ACUTE GLOMERULONEPHRITIS
Acute glomerulonephritis (acute nephritic syndrome) is a collective term to denote many glomerular disorders (see glomerular causes in Table 21.5), all clinically characterized by acute onset of: (a) hematuria, (b) hypertension, (c) oliguria/anuria, and (d) minimal edema/ facial puffiness.
Over 80% of these cases are preceded by streptococcal infections, termed as acute post-streptococcal glomerulonephritis (APSGN), discussed here. However, similar presentation is also seen following many other infections, e.g. staphylococci, pneumococci, etc. and the term “acute post-infectious glomerulonephritisquot; (APIGN) is often used to collectively refer all these cases.
Etiopathogenesis: While over 80 serotypes of group A #946;-hemolytic streptococci (GABHS) are known, APSGN is a consequence of throat or skin infection with selected nephritogenic strains, commonest being M 49 (causing pyoderma) and M 4 and 12 (causing pharyngitis).
While precise mechanism for glomerular injury in APSGN is unclear, it is most likely an immune-complex disease with either:
• Development of anti-streptococcal antibodies and formation of circulatory immune complexes, which are then trapped in glomerular capillaries, leading to complement activation and consequent glomerular injury; or
• Direct subendothelial glomerular injury by GABHS, initiating autoimmune response and in situ formation of immune complexes with complement activation, leading to glomerular injury.
Pathologically, characteristic abnormalities are:
• On light microscopy: Enlarged glomeruli with—(a) diffuse mesangial and endothelial cell proliferation, (b) obliteration of capillary lumen (blood-less appearance), and (c) increased mesangial matrix with neutrophilic infiltration and crescent formation.
• On immunofluorescence microscopy: Lumpy-bumpy deposits of IgG, IgM and C3 along the capillary walls on glomerular basement membrane and in mesangium (Starry-sky appearance),
• On electron microscopy: Subepithelial electron dense hump-like deposits over basement membrane with patchy loss/fusion of epithelial foot processes.
Epidemiology: Preceding history of sore throat or pyoderma is present in gt;60% cases and epidemiology of APSGN runs parallel to that of streptococcal infections, being more common in: (i) school-age children (5-12 years), (ii) boys, and (iii) certain seasons. APSGN due to pharyngogenic strains is more common in winter, while post-dermatogenic disease is common in summer season.
Latent period between infection and gomerular disease also differs between pharyngogenic (10-14 days) and dermatogenic disease (21 days).
Clinical presentation: A typical case presents with sudden onset of four cardinal features:
1. Gross hematuria with dark cola-colored urine,
2. Mild edema or facial puffiness, more in mornings,
3. Oliguria or anuria, and
4. Hypertension with/without symptoms, e.g. headache and vomiting.
Severe cases may also present with complications, e.g.
(a) hypertensive encephalopathy with seizures and altered sensorium, (b) circulatory overload with pulmonary edema with dyspnoea, and (c) acute renal failure with anuria, dyselectrolytemia and acidosis.
Some cases of APSGN present with mixed picture of nephrotic and nephritic syndrome, with marked edema and proteinuria.
Course: Acute phase usually lasts for 2-3 weeks with complete spontaneous recovery in gt;95% cases, though microscopic hematuria may continue for 3-6 months. Acute renal failure during active phase is common but residual damage or recurrence is very rare.
Diagnosis of APSGN depends on:
• Clinical tetrad of hematuria, hypertension, oliguria and early morning facial puffiness;
• History of preceding sore throat or pyoderma
• Laboratory investigations, e.g.:
- Presence of RBCs and RBC casts in urine, with/ without mild proteinuria (lt; 2+) and pyuria.
- Evidence of preceding streptococcal infection, e.g. elevated ASO titers in ~60% cases. ASO titres may be normal in dermatogenic disease due to interference with antigenicity of streptolysin O by skin lipids.
Anti-Dnase B and anti-hyaluronidase titers are elevated in these cases, though rarely used in clinical practice.- Low complement (C3) level is a consistent finding (gt; 90%), suggestive of immune complex injury, which usually normalizes after 6-8 weeks.
- Abnormal renal function tests, e.g. BUN, S. creatinine,
S. electrolytes and blood gas analysis, etc.
- Renal biopsy is not routinely indicated except in cases with persistent—(a) gross hematuria, hypertension or azotemia gt;1 month, (b) persistently low C3 levels for gt;2 months, and (c) persistent microscopic hematuria or proteinuria for gt; 12 months.
D/D: APSGN needs to be differentiated from nephrotic syndrome (Table 21.7) as well as other causes of hematuria (Table 21.5).
Management: While APSGN is a self-limiting disease; hospitalization is necessary during first week of illness to ensure early recognition and prompt management of complications. Important principles of management include:
• Systemic antibiotic therapy with oral penicillin for 7-10 days to control streptococcal infections, if present. However, antimicrobial therapy does not alter the course of APSGN.
• Regular monitoring of fluid intake/output, BP, weight and urinary findings, for early diagnosis of fluid retention and hypertension.
• Salt and water restriction, only if circulatory congestion, azotemia or hypertension is present.
• Treatment of volume overload or pulmonary edema, with fluid restriction and diuretics, if necessary.
• Treatment of hypertension with diuretics and antihypertensive drugs, e.g. enalapril. Hypertensive encephalopathy is an emergency that needs IV antihypertensives (Ch 17.12).
• Treatment of acute renal failure, if established, as discussed in Ch 21.9.
21.6.2