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
