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.

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.

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.

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.

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.

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.

The spectrum of biopsy-proven glomerular diseases in a tertiary Hospital in Southern Brazil.

BACKGROUND: The prevalence and distribution of glomerular diseases differ among countries, and the indication to perform a kidney biopsy varies among centres. In this study, we assessed the prevalence of primary and secondary glomerulopathies based on histological diagnoses, and the correlation between glomerulopathies and demographic and clinical data was evaluated. METHODS: In this study, 1051 kidney biopsies were retrospectively reviewed between 2000 and 2018. Patient demographic, clinical and laboratory data were assessed. The prevalence of primary glomerulonephritis (PG) and secondary glomerulopathies (SG), as well as tubulointerstitial diseases (TIDs), hereditary nephropathies (HNs) and other diagnoses, were determined. The frequency of primary and secondary glomerulopathies was evaluated by age group, and the temporal variation in frequencies across three time periods (2000-2005, 2006-2011, and 2012-2018) was reported. RESULTS: The prevalence of SG predominated (52.4%), followed by PG (29.6%), other diagnoses (10.7%), TID (6.6%) and HN (1.1%). Among the primary forms of glomerular disease, focal segmental glomerulosclerosis (FSGS) was the most common (37.3%), followed by IgA nephropathy (IgAN, 24.4%), membranous nephropathy (MN, 18.6%) and minimal change disease (MCD, 8.4%). Lupus nephritis (LN, 41.1%) was most common in patients with SG, followed by diabetic kidney disease (DKD, 17.8%), systemic vasculitis (SV, 10.2%) and secondary FSGS (2nd FSGS, 10%). Nephrotic syndrome was the most common clinical presentation in patients with PG and also in patients with DRD and 2nd FSGS, whereas in patients with IgAN and SV, nephritic syndrome was the main presentation. For the age group between 18 and 50 years, LN, FSGS and IgAN predominated; for patients aged between 51 and 65 years, the proportion of DKD and 2nd FSGS increased, and SV was more common in patients > 65 years. The temporal variation in PG across the three time periods showed a statistically significant increase in IgAN (p = 0.001) and a reduction in FSGS over time (p < 0.001). In SG, there was a reduction in LN (p = 0.027) and an increase in DKD (p < 0.001) over time, with a tendency for 2nd FSGS to decrease over time (p = 0.053). CONCLUSIONS: In the studied kidney biopsy registry, FSGS and IgAN were the most prevalent diagnoses in patients with PG, and LN and DKD were the most prevalent in patients with SG. Nephrotic syndrome was the major indication for biopsy. When comparing the temporal variation in glomerulopathies, there was a reduction in FSGS and an increase in IgAN in patients with PGs over time, and for patients with SGs, there was a reduction in LN with an increase in cases of DKD over time.

Horseshoe kidney with PLA2R-positive membranous nephropathy.

BACKGROUND: Horseshoe kidney (HSK) is a common congenital defect of the urinary system. The most common complications are urinary tract infection, urinary stones, and hydronephrosis. HSK can be combined with glomerular diseases, but the diagnosis rate of renal biopsy is low due to structural abnormalities. There are only a few reports on HSK with glomerular disease. Here, we have reported a case of PLA2R-positive membranous nephropathy occurring in a patient with HSK. CASE PRESENTATION: After admission to the hospital due to oedema of both the lower extremities, the patient was diagnosed with nephrotic syndrome due to abnormal 24-h urine protein (7540 mg) and blood albumin (25 g/L) levels. Abdominal ultrasonography revealed HSK. The patient's brother had a history of end-stage renal disease due to nephrotic syndrome. Therefore, the patient was diagnosed with PLA2R-positive stage II membranous nephropathy through renal biopsy under abdominal ultrasonography guidance. He was administered adequate prednisone and cyclophosphamide, and after 6 months of treatment, urinary protein excretion levels significantly decreased. CONCLUSION: The risk and difficulty of renal biopsy in patients with HSK are increased due to structural abnormalities; however, renal biopsy can be accomplished through precise positioning with abdominal ultrasonography. In the literature, 20 cases of HSK with glomerular disease have been reported thus far. Because of the small number of cases, estimating the incidence rate of glomerular diseases in HSK is impossible, and the correlation between HSK and renal pathology cannot be stated. Further studies should be conducted and cases should be accumulated to elucidate this phenomenon.

Educational Case: Nephrotic Syndrome in Older Adult.

The following fictional case is intended as a learning tool within the Pathology Competencies for Medical Education (PCME), a set of national standards for teaching pathology. These are divided into three basic competencies: Disease Mechanisms and Processes, Organ System Pathology, and Diagnostic Medicine and Therapeutic Pathology. For additional information, and a full list of learning objectives for all three competencies, see http://journals.sagepub.com/doi/10.1177/2374289517715040.1.

The number of nephrons in different glomerular diseases.

BACKGROUND: The total number of nephrons has been measured mainly from post-mortem studies and only in selected populations. Data from living subjects are scanty, and direct comparisons among different glomerular diseases are lacking. The present work exploits modern methodology to estimate the total nephron number in glomerulopathies with prevalent proteinuria/nephrotic syndrome versus glomerulopathies with nephritic syndrome (IgA nephropathy (IgAN), lupus nephritis), thus extending previous observations about the number and function of glomeruli in different physiological and pathological states. METHODS: This is a retrospective study based on one hundred and seven patients who have undergone renal biopsy. The glomerular density has been estimated from the biopsy specimens and the total cortical volume has been obtained from ultrasound recordings. Stereological methods have been applied to calculate the total number of nephrons and their volume. The correlation between clinical parameters and quantitative morphological data have studied using the Pearson correlation coefficient (r). RESULTS: The total number of nephrons inversely correlated with the systolic blood pressure (r = -0.4, p < 0.05). In proteinuric diseases, such as focal segmental glomerulo-sclerosis (FSGS), membranous nephropathy (MN) and diabetes, the change in estimated GFR (eGFR) directly correlated with the total number of non-sclerotic glomeruli (NSG) (r = 0.62, p < 0.01), whereas in nephritic syndrome no significant correlation was observed. The alterations in eGFR occurring in nephritic syndromes such as IgAN cannot be explained on the basis of the number of NSG. DISCUSSION: The fusion of the podocyte foot-processes that typically occurs in purely proteinuric diseases does not modify the glomerular filtration rate: therefore in these situations, the change in eGFR depends mainly on the number of available glomeruli. On the other side, the eGFR decrease occurring in nephritic syndromes, such as IgAN, cannot be explained simply on the basis of the number of NSG and likely depends on the substantial involvement of the mesangial axis. Future studies should verify whether these changes are reversible with appropriate therapy, thus reversing eGFR decrease.

Gene mutation analysis in 12 Chinese children with congenital nephrotic syndrome.

BACKGROUND: Congenital nephrotic syndrome (CNS) is characterised by increased proteinuria, hypoproteinemia, and edema beginning in the first 3 months of life. Recently, molecular genetic studies have identified several genes involved in the pathogenesis of CNS. A systematic investigation of the genes for CNS in China has never been performed; therefore, we conducted a mutational analysis in 12 children with CNS,with the children coming from 10 provinces and autonomous regions in China. METHODS: Twelve children with CNS were enrolled from 2009 to 2016. A mutational analysis was performed in six children by Sanger sequencing in eight genes (NPHS1, NPHS2, PLCE1, WT1, LAMB2, LMXIB, COQ6 and COQ2) before 2014, and whole-exome sequencing was used from 2014 to 2016 in another six children. Significant variants that were detected by next generation sequencing were confirmed by conventional Sanger sequencing in the patients' families. RESULTS: Of the 12 children, eight patients had a compound heterozygous NPHS1 mutation, one patient had a de novo mutation in the WT1 gene, and another patient with extrarenal symptoms had a homozygous mutation in the COQ6 gene. No mutations were detected in genes NPHS2, PLCE1, LAMB2, LMXIB, and COQ2 in the 12 patients. CONCLUSIONS: This study demonstrates that the majority of CNS cases (67%, 8/12 patients) are caused by genetic defects, and the NPHS1 mutation is the most common cause of CNS in Chinese patients. A mutational analysis of NPHS1 should be recommended in Chinese patients with CNS in all exons of NPHS1 and in the intron-exon boundaries.

Minimal change disease in horseshoe kidney.

The horseshoe kidney is a frequent urological birth defect. The most frequent complications are urinary tract infections, stones and hydronephrosis. The occurrence of glomerular disease in horseshoe kidney is rare. Therefore, we report the first case of minimal change disease occurring in a patient with horseshoe kidney in literature. A 22-year-old Caucasian man without personal or family medical history admitted to the pneumology department for a pulmonary artery embolism. In presence of a generalized oedema, a biological assessment was performed yielding intense nephrotic syndrome with urine protein excretion 22g/day. The abdominal ultrasound revealed a horseshoe kidney. Hence a scanno-guided kidney biopsy was taken yielding minimal change disease. High dose steroids were started, then gradually tapered with good response. Horseshoe kidney is the most common renal fusion anomaly, with a prevalence of 0.25% among the general population. The occurrence of glomerular nephropathy in horseshoe kidney has been reported in few cases. We report the first case of minimal change disease occurring in a patient with horseshoe kidney in literature. The mechanism of the association between the horseshoe kidney and these renal pathologies could not be explained in the previous reports. There is no literature data indicating a high rate of glomerulonephritis in horseshoe kidneys. The co-incidence of two renal diseases in this patient can be only a coincidence. The question that arises is whether this glomerulopathy is associated or not with this anatomical abnormality. Further studies are needed to answer this question.

Clinical Characteristics and Outcome of Post-Infectious Glomerulonephritis in Children in Southern India: A Prospective Study.

OBJECTIVES: To evaluate the clinical characteristics, complications and outcome of post-infectious glomerulonephritis (PIGN). METHODS: This prospective observational study was conducted from January 2013 through July 2014 at a tertiary care hospital in south India. Post-streptococcal glomerulonephritis (PSGN) was diagnosed in the presence of: a) Hematuria and proteinuria b) Clinico-serological evidence of recent streptococcal infection [recent pyodermas or pharyngitis; positive antistreptolysin-O (ASO) titres, anti-DNAse B titres or throat swab positivity for Group A streptococcus], and c) Low serum C3 levels, with normalization on 8 wk follow up. PIGN included PSGN and other infectious etiologies. AKI was classified as per Acute Kidney Injury Network (AKIN) criteria. Clinical features, biochemical and serological investigations in the study subjects were recorded. RESULTS: Among 83 children with acute nephritic syndrome (ANS) recruited, 72 (86.7 %) had PIGN. PSGN was the most common etiology [65(90.3 %)] among the PIGN cases. Pyodermas, upper respiratory infections and varicella preceded hematuria in 58 (80.6 %), 4 (5.6 %) and 2 (2.8 %) cases respectively. Pneumonia, mumps and liver abscess caused PIGN in 7 (9.7 %) cases. Complications included AKI in 15 (20.8 %), hypertensive emergency in 14 (19.4 %), cardiac failure in 8 (11.1 %), encephalopathy in 3 (4.2 %) cases and retinopathy in 1 (1.4 %) case. Among the AKI patients, 3(20 %) were in AKI stage 3, while 1 child required hemodialysis. Twenty three cases (31.9 %) had evidence of residual renal injury at discharge. Renal biopsy showed diffuse proliferative glomerulonephritis in 4 and crescentic glomerulonephritis in one case of PIGN. At 6 mo follow up, one patient continued to have microalbuminuria. CONCLUSIONS: PIGN (including PSGN) remains a significant contributor to morbidity in children with ANS. The study is notable for high incidence of hypertensive emergency and AKI, that often required intensive care management.

Tratamento com plasmaférese da glomerulosclerose segmentar focal recorrente após transplante renal. Relato de caso / Treatment with plasmapheresis of focal segmental glomerulosclerosis after kidney transplantation applicant. Case report

JUSTIFICATIVA E OBJETIVOS: A glomerulosclerose segmentar e focal (GESF) é uma doença progressiva e sem tratamento curativo, levando ao longo da sua progressão à insuficiência renal crônica (IRC) e a outras complicações, sendo a plasmaférese um dos poucos recursos terapêuticos. O objetivo deste estudo foi relatar um caso em que a plasmaférese terapêutica foi utilizada durante o acompanhamento do paciente, mostrando a recorrência da doença mesmo em uso contínuo da plasmaférese. RELATO DE CASO: Paciente do sexo masculino, 13 anos, diagnosticado com GESF e importante comprometimento da função renal, submetido a transplante com posterior rejeição e piora do quadro, sendo submetido à seções periódicas de plasmaférese frente a constante piora clínica e às poucas opções terapêuticas. CONCLUSÃO: Ainda controversa, a plasmaférese é indicada no tratamento da GESF recorrente. A intervenção precoce em pacientes transplantados com GESF recorrente é capaz de mudar o prognóstico ao longo da evolução para IRC. Neste paciente não apresentou resposta satisfatória ao tratamento, mesmo sendo realizadas sessões pré e imediatamente após o segundo transplante e ao longo de seu acompanhamento com o objetivo de diminuir a proteinúria e a recorrência.

BACKGROUND AND OBJECTIVES: Focal segmental glomerulosclerosis (FSGS) is a progressive disease without curative treatment, bringing along their progression to chronic renal failure (CRF) and other complications, plasmapheresis one of the few therapeutic resources. The aim of this study was to report a case in which the plasma therapy was used during the monitoring of the patient showing recurrence of disease even in continuous use of plasmapheresis. CASE REPORT: Male patient, 13 years, diagnosed with FSGS with significant renal disease underwent renal transplant rejection and subsequent worsening of symptoms, underwent plasmapheresis front sections of the periodic steady worsening clinical and few therapeutic options. CONCLUSION: Still controversial, plasmapheresis is indicated for the treatment of FSGS. Early intervention in transplant patients with recurrent FSGS is capable of changing the prognosis during the evolution to CRF. The patient showed no satisfactory response to treatment with plasmapheresis, although sessions held before and immediately after the second transplant and throughout their follow in order to reduce proteinuria and the recurrence.

Estudio comparativo entre nifedipina y captopril en crisis hipertensiva en niños / Nifedipine and captopril in hypertensive crisis in children

Introducción: La crisis hipertensiva es una urgencia pediátrica que se debe manejar con medicamentos de rápida acción, de fácil administración y sin mayores efectos secundarios. El medicamento usado tradicionalmente ha sido el nitroprusiato de sodio endovenoso en infusión continua lo que implica hospitalización en cuidados intensivos con mayores costos y riesgos. Objetivos: Comparar la eficacia y seguridad de la nifedipina y el captopril sublingual en crisis hipertensivas. Material y métodos: Se llevó a cabo un estudio prospectivo en niños entre 1 y 12 años de edad que ingresaron al servicio de pediatría urgencias del Hospital Universitario del Valle en Cali, Colombia, con diagnóstico de crisis hipertensiva. Se realizó monitoreo de la presión arterial sistólica, diastólica y media y de la frecuencia cardíaca antes de administrar los medicamentos y a los 5, 15, 30, 60, 120, 180, 240, 300 y 360 minutos después de administrados. Los dos medicamentos se dieron por vía sublingual a dosis de 0.2 mg/kg. Se vigilaron efectos secundarios después de su administración. Resultados: Durante 16 meses ingresaron 21 pacientes, 10 asignados a nifedipina y 11 a captopril, 13 niños y 8 niñas, con un promedio de edad de 7 años. La reducción de la presión arterial por debajo del percentil 95 inducida por la nifedipina sublingual fue más rápida, en promedio a los 20 minutos, que con captopril (50 minutos). Hasta los 30 minutos las cifras de presión arterial sistólica, diastólica y media fueron estadísticamente inferiores con nifedipina que con captopril, para luego tener una actividad muy similar. Se necesitó una segunda dosis en tres pacientes con nifedipina y uno con captopril. No hubo respuesta en dos pacientes con captopril. No se presentaron efectos secundarios mayores. Con la nifedipina se observó aumento promedio de 10% en la frecuencia cardíaca a los 5 minutos después de ser administrada.

Introduction: Hypertensive crisis is a pediatric emergency which implies medications with fast action and minimal side effects. Sodium nitroprusiate in continuous infusion has been the treatment of choice but implicates admission to intensive care unit. Objectives: To evaluate efficacy and safety of nifedipine and captopril in hypertensive crisis in children. Methodology: A prospective study was performed to evaluate efficacy and safety of sublingual nifedipine and captopril, in children 1-12 years old who were admitted with diagnosis of hypertensive crisis, to the Pediatric Emergency Service at the University Hospital in Cali, Colombia. Systolic, diastolic, mean blood pressure and heart rate were monitored in all patients before administration of the medicaments, time 0, and after the administration at time 5, 15, 30, 60, 120, 180, 240, 300, and 360 minutes. Side effects were observed carefully after the administration. Results: During a period of 16 months, 21 patients were enrolled in the study: 10 were assigned to nifedipine and 11 to captopril; 13 were boys and 8 were girls, with a mean age of 7 years old. Both medications were given sublingual at 0.2mg/kg/dose. Blood pressure reduction under 95 percentil induced by sublingual nifedipine was faster, mean time 20 minutes compared to captopril (50 minutes). Up to 30 minutes post medication systolic, diastolic and mean blood pressure were statistically lower with nifedipine than with captopril; but after 30 minutes both medications had similar activity. Three patients with Nifedipine and 1 with captopril required a second dose. Two patients with captopril had no response. No side effects were registered in either group. Nifedipine induced a 10% asymptomatic heart rate increase at 5 minutes after its administration, captopril did not increase heart rate.