Evaluation of the significance of complement-related genes mutations in atypical postinfectious glomerulonephritis: a pilot study.

BACKGROUND: Postinfectious glomerulonephritis with C3-dominant glomerular deposition (C3-PIGN) involves C3-dominant glomerular deposition without immunoglobulin. Atypical C3-PIGN involves persistent hypocomplementemia. We investigated the clinical features and explored complement-related gene mutations in atypical PIGN patients. METHODS: We enrolled atypical C3-PIGN patients and collected data regarding the clinical presentation and pathological characteristics and follow-up data. We measured the levels of complement associated antibodies and performed whole-exome sequencing (WES) to detect mutations in complement-related genes. RESULTS: The analysis included six atypical C3-PIGN patients. All patients were antistreptolysin-O (ASO) positive. All patients had varying degrees of hematuria, and four patients had proteinuria. None of the patients were positive for complement-related antibodies. All patients possessed mutations of genes related to the complement pathway, including alternative complement pathway genes-CFI, CFH, CFHR3, CFHR5; the lectin pathway gene-MASP2; and the common complement pathway gene-C8A. The rare variant of CFHR3 has been reported in C3 glomerulonephritis. During 56-73 months of follow-up, the levels of urine markers in three patients recovered within 6 months, and the remaining patients had abnormal urine test results over 12 months. Patients who received glucocorticoid therapy recovered faster. CONCLUSIONS: Our study suggested that complement-related gene mutations may be an important cause of persistent hypocomplementemia in atypical C3-PIGN patients. In addition to variations in alternate pathway-related genes, we also found variations in lectin pathway-related genes, especially MASP2 genes. Although the overall prognosis was good, atypical C3-PIGN patients exhibited a longer period for recovery. Our results suggested that atypical C3-PIGN patients should receive more medical attention and need testing for mutations in complement-related genes.

IgA-dominant postinfectious glomerulonephritis: a case report.

Introduction: Acute postinfectious glomerulonephritis (APIGN) is an immunological glomerular disease that is an important health issue in developing countries. The incidence remains high in developing countries with a male-to-female ratio of 2:1 and age predominantly above 50 years. In this case study, we present a patient with a history of Staphylococcus epidermidis infection, a past medical history of diabetes mellitus, and histopathological findings of APIGN with Immunoglobulin A (IgA) deposition. Methods: A 58-year-old male presented to the emergency room with a 6-day history of severe low back pain. Three days later, the patient developed fever, chills, abdominal pain in the upper quadrant and a subsequent lower limb cellulitis. Various immunological tests, imaging studies, and kidney biopsy were performed to arrive at a diagnosis. Results: Following the diagnosis and treatment of Cholangitis and Staphylococcus epidermidis, further investigation led to a diagnosis of IgA-dominant APIGN. IgA-dominant APIGN was treated with antibiotics, renin-angiotensin-aldosterone system inhibitors and steroids, and the patient was discharged from the hospital. Conclusion: In developing countries, APIGN is a relatively common presentation of kidney damage due to acute kidney injury and nephritic syndrome. IgA-dominant APIGN is a rare but increasingly recognized morphological variant in which IgA is the sole or dominant immunoglobulin. This unique presentation and multidisciplinary approach for diagnosing and treating IgA-dominant APIGN need to be considered and understood by healthcare professionals to better help these patients. Further investigation is needed to understand the best treatment of this IgA-dominant APIGN presentation and its prognosis.

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)

Autoimmunity in Infection-Related Glomerulonephritis.

Introduction: Autoimmune (AI) reactivity in the setting of infection-related GN (IRGN) is often viewed as an epiphenomenon and is not well described. Methods: We report a cohort of 17 patients with IRGN during a 7-year period that highlights cases with AI reactivity and describes the clinical and pathologic characteristics of IRGN cases associated with AI reactivity. Results: Of the IRGN cases, 76% had clinical evidence of an autoimmune disease (AD) and/or positive AI serologies. Within the IRGN group with AI reactivity, 12 had positive AI serologies (92%) and 10 had AD (77%). 30% had a prior diagnosis of AD, while the remaining 70% did not have a history of AD and were either diagnosed or suspected of having an AD at the time of biopsy. The most common autoantibody detected was anti-nuclear antibody followed by anti-neutrophil cytoplasmic antibodies and autoantibodies associated with antiphospholipid syndrome. Conclusion: The study is not sufficiently powered to determine any significance but demonstrates the frequency with which AI features occur in IRGN and should prompt further future investigation. In summary, our findings suggest AI manifestations are common in IRGN.

Infection-Related Glomerulonephritis in Children and Adults.

Infection-related glomerulonephritis is an immunologically mediated glomerular injury after an infection. Glomerulonephritis may occur with the infection or after a variable latent period. Poststreptococcal glomerulonephritis (PSGN) is the prototype of infection-related glomerulonephritis. The streptococcal antigens, nephritis-associated plasmin-like receptor and streptococcal exotoxin B, have emerged as major players in the pathogenesis of PSGN. Although PSGN is the most common infection-related glomerulonephritis in children, in adults, glomerulonephritis is secondary to bacteria such as staphylococci, viruses such as hepatitis C, and human immunodeficiency virus, and, rarely, parasitic infections. Supportive therapy is the mainstay of treatment in most infection-related glomerulonephritis. Treatment of the underlying infection with specific antibiotics and antiviral medications is indicated in some infections. Parasitic infections, although rare, may be associated with significant morbidity. Poststreptococcal glomerulonephritis is a self-limiting condition with a good prognosis. However, bacterial, viral, and parasitic infections may be associated with significant morbidity and long-term consequences. Epidemiologic studies are required to assess the global burden of infection-related glomerulonephritis. A better understanding of the pathogenesis of infection-related glomerulonephritis may unravel more treatment options and preventive strategies.

A rare case of Immunoglobulin A dominant post-infectious glomerulonephritis (IgA PIGN) in a young patient.

BACKGROUND: Immunoglobulin A dominant postinfectious glomerulonephritis (IgA PIGN) is a unique medical entity that is rare in the paediatric population. It usually presents with severe renal failure, heavy proteinuria, hypertension, and hypocomplementemia and frequently has an unfavourable prognosis. IgA PIGN generally occurs in association with staphylococcal infections and diabetes mellitus in adult patients. Other pathogens include Escherichia coli and Streptococcus sp. Immunofluorescence studies of kidney biopsy samples show IgA as dominant or codominant antibody. CASE PRESENTATION: We encountered a 3-year-old girl with IgA PIGN presenting with acute renal failure, oedema, hypertension, and heavy proteinuria of 7955 mg/g creatinine. Renal biopsy specimens showed diffuse glomerular endocapillary hypercellularity with prominent neutrophil and monocyte infiltration on light microscopy. Strong deposits of IgA and C3 were observed along the glomerular basement membranes and the mesangium by immunofluorescence microscopy, and electron microscopy revealed the presence of subepithelial humps. The patient was managed with steroid (and probatory antibiotic) therapy and is now undergoing follow-up, with a significant improvement 6 months after the initial presentation (glomerular filtration rate (GFR) and cystatin C clearance rate of 165 ml/min/1.73m2 and 106 ml/min/1.73m2, respectively). No signs of bacterial infection were detectable. CONCLUSION: This variant of IgA PIGN must be distinguished from other clinical entities, especially IgA nephropathy (mesangial IgA deposits) and postinfectious glomerulonephritis (C3, IgG and occasional IgM capillary loop deposits with or without mesangial distribution), since patients with IgA PIGN may require steroid treatment in addition to antibiotic therapy. Differential diagnosis should also include C3 glomerulopathy. IgA PIGN is a recently identified disease entity that generally manifests in adult patients with both IgA and C3 mesangial and glomerular capillary wall deposits. We present a biopsy-proven case of IgA PIGN that manifested in a patient at an exceptionally young age and that has had a good clinical outcome. To the best of our knowledge, this is the youngest IgA PIGN patient reported thus far.

A Case of Immunoglobulin A (IgA)-Dominant Infection-Related Glomerulonephritis Treated With Plasmapheresis.

Immunoglobulin A (IgA)-dominant infection-related glomerulonephritis (IRGN) is mostly associated with Staphylococcal or other bacterial infections like Streptococcus and Gram-negative bacilli. Antibiotics are the cornerstone of treatment in these cases. When the bacterial infection can't be recognized or IRGN persists despite treating the underlying infection, controlling the kidney injury becomes cumbersome and lacks a strong evidence-based approach. In this report, we describe a 38-year-old male patient with a history of polysubstance abuse and chronic hepatitis B and hepatitis C infections who presented with acute kidney injury and nephrotic syndrome due to IgA-dominant IRGN without an active concurrent bacterial infection who responded well to plasmapheresis.

Long-Term Consequences of Puumala Hantavirus Infection.

Several viral infections are associated with acute and long-term complications. During the past two years, there have been many reports on post-infectious symptoms of the patients suffering from COVID-19 disease. Serious complications occasionally occur during the acute phase of Puumala orthohantavirus caused nephropathia epidemica. Severe long-term consequences are rare. Fatigue for several weeks is quite common. Hormonal insufficiencies should be excluded if the patient does not recover normally.

Examining the Efficacy of Antimicrobial Therapy in Preventing the Development of Postinfectious Glomerulonephritis: A Systematic Review and Meta-Analysis.

Postinfectious glomerulonephritis (PIGN) is an immune-mediated acute glomerulonephritis classically seen weeks after infection with Streptococcus pyogenes, although other infectious etiologies have emerged. While it has become increasingly rare in industrialized regions, it continues to affect children in developing countries. There has been debate as to why incidence rates are declining, including the possibility of improved initial treatment of bacterial infections. The ability of antimicrobial therapy in preventing PIGN as infectious sequelae, however, has not been comprehensively assessed. As varying evidence from published studies exists, the objective of this meta-analysis is to determine if antimicrobial therapy utilized to treat an initial infection has an effect in reducing the development of PIGN in humans. EMBASE, MEDLINE, and CENTRAL were searched using a comprehensive terminology strategy. From an initial search that returned 337 publications, 9 articles were included for analysis. Eight studies showed an incidence of PIGN after antimicrobial use ranging from 0.05% to 10% with a mean standardized difference (MSD) of 0.03 (0.01-0.06). Three studies showed an occurrence of PIGN without antibiotic use ranging from 1% to 13% with an MSD of 0.06 (-0.09-0.21). Our findings suggest that antimicrobial treatment for the initial infection may help diminish the development of PIGN. Although Streptococcus pyogenes infections are generally treated aggressively to prevent rheumatic fever, these findings may help further support the early treatment of bacterial infections to prevent postinfectious sequelae, especially as we consider other infectious etiologies of PIGN antimicrobial resistance.

Severe cutaneous necrotizing vasculitis with postinfectious glomerulonephritis secondary to peripherally inserted central catheter bloodstream infection.

Peripherally Inserted Central Catheters (PICCs) are widely used for hospitalized patients particularly in the oncological and hematological field. PICCs are a safe alternative to central venous catheters, mainly for medium- and long-term therapy.

Acute Postinfectious Glomerulonephritis.

Postinfectious glomerulonephritis (PIGN) is a leading cause of acute glomerulonephritis in children. The presentation of PIGN can vary from asymptomatic microscopic hematuria incidentally detected on routine urinalysis to nephritic syndrome and a rapidly progressive glomerulonephritis. Treatment involves supportive care with salt and water restriction, and the use of diuretic and/or antihypertensive medication, depending on the severity of fluid retention and the presence of hypertension. PIGN resolves completely and spontaneously in most children, and the long-term outcomes are typically good with preserved renal function and no recurrence.

Posterior reversible leukoencephalopathy syndrome associated with acute postinfectious glomerulonephritis: systematic review.

BACKGROUND: Kidney diseases are a recognized cause of posterior reversible leukoencephalopathy syndrome, usually abbreviated as PRES. The purpose of this review was to systematically address the association between acute postinfectious glomerulonephritis and PRES. METHODS: We performed a systematic review of the literature on acute postinfectious glomerulonephritis associated with PRES. The principles recommended by the Economic and Social Research Council guidance on the conduct of narrative synthesis and on the Preferred Reporting Items for Systematic Reviews and Meta-analyses were used. Databases searched included Excerpta Medica, US National Library of Medicine, and Web of Science. RESULTS: For the final analysis, we evaluated 47 reports describing 52 cases (32 males and 20 females). Fifty patients were ≤ 18 years of age. Blood pressure was classified as follows: normal-elevated (n = 3), stage 1 hypertension (n = 3), stage 2 hypertension (n = 5), and severe hypertension (n = 41). Acute kidney injury was classified as stage 1 in 32, stage 2 in 16, and stage 3 in four cases. Neuroimaging studies disclosed a classic posterior PRES pattern in 28 cases, a diffuse PRES pattern in 23 cases, and a brainstem-cerebellum PRES pattern in the remaining case. Antihypertensive drugs were prescribed in all cases and antiepileptic drugs in cases presenting with seizures. A resolution of clinical findings and neuroimaging lesions was documented in all cases with information about follow-up. CONCLUSIONS: The main factor associated with PRES in acute postinfectious glomerulonephritis is severe hypertension. Prompt clinical suspicion, rapid evaluation, and management of hypertension are crucial. A higher resolution version of the Graphical abstract is available as Supplementary information.

Clinicopathological and prognostic study of IgA-dominant postinfectious glomerulonephritis.

BACKGROUND: The clinicopathological and prognostic features of IgA-dominant postinfectious glomerulonephritis and its difference from the primary IgA nephropathy remains to be investigated. METHODS: The clinical and pathological data of 6542 patients who underwent renal biopsy from 2009 to 2020 in our hospital were reviewed and 50 patients who met the selection criteria of IgA-dominant postinfectious glomerulonephritis were enrolled to conduct a retrospective and observational single-center study. The selection criteria were: meet the characteristics of IgA dominance or codominance in immunofluorescence, and conform to 3 of the following 5 criteria: 1.Clinical or laboratory evidence show that there is infection before or at the onset of glomerulonephritis; 2.The level of serum complement decreased; 3.Renal pathology is consistent with endocapillary proliferative glomerulonephritis; 4. Glomerular immunofluorescence staining showed complement C3 dominance or codominance; 5. Hump-like subepithelial immune complex deposition was observed under electron microscopy. According to age, sex, renal function (estimated glomerular filtration rate, eGFR) and follow-up time, the control group was constructed with 1:3 matched cases of primary IgA nephropathy. The clinicopathological and prognostic differences between the two groups were analyzed. RESULTS: The most common histological pattern of IgA-dominant postinfectious glomerulonephritis was acute endocapillary proliferative glomerulonephritis and exudative glomerulonephritis. Immunofluorescence showed mainly IgA deposition or IgA deposition only, mainly deposited in the mesangial area (deposition rate 100 %), with typical C3 high-intensity staining (intensity++~+++), mainly deposited in the mesangial area (deposition rate 92.0 %). The fluorescence intensity of kappa is usually not weaker than lambda. The probability of the appearance of typical hump-like electron deposition under electron microscopy is low. Compared to primary IgA nephropathy, patients with IgA-dominant postinfectious glomerulonephritis had higher proportion of crescents (p = 0. 005) and endocapillary hypercellularity (p < 0.001) in pathological manifestations. Using serum creatinine level doubled of the baseline or reached end-stage renal disease as the endpoint, the prognosis of IgA-dominant postinfectious glomerulonephritis patients was worse than that of primary IgA nephropathy patients (p = 0.013). CONCLUSIONS: The clinicopathological features of patients with IgA-dominant postinfectious glomerulonephritis was different from that of primary IgA nephropathy, and the prognosis was worse.

LVAD Vasculitis Case Series: Suggestion of a New Fatal LVAD-Related Phenomenon.

Left ventricular assist devices (LVADs) are surgically implanted mechanical devices indicated for patients with advanced heart failure and are known to come with several complications. Here we present a case series, and review 1 documented report, of LVAD vasculitis, a presumed new LVAD immune/humoral related phenomenon. (Level of Difficulty: Advanced.).

The Continuing Need for Electron Microscopy in Examination of Medical Renal Biopsies: Examples in Practice.

Background: For the better part of the past 6 decades, transmission electron microscopy (EM), together with routine light microscopy and immunofluorescence and/or immunohistochemistry (IHC), has been an essential component of the diagnostic workup of medical renal biopsies, particularly native renal biopsies, with increasing frequency in renal allograft biopsies as well. Studies performed prior to the year 2000 have indeed shown that a substantial fraction of renal biopsies cannot be accurately diagnosed without EM. Still, EM remains costly and labor-intensive, and with increasing pressure to reduce healthcare costs, some centers are de-emphasizing diagnostic EM. This trend has been coupled with advances in IHC and other methods in renal biopsy diagnosis over the past 2-3 decades. Summary: Nonetheless, it has been our experience that the diagnostic value of EM in the comprehensive evaluation of renal biopsies remains similar to what it was 20-30 years ago. In this review, we provide several key examples from our practice where EM was essential in making the correct renal biopsy diagnosis, ranging from relatively common glomerular lesions to rare diseases. Key Messages: EM remains an important component of the diagnostic evaluation of medical renal biopsies. Failure to perform EM in certain cases will result in an incorrect diagnosis, with possible clinical consequences. We strongly recommend that tissue for EM be taken and stored in an appropriate fixative and ultrastructural studies be performed for all native renal biopsies, as well as appropriate renal allograft biopsies as recommended by the Banff consortium.

Changing Frequency of Glomerular Diseases in Western Saudi Arabia: A 26-Year Experience.

INTRODUCTION: The frequency of glomerulonephritis (GN) is reported to be changing in the world over the past four decades. Few studies arise from the western region of Saudi Arabia. AIMS: The aim of this study was to address the frequency of primary GN (1ry GN) and secondary GN (2ry GN) over a period of 26 years in the western region of Saudi Arabia and compare to previous data from other regions of the country. SUBJECTS AND METHODS: The records of adult renal biopsies, 448 1ry GN and 263 2ry GN, are analyzed. Frequencies of GN subtypes are compared for period 1 (1988-19999) and period 2 (2000-2013). RESULTS: Postinfectious GN (PIGN) and minimal change disease (MCD) show significant changes (P ≤ 0.05). PIGN increased to 6.5% in period 2 from 0% in period 1. MCD decreased to 5.9% in period 2 from 13.5% in period 1. Membranous GN is the most common 1ry GN for both periods with similar percentages (23.8% and 24.2%, respectively). Focal segmental glomerulosclerosis (FSGSC) is the second in period 2 (23%); immunoglobulin A nephropathy at 9.6% became the third, and MCD is the last place instead of the fourth in period 1. Lupus nephritis is the most common 2ry GN. Pooled data from Saudi studies show FSGSC the most common 1ry GN in both periods. CONCLUSIONS: The western region of Saudi Arabia presents with a different 1ry GN pattern than the rest of the country that is likely attributed to its unique geographical and environmental characteristics.

Podocytes Intracytoplasmic Dense Inclusions: Are They Associated with Subepithelial Dense Deposits? An Ultrastructural Study.

INTRODUCTION: Podocytes play a crucial role in health and disease. They participate in clearing the filtration barrier by removing accumulated proteins. It is proposed that podocytes have the ability to remove immune complexes and internalize them in the cytoplasm. AIMS: The purpose of this study is to review certain immune complex glomerulonephritis (GN) types and illustrate ultrastructural details of podocytes intracytoplasmic dense inclusions (ICDIs) if present. MATERIALS AND METHODS: A retrospective ultrastructural study of podocytes was conducted to detect cytoplasmic inclusions. The study cases (n = 148) include GN types with subepithelial dense deposits such as membranous GN, postinfectious GN (PIGN), and lupus nephritis. RESULTS: Podocytes ICDIs are detected ultrastructurally in 48 of 148 cases, mostly with PIGN; their morphology resembles the subepithelial dense deposits of the corresponding case. CONCLUSIONS: Podocytes ICDIs represent internalized immune complexes from the adjacent subepithelial dense deposits, suggesting a clearance method of the glomerular basement membrane by podocytes.

Plasmapheresis for the Treatment of Crescentic Postinfectious Glomerulonephritis: A Case Report.

Postinfectious glomerulonephritis (PIGN) is an immune-mediated glomerulonephritis caused by bacterial infections. Treatment of PIGN includes appropriate treatment of underlying infection and supportive treatment of the nephritic syndrome. Immunosuppressive drugs may be used to treat PIGN who have a renal failure with or without crescents and suggested only to the patients who does not have an active infection. We report a case who had PIGN secondary to a chronic foot infection and successfully treated with plasmapheresis for the first time in the literature.

Prevention of parvovirus B19-induced repetitive acute kidney failure by subcutaneous immunoglobulins.

Human parvovirus B19 has been associated with various cases of kidney injuries with different glomerular phenotypes. In immunocompromised individuals, insufficient production of neutralizing antibodies can lead to chronic PVB19 carriage and manifestations. However, PVB19 DNA has been detected in bone marrow and peripheral blood for months or years in seemingly immunocompetent individuals, despite the presence of neutralizing antibodies. We report here PVB19-induced recurrent anuric acute kidney failures in a 57-year-old man over a 7-year period with persistent PVB19 infection and then PVB19-associated cryoglobulinemia. Acute renal failures were preceded by influenza-like syndrome associated with arthralgia, skin rash, and low-grade fever. Serum, bone marrow, renal, and digestive PVB19 replication was found in the different episodes. Endocapillary proliferative glomerulonephritis evolved into membranoproliferative glomerulonephritis. Complete renal recovery occurred after each bout. Off-label subcutaneous immunoglobulin therapy resulted in disappearance of blood and bone marrow PVB19 viral load and stopped the glomerulonephritis recurrence. Subcutaneous immunoglobulin therapy withdrawal resulted in renal relapse with cryoglobulin-associated manifestations.