Glomerulonephritis

Classification

Nephrotic syndrome
- Protein >3g/day
- Edema
- Hyperlipidemia
- Hypoalbuminemia <35g/L
Nephritic syndrome
- Active urinalysis with RBCs and/or casts
- Hypertension
- Azotemia
- Can present with nephrotic syndrome if severe

Differential Diagnosis

Cause	MCD	MN	FSGS	FPGN	MPGN	DPGN	RPGN
Primary	+	+	+	+	+	+
Infections
HIV			+
Malaria		+
Syphilis		+
Hepatitis B		++			+
Hepatitis C		+			++
Drugs
Heroin use			+
Gold and penicillamine		+
Pamidronate	+		+
Lithium	++		+
NSAIDs	+	+
Neoplasms
Hodgkin lymphoma	+
Non-Hodgkin lymphoma		+
Solid-organ malignancy		+
Autoimmune/Inflammatory
Lupus		+		+		+	+
Post-infectious GN						+	+
Mixed cryo						+
IgA nephritis				+
Anti-GBM (linear)							+
ANCA-assoc (pauci-immune)							+
Miscellaneous
Renal transplant rejection					+
Obesity			+

MCD = minimal change disease; MN = membranous nephropathy; FSGS = focal segmental glomerulosclerosis; FPGN = focal proliferative GN; MPGN = membranoproliferative GN; DPGN = diffuse proliferative GN; rapidly-progressive GN

Differential Diagnosis

Non-proliferative (nephrotic syndrome, > 3 g/day)
- Minimal change disease
  - Primary: most common cause in children
  - Hodgkin lymphoma
- Focal segmental glomerulosclerosis
  - Primary
  - HIV
  - African-American (apo-L1 gene)
- Membranous nephropathy
  - Primary: common in adults
  - Cancer (non-Hodgkin lymphoma and solid tumours)
  - Drugs (NSAIDs, gold, penicillamine)
  - Infections (malaria, HBV, HCV)
  - Lupus
Proliferative (nephritic syndrome)
- Membranoproliferative
  - Primary
  - Transplant rejection
  - HCV
- Focal proliferative
  - Primary
  - IgA nephropathy
  - Lupus nephritis
- Diffuse proliferative
  - Primary
  - Hypocomplementemia
    - Lupus
    - Post-infectious nephropathy
    - Essential mixed cryoglobulinemia
- Rapidly-progressing glomerulonephritis (RPGN)
  - Primary
  - Linear immunofluorescence: anti-GBM, Goodpastures
  - Lumpy-bumpy immunofluorescence: post-infectious, lupus
  - Negative immunofluorescence: ANCA vasculitides
Non-glomerulonephritis
- Diabetes
- Amyloidosis

	Minimal Change	Membranous	FSGS	MPGN	Nodular
Secondary causes	Hodgkin lymphoma	HBV, SLE, solid tumours (lung, breast, GI)	Reflux netphropathy, HIV, HBV, obesity, sickle cell disease	HCV, malaria, SLE, leukemia, lymphoma, shunt nephritis	Diabetes, amyloidosis
Drugs	NSAIDs	Gold, penicillamine	Heroin
Therapy	Steroids	BP control, ACEi, steroids	Steroids, ACEi for protein	ASA, ACEi	Underlying cause

graph LR;
GN --> ANCA[ANCA positive]
  ANCA --> cANCA[c-ANCA/PR3]
    cANCA --> GPA
  ANCA --> pANCA[p-ANCA/PR3]
    pANCA --> eGPA[eGPA]
    pANCA --> MPA[MPA]
  GN --> GBM[Anti-GBM positive]
    GBM --> hemopt[Hemoptysis]
      hemopt --> Goodpasture[Goodpasture's]
    GBM --> no_hemoptysis[No hemoptysis]
      no_hemoptysis --> antiGBM[Anti-GBM disease]
  GN --> Complement[Complement-mediated]
    Complement --> low_C3[Low C3]
      low_C3 --> low_C3_syndromes[PSGN, MPGN, SLE, IE, cryo]
    Complement --> normal_C3[Normal C3]
      normal_C3 --> normal_C3_syndromes[IgA nephropathy, fibrillary GN]

Investigations

SPEP/UPEP for amyloidosis
HbA1c for diabetes
If nephrotic:
- Lipid profile
- Albumin
- 24h urine
If suspecting lupus: ANA ±dsDNA ±Sm, C3/C4, ESR/CRP
HIV/HBV/HCV
If suspecting vasculitides
- Anti-GBM antibody
- ANCAs

Management

Age < 20 years, treat empirically with prednisone
Age > 20 years, needs kidney biopsy first
Treatment depends on pathology
- Minimal change disease
  - Low salt diet and lasix for edema, ACEi/ARB for hypertension
  - Prednisone 60mg/day