1. Pathology conference
報告者：fellow 1 陳筱惠

2. Case 01

3. Patient Profile Name: 江O君 Sex: female Age: 39-year-old
Chart number:
Date of admission: 2011/12/20

4. Chief Complaint
Persistent proteinuria for 10 years after pregnancy

5. Present Illness Preeclampsia history 10 years ago
Follow-up at NTUH thereafter
Deterioration of renal function in recent 2 years

6. Past History Underlying diseases:
Preeclampsia history 10 years ago
Chronic kidney disease (stage3, crea 1.3) under follow-up at NTUH
No diabetes mellitus, heart, liver, or other significant systemic diseases

7. Personal History Allergy: no known allergy
Alcohol, betel-nut, cigarette: denied
Over-the-counter medication or chinese herb: denied

8. Family History Father: chronic kidney disease
No family history of diabetes mellitus, malignancy, bleeding diathesis, heart, liver, or hereditary diseases

9. Physical Examination
Vital signs: blood pressure: 101/77mmHg; temperature: 36.8‘C; pulse rate: 67/min; respiratory rate: 18/min
General appearance: fair looking
Eye: conjunctiva: mild pale, sclera: no icteric
Neck: supple, no lymphadenopathy or jugular vein engorgement
Chest: symmetric expansion
breathing sound: bilateral clear
heart sound: regular heart beats, no S3 or S4, no
murmurs
Abdomen: soft, flat, no tenderness, no muscle guarding or
rebounding
liver/spleen: impalpable
bowel sound: normoactive
Extremities: no lower limb pitting edema
Skin: intact, no rash
Positive finding

10. OPD lab data 10/24 Color Yellow Turbidity Clear SP. Gravity 1.013 PH
5.0
Leukocyte -
Nitrite
Protein 3+
Glucose
Ketone
Urobilinogen
0.1
Bilirulin
10/24
Blood 3+
RBC
48 /uL
WBC
4 /uL
Epithelial cell
0 /uL
10/24 Hb
10.8 g/dL
Hct
33.7 %
Crea
1.58 mg/dL

11. 10/24
11/30
IgG
1360 mg/dL
Albumin
3.49 g/dL
IgA
402 mg/dL
12/30
ANA -
RPR
11/16
ASLO
76.6 u/mL
HBsAg
11/3:
Alb/Cre ratio  mg/g
24 urine TP loss  1.89 g/day
24hr Ccr  45.2 ml/min
Anti HCV Ab
Glucose (ac)
99 mg/dL
IgM
163 mg/dL
IgE
< 16.4 mg/dL C3
115 mg/dL C4
23 mg/dL
T-CHOL
220 mg/dL TG
40 mg/dL

12. Kidney Echo – 2011/11/07 Left Kidney Length: 9.5 cm
Right Kidney Length: 9.6 cm
Both kidneys are normal in size with mildly irregular contour.
The cortical echogenicity is increased with adequate thickness.
The pelvocalyceal systems are not dilated.
There is no evidence of renal stone, mass or cyst.

13. Kidney Biopsy – 2011/12/21 IGA NEPHROPATHY, CLASS V H AND E SECTIONS:
10 GLOMERULI  7 ARE OBSOLETE; 1 HAS FIBROUS CRESCENT FORMATION; 3 HAVE HYPERPLASIA WITH FOCAL SCLEROSIS.
THE TUBULES HAVE MODERATE ATROPHY AND PROTEIN CASTS.
THE INTERSTITIUM SHOW MODERATE FIBROSIS AND FOCAL CHRONI INFLAMMATION. THE ARTERIOLES HAVE MODERATE TO SEVERE ATHEROSCLEROSIS.

14. THE IMMUNOFLUORESCENCE SECTIONS:
7 GLOMERULI WITH IGA(2+), IGM(2+) AND C3(2-3+) IN MESANGIAL STAINING
THE VESSELS HAVE FOCAL STAINING OF C3(2+).
ELECTRON MICROSCOPIC STUDY:
2 GLOMERULI  MILD TO MODERATE MESANGIAL HYPERPLASIA WITH MESANGIAL DEPOSITS

15. Methylprednisolone 4mg 1# qd (11/7~)
Mycophenolate
180mg 1# bid (1/30~)
10/24
11/16
11/30
12/21
12/30
1/21
Crea (mg/dL)
1.58
1.71
1.55
1.42
1.53
1.61
U/A
Protein 3+ 2+
Blood
Trace
RBC 48
140

16. Discussion 127 middle-aged women, 45-65 (51 ± 1) years old
No significant differences in age, serum creatinine, urinary protein excretion
Significantly higher systolic blood pressure in the preeclamptic group exhibiting IgA nephropathy group
Pre-eclampsia, IgA nephropathy
日本 CKD
Short- and long-term prognosis of blood pressure and kidney disease in women with a past history of preeclampsia
Clin Exp Nephrol (2008) 12:102–109

17. Reports have varied as to what extent the glomerular lesions of preeclampsia regress after delivery.
Persistent preeclampsia damage or superimposed on an undiagnosed essential hypertension or any of a variety of renal diseases??

18. Women who have preeclampsia and give birth to offspring with low birth weight and short gestation have a substantially increased risk for having a later kidney biopsy.
Preeclampsia or placental dysfunction may cause directly or aggravate an already existing kidney disease.
Kidney disease, preeclampsia, and placental dysfunction may be caused by the same etiological factors (e.g., involving a genetic component).

19. Case 02

20. Patient Profile Name: 朱O標 Sex: male Age: 63-year-old Occupation: 公務員
Chart number:
Date of admission: 2012/01/06

21. Chief Complaint
Bilateral lower limb progressive swelling and pain for 1+ month

22. Present Illness
Underlying diseases: gout, suspect pulmonary tuberculosis
Anti-TB medication for 10 days, then holded himself due to poor appetite
NTM infection, erythromycin for 10 days
2011/11/30: BAL TB-PCR -, AFB and TB culture -
LMD: poor renal function (2011/11 crea 1.48mg/dL  2.8 mg/dL)
Associated S/S: distal extremity numbness, weight loss (7Kg in 4 months)

23. Past History Gout under medication control
No heart, liver, or other significant systemic diseases
Current medicine: anti-TB medication and erythromycin, each for 10 days

24. Personal History Allergy: no known allergy
Alcohol: denied; betel-nut: denied; cigarette: denied
Over-the-counter medication or chinese herb: nil

25. Family History
No family history of diabetes mellitus, malignancy, bleeding diathesis, heart, liver, kidney, or hereditary diseases

26. Physical Examination
Vital signs: blood pressure: 143/94 mmHg; temperature: 36.8‘C; pulse rate: 103/min; respiratory rate: 17/min
General appearance: acute ill looking
Eye: conjunctiva: mild pale, sclera: no icteric
Neck: supple, no lymphadenopathy or jugular vein engorgement
Chest: symmetric expansion
breathing sound: bilateral coarse
heart sound: regular heart beats, no S3 or S4, no
murmurs
Abdomen: soft, flat, no tenderness, no muscle guarding or
rebounding
liver/spleen: impalpable
bowel sound: normoactive
Extremities: lower limb pitting edema, grade 4 with tenderness
Skin: intact, no rash

27. Laboratory data 1/5 WBC 14.4x1000/ul Hgb 8.3 g/dl Hct 25.6 % MCV
85.3 fl
PLT
342 x1000/uL
Segment
90.5 %
1/5
BUN
62.2 mg/dl
Crea
3.91 mg/dl
GPT
67 IU/L NA
132 mEq/L K
4.8 mEq/L
Albumin
2.42 mg/dl
1/6
Myoglobin
1424 ng/mL CK
412.0 U/L 日期

28. Urinalysis – 1/5 Color Yellow Turbidity Cloudy SP. Gravity 1.013 PH
5.0
Leukocyte -
Nitrite
Protein 1+
Glucose
Ketone
Urobilinogen
0.1
Bilirulin
Blood 3+
Granular cast 1
RBC
17/uL
WBC
7/uL
Epithelial cell
1/uL

29. Chest X ray – 1/5

30. Hospitalization course
Lower limb
dupplex echo: -
Kidney echo
Lab data
BUN (mg/dL)
63.7
61.0
L’t kidney: cm
R’t kidney: 12.3 cm
Increased cortical echogenicity
Crea (mg/dL)
3.98
4.01
Na (mEq/L)
134
132
K (mEq/L)
4.1
Ca (mg/dL)
7.5
P (mg/dL)
Myoglobin (ng/mL)
1424
CK (U/L)
412

31. SSEP
MEP
polyneuropathy

32. Kidney biopsy
Methylprednisolone 1g on 1/17 and 500mg on 1/18, 1/19
4mg 3# qd
BUN (mg/dL)
103.9
NECROTIZING CRESCENTIC GLOMERULONEPHRITIS AND NECROTIZING GRANULOMATOUS VASCULITIS
AFB: -
Crea (mg/dL)
6.25
Na (mEq/L)
127
K (mEq/L)
3.6
Ca (mg/dL)
7.5
P (mg/dL)
6.4
U/O (ml/day)
2030
2550

33. Methylprednisolone 4mg 3# qd
BUN (mg/dL)
155.2
125.8
Crea (mg/dL)
5.12
3.63
Na (mEq/L)
134
133
K (mEq/L)
3.5
4.4
Ca (mg/dL)
8.2
8.8
P (mg/dL)
6.0
5.8
CO2 (mEq/L)
20.9
22.3
U/O (ml/day)
2370
1880
1465
1560
1430

34. Methylprednisolone 4mg 3# qd
BUN (mg/dL)
80.9
Crea (mg/dL)
2.79
Na (mEq/L)
130
K (mEq/L)
4.4
Ca (mg/dL)
7.7
P (mg/dL)
3.7
CO2 (mEq/L)
21.1
U/O (ml/day)
1540
1680
1390
1800
2130

35. Methylprednisolone 4mg 3# qd 3# bid Cyclophosphamide 50mg 1# bid
ENT
BUN (mg/dL)
67.4
Crea (mg/dL)
2.54
Na (mEq/L)
133
K (mEq/L)
4.3
Ca (mg/dL)
7.7
P (mg/dL)
CO2 (mEq/L)
21.1
neuropathy

36. Methyprednisolone 4mg 3# bid
Cyclophosphamide 50mg 1# bid
BUN (mg/dL)
67.6
Crea (mg/dL)
2.43
Na (mEq/L)
134
K (mEq/L)
4.1
Ca (mg/dL)
7.5
P (mg/dL)
4.0

37. Methyprednisolone 4mg 3# bid
500mg qd
BUN (mg/dL)
64.7
Crea (mg/dL)
2.13
Na (mEq/L)
136
K (mEq/L)
4.2
Ca (mg/dL)
7.3
P (mg/dL)
3.8

38. Case 03

39. Patient Profile Name: 丁李O英 Sex: female Age: 66-year-old
Chart number:
Date of admission: 2012/01/02

40. Chief Complaint
Nausea and poor appetite for 2 months

41. Present Illness Underlying diseases: hypertension and hyperlipidemia
Nausea and poor appetite for 2 months
Associated S/S: weight loss (10Kg)
2011/11 LMD: diabetes mellitus, poor renal function (2011/11 BUN/crea: 22.8/2.75 mg/dL), and nephrotic syndrome

42. Past History
Underlying diseases: hypertension, diabetes mellitus, and hyperlipidemia
Operation history: left breast cancer s/p op in 1995
No heart, liver, or other significant systemic diseases
Current medicine:
Ramipril (2.5mg) 1# qd + Amlodipine (5mg) 1# qd
Gliclazide (30mg) 1# qd
rosuvastatin (10mg) 1# qd

43. Personal History Allergy: no known allergy
Alcohol, betel-nut, cigarette: denied
Over-the-counter medication or chinese herb: denied

44. Family History Father, mother, and sister: diabetes mellitus
No family history of malignancy, bleeding diathesis, heart, liver, or hereditary diseases

45. Physical Examination
Vital signs: blood pressure: 133/81mmHg; temperature: 35‘C; pulse rate: 64/min; respiratory rate: 16/min
General appearance: fair looking
Eye: conjunctiva: mild pale, sclera: no icteric
Neck: supple, no lymphadenopathy or jugular vein engorgement
Chest: symmetric expansion
breathing sound: bilateral clear
heart sound: regular heart beats, no S3 or S4, no
murmurs
Abdomen: soft, flat, no tenderness, no muscle guarding or
rebounding
liver/spleen: impalpable
bowel sound: normoactive
Extremities: no lower limb pitting edema
Skin: intact, no rash
Positive finding

46. OPD lab data 12/28 Color Yellow Turbidity Clear SP. Gravity 1.009 PH
7.0
Leukocyte -
Nitrite
Protein 4+
Glucose
Ketone
Urobilinogen
0.1
Bilirulin
10/24
Blood 1+
RBC
6 /uL
WBC
3 /uL
Epithelial cell
0 /uL
12/28
WBC
10300/uL Hb
10.2 g/dL
Hct
31.1 %
BUN
72.6 mg/dL
Crea
7.25 mg/dL

47. 12/28 K
4.8 mEq/L
IgG
1120 mg/dL
Albumin
3.01 g/dL
IgA
199 mg/dL
Total protein
6.4 g/dL
IgM
40.3 mg/dL
T-chol
232 mg/dL
IgE
< 16.4 mg/dL TG
268 mg/dL
IgD
<42.3 mg/dL
12/28:
24 urine TP loss  9.50 g/day
24hr Ccr  7.93ml/min
1/5:
PEP  A suspicious faint band at gamma-region
IFE  IgG-kappa IgG(?)-lambda
ANA - RF
< 10.4 U/mL C3
115 mg/dL C4
23 mg/dL
HBsAg
Anti HCV Ab
RPR

48. Kidney Echo – 2011/12/31 Left Kidney Length: 11.08 cm
Right Kidney Length: cm
The both kidneys have relative swelling in size and regular contour.
The cortical echogenicity is increased with normal thickness.
There is mild pelvocalyceal dilatation over bilateral central sinus area (L't>R't).
No stone or mass is noted.

49. Kidney Biopsy – 2012/01/04 AMYLOIDOSIS H & E SECTIONS:
6 GLOMERULI  3 ARE OBSOLETE; 3 HAVE DIFFUSE AMORPHOUS, PINK NODULAR DEPOSITS IN CAPILLARY WALLS. (SUCH DEPOSITS ARE ALSO PRESENT IN INTERSTITIUM.)
THE INTERSTITIUM ALSO HAS SEVERE FIBROSIS AND SEVERE CHRONIC INFLAMMATION.
THE ARTERIOLES HAVE SEVERE SCLEROSIS WITH AMORPHOUS DEPOSITS. THESE DEPOSITS ARE CONSISTENT WITH AMYLOID.

50. IMMUNOFLUORESCENCE SECTIONS: NEGATIVE
THE CONGO RED STAIN: POSITIVE AMYLOID IN GLOMERULI, ARTERIAL WALL AND IN INTERSTITIAL STROMA

51. Bone marrow examination – 2012/01/18
No increase in plasma cells
Pathology:
HYPOCELLULARITY WITH MILD INCREASE OF PLASMA CELLS

52. 12/28
1/3
1/5
1/16
2/4
BUN (mg/dL)
72.6
67.5
70.6
91.2
Crea (mg/dL)
7.25
6.65
6.58
7.05
10.1
Na (mEq/L)
140
137
K (mEq/L)
4.8
4.4
4.2
4.1
3.8
Ca (mg/dL)
9.7
11.6
9.5
P (mg/dL)
7.5
7.7
6.6
CO2 (mEq/L)
16.5
Alb (g/dL)
3.01
2.36
2.44
2.76
2.60

53. Discussion
Drug induced AIN
Arch Pathol Lab Med—Vol 134, April 2010

54. Extracellular matrix proteins

55. The amyloidogenic precursor proteins, folding intermediates, aggregates, and oligomers have tissue and cellular toxicities that contribute to amyloidosis-associated organ dysfunction independent of mature amyloid fibrils.
J Am Soc Nephrol 20: 469–472, 2009

56. Thanks for your listening

57. 1/7 RF
36.90 U/mL
ANA - C3
123 mg/dL C4
22.4 mg/dL
A-DSDNA
< 40.5 U/mL
1/9
ASLO
< IU/Ml
A/G
0.26
PEP/IFE
Chronic inflammation pattern with decrease albumin and polyclonal increase of gamma globulin
No paraprotein
1/9
P-ANCA +
C-ANCA -
1/16
MPO
+, 64.7 U
PR3
-, 3.96 U
1/18
IgG
2920 mg/dL
IgA
157 mg/dL
IgM
42.10 mg/dL
IgE
304 mg/dL