# πŸ”¬ Glomerulonephritis ## 🌟 Featured Module: Systemic Lupus Erythematosus & Lupus Nephritis Comprehensive guide featuring the latest treatment advances including voclosporin (Lupkynis), emerging biologics, and evidence-based protocols for young women πŸ“Š 2019 EULAR/ACR Criteria Calculator πŸ”¬ ISN/RPS Classification πŸŽ† Voclosporin 2021 FDA Approved πŸ‘© Young Women Focus [πŸ“š Study Complete SLE Module](https://urinenephrology.org/2025_UDPA_Lectures_Live/glomerulonephritis/SLE.html) [πŸ“‹ Case 7: Lupus Nephritis](https://urinenephrology.org/2025_UDPA_Lectures_Live/cases/case7_enhanced.html) ### ⚠️ Emergency Recognition **RPGN is a nephrology emergency!** Rapidly worsening kidney function with suspected glomerular inflammation needs immediate nephrology assessment. Hemoptysis or hypoxemia raises concern for a pulmonary–renal emergency. Do not wait for a 50% fall in GFR. ### πŸ“š Chapter Overview Glomerular diseases represent a complex group of disorders affecting the kidney's filtering units. This comprehensive chapter covers both nephritic and nephrotic syndromes, their pathophysiology, diagnostic approaches, and evidence-based treatments essential for PA practice. #### Learning Objectives - Differentiate nephritic from nephrotic syndromes clinically - Interpret complement patterns and serological testing - Recognize and manage rapidly progressive glomerulonephritis - Understand modern treatment approaches and prognosis - Identify secondary causes of glomerular disease ## 🩸 Nephritic vs πŸ’§ Nephrotic Syndrome Differentiation ### Nephritic Syndrome - **Definition:** Inflammatory glomerular disease - **Proteinuria:** Variable; may reach nephrotic range - **Hematuria:** +++ - **RBC Casts:** Strong diagnostic clue when present; absence does not exclude GN - **Hypertension:** +++ - **Edema:** Moderate - **Serum Albumin:** Variable; can fall with heavy protein loss ### Nephrotic Syndrome - **Definition:** Proteinuric disease with hypoalbuminemia - **Proteinuria:** \>3.5 g/day - **Hematuria:** +/- - **RBC Casts:** Usually absent in a bland nephrotic sediment; casts suggest an overlapping inflammatory process - **Hypertension:** +/- - **Edema:** Severe - **Serum Albumin:** \<3.0 g/dL ## 🩸 Nephritic Syndrome - Detailed Review ### πŸ”¬ Urine Microscopy Findings #### πŸ”΄ RBC Casts - Strong Evidence of Glomerular Bleeding **Interpret casts with kidney function, proteinuria, and the full clinical presentation** - Strongly suggest glomerular bleeding in the appropriate clinical setting - Must be differentiated from RBCs alone - Best seen in fresh urine (\<2 hours) - May be missed if urine sits too long **Clinical Pearl:** RBC casts strongly support a glomerular source and warrant prompt evaluation, but do not by themselves establish the cause or immune mechanism. Their absence does not exclude GN. [Biopsy-correlated urine microscopy study](https://pubmed.ncbi.nlm.nih.gov/40406196/). #### πŸ”¬ Dysmorphic RBCs - Distorted RBC morphology - Indicates glomerular origin of bleeding - Contrasts with uniform RBCs from lower urinary tract - Acanthocytes are particularly useful; assess morphology with experienced microscopy rather than requiring a fixed dysmorphic-RBC percentage #### βšͺ WBC Casts - May be present in proliferative GN - Indicates inflammatory response - Less specific than RBC casts - Can also be seen in interstitial nephritis #### 🟀 Granular Casts - Brown, muddy appearance - Indicate tubular damage - May be seen with severe GN - Non-specific finding ## 🧬 Serological Evaluation of Glomerular Disease ### πŸ“Š Complement System Evaluation Measuring **C3 and C4 simultaneously** helps narrow the differential diagnosis. These are typical, nonexclusive patterns: normal levels do not exclude active GN, and low levels do not identify its cause. #### Complement Patterns and Associated Diseases [TABLE] ### 🎯 ANCA Testing Clinical Correlation #### High Positive Predictive Value **C-ANCA with sinusitis + pulmonary infiltrates + active urinary sediment = 98% PPV for GPA** However, C-ANCA with sinusitis alone has only 7-16% PPV #### Combined Testing Approach Use both immunofluorescence pattern AND antigen-specific ELISA (MPO/PR3) for optimal sensitivity and specificity #### Clinical Context is Key ANCA results must always be interpreted in the clinical context. PPV \>95% in patients with classic RPGN features #### ANCA Patterns and Associated Diseases #### P-ANCA/MPO **Microscopic Polyangiitis (MPA)** - Perinuclear staining pattern - Directed against myeloperoxidase (MPO) - More likely renal involvement (80%) - Pulmonary-renal syndrome common - Diffuse capillaritis #### C-ANCA/PR3 **Granulomatosis with Polyangiitis (GPA)** - Cytoplasmic staining pattern - Directed against proteinase 3 (PR3) - Upper respiratory tract involvement - Pulmonary nodules - Necrotizing granulomatous inflammation ## πŸ’§ Nephrotic Syndrome - Detailed Review ### Pathophysiology Flow 1 **Glomerular Basement Membrane Damage** - Loss of charge selectivity and size selectivity 2 **Massive Proteinuria** - Primarily albumin loss (\>3.5 g/day) 3 **Hypoalbuminemia** - Decreased plasma oncotic pressure 4 **Fluid Retention** - Edema formation and volume expansion 5 **Compensatory Liver Synthesis** - Increased protein and lipid production ### πŸ”¬ Urine Microscopy in Nephrotic Syndrome #### Oval Fat Bodies - Tubular epithelial cells containing lipid droplets - Highly characteristic of nephrotic syndrome - Result from reabsorption of filtered lipoproteins - Appear refractile under polarized light #### Fatty Casts - Casts containing lipid droplets - Show "Maltese cross" appearance under polarized light - Pathognomonic for significant proteinuria - May persist even after treatment #### Waxy Casts - Broad, homogeneous casts - May indicate chronic kidney disease - Non-specific finding - Can be seen with prolonged proteinuria #### Minimal Hematuria - Usually \<5 RBCs per high-power field - RBC casts are typically absent - Contrasts with nephritic syndrome - If significant hematuria present, consider mixed picture ### Primary Causes of Nephrotic Syndrome #### Minimal Change Disease (MCD) ##### Epidemiology - Most common cause in children (90%) - 20-25% of adult nephrotic syndrome - Male predominance in children - Peak incidence: 2-6 years old ##### Clinical Features - Sudden onset of edema and proteinuria - Normal blood pressure typically - Normal renal function - Minimal hematuria ##### Treatment 1 **Initial Treatment:** Prednisone 1 mg/kg/day (max 80 mg) for 4-16 weeks 2 **Frequently Relapsing/Steroid-Dependent:** Cyclophosphamide, Calcineurin inhibitors, Mycophenolate mofetil, or Rituximab #### Focal Segmental Glomerulosclerosis (FSGS) ##### Epidemiology - Most common primary cause in adults - Higher prevalence in African Americans - 40% of adult nephrotic syndrome - Increasing incidence over past decades ##### Clinical Features - Often presents with hypertension - Microscopic hematuria common - May have reduced GFR at presentation - More resistant to treatment than MCD ##### Treatment 1 **Initial Treatment:** Prednisone 1 mg/kg/day for at least 8-16 weeks 2 **Steroid-Resistant FSGS:** Calcineurin inhibitors (first-line), Mycophenolate mofetil, or Sirolimus **Note:** African Americans and patients with collapsing FSGS are generally unresponsive to treatment and progress to kidney failure. #### Membranous Nephropathy ##### Epidemiology - Most common cause in older adults - Male predominance (2:1) - Peak incidence: 40-60 years - 30-40% of adult nephrotic syndrome ##### Non-Invasive Diagnosis ###### Anti-PLA2R Antibodies - **Sensitivity:** 78% - **Specificity:** 99% - Positive in 70-80% of primary MN cases - Kidney biopsy not required if positive with appropriate clinical context - Antibody levels correlate with disease activity ##### Risk Stratification (KDIGO 2021) | Risk Category | Criteria | Management | |----|----|----| | **Low Risk** | Normal eGFR, Proteinuria \<3.5 g/day, Serum albumin \>3.0 g/dL | Supportive care only | | **Moderate Risk** | Proteinuria 3.5-8 g/day, Stable eGFR, Albumin 2.5-3.0 g/dL | Rituximab or calcineurin inhibitors | | **High/Very High Risk** | Proteinuria \>8 g/day, Declining eGFR, High anti-PLA2R levels (\>150 RU/mL) | Immunosuppressive treatment required | ##### Treatment Options 1 **Rituximab (First-Line, KDIGO 2021):** 375 mg/mΒ² weekly Γ— 4 doses or 1g Γ— 2 doses 2 **Modified Ponticelli Regimen:** Alternating months of steroids and cyclophosphamide 3 **Calcineurin Inhibitors:** Cyclosporine 3-5 mg/kg/day (trough 125-175 ng/mL) ### Complications of Nephrotic Syndrome #### Thromboembolism (Critical) **Pathophysiology:** Loss of antithrombin III and protein S, increased fibrinogen and platelets, hemoconcentration from diuretic use - Deep vein thrombosis - Pulmonary embolism - Renal vein thrombosis **Management:** Consider prophylactic anticoagulation if albumin \<2.0 g/dL #### Infections **Pathophysiology:** Loss of immunoglobulins in urine, complement factor losses, immunosuppressive medications - Pneumococcal pneumonia - Peritonitis (especially with ascites) - Cellulitis #### Protein Malnutrition - Loss of binding proteins - Muscle wasting - Poor wound healing - Growth retardation in children #### Cardiovascular Disease - Accelerated atherosclerosis - Hypertension - Coronary artery disease - Increased mortality risk ## 🚨 MEDICAL EMERGENCY # Rapidly Progressive Glomerulonephritis Risk of irreversible kidney injury without prompt treatment Time is kidney function Immediate nephrology consultation required ## Emergency Definition & Recognition **RPGN is a clinical syndrome of rapidly worsening kidney function with suspected glomerular inflammation, often over days to weeks. Evaluate urgently while excluding other causes of AKI; do not wait for a specified percentage GFR loss or biopsy crescent burden.** #### Recognition Criteria ##### Rapid GFR Decline **Rapid creatinine rise or falling filtration** with a compatible clinical presentation; a 50% decline is not a referral threshold ##### Nephritic Urine Hematuria, dysmorphic RBCs, **RBC casts**, proteinuria ##### Biopsy Activity and Chronicity Crescents and necrosis support active injury; assess viable glomeruli and chronic scarring. A fixed crescent percentage is not required before urgent evaluation ##### Systemic Features Constitutional symptoms, fever, malaise, arthralgias ### RPGN Classification by Immunofluorescence Pattern #### Type I: Linear Pattern (Anti-GBM Disease) - 10% of RPGN **Pathophysiology:** Autoantibodies against NC1 domain of Ξ±3 chain of type IV collagen in glomerular and alveolar basement membranes ##### Clinical Presentations - **Anti-GBM nephritis:** Kidney involvement only - **Goodpasture syndrome:** Kidney plus lung involvement (pulmonary hemorrhage) ##### Emergency Treatment 1 **Plasmapheresis:** Daily exchanges for 14 days or until anti-GBM antibodies undetectable. Start immediately, do not wait for biopsy results 2 **IV Methylprednisolone:** 1g daily for 3 days, then oral prednisone 1 mg/kg/day 3 **Cyclophosphamide:** 2 mg/kg/day oral or IV monthly pulses #### Type II: Granular Pattern (Immune Complex Disease) - 40% of RPGN ##### Associated Conditions ###### Systemic Lupus Erythematosus - Most common cause in this category - Class IV lupus nephritis - Requires aggressive immunosuppression ###### IgA Nephropathy - Crescents alone do not define rapidly progressive IgAN - Rapid functional decline requires urgent biopsy and specialist selection of treatment - Monitor for progression ###### Post-Infectious GN - Usually self-limiting - Prioritize infection treatment and kidney supportive care; routine immunosuppression is generally inadvisable - Supportive care in most cases ###### Other - Cryoglobulinemia - Endocarditis - MPGN #### Type III: Pauci-Immune (ANCA-Associated) - 50% of RPGN ##### ANCA Patterns and Associated Vasculitides ###### P-ANCA/MPO - Microscopic Polyangiitis (MPA) - More likely renal involvement (80%) - Pulmonary-renal syndrome - Diffuse capillaritis ###### C-ANCA/PR3 - Granulomatosis with Polyangiitis (GPA) - Upper respiratory tract involvement - Pulmonary nodules - Necrotizing granulomatous inflammation ##### Emergency Treatment Protocol 1 **Corticosteroids:** IV methylprednisolone 0.5-1 g/day for 3 days, followed by oral prednisone 1 mg/kg for 1 month 2 **Induction Immunosuppression:** Cyclophosphamide (IV 15 mg/kg or oral 1.5-2 mg/kg daily) OR Rituximab (375 mg/mΒ² weekly for 4 doses) 3 **Plasmapheresis Indications:** Serum creatinine \>4 mg/dL, dialysis dependence, pulmonary hemorrhage, concomitant anti-GBM antibodies 4 **Avacopan β€” historical evidence update:** The pivotal ADVOCATE report ([PMID 33596356; RETRACTED](https://pubmed.ncbi.nlm.nih.gov/33596356/)) was retracted in 2026 ([retraction notice](https://pubmed.ncbi.nlm.nih.gov/42377355/)). Its efficacy claims should not guide treatment. FDA proposed withdrawal on April 27, 2026; this proposal is not a completed withdrawal. Review current status and alternatives with the treating specialist ([FDA notice](https://www.fda.gov/drugs/drug-alerts-and-statements/cder-proposes-withdraw-approval-tavneos)). ##### Maintenance Therapy - **Azathioprine:** 2 mg/kg/day - **Mycophenolate mofetil:** 1g twice daily - **Rituximab:** 500mg every 6 months - **Duration:** Minimum 18-24 months ### Emergency Action Plan for PA Students 1 **Recognition:** Rapidly worsening kidney function with active sediment or systemic features needs immediate evaluation; do not wait for a 50% GFR loss 2 **Immediate Actions:** STAT nephrology consultation, fresh urine microscopy for RBC casts, STAT labs (creatinine, CBC, ANCA, anti-GBM), assess for systemic features 3 **Stabilization:** Manage fluid balance and electrolytes, control blood pressure, prepare for possible dialysis, consider empiric treatment if high suspicion 4 **Definitive Care:** Follow nephrology recommendations, monitor for treatment complications, coordinate multidisciplinary care, long-term follow-up planning ### πŸ“Š RPGN Classification Summary | Type | Pattern | Main Causes | % of RPGN | Treatment Priority | |----|----|----|----|----| | Type I | Linear (Anti-GBM) | Goodpasture's, Anti-GBM nephritis | 10% | Plasmapheresis + Immunosuppression | | Type II | Granular (IC) | Lupus, Post-infectious, IgA | 40% | Treat underlying cause | | Type III | Pauci-immune | ANCA-associated vasculitis | 50% | Steroids + Cyclophosphamide/Rituximab | ## πŸ†• New and Emerging Treatments ### Biologics and Monoclonal Antibodies #### Rituximab - Anti-CD20 monoclonal antibody - Effective steroid-sparing agent - First-line for membranous nephropathy - Pediatric and adult efficacy #### Daratumumab - Anti-CD38 monoclonal antibody - Targets long-lived plasma cells - Being studied in combination with rituximab - Novel approach to B-cell targeting ### Gene Therapy #### Podocyte-Targeted Gene Therapy - Experimental AAV gene delivery studied in human cell and mouse models of NPHS2-related nephrotic syndrome - Restored podocin expression and improved disease measures in those experimental models - Preclinical findings do not establish clinical benefit or safety in people - The 2023 study does not demonstrate a human cure or an available routine treatment ([primary study](https://pubmed.ncbi.nlm.nih.gov/37556557/)) ### Epigenetic Therapies #### HDAC Inhibitors - Anti-fibrotic and anti-inflammatory effects - May attenuate renal sclerosis and proteinuria - Multiple agents under investigation #### Network Pharmacology - Valproic acid and all-trans retinoic acid - Target epigenetic mechanisms - May promote disease regression ## πŸ”„ Secondary Causes of Glomerular Disease ### Systemic Diseases - **Diabetic nephropathy** (most common overall) - **Amyloidosis** (AL, AA, or hereditary) - **Lupus nephritis** - **Multiple myeloma** ### Infections - **Hepatitis B** (membranous pattern) - **Hepatitis C** (MPGN pattern) - **HIV** (collapsing FSGS) - **Syphilis, malaria** ### Medications - **NSAIDs** (MCD pattern) - **Gold, penicillamine** - **Immune checkpoint inhibitors** - **Interferon** ### Malignancies - **Solid tumors** (lung, breast, GI) - **Hodgkin lymphoma** (MCD pattern) - **Non-Hodgkin lymphoma** ## 🎯 Clinical Pearls for PA Practice #### Emergency Recognition **RPGN Emergency:** Suspected RPGN with rapid kidney-function decline needs immediate nephrology consultation. Do not wait for a percentage GFR threshold, urine microscopy results, or a completed biopsy before escalating care. #### RBC Casts Require Clinical Correlation RBC casts strongly support glomerular bleeding and prompt a glomerular workup, but do not identify its cause. Examine fresh urine when possible; absence of casts does not exclude GN. #### Complement Testing Strategy Often-normal C3/C4 suggests ANCA-associated, IgA, or anti-GBM disease; low C3 with relatively preserved C4 suggests infection-related GN or C3 glomerulopathy; low C3/C4 suggests lupus or other immune-complex disease. Exceptions occur; use clinical features, serology, and biopsy. #### ANCA Clinical Correlation C-ANCA with sinusitis + lung nodules + active urine sediment = 98% PPV for GPA. Always correlate ANCA results with clinical presentation. #### Nephrotic Syndrome Complications Watch for thromboembolism (hypercoagulable state), infections (immunoglobulin loss), and protein malnutrition. Consider prophylactic anticoagulation. #### Anti-PLA2R Testing Positive anti-PLA2R with nephrotic syndrome can diagnose membranous nephropathy without biopsy (78% sensitivity, 99% specificity). #### Serial Complement Testing Follow C3/C4 trends when relevant to the suspected disease, alongside creatinine, quantified proteinuria, urine sediment, and clinical findings. Complement trends alone cannot establish activity or treatment response. #### Fresh Urine is Critical RBC casts may dissolve in older urine specimens. Examine fresh urine (\<2 hours) when possible for accurate diagnosis. #### Anticoagulation Decision Assess thrombosis risk against bleeding risk individually, including the underlying disease, severity of hypoalbuminemia, prior thrombosis, and contraindications. A low albumin value alone is not an automatic anticoagulation order. #### Treatment Response Monitoring In PLA2R-positive membranous nephropathy, the goal should be complete disappearance of anti-PLA2R antibodies. #### Secondary Cause Screening Always screen adults with new nephrotic syndrome for secondary causes, especially malignancy and systemic disease. #### Pulmonary-Renal Syndrome Hemoptysis plus rapidly declining kidney function = medical emergency. Consider anti-GBM disease, ANCA vasculitis, or SLE. ## πŸ”„ Diagnostic Algorithm for Glomerular Disease 1 **Suspect and Evaluate Glomerular Disease:** Hematuria + proteinuria Β± hypertension Β± reduced GFR; quantify protein and assess the clinical trajectory 2 **Urine Microscopy:** Look for RBC casts and acanthocytes as clues to glomerular bleeding, plus oval fat bodies and fatty casts for lipiduria; sediment alone does not identify the immune mechanism 3 **Classify Syndrome:** Nephritic (inflammatory) vs Nephrotic (proteinuric) vs Mixed 4 **Complement Testing:** Measure C3 and C4 simultaneously to determine pathway activation 5 **Targeted Serological Testing:** Based on complement pattern and clinical presentation (ANCA, anti-GBM, ANA, anti-PLA2R) 6 **Assess Urgency:** Rapid kidney-function decline with suspected GN or pulmonary–renal features requires immediate nephrology assessment; do not wait for 50% GFR loss 7 **Arrange Renal Biopsy:** Promptly when suspected RPGN or when histology will change management; review activity and chronicity, and investigate infection before immunosuppression ## πŸ“š Related Educational Modules ### 🧬 Systemic Lupus Erythematosus & Lupus Nephritis Comprehensive guide to SLE diagnosis, classification, and treatment with interactive 2019 EULAR/ACR criteria calculator, ISN/RPS classification system, and evidence-based treatment protocols. [πŸ“‹ Study SLE Module](https://urinenephrology.org/2025_UDPA_Lectures_Live/glomerulonephritis/SLE.html) [πŸ“‹ Case 7: Lupus Nephritis](https://urinenephrology.org/2025_UDPA_Lectures_Live/cases/case7_enhanced.html) ### 🚨 RPGN & ANCA Vasculitis: Comprehensive Review Rapidly progressive glomerulonephritis and ANCA-associated vasculitis - emergency recognition, classification, and evidence-based management. [πŸ“‹ Study RPGN & ANCA Module](https://urinenephrology.org/2025_UDPA_Lectures_Live/glomerulonephritis/rpgn-anca-vasculitis.html) ### πŸ”¬ Kidney Biopsy Interpretation Guide Comprehensive guide to renal biopsy findings - light microscopy, immunofluorescence, and electron microscopy patterns in glomerular disease. [πŸ“‹ Study Biopsy Guide](https://urinenephrology.org/2025_UDPA_Lectures_Live/glomerulonephritis/biopsy-interpretation.html) ### πŸ’Š Immunosuppression Protocols in Glomerular Disease Evidence-based immunosuppressive regimens for glomerulonephritis - induction, maintenance, and monitoring strategies. [πŸ“‹ Study Immunosuppression Protocols](https://urinenephrology.org/2025_UDPA_Lectures_Live/glomerulonephritis/immunosuppression-protocols.html) ### πŸ”¬ Additional Glomerular Disease Topics - **IgA Nephropathy** - Most common primary GN worldwide - **Anti-GBM Disease** - Goodpasture syndrome - **Membranous Nephropathy** - Anti-PLA2R testing - **FSGS and Minimal Change** - Nephrotic syndrome causes *Additional modules coming soon...* ## πŸ“– Evidence-Based Resources ### πŸ† Priority Resources - **KDIGO GN Guidelines 2024** - Latest evidence-based recommendations for glomerulonephritis management - **NKF Clinical Guidelines** - National Kidney Foundation practice guidelines - **RPGN Emergency Protocol** - Rapid reference for nephrology emergencies ### πŸ“š Additional Reading - American Journal of Kidney Diseases - Latest research updates - Kidney International - Peer-reviewed nephrology research - Clinical Journal of the American Society of Nephrology - UpToDate - Current clinical recommendations ## πŸ“š Sources 1. **Rovin BH, Adler SG, Barratt J, et al; KDIGO Glomerular Diseases Work Group.** KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases. *Kidney Int.* 2021;100(4S):S1-S276. [PMID: 34556256](https://pubmed.ncbi.nlm.nih.gov/34556256/). *β€” Foundational KDIGO 2021 GD guideline covering IgAN, lupus nephritis, MCD, FSGS, MN, ANCA vasculitis, anti-GBM disease.* 2. **Barratt J, Lafayette R, Kristensen J, et al; NefIgArd Trial Investigators.** Results from part A of the multi-center, double-blind, randomized, placebo-controlled NefIgArd trial (TARPEYO). *Kidney Int.* 2023;103(2):391-402. [PMID: 36270561](https://pubmed.ncbi.nlm.nih.gov/36270561/). *β€” Targeted-release budesonide (Tarpeyo) in IgAN.* 3. **Heerspink HJL, Radhakrishnan J, Alpers CE, et al; PROTECT Investigators.** Sparsentan in patients with IgA nephropathy: a prespecified interim analysis from a randomised, double-blind, active-controlled clinical trial. *Lancet.* 2023;401(10388):1584-1594. [PMID: 37015244](https://pubmed.ncbi.nlm.nih.gov/37015244/). *β€” PROTECT trial; sparsentan dual ET-A/AT1 antagonist in IgAN.* 4. **Trimarchi H, Barratt J, Cattran DC, et al.** Oxford Classification of IgA nephropathy 2016: an update from the IgA Nephropathy Classification Working Group. *Kidney Int.* 2017;91(5):1014-1021. [PMID: 28341274](https://pubmed.ncbi.nlm.nih.gov/28341274/). *β€” Oxford 2016 update β€” MEST-C scoring including C lesions.* 5. Furie RA, Aroca G, Cascino MD, et al. B-cell depletion with obinutuzumab for the treatment of proliferative lupus nephritis: a randomised, double-blind, placebo-controlled trial. *Ann Rheum Dis*. 2022;81(1):100-107. [DOI](https://doi.org/10.1136/annrheumdis-2021-220920) \| [PubMed](https://pubmed.ncbi.nlm.nih.gov/34615636/) . *β€” Phase 2 obinutuzumab + standard-of-care vs SOC in proliferative lupus nephritis. CRR at week 76 approximately 35-38%.* 6. **Rovin BH, Teng YKO, Ginzler EM, et al; AURORA 1 Investigators.** Efficacy and safety of voclosporin versus placebo for lupus nephritis (AURORA 1): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial. *Lancet.* 2021;397(10289):2070-2080. [PMID: 33971155](https://pubmed.ncbi.nlm.nih.gov/33971155/). *β€” AURORA 1 voclosporin in active lupus nephritis.* 7. **Houssiau FA, Vasconcelos C, D'Cruz D, et al.** Immunosuppressive therapy in lupus nephritis: the Euro-Lupus Nephritis Trial. *Arthritis Rheum.* 2002;46(8):2121-2131. [PMID: 12209517](https://pubmed.ncbi.nlm.nih.gov/12209517/). *β€” Euro-Lupus low-dose IV cyclophosphamide regimen.* 8. **Stone JH, Merkel PA, Spiera R, et al; RAVE-ITN Research Group.** Rituximab versus cyclophosphamide for ANCA-associated vasculitis (RAVE). *N Engl J Med.* 2010;363(3):221-232. [PMID: 20647199](https://pubmed.ncbi.nlm.nih.gov/20647199/). *β€” Rituximab non-inferior to cyclophosphamide in ANCA-associated vasculitis induction.* 9. **Glomerular Hematuria for the Diagnosis of Glomerulonephritis.** Biopsy-correlated diagnostic study. [PMID: 40406196](https://pubmed.ncbi.nlm.nih.gov/40406196/). Urine sediment supports diagnosis; its sensitivity and specificity are not absolute. 10. **KDIGO 2024 ANCA-Associated Vasculitis Guideline.** [Official guideline](https://kdigo.org/wp-content/uploads/2024/02/KDIGO-2024-ANCA-Vasculitis-Guideline.pdf). Practice Point 9.1.1: in a compatible rapidly deteriorating presentation with MPO/PR3-ANCA, awaiting biopsy must not delay specialist-directed treatment. 11. **KDIGO 2025 IgAN/IgAV Guideline.** [Official guideline](https://kdigo.org/guidelines/iga-nephropathy/). Crescents without functional deterioration do not alone establish rapidly progressive IgAN. 12. **KDIGO infection-related GN guidance.** [Official clinical takeaways](https://kdigo.org/wp-content/uploads/2017/02/Key-Takeaways-Infection-related-Glomerulonephritis-GD-GL-Clinicians.pdf). Treat infection and provide kidney supportive care; immunosuppression is generally inadvisable. --- [Website version](https://urinenephrology.org/2025_UDPA_Lectures_Live/glomerulonephritis/index.html) Β· Markdown synchronized October 3, 2026.