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Ostermayer: Created page with "Lupus nephritis (LN) is '''renal involvement in Systemic lupus erythematosus''', caused by deposition of immune complexes in the glomeruli, which activates complement and causes inflammation, scarring, and progressive kidney damage.Lupus Nephritis. ''StatPearls''. NCBI. 2025. It is '''clinically evident in 50-60% of SLE patients''' and is histologically present in the majority, even those without clinical signs of renal disease.
2026-03-18T02:27:11Z

Created page with "Lupus nephritis (LN) is '''renal involvement in Systemic lupus erythematosus''', caused by deposition of immune complexes in the glomeruli, which activates complement and causes inflammation, scarring, and progressive kidney damage.<ref name="StatPearls">Lupus Nephritis. ''StatPearls''. NCBI. 2025.</ref> It is '''clinically evident in 50-60% of SLE patients''' and is histologically present in the majority, even those without clinical signs of renal disease.<ref name=..."

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Lupus nephritis (LN) is '''renal involvement in [[Systemic lupus erythematosus]]''', caused by deposition of immune complexes in the glomeruli, which activates complement and causes inflammation, scarring, and progressive kidney damage.<ref name="StatPearls">Lupus Nephritis. ''StatPearls''. NCBI. 2025.</ref> It is '''clinically evident in 50-60% of SLE patients''' and is histologically present in the majority, even those without clinical signs of renal disease.<ref name="Medscape_LN">Lupus Nephritis. ''Medscape''. 2025.</ref> Lupus nephritis is a '''major determinant of SLE prognosis''' — untreated proliferative disease (class III/IV) leads to '''end-stage kidney disease (ESKD)''' in a substantial proportion of patients. The emergency physician encounters LN as '''new-onset [[Nephritic syndrome|nephritic]] or [[Nephrotic syndrome|nephrotic]] syndrome in a patient with SLE features''', '''acute renal failure during a lupus flare''', or '''complications of immunosuppressive therapy''' (infection, cytopenias).

==Background==
SLE predominantly affects '''women of childbearing age''' (female-to-male ratio 9:1); lupus nephritis typically presents at ages '''20-40 years'''<ref name="Medscape_LN"/>
'''Higher incidence and more severe disease''' in African Americans, Hispanics, and Asians
Males with SLE have a '''higher rate of renal involvement''' and '''worse prognosis''' than females
Children with SLE have '''more frequent and more aggressive''' renal disease than adults
Lupus nephritis usually arises '''within the first 5 years''' of SLE diagnosis; may be the '''presenting manifestation''' of SLE
'''Delayed diagnostic biopsy >6 months''' is associated with a 9-fold increased risk of ESKD<ref name="TenTips">Ten tips in lupus nephritis management. ''Rheumatology''. 2025. PMC11770280.</ref>

===ISN/RPS Classification (determines treatment and prognosis)===
{| class="wikitable"
|-
! Class !! Description !! Clinical significance
|-
| '''I''' || Minimal mesangial || Normal urinalysis; no treatment needed; excellent prognosis
|-
| '''II''' || Mesangial proliferative || Microscopic hematuria ± mild proteinuria; usually mild; glucocorticoids if needed
|-
| '''III''' || Focal proliferative (<50% of glomeruli) || '''Active nephritis'''; hematuria, proteinuria, rising creatinine; '''requires immunosuppression'''
|-
| '''IV''' || '''Diffuse proliferative''' (≥50% of glomeruli) || '''Most common and most severe'''; nephritic ± nephrotic features; highest risk of ESKD; '''aggressive immunosuppression required'''
|-
| '''V''' || Membranous || '''Nephrotic syndrome''' predominates; proteinuria may be massive; may overlap with III/IV
|-
| '''VI''' || Advanced sclerotic (>90% sclerosed) || '''ESKD'''; irreversible; renal replacement therapy; immunosuppression not helpful
|}

'''Class IV is the most common biopsy finding''' and carries the worst untreated prognosis
'''Mixed classes''' (III/V or IV/V) have features of both proliferative and membranous disease
'''Class can transform''' — mild disease may progress to severe proliferative disease; repeat biopsy may be needed for flares

===Mechanism===
Anti-dsDNA and other autoantibodies form immune complexes → deposit in mesangium and glomerular capillary walls
Complement activation (classical pathway) → C3, C4 consumption → '''low serum C3 and C4'''
Inflammation → cellular proliferation, crescent formation, fibrinoid necrosis
Chronic inflammation → sclerosis and irreversible nephron loss

==Clinical features==
===Presentations the EM physician will encounter===

====New-onset renal disease in a known SLE patient====
Hematuria (gross or microscopic), proteinuria (detected on urinalysis)
Edema (periorbital, lower extremity, or generalized if nephrotic)
Hypertension (new or worsening)
Rising creatinine, decreased urine output
Often concurrent with '''other signs of lupus flare:''' fever, malar rash, arthritis, oral ulcers, pleurisy, pericarditis, cytopenias

====SLE presenting with renal disease as the first manifestation====
Young woman with '''unexplained nephritic or nephrotic syndrome'''
May have undiagnosed SLE — look for constitutional symptoms, rash, arthritis, photosensitivity, oral ulcers, alopecia, serositis
'''Any young woman with GN should be tested for SLE'''

====Lupus nephritis flare====
Known LN patient with '''worsening proteinuria, rising creatinine, new hematuria, or declining complement levels'''
May be triggered by medication noncompliance, infection, pregnancy, UV exposure
'''Rising anti-dsDNA + falling C3/C4''' often precedes clinical flare by weeks

====Rapidly progressive glomerulonephritis (RPGN)====
'''Class IV with crescents''' — renal function deteriorates over days to weeks
Nephritic sediment + rapidly rising creatinine
'''Nephrology emergency''' — urgent biopsy and aggressive immunosuppression needed

====Complications of immunosuppressive treatment====
'''Infection:''' the most common cause of death in actively treated LN patients; opportunistic infections from cyclophosphamide, mycophenolate, rituximab, steroids
'''Cytopenias:''' from cyclophosphamide, mycophenolate, azathioprine; may present with neutropenic fever
'''Steroid side effects:''' hyperglycemia, psychosis, adrenal crisis on abrupt withdrawal, AVN of femoral head
'''Thrombotic microangiopathy (TMA):''' may occur in LN, especially with '''antiphospholipid antibodies''' — presents with microangiopathic hemolytic anemia, thrombocytopenia, renal failure; consider concurrent antiphospholipid syndrome

===Key clinical signs suggesting SLE in an undiagnosed patient===
'''Malar (butterfly) rash''' — erythematous rash over cheeks/nasal bridge sparing nasolabial folds
'''Photosensitivity'''
'''Oral/nasal ulcers''' (often painless)
'''Arthritis/arthralgias''' (symmetric, non-erosive)
'''Serositis''' (pleuritis, pericarditis)
'''Alopecia'''
'''Raynaud phenomenon'''
'''Cytopenias:''' leukopenia, lymphopenia, thrombocytopenia, hemolytic anemia (Coombs-positive)

==Differential diagnosis==
===Nephritic/nephrotic syndrome in a young patient===
'''Lupus nephritis''' (this page)
'''IgA nephropathy''' — most common GN worldwide; synpharyngitic hematuria; '''normal complement'''
'''Post-streptococcal GN''' — post-infectious latent period; low C3 (normalizes in 6-8 weeks)
'''ANCA-associated vasculitis''' (GPA, MPA) — ANCA positive; '''normal complement'''
'''Anti-GBM disease''' — anti-GBM antibodies; '''normal complement'''; may have pulmonary hemorrhage
'''MPGN / C3 glomerulopathy''' — persistently low C3
'''[[Focal segmental glomerulosclerosis]]''' — nephrotic; biopsy diagnosis; normal complement
'''Minimal change disease''' — nephrotic; steroid-responsive; normal complement
'''Membranous nephropathy''' — nephrotic; may be secondary to SLE, malignancy, hepatitis B
'''Thrombotic thrombocytopenic purpura (TTP)''' — MAHA, thrombocytopenia, AKI, fever, neurologic changes; can coexist with SLE
'''Antiphospholipid syndrome nephropathy''' — may occur with or without SLE; TMA pattern

===Lupus nephritis complement pattern===
'''Low C3 AND low C4''' is characteristic of active lupus nephritis (classical pathway activation)
Distinguishes from PSGN (low C3, usually normal or slightly low C4) and ANCA/anti-GBM disease (normal complement)

==Evaluation==
===ED workup===
'''Urinalysis with microscopy:''' hematuria (dysmorphic RBCs, RBC casts), proteinuria, sterile pyuria
'''Spot urine protein:creatinine ratio:''' quantifies proteinuria; nephrotic range (>3.5) suggests class V or severe III/IV
'''BMP/CMP:''' creatinine (baseline and trending), BUN, potassium (hyperkalemia risk), bicarbonate
'''CBC:''' cytopenias (leukopenia, lymphopenia, thrombocytopenia, Coombs-positive hemolytic anemia — all support SLE diagnosis)
'''Albumin:''' low if nephrotic
'''Blood pressure:''' hypertension common in active disease

===SLE serologic workup (initiate from ED)===
{| class="wikitable"
|-
! Test !! Significance
|-
| '''ANA''' || Sensitive screening test for SLE (>95% positive); not specific; negative ANA makes SLE very unlikely
|-
| '''Anti-dsDNA''' || Highly specific for SLE; '''correlates with disease activity and renal involvement'''; rising titers predict flare
|-
| '''C3, C4 complement''' || '''Low C3 AND low C4''' = active lupus nephritis (classical pathway consumption); serial monitoring useful for tracking flare activity
|-
| '''Anti-Smith (anti-Sm)''' || Highly specific for SLE (but less sensitive than anti-dsDNA)
|-
| '''Antiphospholipid antibodies''' (anticardiolipin, lupus anticoagulant, anti-β2-glycoprotein I) || Identify concurrent antiphospholipid syndrome → increased thrombosis risk, TMA
|-
| '''ESR, CRP''' || Often elevated; ESR tends to track disease activity in SLE (CRP may be normal unless infection or serositis is present)
|}

'''Trend creatinine:''' compare to baseline; a rising creatinine with active sediment suggests active nephritis
'''Renal ultrasound:''' normal or enlarged kidneys in acute disease; small kidneys suggest chronic damage

===Renal biopsy===
'''Gold standard''' for diagnosis and classification — determines ISN/RPS class, activity/chronicity indices, and guides treatment<ref name="PMC_LN">Understanding lupus nephritis: diagnosis, management, and treatment options. ''Int J Womens Health''. 2012;4:213-222. PMC3367406.</ref>
'''Not performed in the ED''' — arranged by nephrology
Indications: new-onset proteinuria (>500 mg/day), active urinary sediment, rising creatinine, suspected flare in known LN patient
'''Biopsy results fundamentally change management''' — mild mesangial disease (class I/II) needs minimal treatment; diffuse proliferative disease (class IV) requires aggressive immunosuppression

==Management==
===ED management of acute lupus nephritis/flare===
'''Manage life-threatening complications first:'''
'''Hypertensive emergency:''' IV antihypertensives (nicardipine, labetalol); loop diuretics for volume overload (see [[Hypertensive emergency]])
'''Hyperkalemia:''' standard protocols (see [[Hyperkalemia]])
'''Pulmonary edema:''' furosemide, oxygen, positive pressure ventilation
'''Severe AKI:''' urgent dialysis if refractory hyperkalemia, acidosis, volume overload, or uremic symptoms
'''Fluid and sodium restriction''' if edematous or volume-overloaded
'''Loop diuretics''' (furosemide) for edema and volume-mediated hypertension
'''Do NOT start immunosuppressive therapy in the ED''' — this requires biopsy-guided decision-making by nephrology/rheumatology
'''Exception:''' if RPGN is strongly suspected (rapidly rising creatinine + active sediment), '''pulse IV methylprednisolone''' (500-1000 mg) may be initiated after nephrology telephone consultation while biopsy is arranged — time is critical for kidney survival

===Medication safety in the ED===
'''Continue hydroxychloroquine''' — it should not be discontinued; it reduces flare risk and has renal-protective effects<ref name="StatPearls"/>
'''Continue existing immunosuppressants''' unless the patient is septic (in which case, hold immunosuppression and consult rheumatology/nephrology)
'''Avoid NSAIDs''' — nephrotoxic; may worsen renal function and hypertension
'''Avoid nephrotoxic agents:''' aminoglycosides, IV contrast (if possible; discuss risk-benefit if imaging is critical)
'''ACE inhibitors/ARBs:''' standard chronic therapy for proteinuria reduction; may need to be held in acute AKI with hyperkalemia

===Disease-specific treatment (nephrology/rheumatology-directed)===
'''All classes:''' hydroxychloroquine (background therapy) + ACE inhibitor/ARB (for proteinuria >500 mg/day)
'''Class I/II:''' monitoring; glucocorticoids for flare; no immunosuppression usually needed
*'''Class III/IV (and mixed III/V, IV/V):'''
'''Induction:''' glucocorticoids + mycophenolate mofetil (first-line) OR IV cyclophosphamide (for severe/refractory disease)
Pulse IV methylprednisolone (500-1000 mg daily for 3 days) followed by oral prednisone taper
**'''Maintenance:''' mycophenolate mofetil (superior to azathioprine) for '''at least 3 years'''
'''Class V (membranous):''' glucocorticoids + mycophenolate mofetil; ACE inhibitor/ARB
'''Class VI:''' renal replacement therapy (dialysis or transplant); immunosuppression not indicated
'''Newer agents:''' belimumab (anti-BAFF; FDA-approved for LN as add-on therapy), voclosporin (calcineurin inhibitor; FDA-approved for LN), rituximab (B-cell depletion; used for refractory disease)

==Disposition==
'''Admit:'''
New-onset lupus nephritis with significant proteinuria, active sediment, or elevated creatinine
Lupus nephritis flare with worsening renal function
RPGN or rapidly rising creatinine — '''urgent nephrology consultation'''
Severe hypertension, hyperkalemia, pulmonary edema
Concurrent severe lupus flare involving other organs (cerebritis, pulmonary hemorrhage, severe cytopenias, serositis)
Infection in an immunosuppressed LN patient
*'''Discharge with close follow-up:'''
Known stable LN patient with mild abnormality on labs and no significant change from baseline
Ensure '''nephrology AND rheumatology follow-up within 48-72 hours'''
**Emphasize medication compliance (especially hydroxychloroquine and immunosuppressants)
*'''Counseling points:'''
'''Never stop hydroxychloroquine''' without specialist guidance — discontinuation increases flare risk
Sun protection (UV exposure triggers SLE flares)
Report signs of flare: edema, decreased urine output, foamy/bloody urine, joint pain, rash, fever
Report signs of infection immediately (immunosuppressed patients)
**'''Pregnancy planning:''' lupus nephritis has major implications for pregnancy; active disease should be in remission before conception; requires close coordination with maternal-fetal medicine, nephrology, and rheumatology

==See Also==
[[Nephritic syndrome]]
[[Nephrotic syndrome]]
[[Focal segmental glomerulosclerosis]]
[[Acute kidney injury]]
[[Hypertensive emergency]]
[[Hyperkalemia]]
[[Systemic lupus erythematosus]]
[[Antiphospholipid syndrome]]
[[Goodpasture syndrome]]
[[Thrombotic thrombocytopenic purpura]]

==External Links==
[https://www.ncbi.nlm.nih.gov/books/NBK499817/ StatPearls — Lupus Nephritis]
[https://emedicine.medscape.com/article/330369-overview Medscape — Lupus Nephritis]
[https://pmc.ncbi.nlm.nih.gov/articles/PMC3367406/ Int J Womens Health — Understanding lupus nephritis: diagnosis, management, and treatment options (2012)]
[https://pmc.ncbi.nlm.nih.gov/articles/PMC11770280/ Rheumatology — Ten tips in lupus nephritis management (2025)]
*[https://www.kidney-international.org/article/S0085-2538(17)30859-1/fulltext Kidney Int — Revision of the ISN/RPS classification for lupus nephritis (2018)]

==References==
<references/>

[[Category:Renal]]
[[Category:Rheumatology]]

Lupus nephritis - Revision history

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