Rationale and design of the Japanese Biomarkers in Nephrotic Syndrome (J-MARINE) study.

INTRODUCTION: Disease subtyping and monitoring are essential for the management of nephrotic syndrome (NS). Although various biomarkers for NS have been reported, their clinical efficacy has not been comprehensively validated in adult Japanese patients. METHODS: The Japanese Biomarkers in Nephrotic Syndrome (J-MARINE) study is a nationwide, multicenter, and prospective cohort study in Japan, enrolling adult (≥18 years) patients with minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), membranous nephropathy (MN), membranoproliferative glomerulonephritis (MPGN), C3 glomerulopathy (C3G), and lupus nephritis (LN). Baseline clinical information and plasma and urine samples will be collected at the time of immunosuppressive therapy initiation or biopsy. Follow-up data and plasma and urine samples will be collected longitudinally based on the designated protocols. Candidate biomarkers will be measured: CD80, cytotoxic T-lymphocyte antigen 4, and soluble urokinase plasminogen activator receptor for MCD and FSGS; anti-phospholipase A2 receptor and thrombospondin type-1 domain-containing protein 7A antibodies for MN; fragment Ba, C3a, factor I, and properdin for MPGN/C3G; and CD11b, CD16b, and CD163 for LN. Outcomes include complete and partial remission, relapse of proteinuria, a 30% reduction in estimated glomerular filtration rate (eGFR), eGFR decline, and initiation of renal replacement therapy. The diagnostic accuracy and predictive ability for clinical outcomes will be assessed for each biomarker. RESULTS: From April 2019 to April 2023, 365 patients were enrolled: 145, 21, 138, 10, and 51 cases of MCD, FSGS, MN, MPGN/C3G, and LN, respectively. CONCLUSION: This study will provide valuable insights into biomarkers for NS and serve as a biorepository for future studies.

Proliferative glomerulonephritis with monoclonal IgG Lambda deposits caused by plasmablastic lymphoma: a case report.

INTRODUCTION: As a very rare form of B-cell lymphoma, plasmablastic lymphoma (PBL) typically occurs in patients with underlying immunosuppression, including human immunodeficiency virus (HIV), organ transplantation, and autoimmune diseases. For HIV-positive patients, PBL normally originates in the gastrointestinal tract, especially from the oral cavity in most cases. It is extremely rare to find abdominal cavity involvement in PBL, and there has been no previously reported instance of proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID) attributed to monoclonal IgG (MIgG) lambda secreted by PBL. CASE PRESENTATION: We report the case of an HIV-negative female with nephrotic syndrome, renal insufficiency, and multiple swollen lymph nodes. Ascitic fluid cytology revealed a high level of plasmablast-like lymphocytes with the restriction of lambda light chains. Besides, the renal biopsy revealed PGNMID, which could presumably be secondary to MIgG-lambda-secreting by PBL. MIgG-lambda-restricted expression was discovered earlier in the kidney tissue than in the blood. CONCLUSION: The diagnostic landscape for PBL is notoriously intricate, necessitating a multifaceted and nuanced approach to mitigate the risks of erroneous identification.

Hypertensive retinopathy and Purtscher-like retinopathy in a child with complement 3 glomerulopathy.

We report the case of a 15-year-old boy with hypertensive retinopathy and Purtscher-like retinopathy eventually diagnosed with complement 3 glomerulopathy (C3G). The patient presented with bilateral severe painless visual loss and posterior pole cotton wool spots, optic disk and macular edema, and macular star-shaped hard exudate depositions, arterial narrowing, and venous tortuosity, indicative of hypertensive retinopathy (with an initial blood pressure of 210/130 mm Hg) and Purtscher-like retinopathy. He was subsequently diagnosed with C3G based on results of a kidney biopsy. There was a mild visual improvement on follow-up examination, and optic disk swelling and subretinal fluid and cotton wool spots resolved.

[Diagnosis and treatment of glomerular diseases with a membranoproliferative glomerulonephritis (MPGN) pattern of injury]. / Diagnose und Therapie glomerulärer Erkrankungen mit einem membranoproliferativen Läsionsmuster (MPGN) ­ 2023.

Membranoproliferative glomerulonephritis (MPGN) represents a heterogeneous group of diseases. The common feature of a membranoproliferative lesion pattern in the kidney biopsy can either be idiopathic/primary or-much more frequently-have a secondary cause. The historical classification into MPGN types I to III has largely been abandoned and replaced in recent years by a pathogenesis-oriented classification. A MPGN with C1q, C3 and/or C4 deposits on light microscopy is referred to as immune complex GN (IC-GN), while a MPGN with dominant C3 deposits is referred to as C3 glomerulopathy (C3G). C3G is further divided into C3 glomerulonephritis (C3GN) and dense deposit disease (DDD). These diagnoses can only be made by a kidney biopsy. Possible causes of MPGN are chronic infections (especially hepatitis B and C, bacterial infections, infections with protozoa), autoimmune diseases (especially lupus, rheumatoid arthritis) or malignancies (especially hematological malignancies). Particularly in the case of C3G a comprehensive analysis of the complement system components is strongly recommended. Due to the low incidence and the heterogeneous clinical appearance of MPGN therapeutic decisions must be made individually; an optimal general therapy is unknown, except that supportive treatment as with other glomerular diseases should be optimized. In the case of a secondary MPGN it is generally recommended to treat the potential cause of the MPGN. If significant proteinuria persists and eGFR remains > 30 ml/min/1.73 m2, treatment with systemic steroids and mycophenolate mofetil is recommended. Other treatment options on an individual level after evaluation and discussion of the risk-benefit ratio with the patient are rituximab and eculizumab. Rapidly progressive MPGN should be treated like ANCA-associated vasculitis. The recurrence rates after kidney transplantation are very high and treatment is challenging.

Gaucher disease in a patient with membranoproliferative glomerulonephritis: case report.

BACKGROUND: Gaucher disease (GD) is a rare autosomal recessive inherited, lysosomal storage disoder that involves liver, spleen, lung, bone, bone marrow even central nervous. However, GD associated membranoproliferative glomerulonephritis (MPGN) is seldom reported. CASE PRESENTATION: Here we described a case of 35-year-old man suffering from GD with hepatosplenomegaly, ascites, bone destruction, myelofibrosis and MPGN. Renal biopsy revealed MPGN and Gaucher cells presented in the glomeruli capillaries. ß-glucosidase activity was 1.95nmol/1 h/mg and gene detection demonstrated that one homozygous pathogenic variant Leu483Pro in GBA. He received the treatment of oral prednisone and mycophenolate mofetil and his ascites and renal outcomes had been significantly improved. CONCLUSIONS: Therapy of prednisone and mycophenolate mofetil may be an optional choice for patients with Gaucher disease who have no opportunity to use enzyme treatment.

Expert Discussion on Challenges in C3G Diagnosis: A Podcast Article on Best Practices in Kidney Biopsies.

Complement 3 glomerulopathy (C3G) is an ultra-rare, progressive kidney disease resulting from dysregulation of the alternative complement pathway. Clinical presentation of C3G is heterogeneous and definitive diagnosis relies on kidney biopsy and immunofluorescence staining. The term C3G encompasses two subgroups, dense deposit disease and C3 glomerulonephritis, distinguished via electron microscopy. In this podcast article, the authors discuss the challenges associated with C3G diagnosis and the central role of kidney biopsy. Using an illustrative case study, key histological observations are described, and best practices are discussed from the perspectives of a nephrologist and a nephropathologist. Podcast Audio (MP4 141866 KB).

Proliferative glomerulonephritis with monoclonal IgG deposits: a unique case with a clinical course of over 46 years.

BACKGROUND: Proliferative glomerulonephritis with monoclonal IgG deposits (PGNMID) is a rare entity first described in 2004. We present a case of PGNMID with recurrent hematuria and nephrotic range proteinuria with three biopsies over 46 years. CASE PRESENTATION: A 79-year-old Caucasian female presents with a history of two separate episodes of biopsy-proven recurrent GN over a course of 46 years. Both biopsies from 1974, and 1987 were reported as membranoproliferative GN (MPGN). The patient presented in 2016 for the third time with symptoms of fluid overload, slight worsening in renal function, and proteinuria along with glomerular hematuria. A third kidney biopsy was performed, and the final diagnosis was proliferative glomerulonephritis with monoclonal IgG/κ deposits. CONCLUSION: With three renal biopsies obtained over 46 years, our case opens a unique window into the natural history of PGNMID. The three biopsies demonstrate the immunologic and morphologic evolution of PGNMID in the kidney.

A child with crescentic glomerulonephritis following SARS-CoV-2 mRNA (Pfizer-BioNTech) vaccination.

BACKGROUND: There are few reports on kidney complications after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) messenger RNA (mRNA) vaccination, especially in the pediatric population. We report a pediatric case diagnosed with crescentic glomerulonephritis (CrGN) after the second dose of the SARS-CoV-2 mRNA vaccine. CASE-DIAGNOSIS/TREATMENT: A 16-year-old girl was admitted due to dyspnea and headache approximately 6 weeks after receiving the second SARS-CoV-2 mRNA vaccine (Pfizer-BioNTech). She had previously experienced fever, nausea, vomiting, and dyspnea after the first vaccination, which persisted for a week. On admission, her blood pressure was 155/89 mmHg with a 7 kg weight gain in a month. She had microhematuria and proteinuria. Laboratory findings were as follows: blood urea nitrogen/creatinine, 66/9.57 mg/dL; and brain natriuretic peptide, 1,167 pg/mL. Anti-neutrophil cytoplasmic antibody (ANCA), anti-glomerular basement membrane (GBM) antibody, and antinuclear antibody findings were negative. Kidney doppler sonography revealed swelling and increased echogenicity of both kidneys with increased resistive index. Cardiac magnetic resonance imaging results showed early minimal fibrosis of myocarditis. We then started hemodialysis. Kidney biopsy showed diffuse extra capillary proliferative glomerulonephritis with diffuse crescent formation. We treated the patient with methylprednisolone pulse therapy with subsequent oral steroids and mycophenolate mofetil. Although dialysis was terminated, the patient remained in the chronic kidney disease stage. CONCLUSIONS: This is the first case of ANCA-negative CrGN after SARS-CoV-2 mRNA vaccination in the pediatric population. As children are increasingly vaccinated with SARS-CoV-2 mRNA vaccines, monitoring for kidney complications is warranted.

Poor outcomes of proliferative glomerulonephritis with monoclonal IgG deposits in renal allografts: a retrospective multicenter study.

BACKGROUND: Proliferative glomerulonephritis with monoclonal IgG deposits (PGNMID) in renal allografts is a rare, renal-limited disease. No study has reported the long-term outcomes and prognostic features of PGNMID in renal allografts in the Chinese population. METHODS: We retrospectively included transplant patients diagnosed with PGNMID who underwent renal allograft biopsy at three transplant centers from April 2012 to July 2020. We observed the clinicopathologic features, explored the long-term graft survival, and investigated the characteristics associated with the prognosis. RESULTS: A total of 13 transplant patients with PGNMID were included, out of 3821 biopsies. The mean follow-up time was 55 months since kidney transplantation (KTx). At diagnosis, all patients presented with proteinuria (100%) and most of them with hematuria (92%). IgG3κ (69%) was the main immunofluorescence (IF) subtype. The median graft survival of the total cohort was 17 months from diagnosis and 49 months from kidney transplantation. During follow-up, 9 patients needed dialysis and 2 out of 9 patients who progressed to dialysis died of infection. Primary membranoproliferative glomerulonephritis (MPGN) (P = 0.014) and MPGN pattern at diagnostic biopsy (P < 0.001) were associated with a higher risk of graft loss. CONCLUSIONS: The long-term outcome of allograft PGNMID was relatively poor in the Chinese population. Primary MPGN and MPGN pattern in renal allograft were associated with  poor outcomes.

A case report of pre-eclampsia-like endothelial injury in the kidney of an 85-year-old man treated with ibrutinib.

BACKGROUND: Glomerular endotheliosis is the pathognomonic glomerular lesion in pre-eclampsia that has also been described in those taking tyrosine kinase inhibitors for cancer treatment. Ibrutinib is a Bruton's tyrosine kinase inhibitor used to treat chronic lymphocytic leukemia (CLL). We report the first known case of glomerular endotheliosis on kidney biopsy in a patient on ibrutinib monotherapy. CASE PRESENTATION: The patient presented with acute on chronic kidney disease, proteinuria, low C3 and C4 and a high rheumatoid factor titer. A kidney biopsy was performed to confirm a preliminary diagnosis of membranoproliferative glomerulonephritis (MPGN), the most common glomerular disease in patients with CLL. Unexpectedly, the kidney biopsy showed pre-eclampsia-like lesions on light and electron microscopy: occlusion of glomerular peripheral capillary lumens by swollen reactive endothelial cells. Findings of glomerulonephritis were not seen, and there were no specific glomerular immune deposits by immunofluorescence or electron microscopy. CONCLUSIONS: CLL is known to cause glomerular lesions, mainly MPGN. There is increasing evidence that ibrutinib, a major treatment for CLL, can cause kidney disease, but the precise pathology is not characterized. We present a patient with CLL on ibrutinib with signs of glomerular endotheliosis. Based on the absence of CLL-induced kidney pathologies typically seen on the kidney biopsy and the non-selectivity of ibrutinib, we attributed the glomerular endotheliosis to ibrutinib. In pre-eclampsia, increased soluble fms-like tyrosine kinase 1 (sFlt1) levels induce endothelial dysfunction by decreasing vascular endothelial growth factor (VEGF). Ibrutinib has been demonstrated to have non-selective tyrosine kinase inhibition, including inhibition of VEGF receptor (VEGFR) and epidermal growth factor receptor (EGFR). VEGFR and EGFR inhibitors have recently been described in the literature to cause hypertension, proteinuria, and glomerular endotheliosis. Kidney biopsy should be performed in CLL patients on ibrutinib that present with acute kidney injury (AKI) or proteinuria to determine whether the clinical picture is attributable to the disease itself or a complication of the therapy.

An Interdisciplinary Diagnostic Approach to Guide Therapy in C3 Glomerulopathy.

Since the re-classification of membranoproliferative glomerulonephritis the new disease entity C3 glomerulopathy is diagnosed if C3 deposition is clearly dominant over immunoglobulins in immunohistochemistry or immunofluorescence. Although this new definition is more orientated at the pathophysiology as mediated by activity of the alternative complement pathway C3 glomerulopathy remains a heterogenous group of disorders. Genetic or autoimmune causes are associated in several but not in all patients with this disease. However, prognosis is poorly predictable, and clinicians cannot directly identify patients that might benefit from therapy. Moreover, therapy may range from supportive care alone, unspecific immune suppression, plasma treatment, or plasma exchange to complement inhibition. The current biopsy based diagnostic approaches sometimes combined with complement profiling are not sufficient to guide clinicians neither (i) whether to treat an individual patient, nor (ii) to choose the best therapy. With this perspective, we propose an interdisciplinary diagnostic approach, including detailed analysis of the kidney biopsy for morphological alterations and immunohistochemical staining, for genetic analyses of complement genes, complement activation patterning in plasma, and furthermore for applying novel approaches for convertase typing and complement profiling directly in renal tissue. Such a combined diagnostic approach was used here for a 42-year-old female patient with a novel mutation in the Factor H gene, C3 glomerulopathy and signs of chronic endothelial damage. We present here an approach that might in future help to guide therapy of renal diseases with relevant complement activation, especially since diverse new anti-complement agents are under clinical investigation.

C3 glomerulopathy: Understanding an ultra-rare complement-mediated renal disease.

C3 glomerulopathy (C3G) describes a pathologic pattern of injury diagnosed by renal biopsy. It is characterized by the dominant deposition of the third component of complement (C3) in the renal glomerulus as resolved by immunofluorescence microscopy. The underlying pathophysiology is driven by dysregulation of the alternative pathway of complement in the fluid-phase and in the glomerular microenvironment. Characterization of clinical features and a targeted evaluation for indices and drivers of complement dysregulation are necessary for optimal patient care. Autoantibodies to the C3 and C5 convertases of complement are the most commonly detected drivers of complement dysregulation, although genetic mutations in complement genes can also be found. Approximately half of patients progress to end-stage renal disease within 10 years of diagnosis, and, while transplantation is a viable option, there is high risk for disease recurrence and allograft failure. This poor outcome reflects the lack of disease-specific therapy for C3G, relegating patients to symptomatic treatment to minimize proteinuria and suppress renal inflammation. Fortunately, the future is bright as several anti-complement drugs are currently in clinical trials.

PGNMID and anti-CD38 monoclonal antibody: a therapeutic challenge.

Monoclonal gammopathy of renal significance (MGRS) designates disorders induced by a monoclonal protein secreted by plasma cells or B-cell clones in patients who do not meet the diagnostic criteria for multiple myeloma or other B-cell malignancies. Proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID) is a form MGRS. Until now, no guidelines to decide the best therapeutic approach to manage PGNMID exist, and most patients progress to End Stage Renal Disease (ESRD) without therapy. Recently, daratumumab has showed an acceptable improvement in proteinuria and renal function in patients with PGNMID. We report the clinical outcome and the histological renal evolution and treatment complication of our patient, who was initially treated with a combination regimen including bortezomib, dexamethasone, and cyclophosphamide and then with anti-CD38 monoclonal antibody-based regimen.

A case of proliferative glomerulonephritis with monoclonal IgG deposits (PGNMID) that responded favorably to steroid therapy.

Proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID) generally has a poor prognosis and the consensus is that it needs to be treated with clone-directed therapy. However, the prognosis of PGNMID is heterogenous and some cases have been successfully treated using other therapeutic strategies. We herein report a case of PGNMID that responded favorably to steroids without clone-directed therapy. An 18-year-old woman was referred to a nephrologist with proteinuria detected in an annual health check-up. Over a 3-year period, the concentration of creatinine (Cr) increased from 0.76 to 1.00 mg/dL and proteinuria from 0.35 to 1.9 g/g Cr. Monoclonal gammopathies were not detected in her serum or urine. Based on the findings of kidney biopsy at the age of 21 years, the patient was diagnosed with proliferative glomerulonephritis with monoclonal IgG1-kappa deposits. The histological feature was mesangial proliferative glomerulonephritis with advanced glomerulosclerosis, which is a rare presentation of PGNMID. Intravenous methylprednisolone pulse therapy was initiated, followed by oral prednisolone at a dose of 30 mg daily. One year later, a second kidney biopsy revealed a significant decrease in mesangial deposits of IgG1-kappa. Prednisolone was gradually tapered and discontinued 2 years after the first kidney biopsy. At the time of prednisolone withdrawal, urinalysis showed proteinuria of 0.2 g/g Cr without hematuria. Kidney function remained stable throughout the treatment period.

Fibronectin Glomerulopathy Confused with Glomerular Endothelial Injury in a Patient with Takotsubo Cardiomyopathy.

A 46-year-old woman developed takotsubo cardiomyopathy and nephrotic syndrome. The first kidney biopsy suggested non-immune-complex-mediated membranoproliferative glomerulonephritis (MPGN), and she was diagnosed with glomerular endothelial injury associated with takotsubo cardiomyopathy. A second biopsy was performed two years later because of persistent proteinuria despite renin-angiotensin system inhibition. This biopsy indicated non-immune-complex-mediated MPGN, but a mesangial and subendothelial substance of a higher electron density than that in the first biopsy was detected, suggesting the possibility of glomerular disease with non-immune deposits rather than endothelial injury. Finally, she was diagnosed with fibronectin nephropathy. Although rare, fibronectin glomerulopathy should be considered in non-immune-complex-mediated MPGN.

Rare Case of C3 Glomerulopathy in a Patient of Type 1 Diabetes Mellitus.

Complement component 3 glomerulopathy (C3G) is a recently defined entity comprising dense deposit disease and C3 glomerulonephritis. It is associated with nonrenal diseases such as diabetes mellitus (DM) type 1, ocular drusen, acquired partial lipodystrophy, and monoclonal gammopathy of undetermined significance. We describe a case of 13-year-old boy of the known case of type 1 DM, who developed proteinuria, and swelling over his face, and lower limbs, which on renal biopsy, was diagnosed as a case of C3G.

Retinal obliterative vasculitis associated to contralateral retinal neovascularization in membranoproliferative glomerulonephritis.

PURPOSE: To report our experience with a peculiar case of asynchronous bilateral retinal vascular occlusion in a patient suffering from membranoproliferative glomerulonephritis. CASE REPORT: A 57-year-old dialysed male affected by membranoproliferative glomerulonephritis who underwent kidney transplantation complained of a sudden vision loss in his right eye (RE). His best-corrected visual acuity (BCVA) was 20/40 in RE and 20/20 in the left eye (LE); ophthalmological and fluorangiographic examinations revealed unilateral retinal obliterative vasculitis with panuveitis and apparent sparing of contralateral eye. About 6 months later the patient developed a branch retinal vein occlusion associated with a papillary neovascular membrane in LE. Corticosteroid therapy was administered and immunosuppressant dosage was increased with macular oedema reduction in both events. CONCLUSION: We report a case of unilateral retinal obliterative vasculitis and subsequent contralateral retinal neovascularization and branch retinal vein occlusion in a patient affected by membranoproliferative glomerulonephritis.

Chronic catheter-related bacteremia of Pseudomonas stutzeri etiology as the cause of membranous-proliferative glomerulonephritis (MPGN) - a case report.

Secondary membranous - proliferative glomerulonephritis most often develops in the course of viral infections (HCV, HBV), autoimmune diseases, paraproteinemia, and also in the course of chronic bacterial infections. Infections with Pseudomonas stutzeri (P. stutzeri) are extremely rare and usually mildly symptomatic. The natural habitat of this bacterium is soil and water. Nevertheless, in the case of P. stutzeri infection, especially in patients frequently hospitalized or receiving immunosuppressive medications, environmental contamination in healthcare facilities should be taken into account when looking for the source of the infection. A CASE REPORT: A 60-year-old man with a previous history of nicotinism and arterial hypertension with a vascular port in the vena cava superior (VCS) after treatment for bladder cancer (stage G2/G3) several years ago was described. The patient underwent the TURBT procedure, and then received intravesical infusions with BCG for 3 years, followed by complications in the form of severe dysuria and lower abdominal pain. Due to severe nausea and the inability to take analgesics orally, the patient was ordered to insert a vascular port into the VCS in order to continue the analgesic and anti - inflammatory therapy. Several years later, after the onset of massive edema of lower limbs, the patient was subjected to a 24-hour urine collection, in which proteinuria amounted to approx. 13 g/day, followed by a diagnostic kidney biopsy. Histopathological examination described membranoproliferative glomerulonephritis (MPGN). Other renal parameters were also abnormal, i.e. serum creatinine concentration was 1.9 mg/ dl and serum urea concentration was 116 mg/dl. Immunosuppressive treatment was initiated. Patient received methylprednisolone intravenously followed by prednisone orally and cyclosporine orally. During the initial period of immunosuppressive therapy, the serum levels of cyclosporine were insufficient (starting from 26.34 ng/ml), which resulted in increasing its dose, ultimately reaching 175 mg/day. After several months of therapy, the patient was hospitalized again, due to infection of the respiratory tract that had lasted for several weeks and was not amenable to antibiotic therapy. Deterioration of renal parameters and increased inflammatory markers suggested diagnosis of catheter - related sepsis. P. stutzeri was grown from the material collected from the catheter and the patient's blood. Appropriate antibiotic therapy was initiated and after the patient's condition improved, cyclosporine therapy was restarted, which was discontinued after the diagnosis of bacteremia. Rapid remission was achieved, allowing the discontinuation of immunosuppressive drugs. CONCLUSIONS: Chronic, asymptomatic infection with a rare pathogen, like Pseudomonas stutzeri, was probably the cause of the glomerulonephritis. After removal of the port and antibiotic therapy, disease remission was achieved.

Myeloperoxidase immunohistochemical staining can identify glomerular endothelial cell injury in dense deposit disease.

BACKGROUND: Previous studies have demonstrated residual complement-mediated deposits in repeat kidney biopsies of C3 glomerulopathies (C3G) (dense deposit disease (DDD) and C3 glomerulonephritis) following eculizumab treatment, despite some clinical improvement. With residual complement deposition, it is difficult to determine whether there is a reduced complement-mediated endothelial cell injury. We validated that myeloperoxidase (MPO) immunohistochemical staining identified glomerular endothelial cell injury in crescentic glomerulonephritis and C3G. CASE (DIAGNOSIS/TREATMENT): We report that MPO staining in the glomerular endothelium of the post-treatment kidney biopsy was significantly reduced after 3 years of eculizumab treatment and clinical improvement in a 5-year-old boy with initial DDD and secondary crescent formation. CONCLUSION: We find that immunostaining for MPO is a useful method to compare glomerular endothelial injury in C3G following eculizumab treatment. This finding also supports the notion that eculizumab, a C5 blocker, may not mainly block C3 deposits in the glomeruli but significantly blocks final activation of the complement cascade, thus reducing glomerular endothelial cell injury.