showed slower CKD progression (-1.67±3.71 vs -4.36±4.56ml/min/1.73 m2/year, P<.0001), and lower average serum potassium concentration (5.1±0.5 vs 5.3±0.5, P<.0001) than those who did not. However, there were no differences in the hospitalisation or mortality rate. CONCLUSION: MA is a common complication of advanced CKD but difficult to manage with current therapies. Due to the significant potential benefit of controlling MA, new, more effective therapies should be further researched.

Association of polymorphisms in leptin and adiponectin genes with long-term outcomes in renal transplant recipients.

The effect of polymorphims in leptin and adiponectin genes on long-term outcomes of renal transplantation is unknown. In 349 renal transplant recipients (RTR), we aimed to determine associations between five SNPs in the leptin receptor (LEPR) and adiponectin (ADIPOQ) genes and these outcomes. Follow-up time ranged from 2 to 25 years (mean 10.29 ± 5.16 years). Two SNPs showed associations with long-term outcomes and their statistical significance greatly increased after 39 RTR with a history of cardiovascular events prior to transplantation were removed from the analysis. Adjusted odds ratios (OR) for LEPR rs1805094 and ADIPOQ rs1501299 and risk of graft loss were 0.35 (0.16-0.74) p = 0.006 and 2.37 (1.28-4.37) p = 0.006, respectively. The assessment of risk for global mortality revealed OR values of 0.20 (0.06-0.62), p = 0.005, and 2.43 (1.08-5.44), p = 0.031 for LEPR rs1805094 and ADIPOQ rs1501299, respectively. Our results show that polymorphism in genes involved in leptin and adiponectin function modify long-term outcomes in renal transplantation.

Polymorphisms in vasoactive eicosanoid genes of kidney donors affect biopsy scores and clinical outcomes in renal transplantation.

Cytochrome P450 (CYP) enzymes metabolize arachidonic acid to vasoactive eicosanoids such as epoxyeicosatrienoic acids (EETs) and 20-Hydroxyeicosatetraenoic acid (20-HETE), whilst soluble epoxide hydrolase, encoded by the EPHX2 gene, is in charge of EETs degradation. We aimed to analyze the influence of common, functional polymorphisms in four genes of the donor on the renal biopsy scores independently assigned by pathologists. Additionally, we examined whether this score or the presence of these SNPs were independent risk factors of clinical outcomes in the first year after grafting. A cohort of 119 recipients and their corresponding 85 deceased donors were included in the study. Donors were genotyped for the CYP4F2 V433M, CYP2C8*3, CYP2J2*7, EPHX2 3'UTR A>G, EPHX2 K55R and EPHX2 R287Q polymorphisms. The association of the donors' SNPs with the biopsy scores and clinical outcomes was retrospectively evaluated by multivariate regression analysis. The CYP2C8*3 polymorphism in the donor was significantly associated with higher scores assigned to pretransplant biopsies [OR = 3.35 (1.03-10.93), p = 0.045]. In turn, higher scores were related to an increased risk of acute rejection [OR = 5.28 (1.32-21.13), p = 0.019] and worse glomerular filtration rate (eGFR) (45.68±16.05 vs. 53.04±16.93 ml/min in patients whose grafts had lower scores, p = 0.010) one year after transplant. Patients whose donors carried the CYP4F2 433M variant showed lower eGFR values (48.96±16.89 vs. 55.94±18.62 ml/min in non-carriers, p = 0.038) and higher risk of acute rejection [OR = 6.18 (1.03-37.21), p = 0.047]. The CYP2J2*7 SNP in the donor was associated with elevated risk of delayed graft function [OR = 25.68 (1.52-43.53), p = 0.025]. Our results taken together suggest that donor genetic variability may be used as a predictor of tissue damage in the graft as well as to predict clinical outcomes and graft function in the recipient.

Asociación entre hiperkaliemia y evolución clínica en la enfermedad renal crónica avanzada / Association of hyperkalemia with clinical outcomes in advanced chronic kidney disease

INTRODUCCIÓN: Los pacientes con enfermedad renal crónica (ERC) tienen un alto riesgo de desarrollo de hiperkaliemia (HK). La relación entre HK y una mala evolución (mortalidad o progresión de la insuficiencia renal) en la ERC avanzada es controvertida. OBJETIVOS: Determinar la incidencia, prevalencia, y factores relacionados con la HK en una cohorte de pacientes con ERC, y su relación con la mortalidad, tasa de hospitalización, progresión de la ERC, y necesidad de inicio de diálisis. MATERIAL Y MÉTODOS: Estudio retrospectivo de observación en una cohorte de pacientes adultos con ERC estadio 4-5. Los criterios de inclusión fueron: tener al menos 3 medidas consecutivas de filtrado glomerular (FG) durante un periodo superior a 3 meses. HK se definió como un K sérico ≥ 5,5 mmol/l. La asociación entre HK y las variables de evolución fue ajustada a los principales factores de confusión mediante análisis mutivariantes. RESULTADOS: Se incluyeron 1079 pacientes (574 hombres, edad media: 65 ± 14 años) con un FG basal 14,8 ± 4,5 ml/min/1,73 m2. El tiempo medio de seguimiento fue de 15 meses y se determinaron una mediana de 7 muestras por paciente. Basalmente un 26% de pacientes tenía HK, un 68% en al menos una muestra durante el periodo individual de seguimiento, y un 33% de forma crónica (HK > 50% del seguimiento individual). Mediante regresión logística multivariable los mejores determinantes de la HK fueron: sexo masculino (OR = 1,529; IC 95% [1,154-2,025], p = 0,003), bicarbonato sérico (OR = 0,863, [0,829-0,900], p < 0,0001), tratamiento diurético (OR = 0,743, [0,556-0,992], p = 0,044), y tratamiento con inhibidores del sistema renina-angiotensina (OR = 4,412, [2,915-6,678], p < 0,0001). Estos pacientes con HK mostraron una progresión de la ERC significativamente más acelerada (−4,05 ± 5,22 vs. −2,69 ± 5,61 ml/min/1,73 m2/año, p < 0,0001), e inicio más frecuente de diálisis (63% vs. 57%, p = 0,115), pero menos mortalidad (9% vs. 17%, p = 0,003), y tasa de hospitalización (2,68 ± 5,94 vs. 3,16 ± 6,77 días/año, p = 0,301) que el resto de los pacientes estudiados. Sin embargo en el análisis multivariante, HK no se asoció de forma independiente con ninguna de las variables de evolución investigadas. CONCLUSIÓN: HK es un hallazgo bioquímico muy frecuente en la ERC avanzada, que se asocia con algunos medicamentos de uso habitual. Sin embargo, HK no se asocia de forma independiente con ninguna de las variables de mala evolución clínica estudiadas

INTRODUCTION: Patients with advanced chronic kidney disease (CKD) are at greatest risk of hyperkalemia (HK). The relationship between HK and negative outcomes (mortality or progression of renal insufficiency) in non-dialysis dependent CKD patients is controversial. AIMS: To determine the incidence, prevalence, and factors related with HK in a cohort of CKD patients, and its relationship with mortality, hospitalization rate, CKD progression, and dialysis initiation. MATERIAL AND METHODS: A retrospective, observational study in an incident cohort of adult patients with stage 4 or 5 CKD not on dialysis. Inclusion criteria were: having at least three consecutive estimated glomerular filtration rate (eGFR) measurements in a follow-up period > 3 months. Decline in renal function was estimated as the slope of the individual linear regression line of eGFR over follow-up time. HK was defined as serum K levels ≥ 5.5 meq/l. Associations of HK with outcomes were adjusted for major confounding variables in the multivariate analysis. RESULTS: The study group consisted of 1079 patients (574 males, mean age: 65 ±14 years) with mean baseline eGFR 14.8 ± 4.5 ml/min/1,73 m2. Mean follow-up time was 15 months with a median of 7 serum sample determinations per patient. HK was observed at baseline in 26% of patients; in at least one serum sample during the individual follow-up period in 68%; or chronically (>50% of samples) in 33% of patients. By multivariate logistic regression, the best determinants of chronic HK were: male sex (OR = 1.529; 95% CI [1.154-2.025], p = .003), serum bicarbonate (OR = 0.863 [0.829-0.900], p <.0001), diuretic treatment (OR = 0.743 [0.556-0.992], p = .044), and angiotensin converting enzyme inhibitor and/or angiotensin receptor blockers (OR = 4.412 [2.915-6.678], p <.0001). Patients whose serum K levels were in the upper quartile showed a significantly faster CKD progression (-4.05±5.22 vs. -2.69 ± 5.61 ml/min/1.73 m2/year, p <.0001), and more frequent dialysis initiation (63% vs. 57%, p = .115), though lower mortality (9% vs. 17%, p = .003) and hospitalization rates (2.68 ± 5.94 vs. 3.16 ± 6.77 days per year, p = .301) than the other study patients. However, in the multivariate analysis, average serum K levels were not independently associated with the clinical outcomes investigated. CONCLUSION: HK is a common biochemical finding in non-dialysis dependent CKD patients, mainly associated with prescribed medication. However, HK was not independently associated with major negative clinical outcomes

Variability in the leptin receptor gene and other risk factors for post-transplant diabetes mellitus in renal transplant recipients.

Aim: Post-transplant diabetes mellitus (PTDM) is one of the main complications after kidney transplantation. It is known that leptin plays an important role in glucose metabolism and mutations in the leptin receptor gene (LEPR) are responsible for different complications in renal transplant recipients. We aimed to analyse the association of polymorphisms in LEPR with the development of PTDM in these patients. Methods: A total of 315 renal transplant recipients were genotyped for the Lys109Arg, Gln223Arg and Lys656Asn polymorphisms. The impact of these genetic variables together with other clinical and demographic parameters on PTDM risk was evaluated in a multivariate regression analysis. Results: The 223Arg variant showed a significant association with PTDM risk [OR = 3.26 (1.35-7.85), p = 0.009] after correcting for multiple testing. Carriers of this variant also showed higher BMI values (26.95 ± 4.23) than non-carriers (25.67 ± 4.43, p = 0.025). In addition, it was BMI at transplant and not the BMI increment in the first year after grafting that was associated with PTDM (p > 0.00001). Haplotype analyses did not reveal significant associations. Conclusions: Our result show, for the first time to our knowledge, that genetic variability in the LEPR may contribute significantly to the risk for PTDM in renal transplant recipients. KEY MESSAGES The LEPR Gln223Arg polymorphism significantly contributes to the development of PTDM in renal transplant recipients. The effect of the 223Arg variant on PTDM is strongly modulated by the age of the recipient. The 223Arg variant in the leptin receptor is related to higher BMI in renal transplant recipients.

Association of hyperkalemia with clinical outcomes in advanced chronic kidney disease. / Asociación entre hiperkaliemia y evolución clínica en la enfermedad renal crónica avanzada.

INTRODUCTION: Patients with advanced chronic kidney disease (CKD) are at greatest risk of hyperkalemia (HK). The relationship between HK and negative outcomes (mortality or progression of renal insufficiency) in non-dialysis dependent CKD patients is controversial. AIMS: To determine the incidence, prevalence, and factors related with HK in a cohort of CKD patients, and its relationship with mortality, hospitalization rate, CKD progression, and dialysis initiation. MATERIAL AND METHODS: A retrospective, observational study in an incident cohort of adult patients with stage 4 or 5 CKD not on dialysis. Inclusion criteria were: having at least three consecutive estimated glomerular filtration rate (eGFR) measurements in a follow-up period >3 months. Decline in renal function was estimated as the slope of the individual linear regression line of eGFR over follow-up time. HK was defined as serum K levels ≥5.5 meq/l. Associations of HK with outcomes were adjusted for major confounding variables in the multivariate analysis. RESULTS: The study group consisted of 1079 patients (574 males, mean age: 65±14 years) with mean baseline eGFR 14.8±4.5 ml/min/1,73 m2. Mean follow-up time was 15 months with a median of 7 serum sample determinations per patient. HK was observed at baseline in 26% of patients; in at least one serum sample during the individual follow-up period in 68%; or chronically (>50% of samples) in 33% of patients. By multivariate logistic regression, the best determinants of chronic HK were: male sex (OR = 1.529; 95% CI [1.154-2.025], p = .003), serum bicarbonate (OR = 0.863 [0.829-0.900], p <.0001), diuretic treatment (OR = 0.743 [0.556-0.992], p = .044), and angiotensin converting enzyme inhibitor and/or angiotensin receptor blockers (OR = 4.412 [2.915-6.678], p <.0001). Patients whose serum K levels were in the upper quartile showed a significantly faster CKD progression (-4.05±5.22 vs. -2.69±5.61 ml/min/1.73 m2/year, p <.0001), and more frequent dialysis initiation (63% vs. 57%, p = .115), though lower mortality (9% vs. 17%, p = .003) and hospitalization rates (2.68±5.94 vs. 3.16±6.77 days per year, p = .301) than the other study patients. However, in the multivariate analysis, average serum K levels were not independently associated with the clinical outcomes investigated. CONCLUSION: HK is a common biochemical finding in non-dialysis dependent CKD patients, mainly associated with prescribed medication. However, HK was not independently associated with major negative clinical outcomes.

A Very Rare Case of Right Insular Lobe Langerhans Cell Histiocytosis (CD1a+) Mimicking Glioblastoma Multiforme in a Young Adult.

BACKGROUND: Langerhans cell histiocytosis (LCH) is a multisystemic dendritic cell proliferation that is relatively uncommon in adults. Central nervous system LCH outside the pituitary gland is even more uncommon. CASE DESCRIPTION: We report the case of a 42-year-old man who had complained of right-side hemicranial pain and left arm minor paresis. The symptoms were due to a right insular lobe heterogeneous-enhancing lesion associated with extensive vasogenic edema. The first diagnostic impression suggested glioblastoma multiforme or localized metastasis. The thoracic, abdominal, pelvic computed tomography scan only detected small upper lung inactive nodules suggesting silent focal LCH. A very hard lesion was almost completely removed through a pterional craniotomy approach, with no fluorescence after aminolevulinic acid infusion. The intraoperative biopsy findings ruled out glioma but could not confirm lymphoma. The definitive cerebral biopsy findings showed lymphocytes and histiocytes (CD1a+, S-1001+), with a diagnosis of intracerebral parenchymal LCH. Fractioned radiotherapy resulted in clinical and radiological remission. CONCLUSIONS: The present case is so rare it should not be used as a guide. We probably will never see a single intraparenchymal supratentorial central nervous system LCH lesion. However, we hope our report will help colleagues in the future with the thought process.