Comparison of EULAR/PRINTO/PReS Ankara 2008 and 2022 ACR/EULAR Classification Criteria for Granulomatosis with Polyangiitis in Children.

OBJECTIVE: Granulomatosis with polyangiitis (GPA) is an antineutrophil cytoplasmic antibody-associated vasculitis. The 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology (ACR/EULAR)-endorsed classification criteria for GPA was derived using data only from adult patients. We aimed to assess the performance of the ACR/EULAR classification criteria for GPA in pediatric patients and compare it with the EULAR/Pediatric Rheumatology International Trials Organization (PRINTO)/Pediatric Rheumatology European Society (PReS)-endorsed Ankara 2008 criteria for GPA. METHODS: Retrospective data of pediatric patients with GPA in 20 centers from 9 countries were evaluated. The diagnosis of GPA was made according to the expert opinion. The sensitivity, specificity, positive predictive value, and negative predictive value of the criteria sets were evaluated. RESULTS: The study included 77 patients with GPA and 108 controls (immunoglobulin A vasculitis (n = 44), Takayasu's arteritis (n = 20), microscopic polyangiitis (n = 16), polyarteritis nodosa (n = 14), Behçet's disease (n = 12), eosinophilic granulomatosis with polyangiitis (n = 1), and Cogan's syndrome (n = 1)) with a median age of 17.8 and 15.2 years, respectively. Of patients with GPA, constitutional symptoms (85.7%) and ear-nose-throat involvement (79.2%) were the most common presentations. In the GPA group, 73 patients fulfilled the Ankara 2008 criteria and 69 the ACR/EULAR classification criteria. Sensitivities of the Ankara 2008 criteria and the ACR/EULAR classification criteria were 94.8% and 89.6%, while specificities were 95.3% and 96.3%, respectively. No significant difference was found between sensitivities and specificities of both classification criteria (p= 0.229 and p= 0.733, respectively). CONCLUSION: In children, both the ACR/EULAR and EULAR/PRINTO/PReS Ankara 2008 classification criteria for GPA perform well and similarly.

Goodpasture syndrome and anti-glomerular basement membrane disease.

Anti-glomerular basement membrane (anti-GBM) disease is a rare life-threatening small vessel vasculitis that typically affects the capillaries of kidneys and lungs, with most of patients developing rapidly progressive crescentic glomerulonephritis, and 40%-60% concomitant alveolar haemorrhage. It is caused by the deposition in alveolar and glomerular basement membrane of circulating autoantibodies directed against antigens intrinsic to the basement membrane. The exact mechanism that induces the formation of autoantibodies is unknown, but probably environmental factors, infections or direct damage to kidneys and lungs may trigger the autoimmune response in genetically susceptible individuals. Initial therapy includes corticosteroids and cyclophosphamide to prevent autoantibodies production, and plasmapheresis to remove the circulating autoantibodies. Good renal outcomes may be achieved by a prompt treatment initiation. However, when patients present with severe renal failure requiring dialysis or with a high proportion of glomerular crescents at biopsy, renal outcomes are bad. Relapses are rare and when renal involvement is present, the suspect of concomitant diseases, such as ANCA-associated vasculitis and membranous nephropathy, should be raised. Imlifidase is showing promising results, which if confirmed will cause a paradigm shift in the treatment of this disease.

Long-term kidney outcome of patients with rheumatological diseases and antineutrophil cytoplasmic antibody-glomerulonephritis: comparison with a primitive ANCA-glomerulonephritis cohort.

OBJECTIVES: Antineutrophil cytoplasmic antibody (ANCA) may appear in the course of rheumatic diseases (RD) but the kidney involvement is very rare and the prognosis poorly defined. METHODS: We retrospectively identified patients with RD among 153 patients with ANCA glomerulonephritis (ANCA-GN). Their clinical/histological presentation and outcome were compared with that of primitive ANCA-GN patients (1:4) matched for sex, age, ANCA type and follow-up. RESULTS: Nine patients (5.9%) were included: three had rheumatoid arthritis, two systemic sclerosis, two psoriatic arthritis, one ankylosing spondylitis and one seronegative spondylarthritis. Seven patients were MPO positive, two PR3 positive. ANCA-GN developed 74 months after RD with microscopic haematuria and acute kidney dysfunction in all but two patients. After 68-month follow-up, four patients (44.4%) achieved response to therapy defined as eGFR >60/min/1,73 m2 or stable, no microscopic haematuria and negative ANCA. At ANCA-GN diagnosis, serum creatinine and C-reactive protein were significantly lower in RD-ANCA-GN (2.38 vs. 3.34mg/dl, p=0.05 and 2.3mg/dl vs. 7.2mg/dl; p=0.05, respectively) while haemoglobin was higher (12.3g/dl vs. 9.3g/dl p<0.01) than in the 36 primitive ANCA-GN patients of control group. At kidney biopsy, focal forms were more frequent in RD patients (44.45% vs. 18.75%, p=0.11). The treatment between the two groups was not significantly different. At last observation, the percentage of patients with ESKD was lower in RD than in controls (11.1%vs. 30.5%; p=0.23). CONCLUSIONS: Patients with RD seem to develop ANCA-GN with less severe clinical/histological kidney involvement, and better long-term kidney survival than primitive ANCA-GN. This is probably due to the strict monitoring of RD patients that allows a prompter ANCA-GN diagnosis and treatment.

Microplastics and Kidneys: An Update on the Evidence for Deposition of Plastic Microparticles in Human Organs, Tissues and Fluids and Renal Toxicity Concern.

Plastic pollution became a main challenge for human beings as demonstrated by the increasing dispersion of plastic waste into the environment. Microplastics (MPs) have become ubiquitous and humans are exposed daily to inhalation or ingestion of plastic microparticles. Recent studies performed using mainly spectroscopy or spectrometry-based techniques have shown astounding evidence for the presence of MPs in human tissues, organs and fluids. The placenta, meconium, breast milk, lung, intestine, liver, heart and cardiovascular system, blood, urine and cerebrovascular liquid are afflicted by MPs' presence and deposition. On the whole, obtained data underline a great heterogeneity among different tissue and organs of the polymers characterized and the microparticles' dimension, even if most of them seem to be below 50-100 µm. Evidence for the possible contribution of MPs in human diseases is still limited and this field of study in medicine is in an initial state. However, increasing studies on their toxicity in vitro and in vivo suggest worrying effects on human cells mainly mediated by oxidative stress, inflammation and fibrosis. Nephrological studies are insufficient and evidence for the presence of MPs in human kidneys is still lacking, but the little evidence present in the literature has demonstrated histological and functional alteration of kidneys in animal models and cytotoxicity through apoptosis, autophagy, oxidative stress and inflammation in kidney cells. Overall, the manuscript we report in this review recommends urgent further study to analyze potential correlations between kidney disease and MPs' exposure in human.

Blood Thiol Redox State in Chronic Kidney Disease.

Thiols (sulfhydryl groups) are effective antioxidants that can preserve the correct structure of proteins, and can protect cells and tissues from damage induced by oxidative stress. Abnormal levels of thiols have been measured in the blood of patients with moderate-to-severe chronic kidney disease (CKD) compared to healthy subjects, as well as in end-stage renal disease (ESRD) patients on haemodialysis or peritoneal dialysis. The levels of protein thiols (a measure of the endogenous antioxidant capacity inversely related to protein oxidation) and S-thiolated proteins (mixed disulphides of protein thiols and low molecular mass thiols), and the protein thiolation index (the molar ratio of the S-thiolated proteins to free protein thiols in plasma) have been investigated in the plasma or red blood cells of CKD and ESRD patients as possible biomarkers of oxidative stress. This type of minimally invasive analysis provides valuable information on the redox status of the less-easily accessible tissues and organs, and of the whole organism. This review provides an overview of reversible modifications in protein thiols in the setting of CKD and renal replacement therapy. The evidence suggests that protein thiols, S-thiolated proteins, and the protein thiolation index are promising biomarkers of reversible oxidative stress that could be included in the routine monitoring of CKD and ESRD patients.

Volume Balance in Chronic Kidney Disease: Evaluation Methodologies and Innovation Opportunities.

BACKGROUND: Patients affected by chronic kidney disease are at a risk of cardiovascular morbidity and mortality. Body fluids unbalance is one of the main characteristics of this condition, as fluid overload is highly prevalent in patients affected by the cardiorenal syndrome. SUMMARY: We describe the state of the art and new insights into body volume evaluation. The mechanisms behind fluid balance are often complex, mainly because of the interplay of multiple regulatory systems. Consequently, its management may be challenging in clinical practice and even more so out-of-hospital. Availability of novel technologies offer new opportunities to improve the quality of care and patients' outcome. Development and validation of new technologies could provide new tools to reduce costs for the healthcare system, promote personalized medicine, and boost home care. Due to the current COVID-19 pandemic, a proper monitoring of chronic patients suffering from fluid unbalances is extremely relevant. Key Message: We discuss the main mechanisms responsible for fluid overload in different clinical contexts, including hemodialysis, peritoneal dialysis, and heart failure, emphasizing the potential impact provided by the implementation of the new technologies.

Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis in Kidney Transplantation.

Due to complex comorbidity, high infectious complication rates, an elevated risk of relapsing for primary renal disease, as well as inferior recipient and allograft survivals, individuals with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAVs) are often considered as poor transplant candidates. Although several aspects of recurrent and de novo AAVs remain unclear, recent evidence suggests that kidney transplantation (KT) represents the best option, which is also the case for this particular subgroup of patients. Special counselling and individualized approaches are strongly recommended at the time of enlistment and during the entire post-transplant follow-up. Current strategies include avoiding transplantation within one year of complete clinical remission and thoroughly assessing the recipient for early signs of renal or systemic vasculitis. The main clinical manifestations of allograft AAV are impaired kidney function, proteinuria, and hematuria with ANCA positivity in most cases. Mixed results have been obtained using high-dose steroids, mycophenolate mofetil, or cyclophosphamide. The aim of the present review was to summarize the available literature on AAVs in KT, particularly focusing on de novo pauci-immune glomerulonephritis.

Adverse events linked with the use of chimeric and humanized anti-CD20 antibodies in children with idiopathic nephrotic syndrome.

AIMS: Anti-CD20 antibodies are increasingly being used to treat idiopathic nephrotic syndrome (INS) in children. While they may allow steroid and calcineurin inhibitor withdrawal, repeated infusions of anti-CD20 antibodies are often required to maintain remission. Data on their potential toxicity in INS are needed, to consider repeated infusions. METHODS: We investigated the side effects associated with the use of rituximab (a chimeric antibody; 130 patients) and ofatumumab (a humanized antibody; 37 patients) in children with INS (steroid-dependent and steroid/calcineurin inhibitor-dependent disease) treated at a national referral centre over a 9-year period (400 treatments; follow-up 1-9 years). RESULTS: Infusion reactions were mainly absent in children with steroid-dependent disease. Rash, dyspnoea, fever, cough and itchy throat (5% and 18% following rituximab and ofatumumab infusion, respectively) were resolved by using premedication with salbutamol. Other short-term reactions (up to 3 months), including arthritis (2%) and lung injury (1%), were more common with rituximab. Infections were observed 3-9 months following infusion, were similarly common in the two groups and resolved with targeted therapies [antibiotic, fluconazole, immunoglobulins (Igs), etc.]. The number of circulating CD19/20 cells fell to 0 at month 1 and were reconstituted at month 3; circulating IgG antibodies remained within the normal range for 1 year. Tetanus and hepatitis B virus immunization was not modified by either treatment; Epstein-Barr virus and John Cunningham virus activation markers were occasionally observed. CONCLUSION: Overall, the toxicity of anti-CD20 monoclonal antibodies was limited to post-infusion side effects in children with more complex disease. The relatively safe profile of anti-CD20 antibodies supports their use as steroid-sparing agents in children with INS.

Treatment strategies for ANCA-associated vasculitides: from standard protocols to future horizons.

INTRODUCTION: ANCA-associated vasculitides (AAV), classified into granulomatosis with polyangiitis, microscopic polyangiitis, and eosinophilic granulomatosis with polyangiitis represent a group of disorders characterized by necrotizing vasculitis of small vessels, endothelial injury and tissue damage. The outcomes and prognosis of AAV have undergone significant changes with the introduction of glucocorticoids (GCs) and other immunosuppressants (cyclophosphamide, azathioprine, methotrexate, and mycophenolate mofetil). The enhanced understanding of pathogenesis has subsequently led to the incorporation into clinical practice of drugs targeting specific therapeutic targets. AREAS COVERED: After an extensive literature search of Pubmed, Medline, Embase of the most recent evidence, we provide an overview of available treatments, highlighting how newer drugs have integrated into standard protocols. Our review also explores potential new therapeutic targets, including B cell depletion and inhibition, T cell inhibition, complement inhibition, and IL-5 and IgE inhibition. EXPERT OPINION: There is hope that the new treatment targets currently under study in AAV may enable a faster and more lasting clinical response, ensuring the reduction of possible side effects from therapies. Moreover, numerous aspects necessitate further exploration in the future, such as tailoring of GCs, integration of GCs-sparing agents, efficacy of combination therapy, optimal maintenance therapy, to reduce organ-damage and improve quality of life.

Is per-protocol kidney biopsy required in lupus nephritis?

Baseline kidney biopsy is recommended in lupus nephritis (LN). Biopsy allows to classify different forms of LN and differentiate other forms of renal involvement, such as tubulo-interstitial nephritis or thrombotic microangiopathy. The indications for repeat biopsy are more controversial. Some authors feel that good clinical monitoring is sufficient to assess prognosis and make therapeutic decisions. Based on the recently demonstrated discordance between clinical and histological response, some physicians recommend per-protocol biopsies either at 6 months in stable patients to verify the response to induction therapy, or after one-to-two years to assess treatment efficacy and tune the duration of maintenance therapy. Others recommend repeating kidney biopsy in case of incomplete response or to discriminate between active and chronic lesions. By definition, a per-protocol kidney biopsy differs from a repeat biopsy in that the former is foreseen at fixed timepoints, regardless of the clinical response. Although any decision should always consider the patient's overall clinical condition, there are no doubts that repeat kidney biopsy represents a useful tool in difficult cases to evaluate treatment response, modulate treatment intensity, and predict long-term renal outcome both in quiescent lupus and during flares. How to harmonize per-protocol biopsies in the LN course remains challenging.

Anti-C1q antibodies: a biomarker for diagnosis and management of lupus nephritis. A narrative review.

Nephritis is a frequent and severe complication of Systemic Lupus Erythematous (SLE). The clinical course of lupus nephritis (LN) is usually characterized by alternating phases of remission and exacerbation. Flares of LN can lead to deterioration of kidney function, necessitating timely diagnosis and therapy. The presence of autoantibodies against C1q (anti-C1qAb) in the sera of SLE patients has been reported in various studies. Some research suggests that the presence and changes in the titer of anti-C1qAb may be associated with the development of LN, as well as with LN activity and renal flares. However, the exact role of anti-C1qAb in LN remains a subject of debate. Despite variability in the results of published studies, anti-C1qAb hold promise as noninvasive markers for assessing LN activity in SLE patients. Measuring anti-C1qAb levels could aid in diagnosing and managing LN during periods of both inactive disease and renal flares. Nevertheless, larger controlled trials with standardized laboratory assays are necessary to further establish the utility of anti-C1qAb in predicting the reactivation and remission of LN and guiding treatment strategies.

Immunohistochemical Evaluation of Renal Biopsy with Anti-PD1 and p53 to Solve the Dilemma between Platinum- and Pembrolizumab-Induced AKI: Case Report and Review.

Introduction: The combination therapy of platinum and pembrolizumab looks like a promising treatment in advanced non-small-cell lung cancer. However, both platinum-based chemotherapy and pembrolizumab can lead to AKI. AKI can occur due to acute tubular necrosis or interstitial nephritis. It is essential to identify the drug responsible for renal damage. For this purpose, we used new immunohistochemistry markers (p53 and anti-PD1 analysis). Case Description: A 77-year-old female patient with advanced non-small-cell lung cancer received the PD-1 inhibitor pembrolizumab and platinum-based chemotherapy carboplatin. The patient, after 60 days, experienced AKI. A kidney biopsy was performed, and two new immunohistochemical techniques for p53 (experimental markers of ATN from platinum) and anti-PDL1 (experimental markers of PD-1 inhibitors nephritis) were employed. Renal biopsies revealed severe tubular damage. No infiltration was detected, and the immunohistochemical assessment of PDL-1 was negative. The expression of p53 was positive. The renal biopsy suggested platinum-induced acute tubular necrosis. After discontinuing steroids and reducing carboplatin, the patient continued with pembrolizumab, and their renal function returned to normal within two months. Discussion: Combining checkpoint inhibitors and platinum-based therapies may result in AKI. The standard method of examining kidney tissue may not provide sufficient information about the effects of these drugs on the kidneys. To address this issue, we recommend incorporating an assessment of the analysis of the expression of PDL1 and p53. This personalized approach will help identify the best treatment option for the patient while ensuring the best possible cancer treatment plan.

The value of the current histological scores and classifications of ANCA glomerulonephritis in predicting long-term outcome.

Background: Three different histological scores-histopathologic classification (Berden), Renal Risk Score (RRS) and the Mayo Clinic Chronicity Score (MCCS)-for anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis (ANCA-GN) were compared to evaluate their association with patient and kidney prognosis of ANCA-GN. Methods: Patients aged >18 years with at least 1 year of follow-up and biopsy-proven ANCA-GN entered this retrospective study. Renal biopsies were classified according to Berden's classification, RRS and MCCS. The first endpoint was end-stage kidney disease (ESKD), defined as chronic dialysis or estimated glomerular filtration rate <15 mL/min/1.73 m2. The second endpoint was ESKD or death. Results: Of 152 patients 84 were males, with median age of 63.8 years and followed for 46.9 (interquartile range 12.8-119) months, 59 (38.8%) reached the first endpoint and 20 died. The Kaplan-Meier curves showed that Berden and RRS were associated with first (Berden: P = .004, RRS: P < .001) and second (Berden: P = .001, RRS: P < .001) endpoint, MCCS with the first endpoint only when minimal + mild vs moderate + severe groups were compared (P = .017), and with the second endpoint (P < .001). Among the clinical/histological presentation features, arterial hypertension [odds ratio (OR) = 2.75, confidence interval (95% CI) 1.50-5.06; P = .0011], serum creatinine (OR = 1.17, 95% CI 1.09-1.25; P < .0001), and the percentage of normal glomeruli (OR = 0.97, 95% CI 0.96-0.99; P = .009) were the independent predictors of ESKD at multivariate analysis. When the three scores were included in multivariate analysis, RRS (OR = 2.21, 95% CI 1.15-4.24; P = .017) and MCCS (OR = 2.03, 95% CI 1.04-3.95; P = .037) remained predictive of ESKD, but Berden (OR = 1.17, 95% CI 0.62-2.22; P = .691) did not. Conclusion: RRS and MCCS scores were independent predictors of kidney survival together with high serum creatinine and arterial hypertension at diagnosis, while Berden classification was not.

Comparative Analysis of Antithrombotic Therapy Outcomes in Mild Traumatic Brain-Injury Patients: A Focus on Bleeding Risk and Hospital-Stay Duration.

BACKGROUND: Traumatic brain injury (TBI) in the elderly is a noteworthy pathology due to the exponential increase in population age, and the effects of antiplatelet and anticoagulation on patients' outcomes are still a matter of dispute. The aim of the present study was to evaluate the impact of various antithrombotic agents on patients with mild TBI, focusing on the risk of intracranial bleeding (ICH) and length of hospitalization (LOS). METHODS: A retrospective analysis was conducted, including patients with a diagnosis of TBI admitted to the Emergency Department between 2021 and 2022. Patients were classified according to the concurrent antithrombotic therapy as aspirin (ASA), antiplatelets, direct oral anticoagulants (DOACs), and low-molecular-weight heparin (LMWH). The primary outcome was the ICH occurrence, while the secondary outcome was the LOS. The statistical analysis was performed via logistic regression models in R and STATA 13.1 software. Fisher's exact test was used for the statistical significance. RESULTS: 267 patients with mild TBI were included; 148 were not on antithrombotic agents, 43 were on aspirin, 33 on DOACs, 5 on LMWH, 22 on antiplatelets, and 16 on VKA. Out of the total, 9 patients experienced ICH, none of which were on DOACs, LMWH, or VKA, but 4-out of 65-were on antiplatelets, and 5-out of 148-were not on antithrombotic therapies. Patients not on antithrombotic therapy had the shortest LOS at 0.46 days, while those on VKA had the longest LOS at 1.19 days; similar trends were observed for patients on DOAC and LMWH. CONCLUSIONS: The results reveal that TBI patients on anticoagulants/antiplatelets had longer hospital stays compared with those on aspirin alone. Notably, VKA was the strongest predictor for an extended LOS. Regarding ICH, patients taking only aspirin were twice as likely to experience bleeding compared with those on anticoagulants/antiplatelets. However, to achieve statistically significant evidence, further research with a larger cohort of patients is needed.

Corrigendum to "Changing Phenotypes and Clinical Outcomes Over Time in Microscopic Polyangiitis" [Kidney International Reports Volume 8, Issue 10, October 2023, Pages 2107-2116].

[This corrects the article DOI: 10.1016/j.ekir.2023.07.008.].

Effect of Sustained Clinical Remission on the Risk of Lupus Flares and Impaired Kidney Function in Patients With Lupus Nephritis.

Introduction: This retrospective study on patients with biopsy-proven lupus nephritis (LN) aimed to assess the probability of sustained clinical remission (sCR) and to investigate sCR effects on disease flares and impaired kidney function (IKF). Methods: sCR was defined as clinical-Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) = 0 and estimated glomerular filtration rate (eGFR) >60 ml/min per 1.73 m2 lasting ≥1 year; IKF: eGFR <60 ml/min per 1.73 m2 for >3 months. We analyzed the probability of achieving and maintaining sCR, and the yearly risk of flare. Cox models were used to identify predictors of sCR and IKF with variables analyzed as time-dependent covariates when appropriate. Results: Of 303 patients followed-up with for 14.8 (interquartile range: 9.8-22) years, 257 (84.8%) achieved sCR. The probability of achieving sCR progressively increased over time reaching 90% at 15 years. Baseline age (hazard ratio [HR]: 1.017; 95% confidence interval [CI]: 0.005-1.029; P = 0.004), hydroxychloroquine intake (HR: 1.385; 95% CI: 1.051-1.825; P = 0.021), and absence of arterial hypertension (HR: 0.699; 95% CI: 0.532-0.921; P = 0.011) were independent predictors of sCR. Among patients who achieved sCR, 142 (55.3%) developed a lupus flare after a median time of 3.6 (2.3-5.9) years. In the remaining 115 patients, sCR persisted for 9.5 (5.8-14.5) years. The probability of sCR to persist at 15 years was 38%. SLE flare risk decreased to 10%, 5%, and 2% in patients with sCR lasting <5, 5 to 10, and >10 years, respectively. At the last observation, 57 patients (18.81%) had IKF. sCR achievement (HR: 0.18, P < 0.001) and its duration (HR: 0.83, P < 0.001) were protective against IKF. Conclusion: sCR is an achievable target in LN management and protects against IKF. The longer the sCR, the higher the chance of its persistence and the lower the risk of SLE flares.

Corrigendum to "Effect of Sustained Clinical Remission on the Risk of Lupus Flares and Impaired Kidney Function in Patients With Lupus Nephritis" [Kidney International Reports Volume 9, Issue 4, April 2024, Pages 1047-1056].

[This corrects the article DOI: 10.1016/j.ekir.2024.01.016.].

Anti-glomerular basement membrane vasculitis.

Antiglomerular basement membrane disease (anti-GBM) is a rare life-threatening autoimmune vasculitis that involves small vessels and it is characterized by circulating autoantibodies directed against type IV collagen antigens expressed in glomerular and alveolar basement membrane. The typical clinical manifestations are the rapidly progressive glomerulonephritis and the alveolar hemorrhage. The diagnosis is usually confirmed by the detection of anti-GBM circulating antibodies. If not rapidly recognized, anti-GBM disease can lead to end stage kidney disease (ESKD). An early diagnosis and prompt treatment with immunosuppressive therapies and plasmapheresis are crucial to prevent a poor outcome. In this review, we discuss the primary form of anti-GBM (the so called Goodpasture syndrome) but also cases associated with other autoimmune diseases such as antineutrophil-cytoplasmic-antibody (ANCA) vasculitis, membranous nephropathy, IgA nephritis and systemic lupus erythematosus (SLE), as well as the few cases of anti-GBM vasculitis complicating kidney transplantation in the Alport syndrome.

C3 glomerulopathies: dense deposit disease and C3 glomerulonephritis.

Dense deposit disease (DDD) and C3 glomerulonephritis (C3GN) are types of membranoproliferative glomerulonephritis classified as C3 glomerulopathies. These conditions are characterized by an increased number of intraglomerular cells and diffuse thickening of the glomerular capillary walls, along with the deposition of C3 and minimal or absent immunoglobulin deposits. The underlying cause of both DDD and C3Gn is an abnormal activation of the alternative complement pathway, which can result from acquired or genetic alteration. In acquired forms of DDD and C3GN, the dysregulation of the alternative pathway is commonly induced by the presence of C3 nephritic factors (C3NeFs), which are autoantibodies that stabilize C3 convertase. Both DDD and C3GN can affect individuals of any age, but DDD is primarily diagnosed in children, whereas C3GN tends to be diagnosed at a significantly higher age. The presenting features of these diseases are variable and may include proteinuria, hematuria, hypertension, or kidney failure. A common finding in these diseases is low serum C3 levels with normal serum C4 levels. Chronic deterioration of renal function is commonly observed in DDD and C3GN, often leading to end-stage renal disease (ESRD), especially in DDD. Kidney transplantation outcomes in patients with these conditions are characterized by histological recurrence, which may contribute to higher rates of allograft failure.