Primary oocytes with cellular senescence features are involved in ovarian aging in mice.

In mammalian females, quiescent primordial follicles serve as the ovarian reserve and sustain normal ovarian function and egg production via folliculogenesis. The loss of primordial follicles causes ovarian aging. Cellular senescence, characterized by cell cycle arrest and production of the senescence-associated secretory phenotype (SASP), is associated with tissue aging. In the present study, we report that some quiescent primary oocytes in primordial follicles become senescent in adult mouse ovaries. The senescent primary oocytes share senescence markers characterized in senescent somatic cells. The senescent primary oocytes were observed in young adult mouse ovaries, remained at approximately 15% of the total primary oocytes during ovarian aging from 6 to 12 months, and accumulated in aged ovaries. Administration of a senolytic drug ABT263 to 3-month-old mice reduced the percentage of senescent primary oocytes and the transcription of the SASP factors in the ovary, in addition, led to increased numbers of primordial and total follicles and a higher rate of oocyte maturation. Our study provides experimental evidence that primary oocytes, a germline cell type that is arrested in meiosis, become senescent in adult mouse ovaries and that senescent cell clearance reduced primordial follicle loss and mitigated ovarian aging phenotypes.

Primary oocytes with cellular senescence features are involved in ovarian aging in mice.

In mammalian females, quiescent primordial follicles serve as the ovarian reserve and sustain normal ovarian function and egg production via folliculogenesis. The loss of primordial follicles causes ovarian aging. Cellular senescence, characterized by cell cycle arrest and production of the senescence-associated secretory phenotype (SASP), is associated with tissue aging. In the present study, we report that some quiescent primary oocytes in primordial follicles become senescent in adult mouse ovaries. The senescent primary oocytes share senescence markers characterized in senescent somatic cells. The senescent primary oocytes were observed in young adult mouse ovaries, remained at approximately 15% of the total primary oocytes during ovarian aging from 6 months to 12 months, and accumulated in aged ovaries. Administration of a senolytic drug ABT263 to 3-month-old mice reduced the percentage of senescent primary oocytes and the transcription of the SASP cytokines in the ovary. In addition, led to increased numbers of primordial and total follicles and a higher rate of oocyte maturation and female fertility. Our study provides experimental evidence that primary oocytes, a germline cell type that is arrested in meiosis, become senescent in adult mouse ovaries and that senescent cell clearance reduced primordial follicle loss and mitigated ovarian aging phenotypes.

A Comparison of Cognitive Performance, Depressive Symptoms, and Incidence of Falls in Brazilian Older Women with and without a Confirmed History of COVID-19.

The study aimed to compare cognitive performance, depressive symptoms, and the incidence of falls in Brazilian older women with and without a confirmed history of COVID-19. This cross-sectional study included 188 women (60-89 years), divided into two groups: one with a history of COVID-19 (n = 139), and one without any history of COVID-19 (n = 49). The instruments used were the Cognitive Telephone Screening Instrument (COGTEL) test battery, the Trail Making Test (TMT), the Geriatric Depression Scale (GDS-15), and the self-reported history of falls since the beginning of mandatory confinement. The higher the age, the higher the incidence of falls. The highest prevalence of falls (57.1%) occurred in the COVID-19 group (p = 0.001), the members of which also indicated a better cognitive performance in the COGTEL test (p = 0.017), TMT-B (p = 0.004), and ∆TMT (B-A) (p = 0.004). In turn, the depressive symptoms were more severe in the COVID-19 group (p < 0.001). We observed that COVID-19 infection without hospitalization did not affect the cognitive performance of older adult women. Future studies should be carried out to monitor the mental health of older adult Brazilian women. Moreover, regardless of their history of COVID-19, older adults should participate in a physical training program focused on preventing falls.

Ketogenic-Diet Shake Containing Uncaria tomentosa-Associated Acute Interstitial Nephritis.

Uncaria tomentosa is a plant that has been used in traditional medicine for its anti-inflammatory, immunomodulatory, and immunostimulant properties. As a result, it can be found in several over-the-counter supplements worldwide. Acute interstitial nephritis (AIN) can be due to an offending medication, infection, or autoimmunity. We present a case of a patient who was on a strict ketogenic diet, utilizing over-the-counter diet shakes containing the herbal supplement Uncaria tomentosa who developed acute kidney injury with a serum creatinine of 3.6 mg/dL up from a baseline of 0.7 mg/dL. Serological evaluation was negative, and kidney biopsy revealed interstitial inflammatory infiltrates including focally prominent eosinophils and multifocal tubulitis. Stopping the keto-diet shake containing Uncaria tomentosa and concomitant corticosteroid therapy resulted in improvement in kidney function to near baseline. To our knowledge, this is the only biopsy-proven case of AIN in the setting of Uncaria tomentosa use.

Bariatric Surgery With Roux-En-Y Gastric Bypass or Sleeve Gastrectomy for Treatment of Obesity and Comorbidities: Current Evidence and Practice.

BACKGROUND: With the growing prevalence of obesity in the global population, alternative measures for weight loss and treatment of comorbidities must be considered due to the increasing difficulty of conservative management alone. Here we discuss the benefits of bariatric surgery on weight loss as well comorbidities that are present in a majority of obese patients.  Methods: In this review, we discuss the current practice and evidence of bariatric surgery as it pertains to weight loss and the beneficial effect on comorbidities commonly present in obesity. RESULTS:  Our review found that bariatric surgery with either the roux-en-y gastric bypass or laparoscopic sleeve gastrectomy can result in weight loss of up to 80% of excess weight. We also found that bariatric surgery has a profound effect on multiple comorbidities such as type 2 diabetes mellitus, hypertension, and hyperlipidemia through remission of the disease. CONCLUSION:  Bariatric surgery serves as an efficacious alternative for treatment of obesity and comorbidities.

Identification of large offspring syndrome during pregnancy through ultrasonography and maternal blood transcriptome analyses.

In vitro production (IVP) of embryos in cattle can result in large/abnormal offspring syndrome (LOS/AOS) which is characterized by macrosomia. LOS can cause dystocia and lead to the death of dam and calf. Currently, no test exists to identify LOS pregnancies. We hypothesized that fetal ultrasonography and/or maternal blood markers are useful to identify LOS. Bovine fetuses were generated by artificial insemination (control) or IVP. Fetal ultrasonographies were taken on gestation D55 (D55) and fetal collections performed on D56 or D105 (gestation in cattle ≈ D280). IVP fetuses weighing ≥ 97 percentile of the control weight were considered LOS. Ultrasonography results show that the product of six D55 measurements can be used to identify extreme cases of LOS. To determine whether maternal blood can be used to identify LOS, leukocyte mRNA from 23 females was sequenced. Unsupervised hierarchical clustering grouped the transcriptomes of the two females carrying the two largest LOS fetuses. Comparison of the leukocyte transcriptomes of these two females to the transcriptome of all other females identified several misregulated transcripts on gestation D55 and D105 with LOC783838 and PCDH1 being misregulated at both time-points. Together our data suggest that LOS is identifiable during pregnancy in cattle.

The Cleveland Clinic Kidney Biopsy Epidemiological Project.

Background: The kidney biopsy is the gold standard for diagnosing glomerular diseases. Large-scale, epidemiologic studies describing the prevalence of kidney diseases are lacking, especially in the United States. We aimed to determine the spectrum of biopsy-proven kidney disease across the Cleveland Clinic enterprise. Methods: We identified all patients with a native kidney biopsy performed or reviewed at the Cleveland Clinic from January 2015 to September 2021. Retrospective chart review was performed to obtain clinical and demographic characteristics. Results were stratified by age, sex, race, and location to determine epidemiologic trends. Results: Of >9600 patients, we excluded transplant and donor biopsies and unavailable records, and included 4128 patients with native kidney biopsy data. The median age was 60 years, with 46% female patients. Self-reported racial demographics included 73% White, 22% Black, 3% multiracial, and 2% Asian background, with 5% Hispanic. Common diagnoses were: FSGS (n=633, 15%), diabetic kidney disease (DKD) (n=602, 15%), IgA nephropathy (n=319, 8%), lupus nephritis (LN) (n=289, 7%), pauci-immune glomerulonephritis (n=275, 7%), membranous nephropathy (n=211, 5%), and amyloidosis (n=110, 3%). There were 3322 patients in Ohio, with 361 patients in Florida. Using multivariate analysis, those aged >70 years were more likely to have FSGS, whereas those <45 years were more likely to have IgA nephropathy or LN. Males were more likely to have FSGS or IgAN, and less likely to have LN. Black patients were more likely to have FSGS, DKD, or LN. Hispanic patients were more likely to have DKD. Finally, patients in Florida were more likely to have LN. There was no change in the disease spectrum before and during the COVID-19 pandemic. Conclusion: Our study catalogs the spectrum of biopsy-proven kidney disease across the Cleveland Clinic enterprise. This lays the foundation for glomerular disease clinical trials, and highlights the need for a standardized national kidney biopsy registry to bolster glomerular and kidney disease research in the United States.

Ternary Composite Nanofibers Containing Chondroitin Sulfate Scavenge Inflammatory Chemokines from Solution and Prohibit Squamous Cell Carcinoma Migration.

Recessive dystrophic epidermolysis bullosa (RDEB), an inherited disease featuring blistering wounds, causes constant inflammation that leads to the eventual development of an aggressive form of squamous cell carcinoma (RDEB SCC). The persistence of inflammatory chemokines such as MCP-1 and Il-8 in RDEB wounds may foster RDEB SCC carcinogenesis. We report the production of ternary composite nanofibers containing pullulan, chondroitin sulfate, and tannic acid as RDEB wound dressings. The swellable fibers are stable to hydration and absorb ∼500% their weight in water. The fibers remove ∼99% of MCP-1 from solution in <2 h. Scavenged media did not promote RDEB SCC migration.

Territorio, lugar y espacio recreativo escolar / Território, lugar e espaço de recreação na escola / Territory, place and school recreational space

La escuela asumida como un espacio de construcción, producción y confrontación simbólica permite la emergencia de múltiples formas en las que se presenta la recreación en ella. Por esto, interesa a este texto mostrar algunas reflexiones con relación a la categoría de espacio recreativo escolar, entendido como la exploración e intervención de la recreación en territorios físicos e interpersonales que permitan edificar y consolidar lugares y ambientes con sentido lúdico y socio-histórico...

A escola assume-se como um espaço de construção, produção e confronto simbólico permite o surgimento de várias maneiras em que a recreação é presente. Por isso, neste texto mostram-se algumas reflexões sobre o tipo de espaço de recreação educativo, entendido como a exploração e intervenção na recreação no territórios físicos e interpessoais que permitem construir e consolidar lugares e ambientes lúdico e sócio-histórico...

Taken as a space of construction, production and symbolic confrontation, school lets come out of multiple ways in which recreation is reveal. Therefore, is intented to show through this written, some considerations regarding school recreational space category, understood as exploration and recreational intervention over physical and interpersonal scopes that allow build and consolidate places and environments with ludic and socio- historical sense...

Genetic variation in cytokine-related genes and migraine susceptibility.

Migraine is classified by the World Health Organization (WHO) as being one of the top 20 most debilitating diseases. According to the neurovascular hypothesis, neuroinflammation may promote the activation and sensitisation of meningeal nociceptors, inducing the persistent throbbing headache characterized in migraine. The tumor necrosis factor (TNF) gene cluster, made up of TNFα, lymphotoxin α (LTA), and lymphotoxin ß (LTB), has been implicated to influence the intensity and duration of local inflammation. It is thought that sterile inflammation mediated by LTA, LTB, and TNFα contributes to threshold brain excitability, propagation of neuronal hyperexcitability and thus initiation and maintenance of a migraine attack. Previous studies have investigated variants within the TNF gene cluster region in relation to migraine susceptibility, with largely conflicting results. The aim of this study was to expand on previous research and utilize a large case-control cohort and range of variants within the TNF gene cluster to investigate the role of the TNF gene cluster in migraine. Nine single nucleotide polymorphisms (SNPs) were selected for investigation as follows: rs1800683, rs2229094, rs2009658, rs2071590, rs2239704, rs909253, rs1800630, rs1800629, and rs3093664. No significant association with migraine susceptibility was found for any of the SNPs tested, with further testing according to migraine subtype and gender also showing no association for disease risk. Haplotype analysis showed that none of the tested haplotypes were significantly associated with migraine.

Renal supportive care and palliative care: revision and proposal in kidney replacement therapy.

Patients with chronic kidney disease may receive sustained renal supportive care and renal palliative care (RPC) starting with the diagnosis of the disease, throughout the various stages of renal replacement therapy (RRT), the cessation of the RRT, and in the decision of whether to provide conservative treatment or non-initiation of RRT. This article reviews the literature on the development of renal palliative care and proposed RPC models. We describe the progression of disease in organ failure, which is very different from other areas of palliative care (PC). We describe important components of resident nephrology training in PC. We discuss the management of pain and symptom control, as well as communication skills and other psychological and ethical aspects in the renal patient. We conclude that in chronic renal patients, a palliative care approach can provide a positive impact on the quality of life of patients and their families, as well as optimizing the complex treatment of the renal patient.

Serum uric acid as a marker of all-cause mortality in an elderly patient cohort.

INTRODUCTION: There is growing evidence of the role of serum uric acid (SUA) as a risk factor for cardiovascular and renal disease. We analysed the association between baseline SUA and overall mortality in a cohort of elderly patients followed prospectively for 5 years. PATIENTS AND METHODS: Eighty clinically stable patients, median age 83 years (range 69-97), 31.3% men, 35% diabetics, 83% hypertensives were randomly recruited at Geriatrics and Nephrology visits between January and April 2006 and followed for 5 years. We measured baseline SUA and serum creatinine and estimated glomerular filtration rate (GFR) with MDRD abbreviated. In Nephrology Department patients, we measured proteinuria in 24-hour urine and in Geriatrics department patients we measured proteinuria (mg/dl)/creatinine (mg/dl) in urine (first morning urine). Predictive variables were: baseline SUA and plasma creatinine; estimated GFR (abbreviated MDRD formula); and we recorded age, gender, baseline comorbidity (Charlson index), individualised cardiovascular treatment and mortality. STATISTICAL ANALYSIS: SPSS15.0. RESULTS: baseline SUA was normally distributed and its median was 5.85 mg/dl. We found no significant differences in levels of SUA by gender, history of diabetes mellitus, hypertension, diuretic drug use, heart disease, peripheral arterial disease or stroke. Patients with a history of heart failure had significantly higher SUA (7.00 ± 1.74 vs 5.90 ± 1.71, P=.031). Some 41 deaths occurred during follow-up (15 men and 26 women): 15 due to general deterioration, 8 due to infections, 4 due to stroke, 4 due to tumours, 3 due to cardiovascular disease, 2 due to complications of fractures and 5 due to unknown causes. Patients with SUA higher than the median had significantly lower GFR and higher mortality at 5 years. In the Cox analysis for overall mortality [independent variables: age, gender, Charlson Index, history of heart failure, SUA, creatinine, proteinuria and GFR (MDRD)] only SUA levels (HR: 1.35; 1.17-1.56 P=.000) were independently associated with mortality. CONCLUSIONS: In our study, levels of SUA are an independent risk factor for mortality in elderly patients.

Cuidados de soporte renal y cuidados paliativos renales: revisión y propuesta en terapia renal sustitutiva / Renal supportive care and palliative care: revision and proposal in kidney replacement therapy

El paciente con enfermedad renal crónica es susceptible de recibir tratamiento de soporte y cuidados paliativos renales (CPR) desde el diagnóstico de la enfermedad, durante las distintas etapas de tratamiento sustitutivo renal (TSR), en el cese de dicho TRS y también si se decide tratamiento conservador o no inicio de TRS. Este artículo revisa la literatura referente al desarrollo de cuidados CPR y los modelos propuestos. Exponemos la trayectoria de la enfermedad en el fallo de órgano, que marca diferencias respecto a otros campos de los cuidados paliativos (CP). Se describen componentes de formación importantes para el residente de nefrología en CP. Abordamos el manejo del dolor y el control de síntomas, así como habilidades de comunicación y otros aspectos psicológicos y éticos en el paciente renal. Concluimos que en la atención al paciente renal crónico, un enfoque desde la medicina paliativa puede suponer un provechoso impacto en la calidad de vida del paciente y su familia, además de optimizar el complejo tratamiento nefrológico del paciente (AU)

Patients with chronic kidney disease may receive sustained renal supportive care and renal palliative care (RPC) starting with the diagnosis of the disease, throughout the various stages of renal replacement therapy (RRT), the cessation of the RRT, and in the decision of whether to provide conservative treatment or non-initiation of RRT. This article reviews the literature on the development of RPC and the models proposed. We describe how organ failure differs compare to other areas of palliative care (PC). We describe important training components in RPC for the resident nephrologist and we approach the management of pain and symptom control, communication skills and other psychological and ethical aspects in the renal patient. We conclude a palliative care approach may have a profitable impact on the quality of life for chronic renal patients and their families as well as optimizing the complex renal patient's treatment (AU)

Utilidad del ácido úrico como marcador de mortalidad global en una cohorte de ancianos / Serum uric acid as a marker of all-cause mortality in an elderly patient cohort

Introducción: Existe evidencia creciente del papel del ácido úrico (AU) como factor de riesgo cardiovascular y renal. En este trabajo analizamos la asociación entre niveles basales de AU y mortalidad global en una cohorte de ancianos seguidos prospectivamente durante 5 años. Pacientes y métodos: 80 pacientes clínicamente estables; mediana de edad, 83 años (rango 69-97); 31,3% varones; 35% diabéticos; 83% hipertensos; reclutados aleatoriamente en consultas de Geriatría y Nefrología entre enero y abril de 2006 y seguidos durante 5 años. Medimos basalmente AU y creatinina en plasma y estimamos filtrado glomerular (FG) con fórmula MDRD abreviada. Asimismo, en los pacientes de Nefrología se midió la proteinuria mediante la recogida de orina de 24 horas, y en los vistos en Geriatría se estimó a partir del cociente proteínas (mg/dl)/creatinina (mg/dl) en primera orina de la mañana. Registramos edad, género, comorbilidad basal (Índice de Charlson), patologías cardiovasculares individualizadas, tratamientos y mortalidad. Estadística: SPSS15.0. Resultados: El AU basal presentaba una distribución normal y su mediana era de 5,85 mg/dl. No encontramos diferencias significativas en los niveles de AU según género, antecedentes de diabetes méllitus, hipertensión arterial, uso de diuréticos, cardiopatía isquémica, arteriopatía periférica o ictus. Los pacientes con antecedentes de insuficiencia cardíaca tenían AU significativamente mayor (7,00 ± 1,74 vs. 5,90 ± 1,71; p = 0,031). 41 pacientes (15 varones y 26 mujeres) fallecieron: 15 por deterioro en el estado general; 8 por infecciones; 4 por ictus; 4 por tumores; 3 por causas cardiovasculares; 2 por complicaciones de fracturas y 5 por causas desconocidas. Los pacientes con AU superior a la mediana tenían un FG significativamente menor y una mortalidad a los 5 años más elevada. En el análisis de Cox para mortalidad global (variables independientes: edad, género, Charlson, antecedentes de insuficiencia cardíaca, AU, creatinina, proteinuria y filtrado glomerular-MDRD) sólo los niveles de AU (riesgo relativo: 1,35; 1,17-1,56, p = 0,000) se asociaban de forma independiente a la mortalidad. Conclusiones: en nuestro estudio, los niveles de AU se muestran como factor de riesgo independiente de mortalidad en ancianos (AU)

Introduction: There is growing evidence of the role of serum uric acid (SUA) as a risk factor for cardiovascular and renal disease. We analysed the association between baseline SUA and overall mortality in a cohort of elderly patients followed prospectively for 5 years. Patients and Methods: Eighty clinically stable patients, median age 83 years (range 69-97), 31.3% men, 35% diabetics, 83% hypertensives were randomly recruited at Geriatrics and Nephrology visits between January and April 2006 and followed for 5 years. We measured baseline SUA and serum creatinine and estimated glomerular filtration rate (GFR) with MDRD abbreviated. In Nephrology Department patients, we measured proteinuria in 24-hour urine and in Geriatrics department patients we measured proteinuria (mg/dl)/creatinine (mg/dl) in urine (first morning urine). Predictive variables were: baseline SUA and plasma creatinine; estimated GFR (abbreviated MDRD formula); and we recorded age, gender, baseline comorbidity (Charlson index), individualised cardiovascular treatment and mortality. Statistical analysis: SPSS15.0. Results: baseline SUA was normally distributed and its median was 5.85mg/dl. We found no significant differences in levels of SUA by gender, history of diabetes mellitus, hypertension, diuretic drug use, heart disease, peripheral arterial disease or stroke. Patients with a history of heart failure had significantly higher SUA (7.00±1.74 vs 5.90±1.71, P=.031). Some 41 deaths occurred during follow-up (15 men and 26 women): 15 due to general deterioration, 8 due to infections, 4 due to stroke, 4 due to tumours, 3 due to cardiovascular disease, 2 due to complications of fractures and 5 due to unknown causes. Patients with SUA higher than the median had significantly lower GFR and higher mortality at 5 years. In the Cox analysis for overall mortality [independent variables: age, gender, Charlson Index, history of heart failure, SUA, creatinine, proteinuria and GFR (MDRD)] only SUA levels (HR: 1.35; 1.17-1.56 P=.000) were independently associated with mortality. Conclusions: In our study, levels of SUA are an independent risk factor for mortality in elderly patients (AU)

Relationship between leptin and all-cause and cardiovascular mortality in chronic hemodialysis patients.

BACKGROUND: We aimed to evaluate the relationship between serum leptin and the leptin/body mass index (BMI) ratio with prevalent cardiovascular disease (CVD), and their influence on all-cause and CVD-related mortality in patients on hemodialysis (HD). METHODS: 118 stable HD patients (50 women, median [interquartile range] age, 65.1 [54.7-72.2] years) were studied. All patients had baseline measurement of serum leptin concentrations. Relationships between leptin and all-cause and CVD mortality were studied by means of survival analysis and Cox regression analysis. RESULTS: The leptin/BMI ratio was similar in patients with and without CVD at baseline (0.65 [0.29-2.23] vs. 0.68 [0.29-1.49] ng·m2/ml·kg, respectively, NS). Multiple logistic regression analysis showed that there was not an independent association between leptin/BMI ratio and prevalent CVD. During the follow-up time, 52 (44.1%) patients died. CVD was the cause of death in 27 out of 52 (51.9%) deceased patients. Survival analysis and Cox proportional multivariate regression analysis showed that there were no significant relationships between leptin levels or the leptin/BMI ratio and all-cause and CVD-related mortality. CONCLUSION: These results do not support that, in stable HD patients, serum leptin concentrations and the leptin/BMI ratio are related with prevalent CVD. Leptin/BMI ratio seems not to be a risk factor for mortality in these patients.

Estimación del filtrado glomerular en personas de 69 años o más: concordancia entre diferentes métodos de cálculo / Estimation of glomerular filtration rate in persons aged 69 years or older: agreement between distinct calculation methods

Introducción El filtrado glomerular (FG) es el marcador de función renal más aceptado. Su cálculo exacto no se hace habitualmente en la clínica. Para su estimación se han desarrollado diversos métodos: clearance creatinine (CCr, ‘aclaramiento de creatinina’) o con fórmulas derivadas de la creatinina sérica (Crs). En este trabajo analizamos la concordancia del FG estimado (FGe) con diferentes métodos. Material y métodos Estudio transversal entre enero y abril de 2006, de 32 ancianos estables, con una edad de 69 años o más, valorados en una consulta de nefrología general. El FGe se calcula con CCr (se considera gold estándar), Cockcroft-Gault (CG) y Modification of Diet in Renal Disease (MDRD). Utilizamos comparación de medias (U de Mann-Whitney), coeficiente de correlación de Spearman y la concordancia entre los diferentes métodos se hace con el coeficiente kappa. Resultados La media±DE global de FGe por CCr es de 36,14±16ml/min (rango: 11,75–69,6); CG de 37,02±16ml/min (rango: 13,3–72,3), y MDRD de 45,52±16ml/min (rango: 19,2–75,36). Las variaciones en el FGe al comparar los métodos son CCr frente a MDRD: −9,37ml/min (IC 95%: −13,85, −4,9); CCr frente CG: −2.54ml/min (IC 95%: −6,95, 1,80), y MDRD frente CG: 9,0ml/min (IC 95%: 5,96, 12). El grado de correlación entre el gold estándar (CCr) y las fórmulas matemáticas derivadas de la Crs es para MDRD: r=0,74 (p<0,001) y para CG: r=0,77 (p<0,001). El valor kappa de CCr con CG es de 0,44 y de CCr con MDRD es de 0,35. En la clasificación por estadios de enfermedad renal crónica, encontramos discrepancias en el porcentaje de pacientes según el método: un estadio 5 (FGe<15ml/min) por CCr en un 9,37%, por CG en un 13,67% y ningún paciente por MDRD. Conclusiones En la estimación de la función renal en el anciano, los niveles de FGe pueden variar en un mismo paciente según el método empleado: dado el grado de concordancia del CG con el CCr, puede ser preferible el uso de esta fórmula matemática frente al MDRD (AU)

MaterialEstimation of glomerular filtration rate (eGFR) is the most widely accepted marker of renal function. Precise calculation is not routinely performed in clinical practice. Several methods have been developed for eGFR: creatinine clearance (CCr) calculation or the use of formulae derived from serum creatinine (sCr). The present study aimed to analyze the agreement between distinct methods of calculating eGFR.ResultsThe overall means±SD of GFRe for CCr were 36.14±16ml/min (range 11.75–69.6); CG: 37.02±16ml/min (range 13.3–72.3) and MDRD: 45.52±16ml/min (range 19.2–75.36). Variations in eGFR on comparison of methods were CCr and MDRD: −9.37ml/min (95% CI:−13.85, −4.9); CCr and CG:−2.54ml/min (95% CI: −6.95, 1.80); MDRD and CG: 9.0ml/min (95% CI: 5.96, 12). The correlation between the gold standard (CCr) and sCr-derived formulae was r=0.74 for MDRD (P<0.001) and r=0.77 for CG (P<0.001). The Kappa value for CCr and CG was 0.44 and was 0.35 for CCr and MDRD. When patients were classified by stage of chronic renal disease, discrepancies were found according to the method used: stage 5 (eGFR<15ml/min) was diagnosed in 13.63% with CG while none were diagnosed with stage 5 with MDRD.ConclusionsIn the estimation of the renal function in the elderly, eGFRe levels can differ in the same patient according to the method used: in view of the degree of concordance between CG and CCr, this mathematical formula should be used in preference to MDRD(AU)

[Estimation of glomerular filtration rate in persons aged 69 years or older: agreement between distinct calculation methods]. / Estimación del filtrado glomerular en personas de 69 años o más: concordancia entre diferentes métodos de cálculo.

MATERIAL: Estimation of glomerular filtration rate (eGFR) is the most widely accepted marker of renal function. Precise calculation is not routinely performed in clinical practice. Several methods have been developed for eGFR: creatinine clearance (CCr) calculation or the use of formulae derived from serum creatinine (sCr). The present study aimed to analyze the agreement between distinct methods of calculating eGFR. MATERIAL AND METHODS: We performed a cross-sectional study between January and April, 2006 in 32 stable elders, aged 69 years or older, evaluated in a general nephrology unit. eGFR was calculated by CCr (considered the gold standard), Cockcroft-Gault (CG) and Modification of Renal Diet in Disease (MDRD) equations. The Mann Whitney U-test, Spearman's correlation coefficient and the Kappa coefficient were used to compare means and determine the concordance between methods. RESULTS: The overall means+/-SD of GFRe for CCr were 36.14+/-16 ml/min (range 11.75-69.6); CG: 37.02+/-16 ml/min (range 13.3-72.3) and MDRD: 45.52+/-16 ml/min (range 19.2-75.36). Variations in eGFR on comparison of methods were CCr and MDRD: -9.37 ml/min (95% CI:-13.85, -4.9); CCr and CG:-2.54 ml/min (95% CI: -6.95, 1.80); MDRD and CG: 9.0 ml/min (95% CI: 5.96, 12). The correlation between the gold standard (CCr) and sCr-derived formulae was r=0.74 for MDRD (P<0.001) and r=0.77 for CG (P<0.001). The Kappa value for CCr and CG was 0.44 and was 0.35 for CCr and MDRD. When patients were classified by stage of chronic renal disease, discrepancies were found according to the method used: stage 5 (eGFR<15 ml/min) was diagnosed in 13.63% with CG while none were diagnosed with stage 5 with MDRD. CONCLUSIONS: In the estimation of the renal function in the elderly, eGFRe levels can differ in the same patient according to the method used: in view of the degree of concordance between CG and CCr, this mathematical formula should be used in preference to MDRD.

Posible implicación del gen RNASEH1 en la etiología de Diabetes Mellitus tipo 1 / Possible implication of the RNASEH1 gene in the etiology of type 1 diabetes mellitus

Las enfermedades complejas se caracterizan porque presentan varios genes además de factores ambientales implicados en su etiología. Las bases genéticas de la diabetes mellitus tipo 1 (T1D) supone un efecto mayor del complejo HLA que interactúa con otros genes y con el ambiente. Mucho se ha descrito acerca de la posible participación de las infecciones virales como desencadenadores de T1D. En esta revisión exploramos los posibles mecanismos por los cuales el gen RNASEH1 podría estar participando en la etiología de T1D, a partir de una infección viral. El gen RNASEH1 se localiza en la región cromosómica 2p25, la cual ha sido recientemente implicada por nosotros en la susceptibilidad a T1D. Este gen ha sido implicado en la enfermedad mediante análisis genético. Acá pretendemos dar sentido biológico a los datos genéticos. Considerando que la enfermedad es multifactorial, este planteamiento no excluye la participación de otros genes u otros factores ambientales.

Complex disorders are characterized by presenting many genes and other environmental factors implicated in their etiology. The genetic bases of type 1 diabetes mellitus (T1D) suppose a major effect of the HLA complex which interacts with other genes and the environment. Much has been written about the possible implication of viral infections as triggers of T1D. This review explores the mechanisms by which the RNASEH1 gene could be involved in the etiology of T1D, due to a viral infection. The RNASEH1 gene is located in chromosome 2p25, which has been recently implicated in the susceptibility to T1D by the authors, through genetic analysis.This text hopes to establish a biological context for the genetic data. Taking into account that this is a multifactorial disease, this approach does not exclude the eventual participation of other genes or environmental factors.