Case presentation: a severe case of cobalamin c deficiency presenting with nephrotic syndrome, malignant hypertension and hemolytic anemia.

BACKGROUND: The etiology of nephrotic syndrome can vary, with underlying metabolic diseases being a potential factor. Cobalamin C (cblC) defect is an autosomal recessive inborn error of metabolism caused by mutations in the MMACHC gene, resulting in impaired vitamin B12 processing. While cblC defect typically manifests with hematological and neurological symptoms, renal involvement is increasingly recognized but remains rare. CASE PRESENTATION: We describe a 7-month-old male patient presenting with fatigue and edema. His first laboratory findings showed anemia, thrombocytopenia, hypoalbuminemia and proteinuria and further examinations reveals hemolysis in peripheric blood smear. During his follow up respiratory distress due to pleural effusion in the right hemithorax was noticed. And fluid leakage to the third spaces supported nephrotic syndrome diagnosis. The patient's condition deteriorated, leading to intensive care admission due to, hypertensive crisis, and respiratory distress. High total plasma homocysteine and low methionine levels raised suspicion of cobalamin metabolism disorders. Genetic testing confirmed biallelic MMACHC gene mutations, establishing the diagnosis of cblC defect. Treatment with hydroxycobalamin, folic acid, and betaine led to remarkable clinical improvement. DISCUSSION/CONCLUSION: This case underscores the significance of recognizing metabolic disorders like cblC defect in atypical presentations of nephrotic syndrome. Early diagnosis and comprehensive management are vital to prevent irreversible renal damage. While cblC defects are more commonly associated with atypical hemolytic uremic syndrome, this case highlights the importance of considering cobalamin defects in the differential diagnosis of nephrotic syndrome, especially when associated with accompanying findings such as hemolysis. Our case, which has one of the highest homocysteine levels reported in the literature, emphasizes this situation again.

Falta de adherencia al control médico en pacientes pediátricos con antecedente de glomerulonefritis infecciosa

Introducción: La glomerulonefritis pos infecciosa (GNPI) en la infancia es un factor de riesgo para el desarrollo de enfermedad renal crónica a largo plazo. La adherencia al control médico permite realizar la nefroprevención secundaria. Objetivo: evaluar la relación entre los factores de riesgo relacionados a la falta de adherencia al control médico de pacientes con GNPI en una cohorte pediátrica. Metodología: estudio descriptivo de asociación cruzada de cohorte retrospectiva de pacientes internados entre enero de 2000 a diciembre de 2018 en un hospital de referencia. Se analizó la relación entre: hacinamiento, colecho, escolaridad materna y paterna, número de hermanos, de convivientes y procedencia, con la falta de adherencia al control médico. Se utilizaron la prueba de chi cuadrado y regresión logística a un nivel de significancia de 0,05. Resultados: Se incluyeron 148 pacientes (103 niños y 45 niñas) entre 2 a 16 años (edad promedio: 8,5± 3,4 años). La falta de adherencia fue encontrada en 73 pacientes (49,3%) que se asoció a procedencia rural (p= 0,012, RR: 1,50, IC95%: 1,10-2,06), baja escolaridad materna (p= 0,046, IC95%: 1,54:1,14-2,08), baja escolaridad paterna (p= 0,02; RR: 1,483, IC95%: 1,09-2,01), >3 convivientes (p=0,007, RR: 1,630, IC95%: 1,21-2,19), colecho (p=0,026; RR: 1,52, IC95%: 1,02-2,27) y hacinamiento (p<0,0001; RR: 1,92, IC95%: 1,39-2,65). Por regresión logística, el hacinamiento (p=0,005; OR= 4,8) y procedencia rural (p=0,022; OR: 2,4) se mantuvieron asociados a la falta de adherencia. Discusión: El hacinamiento y la procedencia rural se asociaron en forma independiente con la pérdida de seguimiento. Se recomienda mayor intervención de la atención primaria de salud.

Introduction: Post-infectious glomerulonephritis (PIGN) in childhood is a risk factor for the development of long-term chronic kidney disease. Adherence to medical control allows secondary nephroprevention to be carried out. Objective: to evaluate the relationship between risk factors related to non-adherence to medical control of patients with IPGN in a pediatric cohort. Methods: descriptive study, with an analytical component of a retrospective cohort of patients hospitalized between January 2000 and December 2018 in a reference hospital. The relationship between: overcrowding, co-sleeping, maternal and paternal education, number of siblings, cohabitants and origin, with lack of adherence to medical control was analyzed. The chi-square test and logistic regression were used at a significance level of 0.05. Results: a total of 148 patients (103 boys y 45 girls) between 2 and 16 years old (mean age: 8.5± 3.4 years) were included. The lack of adherence was found in 73 patients (49.3%) that was associated with rural origin (p= 0.012, RR: 1.50, 95% CI: 1.10-2.06), low maternal education (p= 0.046, 95%CI: 1.54:1.14-2.08), low paternal education (p= 0.02; RR: 1.483, 95%CI: 1.09-2.01), >3 cohabitants (p=0.007, RR: 1.630, 95% CI: 1.21-2.19), co-sleeping (p=0.026; RR: 1.52, 95% CI: 1.02-2.27) and overcrowding (p<0.0001; RR: 1.92, 95% CI: 1.39-2.65). By logistic regression, overcrowding (p=0.005; OR= 4.8) and rural origin (p=0.022; OR: 2.4) remained associated with lack of adherence. Discussion: Overcrowding and rural origin were independently associated with loss to follow-up. Greater intervention by primary health care is recommended.

Immunoglobulin A glomerulonephropathy: A review.

In this editorial, we comment on the article by Meng et al published in the World Journal of Clinical Cases. We comprehensively review immunoglobulin A nephropathy (IgAN), including epidemiology, clinical presentation, diagnosis, and management. IgAN, also known as Berger's disease, is the most frequent type of primary glomerulonephritis (GN) globally. It is mostly found among the Asian population. The presentation can be variable, from microscopic hematuria to a rapidly progressive GN. Around 50% of patients present with single or recurring episodes of gross hematuria. An upper respiratory infection and tonsillitis often precede these episodes. Around 30% of patients present microscopic hematuria with or without proteinuria, usually detected on routine examination. The diagnosis relies on having a renal biopsy for pathology and immunofluorescence microscopy. We focus on risk stratification and management of IgAN. We provide a review of all the landmark studies to date. According to the 2021 KDIGO (kidney disease: Improving Global Outcomes) guidelines, patients with non-variant form IgAN are first treated conservatively for three to six months. This approach consists of adequate blood pressure control, reduction of proteinuria with renin-angiotensin system blockade, treatment of dyslipidemia, and lifestyle modifications (weight loss, exercise, smoking cessation, and dietary sodium restrictions). Following three to six months of conservative therapy, patients are further classified as high or low risk for disease progression. High-risk patients have proteinuria ≥ 1 g/d or < 1 g/d with significant microscopic hematuria and active inflammation on kidney biopsy. Some experts consider proteinuria ≥ 2 g/d to be very high risk. Patients with high and very high-risk profiles are treated with immunosuppressive therapy. A proteinuria level of < 1 g/d and stable/improved renal function indicates a good treatment response for patients on immunosuppressive therapy.

Acute Renal Infarction After a Bilateral Aortic-Iliac Stent Thrombosis.

A renal infarction occurs when kidney's arterial blood supply is compromised, causing parenchymal necrosis and loss of function. It is a relatively uncommon complication and its treatment is time-dependent. We present a case where a female patient with a history of bilateral aortic-iliac stenting over 10 years before presented with chest pain, palpitations, and dyspnea associated with hypertension. The patient progressed with an acute worsening of renal function and anuria, with an urgent need for renal replacement therapy. The abdominal CT angiography confirmed a complete chronic stent thrombosis and a recent occlusion of the right renal artery causing an acute renal infarction; however, this exam was performed more than 72 hours after admission. There was no longer indication for reperfusion therapy, taking into account the time course. This case reinforces the importance of a thorough clinical history and awareness of risk factors to raise the suspicion of renal infarction that should lead to an early contrast-enhanced CT scan so that adequate therapy can be performed.

Changes in renal microcirculation in patients with nephrotic and nephritic syndrome: The role of resistive index.

BACKGROUND: Renal Resistive Index (RRI) is an important and non-invasive parameter of renal damage and it is associated with abnormal microcirculation or to a parenchymal injury. The aim of our study was to compare the RRI in a cohort of patients with renal diseases categorized in three groups: nephrotic syndrome (NS), acute nephritic syndrome (ANS) and patients with urinary abnormalities (UA). METHODS: Four hundred eighty-two patients with median age of 48 years (IQR 34-62) with indications for kidney disease were included in the study. Biochemical analyses, clinical assessment with detection of NS, ANS and UA and comorbidities were reported. Renal Doppler ultrasound with RRI was evaluated in all patients at the time of enrolment. RESULTS: NS was present in 81 (16.8 %) patients while ANS in 81 (16.8 %) and UA in 228 (47.3 %) patients. Patients with ANS showed significant higher RRI compared to both patients with NS [0.71 (IQR 0.67-0.78) vs 0.68 (0.63-0.73), p < 0.001] and UA [0.71 (0.67-0.78) vs 0.65 (0.61-0.71), p < 0.001]; RRI was higher in NS patients than in patients with UA [0.68 (0.63-0.73) vs 0.65 (0.61-0.71), p < 0.001]. Patients with ANS had significantly lower median estimated glomerular filtration rate (eGFR) compared respectively to NS and UA patients [19.7 ml/min vs 54.8 ml/min and vs 72.3 ml/min, p < 0.001], while renal length was significantly higher in patients with NS compared to both patients with ANS and UA [111.88 mm vs 101.98 mm and vs 106.15, p < 0.001]. Patients with ANS had more frequently hematuria and RRI ≥ 0.70 (p < 0.001) compared to both patients with NS and patients with UA. The multiple regression analysis, weighted for age, showed that RRI inversely correlates with eGFR (ß coefficient = -0.430, p < 0.001). CONCLUSIONS: Higher and pathological RRI were found in ANS than NS and UA. Renal resistive index in ANS reflects changes in intrarenal perfusion and microvascular dysfunction related to disease characteristics.

Atypical form of Goodpasture's disease.

Goodpasture's disease and anti-glomerular basement membrane nephritis (anti-GBM nephritis) are rare autoimmune small vessel vasculitis predominantly affecting young men. Goodpasture's disease plays an important part in differential diagnosis of pulmonary - renal syndrome. The evidence of circulating autoantibodies, a typical histological appearance of the kidney biopsy with finding of the crescent glomerulonephritis and clinical presentation of nephritic syndrome play an important role in diagnosis. Our case report describes a case of a young male with anti-GBM nephritis that presents as rapidly progressive glomerulonephritis (RPGN) with progression to dialysis-dependent renal failure. The atypical sign of the case was development of nephrotic syndrome with volume-dependent hypertension. The case was complicated by heparin-induced thrombocytopenia. During combined immunosuppressive therapy with plasmapheresis, the condition of the patient has stabilized. However, renal function did not recover. This previously fatal disease has nowadays a very good survival rate because of immunosuppresion therapy, plasmapheresis and hemodialysis.

Glomerulonefritis aguda posinfecciosa asociada al virus de la gripe B y enterovirus / Postinfectious acute glomerulonephritis associated to influenza B virus and enterovirus

La glomerulonefritis aguda posinfecciosa (GNAPI) es una lesión inflamatoria con afectación principal del glomérulo generada por una infección extrarrenal. Su patogenia es inmune, desencadenada por gran variedad de gérmenes: bacterias, virus y hongos. La causa más frecuente es la glomerulonefritis posestreptocócica (GNAPE). El caso que presentamos fue causado por gripe B y enterovirus, agentes etiológicos de presentación poco frecuente, con manifestación clínica similar a una glomerulonefritis posestreptocócica. Concluimos que, ante una clínica de síndrome nefrítico, se deben tener en cuenta los antecedentes víricos, para hacer un diagnóstico precoz (AU)

Acute post-infectious glomerulonephritis (APIGN) is an inflammatory lesion with main involvement of the glomerulus triggered by an extrarenal infection. Its pathogenesis is immune, triggered by a wide variety of germs: bacteria, viruses and fungi. The most common cause is poststreptococcal glomerulonephritis (PSAGN). The case that we present was associated to influenza B and enterovirus, etiological agents of infrequent presentation, with clinical manifestations similar to post-streptococcal glomerulonephritis. We conclude that, when faced with a nephritic syndrome clinic, the viral history should be taken into account to make an early diagnosis. (AU)

Frecuencia y características de la encefalopatia hipertensiva secundaria a glomerulonefritis posinfecciosa en pacientes internados en un hospital de referencia nacional

Introducción: La glomerulonefritis aguda pos infecciosa (GNPI) puede cursar con complicaciones como la encefalopatía hipertensiva en 7-11% de los casos. Objetivo : determinar la frecuencia y características de la encefalopatía hipertensiva (EH) secundaria a GNPI en pacientes internados en el Departamento de Pediatría del Hospital Nacional en el periodo enero/2000-diciembre/2018. Materiales y Métodos : Estudio observacional, descriptivo, retrospectivo de pacientes con síndrome nefrítico (SN) con C3 disminuido y normalización a los tres meses, con hipertensión arterial (HTA) severa acompañada de manifestaciones neurológicas (cefalea, náuseas, vómitos, alteración de conciencia, convulsiones), que cedieron al regularizarse la HTA. Se estudiaron las características sociodemográficas (edad, sexo, procedencia, escolaridad de los padres, número de hijos) y clínicas (edema periférico, edema agudo de pulmón, hematuria, y manifestaciones neurológicas). Los datos fueron analizados utilizando estadística descriptiva mediante EPIINFO (CDC, Atlanta), expresando las variables cuantitativas como mediana y rango intercuartílico (RIC) y las cualitativas como frecuencia absoluta y porcentual. Resultados: 27 /160 (16,8%) pacientes, desarrollaron EH. La edad varió entre 3 a 16 años (mediana: 10 años; RIC: 5); el antecedente infeccioso más frecuente fue piodermitis (40,7%), seguido de faringitis aguda (37%). Todos los pacientes presentaron edema periférico y cefalea intensa. La duración de la HTA tuvo una mediana de 5 días (RIC: 4) y los días de internación una mediana de 7 (RIC: 6). Ningún paciente requirió diálisis ni quedó con secuelas, no se registraron óbitos. Conclusión: en pacientes con EH debe considerarse el diagnóstico de GNPI, investigando antecedentes infecciosos y valorando adecuadamente la volemia.

Introduction: Acute post-infectious glomerulonephritis (APGN) can present with complications such as hypertensive encephalopathy in 7-11% of cases. Objective: to determine the frequency and characteristics of hypertensive encephalopathy (HE) secondary to APGN in patients admitted to the Department of Pediatrics of the National Hospital from January/2000 to December/2018. Materials and Methods: This was an observational, descriptive and retrospective study of patients with nephritic syndrome (NS) with decreased C3 and normalization at three months, with severe arterial hypertension (AHT) accompanied by neurological manifestations (headache, nausea, vomiting, altered consciousness, seizures), which subsided when the AHT was controlled. Sociodemographic (age, sex, place of residence, parental education level, number of children in home) and clinical (peripheral edema, acute pulmonary edema, hematuria, and neurological manifestations) characteristics were studied. The data were analyzed using descriptive statistics through EPI INFO (CDC, Atlanta), expressing the quantitative variables as median and interquartile range (IQR) and the qualitative ones as absolute frequency and percentage. Results: 27/160 (16.8%) patients developed HE. Age ranged from 3 to 16 years (median: 10 years; IQR: 5); the most frequent infectious history was pyodermitis (40.7%), followed by acute pharyngitis (37%). All patients presented peripheral edema and severe headache. The duration of AHT had a median of 5 days (IQR: 4) and the days of hospitalization a median of 7 (IQR: 6). No patient required dialysis or was left with sequelae, no deaths were recorded. Conclusion: in patients with HE, the diagnosis of APGN should be considered, a history of infections obtained and adequately assessing fluid status.

Glomerulonefritis aguda posinfecciosa como riesgo para desarrollar insuficiencia renal crónica en una cohorte pediátrica de un hospital de referencia en Paraguay

Contexto: la glomerulonefritis aguda posinfecciosa (GNPI) representa un riesgo para el desarrollo de insuficiencia renal a largo plazo. Objetivo: describir la incidencia de proteinuria persistente y factores asociados en pacientes con antecedente de GNPI en una cohorte pediátrica de un hospital de referencia en Paraguay. Metodología: se incluyó a 121 pacientes con síndrome nefrítico con C3 disminuido, con normalización a los tres meses, aunque no se haya comprobado etiología estreptocócica. Se excluyó a los pacientes con enfermedad renal previa, con síndrome nefrítico secundario y con menos de seis meses de seguimiento. Se analizaron las características sociodemográficas, infecciones precedentes, aclaramiento de creatinina, días de hipertensión arterial y de internación, además de la relación de estas con la persistencia de proteinuria a los seis meses y más de seguimiento. Resultados: de los 121 pacientes entre 2 a 16 años de edad incluidos, 75 pacientes tuvieron un seguimiento médico entre 6 y 48 meses, de los cuales 43 (57,3 %) desarrollaron proteinuria persistente, la cual se asoció con un menor aclaramiento de creatinina (p = 0,03; 67,74 ± 25,69 mL/min/1,73 m2 SC vs. 80,22 ± 2,98 mL/min/1,73 m2 SC), con el número promedio de convivientes (6,3 ± 2,8 vs. 5,3 ± 2,3; p = 0,027) y el número promedio de hijos (4,3 ± 2,7 vs. 3,6 ± 2,3; p = 0,048). No se encontró asociación con las otras características. Conclusiones: la incidencia de proteinuria se asoció con un menor aclaramiento de creatinina y con una mayor frecuencia de los determinantes sociales en salud.

Background: Acute post-infectious glomerulonephritis (PIGN) represents a risk for the development of long-term renal failure. Purpose: To describe the incidence of proteinuria in patients with a history of PIGN in a pediatric cohort at a referral hospital in Paraguay. Methodology: a total of 121 patients with nephritic syndrome with decreased C3 and normalization at 3 months, although streptococcal aetiology has not been proven were included. Patients with with previous kidney disease, with secondary nephritic syndrome and with less than 6 months of follow up were excluded. Sociodemographic characteristics, previous infection, creatinine clearance, days of arterial hypertension and hospitalization were analyzed, in addition to their relationship with the persistence of proteinuria at 6 months and more of follow-up. Results: Of the 121 patients between 2 and 16 years of age included, 75 patients had a medical follow-up between 6 and 48 months, 43 (57.3 %) of them developed persistent proteinuria, which was associated with lower creatinine clearance (p = 0.03; 67.74 ± 25.69 mL/min/1.73 m2 BM vs 80.22 ± 2.98 mL/min/1.73 m2 BM), higher average number of cohabitants (6.3 ±2.8 vs 5.3±2.3; p= 0.027) and higher average number of children (4.3±2.7 vs 3.6±2.3; p= 0.048). No association was found with other characteristics. Conclusions: the incidence of proteinuria in this series was associated with lower creatinine clearance and a higher frequency of social determinants in health.

Takayasu arteritis associated with focal and segmentary glomerulosclerosis

Takayasu arteritis (TA) is a large vessel vasculitis that affects young people, related to cardiovascular outcomes and chronic kidney disease. We present the case of a 20-year-old male with a diagnosis of TA, who developed chronic kidney disease, impaired renal blood flow was ruled out, renal biopsy was compatible with focal and segmental glomerulosclerosis of a collapsing variety, other possible aetiologies were excluded. The mechanisms that mediate this association have not been determined, immune-mediated mechanisms are proposed. According to our review, this is the second reported case of this association and the first with a collapsing variety.

La arteritis de Takayasu es una vasculitis de grandes vasos que afecta a personas jóvenes y se relaciona con desenlaces cardiovasculares y enfermedad renal crónica. Se presenta el caso de un paciente masculino de 20 arios, con diagnóstico de arteritis de Takayasu, que desarrolla enfermedad renal crónica. Se descartan alteraciones en el flujo sanguíneo renal, en tanto que la biopsia renal resulta compatible con glomeruloesclerosis focal y segmentaria de variedad colapsante. Se excluyeron otras posibles etiologías. No se han determinado los mecanismos que median en esta asociación; se proponen mecanismos inmunomediados. Según nuestra revisión, se trata del segundo caso reportado de esta asociación y el primero con variedad colapsante.

Sumatriptan poisoning and its clinical presentation in humans: A case report.

This case report displays some of the possible complications of sumatriptan poisoning, including nephritic syndrome.

Management and outcomes of acute post-streptococcal glomerulonephritis in children.

Acute post-streptococcal glomerulonephritis (APSGN) is the major cause of acute glomerulonephritis among children, especially in low- and middle-income countries. APSGN commonly occurs following pharyngitis due to the activation of antibodies and complements proteins against streptococcal antigens through the immune-complex-mediated mechanism. APSGN can be presented as acute nephritic syndrome, nephrotic syndrome, and rapidly progressive glomerulonephritis, or it may be subclinical. The management of APSGN is mainly supportive in nature with fluid restriction, anti-hypertensives, diuretics, and renal replacement therapy with dialysis, when necessary, as the disease is self-limiting. Congestive heart failure, pulmonary edema, and severe hypertension-induced encephalopathy might occur during the acute phase of APSGN due to hypervolemia. APSGN generally has a favorable prognosis with only a small percentage of patients with persistent urinary abnormalities, persistent hypertension, and chronic kidney disease after the acute episode of APSGN. Decreased complement levels, increased C-reactive protein, and hypoalbuminemia are associated with disease severity. Crescent formations on renal biopsy and renal insufficiency on presentation may be the predictors of disease severity and poor outcomes in APSGN in children.

Overcoming obstacles in Panama to starting a renal biopsy program in a rural area during the COVID-19 pandemic.

Due to the many implemented restrictions, the SARS-CoV-2 pandemic has rendered some tasks more difficult, for instance, the evaluation of outpatients. Panama's tertiary care hospital for kidney biopsy referral was transformed into a COVID-only hospital in order to assist the large number of COVID-19 patients. In order to face the impossibility of following patients with nephrotic or nephritic syndrome, a biopsy program was implemented in a southern province in Panama. Thirty kidney biopsies were carried out over a 1-year period. This experience shows that kidney biopsy programs, that are usually run only in large referral centers, can also be implemented in small nephrology centers, allowing to obtain accurate diagnoses and to guide correct treatment.

Glomerular Hematuria and the Utility of Urine Microscopy: A Review.

Evaluation of hematuria and microscopic examination of urine sediment are commonly used tools by nephrologists in their assessment of glomerular diseases. Certain morphological aspects of urine red blood cells (RBCs) seen by microscopy may help in identifying the source of hematuria as glomerular or not. Recognized signs of glomerular injury are RBC casts or dysmorphic RBCs, in particular acanthocytes (ring-shaped RBCs with protruding blebs). Despite being a highly operator-dependent test, urine sediment examination revealing these signs of glomerular hematuria has demonstrated specificities and positive predictive values ranging between 90%-100% for diagnosing glomerular disease, although sensitivity can be quite variable. Hematuria is a commonly used tool for diagnosing patients with proliferative glomerulonephritis such as IgA nephropathy, antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, and lupus nephritis, sometimes even as a surrogate for kidney involvement. Studies examining the role for hematuria in monitoring and predicting adverse outcomes in these diseases have shown inconsistent results, possibly due to inconsistent definitions that often fail to consider specific markers of glomerular hematuria such as dysmorphic RBCs, acanthocytes, or RBC casts. A consensus definition of what constitutes glomerular hematuria would help standardize use in future studies and likely improve the diagnostic and prognostic value of hematuria as a marker of glomerulonephritis.

[The glomerulus in all its states]. / Le glomérule dans tous ses états.

Glomerulonephritis are the result of an inflammatory hit to the glomerulus. They are rare and heterogeneous renal diseases. Each glomerular compartment can be affected. The clinical manifestations present with hematuria, proteinuria and/or impaired renal function, either isolated or combined. Two main clinico-biological syndromes are described: nephrotic syndrome and nephritic syndrome. The latter can present in a more severe form i.e. rapidly progressive glomerulonephritis with the worst prognosis. These different clinical pictures are related to specific glomerular lesions. Thus, podocytic damage is mainly responsible for nephrotic syndromes, mesangial damage is responsible for proteinuria and hematuria and, finally, endothelial damage is responsible for nephritic syndrome and rapidly progressive glomerulonephritis. Therapeutic approaches include non-specific measures, combining both life-style and pharmacological interventions with the aim to reduce risk factors, and specific measures with the use of different immunosuppressive agents.

: Les glomérulonéphrites sont des atteintes inflammatoires du glomérule. Il s'agit de pathologies rénales rares et hétérogènes. Tous les compartiments glomérulaires peuvent être touchés. Les répercussions cliniques sont diverses. Elles se manifestent par une hématurie, une protéinurie et/ou une altération de la fonction rénale, présente chacune de manière isolée ou combinée. Deux principaux syndromes clinico-biologiques sont décrits : le syndrome néphrotique et le syndrome néphritique. Au sein de cette dernière entité, on distingue une forme plus sévère, les glomérulonéphrites rapidement progressives grevées du plus mauvais pronostic. Ces différents tableaux cliniques sont en lien avec des lésions glomérulaires spécifiques. Ainsi, les atteintes podocytaires sont principalement responsables des syndromes néphrotiques, les atteintes mésangiales sont responsables de protéinurie et d'hématurie et les atteintes endothéliales sont responsables de syndromes néphritiques et de glomérulonéphrites rapidement progressives. Les approches thérapeutiques comprennent des mesures non spécifiques, hygiéno-diététiques et pharmacologiques, visant à réduire les différents facteurs de risque, et des mesures spécifiques avec l'utilisation de divers médicaments immunosuppresseurs.

Acute Post-Streptococcal Glomerulonephritis in Children: A Comprehensive Review.

BACKGROUND: Acute post-streptococcal glomerulonephritis (APSGN) is an immune- complex (ICs) mediated glomerular disease triggered by group A ß-hemolytic streptococcus (GAS) or Streptococcus pyogenes infections. APSGN represents a major cause of acquired kidney injury in children. METHODS: This non-systematic review summarizes recent evidence on APSGN. We discuss the epidemiology, pathogenesis, clinical and laboratory findings, histopathology, treatment and prognosis of the disease. RESULTS: The median APSGN incidence in children in developing countries is estimated at 24.3/100,000 per year, compared with 6.2/100,000 per year in developed countries. Nephritis-associated plasmin receptor, identified as glyceraldehyde-3-phosphate dehydrogenase, and the cationic cysteine proteinase streptococcal pyrogenic exotoxin B are thought to be two leading streptococcal antigens involved in the pathogenesis of APSGN, which activate the complement system, mainly via the alternative but also the lectin pathway. This process is critical for the generation of inflammation by the ICs deposited in the glomerulus. The classic phenotype is an acute diffuse proliferative glomerulonephritis leading to features of the nephritic syndrome, including hematuria, oliguria, hypertension and edema. The histopathology shows that the glomeruli are diffusely affected, mostly presenting enlarged glomerular tuffs due to hypercellularity. Proliferative endothelial and mesangial cells and inflammation have also been observed. APSGN frequently has spontaneous recovery. There is no specific therapy, but its morbidity and mortality are drastically reduced by the prevention and/or treatment of complications. CONCLUSION: Despite recent advances, the pathogenesis of APSGN is not fully understood. There is no specific treatment for APSGN. The prognosis is generally good. However, some cases may evolve into chronic kidney disease.

Renal biopsy reports in nephritic syndrome: Update.

BACKGROUND: Nephritic syndrome (NiS) is a major indicator of serious renal diseases necessitating kidney biopsies for histopathological evaluations, but due to the lack of comprehensive reviews in the literature, the current understanding of the syndrome and its significance is limited. AIM: To collect all the evidence retrievable from the literature on the diagnoses made on the renal biopsies performed for NiS as the indication to the procedure. METHODS: A literature search was conducted to find studies reporting final diagnoses on renal biopsies in NiS patients. Data were pooled and analyzed with stratifications on age and regions. Meta-analyzes were performed using Stata v.9. RESULTS: Overall, 26414 NiS patients from the total number of 96738 kidney biopsy diagnoses reported by 47 studies from 23 countries from all continents (except sub-Saharan Africa) were found and analyzed. NiS was the indication for renal biopsy in 21% of the patient populations across the reviewed studies. Immunoglobulin A (IgA) nephropathy was the single most frequent diagnosis in these patients (approximately 38%) followed by lupus nephritis (approximately 8%) and Henoch Schönlein purpura (approximately 7%). IgA nephropathy was the most frequent diagnosis reported for the NiS patients from the East Asia, comprising half of all the cases, and least prevalent in South Asia. Considering the age subgroups, adult (vs pediatric or elderly) patients were by far the most likely age group to be diagnosed with the IgA nephropathy. A myriad of such regional and age disparities have been found and reported. CONCLUSION: As the indication for renal biopsy, NiS represents a very distinctive epidemiology of final renal disease diagnoses compared to the other major syndromes.

Whole exome sequencing identifies monogenic forms of nephritis in a previously unsolved cohort of children with steroid-resistant nephrotic syndrome and hematuria.

BACKGROUND: Alport syndrome (AS), atypical hemolytic-uremic syndrome (aHUS), and fibronectin-glomerulopathy (FG) are rare forms of glomerular diseases that manifest in a combination of proteinuria, hematuria, and hypertension, referred to as nephritic syndrome. Due to phenotypic overlays, steroid-resistant nephrotic syndrome (SRNS) and nephritic syndrome have been difficult to discern diagnostically. SRNS is more common than nephritic syndrome and is the second leading cause of childhood-onset CKD. Fourteen monogenic causes of AS, aHUS, and FG and 60 monogenic causes of SRNS have been identified. As whole exome sequencing (WES) allows for unequivocal molecular genetic diagnostics, we hypothesize to be able to identify causative mutations in genes known to cause nephritic syndrome in patient cohorts with a clinical diagnosis of SRNS. METHODS: We identified patients with hematuria and steroid-resistant proteinuria in an international patient cohort that we had submitted to WES and who were unsolved for known monogenic causes of SRNS. These 70 patients from 65 individual families were subsequently analyzed for causative mutations in 14 AS, aHUS, or FG causing genes. WES data were compared to a control cohort of 76 patients from 75 families that were diagnosed with nephronophthisis-related ciliopathies (NPHP-RC) and to a control cohort of 83 individuals from 75 families with SRNS, but without hematuria. RESULTS: We detected likely pathogenic genetic variants in 3 of 65 families (4.6%) in 2 of the 14 genes analyzed. CONCLUSIONS: We confirmed that in cohorts of childhood-onset SRNS, patients with nephritic syndrome can be discerned by WES. The findings highlight the importance of clinical genetic testing for therapeutic and preventative measures in patients with proteinuria. A higher resolution version of the Graphical abstract is available as Supplementary information.

Efficiency of Rituximab in treating children with refractory nephrotic syndrome / 中华实用儿科临床杂志

Objective:To assess the efficacy of Rituximab (RTX) in treating children with refractory nephro-tic syndrome.Methods:A retrospective study was carried out.Twenty-two children diagnosed with refractory nephrotic syndrome in the Department of Nephrology of Wuhan Children′s Hospital, Tongji Medical College, Huazhong University of Science and Technology from November 2018 to November 2020 were included in the study.All patients were treated with RTX.Patients with CD 19+ B lymphocytes≥1% total lymphocytes in peripheral blood were supplemented with one dose of RTX (375 mg/m 2), and each patient received 3-4 doses of RTX on average.The patients were treated with Mycophenolate mofetil after early discontinuation of calcineurin inhibitors (CNI). The Kaplan-Meier method was used to analyze the proteinuria relapse-free rate and the incidence of frequently recurrent nephrotic syndrome or steroid-dependent nephrotic syndrome in children after RTX treatment.The relapse times before and after using RTX were analyzed by the Wilcoxon signed rank test.Besides, the body mass indexes (BMI) and height of children before and after RTX treatment were compared by the rank sum test. Results:Of 22 patients studied, 20 patients accomplished the therapeutic protocol.One-year and two-year proteinuria relapse-free survival rates were 85% and 40%, respectively.The recurrence rate was reduced under the discontinuation of CNI.Compared with those before RTX treatment, the BMI and height of all children were significantly improved at 1 year and 2 years after RTX treatment (all P<0.05). However, no significant improvement was observed between 1 or 2 years after RTX treatment (all P>0.05). Conclusions:The use of RTX can effectively reduce the recurrence rate of refractory nephrotic syndrome even when hormones and other immunosuppressants are discontinued.At the same time, RTX can significantly improve the BMI and height of children.RTX is safe and effective for treatment of refractory nephrotic syndrome.