Crescentic glomerulonephritis due to linear IgA anti-glomerular basement membrane disease: report of a rare case.

Anti-glomerular basement membrane (GBM) disease is a rare and severe vasculitis that affects the glomerular and pulmonary capillaries and has an incidence of less than 2 cases per million individuals per year. Anti-GBM disease is mediated by autoantibodies against the α3 chain of type IV collagen. In the majority of cases, the autoantibodies are of the immunoglobulin G (IgG) class, with rare cases being mediated by immunoglobulin M (IgM) or immunoglobulin A (IgA); there are less than 15 IgA-mediated cases reported in the literature worldwide. The classic form of this disease manifests with rapidly progressive glomerulonephritis (RPGN), with or without pulmonary hemorrhage, and the diagnosis consists of identifying high titers of autoantibodies in the serum and/or deposited in the tissues. IgA antibodies are not identified in routine immunoassay tests, and renal biopsy with immunofluorescence is essential for diagnosis. We present a case of RPGN due to anti-GBM disease with linear IgA deposition, whose diagnosis was made exclusively by renal biopsy and with an unfavorable prognosis.

Clinical and pathological features of 52 patients with glomerulonephritis with dominant C3. / C3沉积为主的肾小球肾炎52ä¾‹ä¸´åºŠä¸Žç— ç†ç‰¹å¾.

OBJECTIVES: With the in-depth study of complement dysregulation, glomerulonephritis with dominant C3 has received increasing attention, with a variety of pathologic types and large differences in symptoms and prognosis between pathologic types. This study analyzes the clinical, pathological, and prognostic characteristics of different pathological types of glomerulonephritis with dominant C3, aiming to avoid misdiagnosis and missed diagnoses. METHODS: The clinical, pathological, and follow-up data of 52 patients diagnosed as glomerulonephritis with dominant C3 by renal biopsy from June 2013 to October 2022 were retrospectively analyzed. According to the clinical feature and results of pathology, 15 patients with post-infectious glomerulonephritis (PIGN) and 37 patients with of non-infectious glomerulonephritis (N-PIGN) were classified. N-PIGN subgroup analysis was performed, and 16 patients were assigned into a C3-alone-deposition group and 21 in a C3-dominant-deposition group, or 27 in a C3 glomerulopathy (C3G) group and 10 in a non-C3 nephropathy (N-C3G) group. RESULTS: The PIGN group had lower creatinine values (84.60 µmol/L vs179.62 µmol/L, P=0.001), lower complement C3 values (0.36 g/L vs0.74 g/L, P<0.001) at biopsy, and less severe pathological chronic lesions compared with the N-PIGN group. In the N-PIGN subgroup analysis, the C3-dominant-deposition group had higher creatinine values (235.30 µmol/L vs106.70 µmol/L, P=0.004) and higher 24-hour urine protein values (4 025.62 mg vs1 981.11 mg, P=0.037) than the C3-alone-deposition group. The prognosis of kidney in the PIGN group (P=0.049), the C3-alone-deposition group (P=0.017), and the C3G group (P=0.018) was better than that in the N-PIGN group, the C3-dominant-deposition group, and the N-C3G group, respectively. CONCLUSIONS: Glomerulonephritis with dominant C3 covers a variety of pathological types, and PIGN needs to be excluded before diagnosing C3G because of considerable overlap with atypical PIGN and C3G; in addition, the deposition of C1q complement under fluorescence microscope may indicate poor renal prognosis, and relevant diagnosis, treatment, and follow-up should be strengthened.

Case of IgG4-related Disease with Crescentic Glomerulonephritis: An Unusual Presentation of the Disease.

IgG4-related disease (IgG4-RD) is a chronic systemic inflammatory  disease, characterized by tissue infiltration of lymphocytes and  IgG4-secreting plasma cells, presenting by fibrosis of different  tissues, which is usually responsive only to oral steroids therapy.  Kidneys are the most commonly involved organs, exhibiting renal  insufficiency, tubulointerstitial nephritis, and glomerulonephritis.  Here, we describe a patient with acute renal insufficiency who  was presented with edema, weakness, anemia and multiple  lymphadenopathies. Kidney and lymph node biopsy showed  crescentic glomerulonephritis in kidneys and lymphoplasmacytic  infiltration in lymph nodes. After a course of treatment with an  intravenous pulse of corticosteroid and cyclophosphamide, the  patient's symptoms subsided, and kidney function improved. DOI: 10.52547/ijkd.7788.

Clinicopathological characteristics and predictors of outcome of rapidly progressive glomerulonephritis: a retrospective study.

BACKGROUND: Globally, there are regional and time-based variations in the prevalence, etiology, and prognosis of rapidly progressive glomerulonephritis (RPGN). Prognosis of RPGN is poor, with a higher risk of death and end stage renal disease (ESRD) even with immunosuppressive medications. In the Middle East and North Africa, the studies on this disease are very limited. Therefore, we determined the predictors of outcome of RPGN. METHODS: We retrospectively assessed 101 adult patients over age of 18, diagnosed with RPGN based on renal biopsy illustrating crescents in ≥ 50% of the glomeruli. Patients who had crescents in their renal biopsies that were < 50% and those who refused to consent to a renal biopsy were excluded. We categorized the patients into 3 groups based on immunohistochemistry; type I, type II and type III. Then, depending on renal loss, we divided them into ESRD and non-ESRD groups. The clinical history and physical examination were retrieved. Additionally, 24-hour urine protein, urine analysis, renal function tests, serum albumin, complete blood count, antinuclear antibodies, anti-double stranded DNA antibodies, ANCA antibodies and serum complement levels were checked. Each patient underwent a kidney biopsy for immunohistochemistry and light microscopy. The percentage of crescentic glomeruli, number of sclerosed glomeruli, tertiary lymphoid organ (TLO), neutrophil infiltration, endocapillary or mesangial hypercellularity, interstitial fibrosis with tubular atrophy (IFTA) were analyzed. Primary outcomes (remission, ESRD and mortality) and secondary outcomes were assessed. RESULTS: Type II was the most frequent cause of RPGN (47.5%), followed by type III (32.7%) and type I (19.8%). 32 patients (31.7%) died during follow up, whereas 60 patients (59.4%) developed ESRD. In 41 patients (40.6%), remission occurred. Oliguria, serum creatinine, and need for HD at presentation were significantly increased in ESRD group compared to non-ESRD group (P < 0.001 for each). Mesangial proliferation, IFTA, TLO formation, sclerotic glomeruli and fibrous crescents were also significantly increased in ESRD group in comparison to non-ESRD group (P < 0.001 for each). Glomerulosclerosis (P = 0.036), and IFTA (P = 0.008) were predictors of ESRD. Infections (P = 0.02), respiratory failure (P < 0.001), and heart failure (P = 0.004) were mortality risk factors. CONCLUSION: Type II RPGN was the most common. Infection was the most frequent secondary outcome. Oliguria, glomerulosclerosis, the requirement for hemodialysis at presentation, IFTA and TLO formation were predictors of ESRD. Respiratory failure, heart failure and infections were significant predictors of mortality.

Group A Streptococcus Infections.

Group A Streptococcus causes a variety of clinical manifestations, including pharyngitis and skin and soft tissue infections as well as more invasive disease. There are also multiple nonsuppurative complications of group A Streptococcus infection, including acute rheumatic fever and poststreptococcal glomerulonephritis. Pediatricians should be able to diagnose and treat the various presentations of the infection.

To interpret and analyze the changing patterns of histology and direct immunofluorescence findings in membranoproliferative glomerulonephritis.

Background: Membranoproliferative glomerulonephritis has in the recent past been regrouped into immune complex-mediated (ICM MPGN) disease (driven by the classical complement pathway) and complement-mediated (C3GN) disease (driven by the alternative complement pathway) based on pathogenetic role of alternative complement pathway and immunofluorescence deposits. The proposed regrouping lent therapeutic and prognostic support in managing the disease of MPGN. Aims and Objectives: The present study is undertaken to study the patterns of MPGN based on histopathological and DIF examination and sub-categorize the cases into mainly complement dominant and immune complex-mediated diseases for better prognostic and therapeutic utility. Materials and Methods: This is a prospective observational study carried out in a tertiary care center over a period of 2 yrs. The clinically suspected cases of MPGN were subjected to histopathologic and direct immunofluorescence examination (DIF), and the findings were interpreted in light of complement-mediated and immune complex-mediated MPGN. Results: Out of 620 renal biopsies, diagnosis of MPGN was confirmed both on histopathology and DIF in 36 cases accounting for 5.8% of all biopsies. Based on DIF findings, the various groups comprised 20 cases (55.6%) of immune complex deposits, 11 (30.5%) of C3 dominant picture, and 5 (13.9%) of Nil immune deposits. On analysis of the patterns on DIF, 16 cases (80%) of C3 + Ig group and 6 (54.5%) of C3GN group showed predominantly MPGN pattern. Crescentic glomerulonephritis, global glomerulosclerosis, and interstitial fibrosis were markedly observed in C3GN group. Conclusion: DIF is of immense prognostic and therapeutic value in managing cases of MPGN.

Impact of Pretransplant Dialysis Modality on Posttransplant Outcomes: A Single-Center Experience.

OBJECTIVES: It remains unclear whether posttransplant outcomes differ according to the pretransplant dialysis modality (peritoneal dialysis vs hemodialysis). Our aim was to assess posttransplant outcomes in patients with different predialysis modalities. MATERIALS AND METHODS: Two thousand two hundred fifty-eight kidney recipients following up in Hamed Alessa Organ transplant center in Kuwait were included and divided into two groups according to pre-transplant dialysis modality: Group 1: those who received hemodialysis (HD) and group 2: those with peritoneal dialysis (PD). Demographics, pretransplant and posttransplant comorbidities, and patient and graft outcomes were studied. RESULTS: There were 1956 patients on hemodialysis, and 302 patients were on peritoneal dialysis. Most were male patients (1456 vs 802 female patients), with comparable mean age (P = .34). Chronic glomerulonephritis and diabetic nephropathy represented the most common original kidney disease before transplant (27.6% and 21.4%, respectively), with higher prevalence of glomerulonephritis in group 1 and diabetic nephropathy in group 2 (P = .001). The 2 groups were comparable with regard to immunosuppression (induction and maintenance) (P > .05). Posttransplant diabetes and hypertension were significantly higher in the hemodialysis group (P = .004 and P = 003, respectively). There was no significant difference between the 2 groups with regard to the graft outcome (P = .86). However, patient survival was significantly higher in the hemodialysis group (81.2% vs 64.4%). CONCLUSIONS: Compared with peritoneal dialysis, pretransplant hemodialysis is associated with better posttransplant patient survival despite no difference in the graft outcome. Diabetes-related complications could be attributed to such outcomes.

Executive summary of the KDIGO 2024 Clinical Practice Guideline for the Management of ANCA-Associated Vasculitis.

In 2021, the Kidney Disease: Improving Global Outcomes (KDIGO) Guideline for the Management of Glomerular Diseases was published. KDIGO is committed to providing the nephrology community with periodic updates, based on new developments for each disease. For patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), avacopan received regulatory approval in late 2021, leading to this KDIGO guideline update. In addition, the evidence supporting a lower-dose glucocorticoid induction regimen or even complete replacement of glucocorticoids has become stronger. Herein, an executive summary of the most important guideline changes from the AAV chapter is provided as a quick reference.

A 6-year review of acute post-streptococcal glomerulonephritis at a public children's hospital in Cape Town, South Africa.

BACKGROUND: Acute post-streptococcal glomerulonephritis (APSGN) is the most common cause of acute nephritis in children globally and, in some cases, may be associated with progressive kidney injury and failure, cumulating in the need for long-term dialysis and/or kidney transplantation. METHODS: Our retrospective study describes the occurrence of APSGN among children (< 14 years) admitted to a tertiary children's hospital in Cape Town, South Africa, from January 2015 to December 2020. RESULTS: Of 161 children who presented with acute nephritis (haematuria, oedema, oliguria, and hypertension), 100 met the inclusion criteria. Demographic, clinical features, laboratory findings, management, and outcome data were collected. APSGN was defined by the clinical presentation of at least two clinical signs of acute nephritis, and low serum complement 3 (C3) level or evidence of a recent streptococcal infection. Most cases of APSGN were associated with streptococcal skin infections: 55/100 (55%); 10/100 (10%) children presented with hypertensive seizures; C3 levels were low in 86/92 (93.5%) children; 94/94 (100%) children had elevated anti-deoxyribonuclease-B (anti-DNase-B) levels; and 80/94 (85%) also had elevated anti-streptolysin O titre (ASOT) at presentation. Eleven (11%) children had a percutaneous kidney biopsy; 4/11 (36%) showed histological features of post-infectious nephritis, and 7/11(64%) also had crescentic glomerulonephritis with immune complex deposits. Sixty-two (62%) children confirmed recovered, and five (5%) progressed to kidney failure, but 29 presumed recovered as they did not return for follow-up to our institution. CONCLUSIONS: Childhood APSGN remains an important health problem in South Africa (SA) with favourable outcomes in most, apart from those with crescentic glomerulonephritis who progressed to kidney failure.

Antineutrophil Cytoplasmic Autoantibody-negative Pauci-immune Necrotizing Glomerulonephritis with Plasma Cell-rich Tubulointerstitial Nephritis Complicated with Pleuritis and Digital Ischemia.

Antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV) predominantly affects small vessels. Almost all AAV patients are positive for myeloperoxidase- or proteinase 3-ANCA, and ANCA plays a crucial role in the pathogenesis of AAV. We herein report an ANCA-negative AAV patient with pauci-immune necrotizing glomerulonephritis and plasma cell-rich tubulointerstitial nephritis who was complicated with pleuritis and digital ischemia. ANCA-negative AAV is a rare clinical entity that is difficult to diagnose, and pleuritis and digital ischemia are rare manifestations of AAV. An early diagnosis and appropriate treatment are important, as any delay in the diagnosis may worsen the prognosis.

Acute glomerulonephritis with concurrent suspected bacterial pneumonia - is it the tip of the iceberg?

BACKGROUND: Post infectious glomerulonephritis is the most common glomerulopathy in children, occurring several weeks after nephritogenic streptococcal throat or skin infection. Reports of acute glomerulonephritis (AGN) occurring during active bacterial pneumonia in children are rare. The aim of this study was to evaluate the incidence of AGN concurrent with bacterial pneumonia in children. METHODS: We reviewed records of all children admitted with a diagnosis of pneumonia to the pediatric department in a single tertiary medical center between January 2015 and April 2023. Patients with bacterial pneumonia and concurrent glomerulonephritis were included. RESULTS: Eleven (0.98%) of 1,123 patients with bacterial pneumonia had concurrent AGN. All were males with a median age of 2.7 years (range 1-13). Mean time from bacterial pneumonia onset to acute glomerulonephritis symptoms was 2.7 ± 1.5 days. Five (45%) patients had evidence of pneumococcal infection. Hypertension was found in 10 (91%) patients. Mean trough eGFR was 43.5 ± 21.4 ml/min/1.73 m2 (range 11-73). Ten patients (91%) had low C3 levels. Median urinary protein-to-creatinine ratio was 2.5 mg/mg (IQR 2.15-14.75). All patients fully recovered. Microscopic hematuria was the last finding to normalize after a median of 29.5 days (IQR 17.25-38). CONCLUSION: AGN during bacterial pneumonia may be more frequent than previously recognized. Kidney prognosis was excellent in all patients. Prospective studies are needed to evaluate the impact of this condition.

ANCA-associated kidney disease preceded by orbital pseudotumor.

INTRODUCTION: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and IgG4-related disease (IgG4-RD) are distinct immune disorders with overlapping clinical and laboratory features. While ANCA positivity excludes IgG4-RD in the 2019 ACR/EULAR classification, this criterion is not uniformly applied, and AAV can form inflammatory masses in various organs and show increase in IgG4 + plasma cells, similar to IgG4-RD. CASE DIAGNOSIS/TREATMENT: A 5-year-old female with history of orbital mass diagnosed as IgG4-RD presents with acute kidney injury. She has a myeloperoxidase ANCA, and kidney biopsy shows pauci-immune crescentic glomerulonephritis and acute tubulointerstitial nephritis with increased IgG4 + plasma cells and tubular basement membrane (TBM) deposits. CONCLUSION: In isolation, TBM deposits and increased IgG4 + plasma cells are suggestive of IgG4-RD. In the context of a positive ANCA and pauci-immune crescentic glomerulonephritis, however, increased IgG4 + plasma cells due to AAV are favored. In cases with features of IgG4-RD, ANCA positivity suggests an alternate diagnosis of AAV to be more likely.

Nephrotic "full-house" glomerulonephritis successfully treated with antibiotics alone in secondary syphilis: a case report.

A Japanese female in her twenties developed general edema with heavy proteinuria, and was referred to our hospital. She exhibited the common clinical manifestation of idiopathic nephrotic syndrome with massive proteinuria (20.37 g/day), hypoalbuminemia (1.8 g/dL), and hypercholesterolemia (300 mg/dL). Routine admission tests were positive results for both the rapid plasma reagin latex agglutination test for syphilis (RPR) and the Treponema pallidum particle agglutination assay (TPHA). As such, we made her a diagnosis of nephrotic syndrome due to secondary syphilis. Renal biopsy revealed "full-house" nephropathy. Following the commencement of penicillin treatment, she developed skin rash, indicating the Jarisch-Herxheimer reaction (JHR). Her nephrotic syndrome responded rapidly and she achieved complete remission with antibiotic therapy alone after 4 weeks. In light of the increasing incidence of syphilis in Japan, clinicians should consider syphilis as a reversible cause of nephrotic syndrome.

C3 glomerulopathy in a patient with a history of post-infectious glomerulonephritis.

Post-infectious glomerulonephritis (PIGN) is an immune complex mediated glomerular injury occurring because of an infection, most commonly with group A beta-hemolytic streptococcus in children. C3 glomerulopathy (C3G) is a distinct clinicopathological entity occurring secondary to dysregulation of alternate complement pathway encompassing both C3 glomerulonephritis (C3GN) and dense deposit disease (DDD). While most patients with PIGN attain complete remission with normalized complement levels by 6-8 weeks after presentation, patients with C3G continue to have hypocomplementemia with high rates of progressive kidney disease. Here, we report a patient diagnosed with dense deposit disease after his initial presentation with PIGN three years prior. While current literature continues to explore the overlapping and distinguishing features of PIGN and C3G, including how underlying defects in the alternate complement pathway may commonly contribute to both diseases, this case further exemplifies the importance of recognizing the clinico-pathogenic features of PIGN and C3G in pediatric patients with glomerulonephritis.

SARS-CoV-2 infection associated with antineutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis (ANCA-GN): a systematic review and two case reports.

BACKGROUND: It has been observed that SARS-CoV-2 infections are associated with the development of various de-novo autoimmune diseases; little is known on new-onset antineutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis (ANCA-GN) after SARS-CoV-2 infections. METHODS: We conducted a systematic review of previously reported cases with a presumed association of new-onset antineutrophil cytoplasmic antibody-associated glomerulonephritis (ANCA-GN). No language restrictions were applied during the search. The eligible articles included reports of biopsy-proven pauci-immune glomerulonephritis that occurred following SARS-CoV-2 infection. The review was registered in PROSPERO database (CRD42023407786). Two further cases are reported. RESULTS: The mean age of SARS-CoV-2 infection-associated ANCA-GN was 48 ± 19 years. Fifty-six percent of patients showed positivity for myeloperoxidase (MPO)-ANCA. Among tested patients, 36% had concomitantly positive antinuclear antibodies, and 100% had positive rheumatoid factor. Eleven out of the 21 cases (55%) were diagnosed with ANCA-GN during hospitalization due to SARS-CoV-2 infection. The remaining cases were diagnosed after a median of 2.1 months following COVID-19. Seventy-one percent of patients showed improvement in kidney function following different treatments. CASE REPORTS: one patient had positive p-ANCA and cryoglobulin. Another case had positive MPO-ANCA, c-ANCA, cryoglobulinemia, and rheumatoid factor. CONCLUSION: SARS-CoV-2 infection-associated ANCA-GN patients are younger than primary ANCA-GN patients. The presence of atypical ANCA along with co-positivity with other autoantibodies can raise suspicion for SARS-CoV-2 infection-associated ANCA-GN.