1. 報告者： fellow 1 陳筱惠

3.  Name: 江 O 君  Sex: female  Age: 39-year-old  Chart number: 10613576  Date of admission: 2011/12/20

4.  Persistent proteinuria for 10 years after pregnancy

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

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

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

9.  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

10. 10/24 Blood3+ RBC48 /uL WBC4 /uL Epithelial cell0 /uL 10/24 ColorYellow TurbidityClear SP. Gravity1.013 PH5.0 Leukocyte- Nitrite- Protein3+ Glucose- Ketone- Urobilinogen0.1 Bilirulin- 10/24 Hb10.8 g/dL Hct33.7 % Crea1.58 mg/dL

11. 10/2411/30 IgG1360 mg/dLAlbumin3.49 g/dL IgA402 mg/dL12/30 ANA-RPR- 11/16ASLO76.6 u/mL HBsAg- 11/3: Alb/Cre ratio  1435.3 mg/g 24 urine TP loss  1.89 g/day 24hr Ccr  45.2 ml/min Anti HCV Ab- Glucose (ac)99 mg/dL IgM163 mg/dL IgE< 16.4 mg/dL C3115 mg/dL C423 mg/dL T-CHOL220 mg/dL TG40 mg/dL

12.  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.  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. 10/2411/1611/3012/2112/301/21 Crea (mg/dL)1.581.711.551.421.531.61 U/A Protein3+2+ Blood3+ 2+Trace RBC48140 Methylprednisolone 4mg 1# qd (11/7~) 3# qd (½~) Mycophenolate 180mg 1# bid (1/30~)

16. 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  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

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).

20.  Name: 朱 O 標  Sex: male  Age: 63-year-old  Occupation: 公務員  Chart number: 2772470  Date of admission: 2012/01/06

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

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

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

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

26.  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. 1/5 WBC14.4x1000/ul Hgb8.3 g/dl Hct25.6 % MCV85.3 fl PLT342 x1000/uL Segment90.5 % 1/5 BUN62.2 mg/dl Crea3.91 mg/dl GPT67 IU/L NA132 mEq/L K4.8 mEq/L Albumin2.42 mg/dl 1/6 Myoglobin1424 ng/mL CK412.0 U/L

28. ColorYellow TurbidityCloudy SP. Gravity1.013 PH5.0 Leukocyte- Nitrite- Protein1+ Glucose- Ketone- Urobilinogen0.1 Bilirulin- Blood3+ Granular cast1 RBC17/uL WBC7/uL Epithelial cell1/uL

30. BUN (mg/dL)63.761.0L’t kidney: 12.6 cm R’t kidney: 12.3 cm Increased cortical echogenicity Crea (mg/dL)3.984.01 Na (mEq/L)134132 K (mEq/L)4.1 Ca (mg/dL)7.5 P (mg/dL)4.1 Myoglobin (ng/mL)1424 CK (U/L)412 Lower limb dupplex echo: - Kidney echo Lab data

31. SSEP MEP polyneuropathy

32. BUN (mg/dL)103.9NECROTIZING 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)20302550 Kidney biopsy Methylprednisolone 1g on 1/17 and 500mg on 1/18, 1/19 4mg 3# qd

33. BUN (mg/dL)155.2125.8 Crea (mg/dL)5.123.63 Na (mEq/L)134133 K (mEq/L)3.54.4 Ca (mg/dL)8.28.8 P (mg/dL)6.05.8 CO2 (mEq/L)20.922.3 U/O (ml/day)23701880146515601430 Methylprednisolone 4mg 3# qd

34. 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)15401680139018002130 Methylprednisolone 4mg 3# qd

35. 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)4.3 CO2 (mEq/L)21.1 Methylprednisolone 4mg 3# qd 3# bid Cyclophosphamide 50mg 1# bid ENT

36. 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 Methyprednisolone 4mg 3# bid Cyclophosphamide 50mg 1# bid

37. 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 Methyprednisolone 4mg 3# bid 500mg qd Methyprednisolone 4mg 3# bid

39.  Name: 丁李 O 英  Sex: female  Age: 66-year-old  Chart number: 2326262  Date of admission: 2012/01/02

40.  Nausea and poor appetite for 2 months

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

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

45.  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

46. 10/24 Blood1+ RBC6 /uL WBC3 /uL Epithelial cell0 /uL 12/28 ColorYellow TurbidityClear SP. Gravity1.009 PH7.0 Leukocyte- Nitrite- Protein4+ Glucose- Ketone- Urobilinogen0.1 Bilirulin- 12/28 WBC10300/uL Hb10.2 g/dL Hct31.1 % BUN72.6 mg/dL Crea7.25 mg/dL

47. 12/28 K4.8 mEq/LIgG1120 mg/dL Albumin3.01 g/dLIgA199 mg/dL Total protein6.4 g/dLIgM40.3 mg/dL T-chol232 mg/dLIgE< 16.4 mg/dL TG268 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 C3115 mg/dL C423 mg/dL HBsAg- Anti HCV Ab- RPR-

48.  Left Kidney Length: 11.08 cm  Right Kidney Length: 10.56 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.  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.  No increase in plasma cells  Pathology:  HYPOCELLULARITY WITH MILD INCREASE OF PLASMA CELLS

52. 12/281/31/51/162/4 BUN (mg/dL)72.667.570.691.2 Crea (mg/dL)7.256.656.587.0510.1 Na (mEq/L)140 137 K (mEq/L)4.84.44.24.13.8 Ca (mg/dL)9.710.111.69.5 P (mg/dL)7.57.76.6 CO2 (mEq/L)16.5 Alb (g/dL)3.012.362.442.762.60

53. Arch Pathol Lab Med—Vol 134, April 2010

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

57. 1/7 RF36.90 U/mL ANA- C3123 mg/dL C422.4 mg/dL A-DSDNA< 40.5 U/mL 1/9 ASLO< 54.10 IU/Ml A/G0.26 PEP/IFEChronic 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 IgG2920 mg/dL IgA157 mg/dL IgM42.10 mg/dL IgE304 mg/dL