Overview
Acute Nephritic Syndrome
1. Clinical Overview
Summary
Acute Nephritic Syndrome is a clinical presentation of glomerular inflammation (Glomerulonephritis). Unlike Nephrotic syndrome (which is leaky to protein), Nephritic syndrome is inflammatory, causing rupture of glomerular capillaries. This leads to the classic tetrad of Hematuria, Hypertension, Oliguria, and Azotemia (AKI). It ranges from mild (IgA) to catastrophic (RPGN).
Key Facts
- The Definition (Tetrad):
- Hematuria: RBC Casts are pathognomonic ("dysmorphic" red cells).
- Hypertension: Volume overload + RAAS activation.
- Proteinuria: Usually "Sub-nephrotic" (< 3.5g/day).
- AKI: Rising Creatinine + Oliguria.
- Top Cause (Global): IgA Nephropathy (Berger's Disease).
- Top Cause (Children): Post-Streptococcal Glomerulonephritis (PSGN).
- The Killer: Rapidly Progressive Glomerulonephritis (RPGN) - aka Crescentic GN. Doubles creatinine in <3 months. Needs urgent chemo/plasma exchange.
Clinical Pearls
"Coca-Cola Urine": The classic description. This is not fresh blood (which suggests bladder/prostate). It is metabolized hemoglobin from the kidney, turning brown/tea-colored.
Synpharyngitic vs Post-infectious:
- IgA: Blood in urine syn-pharyngitic (1-2 days after sore throat).
- Post-Strep: Blood in urine post-infectious (2-3 weeks later). The gap matters!
Pulmonary-Renal Syndrome: Any patient with Hemoptysis + Renal Failure has Goodpasture's or ANCA Vasculitis until proven otherwise. This is a medical emergency.
2. Nephritic vs Nephrotic
The two poles of glomerular disease. Mixed pictures exist (e.g. Lupus).
| Feature | Nephritic Syndrome | Nephrotic Syndrome |
|---|---|---|
| Primary Defect | Inflammation (Rupture of capillary) | Podocyte Injury (Loss of charge barrier) |
| Urine | Active Sediment (RBC Casts, Dysmorphic RBCs) | Bland Sediment (Fatty Casts, Oval Fat Bodies) |
| Proteinuria | Mild-Moderate (< 3.5 g/day) | Massive (> 3.5 g/day) |
| Edema | Moderate (Periorbital/Peripheral) - due to Na retention | Massive (Anasarca) - due to Hypoalbuminemia |
| Blood Pressure | Hypertension (Frequency high) | Normal / Low |
| Onset | Abrupt | Insidious |
| Classic Example | Post-Strep GN | Minimal Change Disease |
3. Pathophysiology
Mechanism of Injury
- Immune Complex Deposition:
- Circulating antigen-antibody complexes get "stuck" in the glomerulus.
- Outcome: Triggers Complement (C3) consumption and neutrophil recruitment.
- Examples: Lupus, Post-Strep, IgA.
- Direct Antibody Attack:
- Antibodies target antigens on the glomerular basement membrane (GBM).
- Outcome: Linear destruction.
- Example: Goodpasture's (Anti-GBM).
- Pauci-Immune (No Deposits):
- Neutrophils activate and attack the vessel wall directly (Vasculitis).
- Example: ANCA Vasculitis.
The Complement Cascade: "Alternative Pathway" Dysregulation
- Mechanism: Normally, Factor H acts as a "brake" on the Alternative Complement Pathway to prevent it attacking self-cells.
- C3 Glomerulopathy (C3G): Mutations in Factor H or Autoantibodies (C3 Nephritic Factor) remove the brake.
- Result: Uncontrolled C3 deposition in the glomerulus.
- Appearance: "Dense Deposit Disease" on Electron Microscopy.
The "Crescent" (RPGN)
- When the glomerular capillary wall ruptures, fibrin and macrophages spill into Bowman's space.
- They proliferate to form a moon-shaped "Crescent".
- This compresses and destroys the glomerulus.
- Significance: >50% crescents = Rapid loss of kidney function.
4. Etiology Classification (By Complement)
The most useful way to narrow the differential.
Goodpasture's Disease (Anti-GBM)
Pulmonary-Renal Syndrome.
- Pathology: Antibodies against the Alpha-3 chain of Type IV Collagen (found in Lung Alveoli and Kidney Glomerulus).
- Trigger: Often smoking or hydrocarbon exposure (damages lung capillaries, exposing the antigen).
- Presentation: Hemoptysis (Life threatening) followed by RPGN.
- Urgency: Highest. Antibody removal (Plasma exchange) must start before the patient becomes anuric for renal recovery.
The "ANCA Matrix"
Which antibody goes with which disease?
| Disease | Antigen | Antibody Pattern | Clinical Features |
|---|---|---|---|
| GPA (Wegener's) | PR3 (Proteinase 3) | c-ANCA (Cytoplasmic) | Nasal crusting, Saddle nose, Cavitating lung nodules. |
| MPA (Microscopic) | MPO (Myeloperoxidase) | p-ANCA (Perinuclear) | Pulmonary Hemorrhage. No granulomas. |
| EGPA (Churg-Strauss) | MPO | p-ANCA | Asthma + Eosinophilia + Polyps. |
| Drug Induced | MPO/PR3 (Multi) | p-ANCA (Atypical) | Hydralazine, Propylthiouracil, Cocaine (Levamisole). |
Low Complement Levels (Hypocomplementemia)
Consumption of C3/C4 suggests systemic immune complex disease.
- Post-Infectious GN (PIGN):
- usually low C3, normal C4.
- Follows Strep Throat or Skin infection (Impetigo).
- "Lumpy Bumpy" deposits on EM.
- Lupus Nephritis (SLE):
- Low C3 and Low C4. (Classic "Full House" immunofluorescence).
- ANA +, dsDNA +.
- Cryoglobulinemia:
- Associated with Hepatitis C.
- Low C4 (very low).
The "Full House" Effect (Lupus)
Immunofluorescence findings.
- Definition: Positive staining for everything: IgG, IgM, IgA, C3, and C1q.
- Significance: Highly specific for SLE.
- "Wire Looping": Subendothelial deposits seen on Light Microscopy.
- Membranoproliferative GN (MPGN):
- "Tram-tracking" splitting of GBM.
- Associated with Hep C also.
Lupus Nephritis Classification (ISN/RPS)
We treat based on the class.
| Class | Name | Inflammation | Treatment |
|---|---|---|---|
| I | Minimal Mesangial | None. | None. |
| II | Mesangial Proliferative | Mild. | Low dose steroids. |
| III | Focal Proliferative | <50% of Glomeruli. | Aggressive (Cellcept/Cyclo). |
| IV | Diffuse Proliferative | >0% of Glomeruli. | Aggressive (Most severe form). |
| V | Membranous | Nephrotic (Proteinuria). | ACEi / Mycophenolate. |
| VI | Sclerosing | Scarred kidney. | Dialysis prep (Immunosuppression futile). |
Normal Complement Levels
Localised or Pauci-immune.
- IgA Nephropathy:
- Most common GN worldwide. Mesangial IgA deposits.
- Related: Henoch-Schonlein Purpura (HSP) is systemic IgA vasculitis (Rash + Arthralgia + GN).
"Synpharyngitic" Hematuria (IgA)
The timing matches the sore throat.
- Mechanism: Mucosal IgA production in the tonsils spills over into the blood. Galactose-deficient IgA1 deposits in the kidney.
- Trigger: URI (Tonsillitis) or GI infection.
- Clinical: Patient notices red urine while they have the sore throat (1-2 days later).
- Contrast: Post-Strep occurs 2-3 weeks later (Latency).
- ANCA Vasculitis:
- Granulomatosis with Polyangiitis (GPA/Wegener's): c-ANCA (PR3). Sinusitis/Lung nodules.
- Microscopic Polyangiitis (MPA): p-ANCA (MPO). Lung hemorrhage.
- Anti-GBM Disease (Goodpasture's):
- Antibodies against Type IV Collagen.
- Young men (Lung hemorrhage) or Older women (Kidney only).
5. Clinical Examination
Bedside
- Blood Pressure: Hypertension is ubiquitous.
- Fluid Status: JVP elevated, Pedal edema (less severe than Nephrotic), Pulmonary edema (crackles).
- Skin:
- Rash: Purpura (HSP/Vasculitis).
- Impetigo: Honey-crusted lesions (suggests Post-Strep).
- Butterfly Rash: Lupus.
Henoch-Schonlein Purpura (IgA Vasculitis)
Systemic IgA disease.
- Tetrad: Palpable Purpura (legs/buttocks) + Arthritis + Abdominal Pain + Nephritis.
- Prognosis: Usually self limiting in children. Adults have higher risk of CKD.
- Biopsy: Identical to IgA Nephropathy (Mesangial IgA deposits).
Urine
- Dipstick: Blood +++ (Hemoglobin), Protein ++.
- Macroscopic: "Tea colored", "Smoky", "Coca-cola". frothy (if protein high).
Urine Color: The Differential
It's not always blood.
- Red: Fresh blood (Lower tract), Rifampicin, Beetroot (Beeturia).
- Brown/Tea: Old blood (Glomerular), Myoglobin (Rhabdomyolysis), Bile (Obstructive Jaundice).
- Purple: Purple Urine Bag Syndrome (Providencia stuartii infection in catheter).
- Green: Propofol, Methylene Blue.
6. Investigations
Urine Microscopy (The Liquid Biopsy)
Must be fresh spin.
- RBC Casts: Red cells trapped in Tamm-Horsfall protein. Diagnostic of GN.
- Dysmorphic RBCs: "Mickey Mouse ears" (Acanthocytes). Means they squeezed through the damaged glomerulus.
The Urine Sediment Gallery
What the microscope sees.
| Finding | Significance | Disease |
|---|---|---|
| Dysmorphic RBCs | Glomerular Bleeding (Squeezed). | GN (Any). |
| Isomorphic RBCs | Lower Tract Bleeding. | Stone/Tumor/UTI. |
| RBC Casts | Active Glomerulonephritis. | GN (Any). |
| WBC Casts | Tubular Inflammation. | Pyelonephritis / Interstitial Nephritis. |
| Fatty Casts | "Maltese Cross" (Lipid). | Nephrotic Syndrome. |
| Muddy Brown Casts | Dead tubular cells. | Acute Tubular Necrosis (ATN). |
Serology Panel (The "Glomerular Screen")
- ANA / dsDNA: Lupus.
- ANCA (MPO/PR3): Vasculitis.
- Anti-GBM: Goodpasture's.
- Complements (C3/C4).
- ASOT / Anti-DNAse B: Recent Strep infection.
- Viral Serology: Hep B, Hep C, HIV.
The Oxford Classification (MEST-C) for IgA
Predicts prognosis in IgA Nephropathy.
| Letter | Feature | Definition |
|---|---|---|
| M | Mesangial hypercellularity | >0% of glomeruli showing proliferation. |
| E | Endocapillary proliferation | Occlusion of capillary loops. |
| S | Segmental sclerosis | Scarring in part of the tuft. |
| T | Tubular atrophy | >5% fibrosis = Poor prognosis. |
| C | Crescents | Active inflammation. Need steroids. |
Renal Biopsy
The Gold Standard.
- Indications:
- Unexplained AKI + Active Urine.
- Nephrotic Syndrome in adults.
- Suspected Systemic Disease (Lupus/Vasculitis).
- Contraindications: Small kidneys (CKD), Uncontrolled HTN, Bleeding diathesis, Solitary kidney.
Biopsy Complications (The Consent Form)
- Pain: 100%. (Renal capsule stretch).
- Hematuria (Gross): 5-10%. Usually resolves with fluids.
- Hematoma: Perinephric bleed. <1% need embolization/surgery.
- AV Fistula: Arteriovenous fistula formation. Usually asymptomatic.
- Loss of Kidney: Extremely rare (< 1 in 10,000).
7. Management
General Measures (Supportive)
- Fluid Restriction: 1 Litre/day or less if oliguric.
- Diuretics: Furosemide (Loop diuretics) to effect. Need high doses in AKI (e.g. 80-120mg).
- BP Control:
- ACE-Inhibitors (Ramipril) / ARBs are first line (reduce proteinuria).
- Mechanism: Angiotensin II constricts the Efferent arteriole (increasing glomerular pressure). ACEi blocks this, dilating the efferent arteriole -> reducing intraglomerular pressure -> reducing protein leak / scarring.
- Note: Use caution with ACEi if Creatinine is rising rapidly (risk of hyperkalemia).
- Salt Restriction: < 2g Sodium.
Indications for Urgent Dialysis (AEIOU)
When drugs aren't enough.
- A - Acidosis: pH < 7.15 refractory to bicarbonate.
- E - Electrolytes: Hyperkalemia > 6.5 mmol/L (with ECG changes) refractory to medical management.
- I - Intoxication: Lithium, Methanol, Ethylene Glycol (Dialysable toxins).
- O - Overload: Pulmonary Edema refractory to Furosemide.
- U - Uremia: Pericarditis, Encephalopathy, Uremic Bleeding.
Emergency Management: Hyperkalemia
The immediate killer.
- Stabilize: Calcium Gluconate 10% 10ml IV (Protects myocardium).
- Shift:
- Insulin (10u) + Dextrose (50ml 50%).
- Salbutamol Nebs (10-20mg).
- Eliminate: Furosemide (if passing urine). Dialysis (if anuric).
- Binders: Sodium Zirconium Cyclosilicate (Lokelma).
Plasma Exchange (PLEX) Protocol
Washing the blood.
- Indication: Anti-GBM (Goodpasture's) or Severe ANCA vasculitis with Pulmonary Hemorrhage.
- Mechanism: Centrifuge separates plasma from cells. Plasma (containing antibodies) is discarded. Cells are returned with clean Albumin/FFP.
- Regimen: Daily or alternate days for 7-14 sessions (until antibody clears).
- Risks: Bleeding (clotting factors removed), Hypocalcemia (Citrate anticoagulation), Infection.
SGLT2 Inhibitors: The Game Changer
Dapagliflozin / Empagliflozin.
- Original Use: Diabetes drugs.
- Renal Use: Approved for IgA Nephropathy (DAPA-CKD Trial).
- Mechanism: Blocks Sodium-Glucose co-transporter in proximal tubule -> Increases sodium delivery to Macula Densa -> Constricts Afferent Arteriole -> Reduces Glomerular Hypertension.
- Benefit: Slows progression to dialysis by 30-40%.
The Immunosuppression Ladder
Step-wise escalation.
- Supportive: BP Control + Salt Restriction. (Mild IgA / Post-Strep).
- Induction (Pulse): Methylprednisolone 500mg IV x 3 days. (Severe flares).
- Maintenance Steroids: Oral Prednisolone taper.
- Cytotoxics: Cyclophosphamide (for organ threatening disease).
- Biologics: Rituximab (Recurrent/ANCA).
Specific Management (Immunosuppression)
1. IgA Nephropathy
- Low Risk: BP control (ACEi).
- High Risk (Proteinuria >1g, rising Cr): Systemic Steroids (6 months) or Budesonide (Gut-directed). SGLT2 Inhibitors (Dapagliflozin) are new standard of care.
2. ANCA Vasculitis / Lupus (Induction Phase)
- Steroids: IV Methylprednisolone pulse -> Oral Prednisolone taper.
- Cyclophosphamide: The "Big Gun". IV pulses preferred over oral (less bladder toxicity).
- Rituximab: Anti-CD20. Non-inferior to Cyclophosphamide (RAVE trial) and preferred for fertility preservation.
RAVE Trial: Rituximab vs Cyclophosphamide
- The Question: Can we avoid the toxicity of Cyclophosphamide?
- The Answer: Yes. Rituximab (Anti-CD20) is non-inferior for inducing remission in ANCA vasculitis.
- Preferred In:
- Young patients (Fertility preservation).
- Relapsing disease.
- Frail elderly (less infection risk?).
- Downside: Expensive. Risk of Hypogammaglobulinemia (Low IgG).
Cyclophosphamide Safety (The "Red Devil")
- Bladder Toxicity: Acrolein metabolite causes Hemorrhagic Cystitis.
- Prevention: Mesna (binds acrolein) + Hyperhydration.
- Infertility: Gonadotoxic.
- Counseling: Sperm banking / Oocyte preservation before starting.
- Infection: Leukopenia nadir at 10-14 days. PJP Prophylaxis (Co-trimoxazole) mandatory.
3. Anti-GBM Disease
- Plasma Exchange (Plasmapheresis): Urgent daily exchange to physically remove the antibodies.
- Chemo: Cyclophosphamide + Steroids to stop production.
8. Complications
- Hyperkalemia: Life threatening.
- Pulmonary Edema: Volume overload.
- Hypertensive Encephalopathy: Seizures/Confusion from rapid BP rise.
- CKD: Progression to End Stage Renal Disease (ESRD) requiring dialysis.
- Cardiovascular Disease: The #1 cause of death in GN patients is not kidney failure, it is Heart Attack/Stroke.
- Mechanism: Inflammation + Hypertension + Dyslipidemia (Nephrotic range).
- Management: Statins, Aspirin, Ace-Inhibitors are crucial.
9. Differential Diagnosis
| Condition | Distinguishing Features |
|---|---|
| Acute Tubular Necrosis (ATN) | Muddy brown casts (not RBC casts). History of hypotension/toxin. No protein. |
| Pyelonephritis | WBC Casts. Fever. Flank pain. Positive culture. |
| Interstitial Nephritis (AIN) | WBC Casts + Eosinophils. History of new drug (PPI/Antibiotic). |
| Thrombotic Microangiopathy (TTP/HUS) | Hemolysis (Schistocytes). Low Platelets. Normal Coags. |
| Alport Syndrome | Deafness + Hematuria. Family history (X-linked). |
| Thin Basement Membrane | "Benign Familial Hematuria". Normal kidney function. No proteinuria. |
Thin Basement Membrane Nephropathy (TBMN)
The Benign Mimic.
- Prevalence: Common (1% of population).
- EM Finding: GBM is thinned (< 250nm) but structure preserved.
- Prognosis: Excellent. No proteinuria, no hypertension, no kidney failure. Do not biopsying unless confusion with Alport.
The Alport Story
Can't hear, Can't pee.
- Genetics: X-linked usually (COL4A5 mutation). Defect in Type IV Collagen (Basement Membrane).
- Triad:
- Deafness: Sensorineural (high frequency).
- Eyes: Anterior Lenticonus (lens shape abnormality).
- Kidney: Microscopic hematuria -> Proteinuria -> ESRD by age 20-30 (Males).
IgA Nephropathy vs Post-Strep GN
The two most common causes of gross hematuria.
| Feature | IgA Nephropathy | Post-Strep GN (PSGN) |
|---|---|---|
| Latency | 1-2 Days (Synpharyngitic) | 1-3 Weeks (Post-infectious) |
| Age | Young Adults (20s-30s) | Children (5-12) |
| Complement (C3) | Normal | Low (Returns to normal in 6w) |
| Recurrence | Frequent (with every cold) | Rare (Immunity develops) |
| Prognosis | Variable (CKD risk) | Excellent (Spontaneous resolution) |
10. Prognosis
- Post-Strep GN: Excellent. 95% of children recover completely. Adults have worse prognosis.
Pediatric Red Flags
When it's NOT just Post-Strep.
- Age < 4 or > 12: PSGN usually 5-12. Younger could be atypical HUS or Genetic.
- Normal C3: PSGN always has low C3. If normal, think IgA or Alport.
- Systemic Signs: Rash (HSP), Joint pain (Lupus), Lung bleed (Goodpasture's).
- Family History: Deafness (Alport).
- IgA Nephropathy: "Rule of Thirds" - 1/3 resolve, 1/3 stable CKD, 1/3 progress to ESRD over 20 years.
- RPGN: Poor without treatment. 80% survival with aggressive chemo, but many remain dialysis dependent.
Patient Guide: The "Renal Diet"
Protecting the kidneys.
- Salt: < 2g Sodium (one teaspoon). Essential for BP control.
- Potassium (If high): Avoid Bananas, Oranges, Tomatoes, Potatoes, Chocolate.
- Phosphate: Avoid Dairy, Cola, Processed meats. (Phosphate causes itching and bone disease).
- Protein: Moderate restriction (0.8g/kg/day). Too much protein increases glomerular filtration pressure (hyperfiltration).
11. Clinical FAQs (Patient Handout)
The Dialysis Catheter (VasCath)
If we need dialysis, how do we do it?
- Temporary: Non-tunneled line in Internal Jugular Vein (Neck) or Femoral Vein (Groin).
- Infection Risk: High. Strict asepsis mandatory.
- Goal: Bridge the gap until kidneys recover (Acute) or Fistula matures (Chronic).
Q: Will I need dialysis? A: Most cases of mild Nephritic syndrome (like IgA) do not need dialysis. However, if the inflammation is severe (RPGN), temporary dialysis might be needed to rest the kidneys.
Q: Can I catch this from someone? A: No. Even Post-Strep GN is an immune reaction after the infection has gone. The kidney disease is not contagious.
Discharge Checklist (Going Home)
- BP Controlled: < 130/80.
- Fluid Status: No edema. Weight stable.
- Potassium: < 5.0.
- Biopsy: Plan for result follow-up (usually takes 1 week).
- Diet: Low salt education given.
- Immunizations: Influenza/Pneumococcal (especially if on immunosuppression).
Q: Why do I need a biopsy? A: Blood tests give us clues, but looking at the kidney tissue under a microscope is the only way to know exactly which disease it is and how much permanent scarring is already there.
12. References
Primary Sources
- KDIGO Clinical Practice Guideline for the Management of Glomerular Diseases. 2021.
- Jennette JC et al. Chapel Hill Consensus Conference on the Nomenclature of Systemic Vasculitis.
Key Guidelines
- KDIGO: IgA Nephropathy Management.
- EULAR: Management of ANCA-associated vasculitis.
Medical Disclaimer: MedVellum content is for educational purposes and clinical reference. Clinical decisions should account for individual patient circumstances. Always consult appropriate specialists.