Anti-Gbm Disease One and Half Years Experience in a Tertiary Care Centre

BACKGROUND: Anti-glomerular basement membrane (GBM) antibody GN is a rare glomerular disease (0.5-1 per million population) with poor outcome in terms of renal survival. It is caused by auto-antibodies against the non-collagenous domain of the a3 chain of type IV collagen and usually present as a rapidly progressive crescentic GN. Anti-GBM GN may present either as an isolated kidney disease or as a pulmonary-renal syndrome (Goodpasture's syndrome) in 40%-60% of patients. Linear staining of the GBMs for immunoglobulin ( Predominantly IgG & rarely IgA ) in renal biopsy with anti-GBM antibodies in serum is pathognomonic of Anti-GBM disease. Initiating immunosuppression with steroids and cyclophosphamide plus plasmapheresis are the cornerstone of treatment whereas no treatment is recommended if dialysis dependent at presentation 100% crescents or >50% global glomerulosclerosis in an adequate biopsy sample or not having pulmonary hemorrhage. AIM OF THE STUDY: To study demographic and clinical profile treatment administered and outcome (in terms of renal survival) in the patients with biopsy-proven anti-GBM disease. METHOD(S): Single-center prospective observational study (January 2021 to June 2022 ) and study population being the admitted patients in Nephrology Department of I.P.G.M.E.R and SSKM hospital Kolkata. RESULT(S): Total 7 patients were diagnosed as having Anti- GBM disease in this time period with median age of 42 yrs ( range from 11 yrs to 68 yrs), and Female : Male ratio was 5:2. Rapidly Progressive Renal Failure with Oliguria (71.4% ) was the most common presentation and 85.7% required Hemodialysis on presentation. 57.1% patients had 100% crescent in renal biopsy. 1 out of 7 patients had overlap with MPO and did not required RRT at presentation. 1 out of 7 patients had associated pulmonary hemorrhage. 28.5% patients received PLEX while others were treated supportively as per protocol. 28.5% patients previously had COVID 19 infection which was diagnosed retrospectively by detecting COVID 19 IgG antibody in serum. 71.4% patients end up in HD requiring renal failure while 1 patient succumbed to death. CONCLUSION(S): Most of the patients aged between 20 yrs to 60 yrs and were female (both 71.4%). Most of the patients (71.4%) received supportive treatment as per protocol. Only 1 patient (with MPO overlap) is dialysis free with discharge creatinine of 3.3 and receiving EUVAS protocol. Most of the patients who presented late with HD requiring renal failure end up in ESRD.

A CASE OF GRANULOMATOSIS WITH POLYANGIITIS

SESSION TITLE: Critical Systemic Disease Case Report Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Granulomatosis with polyangiitis(GPA) is an autoimmune small vessel vasculitis that is included in the group of anti-neutrophilic cytoplasmic antibody(ANCA)- associated small vessel vasculitides (AAVs). GPA is a systemic disease, however acronym ELK is used to describe the most common involvement of Ear, nose, throat, Lungs, and Kidneys. We report a case of GPA, highlighting its presentation. CASE PRESENTATION: 59-year old female presented with vaginal bleeding, malaise, blurry vision, non productive cough and shortness of breath few days after receiving COVID-19 vaccine. Physical exam was remarkable for bilateral conjunctival injection with right sided ptosis and inguinal lymphadenopathy. Laboratory findings were significant for acute kidney injury and anemia. Computed tomography (CT) of chest revealed bilateral bronchovascular nodules and masses with interlobular septal thickening and enlarged mediastinal lymph nodes. Fine needle aspiration of left inguinal lymph node was negative for malignancy. Bronchoscopy with bronchial brush revealed alveolar hemorrhage with capillaritis;bronchoalveolar lavage(BAL) showed hemosiderin laden macrophages. Tissue biopsy was negative for malignancy. Testing for pulmonary renal syndrome was positive for C-ANCA and proteinase-3 (PR-3) antibodies. Anti-GBM antibody and anti-MPO antibody was negative. Plasmapheresis (PLEX) and pulse dose steroids were initiated however the patient was unable to tolerate the treatment. Her clinical condition continued to decline requiring multiple pressors, broad spectrum antibiotics and continuous renal replacement therapy. She was transitioned to comfort care per family's wishes and passed away. DISCUSSION: GPA is a rare necrotizing granulomatous vasculitis of small to medium sized vessels that can affect any organ but mainly involves the upper and lower respiratory tract. Necrotizing glomerulonephritis is common. Pulmonary involvement can include consolidation, tracheal or subglottic stenosis, diffuse alveolar hemorrhage, pleural effusion and interstitial lung disease. Lymphadenopathy, as seen in our patient is a rare presentation. Tissue biopsy is crucial for the diagnosis. Association with PR-3 ANCA is seen in more than 80% of GPA patients. Cases of AAVs after administration of COVID vaccine have been reported in the literature, although it is difficult to demonstrate causal relationship. Treatment of GPA with immunosuppression, usually corticosteroids, rituximab or cyclophosphamide, is recommended. The role of PLEX continues to evolve with emerging data, but use of this therapy is reasonable for patients with severe kidney injury and DAH secondary to active vasculitis refractory to immunosuppressive therapy. CONCLUSIONS: Early diagnosis of GPA is challenging as it can mimic metastatic lung malignancy. It should be considered in a broad range of differentials when evaluating patients presenting with pulmonary nodules. Reference #1: Greco A, Marinelli C, Fusconi M, Macri GF, Gallo A, De Virgilio A, Zambetti G, de Vincentiis M. Clinic manifestations in granulomatosis with polyangiitis. Int J Immunopathol Pharmacol. 2016 Jun;29(2):151-9. doi: 10.1177/0394632015617063. Epub 2015 Dec 18. PMID: 26684637;PMCID: PMC5806708. Reference #2: Kitching, A. R., Anders, H. J., Basu, N., Brouwer, E., Gordon, J., Jayne, D. R., Kullman, J., Lyons, P. A., Merkel, P. A., Savage, C., Specks, U., & Kain, R. (2020). ANCA-associated vasculitis. Nature reviews. Disease primers, 6(1), 71. https://doi.org/10.1038/s41572-020-0204-y Reference #3: Szymanowska-Narloch, A., Gawryluk, D., Błasińska-Przerwa, K., & Siemińska, A. (2019). Atypical manifestations of granulomatosis with polyangiitis: the diagnostic challenge for pulmonologists. Advances in respiratory medicine, 87(6), 244–253. https://doi.org/10.5603/ARM.2019.0062 DISCLOSURES: No relevant relationships by Sean Davidson No relevant relationships by Eric Flenaugh No relevant relationships by Marilyn Foreman No relevant relationships by KOMAL KAUR No relevant relationships by Gabriela Oprea-Ilies

Leptospirosis: A Consideration When Acute Liver Failure Accompanies Acute Kidney Injury (AKI)

A 48 y.o. male maintenance worker in a rat-infested building with history of tobacco and marijuana smoking, atrial fibrillation on no medications was admitted in July 2021 for fever, headache and body aches for 5 days and new onset of hemoptysis. Initial labs notable for BUN 36 mg/dl, Cr 1.4 mg/dl urine protein 100 mg/dl RBCs 5-10/hpf, platelets 46,000. total bilirubin 3.8 mg/dl direct bilirubin 3.0 SARS-CoV-PCR negative and CXR revealed patchy bilateral infiltrates. He was intubated on day 2 and had ventricular fibrillation and cardiac arrest on day 3 with rapid return of purposeful movement. He had worsening anemia and thrombocytopenia, positive ANA and dsDNA, leading to use of steroids and plasmapheresis on Day 6 when peak bun/cr was 91/3.1 with urine protein/cr ratio 0.7, urine microscopy 2 rbc/hpf, urine Na 20 meq/l, urine osm 775 mosm/kg and cpk 400 U/l. These tests were negative or normal: Anti-GBM, ANCA, repeat ANA, repeat dsDNA, C3, C4, HIV, RF, hepatitis C RNA, cryoglobulins, ASO titer, ADAMTS13, Pneumocystis PCR, Sputum AFB, blood, AFB and fungal cultures, viral and fungal testing, hanta virus antibodies. Leptospira antibodies IgM by Dot Blot were positive and Leptospirosis diagnosis confirmed by NYC Department of Health (DOH) after obtaining confirmatory microscopic agglutination testing from the CDC. Urine and blood Leptospira DNA PCR not detected. He remained intubated with FiO2 requirement at 100% prior to his death on hospital day 16. Initially pulmonary renal syndrome considered but he was later found to have pre-renal azotemia. The elevated bilirubin led to testing for leptospirosis, his final diagnosis. In September 2021 the NYC DOH reported 14 cases of leptospirosis (increased from 5 cases in 2020), 13 of which had acute renal and hepatic failure, with 2 having severe lung involvement (1). This case is the only one in this group who died. The leptospirosis case fatality rate for severe diffuse alveolar hemorrhage exceeds 50%. Early appropriate antibiotic treatment prior to lab confirmation has been recommended by the CDC and may decrease severity of disease.

A CASE OF FSGS IN A PREVIOUSLY HEALTHY MALE AFTER THE SECOND DOSE OF COVID-19 MRNA VACCINE

Case Report Background COVID-19 infection and COVID-19 mRNA vaccines have been associated with the occurrence of de-novo and relapsing glomerulopathies. Although, Focal Segmental Glomerulosclerosis (FSGS) similar HIV associated Nephropathy (HIVAN) has been reported with COVID-19 infection in African American population with Apolipoprotein L1 gene mutation, amongst the few reported cases post-vaccine, Minimal change disease (MCD), IgA nephropathy (IgAN), Anti-Glomerular basement membrane glomerulonephritis (Anti GBM GN), and membranous glomerulonephritis (MGN) have been reported. Case A 26-year-old Caucasian male with a history of tobacco use complained of Frothy urine and edema for 3 weeks post second dose of Moderna COVID-19 vaccine on 06/01/21. He received the first dose on 5/04/21. On his annual wellness visit on 5/18/21, he had no complaints, normal physical examination with serum albumin 5g/dl, and urinalysis significant for trace proteinuria. A repeat urinalysis post-onset of symptoms on 7/18/21 revealed 3+ proteinuria, no RBCs, 24- hour urine revealed 3.2g proteinuria. Further investigations revealed Hypoalbuminemia (2g/dl), persistent proteinuria, and an unremarkable renal ultrasound, ANA, ANCA, Anti-dsDNA, Anti-PLA2R, anti-streptolysin, RF, HIV, hepatitis panel, and serum complement levels. Renal biopsy revealed Tip lesion variant of FSGS with 100% effacement of podocyte foot process. Therapy with Prednisone 60 mg daily was initiated, following which an improvement in edema and serum albumin levels (2.7 g/dl) were noted. Discussion A few de-novo cases of anti-GBM GN, ANCA positive vasculitis, MCD and IgAN, and relapsing cases of IgAN, MCD, MGN, and Thrombotic microangiopathy have been reported post-COVID 19 mRNA vaccination. Most reported cases of MCD occurred after the first dose whereas IgAN flare-up occurred after the second dose. Our case is unique as our Caucasian patient developed FSGS post-second dose of Moderna vaccine. Although the pathogenesis is unclear, it is thought to be related to an acute T-cell immune response involving cytokine production to COVID 19 spike protein which is responsible for inducing or worsening existing podocytopathies. Interestingly fewer cases have been reported following adenovirus vector or inactivated virus vaccination. Most of the reported cases of IgAN flare-up have been mild and a small number of MCN cases required ICU admission for management of fluid overload. As observed in a few prior case reports our patient had a slow response to steroid therapy. Although guidelines on COVID 19 vaccination in patients with existing glomerulopathies remain unclear and are based on case-by-case scenarios, the benefit of COVID 19 vaccination, may in general, outweighs the risk of glomerular diseases. We encourage further studies on this topic, especially in the era of booster doses with ongoing discussion about mixing two types of vaccines.

POS-126 PROLIFERATIVE GLOMERULONEPHRITIS WITH MONOCLONAL IgG DEPOSITS;A NOVEL PATHOLOGIC PRESENTATION

Introduction: Proliferative glomerulonephritis with monoclonal IgG deposits (PGNMID) is a rare form of PGN that mimics immune-complex (IC) GN by light microscopy (LM), but shows monoclonal IgG deposits by immunofluorescence (IF). PGNMID often presents with membranoproliferative (MPGN) pattern or endocapillary hypercellularity. Focal crescents are not uncommon in PGNMID, but diffuse crescentic involvement is very rare. Methods: 78-year-old man with a history of hypertension and multiple cardiovascular comorbidities presented with weakness, dizziness, and anorexia, and was found to have severe hypertension and acute kidney injury with serum creatinine of 12 mg/dl (baseline 1 mg/dl). He was a chronic smoker and alcoholic. He reported productive cough with scanty whitish sputum, but denied hemoptysis. Urine analysis showed marked proteinuria, hematuria, and leukocyturia. Renal ultrasound revealed bilateral decrease corticomedullary differentiation without obstruction. Hemodialysis was initiated. Imaging showed bilateral upper lobe pneumonia with concerns for alveolar hemorrhages. Serology for complements, ANA, dsDNA, ANCA, Hepatitis B and C, Covid19 was negative. Kappa/lambda free light chain ratio was normal. SPEP, UPEP and immunofixation were negative for paraproteinemia. Renal biopsy showed diffuse crescentic and endocapillary PGN with MPGN features, and linear monoclonal IgG3-kappa immune deposits. Given the lack of clinical evidence of cryoglobulinemia and presence of immune-type electron dense deposits without organized substructures by EM, the findings were most consistent with PGNMID. However, the unusual biopsy presentation raised concerns for possible concurrent anti-GBM disease. Subsequently, Solu-Medrol was started followed by prednisone 1 mg/kg. He received 2 sessions of plasmapheresis before anti-GBM serology returned negative. Bone marrow biopsy revealed monoclonal B-cell lymphocytosis with CLL phenotype. Unfortunately, the patient developed Covid19 infection, and passed away before receiving further treatment. [Formula presented] Results: PGNMID is a rare form of renal involvement by monoclonal immunoglobulin deposition that mimics ICGN on renal biopsy. Nephrotic range proteinuria, hematuria and renal insufficiency are usual presentation. Cases of PGNMID classically show IgG3k, in a granular glomerular capillary wall, mesangial, and occasionally subepithelial distribution. By EM, these deposits appear granular typical of ICGN which lack organized substructure. The predominant LM patterns are MPGN and endocapillary hypercellularity. Less frequently focal crescents may be present, but diffuse crescentic involvement is especially rare (~5%). In our case, the diffuse cellular crescents and semilinear to linear GBM staining was unusual. Together with the clinical presentation, the findings prompted concerns for a concomitant Goodpasture syndrome, but anti-GBM antibody returned negative. The pathogenesis is still unclear, but some authors suggest infection as a possible trigger for crescentic transformation in PGNMID. The presence of crescents seem to confer a poorer prognosis and associated with progression to ESRD. Conclusions: Our case is a unique presentation of PGNMID in a patient who presented with clinical and pathologic features concerning for Goodpasture syndrome. PGNMID can rarely present with diffuse crescents and IF findings similar to anti-GBM nephritis in a patient with RPGN. No conflict of interest

POS-131 A STUDY OF ETIOLGIES AND SHORTTERM OUTCOME OF RAPIDLY PROGRESSIVE GLOMERULONEPHRITIS IN A TERTIARY CARE HOSPITAL

Introduction: Rapidly progressive Glomerulonephritis (RPGN) is a syndrome which is caused by glomerulonephritis which results in rapid decline in renal function over a short period of time. Its histological hallmark is extensive crescent formation. It is a heterogeneous disease with various aetiologies leading to glomerular injury. The renal outcome will be dependent on the etiology and mode of treatment and timely initiation of treatment. Methods: The number of renal biopsies performed at our tertiary hospital over a period of 6 months of the study period were determined. The biopsies with crescentic glomerulonephritis were further scrutinized. The demographical data which includes, age, gender, and the baseline estimated glomerular filtration rate (eGFR) as determined by the Modified Diet in Renal Disease (MDRD) formula was collected. The serological test results of ANA, p-ANCA, c-ANCA, ASOT, anti-GBM antibody, C3 and C4 level were also be recorded. The underlying disease process of each of the RPGN cases were recorded into anti-GBM disease, Immune complex mediated, pauci-immune vasculitis, idiopathic or double antibody disease. Treatment of each patient and shorterm renal outcome were recorded. Results: Out of 112 biopsies done over a period of 6 months,16 were crescentric glomerulonephritis. The average age was 30.2 years, there were 5 male and 11 female patients. The majority of them (81.25%) were immune complex mediated and the remainder were ANCA mediated. The underlying cause of the 13 immune complex mediated crescentic glomerulonephritis was lupus nephritis in 8 (61.5%), post infection glomerulonephritis in 3 (23.07%), and antiGBM in 2 (15.38). Pauciimmune glomerulonephritis is 3 out of 16(18.75%) patients. Every patient was treated with immunosuppression. Plasma exchange was done in 2 antiGBM and 2 pauciimmune glomerulonephritis patients. out of 16,10 (62.5%) patients required dialyisis at the time of presentation. 4 out of 10 patients initiated on dialysis became dialysis independent with in 20 days. Renal recovery was not there in both antiGBM patients. one patient of pauciimmune glomerulonephritis succumbed due to Covid- 19 Iinfection. One patient with antiGBM GN had pulmonary alveolar haemorrhage which was responded to plasma exchange. One patient with IRGN was having chronic changes of diabetes on renal biopsy. [Formula presented] Conclusions: The most common cause of RPGN was immune complex mediated GN, mainly SLE lupus nephritis. In our study RPGN was more prevalent in females than males. With early and appropriate treatment renal recovery can be substantially good. Patients with antiGBM GN have poor renal outcomes. No conflict of interest

POS-139 AN ATYPICAL PRESENTATION OF DUAL-POSITIVE ANTI-MYELOPEROXIDASE AND ANTI-GLOMERULAR BASEMENT MEMBRANE ANTIBODIES VASCULITIS WITH PULMONARY-RENAL SYNDROME : A CASE REPORT

Introduction: Double-positive vasculitis with anti-polynuclear cytoplasm (ANCA) and anti-glomerular basement membrane (GBM) antibodies is a rare entity of systemic vasculitis defined by the presence of ANCA and anti-GBM antibodies. Methods: We report a rare case of pulmonary-renal syndrome with atypical clinical presentation. Results: A 52 year-old smoking man with a history of exposure to hydrocarbons and uretheral lithiasis, presented in April 2021 epigastralgia and vomiting. the investigations concluded to H.pylori gastritis and ulcer and he received a quadruple therapy. The kidney function was correct in April 2021. The evolution was marked by the persistence of symptoms and urine output had decreased for a few days. He was found to have renal dysfunction (serum creatinine: 2000 µmol/L). Abdominal CT scan without iodinated contrast injection showed severe hydronephrosis of the right pelvicalyceal system with cortical thinning and dilatation of the right ureter. The two kidneys had regular outlines seat multiple bilateral renal cysts with exophytic development. He had a nephrosomy with secondarily a right double-J stent with slight improvement of renal function. The patient presented then with acute respiratory distress.Testing for COVID-19: PCR and serology were negatives. Chest CT scan showed alveolar syndromeevoking pulmonary overload. No pneumopathy covid was shown. The evolution was marked by the non improvement by depletion and he developed hemoptic sputum and low-abundance epistaxis. The attitude was non-invasive ventilation and broad-spectrum antibiotics therapy. Control chest CT showed emphysematous lung with signs of fibrosis with bilateral subpleural nodules. A rereading of the scanner showed intraalveolar hemorrhage which has regressed on the imaging of the control. Based on these data, pneumo renal syndrome was suspected and a bronchoscopy was performed showing alveolar hemorrhage with 70% siderophageswith Gold score superior to 100. Anti-GBM and p-ANCA and antibodies were positive at a high titer. Electroneuromyogram was without anomaly. Kidney biopsy was not done because of the presence of multiple cysts. The patient received pulse methylprednisone for three days followed by oral prednisone and underwent eleven sessions of plasmapheresis. Intraveinous Cyclophosphamide has been started. He showed remarkable recovery as his lung fields cleared with negativity of GBM antibodies. Kidney function didn't improved and he remained dependent on dialysis. Conclusions: Our observation is exceptional since the clinical and radiological presentation of the patient was not that of a pulmonary-renal syndrome. The elements of this syndrome have in fact been masked by the obstacle on the urinary tract on one hand and the hypothesis of a covid19 pneumonia on the other hand in the face of the epidemiological context. Atypical feature of pulmonary renal syndrome should be kept in mind to avoid diagnostic and treatment delays. No conflict of interest