Post-splenectomy acute glomerulonephritis due to a chronic infection with Plasmodium falciparum and malariae

A 38-year-old Senegalese man with no previous medical history and living in Spain since 2004 was admitted due to fever, hypotension and edemas. The patient had not traveled to malaria endemic areas for the last 2 years, and 43 days before this episode he underwent an elective splenectomy in order to rule out a hematologic neoplasm due to a 27-cm splenomegaly and pancytopenia

The Renal Range of the κ/λ sFLC Ratio: Best Strategy to Evaluate Multiple Myeloma in Patients With Chronic Kidney Disease

Background: Monoclonal serum free light chains (sFLC) are a well-known cause of renal impairment (RI) in patients with multiple myeloma (MM). As an indicator of monoclonality, sFLC ratio has acquired a key role in the diagnosis and monitorization of the disease. However, its interpretation is altered in patients with chronic kidney disease (CKD). This study aims to evaluate the modification of the sFLC ratio reference range in patients with CKD, and propose an optimal range for patients with CKD. Methods: Serum FLC κ/λ ratio and estimated glomerular filtration rate (eGFR) were retrospectively analyzed in 113 control patients (without hematologic disease), 63 patients with MM in complete remission and 347 patients with active MM. The three groups included patients with CKD (eGFR < 90). Results: In the group of patients without active MM (n = 176), the sFLC ratio increased at different stages of CKD without pathological significance, with an increase in the number of false positives specially when eGFR is ≤55 ml/ min. An optimal range was established for patients with eGFR ≤55 ml/min/1.73 m2: 0.82-3,6 with maximum sensitivity + specificity for that group with an improvement in the Area under the curve (AUC), 0.91 (0.84-0.97) compared with the current ranges proposed by Katzmann and Hutchinson. Conclusions: This study confirms the influence of eGFR on the interpretation of the sFLC ratio, showing a decreasing specificity in progressive CKD stages when using the reference sFLC range (Katzmann), especially in patients with eFGR ≤55. According to our results, we suggest a modified optimal range (0.82-3,6) for eGFR ≤55 ml/ min/1.73 m2. It is necessary to validate this modified range in larger and prospective studies

Differentiating Acute Interstitial Nephritis From Immune Checkpoint Inhibitors From Other Causes

Immune checkpoint inhibitors (ICIs) have significantly improved outcomes for patients with neoplasms in advanced stages. On the other hand, ICIs have immune-related adverse events. These adverse events affect mostly other organs than the kidney, such as skin or gastrointestinal tract. The incidence of nephrotoxicity with monotherapy with any ICI is about 2%, which increases to 5% in combination therapy. Acute tubulointerstitial nephritis (AIN) is the most common pattern of kidney damage related to ICIs. Globally, without considering ICI nephrotoxicity, AIN is estimated to account for 15% to 20% of cases of acute kidney injury (AKI). This is crucial because patients who are treated with ICIs, may also be taking other drugs that potentially cause AIN, and therefore, knowing the particularities about ICI-related AIN could be helpful in clinical practice to better understand the phenotypic differences between the 2 types of AIN. In addition, several studies have now shown that being on proton pump inhibitors is a risk factor for AIN from ICI therapy

Creatine Kinase Elevation in Autosomal Dominant Polycystic Kidney Disease Patients on Tolvaptan Treatment

Background: Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary cause of end-stage kidney disease. Currently, tolvaptan is the only treatment that has proven to delay disease progression. The most notable side effect of this therapy is drug-induced liver injury; however, recently, there have been two reports of creatine kinase (CK) elevation in ADPKD patients on tolvaptan treatment. We set out to monitor and determine the actual incidence of CK elevation and evaluate its potential association with other clinical factors. Methods: This is an observational retrospective multicenter study performed in rapidly progressive ADPKD patients on tolvaptan treatment from Barcelona, Spain. Laboratory tests, demographics, treatment dose, and reported symptoms were collected from October 2018 to March 2021. Results: Ninety-five patients initiated tolvaptan treatment during follow-up. The medication had to be discontinued in 31 (32.6%) patients, primarily due to aquaretic effects (12.6%), elevated liver enzymes (8.4%), and symptomatic or persistently elevated CK levels (3.2%). Moreover, a total of 27 (28.4%) patients had elevated CK levels, with most of them being either transient (12.6%), mild and asymptomatic (4.2%), or resolved after dose reduction (3.2%) or temporary discontinuation (2.1%). Conclusion: We pre-sent the largest cohort that has monitored CK levels in a real-life setting, finding them elevated in 28.4% of patients. More research and monitoring will help us understand the clinical implications and the pathophysiological mechanism of CK elevation in this population

Análisis y utilidad del proteoma urinario en el diagnóstico diferencial de la disfunción crónica del injerto renal

[spa] El trasplante renal es la mejor opción disponible para el tratamiento de la enfermedad renal crónica avanzada, tanto en términos de supervivencia como de calidad de vida de los pacientes. La escasez de órganos disponibles para el procedimiento es la mayor limitación de este tipo de terapéutica y por tanto prolongar la vida útil de los injertos renales es la principal prioridad en el contexto del trasplante renal. Después del primer año de funcionamiento del trasplante, la disfunción crónica del injerto (DCI) constituye la principal causa de daño y perdida injerto renal. Esta tesis es un análisis de la correlación del estudio del proteoma urinario mediante espectrometría de masas con la severidad y subtipo histológico de la disfunción crónica del injerto. Los sujetos fueron agrupados según el resultado de la biopsia del injerto y el análisis proteómico mediante espectrometría de masas se realizó en una muestra obtenida antes de realizar la biopsia por indicación clínica. Se realizaron dos tipos de estrategias mediante espectrometría de masas: un primer abordaje, utilizando MALDI- TOF, previa extracción del muestra mediante cromatografía de fase reversa mostró diferencias en el perfil proteómico urinario entre sujetos sanos, pacientes trasplantados con buena función del injerto renal y pacientes con disfunción crónica del injerto. Un segundo estudio mediante LC-MS-MS cuantificó estas diferencias y además aportó información acerca de la secuencia de los péptidos diferenciales. Péptidos específicos derivados de uromodulina y bradiquinina son candidatos a biomarcadores de buen funcionamiento del injerto renal, ya que su presencia en la orina puede ser utilizada para discriminar entre pacientes trasplantados con disfunción del injerto renal y pacientes trasplantados con buena función del injerto. Los niveles elevados del ión 642.5 y niveles bajos del ión 638.0 derivado de uromodulina son característicos de la orina proveniente de pacientes con disfunción crónica del injerto y permiten detectar sus subtipos histológicos. Los iones de m/z 645.59 y m/z 642.61 estaban aumentados de forma significativa en pacientes con rechazo crónico activo mediado por anticuerpos respecto a pacientes con fibrosis intersticial y atrofia tubular aislada (4.4-2.7 fold change) y pacientes trasplantados con función estable del injerto (5.3-14.6 fold change) permitiendo cuantificar las diferencias entre estos dos subtipos de disfunción crónica del injerto ya demostradas en los análisis cualitativo con MALDI-TOF. Este trabajo es la primera prueba de concepto de la utilidad de la proteomica urinaria para detectar biomarcadores y el futuro diseño de una herramienta diagnóstica no invasiva en la disfunción crónica del injerto y en dos de sus subtipos histológicos: Fibrosis intersticial y atrofia tubular sin evidencias de otras lesiones y el Rechazo crónico activo mediado por anticuerpos.[eng] Despite optimal immunosuppressive therapy, more than 50% of kidney transplants fail because of chronic allograft dysfunction. A noninvasive means to diagnose chronic allograft dysfunction may allow earlier interventions that could improve graft half-life. In this proof-of-concept study, we used mass spectrometry to analyze differences in the urinary polypeptide patterns of patients with chronic allograft dysfunction ( with pure interstitial fibrosis and tubular atrophy and with chronic active antibody-mediated rejection) and control subjects (stable recipients and healthy control subjects). Unsupervised hierarchical clustering showed good segregation of samples in groups corresponding mainly to the four biomedical conditions. Moreover, the composition of the proteome of the pure interstitial fibrosis and tubular atrophy group differed from that of the chronic active antibodymediated rejection group, and an independent validation set confirmed these results. Specific peptides derived from uromodulin and kininogen were found to be significantly more abundant in control than in CAD patients and correctly identified the two groups. These peptides are therefore potential biomarkers that might be used for the diagnosis of CAD. In addition, ions at m/z 645.59 and m/z 642.61 were able to differentiate between patients with different forms of CAD with specificities and sensitivities of 90% in a training set and, significantly, of 70% in an independent validation set of samples. Interestingly low expression of uromodulin at m/z 638.03 coupled with high expression of m/z 642.61 diagnosed CAD in virtually all cases. Multiple reaction monitoring experiments further validated the results, illustrating the power of our label-free quantitative LC-MS approach for obtaining quantitative profiles of urinary polypeptides in a rapid, comprehensive, and precise fashion and for biomarker discovery. In summary, this study establishes a pattern for two histologic lesions associated with distinct graft outcomes and constitutes a first step to designing a specific, noninvasive diagnostic tool for chronic allograft dysfunction

Provision of urban amenities and public works analysis in the City of Chihuahua, Mexico

Objective: Identify the basic geostatistical areas (AGEBS) that until 2019 are classified as priority attention areas, and carry out an analysis on the lack of equipment and assess indicators for monitoring the sustainable development of the municipality of Chihuahua in the urban environment.Design/methodology/approach: The methodology used was analytical-synthetic, bibliographic techniques and statistics to study the levels that are reflected at national and municipal level, as well as the indicators of areas with social backwardness, to contribute with proposals for the improvement&nbsp; of these areas. Results: In the city of Chihuahua, Chih., marginalization levels were diagnosed, so it was detected that 3% of the city's population lives in areas where equipment is scarce or null, and this favors the low development of inhabitants found in these areas of the city.Limitations on study/implications: The distances that the different types of equipment have in the city were determined, and access to the different types of equipment that are considered as the most basic, such as education and health, remain within less accessible distances.Findings/conclusions: Present the compact, connected and close city model, densifying the main sub-centers of the city and optimizing the resources required for the provision, of either services or the infrastructure necessary for the provision of urban equipment, to prevent the city from continuing to grow disproportionately. Keywords: geostatistics, urban equipment, services, sustainable development.Objective: To identify the basic geostatistical areas (AGEBS) that until 2019 were classified as priority attention zones, in order to analyze the lack of amenities and to assess indicators for monitoring sustainable development in the urban area of the municipality of Chihuahua. Design/Methodology/Approach: An analytical-synthetic methodology was used. Bibliographical and statistical techniques were applied to study the levels that are reflected at the national and municipal scales, as well as the indicators of socially underdeveloped areas, in order to make proposals for their improvement. Results: Based on a diagnosis of the marginalization levels in the City of Chihuahua, Chih., 3% of the city population lives in areas with scarce or non-existent amenities, generating low development in its inhabitants. Study Limitations/Implications: The distances between the different types of amenities in the city were determined, as well as the access to essential amenities (i.e., education and health). These amenities are located at inaccessible distances. Findings/Conclusions: We would like to propose a compact and connected city model where amenities are nearby. This proposal includes the densification of the main sub-centers of the city, as well as the optimization of the required resources and the necessary infrastructure for the provision of services and urban equipment. The ultimate objective is to prevent the ongoing and disproportionate growth of the city

Documento de consenso del Grupo de Estudio de Enfermedades Glomerulares de la Sociedad Española de Nefrología (GLOSEN) para el diagnóstico y tratamiento de la nefritis lúpica

Resumen: Un número importante de pacientes con lupus eritematoso sistémico (entre 20 a 60%, según diferentes series) desarrolla nefritis lúpica en el curso de su evolución, lo que influye directamente en su calidad de vida y pronóstico vital. En años recientes, el mayor conocimiento sobre la patogénesis del lupus sistémico y de la nefritis lúpica ha permitido avances relevantes en el abordaje diagnóstico y en el tratamiento de estos pacientes, lográndose desarrollar fármacos dirigidos específicamente a bloquear vías patogénicas claves de la enfermedad. Alentadoramente estos agentes inmunomoduladores han demostrado en ensayos clínicos aleatorizados, y bien ponderados, buena eficacia clínica a mediano plazo, definida como remisión de proteinuria y preservación de la función renal, con un aceptable perfil de seguridad y buena tolerabilidad del paciente. Todo esto ha permitido reducir el uso de corticoides y de otras terapias potencialmente más tóxicas, así como incrementar el uso de terapias combinadas. El presento documento de consenso realizado por el Grupo de Trabajo de Enfermedades Glomerulares de la Sociedad Española de Nefrología (GLOSEN) recoge de manera práctica y resumida, pero rigurosa, la mejor evidencia actual disponible acerca del diagnóstico, tratamiento y seguimiento del paciente con nefritis lúpica, incluyendo casos de situaciones especiales, con el objetivo principal de brindar información actualizada y recomendaciones clínicas bien fundamentadas a los médicos tratantes, para mejorar el enfoque diagnóstico y terapéutico a nuestro pacientes. Summary: A significant number of patients with systemic lupus erythematosus (between 20% to 60% according to different reported series) develop lupus nephritis in the course of its evolution, which directly influences their quality of life and vital prognosis. In recent years, the greater knowledge about the pathogenesis of systemic lupus and lupus nephritis has allowed relevant advances in the diagnostic approach and treatment of these patients, achieving the development of drugs specifically aimed at blocking key pathogenic pathways of the disease. Encouragingly, these immunomodulatory agents have shown in well-powered, randomized clinical trials good clinical efficacy in the medium-term, defined as proteinuria remission and preservation of kidney function, with an acceptable safety profile and good patient tolerability. All this has made it possible to reduce the use of corticosteroids and other potentially more toxic therapies, as well as to increase the use of combined therapies. The present consensus document carried out by the Glomerular Diseases Working Group of the Spanish Society of Nephrology (GLOSEN), collects in a practical and summarized, but rigorous way, the best currently available evidence about the diagnosis, treatment, and follow-up of lupus nephritis patients, including cases of special situations, with the main objective of providing updated information and well-founded clinical recommendations to treating physicians, to improve the diagnostic and therapeutic approach to our patients

Kidney Biopsy in Patients with Cancer along the Last Decade: A Multicenter Study

Background: Currently, following the new advances in cancer treatments and the increasing prevalence of kidney disease in the population, more kidney biopsies are being performed. The aim of our study is to analyze clinical and histological characteristics of patients with active solid organ malignancy who underwent kidney biopsy. This is a multi-center collaborative retrospective study supported by groups GLOSEN/Onconephrology from the Spanish Society of Nephrology. Clinical, demographical and histological data were collected. Results: A total of 148 patients with cancer who underwent a kidney biopsy from 12 hospitals were included. 64.3% men and mean age of 66.9 years old. The indications for biopsy were acute renal injury (67.1%), proteinuria (17.1%), exacerbated chronic kidney disease (8.2%), and chronic kidney disease (7.5%). Most frequent malignances were lung (29.1%) and abdominal (25%), with 49.7% metastatic cancer. As oncospecific treatment, 28% received chemotherapy, 29.3% immunotherapy, 19.3% specific therapies, and 2.1% conservative treatment. At the time of kidney biopsy, median creatinine was of 2.58 mg/dL [1.81-4.1 (IQ 25-75)], median urine protein-to-creatinine ratio of 700 mg/g [256-2463 (IQ 25-75)] and 53.1% presented hematuria. The most frequent renal biopsy diagnoses were: acute interstitial nephritis (39.9%), acute tubular necrosis (8.8%), IgA nephropathy (7.4%) and membranous nephropathy (6.1%). Median follow-up was 15.2 months [5.7-31.4 (IQ 25-75)]. Conclusions: There is a new trend in kidney disease and cancer patients in terms of diagnosis and treatment. Acute interstitial nephritis has established itself as the most common kidney injury in patients with cancer who underwent a kidney biopsy. Renal biopsy is a valuable tool for diagnosis, treatment, and prognosis of solid organ cancer patients with kidney damage. Keywords: kidney biopsy; onconephrology; renal pathology; solid organ neoplasm

El radicalismo colombiano del siglo XIX

Dedicado al periodo comprendido entre 1863 y 1878 en Colombia, este texto es el resultado de la segunda versión del seminario programado por la Cátedra de Pensamiento colombiano, organizada por la Universidad Nacional de Colombia. El libro es una colección de ensayos sobre diferentes aspectos del periodo del radicalismo liberal. Sus autores son investigadores de distintas disciplinas académicas que ofrecen su particular visión sobre este importante estadio de la historia colombiana. / Contenido. Preliminares; Capítulo 1 - Ezequiel Rojas y la moral utilitarista Laura Quintana Porras; Capítulo 2 - Salvador Camacho Roldán: entre la normatividad y el espíritu práctico Iván González Puccetti; Capítulo 3 - José María Samper: la decepción del radicalismo Rubén Sierra Mejía; Capítulo 4 - La idea federal en Colombia durante el siglo XIX Salomón Kalmanovitz; Capítulo 5 - Catecismos políticos del siglo XIX Leonardo Tovar González; Capítulo 6 - ¿Libertad, libertinaje, tiranía? La prensa bajo el Olimpo Radical en Colombia, 1863-1885 Eduardo Posada Carbó; Capítulo 7 - Los límites de la libertad: ideología, política y violencia en los radicales Myriam Jimeno Santoyo; Capítulo 8 - El radicalismo y la cuestión militar Fernando Cubides Cipagauta; Capítulo 9 - Los radicales y la guerra civil de 1876-1877 Luis Javier Ortiz Mesa; Capítulo 10 - Iconografía de los radicales Beatriz González; Capítulo 11 - Romanticismo y radicalismo David Jiménez; Capítulo 12 - En los márgenes del radicalismo: Soledad Acosta de Samper y la escritura de la nación Carolina Alzate; Capítulo 13 - Los debates político-religiosos en torno a la fundación de la Universidad Nacional de Colombia, 1867-1876 José David Cortés Guerrero; Capítulo 14 - Los anales de la Universidad Nacional 1868-1880 Clara Helena Sánchez Botero; Capítulo 15 - Los estudios de derecho en el Colegio del Rosario. Algunos aspectos en la formación de abogados en el período radical Víctor Alberto Quinche Ramírez

Results from part A of the multi-center, double-blind, randomized, placebo-controlled NefIgArd trial, which evaluated targeted-release formulation of budesonide for the treatment of primary immunoglobulin A nephropathy

The therapeutic potential of a novel, targeted-release formulation of oral budesonide (Nefecon) for the treatment of IgA nephropathy (IgAN) was first demonstrated by the phase 2b NEFIGAN trial. To verify these findings, the phase 3 NefigArd trial tested the efficacy and safety of nine months of treatment with Nefecon (16 mg/d) versus placebo in adult patients with primary IgAN at risk of progressing to kidney failure (ClinicalTrials.gov: NCT03643965). NefIgArd was a multicenter, randomized, double-blind, placebo-controlled two-part trial. In Part A, 199 patients with IgAN were treated with Nefecon or placebo for nine months and observed for an additional three months. The primary endpoint for Part A was 24-hour urine protein-to-creatinine ratio (UPCR) after nine months. Secondary efficacy outcomes evaluated included estimated glomerular filtration rate (eGFR) at nine and 12 months and the UPCR at 12 months. At nine months, UPCR was 27% lower in the Nefecon group compared with placebo, along with a benefit in eGFR preservation corresponding to a 3.87 ml/min/1.73 m2 difference versus placebo (both significant). Nefecon was well-tolerated, and treatment-emergent adverse events were mostly mild to moderate in severity and reversible. Part B is ongoing and will be reported on later. Thus, NefIgArd is the first phase 3 IgA nephropathy trial to show clinically important improvements in UPCR and eGFR and confirms the findings from the phase 2b NEFIGAN study