Nephritic Syndrome Clinical Overview
I. The "On-Call" Snapshot
Clinical Significance in Malaysia: You will encounter this in the medical wards, usually as a patient admitted for Acute Kidney Injury (AKI) or uncontrolled hypertension with haematuria. Your primary role is to stabilise the patient (fluid, BP) and initiate the diagnostic workup.
High-Yield Definition: Nephritic syndrome is a clinical syndrome, not a single disease. It is defined by the presence of haematuria (with dysmorphic red blood cells and RBC casts in the urine), hypertension, oliguria (or AKI), and sub-nephrotic proteinuria (<3.5 g/day).
Clinical One-Liner: This is acute inflammation of the glomerulus. Think "blood and pressure" (haematuria, HTN), as opposed to nephrotic syndrome, which is "protein and swelling."
II. Etiology & Risk Factors
Etiology: The core mechanism is immune-mediated inflammation of the glomeruli (glomerulonephritis, or GN). This can be:
Primary: The GN is the main disease (e.g., IgA Nephropathy).
Secondary: The GN is a manifestation of a systemic disease (e.g., SLE, Vasculitis) or infection.
Key Risk Factors (Local Context):
Recent Infection: A history of pharyngitis or skin infection (impetigo) 1-3 weeks prior suggests Post-Streptococcal GN (PIGN). This is common.
Autoimmune Disease: Always ask for symptoms of SLE (malar rash, joint pain), especially in young females, as Lupus Nephritis is a major cause here.
Systemic Vasculitis: Ask about sinusitis, cough, or haemoptysis (ANCA-associated vasculitis) or purpuric rash (IgA vasculitis/HSP).
III. Quick Pathophysiology
Immune Complex Deposition: Antibodies or immune complexes (e.g., post-infection, SLE) deposit in the glomeruli.
Inflammation: This triggers a local inflammatory cascade, recruiting neutrophils and macrophages.
Glomerular Damage: The inflammation causes proliferation of glomerular cells (endothelial, mesangial) and physical breaks in the glomerular basement membrane (GBM).
Clinical Signs:
Haematuria & RBC Casts: RBCs leak through the damaged GBM. Casts are formed as RBCs get stuck in the tubular lumen.
Oliguria & AKI: Inflammation and cell proliferation reduce the glomerular surface area for filtration, causing GFR to drop.
Hypertension & Oedema: The drop in GFR leads to salt and water retention. This causes volume-expansion hypertension and mild/moderate oedema (often periorbital).
IV. Classification
Classification is based on etiology, which is ultimately determined by serology and renal biopsy. The most clinically urgent distinction is:
Acute Nephritic Syndrome: The classic, often self-limiting presentation (e.g., PIGN).
Rapidly Progressive Glomerulonephritis (RPGN): This is a nephrological emergency, defined by a >50% loss of GFR within 3 months. It is characterised by "crescents" on histology and portends a very poor prognosis if not treated aggressively. Causes include ANCA vasculitis and Anti-GBM disease.
V. Clinical Assessment
🚩 Red Flags & Immediate Actions:
Rapidly Rising Creatinine (RPGN):
Action: Urgent escalation to nephrology registrar/specialist. Prepare for urgent renal biopsy and high-dose immunosuppression (e.g., pulse methylprednisolone).
Reason: High risk of irreversible renal failure.
Severe Hypertension / Hypertensive Emergency (e.g., BP >180/110 with symptoms):
Action: Secure IV access, start cardiac monitoring, administer IV antihypertensives (e.g., IV Labetalol 20mg).
Reason: Risk of PRES, stroke, or acute heart failure.
Haemoptysis:
Action: Stat CXR, escalate immediately.
Reason: Suspect pulmonary-renal syndrome (e.g., Goodpasture's, ANCA vasculitis). This is life-threatening.
Anuria / Severe Oliguria:
Action: Assess fluid status (JVP, lung bases). Consider fluid challenge if hypovolaemic. Urgent renal ultrasound to rule out obstruction. Prepare for potential dialysis.
Reason: Indicates severe AKI.
History:
Key Diagnostic Clues:
"Coca-cola" or "Teh O" coloured urine (macroscopic haematuria).
Recent sore throat or skin infection (PIGN).
Facial puffiness, worse in the morning (periorbital oedema).
Systemic symptoms: Joint pain, malar rash (SLE); new purpuric rash (Vasculitis); cough, haemoptysis (Pulmonary-renal syndrome).
Symptom Breakdown:
Common (>50%): Haematuria (microscopic or macroscopic), periorbital/pedal oedema, hypertension.
Less Common (10-50%): Oliguria, lethargy, anorexia, arthralgia.
Rare (<10%): Haemoptysis, flank pain, purpuric rash.
Pertinent Negatives:
No frothy urine (suggests sub-nephrotic range proteinuria).
No anasarca or massive ascites (more typical of nephrotic syndrome).
No recent nephrotoxic drugs (rules out other causes of AKI like AIN).
No renal colic or dysuria (rules out urological causes of haematuria).
Physical Examination (OSCE Approach):
General Inspection: Patient may look unwell, puffy face (periorbital oedema), may have pedal oedema (pitting, usually mild-to-moderate). Look for rashes (malar, purpuric).
Vitals: Hypertension is the classic sign. May be tachycardic (fluid overload), low-grade fever.
Disease-Specific Examination:
Fluid Status: Check JVP (likely elevated), listen to lung bases (basal crepitations suggest pulmonary oedema), check for sacral oedema.
Skin: Look for impetigo scars, malar rash (SLE), palpable purpura on lower limbs (IgA vasculitis/HSP).
Cardiovascular: Check apex beat (may be displaced from LVH), listen for 3rd heart sound (fluid overload).
Pertinent Negatives: Absence of massive anasarca. Abdomen is soft, non-tender, no hepatosplenomegaly.
Examination for Differentials: Check for severe pitting oedema +3/+4 (nephrotic). Check renal angle tenderness (pyelonephritis, though less likely).
Clinical Pearl: Always spin the urine and look at the sediment yourself (UFEME). The presence of RBC casts is pathognomonic for glomerulonephritis. It proves the bleeding is from the glomerulus, not the bladder or ureters.
VI. Diagnostic Workflow
Differential Diagnosis:
Nephrotic Syndrome:
Points For: Oedema.
Points Against: No/minimal haematuria, frothy urine, massive proteinuria (>3.5g/day), severe hypoalbuminaemia.
How to Differentiate: Urine dipstick (Protein 4+, Blood 0/1+), urine protein:creatinine ratio (uPCR).
Acute Interstitial Nephritis (AIN):
Points For: AKI.
Points Against: Typically follows drug exposure (NSAIDs, antibiotics), classic triad (fever, rash, eosinophilia) is rare. Haematuria is present, but RBC casts are absent.
How to Differentiate: History of new drug, urine FEME (WBCs, WBC casts, urine eosinophils).
Urological Bleeding (e.g., Renal stones, TCC):
Points For: Macroscopic haematuria.
Points Against: No oedema, no HTN, no proteinuria, no RBC casts. Often has associated flank pain/colic.
How to Differentiate: UFEME (RBCs present, but no casts and RBCs are isomorphic, not dysmorphic). Ultrasound/CT KUB.
Investigations Plan:
Bedside / Initial (First 15 Mins):
Urine Dipstick: Haematuria (+++), Proteinuria (+ or ++).
UFEME: Crucial. Look for dysmorphic RBCs and RBC casts.
ECG: Check for hyperkalaemia (peaked T waves) or LVH (from chronic HTN).
First-Line Labs & Imaging (The AKI Workup):
Renal Profile (Urea, Creatinine, Electrolytes): To stage AKI and check for hyperkalaemia.
FBC: May show anaemia (of chronic disease, or from haemolysis in some GNs).
ESR/CRP: Non-specific markers of inflammation.
Renal Ultrasound: To rule out hydronephrosis (obstruction) and assess kidney size/echogenicity (small kidneys = chronic; large, swollen = acute).
Second-Line (The "Glomerular Workup"):
Complements (C3, C4): This is a key branching point.
Low C3/C4: Suggests complement consumption (e.g., SLE, PIGN, MPGN).
Normal C3/C4: Suggests non-complement-mediated (e.g., IgA Nephropathy, ANCA vasculitis).
ASOT (Anti-streptolysin O titre): Raised in Post-Streptococcal GN.
Autoimmune Screen: ANA, Anti-dsDNA (for SLE).
Vasculitis Screen: ANCA (c-ANCA, p-ANCA).
Anti-GBM Antibody: If pulmonary-renal syndrome suspected.
Virology: Hepatitis B, Hepatitis C, HIV (all can cause secondary GN).
Urine Protein:Creatinine Ratio (uPCR): To quantify proteinuria.
Confirmatory / Gold Standard:
Renal Biopsy: This is the definitive test. It provides the exact histological diagnosis, which guides specific treatment. It also assesses for activity vs. chronicity (fibrosis), which informs prognosis.
VII. Staging & Severity Assessment
Severity is staged clinically based on GFR, degree of hypertension, and volume overload.
Mild: Microscopic haematuria, normal/mild HTN, normal renal function.
Moderate: Macroscopic haematuria, moderate HTN, mild-to-moderate AKI.
Severe (RPGN picture): Oligoanuria, severe HTN (or hypertensive emergency), rapidly rising creatinine, often with systemic features.
VIII. Management Plan
A. Principle of Management:
Supportive Care: Control BP and manage fluid volume. This is your immediate priority.
Specific Therapy: Treat the underlying cause, usually with immunosuppression, guided by biopsy.
Manage Complications: e.g., AKI requiring dialysis.
B. Immediate Stabilisation (The ABCDE Plan for Severe Cases):
A - Airway: Usually patent.
B - Breathing: Give high-flow O2 if hypoxic (SpO2 <94%). Sit patient up. Listen for crackles (pulmonary oedema). Give IV Furosemide 40-80mg stat.
C - Circulation: Secure 2 large-bore IV cannulae.
For Severe HTN: IV Labetalol 20mg slow bolus, or IV Hydralazine 5-10mg.
For Volume Overload: Fluid restriction (<1.5L/day), low salt diet (<2g Na/day), loop diuretics (Furosemide).
D - Disability: Check GCS (risk of hypertensive encephalopathy/PRES).
E - Exposure: Check temperature.
C. Definitive Treatment (The Ward Round Plan):
This is entirely dependent on the underlying biopsy diagnosis.
Supportive (For ALL patients):
Diet: Salt restriction (<2g/day) and fluid restriction.
BP Control: Target <130/80 mmHg.
First-line: ACE-inhibitors (e.g., Perindopril) or ARBs (e.g., Losartan). These are renal-protective and anti-proteinuric. Use with caution and monitor K+ and creatinine if GFR is low.
Second-line: Calcium channel blockers (e.g., Amlodipine) or other agents as needed.
Diuretics: Loop diuretics (Furosemide) for oedema.
Specific (Post-Biopsy Examples):
Post-Infectious GN: Supportive management only. Antibiotics if infection is still active. Prognosis is excellent in children.
IgA Nephropathy: If high-risk (proteinuria >1g/day, rising Cr): Start ACEi/ARB. Consider 6-month course of corticosteroids (as per KDIGO guidelines).
Lupus Nephritis (Class III/IV): Aggressive immunosuppression. Induction with Mycophenolate Mofetil (MMF) or Cyclophosphamide, plus high-dose steroids. (Refer Malaysian CPG for SLE).
RPGN (ANCA/Anti-GBM): This is an emergency.
Pulse IV Methylprednisolone 500mg-1g daily for 3 days.
Followed by Cyclophosphamide (IV or oral) OR Rituximab.
Plasmapheresis is indicated for Anti-GBM disease and severe ANCA vasculitis (e.g., dialysis-dependent, pulmonary haemorrhage).
D. Long-Term & Discharge Plan:
Strict adherence to low-salt diet and medications.
Patient education on "sick day rules" (e.g., stop ACEi if D&V).
Mandatory long-term follow-up under Nephrology clinic (TCA) to monitor BP, renal profile, and uPCR.
IX. Complications
Immediate: Hypertensive emergency (PRES, ICH, MI), acute pulmonary oedema, severe AKI requiring renal replacement therapy (RRT), life-threatening hyperkalaemia.
Short-Term: Uncontrolled hypertension, volume overload.
Long-Term: Progression to Chronic Kidney Disease (CKD) and End-Stage Renal Disease (ESRD).
X. Prognosis
Highly variable and depends entirely on the etiology.
PIGN: Excellent in children (>95% recovery). Worse in adults (up to 50% may develop CKD).
IgA Nephropathy: Variable; "rule of 20s" (20-30% progress to ESRD in 20 years).
RPGN: If untreated, >80% progress to ESRD or death in weeks to months. With aggressive, early treatment, renal survival is possible.
Key Prognostic Factors: Baseline creatinine, degree of proteinuria at presentation, severity of HTN, and histological findings (e.g., percentage of crescents, degree of interstitial fibrosis/tubular atrophy).
XI. How to Present to Your Senior
Use the SBAR format.
(S) Situation: "Dr, I'm calling about Mr. A, a 25-year-old man in Bed 5, who presented with 3 days of 'coca-cola' urine and facial puffiness."
(B) Background: "He was well until 2 weeks ago when he had a sore throat. No other medical history. His vitals on admission are BP 160/100, HR 90, SpO2 98% on room air. He is peripherally oedematous with crackles at both lung bases."
(A) Assessment: "My assessment is acute nephritic syndrome with fluid overload and uncontrolled hypertension. His urine dipstick is Blood 4+, Protein 2+. The UFEME shows >100 RBCs and 5-10 RBC casts per high-power field. His urgent renal profile shows Creatinine 210 (baseline 90), Urea 15, and K+ 5.1. I am suspecting post-streptococcal GN, but we cannot rule out a more aggressive RPGN."
(R) Recommendation: "I have started him on 2g salt restriction and 1.5L fluid restriction. I have also given a stat dose of IV Furosemide 40mg. For his BP, I would like to start Amlodipine 5mg OD. I have also sent off the full 'glomerular workup' including C3/C4, ASOT, and ANA. I will monitor his urine output and repeat the renal profile in the morning. Should we prepare him for a renal biopsy if his creatinine continues to rise?"
XII. Summary & Further Reading
Top 3 Takeaways:
Nephritic syndrome is a clinical diagnosis: Haematuria (RBC casts), HTN, Oliguria, Oedema.
Your first job is to stabilise: Manage fluid overload (diuretics, restriction) and hypertension (anti-hypertensives).
Your second job is to investigate: UFEME is key (RBC casts = glomerular). The "glomerular workup" (complements, autoimmune screen) and renal biopsy are essential to find the cause and guide definitive treatment.
Key Resources:
UpToDate: Search for "Glomerulonephritis: Etiology and classification" and "Overview of the management of glomerulonephritis".
Amboss: Search "Nephritic syndrome".
Local CPGs: There is no single "Nephritic syndrome" CPG. Refer to etiology-specific guidelines, such as the Malaysian CPG on Management of Systemic Lupus Erythematosus (2017) for Lupus Nephritis.
