報告者： fellow 1 陳筱惠

 Name: 黃 O 堯  Sex: male  Age: 25-year-old  Occupation: 車床工程師  Chart number:  Date of admission: 2011/10/07

 Decreased urine output for 1 month

 Underlying diseases:  Chronic kidney disease (the latest crea level: 2009/ mg/dl)  Nephrotic syndrome associated with minimal change disease  Decreased urine output in recent 1 month  No fever, nausea/vomiting, fatigue, dyspnea, anorexia, dizziness

 Underlying diseases: regular Nephro OPD follow up till 2009, then loss of follow up  Chronic kidney disease (the latest crea level: 2009/ mg/dl)  Nephrotic syndrome associated with minimal change disease  Hypertension  dyslipidemia  No diabetes mellitus, heart, liver, or other significant systemic diseases  Current medicine: nil

 Allergy: no known allergy  Alcohol: quitted for 4 years after diagnosing MCD  Betel-nut: denied  Cigarette: 1~2 ppd/day for 9 years  Over-the-counter medication or chinese herb: about 2 years

 Mother: Thalassemia  Grandmother: chronic kidney disease, no hemodialysis  No family history of diabetes mellitus, malignancy, bleeding diathesis, heart, liver, or hereditary diseases

 Vital signs: blood pressure: 157/108mmHg; temperature: 35.8‘C; pulse rate: 86/min; respiratory rate: 18/min  General appearance: chronic ill looking  Eye: conjunctiva: 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

WBC11.9x1000/ul Hgb7.0 g/dl Hct20.4 % MCV56.2 fl PLT287 x1000/uL Segment69.4 % Lymphocyte14.0 % Monocyte2.2 % Eosinophil14.0 % Basophil0.4 % BUN163.5 mg/dl Crea25.09 mg/dl GPT12 IU/L NA140 mEq/L K2.7 mEq/L Cl100 mEq/L Albumin2.45 g/dl Ca< 5 mg/dl PH7.354 PCO228.6 mmHg PO mmHg HCO315.6 mm/L SaO298.2 %

ColorYellow TurbidityCloudy SP. Gravity1.012 PH6.0 Leukocyte- Nitrite- Protein4+ GlucoseTrace Ketone- Urobilinogen0.1 Bilirulin- Blood2+ RBC20 /uL WBC13 /uL Epithelial cell5 /uL

 Left Kidney Length: 13.6 cm  Right Kidney Length: 13.8 cm  The both kidneys are large in size with regular contour.  The cortical echogenicity is slightly increased with adequate thickness.  The central sinus is unremarkable.  No stone, mass, or hydronephrosis

 Left Kidney Length: 11.2 cm  Right Kidney Length: 11.6 cm  Both kidneys are normal in size with regular contour.  The cortical echogenicity is increased with adequate thickness. The pelvocalyceal systems are not dilated.  No obvious evidence of renal stone, mass, or cyst

 MINIMAL CHANGE DISEASE  4 PIECES OF TISSUE  H&E SECTIONS: ▪ 11 GLOMERULI WITH MILD MESANGIAL HYPERPLASIA ▪ INTERSTITIUM  MILD CHRONIC INFLAMMATION ▪ TUBULES  PROTEIN CASTS ▪ PRESERVED ARTERIES  IMMUNOFLUORESCENCE SECTIONS: 13 GLOMERULI, ALL STAINS NEGATIVE  ELECTRON MICROSCOPIC STUDY: ▪ ONE GLOMERULUS WITH DIFFUSE FUSION OF FOOT PROCESSES WITH VILLOUS TRANSFORMATION ▪ NO DEPOSITS

 CRESCENTIC GLOMERULONEPHRITIS WITH ADVANCED SCLEROSIS  TUBULOINTERSTITIAL NEPHRITIS  3 CORES OF KIDNEY TISSUE, YELLOWISH,WHITISH, FRAGMENTED AND SOFT  H&E SECTIONS: ▪ 9 GLOMERULI  5 ARE NEARLY TOTAL OR TOTAL OBSOLETE, 3 HAVE HYPERPLASIA WITH CRESCENT AND SEVERE SCLEROSIS ▪ INTESTITIUM  MARKED INFLAMMATION AND FIBROSIS COMBINED WITH MARKED TUBULAR ATROPHY ▪ THE ARTERIES AND ARTERIOLES  MINIMAL CHANGES.  IMMUNOFLUORESCENCE SECTIONS: 4 GLOMERULI  2 ARE OBSOLETE, ALL NEGATIVE

10/15 RPR- ASLO< 51.6 U/mL A/G1.43 PEP/IFEProtein loss or malnutrition pattern with decrease of protein and albumin No paraprotein is identified. IgG507 mg/dL IgA191 mg/dL IgM124 mg/dL IgE165 mg/dL C376.8 mg/dL C420.8 mg/dL ANA- 10/8 T-CHOL222 mg/dL HBs Ag- Anti HCV Ab- 10/9 24 urine TP loss17.34 g/day 24hr Ccr3.67 ml/min 10/11 i-PTH255.5 pg/mL 10/17 P-ANCA- C-ANCA-

10/810/1110/1310/1510/1710/1910/22 BUN (mg/dL) Crea (mg/dL) Na (mEq/L) K (mEq/L) Ca (mg/dL)< < 55.5 P (mg/dL) CO2 (mEq/L) Alb (g/dL) U/O (ml/day) Solu-cortef (100mg) 1pc iv q8h 10/8~10/21 Kidney biopsy 10/12 Prednisolone (5mg) 3# po bid 10/21~

 Definition: presence of inflammatory infiltrates and edema within the interstitium Acute interstitial nephritis Kidney International (2010) 77, 956–961

 The initial event: expression of endogenous nephritogenic antigens or exogenous antigens processed by tubular cells  Tamm–Horsfall protein  Megalin: a protein localized in the brush border of proximal tubular cells  Components of TBM: tubulointerstitial nephritis antigen

 Cell-mediated immunity:  The inflammatory cellular infiltrates that characterize AIN, mainly composed of T lymphocytes and macrophages.  Increase the production of extracellular matrix and the number of interstitial fibroblasts  Induce an amplification process recruiting more inflammatory cells and eosinophils into the interstitium

 Profibrotic cytokines and growth factors:  Transforming growth factor-b  Platelet-derived growth factor-BB  Endothelin-1  Epidermal growth factor  Fibroblast growth factor-2

 In patients with drug-induced AIN, mean delay between the starting of the offending drug and the appearance of renal manifestations is 10 days.

Early steroid treatment improves renal function recovery in patients with drug-induced acute interstitial nephritis Kidney Int 2008; 73: 940–946. Acute interstitial nephritis: clinical features and response to corticosteroid therapy. Nephrol Dial Transplant 2004; 19: 2778–2783

 Conservative treatment:  Larger number of patients and a longer follow-up revealed that a significant proportion of patients, ranging from not fully recovered their baseline renal function.  Duration of treatment with the offending drug or duration and severity of renal failure have not shown a clear correlation with the levels of serum creatinine at the end of follow-up.

 Steroid: early use  Intravenous pulses of methylprednisolone (250 mg daily for 3 consecutive days) followed by oral prednisone (0.5–1 mg/kg/day) tapering off over 4– 6 weeks  Anti-TBM disease: Plasmapheresis and cytotoxics  Idiopathic AIN resistant to steroids: cyclophosphamide, cyclosporine, mycophenolate mofetil

80-90%

 Pauci-immune (scanty or absent immune deposits): antineutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV)  Linear deposition of IgG on the capillary wall: anti– glomerular basement membrane (GBM) disease  Immune complex glomerulonephritis with granular immune deposits: lupus nephritis, membranoproliferative nephritis, IgA nephropathy, Henoch-Schonlein purpura, postinfectious glomerulonephritis, or cryoglobulinemia Crescentic Glomerulonephritis: New Aspects of Pathogenesis Seminars in Nephrology, Vol 31, No 4, July 2011, pp

 Name: 呂 O 敏  Sex: female  Age: 41-year-old  Occupation: 家庭主婦  Chart number:  Date of admission: 2011/09/24

 Progressive shortness of breath for 7 days

 No systemic diseases before  Progressive shortness of breath for 7 days  Associated symptoms: chest tightness, increased weight and general edema (48 → 57kg in 1 month), decreased urine output, abdominal pain, vomiting, dizziness  No rhinorrhea, productive cough, diarrhea  LMD: intermittent fever, hypoalbuminemia, proteinuria, low C3/C4, equivocal ANA

 No heart, liver, or other significant systemic diseases  Current medicine: nil

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

 Sister’s daughter: SLE  No family history of diabetes mellitus, malignancy, bleeding diathesis, heart, liver, kidney, or hereditary diseases

 Vital signs: blood pressure: 136/77 mmHg; temperature: 37.4 ‘C; pulse rate: 95/min; respiratory rate: 18/min  General appearance: acute ill looking  Eye: conjunctiva: mild pale, sclera: no icteric  Face: malar rash  Neck: supple, no lymphadenopathy or jugular vein engorgement  Chest: symmetric expansion breathing sound: bilateral basal crackles heart sound: regular heart beats, no S3 or S4, no murmurs  Abdomen: soft, flat, mild low abdominal tenderness, no muscle guarding or rebounding liver/spleen: impalpable bowel sound: normoactive  Extremities: lower limb pitting edema, grade 3  Skin: intact, no rash

WBC10.2x1000/ul Hgb8.3 g/dl Hct24.6 % MCV89.5 fl PLT286 x1000/uL Segment88.0 % Band1.0 % Lymphocyte6.0 % BUN78.7 mg/dl Crea2.77 mg/dl GPT6 IU/L NA139 mEq/L K3.9 mEq/L Sugar148 mg/dl T-chol223 mg/dl TG173 mg/dl Albumin2.22 mg/dl CRP13.87 mg/L ANA1:80 (homogenous, speckled) C mg/dL C mg/dL A-DSDNA178.9 U/mL

ColorDark yellow TurbidityTurbid SP. Gravity1.037 PH5.5 Leukocyte- Nitrite- Protein4+ Glucose- KetoneTrace Urobilinogen0.1 Bilirulin- Blood3+ Granular case+ RBC> 500/uL WBC5/uL Epithelial cell3/uL

 Left Kidney Length: 12.7 cm  Right Kidney Length: 12.6 cm  The both kidneys are large and swollen in appearance.  The cortical echogenicity increased to the level of liver. The papillae is prominent. The central sinus is unremarkable.  No stone, mass, or hydronephrosis is noted.

 LUPUS NEPHRITIS, CLASS IV-G(A/C); ACTIVITY (7/24), CHRONICITY (1/12)  GROSS D: ▪ 7 CORES OF KIDNEY TISSUE, WHITE AND SOFT  MICRO D: ▪ H & E SECTIONS: 16GLOMERULI, MODERATE HYPERPLASIA WITH NEUTROPHILS AND KARYORRHEXIS ▪ THE INTERSTITIUM: MODERATE INFLAMMATORY CELLS INFILTRATE WITH MILD FIBROSIS. ▪ THE TUBULES: MILD ATROPHY WITHOUT TUBULITIS ▪ THE ARTERIOLES: MIINIMAL CHANGES ▪ IMMUNOFLUORESCENCE SECTIONS: 12 GLOMERULI, 4+IGG, C3 AND C1Q & 2+IGA & 1+IGM IN DIFFUSE PATTERN. ▪ ELECTRON MICROSCOPIC STUDY: 2 GLOMERULUS, PROMINENT MESANGIAL AND FOCAL SUBENDOTHELIAL DEPOSITS

9/26 RPR- ASLO< 51.6 IU/Ml IgG824 mg/dL IgA355 mg/dL IgM111 mg/dL IgE42.7 mg/dL Indirect Coombs- Coombs- Anti-RNP217 U/ml + Anti-Sm140 U/ml + 9/27 Cardiolipin IgG6.74 U/ml Cardiolipin IgM6.01 U/ml 9/26 24 urine TP loss2.1 g/day 24hr Ccr4.75 ml/min 9/27 P-ANCA- C-ANCA- 9/29 CryoglobulinIgG 1+ Haptoglobin7.21 mg/dL

9/269/2910/110/310/610/12 BUN (mg/dL) Crea (mg/dL) Na (mEq/L) K (mEq/L) Ca (mg/dL) P (mg/dL) CO2 (mEq/L) Alb (g/dL) U/O (ml/day) BW (kg) Hemodialysis 9/26~10/10 Solu-cortef 100mg 1pc iv q8h 9/26~10/6 Solu-medrol (500mg) 1pc ivf qd 10/6~10/8 Prednisolone (5mg) 4# po qd 10/8~ Kidney biopsy 10/7

No outcome difference intraglomerular distribution

 10-year follow-up evaluation  24 SLE patients with active segmental GN in 50% or more of the glomeruli  35 SLE patients with diffuse GN  The incidence of end stage renal disease was significantly greater in patients with segmental GN of 50% or more compared with those with diffuse GN (9/24 [38%] versus 5/35 [14%], P <.05)  The incidence of remission with stable renal function was greater in patients with diffuse GN (22/35 [63%] versus 9/24 [38%], P <.05). Significance of histologic patterns of glomerular injury upon long-term prognosis in severe lupus glomerulonephritis. Kidney Int. 2001;59:

Pathology of lupus nephritis Seminars in Nephrology, Vol 27, No 1, January 2007, pp 22-34