Overview
Definition:
Post-streptococcal glomerulonephritis (PSGN) is an acute nephritic syndrome that develops after a streptococcal infection, typically affecting the skin or pharynx
IgA nephropathy (IgAN), also known as Berger's disease, is a chronic glomerular disease characterized by IgA deposition in the mesangium, leading to recurrent episodes of macroscopic hematuria.
Epidemiology:
PSGN is the most common cause of glomerulonephritis in children globally, with higher incidence in developing countries
Peak incidence is between ages 6-10 years
IgAN is the most common primary glomerulonephritis worldwide, with a bimodal peak in incidence in children and young adults (ages 10-14 and 20-30)
Boys are more commonly affected than girls, with a male:female ratio of 3:1 to 5:1.
Clinical Significance:
Accurate differentiation is crucial for appropriate management and prognosis
PSGN is usually self-limiting with good recovery in children, whereas IgAN can progress to chronic kidney disease (CKD) and end-stage renal disease (ESRD) in a significant proportion of patients
Early diagnosis and management can help slow disease progression in IgAN.
Clinical Presentation
Symptoms:
PSGN: Hematuria (often macroscopic, cola-colored urine)
Edema (periorbital, scrotal, generalized)
Hypertension
Decreased urine output (oliguria)
Malaise, fatigue, fever (preceding infection)
Upper respiratory or skin infection history (2-3 weeks prior)
IgAN: Recurrent macroscopic hematuria, often triggered by upper respiratory infections or physical exertion
Microscopic hematuria and mild proteinuria may be present between macroscopic episodes
Abdominal pain
Occasionally, flank pain
Hypertension and edema are less common at presentation compared to PSGN.
Signs:
PSGN: Peripheral edema
Elevated blood pressure
Crackles on pulmonary auscultation (if fluid overload)
Pallor
Normal or slightly enlarged kidneys on palpation
IgAN: Usually unremarkable physical exam between episodes
During episodes, possible mild hypertension and flank tenderness
Presence of past strep infection stigmata (e.g., skin lesions).
Diagnostic Criteria:
PSGN: Clinical features of acute nephritic syndrome
Recent history of streptococcal infection (pharyngitis or impetigo)
Laboratory evidence of recent streptococcal infection (elevated ASO titer or anti-DNase B titer)
Low serum complement levels (C3, C4) with normalization over time
Renal biopsy showing characteristic immune complex deposition
IgAN: Recurrent macroscopic hematuria with normal renal function between episodes
Microscopic hematuria and proteinuria
Elevated serum IgA levels (variable)
Renal biopsy showing mesangial IgA deposition as the dominant or co-dominant immunoglobulin
Complement levels typically normal.
Diagnostic Approach
History Taking:
Detailed history of recent infections (sore throat, skin rash)
Onset and duration of hematuria, its color and triggers
Presence of edema, hypertension, decreased urine output
History of recurrent hematuria, especially linked to infections
Family history of kidney disease
Medications and recent illnesses
Red flags: Rapidly declining renal function, significant proteinuria (>1g/day), persistent hypertension, significant edema.
Physical Examination:
Thorough cardiovascular exam (BP, heart sounds)
Assessment for edema (pitting, location)
Pulmonary auscultation for crackles
Abdominal palpation for organomegaly or tenderness
Examination of skin for signs of recent infection (impetigo).
Investigations:
Urinalysis: Hematuria (red blood cell casts), proteinuria
Urine electrolytes and creatinine for FeNa
Serum Creatinine and Urea: Assess renal function
Complete Blood Count (CBC): Rule out anemia
Streptococcal Serology: Antistreptolysin O (ASO) titer, anti-DNase B titer (elevated in PSGN)
Complement levels: Low C3 and/or C4, especially C3, in acute PSGN, with normalization over 6-8 weeks
Normal or slightly elevated complement in IgAN
Serum IgA levels: May be elevated in IgAN (40-60% of cases), not diagnostic
Renal Biopsy: Gold standard for IgAN (mesangial IgA deposits)
Shows proliferative glomerulonephritis with endocapillary hypercellularity and subepithelial humps in PSGN
Imaging: Renal ultrasonography to rule out structural abnormalities or hydronephrosis.
Differential Diagnosis:
Other causes of nephritic syndrome: Other post-infectious GN (e.g., HUS, post-viral)
Henoch-Schonlein purpura nephritis
Lupus nephritis
Rapidly progressive glomerulonephritis
Other causes of recurrent hematuria: Urological causes (stones, tumors), bleeding disorders, familial benign hematuria
Differentiating features for PSGN vs IgAN: PSGN has a clear preceding infection, acute onset, typically lower complement levels, and characteristic biopsy findings
IgAN is characterized by recurrent hematuria, normal complement, and mesangial IgA deposits on biopsy.
Management
Initial Management:
Supportive care: Blood pressure control is paramount
Fluid and salt restriction if edema or hypertension present
Diuretics (e.g., furosemide) for edema and hypertension
Bed rest during acute phase for PSGN
Monitoring of renal function and electrolytes.
Medical Management:
PSGN: Primarily supportive
Antibiotics are generally not indicated unless there is a persistent infection source
Proteinuria and hematuria usually resolve spontaneously
IgAN: Management is controversial and focuses on reducing progression
ACE inhibitors or ARBs are used to control proteinuria and hypertension
Steroids and other immunosuppressants are reserved for selected cases with severe proteinuria (>1g/day), progressive renal dysfunction, or significant histological lesions, and their efficacy is debated
Dietary modifications (low salt, limited protein) may be considered
Tonsillectomy is generally not recommended for IgAN treatment.
Surgical Management:
Not applicable for the primary management of either condition.
Supportive Care:
Close monitoring of blood pressure, fluid balance, and renal function
Education of parents/patient regarding the condition and follow-up requirements
Nutritional advice as needed.
Complications
Early Complications:
PSGN: Hypertensive encephalopathy
Acute heart failure due to fluid overload
Acute kidney injury (AKI) requiring dialysis in severe cases
Rapidly progressive GN (rare)
IgAN: Acute kidney injury (AKI) during severe episodes
Progression to chronic kidney disease (CKD).
Late Complications:
PSGN: Generally excellent prognosis with complete recovery in most children
Chronic hypertension or renal impairment is rare
IgAN: Chronic kidney disease (CKD) and end-stage renal disease (ESRD) in 20-30% of patients over 20-25 years
Recurrence in kidney transplants can occur.
Prevention Strategies:
For PSGN: Prompt and adequate treatment of streptococcal pharyngitis and impetigo can reduce the incidence, though not entirely prevent it
For IgAN: Management strategies aimed at reducing proteinuria and controlling hypertension are key to slowing disease progression.
Prognosis
Factors Affecting Prognosis:
PSGN: In children, prognosis is excellent with near-complete recovery in over 95%
Adult PSGN can have a higher risk of progression
IgAN: Factors associated with poorer prognosis include persistent hypertension, significant proteinuria (>1 g/day), declining GFR at diagnosis, and certain histological findings (e.g., crescents, interstitial fibrosis) on renal biopsy.
Outcomes:
PSGN: Resolution of hematuria and proteinuria within weeks to months
Normal renal function is restored
IgAN: Variable
Many children maintain stable renal function for years, but a subset progresses to CKD and ESRD
Early diagnosis and treatment of risk factors can improve outcomes.
Follow Up:
PSGN: Regular monitoring of blood pressure, urinalysis for proteinuria and hematuria for at least 1-2 years
Complete resolution typically occurs
IgAN: Lifelong follow-up is recommended
Regular assessment of blood pressure, renal function (serum creatinine, eGFR), and urinalysis for proteinuria
Renal biopsy follow-up if indicated
Monitoring for progression to CKD.
Key Points
Exam Focus:
Key differences in presentation: PSGN (acute onset, preceding infection, low complement, C3 hypocomplementemia) vs
IgAN (recurrent hematuria, normal complement, mesangial IgA)
Biopsy findings: PSGN (endocapillary proliferation, humps) vs
IgAN (mesangial IgA deposits)
Prognosis: PSGN excellent in children, IgAN variable with risk of CKD.
Clinical Pearls:
Always inquire about a preceding sore throat or skin infection in children with hematuria or edema
The color of urine (cola-colored in PSGN) is a useful clue
Remember that IgAN can be triggered by infections, but it's recurrent hematuria, not a single episode following infection
Complement levels are a crucial differentiator: low C3 in acute PSGN, typically normal in IgAN.
Common Mistakes:
Misdiagnosing IgAN as simply "recurrent hematuria" without performing a renal biopsy for definitive diagnosis
Over-treating PSGN with antibiotics when the infection has resolved
Underestimating the long-term risk of CKD in IgAN patients, leading to inadequate monitoring and management.