Seminar

on
Rapidly Progressive
Glomerulonephritis (RPGN)
DR. MD. SHAFIUL KABIR
HONORARY MEDICAL OFFICER
MEDICINE UNIT-3
DHAKA MEDICAL COLLEGE HOSPITAL
 Scenario
Mr. X, 35 years old, hypertensive, non-diabetic patient got
admitted with the complains of passage of blood in urine for 7
days, hemoptysis for 5 days, reduced urine output. His BP was
160/90 mmHg, Pulse 88 beats/min. On examination, bed side
urine examination revealed albumin (+)
On urine analysis, there was dysmorphic red blood cell present.
Serum Creatinine: 4.30 mg/dl.
Cavitary
Lesion
Provisional Diagnosis:

Rapidly Progressive Glomerulonephritis due to

Granulomatosis with Polyangitis
Content
 Definition
 Incidence
 Etiology
 Pathogenesis
 Approach to RPGN
 Management
Rapidly Progressive Glomerulonephritis
(RPGN)
It is characterized by,
Rapid loss of renal function over a very short period (days to
weeks)
Nephritic urine analysis: proteinuria, micro or macroscopic
hematuria, dysmorphic red blood cells (RBC), RBC casts
Histopathological characteristic on renal biopsy finding; cellular
crescent formation in the glomeruli
Incidence

The incidence of rapidly progressive glomerulonephritis is 7

reported cases per 1 million persons per year.

Male to Female Ratio 1:1

 Etiology
Linear antibody Granular immune Pauci-immune
deposition complex deposition (absence of
disorders deposition)
disorders
e.g: Anti-GBM e.g. PIGN e.g. ANCA
Disease Associated Vasculitis
 Etiology (Continued)
A) Linear antibody (IgG) deposition along GBM
Anti-glomerular basement membrane (GBM) disease:
• Crescentic glomerulonephritis alone (renal limited variant)
• With pulmonary hemorrhage: Goodpasture syndrome
• Associated with the ANCA (dual antibody disease or double
positive)
Etiology (Continued)
B) Granular immune complex deposit disorder:
(Subepithelial & Subendothelial deposition)
• Post-infectious GN
• Lupus nephritis
• IgA Vasculitis (Henoch-Schonlein Purpura)
• IgA Nephropathy without vasculitis
Etiology (Continued)

• Mixed cryoglobulinemia
• Membranoproliferative glomerulonephritis (MCGN)
• Idiopathic
Etiology (Continued)
C) Pauci-immune disorder: almost 80 to 90% of RPGN
cases are ANCA positive.
• Granulomatosis with polyangiitis (GPA)
• Microscopic polyangiitis (MPA)
• Eosinophilic granulomatosis with polyangiitis (EGPA)
Pathogenesis
Pathogenesis of Crescent formation
Anti-GBM Ab Immune Complex ANCA
deposition

Glomerular capillary injury

Increased permeability of glomerular barrier

Inflammatory cells, fibrin and fibronectin enter the urinary space

Activation of podocytes, proliferation of epithelial cells,

Breaks in the bowman capsule

Influx of macrophages and fibrocellular cells

Fibrocellular crescents and scarring
Crescent seen in Histopathology
When are we going to suspect
RPGN
A Patient presenting with features of AKI, who is
hemodynamically stable and non-septic
First we exclude
1. Urinary tract obstruction
 History of loin pain, hematuria, renal colic or difficulty in
micturition. Often clinically silent
Can be excluded by renal ultrasound, which is essential in any
patient with AKI
Prompt relief of the obstruction restores renal function
A Patient presenting with features of AKI, who is
hemodynamically stable and non-septic
2. Acute Interstitial Nephritis
Characterized by small amounts of blood and protein in urine,
often with leukocyturia
Usually caused by and adverse drug reaction (PPI, NSAIDs)
Kidneys are normal in size
Requires cessation of drug and often prednisolone treatment
A Patient presenting with features of AKI, who is
hemodynamically stable and non-septic
3. Drugs & Toxins
Poisoning, paraphenylenediamine hair dye, snake bite, paraquat,
paracetamol, herbal medicines, Cortinarius mushrooms
Therapeutic agents:
Direct toxicity: Aminoglycosides, Amphotericin, Tenofovir
Hemodynamic effects: NSAIDs, ACEI
Phosphate crystallization after IV administration
Bowel preparation
A Patient presenting with features of AKI, who is
hemodynamically stable and non-septic

Rapidly Progressive Glomerulonephritis

(RPGN)
Approach to a patient with RPGN
 RPGN: Classification & Presentation
Linear antibody Granular immune Pauci-immune
deposition complex deposition (absence of
disorders deposition) disorders
e.g. Anti-GBM e.g. PIGN e.g. ANCA Associated
Vasculitis
Associated with Lung Presents with severe Often occurs in
hemorrhage but renal sodium and fluid retention, systemic disease.
or lung disease may hypertension,hematuria, Respond to
occur alone oliguria glucocorticoid and
immunosuppressant
History
History of hematuria, frothing of urine, oliguria/anuria,
Hypertension
Hemoptysis  Vasculitis, Goodpasture’s disease
Poorly controlled Asthma  Vasculitis
Epistaxis, nasal crusting, sinusitis  GPA
P/H/O Throat or Skin infection PSGN
History (Continued)
Upper respiratory tract infection, Coeliac Disease  IgA N
Arthralgia  SLE, Vasculitis
Oral ulcer, photosensitivity  SLE
Abdominal Pain, Diarrhea  Vasculitis
Petechiae, purpura Vasculitis
Proptosis, diplopia, visual disturbance, Deafness GPA
Long standing history of DM/ Hypertension
Physical Examination
Pallor: May or may not be present
Normal/High BP
Peripheral oedema
Pleural effusion  Vasculitis, SLE
Oral ulcer, butterfly rash SLE
Peripheral Neuropathy (Symmetrical)  MPA
Asymmetric mononeuritis multiplex  EGPA
Investigations
 CBC
• Leukocytosis- Sepsis, Vasculitis
•Eosinophilia- EGPA
• Anemia, Leukopenia, Lymphopenia, Thrombocytopenia- SLE
• ESR usually elevated

 Peripheral Blood Film

• Fragmented cells- Microangiopathic Hemolytic Anemia
Investigations(Continued)
 Serum Electrolytes
• Potassium level elevated
 Serum Creatinine- Elevated
 BUN- Elevated
Investigations(Continued)
• Raised ESR, CRP Vasculitis
• Anti HCV Ab MPGN
• Low Complements PSGN, Lupus nephritis,Cryoglobulinemia
Investigations(Continued)
 Urine Analysis
• Red blood cells, RBC casts
• Proteinuria
• Dysmorphic RBC
Investigations(Continued)
 Serological Tests
• ANA, Anti- dsDNA Lupus
• cANCA GPA
• pANCA MPA, EGPA
• Anti-GBM Ab Anti-GBM Disease
• ASO Titre PSGN
• Serum Cryoglobulin Cryoglobulinemia
Investigations(Continued)
 Imaging
• Chest X-ray Cavities, nodules GPA
 Pulmonary hemorrhage  Goodpasture’s disease
• CT Scan of Chest  Pulmonary Hemorrhage
• Abdominal USG Assess size of kidney, echogenicity and
exclude obstruction
Renal Biopsy
 Light Microscopy
Hallmark is Crescent formation
Necrotizing inflammation
Fibrinoid necrosis, peri glomerular granulomas
Renal Biopsy (Continued)
 Immunofluorescence
• Anti-GBM Disease: Linear IgG deposition along GBM
• Immune Complex mediated: Granular glomerular staining
• Pauci Immune: Mild or absent glomerular tufting
Anti-GBM disease Post Streprtococcal GN Pauci Immune GN
Electron Microscopy: Multiple Electron Dense Deposit in MPGN
 RPGN
Clinical/Inv./Biopsy

Linear IgG Immune Complex No deposition

Deposition Deposition ANCA (+ve)
 RPGN
Clinical/Inv./Biopsy

Linear IgG Immune Complex No deposition

Deposition Deposition ANCA (+ve)

Lung Hemorrhage

Yes No

Goodpasture Anti-GBM
Syndrome Glomerulonephritis
 RPGN
Clinical/Inv./Biopsy

Linear IgG Immune Complex No deposition

Deposition Deposition ANCA (+ve)

IgA Acute Streptococcal MPGN Others

Infection
No IgG Complement
Vasculitis Vasculitis

IgAN IgAV PSGN Type-1 Type-2 SLE

 RPGN
Clinical/Inv./Biopsy

Linear IgG Immune Complex No deposition

Deposition Deposition ANCA (+ve)

Systemic Vasculitis No Systemic Features

No Asthma or Granuloma Granuloma

Granulomas No Asthma Asthma
Eosinophilia ANCA GN

MPA GPA EGPA

Management
RPGN in
ANCA Associated Vasculitis (AAV)
Immunosuppressive therapy should not be delayed for kidney
biopsy, especially in patients who are rapidly deteriorating
In organ threatening AAV:
Pulse I/V methylprednisolone (0.5–1 g) for 3 days coupled with
I/V cyclophosphamide (15 mg/kg) every 2 weeks for 3 months
followed by oral glucocorticoids and azathioprine/MTX/MMF
Rituximab & Glucocorticoid is another treatment option for
inducing remission
Plasmapheresis: In fulminant lung disease.
RPGN in Anti-GBM Disease
 Initiation with cyclophosphamide, glucocorticoid and
plasmapheresis in all patients is recommended
Cyclophosphamide should be administered for 2–3 months and
glucocorticoids for about 6 months
Plasma exchange should be performed until anti-GBM titers are
no longer detectable.
No maintenance therapy is necessary.
RPGN in Anti-GBM Disease (Contd.)
Maintenance therapy:
Patients who are Dual-antibody positive (Both Anti-GBM &
ANCA) should be treated with as for patients with AAV.
In refractory case rituximab may be tried.
Kidney transplantation in patients with kidney failure should be
postponed until anti-GBM antibodies remain undetectable for ±6
months
RPGN in PIGN
Usually resolves spontaneously
Antibiotics can be given in poststreptococcal glomerulonephritis
if Streptococci are cultured from any site
Conservative treatment of edema, hypertension and persistent
proteinuria
Value of high dose glucocorticoid remains unproven
RPGN in IgA Nephropathy
Treatment with cyclophosphamide and glucocorticoids similar
to the treatment of AAV.
Prophylactic measures should accompany immunosuppression.
There is insufficient evidence to support the use of rituximab for
the treatment of rapidly progressive IgA N.
Children with rapidly progressive IgA N have poor outcome,
and should be offered treatment with pulsed methylprednisolone
and cyclophosphamide
RPGN in ICGN
Patients presenting with a rapidly progressive crescentic
idiopathic ICGN should be treated with high-dose
glucocorticoids and cyclophosphamide.
Initiate treatment with pulse I/V methylprednisolone (1–3 g)
followed by oral glucocorticoids and oral cyclophosphamide
using a regimen similar to that used for patients with AAV
RPGN in Lupus Nephritis
Treatment according to classification by ISN/RPS criteria
based on biopsy
All patients treated with Hydroxychloroquine
Class I+II: No need for immunosuppressive therapy
Class III+IV+V: Glucocorticoids+Immunosuppressive
(CyC/MMF)
Class VI: Renal Replacement Therapy
 Take Home Message
 In any patient with Azotemia or rapidly deteriorating renal
function, in absence of any co-morbidities, hypovolemia or
sepsis, RPGN should always be considered
Patients with Pulmonary + Renal manifestations should be
evaluated for RPGN
Initiation of treatment should not be delayed for kidney biopsy
Reference
1. Davidson’s Principle and Practice of Medicine; 24th Edition
2. Davidson’s Principle and Practice of Medicine; 22nd Edition
2. Kumar & Clark’s Clinical Medicine
3. KDIGO 2021 Clinical Practice Guideline for the Management
of Glomerular Diseases
4. ACR Guideline for Lupus Nephritis