ANCA associated vasculitis: The journey to complement-targeted therapies.

ANCA associated vasculitis is a serious, very often recurrent disease that despite the current standard treatment with high-dose glucocorticoids and either cyclophosphamide or rituximab, patients have a nine-fold increased mortality risk in the first year compared with healthy controls, attributed to infections, vasculitis activity, and renal disease. During the last few years, novel findings have suggested that activation of the complement system, in particular the alternative complement system, has a significant role in ANCA associated vasculitis pathogenesis. Detection of several components of this system in the circulation and urine reflects disease activity, and thus may be useful for clinical prognosis and to set up personalised treatments. In fact, some components of the complement system, such as C5a, might be potential targets for therapy. In this Review an update on clinical evidence for the role of complement activation in AAV is provided and subsequently we discuss potential therapeutic strategies that target complement components and open the way for clinical use of this target therapy in the near future

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

Kidney biopsy; Renal pathology; Solid organ neoplasmBiòpsia renal; Patologia renal; Neoplàsia d'òrgans sòlidsBiopsia renal; Patología renal; Neoplasia de órganos sólidosBackground: 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.This work was supported by grants from Fondo de Investigación Sanitaria-FEDER, ISCIII, Río Hortega CM20/00111, PI17/00257, PI21/01292, Marató TV3 2020 421/C/2020, Marató TV3 2021 215/C/2021, RD16/0009/0030 (REDINREN), EIN2020-1123381, and RD21/0005/0016 (RICORS 2040)

Kidney biopsy in lupus nephritis after achieving clinical renal remission: paving the way for renal outcome assessment.

The role of repeat kidney biopsy in lupus nephritis (LN) with renal remission is unclear. The aim of this study was to assess this role in a real-life scenario. This retrospective, single-centre study included 56 patients with LN diagnosed from 1998 to 2019, with an initial kidney biopsy (KB1) at the onset of LN and a second kidney biopsy (KB2) after achieving renal remission. A total of 51 (91.1%) patients were women with a median age of 29.9 years [interquartile range (IQR) 23.4-40.6] at the time of LN diagnosis. KB2s were performed after 41.1 months (IQR 30.1-52.5) of KB1. At the time of KB2, complete renal response was achieved in 51 (91.1%) patients. The median activity index decreased from a baseline value of 6.5 (IQR 2.8-11) to 0 (IQR 0-2) (P < .001). The chronicity index worsened from 1 (IQR 0-2) to 2 (IQR 1-3) (P = .01). In patients with proliferative/mixed forms at KB2, the chronicity index median value increased to 3 (IQR 1.5-4), as well as interstitial fibrosis and tubular atrophy [Formula: see text]25%, from 5.4% to 13.5%. Persistent histological active LN (activity index ≥2) was present in 11 (19.6%) KB2s. There were no differences when comparing immunological parameters between both groups (activity index ≥2 versus <2) at KB2, nor in the percentage of patients who presented renal flare. Immunosuppressive treatment was withdrawn in 35 (62.5%) patients and maintained/switched in 21 (37.5%). Afterward, new renal flare occurred in 9 patients per group (25.7% and 43%, respectively), after a median time of 39 months (IQR 6.5-55) and 7 months (IQR 6-30), respectively. There was no difference in the number of patients who developed chronic kidney disease [n = 14 (25%)] according to the treatment. In conclusion, KB2 provides valuable information to guide immunosuppressive maintenance therapy

Extracapillary proliferation scoring correlates with renal outcome and contributes to stratification in adult patients with immunoglobulin A nephropathy

Background. The revised Oxford classification of diagnostic renal biopsies has been proposed to aid in the prediction of renal outcome. We aimed to validate the histological crescents and interstitial fibrosis and tubular atrophy (IFTA) subgrouping, and to investigate the additional value of the proportion of crescents (CatPE) in the prediction of renal outcome. Methods. Data were retrospectively collected over 10 years, from the time of diagnosis, by systematic review of medical records from 90 patients with renal biopsies recruited to cohorts from two hospitals in Spain. Patients were classified into three groups for the analysis: CatPE >25% (C2), CatPE 50% reduction in glomerular filtrate rate or end-stage renal disease. Results. Renal survival at 5 years was 90% in group C0, 81% in group C1 and 31% in group C2 (P 1⁄4 0.013). The presence of >25% crescents in the sample was associated with more severe disease when compared with 50% had poorer renal function compared with the other groups. Conclusions. We have confirmed the predictive value for renal survival of the revised Oxford classification in a two-centre study. We found worse renal outcome in patients with severe tubulointerstitial fibrosis and atrophy. Patients with extracapillary lesions >25% and IFTA >50% had a worse renal prognosis due to more severe kidney injury. These results contribute to patient stratification in immunoglobulin A nephropathy for therapeutic, epidemiological and basic research

Impact of cardiac surgery associated acute kidney injury on 1-year major adverse kidney events

BackgroundThe incidence of acute kidney injury following cardiac surgery (CSA-AKI) is up to 30%, and the risk of chronic kidney disease (CKD) has been found to be higher in these patients compared to the AKI-free population. The aim of our study was to assess the risk of major adverse kidney events (MAKE) [25% or greater decline in estimated glomerular filtration rate (eGFR), new hemodialysis, and death] after cardiac surgery in a Spanish cohort and to evaluate the utility of the score developed by Legouis D et al. (CSA-CKD score) in predicting the occurrence of MAKE.MethodsThis was a single-center retrospective study of patients who required cardiac surgery with cardiopulmonary bypass (CPB) during 2015, with a 1-year follow-up after the intervention. The inclusion criteria were patients over 18 years old who had undergone cardiac surgery [i.e., valve substitution (VS), coronary artery bypass graft (CABG), or a combination of both procedures].ResultsThe number of patients with CKD (eGFR &lt; 60 mL/min) increased from 74 (18.3%) to 97 (24%) within 1 year after surgery. The median eGFR declined from 85 to 82 mL/min in the non-CSA-AKI patient group and from 73 to 65 mL/min in those with CSA-AKI (p = 0.024). Fifty-eight patients (1.4%) presented with MAKE at the 1-year follow-up. Multivariate logistic regression analysis showed that the only variable associated with MAKE was CSA-AKI [odds ratio (OR) 2.386 (1.31–4.35), p = 0.004]. The median CSA-CKD score was higher in the MAKE cohort [3 (2–4) vs. 2 (1–3), p &lt; 0.001], but discrimination was poor, with a receiver operating characteristic curve (AUC) value of 0.682 (0.611–0.754).ConclusionAny-stage CSA-AKI is associated with a risk of MAKE after 1 year. Further research into new measures that identify at-risk patients is needed so that appropriate patient follow-up can be carried out

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

Thrombotic microangiopathies assessment: mind the complement.

When faced withmicroangiopathic haemolytic anaemia, thrombocytopenia and organ dysfunction, clinicians should suspect thrombotic microangiopathy (TMA). The endothelial damage that leads to this histological lesion can be triggered by several conditions or diseases, hindering an early diagnosis and aetiological treatment. However, due to systemic involvement in TMA and its lowincidence, an accurate early diagnosis is often troublesome. In the last few decades,major improvements have been made in the pathophysiological knowledge of TMAs such as thrombotic thrombocytopenic purpura [TTP, caused by ADAMTS-13 (a disintegrin andmetalloproteinase with a thrombospondin Type 1motif,member 13) deficiency] and atypical haemolytic uraemic syndrome (aHUS, associated with dysregulation of the alternative complement pathway), together with enhancements in patientmanagement due to newdiagnostic tools and treatments. However, diagnosis of aHUS requires the exclusion of all the other entities that can cause TMA, delaying the introduction of terminal complement blockers, which have shown high efficacy in haemolysis control and especially in avoiding organ damage if used early. Importantly, there is increasing evidence that other forms of TMA could present overactivation of the complement system, worsening their clinical progression. This review addresses the diagnostic and therapeutic approach when there is clinical suspicion of TMA, emphasizing complement evaluation as a potential tool for the inclusive diagnosis of aHUS, as well as for the improvement of current knowledge of its pathophysiological involvement in other TMAs. The development of both new complement activation biomarkers and inhibitory treatments will probably improve themanagement of TMA patients in the near future, reducing response times and improving patient outcomes

EVALUACION DEL COMPORTAMIENTO BIOLOGICO, CLINICO Y MICROBIOLOGICO DE RESINAS DE ULTIMA GENERACION

An study of three clases of resins of last generation was done evaluating the clinical conduct histological, microbiological and microfiltración through electronical microscopic concluting that the clinical answer in the three tippies of resins in casties of 3 mm of intensity were not present, in histologic grade you cannot see qualitive changes, in the microbiological aspect it was verified y kal the efect antimi crobianie is only produced with direct contact with the resens through the shape of an halo, with reference to the microscopic observation one of resens presented a total of a hyborderm cave.Se realizó un estudio sobre tres clases de resinas de última generación evaluándose el comportamiento clínico, histológico, microbiológico y microfiltración a través del microscopio electrónico de barrido, concluyéndose que la respuesta clínica en los tres tipos de resinas en cavidades de 3 mm de profundidad estuvo ausente, a nivel histológico no se aprecian cambios cualitativos, en el aspecto microbiológico se verificó que el efecto antimicrobiano solo se produce en contacto directo con la resina a través de la formación de un halo de inhibición, con respecto a la observación microscópica una de las resinas presentó formación total de capa híbrida

Efecto de las intervenciones con ingesta de leguminosas y/o ejercicio supervisado sobre el perfil lipídico de mujeres jóvenes, sanas y sedentarias

Objective: To contribute to the knowledge of some aspects of the Healthy Life Style by studying the effects of including legumes in the diet and exercise at two intensity levels, along with the lipid profile of young sedentary women living at 2640 meters above sea level. Materials and methods: The study included a non-randomized clinical trial with four intervention groups: exercise at 45% VO2 peak plus legumes in diet, exercise at 65% VO2 peak plus legumes in diet, only exercise at 65% VO2 peak, and only inclusion of legumes in diet. In each group, 20 to 23 sedentary women were included. The intervention was carried out for four weeks, three days a week. Exercise prescription was based on measurement of VO2 peak by ergospirometry; and the current intervention was monitored with heart-rate monitors. The outcome variables were total serum cholesterol, LDL cholesterol, HDL cholesterol, and triacylglycerols measured at baseline and after two and four weeks of intervention. Results: The measurements taken of participants in the group of exercise at 65% VO2 peak plus legumes in diet showed a reduction of 19.8 mg/dl in total cholesterol, of 21.8 mg/dl of LDL cholesterol, of 20.7 mg/dl of tracylglycerol, and an increase of 6.2 mg/dl of HDL cholesterol. The serum levels of HDL also increased in the group of only exercise at 65% VO2 peak. No significant changes in serum levels were documented for participants in the group with only dietary modifications. Conclusions: The results suggest that different interventions that meet some of the criteria for healthy eating and life style show different effects with regards to the level of change in the lipid profile components. Objetivo: Contribuir al conocimiento de algunos aspectos prácticos para llevar a cabo una alimentación y estilo de vida saludable, mediante el estudio de los efectos en el perfil lipídico de la inclusión de leguminosas (fríjol, lenteja y garbanzos) en la dieta de mujeres sanas pero sedentarias, acompañada de ejercicio con dos niveles de intensidad, moderada y alta, efectuados a una altura de 2,640 metros sobre el nivel del mar (msnm) Material y métodos: Estudio de intervención clínica no aleatorizada con cuatro grupos de intervención: ejercicio a 45% VO2 pico + leguminosas, ejercicio a 65% VO2 pico + leguminosas, sólo ejercicio a 45% VO2 picoy sólo inclusión de leguminosas en la dieta. En cada grupo se incluyeron de 20 a 23 mujeres jóvenes sedentarias evaluadas mediante el International Physical Activity Questionnaire (IPAQ), y la intervención se llevó a cabo durante 4 semanas. La prescripción del ejercicio se hizo previa determinación del VO2 pico por ergo espirometría, y su realización se monitoreó con sensores de frecuencia cardíaca. El efecto de la intervención se evaluó mediante los cambios en los niveles séricos de colesterol total (CT), colesterol LDL (cLDL), colesterol HDL (cHDL) y triacilgliceroles (TAG), tomados a las semanas cero, dos y cuatro. Resultados: En el grupo «ejercicio a 65% del VO2 pico, más inclusión de leguminosas en la dieta» se obtuvieron los siguientes resultados significantes: una reducción promedio del colesterol total de 19.8 mg/dl (p=0.0015), del colesterol LDL de 21.8 mg/dl (p=0.0001), un aumento de colesterol HDL de 6.2 mg/dl (p=0.0001) y una disminución de los triacilgliceroles de 20.7 mg/dl (p=0.0001). En el grupo de sólo ejercicio a 65% del VO2 pico se obtuvo un aumento del HDL. No hubo modificaciones al perfil lipídico en el grupo correspondiente a sólo inclusión de leguminosas en la alimentación. Conclusiones: Los resultados sugieren que en mujeres jóvenes sedentarias que viven a 2,640 metros sobre el nivel del mar, la combinación de ejercicio de intensidad alta e inclusión de leguminosas (fríjol, lenteja o garbanzos) producen un mayor cambio benéfico en el perfil lipídico que una intervención con sólo ejercicio de intensidad alta o sólo inclusión de leguminosas en la alimentación. Los cambios benéficos significantes se obtuvieron luego de 4 semanas de intervención en el colesterol total, colesterol LDL, colesterol HDL y triacilgliceroles, lo que pone de presente la bondad de esta intervención, así como la utilidad del perfil lipídico como indicador temprano de cambios en los estilos de vida. Las intervenciones estudiadas, compatibles con alimentación y estilo de vida saludables, producen efectos diferentes en los niveles del perfil lipídico estudiados, y al poner de presente las debilidades de un diseño no aleatorizado, se puede recomendar que se insista en las intervenciones de salud pública que contemplen cambios en la dieta y cambios en la actividad física