Glomerulonephritis

Nephritic Pathophysiology

Inflammation damages glomerular capillary walls, allowing RBCs and protein to enter the filtrate. Inflammatory infiltration, mesangial responses, and capillary obstruction reduce effective filtration. The combined result is hematuria, RBC casts, variable proteinuria, declining GFR, sodium-water retention, edema, and hypertension (Perlman & Heung, 2019).

Major Patterns

Pattern	Time course	Mechanism/clue	Typical findings	Discriminator
Acute GN	Abrupt	Acute inflammatory glomerular injury	Hematuria, RBC casts, proteinuria, edema, HTN, ↓GFR	Acute nephritic syndrome
RPGN	Weeks to months	Severe injury with crescents	Rapid renal decline + nephritic sediment	Crescents; classify immune mechanism
IgA nephropathy	Recurrent/variable	Mesangial IgA deposition	Recurrent hematuria ± proteinuria	Hematuria occurs around URI
Postinfectious GN	Acute after infection	Immune-complex/complement injury	Nephritic syndrome, often low complement	Latent interval after infection
Chronic GN	Years	Progressive sclerosis/nephron loss	Persistent urinary abnormalities, HTN, declining GFR	Slow irreversible progression

Immune Patterns in Rapidly Progressive GN

Pattern	Mechanism	Immunofluorescence clue	Examples
Anti-GBM	Antibodies bind basement-membrane antigen	Linear immunoglobulin deposition	Anti-GBM disease
Immune complex	Deposited antigen-antibody complexes activate inflammation	Granular deposition	Postinfectious GN, lupus, IgA nephropathy
Pauci-immune	Necrotizing inflammation with few deposits	Little/no immune staining	ANCA-associated vasculitis

Mechanism-Directed Laboratory Clues

Pattern	Useful laboratory/biopsy clue	Interpretive point
Anti-GBM disease	Circulating anti-GBM antibody; linear immunoglobulin deposition	Supports antibody directed against intrinsic GBM antigen
Pauci-immune GN	ANCA may be present; few or no immune deposits	Suggests ANCA-associated small-vessel vasculitis when clinical context fits
Immune-complex GN	Granular immunoglobulin/complement deposits; complement may be reduced depending on cause	Includes postinfectious GN, lupus nephritis, IgA nephropathy, and related disorders
Postinfectious GN	Evidence of recent infection; often reduced C3	Latent interval after infection helps distinguish from IgA nephropathy
IgA nephropathy	Mesangial IgA deposition; serum complement usually normal	Hematuria typically occurs during or soon after mucosal infection

Diagnostic Approach

• Urinalysis and sediment: hematuria, dysmorphic RBCs, RBC casts, and proteinuria support a glomerular source (Norris, 2020; Perlman & Heung, 2019).
• Assess creatinine/eGFR and the rate of decline; rapid deterioration raises concern for RPGN (Norris, 2020; Perlman & Heung, 2019).
• Use complement and disease-directed serologies such as anti-GBM antibodies, ANCA, ANA/anti-dsDNA, and evidence of recent infection when indicated (Norris, 2020; Perlman & Heung, 2019).
• Renal biopsy may be required to define the lesion using light microscopy, immunofluorescence, and electron microscopy (Norris, 2020; Perlman & Heung, 2019).

Nephritic Versus Nephrotic

Feature	Nephritic	Nephrotic
Primary mechanism	Inflammatory glomerular injury	Filtration-barrier/podocyte injury
Hematuria	Prominent	Less characteristic
RBC casts	Characteristic	Not typical
Proteinuria	Variable	Heavy
GFR	Often reduced	May initially be preserved
Major complication pattern	AKI/oliguria/volume retention	Hypoalbuminemia, thrombosis, infection, hyperlipidemia

Clinical Manifestations

A nephritic presentation commonly includes microscopic or gross hematuria, RBC casts, variable proteinuria, oliguria, edema, hypertension, and reduced GFR. Rapidly progressive disease produces worsening renal function over weeks to months and may be accompanied by systemic findings from the underlying autoimmune, infectious, or vasculitic process (Norris, 2020; Perlman & Heung, 2019).

Findings That Argue Against Predominant Glomerulonephritis

A bland sediment with clear hypoperfusion favors prerenal AKI; muddy brown casts favor ATI; dominant heavy proteinuria with hypoalbuminemia and little inflammatory sediment favors a nephrotic process; lower-tract bleeding does not produce RBC casts. Mixed syndromes can occur, so these are discriminators rather than absolute exclusions (Perlman & Heung, 2019).

Differential Diagnosis

Important competing or overlapping diagnoses include ATI, acute interstitial nephritis, nephrotic syndromes, urinary-tract bleeding, thrombotic microangiopathy, and systemic vasculitis. Complement pattern, disease-directed serologies, urine microscopy, and renal biopsy help define the mechanism (Norris, 2020; Perlman & Heung, 2019).

Treatment Principles

Therapy is cause-specific. Management may include treatment of an inciting infection, immunosuppressive or plasma-exchange strategies for selected immune-mediated diseases, blood-pressure and volume management, and kidney-supportive care. Rapidly progressive GN is time-sensitive because untreated crescentic injury can produce irreversible nephron loss (Perlman & Heung, 2019).

Red Flags

• Rapid creatinine rise with hematuria and RBC casts (Norris, 2020; Perlman & Heung, 2019).
• Pulmonary hemorrhage or respiratory symptoms with suspected anti-GBM disease or vasculitis (Norris, 2020; Perlman & Heung, 2019).
• Severe hypertension, oliguria, hyperkalemia, pulmonary edema, or other AKI complications (Norris, 2020; Perlman & Heung, 2019).
• Systemic autoimmune or vasculitic features accompanying active urinary sediment (Norris, 2020; Perlman & Heung, 2019).

High-Yield Distinctions

• GN is a category of diseases, not a single diagnosis.
• RBC casts strongly support a glomerular source of bleeding.
• Postinfectious GN follows infection after a latent interval; IgA nephropathy often produces hematuria during or soon after a respiratory infection.
• RPGN describes a rapidly progressive clinical-pathologic syndrome; anti-GBM, immune-complex, and pauci-immune patterns identify different mechanisms.

Related YourDNP Resources

• Renal Pathophysiology Foundations
• Acute Kidney Injury
• Chronic Kidney Disease

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References

Norris, T. L. (2020). Porth’s essentials of pathophysiology (5th ed.). Wolters Kluwer.

Perlman, R. L., & Heung, M. (2019). Renal disease. In G. D. Hammer & S. J. McPhee (Eds.), Pathophysiology of disease: An introduction to clinical medicine (8th ed., pp. 493–518). McGraw-Hill Education.