C3 Glomerulonephritis Research Articles

Novel use of Siltuximab in a patient with VEXAS Syndrome.

VEXAS syndrome (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) is an increasingly recognized disorder that occurs due to somatic mutations of a ubiquitin-activating enzyme encoded by ubiquitin-like modifier activating enzyme 1 gene, UBA1. Clinical findings associated with VEXAS syndrome include recurrent fevers, polychondritis, periorbital edema, pleural effusions, myocarditis and/or pericarditis, hepatosplenomegaly, myelodysplastic syndrome, cytopenias, inflammatory arthritis, neutrophilic dermatosis, and deep venous thrombosis. Novel renal manifestations like interstitial nephritis are infrequent, and to our knowledge, acute renal failure due to C3 glomerulonephritis (C3GN) has not yet been reported. Overwhelming systemic inflammation can result in morbid end-organ damage and death. While there is no formal guideline or established protocol for its management, treatment of VEXAS syndrome with tocilizumab, an interleukin-6 (IL-6)-directed therapy, has been described in the literature. Here, we report a case of a 71-year-old male patient presenting with C3GN as an initial manifestation of VEXAS syndrome and explore the rationale for our approach to treatment with IL-6 blockade. Our patient was initially treated with two inpatient doses of tocilizumab with successful transition to siltuximab in the outpatient setting. He continues to benefit from ongoing siltuximab treatment for more than one year to date without any safety issues or relapse of VEXAS syndrome.

C3 Glomerulonephritis in a Child with Elevated Anti-streptolysin O (ASO) Titer

C3 Glomerulonephritis in a Child with Elevated Anti-streptolysin O (ASO) Titer

A Case of MGRS-Associated C3 Glomerulonephritis following Acute COVID-19 Infection

A Case of MGRS-Associated C3 Glomerulonephritis following Acute COVID-19 Infection

Mesoamerican Nephropathy and C3 Glomerulonephritis Leading to Kidney Failure in a Young Male from Guatemala

Mesoamerican Nephropathy and C3 Glomerulonephritis Leading to Kidney Failure in a Young Male from Guatemala

Truncated Complement Factor H Y402 Gene Therapy Cures C3 Glomerulonephritis.

Patients with both age-related macular degeneration (AMD) and C3 glomerulonephritis (C3G) are challenged by the absence of effective therapies to reverse and eliminate their disease burden. Capitalizing on complement dysregulation as both a significant risk factor for AMD and the known pathophysiology of C3G, we investigated the potential for adeno-associated virus (AAV) delivery of complement factor H (CFH) to rescue C3G in a Cfh-/- mouse model of C3G. While past efforts to treat C3G using exogenous human CFH resulted in limited success before immune rejection led to a foreign protein response, our findings demonstrate the capacity for long-term AAV-mediated delivery of truncated CFH (tCFH) to restore inhibition of the alternative pathway of complement and ultimately reverse C3G without immune rejection. Comparing results from the administration of several tCFH vectors also revealed significant differences in their relative efficiency and efficacy. These discoveries pave the way for subsequent development of AAV-mediated tCFH replacement therapy for patients with C3G, while simultaneously demonstrating proof of concept for a parallel AAV-mediated tCFH gene augmentation therapy for patients with AMD.

Outcome of Glomerular Disease Manifesting After Vaccination Against Severe Acute Respiratory Syndrome Coronavirus 2.

Introduction Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can upregulate the immune system and may contribute to glomerular disease (GD). Here, we describe a spectrum of GD that manifested following vaccination against SARS-CoV-2 (COVID-19 vaccinations). Material and methods This was a descriptive study of 10 cases enrolled between January 2021 and January 2023. Patients with biopsy-proven GD that manifested following COVID-19 vaccinations were included. Results We found 10 cases of biopsy-proven GD following the COVID-19 vaccination. This included five cases of minimal change disease (MCD), three cases of focal segmental glomerulosclerosis (FSGS), one case of C3 glomerulonephritis (C3GN), and one case of IgA nephropathy (IgAN). The pre-existing disease was found in the last two patients (IgAN and C3GN) who got unmasked following vaccination. We did not observe any relation between vaccine type (Covisheld; six cases vs. Covaxin; four cases) and GD. In most cases (8/10 cases, 80.0%), GD developed after a repeat dose (second or booster dose). The onset time following vaccination was typically less than a week, and even less following a repeat dose. Conclusion Post-vaccination GD can be either de novo or a flare-up of a pre-existing one. The onset time following vaccination was typically less than a week for both Covishield and Covaxin.

Kidney involvement in myelodysplastic syndromes.

The objective of this study was to describe kidney involvement in patients with myelodysplastic syndromes (MDS), their treatments, and outcomes. We conducted a multicenter retrospective study in seven centers, identifying MDS patients with acute kidney injury (AKI), chronic kidney disease (CKD), and urine abnormalities. Fifteen patients developed a kidney disease 3 months after MDS diagnosis. Median urine protein-to-creatinine ratio was 1.9g/g, and median serum creatinine was 3.2mg/dL. Ten patients had AKI at presentation, and 12 had extra-renal symptoms. The renal diagnoses included anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), ANCA negative vasculitis, C3 glomerulonephritis, immune complex-mediated glomerulonephritis, polyarteritis nodosa, and IgA vasculitis. All patients but one received a specific treatment for the MDS-associated kidney injury. The effect of MDS treatment on kidney injury could be assessed in six patients treated with azacitidine, and renal function evolution was heterogenous. After a median follow-up of 14 months, four patients had CKD stage 3, five had CKD stage 4, and three had end stage kidney disease. On the other hand, three evolved to an acute myeloid leukemia and three died. Compared to 84 MDS controls, patients who had kidney involvement were younger, had a higher number of dysplasia lineages, and were more eligible to receive hypomethylating agents, but no survival difference was seen between the two groups. Compared to 265 AAV without MDS, the ten with MDS-associated pauci-immune vasculitis were older, ANCA serology was more frequently negative, and more cutaneous lesions were seen. The spectrum of kidney injuries associated with MDS is mostly represented by vasculitis with glomerular involvement, and especially AAV.

C3 Glomerulonephritis Associated with Monoclonal Gammopathy

C3 glomerulonephritis (C3GN) is rare. It is a proliferative glomerulonephritis resulting from glomerular deposition of complement factors due to dysregulation of the alternative pathway of complement. The association between monoclonal protein production and development of C3GN was described. We report a 74-year-old man with rapid worsening of kidney function and dialysis needed due to C3GN. In this case, serum protein electrophoresis showed no monoclonal spike but serum immunoelectrophoresis showed a lambda light chain monoclonal gammopathy. Once the diagnosis was made, the patient was treated with immunosuppression with complete kidney recovery. This case shows the importance of accurate and prompt diagnosis and appropriate treatment.

#627 C3 glomerulonephritis and C3-dominant infection related glomerulonephritis—are they similar?

Abstract Background C3 glomerulonephritis (C3GN) and C3 dominant infection related glomerulonephritis (C3-IRGN) comprise two important immune complex mediated diseases. C3GN is caused by dysregulation of the alternate pathway by congenital or acquired abnormalities in the complement pathway. C3-IRGN is often preceded by infection followed by recovery after the infection resolves. Although kidney biopsy findings may be similar in both conditions, the clinical course and treatment differs. We aimed to compare the demographic, clinical and lab parameters of C3GN and C3-IRGN. Methods All kidney biopsies conducted at Institute of Nephrourology, Bengaluru with dominant C3 on immunofluorescence from Jan. 2019-Dec. 2022 were included. The diagnosis of C3-IRGN was established using established criteria. Patients with C3GN had persistently low C3 for more than 12 weeks and no identifiable source of infection. Patients with C3GN were treated with steroids and cyclophosphamide, while those with C3-IRGN received antibiotics along with supportive medical management (including renin-angiotensin-aldosterone inhibition). Demographic, clinical and lab parameters were recorded and compared. Results 23 cases of C3-IRGN and 19 cases of C3GN were included in the study. The mean duration of follow-up was 2.79 ± 0.92 years for those with C3GN and 2.78 ± 0.90 years for those with C3-IRGN. C3GN was common in younger patients (second decade of life) while C3-IRGN was common in the fourth and fifth decades of life. C3GN (57.9%) and C3-IRGN (73.9%) were both common in males. Previous infection (26.1% vs 5.3%) and present infection (39.1% vs 15.8%) were significantly more common in C3-IRGN. Hematuria (52.6% vs 34.8%), patient reported “frothy” urine (47.4% vs 21.7%) was significantly more common in C3GN compared to C3-IRGN. 36.8% of patients with C3GN had IFTA of >50% compared to only 8.7% in C3-IRGN. Patients with both conditions most commonly presented with either acute nephritic syndrome or rapidly progressive glomerulonephritis. In contrast, presentation with CKD was significantly more common in C3GN (36.8% vs 0%, P = 0.002) compared to C3-IRGN, and patients with C3GN were more likely to require kidney replacement therapy (47.4% vs 21.7%, P = 0.002). At the end of follow up, 65.2% of patients with C3-IRGN attained complete recovery, compared with only 47.4% of C3GN patients. Conclusion There are characteristic differences between individuals with C3-IRGN and C3GN that may help to better ascertain diagnosis at presentation. Patients with C3GN tend to have worse prognosis, emphasizing the importance of treatments to slow CKD progression and avoid the need for kidney replacement therapy.

#2187 Rare disease, novel approach: C3GN and Iptacopan case report

Abstract Background and Aims C3 glomerulonephritis (C3GN) is a rare disease characterised on biopsy by proliferative lesions of predominant C3 deposition on immunofluorescence, particularly deposits within the mesangium and capillary walls. Dysregulation of the alternative complement pathway is thought to be the underlying mechanism [1]. There are no approved treatments for C3G and prognosis is poor, with 50% progression to kidney failure over 10 years and similar rates of transplant loss due to disease recurrence. Iptacopan (a selective Factor B complement inhibitor) is proposed to suppress key enzymes involved in the alternative pathway cascade [2]. It is being studied in clinical trials of C3G [3]. We sought to describe our experience in diagnosing and managing a 25-year-old with C3GN who presents with nephrotic syndrome, hypertension, and a reduction in his estimated glomerular filtration rate (eGFR) with a novel small molecule therapeutic. Method This report charts the clinical course of one male patient over 11 months from presentation with C3GN, to the introduction of immunosuppression and of Iptacopan, and the assessment of his response to the foregoing. The patient consented to the publication of his case. Results A 25-year-old male with a background of autism spectrum disorder was referred to his regional nephrology service due to reduction in his eGFR and proteinuria. His creatinine was 158 µmol/L with an eGFR was 51.8 ml/ml/1.73 m2 (CKD-EPI equation); urinary protein creatinine ratio (uPCR) 500 mg/mmol; urinary albumin creatinine ratio (uACR) 400.2 mg/mmol. Serum album 32g/L. His C3 0.22 (normal range 0.82–1.85 g/L); C4 0.27 (normal 0.15–0.53 g/L). A renal biopsy was performed which demonstrated diffuse MPGN dominant C3 staining; cholesterol crystals; and moderate to severe chronic tubulointerstitial damage. 1 mg/kg oral prednisolone with mycophenolate mofetil (MMF) titrated up to a dose of 1g twice a day was initiated. As he was established on the therapy his eGFR rose back to 57.9 ml/min over approximately 8 weeks from a nadir of 33.8 ml/min. Following initial weaning of his prednisolone dose, his eGFR dropped back down to 29.7 ml/min with a creatinine of 250 µmol/L. With involvement and clinical support from the National Renal Complement Therapeutics Centre an application was made to Novartis for the compassionate use of Iptacopan which was commenced early August 2023 (he would not have been eligible for recruitment into any current clinical trials). His latest eGFR is 47.5 ml/ml/1.73 m2 with a uACR of 9.1 mg/mmol and normal C3 and C5b-9 levels after 5 months of Iptacopan. His prednisolone dose is 10 mg. MMF continues at 2g total dose. Conclusion Iptacopan has so far resulted in the normalisation of serum C3 levels, reduction of uACR and stabilisation of serum creatinine as we have reduced the prednisolone dose.

#2113 Membranoproliferative glomerulonephritis experience over 20 years in a tertiary centre in the United Kingdom

Abstract Background and Aims Membranoproliferative Glomerulonephritis (MPGN) is a histological pattern of injury which typically accounts for light microscopy findings on 1-3% of kidney biopsies. It is classified based on immunofluorescence into complement-mediated, immune complex-mediated (IC) and immunofluorescence negative. The underlying aetiologies such as C3 Glomerulopathy are rare diseases, and thus longitudinal real-world experience in terms of underlying causes, treatment and outcomes is valuable. Method This study presents a retrospective review of biopsy data from January 2000 through to December 2020 in a tertiary renal referral centre in the United Kingdom (UK). This review was conducted using the organisation's biopsy database, with patient demographics and clinical information obtained from the Electronic Patient Record. All patients with an MPGN pattern on biopsy were reviewed. Those with new MPGN post-transplant, with an MPGN pattern on biopsy but subsequently diagnosed as IgA Nephropathy, and with an MPGN pattern but a known lupus diagnosis, were excluded. Results A histological finding of MPGN on kidney biopsy was found in 67 patients. Of these, 41 remained in the study following application of the exclusion criteria, with an additional 3 excluded as there was insufficient information available for classification in their biopsy reports. Of the 38 remaining, 28 had IC MPGN and 10 had C3 Glomerulopathy (C3G) - 8 with C3 Glomerulonephritis (C3GN) and 2 with C3 Dense Deposit Disease (DDD). Median follow up was 72 (range 45-126) months. Median age was 64 years in the IC MPGN and 55 years in the C3G groups (p 0.125). The majority in both groups were female, 60.7% (17) and 60% (6) respectively. There was no significant difference in renal function, blood pressure, or proteinuria at presentation between the groups. MPGN was associated with infections in 8 patients (21.1%), connective tissue disease in 3 patients (7.9%), monoclonal gammopathies or haematological malignancies in 8 patients (21.1%), and 2 had identified complement deficiencies (5.3%). Over the study period 47.4% (18) of patients progressed to end stage kidney disease and 50% (19) died. There was no significant difference in these outcomes between the IC MPGN and the C3G groups. Progression to renal replacement therapy (RRT) was seen in 42.9% (12) of the IC MPGN group, and 60% (6) of the C3G group (p=0.287). This included two patients who received a kidney transplant (both in the C3G group), one of whom developed recurrence during the available follow up. Conclusion This study adds a UK perspective with long term data and outcomes in a rare condition. Almost half of patients progressed to RRT and half of patients died during the follow-up period. These outcomes were seen at similar rates in those with IC MPGN and those with C3G. A variety of associated conditions were observed, and the low number of complement deficiencies identified is likely due to the historical nature of the review with reduced screening for complement abnormalities and genetics in the earlier period. Outcomes on follow-up:

A Practical Method for Synthesizing Iptacopan.

Iptacopan, the first orally available small-molecule complement factor B inhibitor, was developed by Novartis AG of Switzerland. Iptacopan for the treatment of PNH was just approved by the FDA in December 2023. Other indications for treatment are still in phase III clinical trials. Iptacopan is a small-molecule inhibitor targeting complement factor B, showing positive therapeutic effects in the treatment of PNH, C3 glomerulonephritis, and other diseases. Although Iptacopan is already on the market, there has been no detailed synthesis process or specific parameter report on the intermediates during the synthesis of its compounds except for the original research patent. In this study, a practical synthesis route for Iptacopan was obtained through incremental improvement while a biosynthesis method for ketoreductase was used for the synthesis of the pivotal intermediate 12. Moreover, by screening the existing enzyme library of our research group on the basis of random as well as site-directed mutagenesis methods, an enzyme (M8) proven to be of high optical purity with a high yield for biocatalectic reduction was obtained. This enzyme was used to prepare the compound benzyl (2S,4S)-4-hydroxy-2-(4-(methoxycarbonyl)-phenyl)-piperidine-1-carboxylate) white powder (36.8 g HPLC purity: 98%, ee value: 99%). In the synthesis of intermediate 15, the reaction was improved from two-step to one-step, which indicated that the risk of chiral allosterism was reduced while the scale was expanded. Finally, Iptacopan was synthesized in a seven-step reaction with a total yield of 29%. Since three chiral intermediate impurities were synthesized directionally, this paper lays a solid foundation for the future of pharmaceutical manufacturing.

Clinical characteristics and outcomes of immune-complex membranoproliferative glomerulonephritis and C3 glomerulopathy in Japanese children

BackgroundMembranoproliferative glomerulonephritis (MPGN) can be divided into immune-complex MPGN (IC-MPGN) and C3 glomerulopathy (C3G), which includes dense deposit disease (DDD) and C3 glomerulonephritis (C3GN). These conditions result from abnormalities in different complement pathways and may lead to different prognoses. However, there are limited studies describing the respective clinical courses.MethodsIn this study, Japanese pediatric patients diagnosed with MPGN based on kidney biopsies conducted between February 2002 and December 2022 were reclassified as having IC-MPGN or C3G (DDD or C3GN). We retrospectively analyzed the clinical characteristics and outcomes of these patients.ResultsOut of 25 patients with MPGN, three (12.0%) were diagnosed with DDD, 20 (80.0%) with C3GN, and two (8.0%) with IC-MPGN. There were 13 (65.0%) patients and one (33.3%) patient in remission after treatment for C3GN and DDD, respectively, and no patients with IC-MPGN achieved remission. The median follow-up period was 5.3 (2.5–8.9) years, and none of the patients in either group progressed to an estimated glomerular filtration rate < 15 ml/min/1.73 m2. Patients with C3GN presenting mild to moderate proteinuria (n = 8) received a renin-angiotensin system inhibitor (RAS-I) alone, and these patients exhibited a significant decrease in the urinary protein creatinine ratio and a notable increase in serum C3 levels at the last follow-up.ConclusionsMost patients with MPGN were diagnosed with C3GN. The remission rate for C3GN was high, and no patients developed kidney failure during the approximately 5-year follow-up. Additionally, patients with C3GN with mild to moderate proteinuria had good outcomes with RAS-I alone, but continued vigilance is necessary to determine long-term prognosis.Graphical abstractA higher resolution version of the Graphical abstract is available as Supplementary information

146 De novo C3 glomerulonephritis associated with factor H autoantibody post kidney transplant in a patient with systemic lupus erythematosus: A case report

146 De novo C3 glomerulonephritis associated with factor H autoantibody post kidney transplant in a patient with systemic lupus erythematosus: A case report

Apolipoprotein E is enriched in dense deposits and is a marker for dense deposit disease in C3 glomerulopathy

C3 glomerulopathy (C3G) is a rare disease resulting from dysregulation of the alternative pathway of complement. C3G includes C3 glomerulonephritis (C3GN) and dense deposit disease (DDD), both of which are characterized by bright glomerular C3 staining on immunofluorescence studies. However, on electron microscopy (EM), DDD is characterized by dense osmiophilic mesangial and intramembranous deposits along the glomerular basement membranes (GBM), while the deposits of C3GN are not dense. Why the deposits appear dense in DDD and not in C3GN is not known. We performed laser microdissection (LCM) of glomeruli followed by mass spectrometry (MS) in 12 cases each of DDD, C3GN, and pretransplant kidney control biopsies. LCM/MS showed marked accumulation of complement proteins C3, C5, C6, C7, C8, C9 and complement regulating proteins CFHR5, CFHR1, and CFH in C3GN and DDD compared to controls. C3, CFH and CFHR proteins were comparable in C3GN and DDD. Yet, there were significant differences. First, there was a six-to-nine-fold increase of C5-9 in DDD compared to C3GN. Secondly, an unexpected finding was a nine-fold increase in apolipoprotein E (ApoE) in DDD compared to C3GN. Most importantly, immunohistochemical and confocal staining for ApoE mirrored the dense deposit staining in the GBM in DDD but not in C3GN or control cases. Validation studies using 31 C3G cases confirmed the diagnosis of C3GN and DDD in 80.6 % based on ApoE staining. Overall, there is a higher burden of terminal complement pathway proteins in DDD compared to C3GN. Thus, our study shows that dense deposits in DDD are enriched with ApoE compared to C3GN and control cases. Hence, ApoE staining may be used as an adjunct to EM for the diagnosis of DDD and might be valuable when EM is not available.

Membranoproliferative Glomerulonephritis over 20 Years at a Tertiary Referral Center in the UK.

Membranoproliferative glomerulonephritis (MPGN) is a pattern of injury seen on kidney biopsy, with various underlying etiologies. The component types, including complement-mediated MPGN, are relatively rare. This study presents longitudinal real-world data over 20 years in a tertiary renal center in the UK. All patients with an MPGN pattern on kidney biopsy between 2000 and 2020 were identified. After applying exclusion criteria, 38 patients remained. Data including patient demographics, details of the renal histology from the kidney biopsy, baseline laboratory results, treatments received, and clinical outcomes including renal replacement therapy and death were collected from the organization's electronic patient record. Twenty-eight of the cohort had immune complex-mediated MPGN, and 10 had complement-mediated MPGN (8 with C3 glomerulonephritis and 2 with dense deposit disease). Median follow-up was 72 months. Median age was 61 years. Overall, 60.5% were female, and 92.1% white. At presentation, median eGFR was 31.5 mL/min/1.73 m2 and uPCR 394 mg/mmol. Here, 78.9% received renin-angiotensin-aldosterone system inhibitors and 71.1% received any immunosuppression. In total, 47.4% progressed to ESKD and 50% died during follow-up. The study found an older patient population than typically reported. Poor outcomes were observed in the overall cohort with progression to ESKD and mortality both at almost 50%. This may be influenced by the older patient population. Individualized management of patients with an MPGN biopsy finding is paramount, with comprehensive evaluation for triggers and complement abnormalities. Going forward, registry enrolment and collaborative studies may enhance knowledge and outcomes.

Multiple Pyoderma Gangrenosum Overlying AV Fistula Treated With Colchicine: A Case Report.

Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis which gives rise to painful ulcers. Pyoderma gangrenosum can be triggered by trauma, a phenomenon called pathergy. Here, we report the first case of PG arising from pathergy due to needle insertion overlying an arteriovenous fistula (AVF). This case report seeks to inform nephrologists about PG, this yet unreported presentation, and management in the context of hemodialysis. A 69-year-old woman presented to dermatology clinic for erythemato-violaceous plaques with central ulceration at the site of needle insertion overlying her AVF. The patient was known for chronic renal insufficiency secondary to C3 glomerulonephritis, for which she received hemodialysis. After an accidental burn which lead to appearance of a painful ulcer, following each needle insertion for hemodialysis, she would develop an erythematous papule that progressed to a painful ulcer with erythematous-violaceous borders. Pyoderma gangrenosum was clinically diagnosed and both clinical and paraclinical evaluation did not reveal any secondary cause of PG. Dialysis via AVF was suspended due to the risk of triggering more PG and was temporarily pursued by central venous catheter. The patient was initially treated with prednisone and topical corticosteroids. Furthermore, owing to the high recurrence rate of PG, colchicine was initiated in prevention to avoid resorting to immunosuppressive or long-term corticotherapy. The patient's lesions improved on prednisone, which was then tapered over 1 month. Following prednisone taper and continuing improvement of PG on colchicine and topical corticosteroids alone, the decision was taken to recommence dialysis via AVF after performing a negative pathergy test. Topical corticosteroids were ceased due to the risk of cutaneous atrophy and were replaced by pimecrolimus ointment. The patient has continued dialysis via AVF ever since, without recurrence. This is the first case reported of PG arising from pathergy due to needle insertion overlying an AVF. Colchicine may be a safe and effective therapy for long-term treatment of PG in the context of hemodialysis.

Rare Case of Dense Deposition Disease with Combined C3 and C4d Deposits with MYH9-related Mutation

Background: The C3 glomerulopathies are a group of rare forms of glomerulonephritis with an incidence of 1-2 cases per million. It is mainly characterized by dysregulation of the alternative complement pathway. It is further classified morphologically based on electron microscopy ultrastructural findings into Dense Deposition Disease (DDD) and C3 glomerulonephritis. DDD is normally characterised by C3 Deposits. Case: We report a rare case of a young Emirati male who presented with sub nephrotic proteinuria and microscopic haematuria on routine evaluation. Renal biopsy showed features of DDD with combined C3 and C4 deposits. The retinal evaluation showed features of Drusen classically seen in DDD. Genomic study showed heterozygous mutation in c.5842G&gt;C (p.Asp1948His) variant of uncertain significance in MYH9 gene. Discussion: C3 Glomerulopathy is a type of immune mediated disease previously classified as membranoproliferative glomerulonephritis. DDD is mainly characterised by C3 deposits in the glomerular basement Membrane. Our case has both C3 and C4d deposits, which is a rare entity. It shows the activation of both classical and alternate pathways. Conclusion: Dense deposition disease is a rare complement mediated glomerulopathy. It is characterised by C3 deposits. Dense deposition disease with combined C3 and C4d deposits is a new entity. The treatment and prognosis of such cases will be different and unique compared to the normal cases of DDD.

AA Amyloid Masquerading as C3 Glomerulonephritis

AA Amyloid Masquerading as C3 Glomerulonephritis

Spatially Resolved Transcriptomic Profiling for Glomerular and Tubulointerstitial Gene Expression in C3 Glomerulonephritis

Spatially Resolved Transcriptomic Profiling for Glomerular and Tubulointerstitial Gene Expression in C3 Glomerulonephritis