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Introduction. Eighty percent of children with primitive nephrotic syndrome (NS) will have at least one relapse in their life. Specific risk factors could be associated with a higher incidence of relapses and a worse prognosis. This study aims to deepen the demographic and onset-related risk factors in children with known diagnosis of primitive NS attending the Pediatric Nephrology Unit of the University Hospital of Padua. Methods. Observational, descriptive study of all children (1-11 years old) with a known diagnosis of Primitive NS who attended our Pediatric Nephrology Unit between 1 January 2002 and 31 March 2023. Results. 49 patients were involved. 79.5% had at least one episode of NS relapse during their lifetime. 69.4% were classified as frequently relapsing or steroid-dependent NS. The relapse risk factor "non-Western ethnicity" was related to a worse prognosis and steroid-dependent NS classification (p = 0.041). The onset-related risk factor "thrombocytosis" appears to be related to a better prognosis (p = 0.03). Conclusion. The relapse risk factors "non-Western ethnicity" and "thrombocytosis" are characterized by worse and better prognosis, respectively. This evidence could support the follow-up of primitive NS in pediatric age.
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Síndrome Nefrótico , Recurrencia , Humanos , Factores de Riesgo , Niño , Preescolar , Masculino , Femenino , Lactante , PronósticoAsunto(s)
Vasculitis por IgA , Síndrome Nefrótico , Humanos , Síndrome Nefrótico/diagnóstico , Síndrome Nefrótico/inmunología , Síndrome Nefrótico/tratamiento farmacológico , Vasculitis por IgA/diagnóstico , Vasculitis por IgA/tratamiento farmacológico , Vasculitis por IgA/complicaciones , Vasculitis por IgA/inmunología , Resultado del Tratamiento , Niño , Masculino , Femenino , Inmunoglobulina A/sangre , Inmunoglobulina A/inmunología , Inmunosupresores/uso terapéutico , BiopsiaRESUMEN
BACKGROUND: Low albumin level is a risk factor for thromboembolic events in patients with NS (nephrotic syndrome). However, little is known about the proportion and characteristics of patients with NS who experience thromboembolic events with relatively high albumin levels (≥ 25 g/L). Therefore, we explored the features of this specific group of patients. METHODS: This study included all hospitalized patients in our center for the past 10 years who had diagnoses of NS and relevant thromboembolic events. We divided them into 2 groups based on their serum albumin level when the thromboembolic event occurred. The clinical data were analyzed with SPSS software. RESULTS: There were 312 patients enrolled in our study. Eighty-four (26.9%) of them had relatively high albumin levels (≥ 25 g/L). Patients with NS with high albumin levels had significantly lower levels of 24-h proteinuria (P < 0.01) and a higher rate of autoimmune disease (P = 0.03) than the low-albumin group. Membranous nephropathy (MN) was the most frequent pathological type of NS in patients with thromboembolic events, regardless of their albumin level. There were significantly fewer patients with anti-PLA2R (M-type phospholipase A2 receptor)-positive MN in the high-albumin group than in the low-albumin group (P < 0.01). CONCLUSIONS: Our study found that there was still a high risk for patients with NS and relatively high albumin levels to develop thromboembolic events.
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Síndrome Nefrótico , Albúmina Sérica , Tromboembolia , Humanos , Masculino , Femenino , Síndrome Nefrótico/sangre , Síndrome Nefrótico/complicaciones , Tromboembolia/sangre , Tromboembolia/etiología , Tromboembolia/epidemiología , Persona de Mediana Edad , Albúmina Sérica/metabolismo , Albúmina Sérica/análisis , Factores de Riesgo , Adulto , Anciano , Estudios RetrospectivosRESUMEN
OBJECTIVES: To investigate the incidence and risk factors for acute kidney injury (AKI) in children with primary nephrotic syndrome (PNS), as well as the role of neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) in the early identification of AKI in these children. METHODS: A prospective collection of clinical data from children hospitalized with PNS at the Children's Hospital of the Capital Institute of Pediatrics from January 2021 to October 2022 was conducted. The children were divided into two groups based on the presence of AKI: the AKI group (47 cases) and the non-AKI group (169 cases). The risk factors for AKI in children with PNS were identified by multivariate logistic regression analysis. Urinary KIM-1 and NGAL levels were compared between the AKI and non-AKI groups, as well as among the different stages of AKI. RESULTS: The incidence of AKI in children with PNS was 21.8%. Multivariate logistic regression analysis revealed that steroid-resistant nephrotic syndrome, gastrointestinal infections, and heavy proteinuria were independent risk factors for AKI in these children with PNS (P<0.05). Urinary KIM-1 and NGAL levels were higher in the AKI group compared to the non-AKI group (P<0.05), and the urinary NGAL and KIM-1 levels in the AKI stage 2 and stage 3 subgroups were higher than those in the AKI stage 1 subgroup (P<0.017). CONCLUSIONS: KIM-1 and NGAL can serve as biomarkers for the early diagnosis of AKI in children with PNS. Identifying high-risk populations for AKI in children with PNS and strengthening the monitoring of related risk factors is of significant importance.
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Lesión Renal Aguda , Receptor Celular 1 del Virus de la Hepatitis A , Lipocalina 2 , Síndrome Nefrótico , Humanos , Síndrome Nefrótico/complicaciones , Síndrome Nefrótico/orina , Masculino , Femenino , Lesión Renal Aguda/etiología , Lesión Renal Aguda/orina , Lesión Renal Aguda/diagnóstico , Preescolar , Niño , Lipocalina 2/orina , Receptor Celular 1 del Virus de la Hepatitis A/análisis , Factores de Riesgo , Estudios Prospectivos , Lactante , Modelos Logísticos , Diagnóstico PrecozRESUMEN
Background: A renal biopsy is essential for the identification and management of renal disorders. Although considered an invasive operation, it is necessary for a definitive diagnosis and treatment of many renal diseases. The primary goal of this study was to assess the clinicopathological aspect of renal diseases undergoing biopsy in children receiving tertiary care.Patients and Methods: Children (≤18 years) hospitalized with nephrotic syndrome were the subjects of this cross-sectional study, and comprehensive assessments confirmed the need for a kidney biopsy. Included were 277 children who met the inclusion and exclusion criteria. Data on patient outcomes, biopsy indications, complications, histopathologic results, and demographic information were documented.Results: Of the 277 patients who underwent renal biopsy, 63.2% were male, and 36.8% were female. Average age of the patients was 15 ± 2.9 years, with age distribution ranging from 3 to 18 years. The most frequent indication for renal biopsy was atypical age of <1 and >10-years-old (91.7%), steroid-resistant (5.1%), asymptomatic hematuria (21.3%), abnormal glomerular filtration rate (16.2%), and proteinuria (14.8%). The most common histopathological findings were focal segmental glomerulosclerosis (FSGS) (36.5%), followed by minimal change disease (MCD) (13.4%), membranoproliferative glomerulonephritis (MPGN) (10.5%), membranous glomerulonephritis (MGN) (7.94%), IgA nephropathy (IGAN) (7.58%), non-proliferative glomerulonephritis (NPGN) (7.58%), diffuse proliferative glomerulonephritis (DPGN) (6.9%), crescentic GN (5.8%), and systemic lupus erythematosus (SLE) (3.97%). The high frequency of positive samples was seen in SLE, followed by DPGN, MPGN, IGAN, and MGN. In contrast, MCD, crescentic GN, and NPGN showed negativity in all differential item functioning (DIF) parameters.Conclusion: Renal biopsy is a safe and effective procedure in the diagnosis and treatment of in children with nephrotic syndrome. FSGS had the highest frequency in examined biopsies.
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Riñón , Síndrome Nefrótico , Humanos , Síndrome Nefrótico/patología , Femenino , Masculino , Niño , Adolescente , Biopsia , Preescolar , Estudios Transversales , Riñón/patología , Glomeruloesclerosis Focal y Segmentaria/patología , Glomeruloesclerosis Focal y Segmentaria/diagnósticoRESUMEN
INTRODUCTION: There is a scarcity of research comparing the efficacy of cyclophosphamide and mycophenolate mofetil in childhood nephrotic syndrome. The aim was to evaluate the efficacy and safety of oral cyclophosphamide (CYC) and mycophenolate mofetil (MMF) in children with steroid-sensitive nephrotic syndrome in terms of the proportion of children who have been off steroids for at least 6 months without proteinuria (responders). METHODS: This open-label retrospective-prospective comparative study was conducted in a pediatric nephrology clinic of a referral center for children between 1 and 18 years of age with FR/SD nephrotic syndrome. Group A consisted of patients who received oral cyclophosphamide (100, 25% female) at a dose of 2-2.5 mg/kg once daily for a period of 8-12 weeks. Group B consisted of patients who received oral mycophenolate mofetil (n = 61, 18% female) (dose: 800-1200 mg/m2) for at least 12 months. Responders were defined as children who were off steroids for at least 6 months along with absence of proteinuria. RESULTS: In the CYC group, 50% of the patients were responders, whereas 54% of the patients in the MMF group were responders (p = 0.614). The time to first relapse with CYC was 7 months (IQR 5.25-11) compared to 7 months (IQR 3.5-12) with MMF (p = 0.092). The relapse rate in the CYC group was 1.77 relapses per patient-year compared to 1.295 relapses per patient-year in the MMF group. The difference in relapse rate was significant (-0.474; 95% CI, 0.09 to 0.86 relapses/person-year) (p value = 0.009). Multivariate analysis revealed that an age of less than 5 years at the start of treatment was a significant factor for a better response to MMF (p value = 0.039, OR = 2.988, CI -1.055-8.468). CONCLUSIONS: The efficacy of MMF was similar to that of CYC in terms of response (6 months without steroids) in children with FR/SD nephrotic syndrome. MMF showed a favorable response in terms of the frequency of relapse and treatment failure. REGISTRATION OF THE STUDY WITH CLINICAL TRIALS REGISTRY OF INDIA: ( http://ctri.nic.in ;CTRI/2021/06/034421) (Dt: 28/06/2021).
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Ciclofosfamida , Inmunosupresores , Ácido Micofenólico , Síndrome Nefrótico , Humanos , Ácido Micofenólico/uso terapéutico , Ácido Micofenólico/administración & dosificación , Síndrome Nefrótico/tratamiento farmacológico , Femenino , Niño , Masculino , Ciclofosfamida/uso terapéutico , Ciclofosfamida/administración & dosificación , Ciclofosfamida/efectos adversos , Preescolar , Adolescente , Inmunosupresores/uso terapéutico , Inmunosupresores/administración & dosificación , Inmunosupresores/efectos adversos , Administración Oral , Lactante , Resultado del Tratamiento , Estudios Retrospectivos , Estudios ProspectivosRESUMEN
Amyloidosis is a localized or systemic disease caused by deposition of proteins in the extracellular space of various organs and tissues. As part of the disease, proteins that were originally soluble misfold and acquire a fibrillar conformation that renders them insoluble and resistant to proteolysis. Systemic amyloidosis is a rare, often underdiagnosed condition. In recent years, the incidence of newly diagnosed cases of amyloidosis has been increasing in association with the aging of the population and greater access to diagnostic tests. From a clinical perspective, systemic amyloidosis is frequently associated with involvement of the kidneys (causing nephrotic syndrome), heart (cardiac failure and arrhythmia), and peripheral nervous system (sensorimotor polyneuropathy and autonomic dysfunction). This condition is important to the rheumatologist for several reasons, such as its systemic involvement that mimics autoimmune rheumatic diseases, its musculoskeletal manifestations, which when recognized can allow the diagnosis of amyloidosis, and also because reactive or secondary AA amyloidosis is a complication of rheumatic inflammatory diseases. The treatment of amyloidosis depends on the type of amyloid protein involved. Early recognition of this rare disease is fundamental for improved clinical outcomes.
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Amiloidosis , Enfermedades Reumáticas , Humanos , Amiloidosis/diagnóstico , Amiloidosis/complicaciones , Enfermedades Reumáticas/complicaciones , Síndrome Nefrótico/etiología , Reumatólogos , Diagnóstico Diferencial , Proteína Amiloide A SéricaRESUMEN
BACKGROUND: In nephrotic syndrome, protein leaks from the blood into the urine through the glomeruli, resulting in hypoproteinaemia and generalised oedema. While most children with nephrotic syndrome respond to corticosteroids, 80% experience a relapsing course. Corticosteroids have reduced the death rate to around 3%; however, corticosteroids have well-recognised potentially serious adverse events such as obesity, poor growth, hypertension, diabetes mellitus, osteoporosis, cataracts, glaucoma and behavioural disturbances. This is an update of a review first published in 2000 and updated in 2002, 2005, 2007, 2015 and 2020. OBJECTIVES: The aim of this review was to assess the benefits and harms of different corticosteroid regimens in children with steroid-sensitive nephrotic syndrome (SSNS). The benefits and harms of therapy were studied in two groups of children: 1) children in their initial episode of SSNS and 2) children who experience a relapsing course of SSNS. SEARCH METHODS: We contacted the Information Specialist and searched the Cochrane Kidney and Transplant Register of Studies up to 9 July 2024 using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal, and ClinicalTrials.gov. SELECTION CRITERIA: Randomised controlled trials (RCTs) performed in children (one to 18 years) during their initial or subsequent episode of SSNS, comparing different durations, total doses or other dose strategies using any corticosteroid agent. DATA COLLECTION AND ANALYSIS: Summary estimates of effects were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes and mean difference (MD) and 95% CI for continuous outcomes. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. MAIN RESULTS: In this 2024 update, we included five new studies, resulting in 54 studies randomising 4670 children. Risk of bias methodology was often poorly performed, with only 31 studies and 28 studies respectively assessed to be at low risk for random sequence generation and allocation concealment. Ten studies were at low risk of performance bias (blinding of participants and personnel), and 12 studies were at low risk of detection bias (blinding of outcome assessment); nine of these studies were placebo-controlled RCTs. Twenty-seven studies (fewer than 50%) were at low risk for attrition bias, and 26 studies were at low risk for reporting bias (selective outcome reporting). In studies at low risk of selection bias evaluating children in their initial episode of SSNS, there is little or no difference in the number of children with frequent relapses when comparing two months of prednisone with three months or more (RR 0.96, 95% CI 0.83 to 1.10; 755 children, 5 studies; I2 = 0%; high certainty evidence) or when comparing three months with five to seven months of therapy (RR 0.99, 95% CI 0.74 to 1.33; 376 children, 3 studies; I2 = 35%; high certainty evidence). In analyses of studies at low risk of selection bias, there is little or no difference in the number of children with any relapse by 12 to 24 months when comparing two months of prednisone with three months or more (RR 0.93, 95% CI 0.81 to 1.06; 808 children; 6 studies; I2 = 47%) or when comparing three months with five to seven months of therapy (RR 0.88, 95% CI 0.70 to 1.11; 377 children, 3 studies; I2 = 53%). Little or no difference was noted in adverse events between the different treatment durations. Amongst children with relapsing SSNS, four small studies (177 children) utilising lower doses of prednisone compared with standard regimens found little or no differences between groups in the numbers with relapse (RR 1.01, 95% CI 0.85 to 1.20; I2 = 0%). A fifth study (117 children) reported little or no difference between two weeks and four weeks of alternate-day prednisone after remission with daily prednisone. A recent large, well-designed study with 271 children found that administering daily prednisone compared with alternate-day prednisone or no prednisone during viral infection did not reduce the risk of relapse. In contrast, four previous small studies in children with frequently relapsing disease had reported that daily prednisone during viral infections compared with alternate-day prednisone or no treatment reduced the risk of relapse. AUTHORS' CONCLUSIONS: There are four well-designed studies randomising 823 children, which have demonstrated that there is no benefit of prolonging prednisone therapy beyond two to three months in the first episode of SSNS. Small studies in children with relapsing disease have identified no differences in efficacy using lower induction doses or shorter durations of prednisone therapy. Large, well-designed studies are required to confirm these findings. While previous small studies had suggested that changing from alternate-day to daily prednisone therapy at the onset of infection reduced the likelihood of relapse, a much larger and well-designed study found no reduction in the number relapsing when administering daily prednisone at the onset of infection.
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Síndrome Nefrótico , Ensayos Clínicos Controlados Aleatorios como Asunto , Recurrencia , Síndrome Nefrótico/tratamiento farmacológico , Humanos , Niño , Preescolar , Adolescente , Lactante , Corticoesteroides/uso terapéutico , Corticoesteroides/efectos adversos , Sesgo , Glucocorticoides/uso terapéutico , Glucocorticoides/efectos adversos , Dexametasona/uso terapéuticoRESUMEN
Objective: To investigate the factors affecting the time taken for B cell reconstitution after rituximab (RTX) treatment in children with steroid-sensitive nephrotic syndrome. Methods: This was a retrospective cohort study. The clinical data of 42 children with SSNS who received treatment with RTX in Department of Nephrology, Rheumatology and Immunology, Children's Hospital Affiliated to Zhengzhou University between December 2019 and May 2023 were analyzed retrospectively. The data of demographics, immunosuppressant treatment and laboratory tests such as CD19+B cell count, urinary protein quantification were collected. The patients were divided into 2 groups, the early B cell reconstruction group and the late reconstruction group based on the average time of B cell reconstruction. A multivariate logistic regression model was used to analyze the factors impacting the timing of B cell reconstruction, and the predictive value of these factors was assessed by plotting the receiver operating characteristic (ROC) curve. Results: There were 42 children, with 35 males and 7 females. They were aged 3.5 (2.2, 5.9) years at the onset of PNS and (8.4±3.3) years at their first RTX treatment. The time for B cell reconstitution was (152±53) d. There were 20 children in the early reconstruction group and 22 children in the late reconstruction group. There were no statistically significant differences (all P>0.05) between the 2 groups in terms of the cumulative dose of steroids within 1 year before receiving RTX infusion (0.29 (0.16, 0.50) vs. 0.29 (0.19, 0.46) mg/(kg·d)), the percentage of children using tacrolimus before RTX (65%(13/20) vs. 45%(10/22)) and cumulative doses (0.04 (0.03, 0.05) vs. 0.03 (0.03, 0.06) mg/(kg·d)), the steroid doses at the time of RTX infusion (0.73 (0.49, 0.90) vs. 0.71 (0.58, 0.89) mg/(kg·d)), the percentage of children using tacrolimus at the initial RTX infusion (50% (10/20)vs. 41% (9/22)) and the doses (0.03 (0.02, 0.04) vs. 0.02 (0.01, 0.04) mg/(kg·d)), the discontinuation time of tacrolimus post-RTX infusion (71 (42, 91) vs. 64 (42, 91) d). A multivariate analysis revealed a correlation (OR=0.26, 95%CI 0.10-0.68, P=0.006) between B cell count following the second RTX infusion and the time taken for B cell reconstruction. The area under the ROC curve for B cell count after the RTX infusion in predicting the time to B cell reconstruction was 0.89 (95%CI 0.78-0.99, P<0.001) and the cut-off value was 0.925×106/L. Conclusions: The time of B cell reconstruction is not influenced by the previous or concurrent use of tacrolimus, regardless of its duration and the dosage of steroid and tacrolimus prior to the RTX infusion. Insteadly, the peripheral blood B cell count (0.925×106/L) following the second RTX infusion for SSNS is identified as an independent predictor of reconstruction time, allowing for a more precise prediction and early intervention to maintain disease remission.
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Linfocitos B , Síndrome Nefrótico , Rituximab , Humanos , Rituximab/uso terapéutico , Rituximab/administración & dosificación , Femenino , Masculino , Síndrome Nefrótico/tratamiento farmacológico , Estudios Retrospectivos , Niño , Linfocitos B/inmunología , Preescolar , Inmunosupresores/uso terapéutico , Inmunosupresores/administración & dosificación , Antígenos CD19 , Factores de TiempoRESUMEN
BACKGROUND: Globally, the predominant histopathologic characteristic of childhood nephrotic syndrome has been minimal change nephropathy (MCN). However, some studies from Africa and Nigeria have revealed otherwise. It is imperative that this pattern is re-examined from time to time given changing disease and environmental dynamics from place to place. OBJECTIVE: This study aimed to determine the histopathological characteristics of childhood nephrotic syndrome in Ilorin, northcentral Nigeria. METHODS: A prospective study of all new patients aged 2-14 years who presented with clinical features of nephrotic syndrome between January 2010 to December 2023 at the University of Ilorin Teaching Hospital, Ilorin was carried out. All eligible patients underwent renal biopsy. RESULTS: A total of 47 children with nephrotic syndrome were biopsied comprising of 21 males and 26 females making an M: F ratio of 1:1.2. The age range of subjects was 2-14 years with a mean of 7.8 ±3.6 years. The most common histological type of nephrotic syndrome was minimal change nephrotic syndrome (MCNS) which occurred in 35(74.5%) children followed by membranoproliferative glomerulonephritis (MPGN) in 5(10.6%) and focal segmental glomerulosclerosis (FSGS) in 2(4.3%). Of the 35 MCNS patients, 31(88.6%) were steroid sensitive while 4(11.4%) were steroid resistant. CONCLUSION: The predominant histopathological characteristic of childhood nephrotic syndrome was minimal change nephrotic syndrome, which was mostly steroid-sensitive.
CONTEXTE: Au niveau mondial, la principale caractéristique histopathologique du syndrome néphrotique de l'enfant a été la néphropathie à lésions minimales (NLM). Cependant, certaines études en Afrique et au Nigeria ont montré des résultats différents. Il est essentiel de réévaluer ce modèle régulièrement en raison de l'évolution des maladies et de l'environnement d'un endroit à l'autre. OBJECTIF: Cette étude visait à déterminer les caractéristiques histopathologiques du syndrome néphrotique de l'enfant à Ilorin, dans le nord-centre du Nigeria. MÉTHODES: Une étude prospective de tous les nouveaux patients âgés de 2 à 14 ans présentant des signes cliniques de syndrome néphrotique entre janvier 2010 et décembre 2023 à l'hôpital universitaire d'Ilorin, à Ilorin, a été réalisée. Tous les patients éligibles ont subi une biopsie rénale. RÉSULTATS: Au total, 47 enfants atteints du syndrome néphrotique ont été biopsiés, dont 21 garçons et 26 filles, soit un ratio H/F de 1/1,2. La tranche d'âge des sujets était de 2 à 14 ans avec une moyenne de 7,8 ± 3,6 ans. Le type histologique le plus fréquent du syndrome néphrotique était la néphropathie à lésions minimales (NLM), obser vée chez 35 (74,5 %) enfants, suivie de la glomérulonéphrite membranoproliférative (GMPN) chez 5 (10,6 %) et du sclérose segmentaire et focale (SSF) chez 2 (4,3 %). Parmi les 35 patients atteints de NLM, 31 (88,6 %) étaient cortico-sensibles et 4 (11,4 %) cortico-résistants. CONCLUSION: La principale caractéristique histopathologique du syndrome néphrotique de l'enfant était la néphropathie à lésions minimales, qui était principalement cortico-sensible. MOTS-CLÉS: Syndrome néphrotique, Enfant, Histopathologie, Nigeria.
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Nefrosis Lipoidea , Síndrome Nefrótico , Humanos , Masculino , Niño , Femenino , Nigeria/epidemiología , Adolescente , Preescolar , Síndrome Nefrótico/patología , Síndrome Nefrótico/epidemiología , Estudios Prospectivos , Nefrosis Lipoidea/patología , Nefrosis Lipoidea/epidemiología , Biopsia/métodos , Glomeruloesclerosis Focal y Segmentaria/patología , Glomeruloesclerosis Focal y Segmentaria/epidemiología , Centros de Atención Terciaria , Glomerulonefritis Membranoproliferativa/patología , Glomerulonefritis Membranoproliferativa/epidemiología , Riñón/patologíaRESUMEN
BACKGROUND: Nephrotic syndrome (NS) is a rare complication that can occur after haematopoietic stem cell transplantation (HSCT). In patients with membranous nephropathy (MN) who have undergone allogeneic HSCT, a new antigen called protocadherin FAT1 has been identified. Our objective is to present a case series of MN patients after HSCT with a novel antigen-based stratification. CASE PRESENTATIONS: Patients who developed full-blown NS due to MN after an HSCT were enrolled in the University Hospital Centre Zagreb study. The first two patients were treated with an HSCT for acute myeloid leukaemia, and both developed NS after cessation of graft versus host disease (GVHD) prophylaxis. The first patient had reduced kidney function, while the second had completely preserved function. Kidney biopsy showed MN with only subepithelial deposits. A thorough examination revealed that there was no secondary cause of the disease. The patients achieved complete remission after undergoing immunosuppression treatment. The third patient underwent HSCT for acute lymphoblastic leukaemia. He developed both acute and chronic GVHD and also experienced avascular hip necrosis. After sixteen years, the patient developed NS with preserved kidney function. The kidney specimen showed membranous nephropathy (MN) with mesangial and subepithelial deposits. Extensive research was conducted, but no secondary cause for the MN was detected. All three cases tested negative for anti-PLA2R antibodies. Biopsy tissue samples were analysed using laser microdissection and tandem mass spectrometry of glomeruli for the detection of different specific antigens. Patients one and two tested positive for FAT1, whereas patient three tested positive for PCSK6. CONCLUSIONS: MN can develop at various time intervals after HSCT. Specific antigen testing can help establish the relationship between MN and HSCT. In the future, serum testing for anti-FAT1 antibodies in HSCT patients could be significant in diagnosing FAT1-associated MN, similar to how anti-PLA2R antibodies are significant in diagnosing PLA2R-associated MN.
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Glomerulonefritis Membranosa , Trasplante de Células Madre Hematopoyéticas , Humanos , Glomerulonefritis Membranosa/inmunología , Glomerulonefritis Membranosa/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Masculino , Adulto , Persona de Mediana Edad , Leucemia Mieloide Aguda/terapia , Síndrome Nefrótico/etiologíaRESUMEN
BACKGROUND: Minimal Change Disease (MCD) and Focal Segmental Glomerulosclerosis (FSGS) are a spectrum of disease causing the nephrotic syndrome (NS), characterised by proteinuria with debilitating oedema, as well as a high risk of venous thromboembolic disease and infection. Untreated, 50-60% patients with FSGS progress to end stage kidney disease after 5 years. These diseases respond to immunosuppression with high dose glucocorticoids, but 75% will relapse as the glucocorticoids are withdrawn, leading to significant morbidity associated with prolonged use. In children, the B cell depleting monoclonal antibody rituximab reduces relapse risk, but this drug has not been tested in randomised controlled trial in adults. METHODS: 130-150 adults with new or relapsing MCD/FSGS, from UK Renal Units, are being randomised to receive either rituximab (two 1 g infusions two weeks apart) or placebo. Partipicipants are recruited when they present with nephrosis, and all are treated with glucocorticoids as per KDIGO guidelines. Once in remission, prednisolone is withdrawn according to a pre-specified regimen. If in remission at 6 months, participants receive a further dose of trial drug. If they relapse, they are unblinded, and if they have received placebo, they are offered open label rituximab with protocolised prednisolone as in the main phase of the trial. The primary end point is time from remission to relapse. A number of secondary endpoints will be assessed including the effect of rituximab on: (1) NHS and societal resource use and hence cost: (2) safety: (3) other measures of efficacy, such as achievement of partial and complete remission of NS and the preservation of renal function: (4) health status of participant. TRIAL REGISTRATION: TURING received ethical approval on 14 Jun 2019 - REC reference: 19/LO/0738. It is registered on EudraCT, with ID number: 2018-004611-50, with a start date of 2019-06-14.
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Análisis Costo-Beneficio , Glomeruloesclerosis Focal y Segmentaria , Nefrosis Lipoidea , Síndrome Nefrótico , Rituximab , Humanos , Rituximab/uso terapéutico , Método Doble Ciego , Nefrosis Lipoidea/tratamiento farmacológico , Glomeruloesclerosis Focal y Segmentaria/tratamiento farmacológico , Síndrome Nefrótico/tratamiento farmacológico , Recurrencia , Factores Inmunológicos/uso terapéutico , Factores Inmunológicos/economía , Resultado del Tratamiento , Adulto , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
OBJECTIVE: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) target the reabsorption of sodium and glucose in the kidney proximal tubules to reduce blood sugar levels. However, clinical randomized controlled trials on SGLT2i have yielded inconsistent results, necessitating further research into their efficacy and safety for specific cardiac and renal diseases. METHODS: "Sodium in urine" was selected as a downstream biomarker of SGLT2i. Single nucleotide polymorphisms were extracted from genome-wide association study data as instrumental variables. Mendelian randomization analysis was then conducted for cardiac and renal diseases and potential adverse events. The causal effects of SGLT2i on these diseases were determined based on inverse variance weighted results, followed by sensitivity and pleiotropy tests. RESULTS: SGLT2i had a significant protective effect against nephrotic syndrome (odds ratio [OR] 0.0011, 95% confidence interval [CI] 0.000-0.237), chronic glomerulonephritis (OR 0.0002, 95% CI 0.000-0.21), and hypertensive nephropathy (OR 0.0003, 95% CI 0.000-0.785). No causal effects were observed between SGLT2i and cardiac diseases or potential adverse events. CONCLUSIONS: SGLT2i can act as protective factors against nephrotic syndrome, chronic glomerulonephritis, and hypertensive nephropathy.
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Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Polimorfismo de Nucleótido Simple , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Humanos , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Inhibidores del Cotransportador de Sodio-Glucosa 2/efectos adversos , Síndrome Nefrótico/genética , Síndrome Nefrótico/tratamiento farmacológico , Enfermedades Renales/genética , Sodio/orina , Sodio/sangre , Glomerulonefritis/genética , Glomerulonefritis/tratamiento farmacológico , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Cardiopatías/genéticaRESUMEN
BACKGROUND: Personalized disease models are crucial for evaluating how diseased cells respond to treatments, especially in case of innovative biological therapeutics. Extracellular vesicles (EVs), nanosized vesicles released by cells for intercellular communication, have gained therapeutic interest due to their ability to reprogram target cells. We here utilized urinary podocytes obtained from children affected by steroid-resistant nephrotic syndrome with characterized genetic mutations as a model to test the therapeutic potential of EVs derived from kidney progenitor cells (nKPCs). METHODS: EVs were isolated from nKPCs derived from the urine of a preterm neonate. Three lines of urinary podocytes obtained from nephrotic patients' urine and a line of Alport syndrome patient podocytes were characterized and used to assess albumin permeability in response to nKPC-EVs or various drugs. RNA sequencing was conducted to identify commonly modulated pathways after nKPC-EV treatment. siRNA transfection was used to demonstrate the involvement of SUMO1 and SENP2 in the modulation of permeability. RESULTS: Treatment with the nKPC-EVs significantly reduced permeability across all the steroid-resistant patients-derived and Alport syndrome-derived podocytes. At variance, podocytes appeared unresponsive to standard pharmacological treatments, with the exception of one line, in alignment with the patient's clinical response at 48 months. By RNA sequencing, only two genes were commonly upregulated in nKPC-EV-treated genetically altered podocytes: small ubiquitin-related modifier 1 (SUMO1) and Sentrin-specific protease 2 (SENP2). SUMO1 and SENP2 downregulation increased podocyte permeability confirming the role of the SUMOylation pathway. CONCLUSIONS: nKPCs emerge as a promising non-invasive source of EVs with potential therapeutic effects on podocytes with genetic dysfunction, through modulation of SUMOylation, an important pathway for the stability of podocyte slit diaphragm proteins. Our findings also suggest the feasibility of developing a non-invasive in vitro model for screening regenerative compounds on patient-derived podocytes.
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Vesículas Extracelulares , Síndrome Nefrótico , Podocitos , Podocitos/metabolismo , Podocitos/efectos de los fármacos , Podocitos/patología , Humanos , Síndrome Nefrótico/patología , Síndrome Nefrótico/tratamiento farmacológico , Síndrome Nefrótico/metabolismo , Vesículas Extracelulares/metabolismo , Evaluación Preclínica de Medicamentos , Modelos Biológicos , Células Madre/metabolismo , Esteroides/farmacología , Riñón/patología , Riñón/metabolismo , Resistencia a Medicamentos , Recién Nacido , MasculinoRESUMEN
Schimke immuno-osseous dysplasia is a rare multisystemic disorder caused by biallelic loss of function of the SMARCAL1 gene that plays a pivotal role in replication fork stabilization and thus DNA repair. Individuals affected from this disease suffer from disproportionate growth failure, steroid resistant nephrotic syndrome leading to renal failure and primary immunodeficiency mediated by T cell lymphopenia. With infectious complications being the leading cause of death in this disease, researching the nature of the immunodeficiency is crucial, particularly as the state is exacerbated by loss of antibodies due to nephrotic syndrome or immunosuppressive treatment. Building on previous findings that identified the loss of IL-7 receptor expression as a possible cause of the immunodeficiency and increased sensitivity to radiation-induced damage, we have employed spectral cytometry and multiplex RNA-sequencing to assess the phenotype and function of T cells ex-vivo and to study changes induced by in-vitro UV irradiation and reaction of cells to the presence of IL-7. Our findings highlight the mature phenotype of T cells with proinflammatory Th1 skew and signs of exhaustion and lack of response to IL-7. UV light irradiation caused a severe increase in the apoptosis of T cells, however the expression of the genes related to immune response and regulation remained surprisingly similar to healthy cells. Due to the disease's rarity, more studies will be necessary for complete understanding of this unique immunodeficiency.
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Reparación del ADN , Osteocondrodisplasias , Enfermedades de Inmunodeficiencia Primaria , Humanos , Enfermedades de Inmunodeficiencia Primaria/genética , Enfermedades de Inmunodeficiencia Primaria/diagnóstico , Enfermedades de Inmunodeficiencia Primaria/inmunología , Osteocondrodisplasias/genética , Osteocondrodisplasias/inmunología , Reparación del ADN/genética , ADN Helicasas/genética , Síndrome Nefrótico/etiología , Síndrome Nefrótico/genética , Linfocitos T/inmunología , Arteriosclerosis/genética , Arteriosclerosis/etiología , Arteriosclerosis/inmunología , Masculino , Femenino , Embolia Pulmonar/genética , Embolia Pulmonar/etiología , Enfermedades Óseas Metabólicas/etiología , Enfermedades Óseas Metabólicas/genética , Trastornos del Crecimiento/genética , Trastornos del Crecimiento/etiología , Rayos Ultravioleta/efectos adversos , Niño , Apoptosis/genética , Síndromes de Inmunodeficiencia/genética , Síndromes de Inmunodeficiencia/inmunologíaRESUMEN
Cryptococcal infection of central nervous system commonly involves meningitis or meningoencephalitis, but rarely mimics inflammatory myelitis. We present short segment myelitis as a dominant manifestation caused by Cryptococcus neoformans in a patient with nephrotic syndrome under immunosuppressive therapy. This case report highlights Cryptococcus neoformans as a potential etiological factor for short segment myelitis in immunocompromised hosts.
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Criptococosis , Cryptococcus neoformans , Mielitis , Humanos , Mielitis/microbiología , Mielitis/tratamiento farmacológico , Mielitis/diagnóstico , Criptococosis/tratamiento farmacológico , Criptococosis/microbiología , Criptococosis/diagnóstico , Cryptococcus neoformans/aislamiento & purificación , Masculino , Huésped Inmunocomprometido , Persona de Mediana Edad , Síndrome Nefrótico/complicaciones , Inmunosupresores/uso terapéutico , Imagen por Resonancia MagnéticaRESUMEN
Genetic testing in nephrotic syndrome may identify heterozygous predicted-pathogenic variants (HPPVs) in autosomal recessive (AR) genes that are known to cause disease in the homozygous or compound heterozygous state. In such cases, it can be difficult to define the variant's true significance and questions remain about whether a second pathogenic variant has been missed during analysis or whether the variant is an incidental finding. There are now known to be over 70 genes associated with nephrotic syndrome, the majority inherited as an AR trait. Knowledge of whether such HPPVs occur with equal frequency in patients compared to the general population would assist interpretation of their significance. Exome sequencing was performed on 187 Steroid-Resistant Nephrotic Syndrome (SRNS) paediatric patients recruited to a UK rare disease registry plus originating from clinics at Evelina, London. 59 AR podocytopathy linked genes were analysed in each patient and a list of HPPVs created. We compared the frequency of detected HPPVs with a 'control' population from the gnomAD database containing exome data from approximately 50,000 individuals. A bespoke filtering process was used for both patients and controls to predict 'likely pathogenicity' of variants. In total 130 Caucasian SRNS patients were screened across 59 AR genes and 201 rare heterozygous variants were identified. 17/201 (8.5%) were assigned as 'likely pathogenic' (HPPV) using our bespoke filtering method. Comparing each gene in turn, for SRNS patients with a confirmed genetic diagnosis, in 57 of the 59 genes we found no statistically significant difference in the frequency of these HPPVs between patients and controls (In genes ARHGDIA and TP53RK, we identified a significantly higher number of HPPVs in the control population compared with the patients when filtering was performed with 'high stringency' settings only). In the SRNS patients without a genetics diagnosis confirmed, there was no statistically significant difference identified in any gene between patient and control. In children with SRNS, we propose that identification of HPPV in AR podocytopathy linked genes is not necessarily representative of pathogenicity, given that the frequency is similar to that seen in controls for the majority. Whilst this may not exclude the presence of genetic kidney disease, this type of heterozygous variant is unlikely to be causal and each result must be interpreted in its clinical context.
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Secuenciación del Exoma , Heterocigoto , Síndrome Nefrótico , Humanos , Síndrome Nefrótico/genética , Niño , Masculino , Femenino , Preescolar , Adolescente , Lactante , Pruebas Genéticas , Predisposición Genética a la Enfermedad , MutaciónRESUMEN
Patients with nephrotic syndrome (NS) present with edema, proteinuria, hypoalbuminemia, and hyperlipidemia. In children, the most common causes are idiopathic minimal change disease and focal segmental glomerulosclerosis (FSGS). In adults, FSGS and membranous nephropathy (MN) are the most common primary causes. There are numerous secondary causes, including diabetes, amyloidosis, systemic lupus erythematosus, hematologic malignancies, and infections. In addition to confirming the diagnosis of NS by measuring proteinuria and serum albumin and lipid levels, evaluation should assess for secondary causes. In children, most cases are due to minimal change disease, which is responsive to steroid treatment. A glucocorticoid should be prescribed for children younger than 12 years. If the patient improves with steroid treatment, no biopsy is needed. If the patient does not improve, genetic testing and kidney biopsy are warranted to determine the diagnosis. In adults, biopsy typically is indicated for diagnosis, except in patients with positive test results for serum anti-phospholipase A2 receptor antibodies. This is diagnostic of MN. For patients with NS, management of initial and infrequent recurrences involves reduction of proteinuria with glucocorticoids. Frequent recurrences and/or the inability to discontinue glucocorticoids requires alternative therapies. Steroid-resistant NS also requires use of alternative therapies. Long-term NS management includes dietary sodium restriction, edema management, and blood pressure control. Thromboembolism prophylaxis should be considered for patients with NS and high risk of thromboembolism, particularly those with MN.
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Síndrome Nefrótico , Humanos , Síndrome Nefrótico/diagnóstico , Síndrome Nefrótico/etiología , Síndrome Nefrótico/terapia , Glomeruloesclerosis Focal y Segmentaria/diagnóstico , Glomeruloesclerosis Focal y Segmentaria/terapia , Glomerulonefritis Membranosa/diagnóstico , Glomerulonefritis Membranosa/terapia , Glucocorticoides/uso terapéutico , Adulto , Niño , Nefrosis Lipoidea/diagnóstico , Nefrosis Lipoidea/terapia , Proteinuria/diagnóstico , Proteinuria/etiologíaRESUMEN
Objective: To investigate the clinicopathological features of renal leukocyte chemokine type 2 amyloidosis (ALECT2). Methods: The prevalence, clinical characteristics, renal histopathological features, and renal outcome of 15 patients with ALECT2 by kidney biopsy were collected in the Department of Kidney Pathology, Shanxi Medical University Second Hospital, Taiyuan, China from January 1993 to December 2023. Immunohistochemistry and mass spectrometry for amyloid proteins were carried out. Results: Fifteen patients with ALECT2 were included in the study, representing 12.93% (15/116) of the renal biopsy-proven amyloidosis cases. There were 5 males and 10 females. The median age at diagnosis was 61 years. All patients had various degrees of proteinuria; 7 patients had nephrotic syndrome; 3 patients had renal insufficiency; 7 patients had microscopic hematuria. Renal biopsy showed that strongly orangophilic amyloid proteins distributed mainly in the renal cortical interstitium, vascular walls, the glomerular mesangium and/or glomerular basement membrane. Eight cases were diagnosed with ALECT2 alone and 7 cases combined with other renal diseases, including 4 cases with membranous nephropathy, 2 cases with IgA nephropathy, and 1 case with subacute tubular interstitial nephropathy. ALECT2 patients with concurrent renal disease showed a higher proteinuria level than those without (3.48 g/24 h versus 4.58 g/24 h). All patients were corroborated by immunohistochemistry to exhibit the specific location of LECT2 in the amyloid fibrils. Mass spectrometry analysis revealed LECT2 polypeptide in 9 patients. Except two patients with worsening renal function, the others showed stable renal function during the mean follow-up period of 12.5 months. Conclusions: ALECT2 is the second common type of renal amyloidosis in our center. The majority of ALECT2 patients show concurrent renal diseases, with a high rate of membranous nephropathy. Amyloid deposits distribute mainly in the cortical interstitium of the kidney, the glomerular mesangium and vascular walls. Mass spectrometry is the most sensitive and specific method for detecting LECT2 amyloidosis.
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Amiloidosis , Enfermedades Renales , Riñón , Síndrome Nefrótico , Humanos , Masculino , Amiloidosis/metabolismo , Amiloidosis/patología , Amiloidosis/diagnóstico , Femenino , Persona de Mediana Edad , Síndrome Nefrótico/metabolismo , Síndrome Nefrótico/patología , Riñón/patología , Enfermedades Renales/patología , Enfermedades Renales/metabolismo , Proteinuria , Biopsia , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Glomerulonefritis Membranosa/patología , Glomerulonefritis Membranosa/metabolismo , Glomerulonefritis por IGA/patología , Glomerulonefritis por IGA/metabolismo , Anciano , Hematuria/etiología , Insuficiencia Renal/metabolismoRESUMEN
BACKGROUND: Nephrotic syndrome (NS) is associated with a high risk of thrombotic complications. In this group of patients, routine local tests for assessing hemostasis do not accurately reflect hypercoagulable state. Global functional tests for assessing hemostasis, including thrombodynamics (TD), are considered promising for assessing disorders in the blood coagulation system of these patients. AIM: To compare the rate of hypercoagulability according to routine hemostatic tests and TD and to evaluate the factors associated with increased risk of thrombotic complications in patients with chronic glomerulonephritis (CGN). MATERIALS AND METHODS: The study included 94 patients with active CGN who were not receiving anticoagulant therapy; 63 (80.3%) patients had NS, and 31 (19.7%) had active CGN without NS. Hemostasis parameters were assessed using local coagulation tests and TD test. Using logistic regression analysis, factors associated with the risk of thrombosis were assessed. RESULTS: Of the 94 patients with active CGN in 63 without preventive anticoagulant therapy, hypercoagulability according to routine tests was detected in 6 (9.5%) patients with NS and in 3 (9.7%) patients without NS (p<0.05). Hypercoagulability according to the TD test was detected in 24 (53.9%) patients with NS and in 5 (32.2%) without NS (p<0.05). The formation of spontaneous clots was observed in 29 (30.9%) of patients with CGN, most of them 24 (83%) with NS. 10.6% of patients in our cohort experienced thromboembolic events. The risk of thromboembolic events according to the univariate regression analysis was associated with older age, higher lipid levels, use of glucocorticosteroids and detection of spontaneous clots by the TD test. No association of thromboembolic events with abnormalities in routine hemostasis tests was obtained. CONCLUSION: In patients with CGN with nephrotic syndrome, hypercoagulability is detected in 9.5% of cases with routine coagulation tests and in 53.9% of cases with TD test. Detection of spontaneous clots by TD test is associated with a risk of thromboembolic events.