Cause Of Glomerulonephritis Research Articles

Diagnosis and Treatment of Hematuria

Hematuria is a common manifestation caused by various factors such as infection, inflammation, trauma, urinary stone and malignancy. Hematuria reflects pathological state of urinary system. Isolated microscopic hematuria without any abnormalities besides of hematuria on urine microscopic examination usually presents a good clinical course or outcome. However, significant proteinuria or hypertension, which accelerates renal dysfunction, can often develop during follow-up period in patients with isolated microscopic hematuria. Compared with non-glomerular hematuria, glomerular hematuria shows several characteristic findings such as dysmorphic red blood cell (RBC) or RBC casts or significant proteinuria on urinalysis. If glomerular hematuria is strongly suspected, a kidney biopsy may be required to differentiate the cause of glomerulonephritis. In this review, we tried to review the differential diagnosis and diagnostic approach and treatment of hematuria.

#735 The clinicopathologic prognostic factors to estimate ESRD in patients with FSGS from national wide cohort of renal biopsy

Abstract Background and Aims Focal segmental glomerulosclerosis (FSGS) is one of the leading causes of glomerulonephritis in Korea. FSGS can be caused by heterogenous aetiologies with subdivided by primary, secondary, and genetical forms. The proposed clinicopathologic classification is dependent on amount of proteinuria, laboratory findings of possible secondary causes, and genetic profiles, however, that may not provide definite subtypes of FSGS. Therefore, it is important to search for prognostic markers of any form of FSGS. Method We enrolled a total of 20,404 adult patients who underwent native renal biopsy from 1979 to 2018 in 18 hospitals in Korea. Clinical, demographic, and laboratory data were collected in conjunction with pathologic findings. Among diagnosis of FSGS by pathologists of each hospital, we selected patients with definite segmental sclerosis by light microscopic examination including ≥10 glomeruli and without electron dense deposits by electron microscopic examination. We excluded patients with other forms of pathologic diagnosis except FSGS, with diabetes mellitus, or with follow-up period < 6 months after renal biopsy. We evaluated prognostic factors to estimate the risk of ESRD which event was found from ESRD registry of the Korean Society of Nephrology or the data from each hospital. Results Among 511 selected FSGS patients, 314 (61.4%) men were included. Mean age was 45.0 ± 17.9 years at biopsy. The laboratory finding of serum creatinine, estimated GFR, and urine protein to creatinine ratio (UPCR) was 1.38 ± 0.85 mg/dl, 71.8 ± 36.6 ml/min/1.73 m2, and 4.32 ±4.84 g/g creatinine, respectively (there were no missing data). GFR <60 ml/min/1.73 m2 was found in 41.5 % of patients and UPCR ≥ 3.0 g/g creatinine in 41.1 % of patients. During 117.5 ± 100.1 months of follow-up period, there were 97 (19.0%) patients with incident ESRD. Clinical prognostic factors to incident ESRD were estimated GFR, diastolic blood pressure, and year of renal biopsy. Pathologic prognostic factors were glomerular size, amount of global sclerosis and segmental sclerosis, severity of increase in glomerular matrix, interstitial fibrosis, interstitial inflammation, and tubular atrophy, and presence of artherosclerosis of intrarenal vessels. Adjusted with clinicopathologic factors related to incident ESRD, Cox's proportional hazard models revealed only pathologic findings of amount of glomerular global sclerosis and segmental sclerosis and presence of tubular atrophy were the independent prognostic factors (Model with 3.5 % of missing cases and -2 log likelihood ratio is 956.9, p < 0.001). GFR and UPCR showed significant relationship with incidence of ESRD, however, the significance was gone in the model adjusted with pathologic findings. AUC by ROC to estimate the event of ESRD by percentage of global sclerosis (GS) was 0.601 (range; 0.538-0.663, p = 0.002) and, by percentage of segmental sclerosis (SS), 0.679 (range; 0.616-0.743, p < 0.001). We grouped patients with three pathology categorical variables of a criterion of GS 30.9%, SS 10.5 %, and moderate degree in severity of tubular atrophy (TA), resulted in 8 groups, and summarized into 4 groups according to the relative risk to develop ESRD (Fig. 1). UPCR was a significant risk factor to estimate ESRD only in Group 4 with the criterion of 2 g/g creatinine by the Kaplan-Meier test (p = 0.034). GFR was not a prognostic factor in any pathology subgroup. Conclusion Important prognostic factors to estimate incident ESRD were pathologic findings of global sclerosis, segmental sclerosis, and tubular atrophy in FSGS patients. Significance of UPCR and GFR as prognostic factors was varied according to pathologic findings. We need to reconsider the criterion of UPCR to initiate immunosuppressive treatment and to break down the effect of immunosuppressive treatments for FSGS according to pathologic findings at renal biopsy.

#1253 Predicting renal outcomes in ANCA-associated vasculitis—validation of ANCA Renal Risk Score in a Portuguese cohort

Abstract Background and Aims Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a rare cause of glomerulonephritis and clinical presentation can be diverse. Despite recent developments in immunosuppressive treatments, AAV with renal involvement is still associated with poor renal prognosis and a high risk of end-stage renal disease (ESRD). Kidney biopsy confirms the diagnosis, details the degree of active inflammation and chronicity of disease, also informing of renal prognosis. Berden histological classification categorizes renal histological findings into four classes but the ability to accurately predict renal outcomes varies among studied cohorts. In 2018 Brix et al developed and validated a new risk score, ANCA Renal Risk Score (ARRS), to determine renal outcomes based on histopathological and clinical indicators, with accurate ESRD prediction at 36 months. This study aims to assess the predictive value of ARRS in renal survival on a Portuguese cohort with newly diagnosed AAV with kidney involvement. Method We designed a retrospective study examining ANCA vasculitis in native kidney biopsies evaluated in a Portuguese kidney histomorphology-dedicated center between 2004 and 2023. Data collected from biopsies included percentage of normal glomeruli (PNG) and interstitial fibrosis/tubular atrophy (IFTA). Clinical and demographical data was also collected, including age, sex, estimated glomerular filtration rate (eGFR) at presentation, date of diagnosis, ESRD and date of death. We calculated ARRS based on eGFR, PNG and IFTA, and patients were classified as being at low, intermediate and high risk of developing ESRD by 36 months. Primary endpoint was established as difference in kidney survival at 36 months. Secondary endpoint included difference in overall survival at 36 months and the contribution of each of the ARRS parameters in a Cox regression model. Results A total of 143 patients were obtained, 46.2% female, with a mean age at diagnosis of 67.1 years. There was a predominancy of MPO-related disease (77.2%) and 69% presented with rapidly progressive renal insufficiency. Median ARRS was 6.5, with 10.8%, 44.3% and 44.9% classified as low, intermediate, and high risk, respectively. Kaplan Meier estimates for renal survival computed at 36 months revealed an overall mean time to dialysis of 20 months, which decreased with an increase in risk category [33.4 (low risk), 24.7 (intermediate risk), 12.7 months (high risk), Log-R test: χ2(2) = 24.9, p < 0.001] with an ESRD survival of 92.9%, 63.6% and 29.7% at 36 months, respectively. Regarding secondary endpoints, overall survival at 36 months was not different between groups [33.7 (low risk) vs. 33.2 (intermediate risk) vs. 32.2 months (high risk), Log-R test: χ2(2) = 0.3, p = 0.9]. Cox regression, plotted for ESRD at 36 months using the three score variables, revealed eGFR at presentation as the strongest predictor of kidney survival (HR: 0.96, 95% CI: 0.93-0.99, p = 0.004) whereas PNG and IFTA did not achieve significance (p = 0.189 and p = 0.066, respectively). Conclusion Our results corroborate Brix et al ARRS, accurately predicting ESRD in a Portuguese cohort of patients with renal involvement by ANCA vasculitis. Patients assessed as high-risk of developing ESRD had a lower mean time to dialysis, although overall survival did not differ between groups. Contrary to Brix et al findings, which revealed PGN as the only independent predictor of ESRD, in our study lower eGFR at the time of diagnosis was an independent risk factor. Type of immunosuppression used in each patient was not considered in this study and could maybe alter results of renal and overall survival. Despite this, Brix et al reported that, in their population, validity of ARRS was not influenced by immunosuppressive treatment. This new scoring system still requires validation in a larger cohort, but results seem promising and, in the future, may aid clinicians with treatment decisions. This is relevant since full immunosuppression induction schemes may be halted in patients with high probability of ESRD, diminishing infectious complications and potentially decreasing morbidity and mortality associated with AAV.

Daratumumab therapy in a pediatric case of C3 nephritic factor-positive proliferative glomerulonephritis with monoclonal IgG deposits.

Proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID) is an exceedingly rare cause of glomerulonephritis among children for which prognosis is generally poor, with low incidence of remission and high rates of recurrence after transplant. While there are more cases reported in the adult literature, substantial differences in pediatric vs. adult PGNMID render it essential that we further characterize pediatric cases to optimize management. We report the case of a 12-year-old male presenting initially with edema and hypertension who was subsequently diagnosed with IgG3/Kappa-dominant PGNMID. In the absence of any proven therapy and though without a detectable clone, he was empirically treated with daratumumab with positive effect to date. This is the first reported case of daratumumab monotherapy in pediatric PGNMID, as well as the first PGNMID case to detect presence of C3 nephritic factor.

Acute Post-streptococcal Glomerulonephritis in a Pediatric Population: A Five-Year Retrospective Study.

Post-streptococcal glomerulonephritis is a kidney disease that occurs after infection with a certain strain of streptococcal bacteria. It has a high hospitalization rate, especially in developing countries. It is characterized by the sudden appearance of edema, hematuria, proteinuria, and hypertension. The objective of this retrospective descriptive study conducted at James L. Gordon Memorial Hospital in Olongapo, Zambales, Philippines, is to analyze the demographic distribution, clinical presentation, complication, and outcome of acute post-streptococcal glomerulonephritis (APSGN) in a pediatric population. Methods: A retrospective descriptive study was done in patients (below 18 years of age) admitted with the diagnosis of post-streptococcal glomerulonephritis during a five-year period in the pediatric ward of a tertiary hospital in the Philippines. All patients underwent detailed clinical history and examination and were closely monitored during treatment. The course of disease progression was closely monitored and recorded. Seventy-seven children were treated for APSGN with a mean age of 7.8 years and with standard deviation of 3.85. Edema and gross hematuria were noted in 53 (68.8%) and 24 (31.1%) cases, respectively. Hypertension was present in 54 patients (70.1%). Among those 54 patients, 49 (63.6%) patients developed acute renal injury (based on normal creatinine for age), three cases (3.8%) had pleural effusion, and two patients (2.5%) developed hypertensive encephalopathy. All patients underwent KUB (kidneys, ureters, and bladder) ultrasound, among which 13 (16.88%) had diffuse parenchymal swelling which improved and eventually were discharged. Increased blood urea nitrogen (BUN) was noted in 60-65% of patients. Hypoalbuminemia and lower hemoglobin were also quite common. There was no mortality during treatment and hospital stay. APSGN remains one of the most common causes of glomerulonephritis in the region. Edema, hypertension, and hematuria were the most common presenting features. Early identification and comprehensive monitoring and management are required to prevent morbidity and mortality. The prognosis is generally good if early treatment is done.

IgA Vasculitis in an Adult Man- a Case Report

IgA vasculitis is rare in adult. A significant portion of adult cases may present with renal involvement. Although most of these cases can be managed symptomatically, some cases may require immunosuppressive treatment. Unless diagnosis and appropriate treatment is initiated early IgA nephropathy in adult may result in chronic kidney disease. Immunoglobulin A vasculitis (IgAV) is an acute disorder causing generalized vasculitis principally involving skin, gastrointestinal (GI) tract, kidneys and joints. Here, a 28 year old man was presented with purpuric rash with leg ulcer, inflammatory arthritis involving multiple joints, abdominal pain and vomiting. He had mild pedal edema and normal blood pressure. Investigations showed raised inflammatory markers, haematuria, and nephrotic range proteinuria with normal liver and renal function. Biochemical and immunological evaluation of lupus nephritis, ANCA associated vasculitis and other causes of glomerulonephritis were negative. Renal biopsy with direct immunofluorescence showed features of IgA nephropathy. Patient was treated with steroid and mycophenolate mofetil with a good response. Bangladesh Med J. 2022 Sept; 51(3): 47-50

#6949 MPO ANCA-ASSOCIATED VASCULITIS IN A PATIENT WITH A HISTORY OF METHAMPHETAMINE ABUSE

Abstract Background and Aims Methamphetamines cause kidney damage by different mechanisms. The most common is the tubular lesion associated with myoglobinuria secondary to rhabdomyolysis. Other renal effects include prerenal azotemia, acute tubular necrosis, malignant hypertension, and necrotizing vasculitis have been reported. It is important to consider this drug as a possible cause of glomerulonephritis. Method We present the case report of a patient with suspected MPO ANCA-associated vasculitis from methamphetamines. Results A 24-year-old male, he was admitted to nephrology due to hematuria and proteinuria accompanied by serum creatinine elevation (2.5 mg/dl). He reported inhaled methamphetamine abuse since the age of 14, smoking and occasional ethylism. His symptoms began in October 2022 with asthenia and adinamia, accompanied by generalized pallor and edema in both malleoli. At admission with normal blood pressure (112/70 mmHg). Laboratory tests revealed: leukocytes 6.35 thousand/UL, hemoglobin 7.7 g/dl, platelets 698,000 thousand/UL, urea 70.81 mg/dl, sodium 137 mmol/L, potassium 4.72 mmol/L, albumin 3.85 g/dl, urine test with proteinuria 25 mg/dl, hemoglobinuria 250 eri/microL, leukocytes 15-20 field and countless erythrocytes, albuminuria 450.87 mg/day, globular sedimentation rate 18 mm/hr, reactive protein C 37 mg/L. Complement levels were normal, negative serologies for hepatitis B, C, human immunodeficiency viruses, antinuclear antibodies, double-stranded anti DNA and anti-proteinase 3, but was positive for IgG anti myeloperoxidase (anti-MPO) 33.6 U/ml. Urinary sediment showed the presence of dysmorphic erythrocytes, as well as abundant erythrocyte and granular casts. Ultrasound-guided renal biopsy was performed; light microscopy reported 21 glomeruli, 6 globally sclerosed, 4 with irregular segmental sclerosis, 4 with destruction and granuloma formation. Immunofluorescence showed traces of mesangial IgM, the rest negative for IgG, IgA, C3, C1q, fibrinogen, kappa and lambda. The patient received 3 pulses of methylprednisolone 500 mg followed by oral prednisone and rituximab. Baseline creatinine decreased to 1.88 mg/dl. Conclusion Inhaled methamphetamine is commonly used in young people, it is important to consider this drug as a possible cause of crescentic and necrotizing glomerulonephritis.

Mitochondrial DNA copy number in peripheral blood of IgA nephropathy: a cross-sectional study

Mitochondrial DNA (mtDNA) copy number (CN) is a biomarker of mitochondrial function and has been reported associated with kidney disease. However, its association with IgA nephropathy (IgAN), the most common cause of glomerulonephritis (GN), has not been evaluated. We included 664 patients with biopsy-proven IgAN and measured mtDNA-CN in peripheral blood by multiplexed real-time quantitative polymerase chain reaction (RT-qPCR). We examined the associations between mtDNA-CN and clinical variables and found that patients with higher mtDNA-CN had higher estimated glomerular filtration rate (eGFR) (r = 0.1009, p = .0092) and lower serum creatinine (SCr), blood urea nitrogen (BUN), and uric acid (UA) (r=−0.1101, −0.1023, −0.07806, respectively, all p values <.05). In terms of pathological injury, mtDNA-CN was higher in patients with less mesangial hypercellularity (p = .0385, M0 vs. M1 score by Oxford classification). Multivariable logistic regression analyses also showed that mtDNA-CN was lower for patients with moderate to severe renal impairment (defined as eGFR < 60 mL/min/1.73 m2) vs. mild renal impairment, with the odds ratio of 0.757 (95% confidence interval: 0.579–0.990, p = .042). In conclusion, mtDNA-CN was correlated with better renal function and less pathological injury in patients with IgAN, proposing that systemic mitochondrial dysfunction may be involved in or reflect the development of IgAN.

Preventing progression in IgA nephropathy: a managed care focus on emerging therapies.

Immunoglobulin A nephropathy (IgAN) is an autoimmune disease that is the most common cause of glomerulonephritis. In IgAN, the glomeruli are impaired by deposits of IgA-complexes in the kidney, which leads to the progression of chronic kidney disease, often resulting in end-stage renal disease requiring dialysis or kidney transplantation. This progression is associated with impaired health-related quality of life and a significant economic burden. Better overall patient outcomes have been seen in patients who are diagnosed and receive treatment earlier in the disease process. Supportive therapy is the mainstay of treatment, but there have also been recent advances with targeted therapies that may provide additional therapeutic options to meet treatment goals. Managed care professionals are well positioned to design clinical programs and pathways to promote earlier diagnosis, better efficacy and safety monitoring, and timely access to targeted therapies to slow progression, reduce kidney damage, and delay or prevent end-stage renal disease.

Glomerulonephritis pattern based on renal biopsy at the tertiary center of King Abdulaziz University Hospital, Saudi Arabia

Aim: To investigate the glomerulonephritis pattern based on renal biopsies obtained from patients who attended King Abdulaziz University (KAU) hospital. Methods: This retrospective analysis was conducted at King Abdulaziz University (KAU) hospital. Data were retrieved from the pathology registry of renal biopsies performed at KAU hospital between 2010-2018. Demographics, background data, and the result of the biopsy Data were entered and analyzed using SPSS 23. Continuous data were expressed using mean ± SD. A P-value of &lt;0.05 (two-tailed) was determined to establish statistical significance. A Chi-square test was utilized to evaluate the association between categorical variables. In addition, a one-way ANOVA test was utilized when appropriate. Results: Among the 55 cases Focal segmental glomerulosclerosis (FSGS) is the most common cause of primary glomerulonephritis (56%). Whereas lupus nephritis was the most prevalent pathology in the case of secondary glomerulonephritis (60%) with a female predominance, followed by anti-neutrophilic cytoplasmic autoantibody vasculitis (16.7%) and diabetic nephropathy (13.3%). While IgA nephropathy represents (12%) of all the cases. Conclusion: Lupus nephritis is the prevalent cause of ESRD based on histopathology results. Lupus nephritis was the commonest cause of glomerulonephritis diseases with a female predominance. It is recommended that a nationwide multicenter study should be conducted to determine the current status, and ensure early intervention which will guide better planning and management of glomerulonephritis. This report should be considered an as urgent call to establish a national registry for glomerulonephritis renal biopsies.

POS-058 CLINICAL OUTCOMES IN IRGN - A SINGLE CENTRE EXPERIENCE IN 21 PATIENTS FROM SOUTH INDIA

IRGN is one of the common causes of glomerulonephritis in India with a changing spectrum of clinical presentation and variable course. The most classical description of Light microscopy is diffuse endocapillary proliferative exudative Glomerulonephritis, but other findings of Light microscopy can also be found.

POS-038 EPIDEMIOLOGICAL, CLINICAL AND PROGNOSTIC ASPECTS OF ACUTE POST-INFECTIOUS GLOMERULONEPHRITIS FROM JUNE 2014 TO JUNE 2018: A SINGLE HAITIAN HOSPITAL-BASED STUDY

Acute post-infectious glomerulonephritis (APIGN) is one of the main causes of glomerulonephritis in children with a clear male predominance. It is more common in countries with limited resources and is associated with high morbidity and mortality. Through this study, we wanted to evaluate the burden of this glomerulopathy in children admitted at the only pediatric hospital in Haiti by reviewing its epidemiological, clinical, and prognostic characteristics

MO244: PCSK9 Inhibitors are Efficient in Treatment of Resistant Hypercholesterolemia in Nephrotic Syndrome

Abstract BACKGROUND AND AIMS Hypercholesterolemia in nephrotic syndrome is commonly resistant to statin therapy and represents an important clinical challenge both for cardiovascular risk prevention and to eliminate lipotoxic effect on podocytes. Serum PCSK9 level is elevated in nephrotic syndrome and has a key pathophysiologic role in development and persistance of hyperlipidemia. Thus, we aimed to investigate the role of PCSK9 inhibitors in control of hypercholesterolemia in patients with neprotic syndrome. METHOD Consecutive patients with nephrotic syndrome and elevated atherogenic Lp (a) (n = 4) and patients with resistant secondary glomerulonephritis with nephrotic proteinuria (n = 2) were included. In all patients, in addition to full dose statin therapy, evolocumab 420 mg s.c. monthly was introduced. Lipid levels were measured after a median of 4 (range 2–9) months after starting evolocumab. RESULTS Nephrotic syndrome was caused by focal segmental glomerulosclerosis in four patients (66.7%) and membranous nepropathy was the cause in two patients (33.3%). Median age of included patients was 49.5 (range 24–70) years. Four patients with primary cause of glomerulonephritis received specific imunosupressive treatment. During follow-up, we observed descrease in glomerular filtration rate (eGFR median 58.5 interquartile range (IQR) [46.7–98.7] mL/min/1.73 m2 versus median 47 IQR [38.25–89.25] mL/min/1.73 m2; P = .046) and persistence of proteinuria [median 11 970 IQR (3862–13 765) mg/dU versus median 10 847 (5407–14 340) mg/dU; P = .753]. However, despite persistent proteinuria and decrease in eGFR, significant decrease in total cholesterol [median 9.10 IQR (6.92–10.87) mmol/L versus median 6.81 (5.4–8.45) mmol/L; P = .028] and LDL cholesterol [median 5.40 IQR (4.12–7.25) versus median 4.04 IQR (2.70–4.60); P = .046] was observed. There was no significant difference in Lp (a) and triglyceride levels. CONCLUSION PCSK9 inhibitors are a promising new therapeutic option for hyperlipidemia in patients with nephrotic syndrome. Further research, including a larger number of patients, is needed to correctly position PCSK9 inhibitors in treatment of hyperlipidemia in patients with nephrotic syndrome.

Glomerulonephritis with crescents in childhood; etiologies and significance of M2 macrophages.

Crescentic glomerulonephritis (CGN) is a rapidly progressive and rare cause of glomerulonephritis in childhood. The aim of this study is to evaluate demographic data of children with crescentic glomerulonephritis, to classify the etiologies and to investigate the correlation between the severity of kidney disease and the expression of CD163+ macrophages. Between the years 2000 and 2016 in a single center, patients under 18 years of age with kidney biopsies containing crescents were included in the study. A total of 88 children were enrolled. The expression of CD163 in kidney tissues was detected by immunohistochemistry in 61 patients. Clinical features and outcome were collected from their medical records. The most common etiology was Henoch-Schönlein purpura (HSP) nephritis/Immunglobulin A vasculitis (26.1%), followed by lupus nephritis (22.7%) and idiopathic crescentic glomerulonephritis (18.2%). CD163 positive cell counts in patients with GFR levels less and more than 60 ml/min/1.73 m2 at their last visit were 7.6±6.6 cells vs. 2.0±3.0 cells (p=0.057) per one glomerulus and 52.2±18.2 cells/hpf vs. 33.3±10.0 cells/hpf (p < 0.05) in tubulointerstitium, respectively. Tubulointerstitital CD163+ cells were also found to be higher in patients with end stage kidney disease than complete and partial responders (68 cells/hpf vs 39 cells/hpf, p < 0.05). CD163 positive cell counts, particularly in tubulointerstitial areas, have been associated with poor prognosis of CGN.

Overview on Acute Poststreptococcal Glomerulonephritis in Pediatrics: A Review

Acute poststreptococcal glomerulonephritis (APSGN) is the most common kind of post-infectious glomerulonephritis and is caused by group A streptococcus (Streptococcus pyogenes). Although the prevalence of PSGN has decreased in affluent nations, non-streptococcal species are becoming more common. and it is still the major cause of glomerulonephritis in children. APSGN can manifest itself in epidemic outbreaks or clusters of instances, as well as in single persons. Epidemic outbreaks have previously been documented as a result of upper respiratory or cutaneous streptococcal infections in various parts of the world. In developed nations, APSGN is now mostly a disease of the elderly, who are more likely to have disabling illnesses such as cancer, alcoholism, or diabetes. Children between the ages of 3 and 12 (with a peak incidence between the ages of 5 and 6 years) and seniors over the age of 60 are the most commonly affected. The pathophysiology of APSGN is complicated by inflammation. (APSGN) often occurs one to two weeks after a throat infection and three to five weeks after a skin infection. Hematuria, edoema, azotemia, and hypertension are the most common clinical signs. Loop or thiazide diuretics, are the most effective therapy for hypertension and edoema in PSGN. In this review we’ll be looking at the disease causes, epidemiology, presentation and treatment.

Immunoglobulin A nephropathy in paediatrics: An up‐to‐date

Immunoglobulin A nephropathy is the main cause of glomerulonephritis globally and an important aetiology of end-stage renal disease in children. It has been considered an autoimmune disease that can lead to the production of autoantibodies against abnormal IgA1 and formation of immune complexes. These autoantibodies and immune complexes deposit in the glomeruli, resulting in renal injury. At the beginning of IgA nephropathy course, most patients are asymptomatic and the first clinical manifestations in children are macroscopic hematuria and proteinuria. The diagnosis is defined by the detection of IgA mesangial deposits in kidney biopsy using immunofluorescence techniques. The Oxford MEST-C score is the most used classification to associate histological findings and clinical outcomes, being validated for application in children. Recommended treatment options are antihypertensive and antiproteinuric therapy, corticosteroids, immunosuppressive agents, and other non-pharmacological approaches. There is no ideal prognosis indicator but new perspectives are in science's scope to find possible biomarkers of the disease through OMICS's research. This review aims to summarize and to up-to-date the scientific literature on paediatric IgA nephropathy, focusing on pathophysiology, clinical findings, histopathology, current treatment, prognosis, and future perspectives.

Evaluation of renal fibrosis in various causes of glomerulonephritis by MR elastography: a clinicopathologic comparative analysis.

Renal parenchymal fibrosis is the most important determinant of kidney disease progression and it is determined via biopsy. The aim of this study is to evaluate the renal stiffness noninvasively by magnetic resonance elastography (MRE) and to compare it with clinicopathologic parameters in glomerulonephritis and AA amyloidosis patients. Thirty-four patients with glomerular filtration rate (GFR) over 20ml/min/1.73m2 had non-contrast MRE prospectively. Kidney stiffness values were obtained from whole kidney, cortex, and medulla. Values were correlated with GFR, albuminuria, proteinuria, and degree of fibrosis that are assessed via renal biopsy. Patients were grouped clinicopathologically to assess the relation between stiffness and chronicity. Mean whole kidney, cortex, and medulla stiffnesses were 3.78 (± 1.26), 3.63 (± 1.25), and 4.77 (± 2.03) kPa, respectively. Mean global glomerulosclerosis was 22% (± 18%) and median segmental glomerulosclerosis was 4% (min-max: 0%-100%). Extent of tubulointerstitial fibrosis was less than 25% in 26 of the patients (76.5%), 25%-50% in 6 of the patients (17.6%), and higher than 50% in 2 of the patients (5.9%). Fourteen patients were defined to have chronic renal parenchymal injury. MRE-derived stiffness values correlated negatively with parameters of fibrosis. Lower stiffness values were observed in patients with chronic renal injury compared to those without (P < 0.05 for whole kidney and medulla MRE-derived stiffness). MRE-derived stiffness values were lower in patients with chronic injury. Stiffness decreases as glomerulosclerosis and tubulointerstitial fibrosis progresses in patients with primary glomerulonephritis and AA amyloidosis. With future studies, there may be a role for MRE to assess renal function in concert with conventional markers.

To the pathogenesis of acute glomerulonephritis.

According to research F a h r ъa (Dent. Med. Woch., 1926, No. 18) in this disease, the inflammatory process primarily occurs in the glomeruli and only then spreads to the arterioles. Therefore, the opinion of Volhad a, that the cause of glomerulonephritis lies in the primary spasm of small renal vessels, cannot be considered correct.

Eculizumab as a New Treatment for Severe Acute Post-infectious Glomerulonephritis: Two Case Reports

Acute post-infections glomerulonephritis (APIGN) is a frequent cause of glomerulonephritis and represents the most common cause of acute glomerulonephritis in children. It can evolve to severe acute renal failure and chronic kidney disease or even end-stage kidney disease. The precise pathophysiological mechanisms of APIGN are still incompletely understood. The implication of the alternative complement pathway and the potential benefits of C5 blockade have been recently highlighted, in particular in the presence of a C3 Nephritic Factor (C3Nef), anti-Factor B or H autoantibodies. We report two children with severe APIGN, successfully treated with eculizumab. The first patient presented a severe form of APIGN with advanced renal failure and anuria, associated with a decreased level of C3 and an increased level of soluble C5b-9, in the presence of a C3NeF autoantibody. The second case had a severe oliguric APIGN associated with low C3 level. Kidney biopsy confirmed the diagnosis of APIGN in both cases. Eculizumab allowed full renal function recovery and the avoidance of dialysis in both cases. In conclusion, the alternative and terminal complement pathways activation might be common in PIGN, and in severe cases, eculizumab might help.

Recurrent Focal Segmental Glomerulosclerosis After Kidney Transplantation in African Americans: Review of the Current Evidence.

In many countries of sub-Saharan Africa, the most common causes of end-stage kidney disease are hypertension, chronic glomerulonephritis, and diabetes mellitus. So far, literature on recurrent focal segmental glomerulosclerosis in sub-Saharan African populations is limited. With the intention of providing guidance for best practices in sub-Saharan Africa, we reviewed available evidence for African Americans, a population with a similar genetic background. We chose this population as a pseudo-population to show how similar genetic backgrounds can predict disease occurrence in similar populations residing in different continents. Our extended PubMed and Scopus literature search used these key words: "focal segmental glomerulosclerosis in African Americans" (search 1), "recurrent focal segmental glomerulosclerosis after kidney transplantation" (search 2), "risk factors for recurrent focal segmental glomerulosclerosis" (search 3); and "APOL1 gene and kidney transplantation" (search 4). Search 1 yielded 4 articles, search 2 yielded 44 articles, search 3 yielded 6 articles, and search 4 yielded 8 articles. African Americans were shown to be disproportionately predisposed to endstage kidney disease, traceable to focal segmental glomerulosclerosis (the most common cause of glomerulonephritis leading to end-stage kidney disease). Apolipoprotein L1 presence in 22% of African Americans explained the odds ratio of 17 in developing focal segmental glomerulosclerosis and 8 times lifetime risk of end-stage kidney disease. Focal segmental glomerulosclerosis recurred in 30% of kidney transplant recipients; risk factors included young age, rapid progression to end-stage kidney disease, and White race recipient. Circulating permeability factors played a central role in primary and recurrent focal segmental glomerulosclerosis. For recurrent cases, transplant biopsy has remained the gold standard for diagnosis, with treatment involving a multi-modal approach, often resulting in partial or complete remission of proteinuria; allograft loss can occur if treatment is not successful. More randomized clinical trials are needed to chart the way forward for prolonged allograft function.