Nephritic syndrome

Background

  • 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[1]
  • 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
  • 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[2]
  • 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)[3]
  • 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


Causes of Glomerulonephritis

Hyperkalemia

  • Pseudohyperkalemia: hemolyzed specimen, prolonged tourniquet use prior to blood draw, thrombocytosis or leukocytosis
  • Redistribution (shift from intracellular to extracellular space)
  • Increased total body potassium
    • Inadequate excretion: Acute/chronic renal failure, Addison's disease, type 4 RTA
    • Drug-induced: potassium-sparing diuretic (spironolactone), angiotensin converting enzyme inhibitors (ACE-I), nonsteroidal anti-inflammatory drugs (NSAIDs)
    • Excessive intake: diet, blood transfusion
  • Other causes: succinylcholine, digitalis, beta-blockers

Evaluation

ED workup

  • Urinalysis with microscopy the single most important test[4]
    • 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

External Links

References

  1. ↑ Nephritic Syndrome. StatPearls. NCBI. 2023.
  2. ↑ Glomerulonephritis. StatPearls. NCBI. 2023.
  3. ↑ Nephritic syndrome. Wikipedia. 2025.
  4. ↑ Acute Glomerulonephritis Workup. Medscape. 2024.
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