Glomerulonefritis Akut Pasca-Streptokokus (GNAPS)

01Pathophysiology

PSGN is the prototype of nephritic syndrome and serves as one of the most commonly tested examples of immune complex-mediated glomerulonephritis. Understanding its mechanism is essential because the pathophysiology directly explains every symptom the patient develops.

The disease begins with an infection by a nephritogenic strain of Group A Streptococcus. Not all streptococcal strains cause glomerulonephritis; only those expressing certain virulence factors (such as nephritis-associated plasmin receptor [NAPlr] and streptococcal pyrogenic exotoxin B [SPE B]) are capable of triggering the renal immune response. The latent period between infection and renal disease is important: 1 to 3 weeks after pharyngitis and 3 to 6 weeks after skin infection (impetigo). This delay reflects the time required for antibody production and immune complex formation.

During the infection, the host immune system generates antibodies against streptococcal antigens. These antibodies form circulating immune complexes (antigen-antibody complexes) that deposit in the glomerular basement membrane (GBM), predominantly in the subepithelial space. Additionally, streptococcal antigens may "plant" themselves in the glomerulus first, with antibodies binding to them in situ. Both mechanisms activate the classical complement pathway, leading to consumption of C3 (which is why serum C3 is low). The complement activation recruits neutrophils and monocytes, which infiltrate the glomerulus, causing endocapillary proliferative glomerulonephritis.

The resulting glomerular inflammation has several downstream consequences:

Reduced glomerular filtration rate (GFR): Inflammatory cell infiltration and mesangial proliferation compress and obstruct the glomerular capillary lumen. The drop in GFR leads to oliguria, azotemia (elevated BUN and creatinine), and retention of sodium and water.

Hematuria: Damage to the glomerular capillary wall allows red blood cells to pass through, producing dysmorphic RBCs (distorted as they squeeze through the damaged basement membrane) and RBC casts (formed when red cells aggregate in the renal tubules). The gross hematuria gives urine its characteristic "cola-colored" or "tea-colored" appearance.

Proteinuria: The disrupted filtration barrier also leaks protein, though typically in the subnephrotic range (less than 3.5 g/day in adults, or less than 40 mg/m${}^2^2$/hr in children). This distinguishes nephritic from nephrotic syndrome at the clinical level.

Edema and hypertension: The primary mechanism of edema in nephritic syndrome is salt and water retention due to decreased GFR, not hypoalbuminemia (as in nephrotic syndrome). This volume expansion also drives hypertension. The edema characteristically affects the periorbital region and is worse upon waking because the loose periorbital connective tissue readily accumulates interstitial fluid when the patient is supine overnight.

On electron microscopy, the hallmark finding is subepithelial "humps" or dense deposits that appear as dome-shaped electron-dense deposits on the outer surface of the GBM. On light microscopy, there is diffuse endocapillary proliferation with neutrophil infiltration. On immunofluorescence, a "starry sky" or "lumpy-bumpy" granular pattern of IgG and C3 deposition is seen along the capillary walls and mesangium.

02Classification and Clinical Manifestation

By Preceding Infection Type

03Diagnostic Workup

The best initial test is a urinalysis with microscopy. When a child presents with periorbital edema and dark urine after a recent sore throat, the urinalysis will reveal hematuria (often gross), proteinuria, and the critical finding of RBC casts. The presence of RBC casts localizes the bleeding to the glomerulus, confirming glomerulonephritis rather than a lower urinary tract source.

The next step is to check serum complement levels, particularly C3. A low C3 with normal C4 is characteristic of PSGN and reflects activation of the alternative complement pathway. This finding is extremely high-yield because it narrows the differential significantly. If C3 remains low beyond 8 weeks, you must reconsider the diagnosis and suspect conditions like membranoproliferative glomerulonephritis (MPGN) or C3 glomerulopathy, where hypocomplementemia persists.

Simultaneously, you should obtain streptococcal serologies to establish evidence of a preceding GAS infection. For pharyngitis, the ASO titer is the test of choice. For impetigo, ASO is often not elevated, and you should rely on anti-DNase B instead. These titers confirm that a streptococcal infection preceded the nephritic episode, which is essential for diagnosis, since the culture may already be negative by the time kidney symptoms appear.

Renal biopsy is not routinely performed in PSGN. Most cases in children follow a classic, self-limiting course, and the clinical and serologic picture is sufficient for diagnosis. Biopsy is reserved for atypical presentations:

• C3 remains depressed beyond 8 weeks

• Renal function progressively worsens instead of improving

• Nephrotic-range proteinuria dominates the clinical picture

• The patient is an adult (where the prognosis is less predictable)

• There is clinical suspicion for an alternative diagnosis (e.g., IgA nephropathy, lupus nephritis)

When biopsy is performed, the most accurate (confirmatory) test reveals the triad of diffuse proliferative GN on light microscopy, granular IgG/C3 on immunofluorescence, and subepithelial electron-dense deposits ("humps") on electron microscopy.

04Management and Treatment

PSGN management is primarily supportive. There is no treatment that shortens the disease course or reverses the immune-mediated glomerular injury once it has occurred. The goal is to manage complications while the disease self-resolves.

Step 1: Volume and sodium management. Because edema and hypertension in PSGN result from salt and water retention (not from hypoalbuminemia as in nephrotic syndrome), the first intervention is restricting sodium and fluid intake. This alone can significantly improve mild edema and blood pressure.

Step 2: Loop diuretics. Furosemide is the diuretic of choice. It promotes natriuresis and diuresis, helping to relieve edema and lower blood pressure. The dose is 1 to 2 mg/kg/dose, given intravenously for moderate to severe cases or orally for milder presentations, every 6 to 12 hours as needed. Thiazide diuretics are generally avoided because they are less effective when GFR is significantly reduced.

Step 3: Antihypertensive therapy. If blood pressure remains elevated despite fluid restriction and diuretics, add a second-line antihypertensive. Calcium channel blockers like amlodipine are commonly used. For hypertensive urgency or encephalopathy, IV hydralazine (0.2 to 0.6 mg/kg/dose) or IV nicardipine infusion may be necessary. ACE inhibitors and ARBs should be used cautiously acutely because the patient may have hyperkalemia and reduced GFR; however, they may be considered later if significant proteinuria persists.

Step 4: Antibiotics. A full course of antibiotics is given to eradicate any residual GAS from the pharynx or skin, even though the infection may have already resolved. The rationale is twofold: to prevent spread of nephritogenic strains to close contacts and to eliminate any ongoing antigenic stimulation. Penicillin V for 10 days is standard. For penicillin-allergic patients, use a macrolide (azithromycin 12 mg/kg/day for 5 days, or erythromycin). Importantly, antibiotics do not alter the course of the glomerulonephritis itself and do not prevent PSGN if started after the latent period.

Step 5: Monitoring and follow-up. Most children recover completely. Hematuria resolves over weeks to months. Proteinuria may persist for up to a year. C3 complement should normalize within 6 to 8 weeks. A C3 that remains low beyond 8 weeks is a red flag requiring reevaluation and possible biopsy.

Prognosis: In children, the prognosis is excellent, with greater than 95% making a full recovery. In adults, PSGN carries a less favorable prognosis with a higher risk of persistent renal impairment.

05Differential Diagnosis and Distractors

06Traps and High-Yield Pearls

The most common way students lose points on PSGN questions is by confusing PSGN with IgA nephropathy. Both conditions present as hematuria following an upper respiratory infection in a young patient, and test-writers deliberately exploit this overlap. The discriminator is the latent period: PSGN has a gap of 1 to 3 weeks between pharyngitis and renal symptoms, while IgA nephropathy presents with synpharyngitic hematuria (hematuria occurring simultaneously with or within 1 to 2 days of the URI). If the vignette says the patient develops hematuria "during" or "immediately after" a sore throat, think IgA nephropathy. If there is a clear interval of weeks, think PSGN.

A second common trap involves complement levels. Students may forget that PSGN causes a transient drop in C3, and that C3 should normalize by 6 to 8 weeks. When a vignette describes persistent hypocomplementemia beyond this window, the answer shifts to MPGN or C3 glomerulopathy. Test-writers use the timeline of complement normalization as a pivot point in follow-up questions.

A third pitfall is the assumption that antibiotics treat or prevent PSGN. Antibiotics eradicate the organism and prevent spread, but they do not reverse the glomerulonephritis or prevent it if given after the latent period has begun. Questions may present a scenario asking whether early antibiotic therapy during pharyngitis prevents PSGN. The answer is no, unlike rheumatic fever, which can be prevented by timely antibiotic treatment.

Students also sometimes confuse the mechanism of edema in nephritic versus nephrotic syndrome. In PSGN (nephritic), the edema is driven by salt and water retention from reduced GFR, and the treatment is diuretics and sodium restriction. In nephrotic syndrome, the edema is driven by hypoalbuminemia and reduced oncotic pressure. A question that asks the "most likely mechanism of edema" in a child with cola-colored urine, RBC casts, and low C3 is testing whether you recognize the nephritic mechanism.

Finally, remember that PSGN is not an indication for immunosuppressive therapy (steroids, cyclophosphamide). This is a self-limited immune complex disease in children. Immunosuppression is reserved for crescentic (rapidly progressive) GN, which is a rare complication. A question offering steroids as a management option for typical PSGN is a distractor designed to test whether you understand the supportive nature of treatment.

The core competency being tested across all PSGN questions is pattern recognition: linking the triad of cola-colored urine + periorbital edema + low C3 to a child with a recent streptococcal infection, and then correctly sequencing the workup (urinalysis first, then complement and streptococcal serologies) and management (supportive care, not immunosuppression).