Nephritic syndrome is one of those Step 1 “pattern-recognition” topics that pays off fast: a patient with dark (cola-colored) urine, hypertension, and RBC casts should immediately push you toward an inflammatory glomerular process. The two highest-yield etiologies you’ll see early (and test often) are IgA nephropathy and post-streptococcal glomerulonephritis (PSGN)—and the key is learning how to separate them by timing, serologies, and histology.
Nephritic Syndrome: The Core Definition (Know This Cold)
Nephritic syndrome = inflammation of the glomerulus leading to:
- Hematuria (often gross, “tea/cola-colored”)
- RBC casts (bleeding that occurred within the nephron)
- Mild-to-moderate proteinuria (typically < 3.5 g/day)
- Azotemia (↓ GFR → ↑ BUN/Cr)
- Oliguria
- Hypertension (salt/water retention + RAAS)
- Periorbital edema (can occur, but classically more dramatic in nephrotic syndromes)
Why RBC casts matter (Step 1 logic)
RBCs + Tamm-Horsfall protein in tubules → RBC casts → strongly suggests glomerular bleeding, not lower-tract bleeding.
First Aid cross-reference: Renal → Glomerular diseases; Nephritic vs nephrotic syndromes tables; Poststreptococcal GN and IgA nephropathy.
Pathophysiology: What “Nephritic” Really Means
Nephritic syndromes are driven by immune-mediated injury → inflammation → damage to the glomerular filtration barrier.
Key mechanisms
- Immune complex deposition (classic for IgA nephropathy, PSGN)
- Complement activation (often low C3 in PSGN)
- Leukocyte recruitment + proliferation of glomerular cells
- Capillary wall damage → RBC leak → hematuria + casts
- Reduced filtration surface area → ↓ GFR → azotemia, HTN, oliguria
Big Picture: IgA Nephropathy vs PSGN (Quick Compare Table)
| Feature | IgA Nephropathy (Berger) | Post-strep GN (PSGN) |
|---|---|---|
| Typical trigger | URI/GI infection | Strep throat or impetigo |
| Timing after infection | Days (often synpharyngitic) | Weeks (classically 1–3 weeks after pharyngitis; 3–6 weeks after skin infection) |
| Complement | Usually normal | Low C3 (hypocomplementemia) |
| Serologies | No classic single marker (IgA may be ↑) | ↑ ASO, ↑ anti-DNase B |
| LM | Mesangial proliferation | Hypercellular glomeruli (diffuse) |
| IF | Mesangial IgA deposition | “Lumpy-bumpy” granular deposits (IgG, IgM, C3) |
| EM | Mesangial electron-dense deposits | Subepithelial humps |
| Clinical pearl | Often recurrent episodes with URIs | First episode after strep; kids common |
| Prognosis | Variable; can progress to CKD | Often resolves in children; worse in adults |
IgA Nephropathy (Berger Disease): High-Yield Deep Dive
What it is
An immune complex–mediated nephropathy characterized by IgA deposition in the mesangium, often after mucosal infections.
Pathophysiology (board-friendly version)
- Mucosal immune activation → production of abnormally glycosylated IgA
- Formation of IgA-containing immune complexes
- Mesangial deposition → complement activation (often via alternative/lectin pathways) → inflammation
Clinical presentation
- Episodic hematuria (gross or microscopic)
- Occurs within days of an URI (“synpharyngitic”)
- May have:
- Mild proteinuria
- Hypertension
- Elevated creatinine if more severe
HY association: HSP (IgA vasculitis)
IgA nephropathy is closely related to Henoch–Schönlein purpura (IgA vasculitis):
- Palpable purpura (buttocks/legs)
- Arthralgias
- Abdominal pain
- Renal involvement identical pattern (IgA deposition)
First Aid cross-reference: Immunology/Rheumatology → Henoch-Schönlein purpura; Renal → IgA nephropathy.
Diagnosis
Often suspected clinically, confirmed by biopsy if needed (atypical course, significant proteinuria, declining kidney function).
Biopsy findings you must know:
- LM: Mesangial proliferation/expansion
- IF: Granular mesangial IgA
- EM: Mesangial electron-dense deposits
Treatment (Step 1 + Step 2 angle)
- Supportive: BP control (ACEi/ARB especially if proteinuria)
- In higher-risk disease: immunosuppression may be considered (typically specialist-driven)
- Monitor for progression to CKD
Prognosis
Variable. Some have benign recurrent hematuria; others progress to CKD (risk rises with significant proteinuria, HTN, reduced GFR).
Post-streptococcal Glomerulonephritis (PSGN): High-Yield Deep Dive
What it is
A nephritic syndrome occurring after infection with nephritogenic strains of group A strep:
- Strep pyogenes causing pharyngitis
- or impetigo
Timing is everything
- 1–3 weeks after pharyngitis
- 3–6 weeks after impetigo
If hematuria happens at the same time as the sore throat, think IgA nephropathy, not PSGN.
Pathophysiology
- Formation of immune complexes involving streptococcal antigens
- Deposition in glomeruli → complement activation → inflammation
- Classic lab: low C3 due to complement consumption
Clinical presentation (classic vignette)
Child with:
- Recent strep infection
- Dark urine + periorbital edema
- Hypertension
- Oliguria
- Possibly mild proteinuria
Diagnosis
Key supportive labs:
- Elevated anti-streptolysin O (ASO) (more useful after pharyngitis)
- Elevated anti–DNase B (more useful after skin infections)
- Low C3 (complement consumption)
Urinalysis:
- Hematuria
- RBC casts
- Mild-to-moderate proteinuria
Biopsy findings (must memorize):
- LM: Enlarged, hypercellular glomeruli (diffuse proliferative pattern)
- IF: “Lumpy-bumpy” granular deposits of IgG, IgM, C3 along GBM and mesangium
- EM: Subepithelial humps (immune complex deposits)
First Aid cross-reference: Renal → Poststreptococcal GN; Microbiology → Strep pyogenes complications (rheumatic fever vs PSGN).
Treatment
- Supportive care: control blood pressure, manage volume overload (diuretics), monitor renal function/electrolytes
- Treat active infection if still present (antibiotics prevent transmission; they don’t reliably prevent PSGN once immune response is triggered)
Prognosis
- Children: often recover completely
- Adults: higher risk of persistent renal dysfunction
How to Nail the Differential on Test Day
Nephritic syndrome vs nephrotic syndrome (rapid distinction)
- Nephritic: hematuria + RBC casts + HTN + azotemia; proteinuria is present but not massive
- Nephrotic: heavy proteinuria > 3.5 g/day, edema, hyperlipidemia, lipiduria (fatty casts)
IgA nephropathy vs PSGN (rapid distinction)
Ask:
- When did hematuria start relative to infection?
- Days = IgA nephropathy
- Weeks = PSGN
- Complement low?
- Low C3 = PSGN (classically)
- Serologies for strep?
- ASO / anti-DNase B elevated = PSGN
High-Yield Associations & “Buzz Phrases” (Memorize)
IgA nephropathy
- “Synpharyngitic hematuria”
- “Mesangial IgA deposition”
- Associated with HSP (IgA vasculitis)
PSGN
- “1–3 weeks after strep throat”
- “3–6 weeks after impetigo”
- “Subepithelial humps” (EM)
- “Lumpy-bumpy” granular IF
- Low C3, ↑ ASO, ↑ anti-DNase B
Mini Self-Quiz (Quick Vignette Practice)
- Teen develops gross hematuria 2 days after a sore throat. Complement is normal. Most likely diagnosis?
- IgA nephropathy
- Child had impetigo 4 weeks ago, now has cola-colored urine and periorbital edema. Labs show low C3 and elevated anti–DNase B. Biopsy EM shows what?
- Subepithelial humps (PSGN)
- UA shows RBC casts and mild proteinuria in both conditions. What feature most strongly points to PSGN?
- Low C3 + weeks-later timing after strep infection