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
• 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
• 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

Causes of Glomerulonephritis

• Poststreptococcal glomerulonephritis
• Hemolytic-uremic syndrome
• Henoch-Schonlein purpura
• IgA nephropathy
• Lupus nephritis
• Alport syndrome
• Goodpasture syndrome
• Paraneoplastic

Hyperkalemia

• Pseudohyperkalemia: hemolyzed specimen, prolonged tourniquet use prior to blood draw, thrombocytosis or leukocytosis
• Redistribution (shift from intracellular to extracellular space)
  • Acidemia (see DKA)
  • Cellular breakdown: see Rhabdomyolysis/Crush syndrome, electrical/thermal burn, hemolysis, see Tumor lysis syndrome
• 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
  • 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