Pathophysiology
P-II-9. Kidney disease, Case 1
腰疾患 症例1
Complaints:
- 20-year-old woman
- In the last month: fatigue, headache
- Leg swelling (about six months)
- Alopecia: hair loss
- Joint pains
Symptoms:
- Blood pressure: 150/90 mmHg
- Face: butterfly-shaped rash/erythema
Laboratory (blood):
- Haemoglobin (Hb): 80 g/L (low)
- Haematocrit (HTK): 24% (low)
- MCV: 85 fL
- White blood cell count (WBC): 12 × 10⁹/L (high)
- Thrombocytes (PLT): 172 × 10⁹/L
- Sodium (Na⁺): 136 mmol/L
- Potassium (K⁺): 4.2 mmol/L
- Urea: 26.4 mmol/L (high)
- Creatinine: 176 μmol/L (high)
- Glucose: 4.8 mmol/L
- Albumin: 19 g/L (low)
- Sedimentation rate (ESR): 70 mm/h (high)
- eGFR (CKD-EPI): 35.2 mL/min/1.73m²
Laboratory (urine) — chemistry test strip:
- Bilirubin: neg
- Urobilinogen: 0.2 mg/dL
- Ketone: neg
- Vitamin C: neg
- Glucose: 28 mg/dL
- Protein: 500 mg/dL
- RBC: 300 RBCs/uL
- pH: 7.5
- Nitrite: neg
- White blood cell (LEU): 25 WBCs/uL
- Specific gravity: 1.001
- Turbidity: turbid
- Colour: red-brown
Urine sediment:
- Red blood cell (RBC): 1564 /uL
- White blood cell (WBC): 54.1 /uL
- Crystal: 2.6
- Hyaline cast: 1.8
- Pathologic cast: 2.6
- Non-epithelial cell: 3.1
- Epithelial cell: 4
- Bacterium: 72.6
- Mucus: 81.8
Blood — autoimmune / autoantibody panel:
- Antinuclear antibody (ANA) titre: 1:2560
- Anti-dsDNA antibody titre: >1000 IU/mL
- Anti-Smith (Sm) antibody: 142 units
- Anti-ribonucleoprotein (RNP) antibody: 114 units
- SS-A: 121 units
- SS-B: 39 units
- Complement C3: 36 mg/dL (low)
- Complement C4: 6 mg/dL (low)
Histology: IgG immunofluorescence performed.
Electron microscopy (EM): electron-dense (immune complex) deposits along the glomerular basement membrane (GBM).
Key Quotes & What They Tell Us
| Quote / Value | Interpretation |
|---|---|
| “butterfly-shaped rash/erythema”; alopecia; joint pains | Classic multisystem features of systemic lupus erythematosus (SLE) |
| ANA 1:2560; anti-dsDNA > 1000; anti-Sm positive; C3 36, C4 6 (low) | Highly specific lupus serology with complement consumption → active immune-complex disease |
| Protein 500 mg/dL; albumin 19 g/L (low); leg/face swelling | Heavy proteinuria with hypoalbuminaemia → nephrotic-range glomerular damage |
| Urine RBC 1564/µL; red-brown turbid urine; “pathologic casts” | Glomerular haematuria with casts → an active nephritic process |
| Urea 26.4, creatinine 176 µmol/L; eGFR 35 | Significant impairment of renal function (renal failure) |
| EM: “electron-dense (immune complex) deposits along the GBM”; IgG immunofluorescence | Immune-complex glomerulonephritis → confirms lupus nephritis |
| Hb 80 g/L; ESR 70 mm/h; WBC 12 | Anaemia of chronic disease/inflammation with a high inflammatory state |
Key Points
- Diagnosis: Lupus nephritis — glomerulonephritis as a manifestation of systemic lupus erythematosus.
- Mixed picture: Both nephritic (haematuria, casts, hypertension, renal impairment) and nephrotic (heavy proteinuria, hypoalbuminaemia, oedema) features.
- Serology: ANA, anti-dsDNA, and anti-Sm with low C3/C4 are the key diagnostic markers.
- Pathophysiology: Circulating immune complexes deposit in the glomerular basement membrane → complement activation → inflammation and glomerular injury.
- Demographic: Young woman — the typical SLE patient.
一問一答
▶What is the significance of anti-dsDNA antibodies in lupus?
They are highly specific for SLE and their levels correlate with disease activity, especially lupus nephritis.
▶What is the diagnosis in a 20-year-old woman with a butterfly rash, joint pains, heavy proteinuria, haematuria and renal impairment?
Lupus nephritis — glomerulonephritis as a manifestation of systemic lupus erythematosus (SLE).
▶Which clinical features point to systemic lupus erythematosus?
Butterfly-shaped facial rash, alopecia, and joint pains (a multisystem pattern).
▶Why are complement C3 and C4 low in active lupus nephritis?
Immune-complex formation consumes complement, so C3 and C4 fall during active disease.
▶Which autoantibodies are most specific for SLE?
Anti-dsDNA and anti-Smith (anti-Sm) antibodies (with a positive ANA).
▶Which findings indicate a nephrotic component in this patient?
Heavy proteinuria (500 mg/dL), hypoalbuminaemia (19 g/L), and oedema (leg/face swelling).
▶Which findings indicate a nephritic component in this patient?
Glomerular haematuria with red cells and pathologic casts, hypertension, and impaired renal function.
▶Why is lupus nephritis described as a mixed nephritic-nephrotic picture?
It combines nephritic features (haematuria, casts, hypertension) with nephrotic features (heavy proteinuria, hypoalbuminaemia, oedema).
▶What does electron microscopy show in lupus nephritis?
Electron-dense immune-complex deposits along the glomerular basement membrane.
▶What does IgG immunofluorescence demonstrate in lupus nephritis?
Granular deposition of immunoglobulin (and complement) in the glomeruli, confirming immune-complex disease.
▶What is the core pathophysiology of lupus nephritis?
Circulating immune complexes deposit in the glomerular basement membrane, activating complement and causing inflammation and glomerular injury.
▶Which hypersensitivity reaction underlies lupus nephritis?
Type III (immune-complex-mediated) hypersensitivity.
▶Why is the urine red-brown and turbid?
Glomerular haematuria (red cells from damaged glomeruli) plus cells/casts cause the discolouration and turbidity.
▶What is the significance of red blood cell / pathologic casts in the urine?
They indicate glomerular bleeding and an active glomerulonephritic process.
▶What lab values show impaired renal function in this patient?
Elevated urea (26.4 mmol/L) and creatinine (176 µmol/L) with a reduced eGFR (35 mL/min/1.73m²).
▶Why does this patient have anaemia and a high ESR?
Anaemia of chronic disease/inflammation, reflecting the high systemic inflammatory state of active SLE.
▶What does a very low urine specific gravity (1.001) indicate?
Impaired renal concentrating ability from glomerular/tubular damage.
▶Why does the patient have hypertension (150/90)?
Glomerular injury causes salt and water retention and activation of the renin-angiotensin system, raising blood pressure.
▶What is the typical demographic for SLE?
Young women of childbearing age.
▶How do the serology and renal biopsy together confirm lupus nephritis?
Specific lupus serology (ANA, anti-dsDNA, anti-Sm, low C3/C4) plus immune-complex deposits on biopsy/EM establish the diagnosis.