Case Discussion < Case History >       A 23-year-old male was a previously healthy college boy. Decreased urine amount, bilateral lower legs edema, and body weight gain developed since one week ago. Routine urinalysis at OPD showed RBC: 5-10 per high power field and protein (+++). Under the impression of nephrotic syndrome, he was admitted for further evaluation and renal biopsy.      At admission, physical examination revealed regular pulse with 80/minute, BP 140/94 mmHg, and body weight 70 Kg. Nothing specific was found during physical examination except moderate degree of bilateral lower legs pitting edema. Laboratory examinations showed: prothrombin time and activated partial thromboplastin time were within normal limits. Plasma electrolytes levels were normal, but urine sodium was only 7 mEq/l. Urinalysis showed severe proteinuria and microscopic hematuria with dysmorphic changes. His creatinine clearance was only 9.8 ml/min and his daily protein loss was 10.1 grams. Ultrasonography revealed enlarged bilateral kidneys with increased echogenecity.       However, progressive dyspnea with oliguria was noted after an operation for a peritonitis episode, and marked pulmonary congestion progressed despite of the use of diuretics, which made temporary hemodialysis necessary. Severe dyspnea developed after two smooth sessions of hemodialysis. CPR and mechanical ventilation with 100% oxygen were given immediately. His arterial blood gas was: pH 7.325, PaCO2 28.2 mmHg, PaO2 42.9 mmHg, HCO3-  14.3 mEq/l, and O2 saturation 76%. Pulmonary embolism was highly suspected because of the great arterial-alveolar difference in oxygen pressure gradient (634.8 mmHg; normal < 15 mmHg). Serum fibrinogen was 1308 mg/dl (normal 151~375 mg/dl). D-dimer was negative. Heparinization using low-molecular-weight heparin (LMWH) was given subcutaneously three times per day. He was also treated with methyl-prednisolone, 500 mg twice a day for three days followed by oral 1 mg/Kg/day prednisolone. His renal function deteriorated due to the unsteady cardio-pulmonary condition, and continuous arterio-venous hemodialysis was given.       99mTc-MAA/ DTPA aerosol lung perfusion & ventilation scan revealed significant segmental perfusion defects in the posterior basal segment of right lung. MRA revealed complete obliteration of right superior pulmonary artery and focal filling defect of right inferior pulmonary artery with decreased vascularity over right lower lung (Fig. 1 ). His respiratory condition was stable there after and renal biopsy was done. He was discharged and followed as an outpatient, treated with 1 mg/Kg/day prednisolone and 2.5 mg/day warfarin. MRA was performed 5 months later, and it revealed completed remission. (Fig.2 ) < Laboratory Data > 項目 WBC RBC Hb Hct MCV PLT 單位 K/μL M/μL g/dL % fL K/μL 2/13 6.28 5.32 14.7 43.7 89.2 322 項目 Alb GOT GPT Chol TG BUN Crea UA 單位 g/dL  IU/L IU/L mg/dL  mg/dL mg/dL mg/dL mg/dL 2/13 2.03 24 28 365 95 37 1.6 9.0 2/19           95 3.5   8/29 4.4         18 1.2    項目 IgG IgA IgM C3 C4 ANA 單位 mg/dL mg/dL mg/dL mg/dL mg/dL     107 136 87.3 102 23.1  Neg.        項目 Fibrinogen 3-P D-dimer 單位 mg/dL   μg/mL 參考值 151~375 Negative <0.5 檢驗值 1308 1:10 － 病例分析       此位23歲男性一開始以腎病症候群的最常見症狀－水腫來表現，故住院安排腎臟穿刺檢查。住院中之生化檢驗發現該病患合併有腎病症候群常見的低白蛋白血症及高脂血症，而且腎功能也不正常。此病患在住院隔天因突發的腹膜炎而接受開刀及輸液，導致急性的水分累積，造成肺水腫情形，腎功能亦更加惡化，故接受兩次的臨時性血液透析治療移除多餘水分，以緩解症狀。       該病患於病情穩定之後，不幸又突發呼吸困難及hypoxia的情形，並因呼吸衰竭而使用呼吸器輔助治療。經評估血氧指標，發現有很高的 P(A-a) O2，故懷疑有肺栓塞情形，後來並經過Ventilation-perfusion lung scan 及核磁共振MRA的影像學證實。其治療方式是使用抗凝血劑治療，但因該病患接受手術後不久，且曾有短暫性上消化道出血情形，故使用較不具出血傾向的低分子量肝素治療，治療效果顯著。而腎病症候群的部分於嚴重期使用 pulse steroid 治療，而後並須口服Prednisolone一段時間，並慢慢減量，最後也達成治療目標－沒有尿蛋白、腎功能好轉。當患者對類固醇反應不佳時，可能需合併使用免疫抑制劑，如cyclophosphamide等。       肺栓塞常發生於下肢靜脈病變、癌症、心衰竭、長期臥床、近期大手術後之患者，而孕婦及使用口服避孕藥女性也是高危險群。腎病症候群患者因腎臟流失大量蛋白質而導致肝臟加速製造一系列蛋白，而促使一些分子量較大的凝血因子增加，進而造成腎病症候群患者的這種易凝血及栓塞的狀態。最常見的情形是下肢深部靜脈栓塞，腎靜脈栓塞及肺栓塞也不算少見。                            繼續教育考題 1. (A) 腎病症候群的診斷，最主要是依據 A Daily urinary protein loss more than 3.5 g. B Hypoalbuminemia. C Hyperlipidemia. D 以上皆需要才成立 2. (D) 本病患若接受腎臟切片檢查，下列病理變化哪一種最不可能？ A Minimal change disease. B Focal segmental glomerulosclerosis. C Diabetic nephropathy. D Thin basement membrane disease. 3. (B) 本病患對類固醇反應相當良好，依病患年齡及對類固醇的良好反應，本病患的腎絲球病變最可能是： A Focal segmental glomerulosclerosis. B Minimal change disease. C Membranoproliferative glomerulonephritis. D Membranous glomerulopathy. 4. (C) 一老人因腎病症候群來求診，腎臟切片顯示下列哪一種結果時，我們需特別小心該患者是否有合併其他惡性腫瘤病變？ A Minimal change disease. B Focal segmental glomerulosclerosis. C Membranous glomerulopathy. D Membranoproliferative glomerulonephritis. 5. (D) 腎病症候群患者易產生下列何種栓塞情形？ A Deep vein thrombosis. B Renal vein thrombosis. C Pulmonary embolism. D All of above. 6. (D) 本患者懷疑有肺栓塞，下列何種症狀屬於肺栓塞的可能症狀？ A Hypotesion and cyanosis. B Pleuritic chest pain. C Cough with hemoptysis. D 以上皆有可能 7. (C) 下列檢查何者是肺栓塞最具特異性的確定診斷方法？ A High P(A-a)O2 B Ventilation-perfusion lung scan C Selective pulmonary angiography. D Echocardiography. 8. (D) 下列何者是造成本患者成為肺栓塞的高危險群的原因？ A 腎病症候群造成大分子的凝血因子 (如Factor V, VIII) 累積增加 B 利尿劑使用及透析移除水分過程，造成血液較濃縮而黏稠度增加 C 小分子的抗凝血因子 (如 Antithrombin III) 由尿中流失過多 D 以上皆有可能 9. (B) 有關抗凝血劑的使用，下列何者為非？ A Heparin 的使用在Loading dose後, Maintain dose劑量須以aPTT (activated partial thromboplastin time) 為常規的評估方式 B 低分子量肝素的使用劑量以PT (prothrombin time) 為常規的評估方式 C Warfarin 的使用劑量以PT INR (prothrombin time) 為常規的評估方式 D Warfarin 的使用最好與Heparin有部分的時間重疊 10. (D) 對於肺栓塞的治療方式，下列何者正確？ A 必須先給予支持療法，氧氣供應及穩定血壓 B 若無absolute contraindication，則可給予thrombolytic therapy。必要時外科進行Embolectomy. C 可給予Anticoagulant 或inferior vena cava filter 做預防 D 以上皆對

答案解說 腎病症候群最主要的診斷依據就是尿蛋白每日3.5克以上，hypoalbuminemia及hyperlipidemia 均是可能發生的結果，並不一定會出現。 Thin basement membrane disease主要以血尿為主。 80% minimal change disease(MCD)的患者對類固醇治療有反應，且MCD的發生年齡較低。 Membranous glomerulopathy 與相當多惡性腫瘤有關，如乳癌、肺癌、大腸癌、胃癌、腎臟細胞癌等。MPGN則與Lymphoma、leukemia有關. MCD則與Hodgkin’s disease有關。 以上皆可能。  以上皆可能，大面積栓塞可造成呼吸衰竭，右心衰竭，低血壓，胸痛等情形；小面積栓塞可能造成咳嗽或咳血現象。 肺血管攝影為最能確定診斷的方法，利用Contrast enhanced spiral CT 或MRA也可達到檢查目的。Ventilation-perfusion lung scan為最初步篩選方法。 以上皆有可能。 低分子量肝素目前無較簡單的監測方式，有研究顯示可用Anti-Xa activity來評估。 以上皆對。