Nefropatía membranosa: genética, antígenos y anticuerpos

La nefropatía membranosa es un trastorno renal caracterizado por el engrosamiento de la membrana basal glomerular, que causa el síndrome nefrótico. Puede deberse a diversas afecciones subyacentes que provocan daños en las unidades de filtración de los riñones, conocidas como nefronas, produciendo proteinuria masiva, hipoalbuminemia, edema e hiperlipidemia. Entre el 30 y el 40% de los casos de síndrome nefrótico en adultos se deben a una nefropatía membranosa. En las últimas décadas se ha avanzado en el descubrimiento de antígenos, anticuerpos y genes implicados en la fisiopatología de la enfermedad y se ha propuesto un nuevo sistema de clasificación. La presencia de complejos antígeno-anticuerpo junto con factores genéticos puede influir en la susceptibilidad a dicha desregulación inmunológica, y establece nueva información en un lo que se conocía entre las etiologías de causas primarias y secundarias.La comprensión de los antígenos implicados en la nefropatía membranosa es un área de investigación activa, y es posible que se identifiquen antígenos adicionales a medida que nuestro conocimiento de la enfermedad siga evolucionando. Este artículo resume algunos conceptos y hallazgos recientes sobre este tema. (provisto por Infomedic International)

Membranous nephropathy is a kidney disorder characterized by thickening of the glomerular basement membrane, that causes nephrotic syndrome. It can be caused by various underlying conditions that result in damage to the filtering units of the kidneys, known as nephrons, producing massive proteinuria, hypoalbuminemia, edema and hyperlipidemia.  Between 30 to 40% of cases of nephrotic syndrome in adults are due to membranous nephropathy. In recent decades, progress has been made with the discovery of antigens, antibodies and genes involved in the pathophysiology of the disease and a new classification system has been proposed. The presence of antigen-antibody complexes together with genetic factors may influence the susceptibility to such immune dysregulation, and states new information in a what was known between the etiologies of primary and secondary causes. The understanding of the antigens involved in membranous nephropathy is an area of active research, and additional antigens may be identified as our knowledge of the disease continues to evolve. This article summarizes some concepts and recent findings made on this topic. (provided by Infomedic International)

Acute Presentation of Mesoamerican Nephropathy in an Agricultural Worker From Panama.

Mesoamerican nephropathy (MeN) is Central America's growing endemic renal disorder. No single cause is established, but many risk factors are hypothesized, such as young and medium-aged adults, male sex, work environment, heavy metals and agrochemicals exposure, occupational heat stress, nephrotoxic drug use, and low socioeconomic status. The diagnosis is confirmed by renal biopsy with chronic tubular atrophy and tubulointerstitial nephritis. If biopsies are unavailable, MeN is clinically suspected in patients residing in hotspot regions with a reduced estimated glomerular filtration rate (eGFR) and the absence of defining etiology, such as hypertension, diabetes, or glomerulonephritis. Currently, there is no specific treatment for which early diagnosis and intervention on risk factors is the primary strategy to improve prognosis. We report a case of a young male with agricultural labor exposure who presented with acute abdominal pain, back pain, and renal dysfunction that later progressed to chronic kidney disease (CKD) due to MeN. This case is significant because, although MeN is well-described in the literature, few cases of acute presentation have been documented.

Vaccination and mortality from COVID-19: a comparative study between hemodialysis, peritoneal dialysis, and non-dialysis adult population in Panama.

PURPOSE: Dialysis patients have a different response than the non-dialysis population to infection with COVID-19. This study evaluates the prevalence of infection and lethality in patients receiving hemodialysis or peritoneal dialysis in Panama, compared to non-dialysis adult population, and reports of adverse events of vaccination. METHODS: This is a prospective, multi-center cohort study of spatients aged 18 years or older and receiving in-center hemodialysis or ambulatory peritoneal dialysis in 13 centers in Panama from March 2021 to 2022. For comparison with general population, the study used an extended period of two years. RESULTS: A total of 1531 patients receiving dialysis treatment accepted to participate. PD patients represented an 18% of study patients. Lethality was higher in peritoneal dialysis patients with COVID-19 infection than in hemodialysis in the study group (p 0.02). Total deaths in dialysis patients for 2020 were 156 patients, before vaccination; 79 in 2021; and 25 for the first trimester of 2022. Lethality for the period of 2020-2022 was 9.3% for dialysis patients and 0.2% for non-dialysis population. There was no difference in symptoms in first dose, but with second dose, hemodialysis patients reported fewer symptoms than peritoneal dialysis patients (p < 0.0001). CONCLUSION: Ninety one percent of people in the country received BNT162b2 Pfizer BionTech vaccine. Lethality decreased from 30 to 5% once vaccination was available. There were no severe adverse effects and symptoms reported were less frequent than in general population, probably due to low reactogenicity in dialysis patients, or better tolerance to pain.

Overcoming obstacles in Panama to starting a renal biopsy program in a rural area during the COVID-19 pandemic.

Due to the many implemented restrictions, the SARS-CoV-2 pandemic has rendered some tasks more difficult, for instance, the evaluation of outpatients. Panama's tertiary care hospital for kidney biopsy referral was transformed into a COVID-only hospital in order to assist the large number of COVID-19 patients. In order to face the impossibility of following patients with nephrotic or nephritic syndrome, a biopsy program was implemented in a southern province in Panama. Thirty kidney biopsies were carried out over a 1-year period. This experience shows that kidney biopsy programs, that are usually run only in large referral centers, can also be implemented in small nephrology centers, allowing to obtain accurate diagnoses and to guide correct treatment.

Chronic kidney disease of nontraditional causes in central Panama.

BACKGROUND: Over the last three decades, the mesoamerican region has seen an increase in the frequency of patients diagnosed with Chronic Kidney Disease of nontraditional causes (CKDnt) also known as Meso-American Nephropathy (MeN). A region with an increased frequency of patients with Chronic Kidney Disease (CKD) has been identified in central Panama. The present study aims to characterize the clinical presentation of patients with CKDnt in an understudied population of the central region of Panama and to compare them with patients with traditional chronic kidney disease (CKDt). METHODS: A retrospective descriptive study was conducted in a nephrology reference hospital in the central provinces of Herrera and Los Santos, comparing a group of 15 patients with CKDnt to 91 patients with CKDt. Sociodemographic variables, personal history, laboratory parameters, and of renal ultrasound were compared. RESULTS: Patients with CKDnt had a median age of 58 years (IQR: 52-61), significantly lower (P < 0.001) than patients with CKDt with a median age of 71 years (IQR: 64-78). Patients with CKDnt had a history of being agricultural (60%) and transportation (20%) workers, significantly higher than patients with CKDt (15%, P < 0.001 and 0%, P < 0.01 respectively). Renal atrophy and hyperuricemia are significant clinical markers of CKDnt (P < 0.001 and P < 0.05 respectively). CONCLUSION: To our knowledge, this is the first study in Panama to investigate the clinical presentation of patients with CKDnt and one of the few in Central America and the world that compares them with patients with CKDt. In central Panama the typical CKDnt patient is a male in his 50 s who is primarily engaged in agriculture or as a public transport driver. Renal atrophy and hyperuricemia are significant clinical markers of CKDnt. Further studies are needed to help understand the common determinants and risk factors for CKDnt development in Panama and Mesoamerica.

Diagnostic evaluation and assessment of anemia in a patient with chronic kidney disease and gastrointestinal angioectasias undergoing hemodialysis.

Anemia in patients with chronic kidney disease may have underlying causes that require a broad approach. Here, we present a clinical case of anemia in a patient with chronic kidney disease and gastrointestinal angioectasias undergoing hemodialysis.

Infección por COVID-19 en pacientes en Hemodiálisis en Panamá 2020

Antecedentes y objetivo: Los pacientes con Enfermedad Renal Crónica (ERC) en Hemodiálisis son pacientes que tienen condiciones que los hacen pacientes de riesgo para la infección por COVID-19. Los pacientes en hemodiálisis han sido un grupo muy afectado, debido a que no pueden suspender sus tratamientos para mantener el aislamiento domiciliario, lo que aumenta su exposición y riesgo a infección por COVID-19. Para evaluar el comportamiento de la infección por SARS-CoV-2 en los pacientes en hemodiálisis crónica en Panamá, realizamos un estudio prospectivo de los pacientes infectados por COVID-19 en las Unidades de Hemodiálisis de la CSS de todo el país, para determinar las características de los pacientes afectados, los síntomas que presentaron, su evolución clínica y el desenlace de los pacientes infectados. Materiales y Médodos: Realizamos un estudio longitudinal descriptivo prospectivo multicéntrico de los casos positivos que se diagnosticaron desde el 15 de julio hasta el 31 de diciembre de 2020 en las 14 Unidades de Hemodiálisis de la CSS del país.  Resultados y conclusiones: Fueron incluidos un total de 333 pacientes en hemodiálisis con diagnóstico positivo para  infección  por SARS-CoV-2, de un total de 2194 pacientes que realizan hemodiálisis en las Unidades de la Caja de Seguro Social.  El 59.5% de los afectados fueron de sexo masculino.  La edad promedio fue de 56.75 años (DS 15.1 años).  La Tasa de Mortalidad encontrada en nuestro estudio fue de 26%. La incidencia acumulada de COVID-19 en pacientes en Hemodiálisis fue de 16% para el período de estudio del 2020. (provisto por Infomedic International)

Background and objective: Patients with Chronic Kidney Disease (CKD) on Hemodialysis are patients who have conditions that make them patients at risk for COVID-19 infection. Hemodialysis patients have been a highly affected group because they cannot stop their treatments to maintain home isolation, which increases their exposure and risk of COVID-19 infection. To evaluate the behavior of SARS-CoV-2 infection in patients on chronic hemodialysis in Panama, we conducted a prospective study of patients infected by COVID-19 in hemodialysis units throughout the country, to determine the characteristics of the affected patients, the symptoms they presented, their clinical evolution and the outcome of the infected patients. Materials and Methods: We conducted a multicenter prospective descriptive longitudinal study of the positive cases that were diagnosed from July 15, 2020 to December 31, 2020 in the 14 Hemodialysis Units of the Social Security Fund of the country. Results and conclusions: A total of 333 hemodialysis patients with a positive diagnosis for SARS-CoV-2 infection were included, out of a total of 2194 patients undergoing hemodialysis in the Units of the Social Security Fund. Fifty nine percet of those affected were male.  The mean age was 56.75 years (DS 15.1 years).  The Mortality Rate found in our study was 26%. The cumulative incidence of COVID-19 in hemodialysis patients was 16% for the 2020 study period. (provided by Infomedic International)

Síndrome de Alport: una actualización en fisiopatología, genética, diagnóstico y tratamiento / Alportsyndrome: anupdate in pathophysiology, genetics, diagnosis, and treatment

RESUMEN El síndrome de Alport es una enfermedad renal hereditaria de curso progresivo, que ocurre por defectos genéticos en los genes responsables de la constitución de la membrana basal glomerular. Las mutacionespatogénicas en los genes para el colágeno tipo IV (COL 4A3/4/5) producen una alteración en el arreglo correcto de la membrana basal a nivel glomerular.La presentación clínica puede variar dependiendo de la mutación que presente el paciente. Luego de confirmar el diagnóstico,con estudios genéticoso mediante biopsia, se hace necesaria la correlación genotipo-fenotipo para determinar pronóstico y tratamiento. La reducción de la proteinuria, según sugieren las guías de manejo, ha resultado en un retraso en la progresión a enfermedad renal crónica, mientras se concluyen los estudios con medicamentos innovadores dirigidos a receptores específicos.

ABSTRACT Alportsyndromeis a renal hereditarydisease of progressivecourse, causedby geneticdefects in the genes responsible for the constitution of the glomerular basementmembrane. Mutation in genes fortype IV collagen occurs at COL 4A3/4/5, whichproducesinterference in thecorrectmembranearrangement. Clinicalpresentationmayvarydependingonmutationtype. Afterconfirming diagnosis, withgenetic studiesorbiopsies, managementincludesidentification of risk and treatment. Reduction of proteinuria, as managementguidelinessuggest, has resulted in delay in progressiontochronickidneydisease. In themeantime, studiesfor new treatmentdevelopments are in progress, directedtospecificreceptors.

Proceso de desensibilización ANTI-HLA en receptores de donante vivo HLA Clase II incompatible con anticuerpos donante específico

Introducción: El trasplante renal es la opción terapéutica que ofrece la mejor expectativa de vida en los pacientes con enfermedad renal crónica. Muchos pacientes sensibilizados permanecen largo tiempo en lista de espera, aumentando su morbi-mortalidad en diálisis. Objetivos: evaluar el uso de terapia de desensibilización en pacientes con anticuerpos anti HLA Clase II contra su donante vivo relacionado, identificar factores de riesgo temprano de requerimiento de biopsia renal por sospecha de rechazo y evaluar los costos relacionados. Resultados: Realizamos valoración de terapia de desensibilización a 3 pacientes, con una disminución en los valores de anticuerpos donante específico a menos de 1000 de MFI, con un índice de RIS bajo, por lo que se procedió con el trasplante, sin complicaciones inmediatas y con un seguimiento a 18 meses sin deterioro de función renal. Conclusiones: La desensibilización previa a trasplante renal permite disminuir el título de anticuerpos donantes específicos preformados y llevar a cabo el trasplante renal, con una buena evolución del paciente y del injerto superior a permanecer en diálisis. (provisto por Infomedic International)

Global Cardiovascular and Renal Outcomes of Reduced GFR.

The burden of premature death and health loss from ESRD is well described. Less is known regarding the burden of cardiovascular disease attributable to reduced GFR. We estimated the prevalence of reduced GFR categories 3, 4, and 5 (not on RRT) for 188 countries at six time points from 1990 to 2013. Relative risks of cardiovascular outcomes by three categories of reduced GFR were calculated by pooled random effects meta-analysis. Results are presented as deaths for outcomes of cardiovascular disease and ESRD and as disability-adjusted life years for outcomes of cardiovascular disease, GFR categories 3, 4, and 5, and ESRD. In 2013, reduced GFR was associated with 4% of deaths worldwide, or 2.2 million deaths (95% uncertainty interval [95% UI], 2.0 to 2.4 million). More than half of these attributable deaths were cardiovascular deaths (1.2 million; 95% UI, 1.1 to 1.4 million), whereas 0.96 million (95% UI, 0.81 to 1.0 million) were ESRD-related deaths. Compared with metabolic risk factors, reduced GFR ranked below high systolic BP, high body mass index, and high fasting plasma glucose, and similarly with high total cholesterol as a risk factor for disability-adjusted life years in both developed and developing world regions. In conclusion, by 2013, cardiovascular deaths attributed to reduced GFR outnumbered ESRD deaths throughout the world. Studies are needed to evaluate the benefit of early detection of CKD and treatment to decrease these deaths.

Paricalcitol for secondary hyperparathyroidism in renal transplantation.

Secondary hyperparathyroidism contributes to post-transplant CKD mineral and bone disorder. Paricalcitol, a selective vitamin D receptor activator, decreased serum parathyroid hormone levels and proteinuria in patients with secondary hyperparathyroidism. This single-center, prospective, randomized, crossover, open-label study compared the effect of 6-month treatment with paricalcitol (1 µg/d for 3 months and then uptitrated to 2 µg/d if tolerated) or nonparicalcitol therapy on serum parathyroid hormone levels (primary outcome), mineral metabolism, and proteinuria in 43 consenting recipients of renal transplants with secondary hyperparathyroidism. Participants were randomized 1:1 according to a computer-generated sequence. Compared with baseline, median (interquartile range) serum parathyroid hormone levels significantly declined on paricalcitol from 115.6 (94.8-152.0) to 63.3 (52.0-79.7) pg/ml (P<0.001) but not on nonparicalcitol therapy. At 6 months, levels significantly differed between treatments (P<0.001 by analysis of covariance). Serum bone-specific alkaline phosphatase and osteocalcin decreased on paricalcitol therapy only and significantly differed between treatments at 6 months (P<0.001 for all comparisons). At 6 months, urinary deoxypyridinoline-to-creatinine ratio and 24-hour proteinuria level decreased only on paricalcitol (P<0.05). L3 and L4 vertebral mineral bone density, assessed by dual-energy x-ray absorption, significantly improved with paricalcitol at 6 months (P<0.05 for both densities). Paricalcitol was well tolerated. Overall, 6-month paricalcitol supplementation reduced parathyroid hormone levels and proteinuria, attenuated bone remodeling and mineral loss, and reduced eGFR in renal transplant recipients with secondary hyperparathyroidism. Long-term studies are needed to monitor directly measured GFR, ensure that the bone remodeling and mineral effects are sustained, and determine if the reduction in proteinuria improves renal and cardiovascular outcomes.

Global, regional, and national prevalence of overweight and obesity in children and adults during 1980-2013: a systematic analysis for the Global Burden of Disease Study 2013.

BACKGROUND: In 2010, overweight and obesity were estimated to cause 3·4 million deaths, 3·9% of years of life lost, and 3·8% of disability-adjusted life-years (DALYs) worldwide. The rise in obesity has led to widespread calls for regular monitoring of changes in overweight and obesity prevalence in all populations. Comparable, up-to-date information about levels and trends is essential to quantify population health effects and to prompt decision makers to prioritise action. We estimate the global, regional, and national prevalence of overweight and obesity in children and adults during 1980-2013. METHODS: We systematically identified surveys, reports, and published studies (n=1769) that included data for height and weight, both through physical measurements and self-reports. We used mixed effects linear regression to correct for bias in self-reports. We obtained data for prevalence of obesity and overweight by age, sex, country, and year (n=19,244) with a spatiotemporal Gaussian process regression model to estimate prevalence with 95% uncertainty intervals (UIs). FINDINGS: Worldwide, the proportion of adults with a body-mass index (BMI) of 25 kg/m(2) or greater increased between 1980 and 2013 from 28·8% (95% UI 28·4-29·3) to 36·9% (36·3-37·4) in men, and from 29·8% (29·3-30·2) to 38·0% (37·5-38·5) in women. Prevalence has increased substantially in children and adolescents in developed countries; 23·8% (22·9-24·7) of boys and 22·6% (21·7-23·6) of girls were overweight or obese in 2013. The prevalence of overweight and obesity has also increased in children and adolescents in developing countries, from 8·1% (7·7-8·6) to 12·9% (12·3-13·5) in 2013 for boys and from 8·4% (8·1-8·8) to 13·4% (13·0-13·9) in girls. In adults, estimated prevalence of obesity exceeded 50% in men in Tonga and in women in Kuwait, Kiribati, Federated States of Micronesia, Libya, Qatar, Tonga, and Samoa. Since 2006, the increase in adult obesity in developed countries has slowed down. INTERPRETATION: Because of the established health risks and substantial increases in prevalence, obesity has become a major global health challenge. Not only is obesity increasing, but no national success stories have been reported in the past 33 years. Urgent global action and leadership is needed to help countries to more effectively intervene. FUNDING: Bill & Melinda Gates Foundation.