C3 Glomerulopathy Recurs Early after Kidney Transplantation in Serial Biopsies Performed within the First Two Years Post-Transplantation.

BACKGROUND: C3 glomerulopathy (C3G), which encompasses C3 glomerulonephritis (C3GN) and dense deposit disease (DDD), results from dysregulation of the alternative complement pathway. Data on disease recurrence after kidney transplantation is limited, and details on histologic features of recurrent C3G are scarce. We aimed to evaluate C3G recurrence in the allograft, with a focus on histologic presentation and progression. METHODS: We retrospectively analyzed 18 patients with native kidney failure attributed to C3G (12 C3GN and six DDD) who received a kidney transplant from January 2016 to January 2023. Demographic, genetic, clinical, and histologic data were studied. The Nanostring 770 genes immune profiling panel was used for transcriptomic analysis. Disease recurrence was the primary outcome. RESULTS: During a median (IQR) follow-up period of 37 (18, 56) months, C3G recurrence occurred in 16 (89%) of patients (11 with C3GN and five with DDD), at a median (IQR) of 33 (13, 141) days post-transplantation. Over a third (38%) of recurrent cases were detected in protocol biopsies, and only 31% of patients presented with >300 mg/g of proteinuria. Recurrence in index biopsies was mainly established through a combination of immunofluorescence and electron microscopy findings, while it showed only subtle histologic alterations and no characteristic transcriptomic signals. Over time, histologic chronicity indices increased, but all allografts were functioning at the end of follow-up. Patients with recurrence of C3GN and DDD showed overlapping immunofluorescence and electron microscopy findings and had similar recurrence rate and time to recurrence. CONCLUSIONS: The majority of patients with native kidney failure attributed to C3G developed disease recurrence very early after kidney transplantation, usually with minimal proteinuria, mild histologic alterations, and favorable short-term allograft survival. Immunofluorescence and electron microscopy played a crucial role in detecting early, sub-clinical recurrence of C3GN and DDD, which showed significant overlapping features.

Sodium-glucose cotransporter 2 inhibition in primary and secondary glomerulonephritis.

BACKGROUND: The role of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in the management glomerular/systemic autoimmune diseases with proteinuria in real-world clinical settings is unclear. METHODS: This is a retrospective, observational, international cohort study. Adult patients with biopsy-proven glomerular diseases were included. The main outcome was the percentage reduction in 24-h proteinuria from SGLT2i initiation to 3, 6, 9 and 12 months. Secondary outcomes included percentage change in estimated glomerular filtration rate (eGFR), proteinuria reduction by type of disease and reduction of proteinuria ≥30% from SGLT2i initiation. RESULTS: Four-hundred and ninety-three patients with a median age of 55 years and background therapy with renin-angiotensin system blockers were included. Proteinuria from baseline changed by -35%, -41%, -45% and -48% at 3, 6, 9 and 12 months after SGLT2i initiation, while eGFR changed by -6%, -3%, -8% and -10.5% at 3, 6, 9 and 12 months, respectively. Results were similar irrespective of the underlying disease. A correlation was found between body mass index (BMI) and percentage proteinuria reduction at last follow-up. By mixed-effects logistic regression model, serum albumin at SGLT2i initiation emerged as a predictor of ≥30% proteinuria reduction (odds ratio for albumin <3.5 g/dL, 0.53; 95% CI 0.30-0.91; P = .02). A slower eGFR decline was observed in patients achieving a ≥30% proteinuria reduction: -3.7 versus -5.3 mL/min/1.73 m2/year (P = .001). The overall tolerance to SGLT2i was good. CONCLUSIONS: The use of SGLT2i was associated with a significant reduction of proteinuria. This percentage change is greater in patients with higher BMI. Higher serum albumin at SGLT2i onset is associated with higher probability of achieving a ≥30% proteinuria reduction.

Complement inhibitors for kidney disease.

A refined understanding of the role of complement in the pathogenesis of glomerular and other kidney diseases has, over the past two decades, been matched by the development of novel, complement-targeting therapies. As we increasingly recognize the important role that complement activation across all three pathways-classical, lectin and alternative-plays in glomerular lesions both rare (e.g. C3 glomerulopathy) and common (e.g. immunoglobulin A nephropathy), we can identify avenues for precise, targeted approaches to modifying the natural history of these kidney diseases. In this review, we survey the evidence on using complement inhibition from the earliest, small-scale studies focusing on C5-targeting agents to more recent, large, multicenter, randomized trials utilizing complement blockade higher up in the complement pathway at the level of C3. We conclude by examining where the field of complement targeting therapy may be headed in light of these studies.

Effect of high cut-off dialysis for acute kidney injury secondary to cast nephropathy in patients with multiple myeloma: a systematic review and meta-analysis.

BACKGROUND: Acute kidney injury (AKI) caused by cast nephropathy is associated with increased morbidity and mortality among patients with multiple myeloma (MM). High cut-off haemodialysis (HCO-HD) has proven to be effective in the removal of serum light chains but the effect on clinical outcomes, especially renal recovery, remains uncertain. METHODS: A systematic review and meta-analysis were performed examining all randomized controlled trials (RCTs) and observational studies (OBSs) assessing the effect of HCO-HD on clinical outcomes of patients with MM complicated by cast nephropathy-induced severe AKI. The primary outcome was all-cause mortality at the end of the study. The secondary outcomes included all-cause mortality at 12 months, HD independence and serum kappa and lambda light chain reduction. Pooled analysis was performed using random effects models. RESULTS: We identified five studies, comprising two RCTs and three retrospective cohort studies, including 276 patients with a mean follow-up of 18.7 months. The majority of the studies were of suboptimal quality and underpowered. Compared with patients treated with conventional HD, HCO-HD was not associated with a survival benefit at 12 months {five studies, 276 patients, relative risk [RR] 1.02 [95% confidence interval (CI) 0.76-1.35], I 2 = 33.9%} or at the end of the studies at an average of 34 months [five studies, 276 patients, RR 1.32 (95% CI 0.71-2.45), I 2 = 62.0%]. There was no difference in HD independence at 90 days [two trials, 78 patients, RR 2.23 (95% CI 1.09-4.55)], 6 months [two studies, 188 patients, RR 1.19 (95% CI 0.68-2.06)] or 12 months [two studies, 188 patients, RR 1.14 (95% CI 0.58-2.26)]. Patients receiving HCO dialysis, however, had a greater reduction in serum kappa [two studies, 188 patients, weighted mean difference (WMD) 46.7 (95% CI 38.6-54.7), I 2 = 52.0%] and lambda [two studies, 188 patients, WMD 50.3 (95% CI 21.4-79.3), I 2 = 95.1%] light chain levels. CONCLUSION: Current evidence from RCTs and OBSs suggests HCO dialysis is able to reduce serum free light chains but makes no significant improvement in all-cause mortality and renal outcomes compared with conventional HD for patients with myeloma cast nephropathy. However, there is a trend towards better renal outcomes with the use of HCO dialysis. The lack of long-term data and the small sample sizes of the included studies limit this analysis. Therefore further large-scale RCTs with longer follow-up are needed to assess the effect of HCO dialysis on clinical outcomes in patients with myeloma cast nephropathy.

Una visión nefrológica del tratamiento sustitutivo renal en el paciente crítico con fracaso renal agudo: horizonte 2020 / Renal replacement therapy in critically ill patients with acute kidney injury: 2020 nephrologist's perspective

Las terapias de reemplazo renal (TRR) para el abordaje del fracaso renal agudo (FRA) de los pacientes inestables en la unidad de cuidados intensivos (UCI) se han convertido en una medida rutinaria e imprescindible para su manejo de tal manera que, tanto la hemodiálisis intermitente (HD), como las formas híbridas (HD extendida) o continuas (TRR continua) pueden emplearse indistintamente en estos enfermos. Con esta revisión pretendemos resumir de forma ordenada la evidencia disponible en cuanto a indicación, selección de modalidad, momento de inicio, dosificación y aspectos técnicos de las TRR. Hemos realizado una revisión narrativa a partir de las guías vigentes, documentos de consenso de los principales grupos de trabajo y últimos ensayos clínicos relevantes sobre la TRR. En nuestra revisión no hemos encontrado evidencia de que ninguna modalidad de TRR prescrita en pacientes en UCI obtenga beneficios tangibles en términos de supervivencia, estancia en UCI/hospitalización ni recuperación de la función renal; a pesar de su optimización en cuanto a indicaciones, selección de modalidad, momento y/o intensidad de inicio de la técnica. Es más, en la literatura actual todavía existe controversia sobre la superioridad de una modalidad de TRR sobre otra ya que, sólo en los pacientes post- quirúrgicos hemodinámicamente inestables se ha podido demostrar un beneficio al emplearse una TRR continua de alto flujo e inicio precoz frente a una HD. Con la evidencia actual pormenorizada en nuestra revisión pretendemos poner de manifiesto la tendencia actual al manejo multidisciplinar por intensivistas y nefrólogos de estas terapias en UCI, lo cual podría reportar beneficios en la evolución clínica de los enfermos críticos y dar cabida a que el punto de vista del nefrólogo se tuviera en cuenta de manera rutinaria en la toma de decisiones sobre el estado hemodinámico, las condiciones médicas coexistentes, la disponibilidad recursos y el posible efecto sobre la función renal a largo plazo a la hora de seleccionar y gestionar los problemas de cada modalidad de TRR seleccionada

Renal replacement therapies (RRT) as support for acute kidney injury in critically ill patients have become a routine and essential practice in their management, resulting in the widespread use of various techniques among these patients, such as intermittent hemodialysis (IHD), extended hemodialysis and continuous RRT (CRRT). In this review we aim to summarize current evidence of indication, choice of modality, timing of initiation, dosing and technical aspects of RRT. We carried out a narrative review based on guidelines, consensus documents by main working groups and the latest relevant clinical trials on RRT in the critically ill. We did not find enough evidence of any RRT modality having superior benefits in terms of patient survival, length of intensive care unit/hospital stay or renal outcomes among critically ill patients, in spite of optimization of clinical indication, modality, timing of initiation and intensity of initial therapy. This is still a controverted matter, since only early start of high-flux CRRT has been proven beneficial over IHD among hemodynamically unstable postoperative patients. Our objective is to portrait current RRT practices in multidisciplinary management of critically ill patients by intensive care and nephrology professionals. Implication of a nephrologist in the assessment of hemodynamic status, coexisting medical conditions, renal outcome expectations and management of resources could potentially have benefits at the time of RRT selection and troubleshooting

Fracaso renal agudo en pacientes hospitalizados por COVID-19 / Acute kidney failure in patients admitted due to COVID-19

ANTECEDENTES Y OBJETIVO: En diciembre de 2019 surgió en Wuhan, China, la COVID-19, causada por el virus SARS-CoV-2 y declarada pandemia global por la Organización Mundial de la Salud en marzo de 2020. Es una infección respiratoria con complicaciones a nivel cardiaco, hematológico, digestivo, neurológico y renal. El fracaso renal agudo (FRA) en pacientes hospitalizados por COVID-19 se presenta en el 0,5-25% y es un factor de mal pronóstico. Los mecanismos de afectación renal no están completamente aclarados. Presentamos la evolución clínica de pacientes ingresados por COVID-19 con FRA que requirieron atención por Nefrología en un hospital terciario de la Comunidad de Madrid, España. MÉTODOS: Este es un estudio observacional prospectivo de todos los casos que ingresaron por COVID-19 entre el 6 de marzo y el 12 de mayo de 2020 y requirieron atención por Nefrología. Se recogieron datos clínicos y analíticos de características basales, y la evolución de la COVID-19 y del FRA. RESULTADOS: Se analizaron 41 pacientes con una edad media de 66,8 años (DE 2,1), el 90,2% varones, y con enfermedad renal crónica previa en el 36,6%. El 56,1% presentaron neumonía grave o síndrome de distrés respiratorio agudo y el 31,7% requirió ingreso en UCI. El FRA fue de etiología prerrenal en el 61%, necrosis tubular aguda en contexto de sepsis en el 24,4%, glomerular en el 7,3% y por toxicidad tubular en el 7,3%. Se registró proteinuria en el 88,9% y hematuria en el 79,4%. El 48,8% de los pacientes requirió terapia de sustitución renal. La mediana de estancia fue de 12 días (RIC 9-23), y el 22% fallecieron. Los pacientes que desarrollaron FRA durante el ingreso presentaron valores más altos de proteína C reactiva, LDH y dímero-D, una afectación pulmonar más grave, más necesidad de ingreso en UCI, más tratamiento con lopinavir/ritonavir y fármacos biológicos, y mayor necesidad de terapia de sustitución renal. CONCLUSIONES: La hipovolemia y la deshidratación son una causa frecuente de FRA en pacientes con COVID-19. Aquellos que desarrollan FRA intrahospitalario presentan un perfil de peor pronóstico respiratorio, analítico y renal. Creemos que la monitorización de marcadores renales, así como el manejo individualizado de la volemia, pueden ser determinantes para prevenir el FRA

BACKGROUND AND AIM: In December 2019, a coronavirus 2019 (COVID-19) outbreak, caused by SARS-CoV-2, took place in Wuhan, China, and was declared a global pandemic in March 2020 by the World Health Organization. It is a prominently respiratory infection, with potential cardiological, hematological, gastrointestinal and renal complications. Acute kidney injury (AKI) is found in 0.5-25% of hospitalized COVID-19 patients and constitutes a negative prognostic factor. Renal damage mechanisms are not completely clear. We report the clinical evolution of hospitalized COVID-19 patients who presented with AKI requiring attention from the Nephrology team in a tertiary hospital in Madrid, Spain. METHODS: This is an observational prospective study including all COVID-19 cases that required hospitalization and Nephrology management from March 6th to May 12th 2020. We collected clinical and analytical data of baseline characteristics, COVID-19 and AKI evolutions. RESULTS: We analyzed 41 patients with a mean age of 66.8 years (SD 2.1), 90.2% males, and with a history of chronic kidney disease in 36.6%. A percentage of 56.1 presented with severe pneumonia or acute respiratory distress syndrome, and 31.7% required intensive care. AKI etiology was prerenal in 61%, acute tubular necrosis in the context of sepsis in 24.4%, glomerular in 7.3% and tubular toxicity in 7.3% of the cases. We reported proteinuria in 88.9% and hematuria in 79.4% of patients. A percentage of 48.8 required renal replacement therapy. Median length of stay was 12 days (IQR 9-23) and 22% of the population died. Patients who developed AKI during hospital stay presented with higher C-reactive protein, LDH and D-dimer values, more severe pulmonary damage, more frequent ICU admission, treatment with lopinavir/ritonavir and biological drugs and renal replacement therapy requirement. CONCLUSIONS: Hypovolemia and dehydration are a frequent cause of AKI among COVID-19 patients. Those who develop AKI during hospitalization display worse prognostic factors in terms of pulmonary damage, renal damage, and analytical findings. We believe that monitorization of renal markers, as well as individualized fluid management, can play a key role in AKI prevention

Acute kidney failure in patients admitted due to COVID-19.

BACKGROUND AND AIM: In December 2019, a coronavirus 2019 (COVID-19) outbreak, caused by SARS-CoV-2, took place in Wuhan and was declared a global pandemic in March 2020 by the World Health Organization (WHO). It is a prominently respiratory infection, with potential cardiological, hematological, gastrointestinal and renal complications. Acute kidney injury (AKI) is found in 0.5%-25% of hospitalized COVID-19 patients and constitutes a negative prognostic factor. Renal damage mechanisms are not completely clear. We report the clinical evolution of hospitalized COVID-19 patients who presented with AKI requiring attention from the Nephrology team in a tertiary hospital in Madrid, Spain. METHODS: This is an observational prospective study including all COVID-19 cases that required hospitalization and Nephrology management from March 6th to May 12th. We collected clinical and analytical data of baseline characteristics, COVID-19 and AKI evolutions. RESULTS: We analyzed 41 patients with a mean age of 66.8 years (SD 2.1), 90.2% males, and with a history of chronic kidney disease (CKD) in 36.6%. 56.1% of patients presented with sever pneumonia or acute respiratory distress syndrome (ARDS), and 31.7% required intensive care. AKI etiology was prerenal in 61%, acute tubular necrosis in the context of sepsis in 24.4%, glomerular in 7.3% and tubular toxicity in 7.3% of the cases. We reported proteinuria in 88.9% and hematuria in 79.4% of patients. 48.8% of patients required renal replacement therapy (RRT). Median length of stay was 12 days (interquartilic range 9-23) and 22% of the population died. Patients who developed AKI during hospital stay presented with higher C-reactive protein, Lactate dehydrogenase-LDH and d-dimer values, more severe pulmonary damage, more frequent intensive care unit-ICU admission, treatment with lopinavir/ritonavir and biological drugs and RRT requirement. CONCLUSIONS: Hypovolemia and dehydration are a frequent cause of AKI among COVID-19 patients. Those who develop AKI during hospitalization display worse prognostic factors in terms of pulmonary damage, renal damage, and analytical findings. We believe that monitorization of renal markers as well as individualized fluid management can play a key role in AKI prevention.

Renal replacement therapy in critically ill patients with acute kidney injury: 2020 nephrologist's perspective.

Renal replacement therapies (RRT) as support for acute kidney injury in critically ill patients have become a routine and essential practice in their management, resulting in the widespread use of various techniques among these patients, such as intermittent hemodialysis (IHD), extended hemodialysis and continuous RRT (CRRT). In this review we aim to summarize current evidence of indication, choice of modality, timing of initiation, dosing and technical aspects of RRT. We carried out a narrative review based on guidelines, consensus documents by main working groups and the latest relevant clinical trials on RRT in the critically ill. We did not find enough evidence of any RRT modality having superior benefits in terms of patient survival, length of intensive care unit/hospital stay or renal outcomes among critically ill patients, in spite of optimization of clinical indication, modality, timing of initiation and intensity of initial therapy. This is still a controverted matter, since only early start of high-flux CRRT has been proven beneficial over IHD among hemodynamically unstable postoperative patients. Our objective is to portrait current RRT practices in multidisciplinary management of critically ill patients by intensive care and nephrology professionals. Implication of a nephrologist in the assessment of hemodynamic status, coexisting medical conditions, renal outcome expectations and management of resources could potentially have benefits at the time of RRT selection and troubleshooting.

Renal replacement therapy in critically ill patients with acute kidney injury: 2020 nephrologist's perspective. / Una visión nefrológica del tratamiento sustitutivo renal en el paciente crítico con fracaso renal agudo: horizonte 2020.

Renal replacement therapies (RRT) as support for acute kidney injury in critically ill patients have become a routine and essential practice in their management, resulting in the widespread use of various techniques among these patients, such as intermittent hemodialysis (IHD), extended hemodialysis and continuous RRT (CRRT). In this review we aim to summarize current evidence of indication, choice of modality, timing of initiation, dosing and technical aspects of RRT. We carried out a narrative review based on guidelines, consensus documents by main working groups and the latest relevant clinical trials on RRT in the critically ill. We did not find enough evidence of any RRT modality having superior benefits in terms of patient survival, length of intensive care unit/hospital stay or renal outcomes among critically ill patients, in spite of optimization of clinical indication, modality, timing of initiation and intensity of initial therapy. This is still a controverted matter, since only early start of high-flux CRRT has been proven beneficial over IHD among hemodynamically unstable postoperative patients. Our objective is to portrait current RRT practices in multidisciplinary management of critically ill patients by intensive care and nephrology professionals. Implication of a nephrologist in the assessment of hemodynamic status, coexisting medical conditions, renal outcome expectations and management of resources could potentially have benefits at the time of RRT selection and troubleshooting.

[Acute kidney failure in patients admitted due to COVID-19]. / Fracaso renal agudo en pacientes hospitalizados por COVID-19.

BACKGROUND AND AIM: In December 2019, a coronavirus 2019 (COVID-19) outbreak, caused by SARS-CoV-2, took place in Wuhan, China, and was declared a global pandemic in March 2020 by the World Health Organization. It is a prominently respiratory infection, with potential cardiological, hematological, gastrointestinal and renal complications. Acute kidney injury (AKI) is found in 0.5-25% of hospitalized COVID-19 patients and constitutes a negative prognostic factor. Renal damage mechanisms are not completely clear. We report the clinical evolution of hospitalized COVID-19 patients who presented with AKI requiring attention from the Nephrology team in a tertiary hospital in Madrid, Spain. METHODS: This is an observational prospective study including all COVID-19 cases that required hospitalization and Nephrology management from March 6th to May 12th 2020. We collected clinical and analytical data of baseline characteristics, COVID-19 and AKI evolutions. RESULTS: We analyzed 41 patients with a mean age of 66.8 years (SD 2.1), 90.2% males, and with a history of chronic kidney disease in 36.6%. A percentage of 56.1 presented with severe pneumonia or acute respiratory distress syndrome, and 31.7% required intensive care. AKI etiology was prerenal in 61%, acute tubular necrosis in the context of sepsis in 24.4%, glomerular in 7.3% and tubular toxicity in 7.3% of the cases. We reported proteinuria in 88.9% and hematuria in 79.4% of patients. A percentage of 48.8 required renal replacement therapy. Median length of stay was 12 days (IQR 9-23) and 22% of the population died. Patients who developed AKI during hospital stay presented with higher C-reactive protein, LDH and D-dimer values, more severe pulmonary damage, more frequent ICU admission, treatment with lopinavir/ritonavir and biological drugs and renal replacement therapy requirement. CONCLUSIONS: Hypovolemia and dehydration are a frequent cause of AKI among COVID-19 patients. Those who develop AKI during hospitalization display worse prognostic factors in terms of pulmonary damage, renal damage, and analytical findings. We believe that monitorization of renal markers, as well as individualized fluid management, can play a key role in AKI prevention.

Incidence of Hypersensitivity Reactions During Hemodialysis.

BACKGROUND/AIMS: A recent alert from Spanish health authorities warned of a higher incidence of reported hypersensitivity reactions to hemodialysis membranes with polysulfone, in the 2017 review of acute reactions to dialyzers found only published reports in the 21st century on polysulfone and its derivatives. The aim is to assess/evaluate the current incidence and characteristics of hypersensitivity reactions in hemodialysis patients. METHODS: A retrospective multicentre study in 9 Spanish hospitals evaluated patients in whom a hypersensitivity reaction required a change in dialyzer membrane. RESULTS: A total of 37 patients out of 1561 (2.37%) had hypersensitivity reactions and clinical, epidemiological and analytical data were available for 33 patients (2.11%). The membranes involved were polysulfone (n=23), polynephron (n=8), polyethersulfone (n=1) and polyacrylonitrile (n=1). This distribution reflected the frequency of use of membranes in the participating dialysis units. The reactions were described as type A in 18 cases and type B in 15 cases. There were no significant differences between the two types in clinical symptoms, the composition of the membrane involved, the method of sterilization, the season, or the time during the session in which they occurred. The most frequent symptom was dyspnea/breathlessness (64% of reactions). Eosinophilia was common (74%). 54% of the reactions occurred within the first 30 minutes of hemodialysis, 64% occurred during the first year of dialysis, and 54% required discontinuation of dialysis session. Cellulose triacetate was used as an alternative dialyzer in 78% of the cases. CONCLUSION: The incidence of hypersensitivity reactions was in the range found in reports from 20 years ago and is observed associated with synthetic membranes, not just polysulfones. Cellulose triacetate appears to be a good alternative for these patients.