Accesibilidad, disponibilidad y asequibilidad de medicamentos para Niños con Enfermedad Renal Crónica en Guatemala / Access, availability and affordability of medications for children with Advanced Chronic Kidney Disease in Guatemala

El artículo tiene como objetivo analizar la disponibilidad, acceso y asequibilidad de los medicamentos para niños con Enfermedad Renal Crónica (ERC) en tratamiento con hemodiálisis (HD) en un país de bajos a medianos ingresos. Se llevó a cabo un estudio transversal para determinar los medicamentos más utilizados en una unidad de hemodiálisis pediátrica, incluyendo el nombre del medicamento, dosis, frecuencia, forma farmacéutica y vía de administración. Dos farmacias dentro del perímetro del hospital, una pública y una privada, fueron consultadas para determinar el costoy disponibilidad de medicamentos genéricos y de marca. De un total de 30 pacientes de la unidad de hemodiálisis, 22 expedientes fueron revisados. En general 94% de marca se encontraban disponibles en las farmacias consultadas en comparación a un 52% de los medicamentos genéricos. En farmacias públicas, 41% de medicamentos de marca y 29% de medicamentos genéricos se encontraban disponibles. El costo promedio para un mes de tratamiento con medicamentos de marca adquiridos en una farmacia privada era de $495.00 vs $299.00 en una farmacia pública. Para medicamentos genéricos, el costo promedio correspondía a $414.00 y $239.00 en farmacias privadas y públicas respectivamente. En promedio, los medicamentos de marca adquiridos en una farmacia privada requieren 41 días de trabajo en un mes a comparación de 25 días si se adquieren en una farmacia pública. Los medicamentos genéricos adquiridos en farmacias privadas corresponden a 34 días de trabajo vs 20 días en farmacias públicas. En general existió un acceso limitado a medicamentos genéricos y los medicamentos poseen un costo general más elevado a comparación de otros países lo que implica un posible impacto en la adherencia terapéutica y los padecimientos secundarios de la ERC en los pacientes pediátricos en Guatemala. Esta realidad se puede aplicar a otros países de bajos a medianos ingresos.

This article aims to analyze the availability, access, and affordability of medications for children with advanced Chronic Kidney Disease (CKD) treated with hemodialysis (HD) in a low to middle income country (LMIC). A cross- sectional chart review was carried out to determine the most common medications used in an HD pediatric unit, including medication name, dose, frequency, dosage form, and route of administration. Two pharmacies within the hospital perimeter, one public and one private, were consulted to determine medication cost and availability for generic and brand-name equivalents. From 30 patients attending the HD unit, 22 records were reviewed. Overall, 94 % of brand name medications were available at pharmacies consulted, versus and 52% of generic medications. In public pharmacies, 41% of brand name, and 29% of generic medications were available. The average cost for a full month´s treatment for brand name drugs in the private pharmacy was 495.00 USD versus 299.00 USD in the public pharmacy. For generic drugs, the average cost was 414.00 USD, and 239.00 USD in private and public pharmacies respectively. On average, brand-name drugs in the private pharmacy cost 41 days' wages versus 25 in the public pharmacy. Generic drugs in the private pharmacy cost 34 days' wages versus 20 in the public pharmacy. Overall, there was limited access to generic medications, medications had an overall high cost compared to other countries both of which have the potential to impact treatment adherence and overall outcomes of CKD5 pediatric patients in Guatemala. This reality can be translated to other LMIC.

Addressing Health Inequities and Disparities in Children With Kidney Disease in Disadvantaged Areas: the Latin American and Caribbean Experience.

Purpose of Review: Compared with high-income countries, healthcare disparities and inequities are more evident in low, lower-middle, and upper-middle-income countries with poorer housing and nutrition conditions. At least 20% of Latin America and the Caribbean are low and lower-middle-income countries. Despite the majority of the other countries being upper-middle income, the United Nations Children's Fund had classified all the regions as "less developed," with limited access to health care for the most vulnerable, the children. Latin America and the Caribbean regions represent an extensive territory with communication limitations and an unstable socio-political and economic environment. After considering the vast population affected by poverty worldwide and the long-term impact of kidney disease starting in childhood, it is crucial to better understand and analyze the multifactorial limiting conditions in accessing specialized care such as pediatric nephrology in disadvantaged areas. Recent Findings: Constraints in accessing basic healthcare in rural areas make it impossible to receive specialized pediatric nephrology care including dialysis and transplantation. Disturbingly, incidence and prevalence figures of acute kidney injury, chronic and end-stage kidney disease in some Latin American and the Caribbean countries are unknown, and these conditions still represent a death sentence for underprivileged populations. However, the monumental efforts of the dedicated healthcare providers and stakeholders that pioneered the actions in the past 50 years have shown remarkable progress in developing pediatric nephology services across the continent. Summary: In this review, we compile some of the latest evidence about the care of children and adolescents with kidney conditions in Latin America and the Caribbean, along with the experiences from the field in the care of these patients facing adverse conditions. We also highlight recommendations to address inequities and disparities.

IPNA clinical practice recommendations for the diagnosis and management of children with steroid-sensitive nephrotic syndrome.

Idiopathic nephrotic syndrome is the most frequent pediatric glomerular disease, affecting from 1.15 to 16.9 per 100,000 children per year globally. It is characterized by massive proteinuria, hypoalbuminemia, and/or concomitant edema. Approximately 85-90% of patients attain complete remission of proteinuria within 4-6 weeks of treatment with glucocorticoids, and therefore, have steroid-sensitive nephrotic syndrome (SSNS). Among those patients who are steroid sensitive, 70-80% will have at least one relapse during follow-up, and up to 50% of these patients will experience frequent relapses or become dependent on glucocorticoids to maintain remission. The dose and duration of steroid treatment to prolong time between relapses remains a subject of much debate, and patients continue to experience a high prevalence of steroid-related morbidity. Various steroid-sparing immunosuppressive drugs have been used in clinical practice; however, there is marked practice variation in the selection of these drugs and timing of their introduction during the course of the disease. Therefore, international evidence-based clinical practice recommendations (CPRs) are needed to guide clinical practice and reduce practice variation. The International Pediatric Nephrology Association (IPNA) convened a team of experts including pediatric nephrologists, an adult nephrologist, and a patient representative to develop comprehensive CPRs on the diagnosis and management of SSNS in children. After performing a systematic literature review on 12 clinically relevant PICO (Patient or Population covered, Intervention, Comparator, Outcome) questions, recommendations were formulated and formally graded at several virtual consensus meetings. New definitions for treatment outcomes to help guide change of therapy and recommendations for important research questions are given.

Effects of Prematurity and Growth Restriction on Adult Blood Pressure and Kidney Volume.

Gaining insight into the complex cycle of renal programming and its early-life clinical associations is essential to understand the origins of kidney disease. Prematurity and intrauterine growth restriction are associated with low nephron endowment. This increases the risk of developing hypertension and chronic kidney disease later in life. There is appreciable evidence to support mechanistic links between low nephron endowment secondary to intrauterine events and kidney size, kidney function, and blood pressure in postnatal life. A clear understanding of the cycle of developmental programming and consequences of fetal insults on the kidney is critical. In addition, the impact of events in the early postnatal period (accelerated postnatal growth, development of obesity, exposure to nephrotoxins) on the cardiovascular system and blood pressure of individuals born prematurely or with low birth weight is discussed. In summary, this review draws attention to the concepts of renal programming and nephron endowment and underscores the associations between intrauterine growth restriction, prematurity, and its clinical consequences in adult life.

PCRRT-ICONIC critical care pediatric nephrology course: the global prevalence of COVID-19 and associated sequelae.

After nearly three years of the COVID-19 pandemic, research has affirmed that COVID-19 is more than just a respiratory virus. There have been significant breakthroughs made surrounding the development of acute kidney injury (AKI) and chronic kidney disease (CKD), in pediatric populations. Additionally, patient populations susceptible to renal complications consist of pediatric transplant recipients, multisystem inflammatory syndrome (MIS-C), and dialysis. Although research is gradually becoming more available surrounding this prevalent topic, knowledge is sparse on the deleterious effects of COVID-19 on pediatric patients with kidney disease and requires more in-depth analysis. The virtual international conference, Pediatric Critical Care Nephrology & Dialysis Course, on August 7th, 2021, reviewed the severe cases of COVID-19 in the global pediatric population. By integrating international perspectives, statistics, techniques, and treatments for managing renal complications, we further develop scientific understanding of the renal complications seen in children with COVID-19 globally.

Paediatric nephrology in under-resourced areas.

BACKGROUND: Nearly 50% of the world population and 60% of children aged 0 to 14 years live in low- or lower-middle-income countries. Paediatric nephrology (PN) in these countries is not a priority for allocation of limited health resources. This article explores advancements made and persisting limitations in providing optimal PN services to children in such under-resourced areas (URA). METHODS: Medline, PubMed and Google Scholar online databases were searched for articles pertaining to PN disease epidemiology, outcome, availability of services and infrastructure in URA. The ISN and IPNA offices were contacted for data, and two online questionnaire surveys of IPNA membership performed. Regional IPNA members were contacted for further detailed information. RESULTS: There is a scarcity of published data from URA; where available, prevalence of PN diseases, managements and outcomes are often reported to be different from high income regions. Deficiencies in human resources, fluoroscopy, nuclear imaging, immunofluorescence, electron microscopy and genetic studies were identified. Several drugs and maintenance kidney replacement therapy are inaccessible to the majority of patients. Despite these issues, regional efforts with support from international bodies have led to significant advances in PN services and infrastructure in many URA. CONCLUSIONS: Equitable distribution and affordability of PN services remain major challenges in URA. The drive towards acquisition of regional data, advocacy to local government and non-government agencies and partnership with international support bodies needs to be continued. The aim is to optimise and achieve global parity in PN training, investigations and treatments, initially focusing on preventable and reversible conditions.

Mesoamerican Endemic Nephropathy (MeN): A Disease Reported in Adults That May Start Since Childhood?

Mesoamerican endemic nephropathy (MeN) is a type of chronic kidney disease (CKD) of uncertain etiology that occurs along the Pacific coast of the southern part of Mexico and Central America. During the past 20 years MeN has become a leading cause of death in the region, clamming close to 50,000 lives, with 40% of these deaths occurring in young people. The cause remains unknown, but most researchers believe in a multifactorial etiology that includes social determinants of poverty. Existing evidence suggests that subclinical kidney injury begins early in life and leads to a higher than expected prevalence of CKD among children in Central America. Access to health services in the region, specifically kidney replacement therapy, remains limited. We proposed a strategy to address the perceived needs and urge coordinated efforts of governments, academic organizations, and international bodies to develop a comprehensive plan of action to mitigate this situation among the vulnerable and economically disadvantaged population.

Mortalidad hospitalaria por disfunción ventricular derecha diagnosticada por ecocardiografía en pacientes con sepsis y shock séptico, atendidos de mayo a agosto de 2022, hospital militar central / Hospital mortality due to right ventricular dysfunction diagnosed by echocardiography in patients with sepsis and septic shock, seen from May to August 2022, central military hospital

Los pacientes con sepsis y shock séptico presentan una alta mortalidad, representan un importante problema de salud; en estos pacientes, la incidencia de depresión miocárdica es conocida y ha sido documentada. La presente investigación encuentra la mortalidad asociada a la disfunción ventricular derecha, diagnosticada por ecocardiografía transtorácica al pie de cama, que se presenta o desarrolla secundaria a sepsis y su relación con la mortalidad, destacando la utilidad diagnóstica de esta técnica de imagen a través de la evaluación de parámetros ecocardiográficos medíbles y de fácil para cuantificar al lado de la cama del paciente. Metodología: fue un estudio observacional prospectivo analítico de cohorte única, en el Hospital Militar Central, San Salvador, El Salvador, diseñado para incluir pacientes atendidos o ingresados al servicio de medicina interna y cuidados intensivos en un periodo de 4 meses durante el año 2022, que cumplan con los criterios de sepsis y shock séptico, según sepsis-3 utilizando el ecocardiograma transtorácico. Se realizo el ecocardiograma como técnica para evaluar la función del ventrículo derecho (VD) en dos momentos, en las primeras 48 horas y el día 4 desde el diagnóstico de sepsis o shock séptico, definimos disfunción ventricular derecha (DVD) según el tipo: disfunción sistólica VD: TAPSE <1,6 cm, disfunción diastólica VD: cociente E/A <0,8 >2, se cuantificó el balance hídrico acumulado hasta el día 4. Se dio seguimiento a cada paciente para registrar muerte o egreso hospitalario en condición de vivo, relacionando estos desenlaces con disfunción ventricular derecha y balance hídrico. Análisis y resultados: La mortalidad se expreso mediante la razón proporcional de mortalidad intrahospitalaria asociada a DVD, se registró en 46,15%, RR: 1,81, la mortalidad fue mayor en quienes presentaron disfunción diastólica del ventrículo derecho. Interpretación: La disfunción del ventrículo derecho de cualquier tipo o global y el balance de líquidos mayor a 1 litro, se asoció directamente con una mayor mortalidad intrahospitalaria.

Patients with sepsis and septic shock carry high mortality even today, which is why it represents an important health problem; In these patients, the incidence of myocardial depression is known and has been documented. Research: to know the associated mortality with right ventricular dysfunction, diagnosed by transthoracic echocardiography at the bedside, which presents or develops secondary to sepsis and its relationship with mortality, highlighting the diagnostic utility of this imaging technique through the evaluation of measurable echocardiographic parameters and easy to quantify at the patient's bedside. Study Design and Methods: The Study is Observational Prospective Analytical Single Cohort, Monocentric (Hospital Militar Central, San Salvador, El Salvador). designed to include a cohort treated or admitted to the internal medicine and intensive care service in a period of 4 months during the year 2022, who meet the criteria for sepsis and septic shock, according to sepsis-3, a transthoracic echocardiogram was used as a research technique for those who had their right ventricular(RV) function evaluated in two moments, the first 48 hours and on day 4 from the diagnosis of sepsis or septic shock, to To document the presence or absence of an exposure factor: Right Ventricular Dysfunction (DVD) of any type, we defined RV Systolic Dysfunction: TAPSE <1.6 cm, RV Diastolic Dysfunction: E/A ratio <0.8 >2, and the accumulated fluid balance was quantified up to the day 4. Consecutively, each patient was followed up to record in-hospital death or Discharge in Living Condition, relating these outcomes with Right ventricular dysfunction and fluid balance. Results: The proportional ratio of Intrahospital Mortality due to DVD was recorded at 46.15%, RR: 1.81, Mortality was higher in those who presented diastolic dysfunction of the Right Ventricle. Interpretation: Right ventricular dysfunction of any type or global together with fluid balance greater than 1 liter, was directly associated with increased in-hospital mortality.

Importance of clinical practice guidelines to practicing pediatric nephrologists and IPNA survey.

Clinical practice guidelines (CPGs) are systematically developed statements backed by scientific evidence to assist practitioners in management in clinical practice. An international cross-sectional survey was conducted by the IPNA to examine the perceptions of pediatric nephrologists on guidelines and their usage and to identify important diseases for future clinical practice guidelines (CPGs). The survey found that the majority of pediatric nephrologists find CPGs useful in clinical practice and admitted to using them most of the time. Developing CPGs is challenging and there are standards available to develop trustworthy guidelines. While evidence-based global guidelines are ideal, pediatric nephrologists expressed the desire that they address regional differences. Most respondents (89.2%) to the survey agreed that adult guidelines did not cover the pediatric perspective adequately and 71.4% opined that consensus-based pediatric guidelines can be developed when evidence for the pediatric population is lacking. The development of high-quality practice guidelines requires substantial resources and may not be feasible in resource-poor countries. Adaptation of an existing guideline has been suggested as an alternative and the ADAPTE collaboration provides a systematic approach to adapting guidelines. Several diseases where pediatric guidelines are needed as a priority including IgA and C3 glomerulopathy were identified in the survey. Implementation of guideline-based care is challenging and the survey found that lack of availability of guidelines (43%) and resources (22.8%) are important reasons for poor implementation in lower-middle and low-income countries. Perceived complexity of guidelines, physician attitudes, and lack of training also contribute to non-adherence to guidelines.

Disaster Management in a Nephrology Service: Lessons Learned from Hurricane Maria.

BACKGROUND: Puerto Rico suffered a major humanitarian -crisis after Hurricane Maria. We describe our experience with patients with renal disease in an academic medical center. SUMMARY: A comprehensive emergency response plan should be developed, shared and discussed with the team and the patients prior to the hurricane. The needs of the staff should not be ignored to ensure their ability to participate as responders. Physical damage to facilities, lack of basic services, shortage of disposable products, and the inability to get to treatment centers are the most common threats. Preemptive dialysis can avoid serious complications. A contingency plan to move patients to another center should be prearranged in case the unit is rendered nonfunctional after the storm. Patients must receive preventive education about fluid and dietary restrictions and the possible use of potassium binding drugs if they cannot reach a dialysis unit. A list of alternative drugs that could be used if patients are not able to fill their medications is required. The Internet and social media proved to be an invaluable communication tool. A registry of patients with updated contact information, as well as contact information for relatives and a physical address where an emergency rescue team can be dispatched is essential. Water safety should be reinforced. Key Message: Our experience showed us that preparing for the worst is not enough. Advanced planning of a streamlined response is the best tactic to decrease harm.

Endothelial cell activation on 3D-matrices derived from PDGF-BB-stimulated fibroblasts is mediated by Snail1.

Carcinomas, such as colon cancer, initiate their invasion by rescuing the innate plasticity of both epithelial cells and stromal cells. Although Snail is a transcriptional factor involved in the Epithelial-Mesenchymal Transition, in recent years, many studies have also identified the major role of Snail in the activation of Cancer-Associated Fibroblast (CAF) cells and the remodeling of the extracellular matrix. In CAFs, Platelet-derived growth factor (PDGF) receptor signaling is a major functional determinant. High expression of both SNAI1 and PDGF receptors is associated with poor prognosis in cancer patients, but the mechanism(s) that underlie these connections are not understood. In this study, we demonstrate that PDGF-activated fibroblasts stimulate extracellular matrix (ECM) fiber remodeling and deposition. Furthermore, we describe how SNAI1, through the FAK pathway, is a necessary factor for ECM fiber organization. The parallel-oriented fibers are used by endothelial cells as "tracks", facilitating their activation and the creation of tubular structures mimicking in vivo capillary formation. Accordingly, Snail1 expression in fibroblasts was required for the co-adjuvant effect of these cells on matrix remodeling and neoangiogenesis when co-xenografted in nude mice. Finally, in tumor samples from colorectal cancer patients a direct association between stromal SNAI1 expression and the endothelial marker CD34 was observed. In summary, our results advance the understanding of PDGF/SNAI1-activated CAFs in matrix remodeling and angiogenesis stimulation.

Differential distribution and enrichment of non-coding RNAs in exosomes from normal and Cancer-associated fibroblasts in colorectal cancer.

Exosome production from cancer-associated fibroblasts seems to be an important driver of tumor progression. We report the first in-depth biotype characterization of ncRNAs, analyzed by Next Generation Sequencing and Bioinformatics, expressed in established primary human normal and cancer-associated fibroblasts (CAFs) from cancer and normal mucosa tissues from 9 colorectal cancer patients, and/or packaged in their derived exosomes. Differential representation and enrichment analyses based on these ncRNAs revealed a significant number of differences between the ncRNA content of exosomes and the expression patterns of the normal and cancer-associated fibroblast cells. ncRNA regulatory elements are specifically packaged in CAF-derived exosomes, supporting a specific cross-talk between CAFs and colon cancer cells and/or other stromal cells, mediated by exosomes. These sncRNAs are potential biomarkers present in cancer-associated fibroblast-derived exosomes, which should thereby contribute to developing new non-invasive diagnostic, prognostic and predictive methods for clinical applications in management of cancer patients.

Loss of 5hmC identifies a new type of aberrant DNA hypermethylation in glioma.

Aberrant DNA hypermethylation is a hallmark of cancer although the underlying molecular mechanisms are still poorly understood. To study the possible role of 5-hydroxymethylcytosine (5hmC) in this process we analyzed the global and locus-specific genome-wide levels of 5hmC and 5-methylcytosine (5mC) in human primary samples from 12 non-tumoral brains and 53 gliomas. We found that the levels of 5hmC identified in non-tumoral samples were significantly reduced in gliomas. Strikingly, hypo-hydroxymethylation at 4627 (9.3%) CpG sites was associated with aberrant DNA hypermethylation and was strongly enriched in CpG island shores. The DNA regions containing these CpG sites were enriched in H3K4me2 and presented a different genuine chromatin signature to that characteristic of the genes classically aberrantly hypermethylated in cancer. As this 5mC gain is inversely correlated with loss of 5hmC and has not been identified with classical sodium bisulfite-based technologies, we conclude that our data identifies a novel 5hmC-dependent type of aberrant DNA hypermethylation in glioma.

Potassium regulation in the neonate.

Potassium, the major cation in intracelluar fluids, is essential for vital biological functions. Neonates maintain a net positive potassium balance, which is fundamental to ensure somatic growth but places these infants, especially those born prematurely, at risk for life-threatening disturbances in potassium concentration [K+] in the extracellular fluid compartment. Potassium conservation is achieved by maximizing gastrointestinal absorption and minimizing renal losses. A markedly low glomerular filtration rate, plus adaptations in tubular transport along the nephron, result in low potassium excretion in the urine of neonates. Careful evaluation of clinical data using reference values that are normal for the neonate's postmenstrual age is critical to avoid over-treating infants with laboratory results that represent physiologic values for their developmental stage. The treatment should be aimed at correcting the primary cause when possible. Alterations in the levels or sensitivity to aldosterone are common in neonates. In symptomatic patients, the disturbances in [K+] should be corrected promptly, with close electrocardiographic monitoring. Plasma [K+] should be monitored during the first 72 h of life in all premature infants born before 30 weeks of postmenstrual age as these infants are prone to develop non-oliguric hyperkalemia with potential serious complications.

Snail1-Dependent Activation of Cancer-Associated Fibroblast Controls Epithelial Tumor Cell Invasion and Metastasis.

Snail1 transcriptional factor is essential for triggering epithelial-to-mesenchymal transition (EMT) and inducing tumor cell invasion. We report here an EMT-independent action of Snail1 on tumor invasion, as it is required for the activation of cancer-associated fibroblasts (CAF). Snail1 expression in fibroblasts requires signals derived from tumor cells, such as TGFß; reciprocally, in fibroblasts, Snail1 organizes a complex program that stimulates invasion of epithelial cells independent of the expression of Snail1 in these cells. Epithelial cell invasion is stimulated by the secretion by fibroblast of diffusible signaling molecules, such as prostaglandin E2 The capability of human or murine CAFs to promote tumor invasion is dependent on Snail1 expression. Inducible Snail1 depletion in mice decreases the invasion of breast tumors; moreover, epithelial tumor cells coxenografted with Snail1-depleted fibroblasts originated tumors with lower invasion than those transplanted with control fibroblasts. Therefore, these results demonstrate that the role of Snail1 in tumor invasion is not limited to EMT, but it is also dependent on its activity in stromal fibroblasts, where it orchestrates the cross-talk with epithelial tumor cells. Cancer Res; 76(21); 6205-17. ©2016 AACR.

Exosomes enriched in stemness/metastatic-related mRNAS promote oncogenic potential in breast cancer.

Cancer cells efficiently transfer exosome contents (essentially mRNAs and microRNAs) to other cell types, modifying immune responses, cell growth, angiogenesis and metastasis. Here we analyzed the exosomes release by breast tumor cells with different capacities of stemness/metastasis based on CXCR4 expression, and evaluated their capacity to generate oncogenic features in recipient cells. Breast cancer cells overexpressing CXCR4 showed an increase in stemness-related markers, and in proliferation, migration and invasion capacities. Furthermore, recipient cells treated with exosomes from CXCR4-cells showed increased in the same abilities. Moreover, inoculation of CXCR4-cell-derived exosomes in immunocompromised mice stimulated primary tumor growth and metastatic potential. Comparison of nucleic acids contained into exosomes isolated from patients revealed a "stemness and metastatic" signature in exosomes of patients with worse prognosis. Finally, our data supported the view that cancer cells with stem-like properties show concomitant metastatic behavior, and their exosomes stimulate tumor progression and metastasis. Exosomes-derived nucleic acids from plasma of breast cancer patients are suitable markers in the prognosis of such patients.