Nephritic syndrome

Nephritic syndrome is a clinical syndrome resulting from glomerular inflammation (glomerulonephritis), characterized by hematuria (with dysmorphic RBCs and RBC casts), hypertension, oliguria, edema, and subnephrotic proteinuria. It is distinguished from Nephrotic syndrome primarily by the presence of hematuria and active urinary sediment. The EM physician encounters nephritic syndrome as "cola-colored" urine in a child 1-3 weeks after a sore throat (post-streptococcal GN), acute renal failure with hypertension and pulmonary edema, or hemoptysis with renal failure (pulmonary-renal syndrome). The key ED tasks are to recognize the syndrome via urinalysis, manage life-threatening complications (hypertensive emergency, hyperkalemia, pulmonary edema, AKI), identify rapidly progressive glomerulonephritis (RPGN) as a true emergency requiring immediate nephrology involvement, and initiate targeted serologic workup.

Background

• Nephritic syndrome is a pattern of glomerular disease, not a single diagnosis — many diseases present this way
• Children: post-streptococcal glomerulonephritis (PSGN) is the most common cause
• Adults: IgA nephropathy, lupus nephritis, ANCA-associated vasculitis, and infection-associated GN are more common
• The distinction between nephritic and nephrotic syndromes is fundamental to the ED evaluation of renal disease:

Feature	Nephritic syndrome	Nephrotic syndrome
Primary mechanism	Glomerular inflammation	Podocyte injury (permeability defect)
Hematuria	Prominent (dysmorphic RBCs, RBC casts)	Absent or minimal
Proteinuria	Subnephrotic (<3.5 g/day)	Nephrotic-range (>3.5 g/day)
Edema	Mild-moderate (volume overload)	Severe (hypoalbuminemia)
Hypertension	Prominent (salt/water retention)	Variable
Serum albumin	Normal or mildly low	Markedly low (<3.0 g/dL)
Hyperlipidemia	Absent	Present
Urine sediment	Active: RBC casts, dysmorphic RBCs, WBCs	Bland: oval fat bodies, fatty casts; no RBC casts
Renal function	Often impaired (elevated creatinine)	Usually preserved early

• Some diseases (MPGN, lupus nephritis, FSGS) can present with overlap features of both syndromes

Clinical features

Classic acute nephritic syndrome

• Hematuria: "cola-colored," "tea-colored," or "smoky" urine (gross hematuria); or microscopic hematuria
• Edema: periorbital (especially on waking), lower extremity; mild to moderate
• Hypertension: from sodium/water retention and intravascular volume expansion; may be severe
• Oliguria: reduced urine output (<400 mL/day in adults; <0.5 mL/kg/hr in children)
• Proteinuria: present but usually subnephrotic
• Malaise, fatigue, anorexia, nausea
• Flank or abdominal pain (especially in children)
• Onset is often abrupt (days to 1-2 weeks)

Post-streptococcal glomerulonephritis (PSGN) — the prototype

• Most common cause in children (ages 5-12 years); declining incidence in developed countries
• Latent period: 1-2 weeks after pharyngitis; 3-6 weeks after skin infection (pyoderma/impetigo)
• Not present during the infection — symptoms appear after a latent period (distinguishes from IgA nephropathy, which is synpharyngitic)
• Gross hematuria in >50% of cases; "smoky" or "cola-colored" urine
• Edema and hypertension from salt/water retention
• Low C3 complement (returns to normal within 6-8 weeks — failure to normalize suggests MPGN or C3 glomerulopathy)
• Usually self-limited in children (>95% recover completely); adults have worse prognosis

IgA nephropathy (Berger disease) — the most common GN worldwide

• Synpharyngitic hematuria: gross hematuria occurring within 1-2 days of an upper respiratory infection (NOT after a latent period — key distinction from PSGN)
• Recurrent episodes of gross hematuria
• Between episodes: persistent microscopic hematuria ± proteinuria
• Normal complement levels (unlike PSGN)
• May overlap with Henoch-Schönlein purpura (IgA vasculitis) — systemic form with palpable purpura, arthritis, abdominal pain, and GN

Rapidly progressive glomerulonephritis (RPGN) — the EM emergency

• Defines >50% loss of renal function within 3 months
• Nephritic sediment + rapidly rising creatinine over days to weeks
• Pathologic hallmark: crescent formation in glomeruli on biopsy
• Three immunologic categories:

Type	Mechanism	Classic disease	Key lab findings
Type I (anti-GBM)	Anti-glomerular basement membrane antibodies	Goodpasture syndrome (anti-GBM + pulmonary hemorrhage)	Anti-GBM antibodies positive; complement normal
Type II (immune complex)	Immune complex deposition	Lupus nephritis, PSGN (severe), IgA nephropathy, MPGN, endocarditis-related	ANA, anti-dsDNA (lupus); low complement (C3, C4); cryoglobulins
Type III (pauci-immune)	ANCA-associated vasculitis (minimal immune deposits)	Granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA)	ANCA positive (c-ANCA/PR3 for GPA; p-ANCA/MPO for MPA); complement normal

• RPGN is a true nephrology emergency — delay in treatment leads to irreversible ESKD
• Requires immediate nephrology consultation, renal biopsy, and aggressive immunosuppression ± plasma exchange

Pulmonary-renal syndrome

• Hemoptysis + nephritic syndrome = pulmonary-renal syndrome until proven otherwise
• Causes: Goodpasture syndrome (anti-GBM), GPA, MPA, lupus, cryoglobulinemia
• May present with diffuse alveolar hemorrhage (DAH): hemoptysis, dyspnea, bilateral infiltrates on CXR, dropping hemoglobin
• Life-threatening — requires ICU admission, urgent nephrology and pulmonology consultation

Differential diagnosis

By complement level (high-yield ED approach)

Low C3 (hypocomplementemic)

• Post-streptococcal GN (low C3; C4 normal or slightly low; normalizes by 6-8 weeks)
• Lupus nephritis (low C3 AND C4)
• MPGN / C3 glomerulopathy (persistently low C3)
• Endocarditis-associated GN (low C3; blood cultures positive)
• Cryoglobulinemic GN (low C3 and C4; hepatitis C associated)

Normal complement

• IgA nephropathy
• ANCA-associated vasculitis (GPA, MPA)
• Anti-GBM disease (Goodpasture)
• Henoch-Schönlein purpura
• Hereditary nephritis (Alport syndrome)

Non-glomerular causes of hematuria to exclude

• Urinary tract infection (positive urine culture; normal RBC morphology)
• Nephrolithiasis (flank pain; isomorphic RBCs; no casts)
• Trauma
• Urologic malignancy (adults; painless hematuria)
• Menstrual contamination
• Exercise-induced hematuria

Key to glomerular vs non-glomerular hematuria

• Glomerular: dysmorphic RBCs (acanthocytes), RBC casts (virtually pathognomonic), proteinuria, brown/cola-colored urine, no clots
• Non-glomerular: normal/isomorphic RBCs, no casts, pink/red urine, may have clots

Evaluation

ED workup

• Urinalysis with microscopy: the single most important test
  • RBC casts: virtually pathognomonic for glomerulonephritis
  • Dysmorphic RBCs (acanthocytes — best seen with phase-contrast microscopy; >30% dysmorphic is highly specific for glomerular origin)
  • Proteinuria (usually 1-3+ on dipstick)
  • Sterile pyuria (WBCs without bacteria)
• BMP/CMP:
  • Creatinine (elevated = impaired GFR; trending creatinine is critical for identifying RPGN)
  • Potassium (hyperkalemia from impaired excretion — potentially life-threatening)
  • Bicarbonate (metabolic acidosis)
  • BUN (elevated; disproportionately elevated BUN:creatinine ratio in prerenal azotemia)
• CBC: anemia (dilutional or from chronic disease); thrombocytopenia (TTP-HUS, SLE)
• Spot urine protein:creatinine ratio: quantifies proteinuria; helps distinguish nephritic (<3.5) from nephrotic (>3.5)
• Albumin: usually near-normal (mildly low at most); if markedly low, consider nephrotic overlap
• Blood pressure: frequently elevated; may be severely hypertensive

Targeted serologic workup (initiate from ED based on clinical suspicion)

Test	What it identifies
C3, C4 complement	Low C3: PSGN, lupus, MPGN, endocarditis GN; Low C3+C4: lupus, cryoglobulinemia
ASO titer, anti-DNase B	Post-streptococcal GN (ASO elevated after pharyngitis; anti-DNase B after skin infection)
ANA, anti-dsDNA	Lupus nephritis
ANCA (c-ANCA/PR3, p-ANCA/MPO)	ANCA-associated vasculitis (GPA, MPA)
Anti-GBM antibodies	Goodpasture syndrome / anti-GBM disease
Blood cultures	Endocarditis-associated GN
Hepatitis B, C serologies	Hepatitis-associated GN, cryoglobulinemia, MPGN
Cryoglobulins	Cryoglobulinemic GN (often hepatitis C-associated)
HIV	HIV-associated nephropathy
Serum IgA	Elevated in ~50% of IgA nephropathy (nonspecific)

Imaging

• Renal ultrasound: assess kidney size (normal or enlarged in acute GN; small in chronic GN), exclude obstruction
• Chest X-ray: if dyspnea (pulmonary edema, pulmonary hemorrhage/DAH), cough, hemoptysis
• CT head: if hypertensive encephalopathy suspected (altered mental status, seizures, visual changes)
• Echocardiography: if endocarditis suspected

Renal biopsy

• Not an ED procedure — arranged by nephrology
• Indicated for most adults with nephritic syndrome (PSGN in children with typical presentation usually does not require biopsy)
• Urgent biopsy indications: suspected RPGN, rapidly deteriorating renal function, unclear diagnosis

Management

Life-threatening emergencies (manage first)

Hypertensive emergency

• May present with encephalopathy, seizures, visual changes, pulmonary edema
• Salt and water restriction
• Loop diuretics: furosemide 1-2 mg/kg IV (children) or 40-80 mg IV (adults) — first-line for volume-overload hypertension
• IV antihypertensives if diuretics insufficient: nicardipine infusion, labetalol, or hydralazine
• Avoid ACE inhibitors/ARBs in the acute setting with AKI and hyperkalemia (may worsen both)
• Target: gradual reduction; do not lower BP >25% in the first hour

Hyperkalemia

• Impaired renal excretion → dangerous hyperkalemia
• Manage per standard Hyperkalemia protocols: calcium gluconate (cardiac membrane stabilization), insulin + dextrose, albuterol, sodium bicarbonate, kayexalate/patiromer, dialysis if refractory

Pulmonary edema / volume overload

• IV furosemide (high-dose may be needed with impaired GFR)
• Oxygen, positive pressure ventilation (CPAP/BiPAP or intubation) if severe
• Fluid and sodium restriction
• Dialysis if refractory pulmonary edema unresponsive to diuretics

Pulmonary hemorrhage (pulmonary-renal syndrome)

• ICU admission
• Urgent nephrology and pulmonology consultation
• Plasma exchange (plasmapheresis): especially for anti-GBM disease (removes pathogenic antibodies)
• Pulse IV methylprednisolone (1 g daily for 3 days) ± cyclophosphamide — initiated by specialist
• Intubation and mechanical ventilation if significant hemorrhage/respiratory failure
• Type and crossmatch — transfuse for significant anemia from hemorrhage

General ED management of acute nephritic syndrome

• Fluid restriction: limit to insensible losses + urine output
• Sodium restriction
• Loop diuretics: for edema and hypertension
• Monitor: urine output, blood pressure, electrolytes (especially potassium), creatinine q6-12 hours
• Treat underlying infection: antibiotics for endocarditis; note that PSGN treatment targets the complication (not the strep infection itself — the GN is post-infectious; antibiotics do not alter the course of GN but may eradicate ongoing streptococcal infection)
• Hold nephrotoxic medications: NSAIDs, aminoglycosides, contrast dye

Disease-specific treatment (nephrology-directed)

• PSGN: supportive care; usually self-limited; antibiotics only to eradicate residual streptococcal infection
• Lupus nephritis: corticosteroids ± mycophenolate mofetil or cyclophosphamide
• ANCA-associated vasculitis: pulse steroids + cyclophosphamide or rituximab; plasma exchange for severe disease
• Anti-GBM disease: plasma exchange + steroids + cyclophosphamide — true emergency; outcomes are time-dependent
• IgA nephropathy: ACE inhibitor/ARB; immunosuppression for severe/progressive disease
• Endocarditis-associated GN: treat the endocarditis; immunosuppression is contraindicated (would worsen infection)

Disposition

• Admit:
  • Hypertensive emergency or severely elevated blood pressure
  • Hyperkalemia
  • Pulmonary edema or respiratory distress
  • Rapidly rising creatinine (suspect RPGN) — urgent nephrology consult
  • Pulmonary hemorrhage / pulmonary-renal syndrome — ICU
  • Significant AKI (creatinine >2x baseline, oliguria, need for dialysis)
  • New-onset nephritic syndrome in adults (most require biopsy and specialist evaluation)
• Consider discharge with close follow-up (48-72 hours):
  • Child with classic PSGN presentation: mild edema + mild hypertension + stable renal function + no hyperkalemia + confirmed strep history
  • Ensure nephrology or pediatric nephrology follow-up within 48-72 hours
  • Return precautions: decreased urine output, worsening edema, headache, visual changes, seizures, difficulty breathing
• Always obtain nephrology consultation for: RPGN, pulmonary-renal syndrome, unclear diagnosis, adults with nephritic syndrome, renal failure requiring dialysis

See Also

• Nephrotic syndrome
• Focal segmental glomerulosclerosis
• Acute kidney injury
• Hyperkalemia
• Hypertensive emergency
• Post-streptococcal glomerulonephritis
• IgA nephropathy
• Lupus nephritis
• Goodpasture syndrome
• Henoch-Schönlein purpura
• Pulmonary embolism

External Links

• StatPearls — Nephritic Syndrome
• StatPearls — Glomerulonephritis
• PMC — Clinical Presentation & Management of Glomerular Diseases
• Medscape — Acute Glomerulonephritis Workup
• MSD Manual — Overview of Nephritic Syndrome