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.

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.

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.

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.

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.

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.

[Macrohematuria in children and adolescents]. / Makrohämaturie im Kindes- und Jugendalter.

Hematuria is usually only noticed early in the case of macrohematuria. In around half of affected children, macrohematuria is caused by a urinary tract infection. In all other cases, a careful diagnosis is required. In addition to a detailed medical history, this builds upon a precise examination of the urine (microscopy, quantitative determination of proteinuria [mg albumin/g creatinine in spontaneously voided urine]) and measurement of blood pressure. The work-up usually includes sonography as the primary imaging modality. Invasive diagnostic tests using cystoscopy are only necessary in exceptional cases. If there is evidence of glomerulonephritis, a kidney biopsy may be indicated. Careful attention should be given to persisting microhematuria (> 6 months) and Alport syndrome should be confirmed or ruled out. Heterozygotic Alport syndrome can also be a possible cause of chronic renal failure.

Ultrasound-Based Radiomics for the Classification of Henoch-Schönlein Purpura Nephritis in Children.

Henoch-Schönlein purpura nephritis (HSPN) is one of the most common kidney diseases in children. The current diagnosis and classification of HSPN depend on pathological biopsy, which is seriously limited by its invasive and high-risk nature. The aim of the study was to explore the potential of radiomics model for evaluating the histopathological classification of HSPN based on the ultrasound (US) images. A total of 440 patients with Henoch-Schönlein purpura nephritis proved by biopsy were analyzed retrospectively. They were grouped according to two histopathological categories: those without glomerular crescent formation (ISKDC grades I-II) and those with glomerular crescent formation (ISKDC grades III-V). The patients were randomly assigned to either a training cohort (n = 308) or a validation cohort (n = 132) with a ratio of 7:3. The sonologist manually drew the regions of interest (ROI) on the ultrasound images of the right kidney including the cortex and medulla. Then, the ultrasound radiomics features were extracted using the Pyradiomics package. The dimensions of radiomics features were reduced by Spearman correlation coefficients and least absolute shrinkage and selection operator (LASSO) method. Finally, three radiomics models using k-nearest neighbor (KNN), logistic regression (LR), and support vector machine (SVM) were established, respectively. The predictive performance of such classifiers was assessed with receiver operating characteristic (ROC) curve. 105 radiomics features were extracted from derived US images of each patient and 14 features were ultimately selected for the machine learning analysis. Three machine learning models including k-nearest neighbor (KNN), logistic regression (LR), and support vector machine (SVM) were established for HSPN classification. Of the three classifiers, the SVM classifier performed the best in the validation cohort [area under the curve (AUC) =0.870 (95% CI, 0.795-0.944), sensitivity = 0.706, specificity = 0.950]. The US-based radiomics had good predictive value for HSPN classification, which can be served as a noninvasive tool to evaluate the severity of renal pathology and crescentic formation in children with HSPN.

A novel case of acute glomerulonephritis with concurrent acute non-rheumatic myocarditis following group a streptococcal infection.

Streptococcal infection is a common cause of acute glomerulonephritis. Cardiac damage associated with streptococcal infection commonly occurs in acute rheumatic fever. However, cases of acute non-rheumatic streptococcal myocarditis have been reported in recent years. We report a novel case of concurrent acute glomerulonephritis and non-rheumatic myocarditis following streptococcal infection. A good prognosis was achieved with antibiotic and immunosuppressive therapy, indicating that Streptococcus causes cardiorenal syndrome type 5 via an immune-mediated response. A better understanding of post-streptococcal cardiorenal syndrome is warranted to enable the early diagnosis and treatment of affected patients.

Waldenström's Macroglobulinemia and Cryoglobulinemic Glomerulonephritis: An Unusual Case of Monoclonal Gammopathy of Renal Significance.

Cryoglobulins are immunoglobulins that precipitate at temperatures below 37 °C and dissolve upon reheating. They can induce small-vessel vasculitis with renal involvement. Cryoglobulinemic glomerulonephritis is a rare manifestation that occurs in patients with monoclonal gammopathy, specifically Waldenström's macroglobulinemia. We present the case of a 52-year-old patient with a history of cutaneous vasculitis and hypothyroidism, who presented with generalized edema, moderate anemia, hypercholesterolemia, nephrotic range proteinuria of 12.69 g/day, microhematuria, arterial hypertension, and hypocomplementemia via the classical pathway, without acute kidney injury and with negative serological studies and positive cryoglobulins in the second determination. Serum and urine protein electrophoresis and immunofixation studies showed a monoclonal band of IgM and kappa light chain. Renal biopsy was consistent with cryoglobulinemic glomerulonephritis. In the context of dysproteinemia and cryoglobulinemic glomerulonephritis, bone-marrow aspiration and biopsy were performed, leading to the diagnosis of Waldenström's macroglobulinemia. Monoclonal gammopathies have been described in association with type I cryoglobulinemias. This described association is uncommon, which is why we present this case, along with a review of the literature.

[Nephrotic syndrome during pregnancy. Is it chronic glomerulonephritis or preeclampsia? Case report].

Nephrotic syndrome (NS) during pregnancy is a fairly rare pathology and its descriptions in the literature are few. For a long time, NS was associated only with an exacerbation of chronic glomerulonephritis or de novo nephritis, however, the experience of recent years has shown that NS can be a manifestation of the classical obstetric pathology - preeclampsia (PE). The appearance of massive proteinuria with the development of NS is most typical for early PE, which, of course, makes diagnosis difficult, especially if PE develops at an unusually early time (up to 20 weeks). To describe PE that does not fit into the classical criteria, the term "atypical" PE is now used, the development of which can be promoted by both obstetric and somatic risk factors. The presented clinical observation describes the development of early (within 14 weeks) severe PE with the NS at the onset of the disease in a patient with the first multiple pregnancy and complete hydatidiform mole (HM) of one of the fetuses. The progression of nephropathy with the addition of thrombotic microangiopathy and HELLP syndrome made it possible to assume the diagnosis of PE with a high probability. The rapid relief of all clinical manifestations after delivery confirmed this assumption. The role of HM as the main trigger of unusually early PE is discussed. Apparently, the patient's trophoblast disease in the form of hydatidiform mole caused the formation of a severe angiogenic imbalance already in the early stages of pregnancy, which led to the development of PE, which manifested NS as a consequence of podocytopathy due to VEGF deficiency. Thus, the development of NS in a pregnant patient without a history of kidney disease dictates, first of all, the exclusion of PE, until proven otherwise.

Metabolome panels as potential noninvasive biomarkers for primary glomerulonephritis sub-types: meta-analysis of profiling metabolomics studies.

Primary glomerulonephritis diseases (PGDs) are known as the top causes of chronic kidney disease worldwide. Renal biopsy, an invasive method, is the main approach to diagnose PGDs. Studying the metabolome profiles of kidney diseases is an inclusive approach to identify the disease's underlying pathways and discover novel non-invasive biomarkers. So far, different experiments have explored the metabolome profiles in different PGDs, but the inconsistencies might hinder their clinical translations. The main goal of this meta-analysis study was to achieve consensus panels of dysregulated metabolites in PGD sub-types. The PGDs-related metabolome profiles from urine samples in humans were selected in a comprehensive search. Amanida package in R software was utilized for performing the meta-analysis. Through sub-type analyses, the consensus list of metabolites in each category was obtained. To identify the most affected pathways, functional enrichment analysis was performed. Also, a gene-metabolite network was constructed to identify the key metabolites and their connected proteins. After a vigorous search, among the 11 selected studies (15 metabolite profiles), 270 dysregulated metabolites were recognized in urine of 1154 PGDs and control samples. Through sub-type analyses by Amanida package, the consensus list of metabolites in each category was obtained. Top dysregulated metabolites (vote score of ≥ 4 or ≤ - 4) in PGDs urines were selected as main panel of meta-metabolites including glucose, leucine, choline, betaine, dimethylamine, fumaric acid, citric acid, 3-hydroxyisovaleric acid, pyruvic acid, isobutyric acid, and hippuric acid. The enrichment analyses results revealed the involvement of different biological pathways such as the TCA cycle and amino acid metabolisms in the pathogenesis of PGDs. The constructed metabolite-gene interaction network revealed the high centralities of several metabolites, including pyruvic acid, leucine, and choline. The identified metabolite panels could shed a light on the underlying pathological pathways and be considered as non-invasive biomarkers for the diagnosis of PGD sub-types.