< Presentation of Case >
A 28-year-old woman, G1P0, who had been otherwise well and pregnant for 6 months, presented with microscopic hematuria in a routine prenatal examination. The pre-marrital health exam was unremarkable; however, she was found to have 1+ hematuria on three urine dipstick examinations during recent prenatal care. Further urine analysis revealed microscopic hematuria (>20 RBC/high power field). The proteinuria was negative using dipstick examination. The microscopic hematuria remains positive in the following two visits (two months), and therefore, she was referred for a further investigation. She experienced no discomfort during urination, such as dysuria, frequency or burning sensation. She was not aware of any symptoms suggestive of respiratory tract infection recently. There was no known family history of systemic disease or renal disease. She denied a history of exposure to heavy metal, toxic chemical substances or long-term Chinese herbal remedies. She consumed alcohol only on social occasions before pregnancy, but did not smoke. Current medications included daily multi-vitamin and folic acid pills. At outpatient clinic, the physical examination revealed a well-developed young woman without ill-looking. The body height was 158 cm and weight was 57 kg. Her heart rate was 84 bpm, temperature 36.8 ℃, and blood pressure 128/68 mmHg in the absence of distress. There was no pale conjunctiva or icteric sclera. The heart beat was regular without murmurs. Auscultation of the lung fields was normal. No remarkable finding on examination of the abdomen was found other than an ovoid abdomen from the pregnancy. No lower leg edema was noted.
< Laboratory and Image Study >
1. CBC
Day after admission |
WBC
K/μL |
Hgb
g/dL |
MCV
fL |
MCHC
% |
Hct
% |
Plt
K/μL |
Routine prenatal exam |
6.72 |
13.8 |
92 |
33 |
40 |
410 |
OPD |
6.69 |
13.9 |
92 |
33 |
39.8 |
415 |
N.B. No obvious variation in results between each prenatal exam
2. Biochemistry
Day after admission |
BUN
mg/dl |
Cre
mg/dl |
Na
mmol/l |
K
mmol/l |
Ca mg/dl |
P
mg/dl |
GOT
U/l |
GPT
U/l |
Albumin
g/dl |
Routine prenatal exam |
14 |
0.6 |
137 |
4.2 |
10.3 |
3.8 |
27 |
26 |
4.2 |
OPD-2 |
16 |
0.6 |
N/A |
N/A |
N/A |
N/A |
N/A |
N/A |
N/A |
N.B. No obvious variation in results between each prenatal exam
3. Urinalysis
Date |
Appearance |
Specific gravity |
pH |
Protein
(mg/dl) |
Glucose |
Ketone |
Occult blood |
Routine prenatal exam |
yellow, clear |
1.006 |
6.5 |
-- |
-- |
-- |
+ |
OPD |
yellow, clear |
1.005 |
6.6 |
-- |
-- |
-- |
+ |
Date |
Urobilinogen |
Bilirubin |
RBC |
WBC |
Epithelial cells |
Cast |
Bacteria |
Routine prenatal exam |
0.1 |
-- |
>20 |
<5 |
-- |
-- |
-- |
OPD |
0.1 |
-- |
>20 |
<5 |
-- |
hyaline |
-- |
24 hour urine total protein amount: 150 mg/day (OPD-1)
Urine cytology (three sets): negative for malignancy
Urine culture: negative for bacteria
4. Serology study: Rheumatoid factor: negative, ANA: negative, Anti-HBc: negative, Anti-HBs: positive, Anti-HCV: negative
5. Renal sonography: Bilateral kidneys were mildly enlarged. Mild bilateral hydroureter was noted. No obvious cystic lesion, mass, or hyperechoic lesion was identified.
< Course and Treatment >
The urianlysis did not reveal any dysmorphic RBC, which argued against the possibility of underlying or de novo glomerulonephritis. The 24-hour urine protein excretion was 150 mg/day. Even though this woman suffered from microscopic hematuria and bilateral hydroureter, observation was still suggested because there was no underlying renal disease before pregnancy; urine analysis did not identify active urine sediment; the patient did not have hypertension, glomerulonephritis, nephrotic syndrome, urinary tract infection, renal tumor, or calculi. Three months later, this woman delivered a healthy boy without complication. The microscopic hematuria disappeared shortly postpartum.
< Analysis >
一般來說，臨床上見到microscopic hematuria，可先依尿中紅血球的形態來區分屬於腎絲球性或非腎絲球性血尿，之後再依年齡來做初步鑑別診斷 (Figure 1)。雖然根據2003年NEJM的建議 (reference 2)，可直接安排電腦斷層，但是在那之前還是可以先以超音波作篩檢並輔以尿液細胞學檢查。一般來說，年紀小於50歲的血尿病患，尤其是如本病例年輕的病患，發生腫瘤的機會相對較年紀大的病患來的低，不過臨床上如有懷疑結石或腫瘤(在適產齡婦女少見)，仍要輔以其他進一步診斷工具來排除可能性，當然在此病例，超音波也遠比電腦斷層適合。由於此病患並沒有任何systemic symptom/sign，加上初步檢查都呈陰性，所以診斷與懷孕有關。腎臟在懷孕時會產生相對應的生理變化，這些變化可簡單歸類為構造上、血流動力學及腎功能方面。在構造上最明顯可見到的就是hydroureter及腎臟體積增加，而腎臟體積的增加是由於懷孕時體內水分增加，因此腎臟大小增加，但腎臟本身並沒有肥大(hypertrophy)。另外，懷孕時常可見到雙側hydroureter，尤其是右側會較左側嚴重。發生hydroureter的原因，可能是受到progesterone濃度上升及因懷孕導致輸尿管受到拉扯所致。
懷孕時的microscopic hematuria必須先排除陰道出血或泌尿道感染，因此產科檢查及尿液培養是必須考慮的，接者須再排除病理性血尿。懷孕時發生病理性血尿的最主要原因為glomerulonephritis及pre-eclampsia，所以檢查尿中紅血球的型態是必要的，此外超音波及腎功能檢查也要考慮。排除其他後，則屬於懷孕時不明原因的生理性血尿。九成以上的microscopic hematuria會在產前或產後短期內消失，不需處理。懷孕時的血尿多以microscopic hematuria為主，至於懷孕時microscopic hematuria的標準，目前並無很好的定義，而目前一般研究所採用的定義為兩次或以上可用尿液篩檢試紙檢出1+程度以上的microscopic hematuria即算。但是一般臨床上採用的標準為在顯微鏡的high-power field下，可發現5個以上的紅血球即是。在針對一般人的研究顯示microscopic hematuria的盛行率約為5%，而在國外針對懷孕時發生microscopic hematuria的一項前瞻性研究發現，孕婦的microscopic hematuria之盛行率可高達約20% (reference 3)，但是在根據香港華人的回溯性研究則發現，約只在2.7%的懷孕婦女發現microscopic hematuria (reference 4)，這差距可能與研究方法或人種不同有關。若血尿起因於陰道出血或泌尿道感染，則根據病因及培養結果治療，但若檢查後判斷孕婦的microscopic hematuria是屬於腎炎性如尿中出現dysmorphic RBC及產後仍未消失，則以thin basement disease及IgA nephropathy為最常見。不過由於懷孕時並不適合腎臟切片，因此仍以觀察為主，並不建議治療。而95%孕婦的蛋白尿<200 mg/day。
最後，根據研究顯示，孕婦的生理性microscopic hematuria，與懷孕的預後並沒有明顯相關，但在產後持續的血尿(如超過三個月)，則要注意是否有潛在性的glomerulonephritis。
< References >
- Comprehensive Clinical Nephrology 4th edition
- N Engl J Med 2003;348:2330-8
- Am J Kidney Dis 2005;45:667-673
- Nephron Clin Pract 2007;105:c147-152
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Case Discussion
繼續教育考題