Abstract
目的
分析急性肾梗死的临床特征,探讨急性肾梗死并发血尿的相关临床及实验室因素。
方法
回顾性分析经影像证实的52例急性肾梗死患者的临床资料,包括人口学数据、危险因素、临床表现、实验室检查、诊断、治疗及预后情况,并比较并发血尿患者与无血尿患者上述指标的差异。
结果
52例急性肾梗死患者,其中34例男性、18例女性,平均年龄(56.3±14.8)岁。左、右肾及双肾受累比例分别为44.2%、34.6%和21.2%。局灶性、多灶性及大面积梗死的比例分别为36.5%、50.0%和13.5%。38.5%的患者同时合并其他脏器血栓栓塞事件,44.2%的患者合并心房颤动。常见症状包括胁腹痛(71.2%)、恶心(55.8%)、腰痛(53.9%)、呕吐(48.1%)、发热(48.1%)和腹泻(21.2%)。肾区叩痛是最常见的体征(40.4%)。血清乳酸脱氢酶、血白细胞计数及C-反应蛋白升高的患者比例分别为86.5%、67.3%和54.5%。38.5%的患者在就诊时并发血尿。血清D-二聚体升高仅见于56.5%的患者。就诊至确诊的中位时间为41.5 h(2~552 h)。47例患者(90.4%)经增强计算机断层显像明确诊断、5例患者(9.6%)经肾动脉造影明确诊断。抗凝治疗是最常采用的治疗方法。所有患者平均随访(39.4±35.8)个月,大多数患者肾功能稳定,4例需要持续透析治疗,1例死于心力衰竭。血尿患者的血清乳酸脱氢酶显著高于无血尿患者[773.5 IU/L (153.0~3 159.0 IU/L) vs. 488.0 IU/L (137.0~3 370.0 IU/L),P=0.041],其他临床表现、诊断、治疗及预后情况组间差异无统计学意义。
结论
心源性血栓栓塞是急性肾梗死最常见的病因,对于持续腰腹痛、血乳酸脱氢酶升高且存在危险因素的患者宜进行腹部增强计算机断层显像以助早期诊断。血尿并非常见的临床表现且与预后无关,其出现与否可能取决于梗死的严重程度。
Keywords: 急性肾梗死, 血栓栓塞, 血尿, 增强计算机断层显像, 乳酸脱氢酶
Abstract
Objective
To investigate the clinical characteristics of patients with acute renal infarction (ARI) and explore the possible clinical and/or laboratory parameters relative to hematuria.
Methods
Medical records of 52 patients hospitalized with radiologic proven ARI were retrospectively reviewed. Clinical characteristics, including demographic data, risk factors for thromboembolism, initial clinical presentations, laboratory data, diagnosis, treatment programs and outcomes were evaluated and compared between hematuria(+) and hematuria(-) patients.
Results
The mean age of the patients (34 men and 18 women) was (56.3±14.8) years. The left, right, and bilateral kidneys were involved in 44.2%, 34.6% and 21.2% of the patients, respectively. Focal, multiple and massive infarctions were involved in 36.5%, 50.0% and 13.5% of the patients. The prevalence of concurrent thromboembolic events was 38.5%. Atrial fibrillation was complicated in 44.2% of the patients. ARI often presented with non-specific symptoms, including abdominal/flank pain (71.2%), nausea (55.8%), lumbar pain (53.9%), vomiting (48.1%), fever (48.1%), and diarrhea (21.2%). Percussion tenderness over kidney region was the most common sign (40.4%). The levels of serum lactate dehydrogenase, white blood cell count and C-reactive protein were elevated in 86.5%, 67.3%, and 54.5% of cases, respectively. Hematuria was detected in only 38.5% of the cases on admission. Elevation of serum D-dimer was only noted in 56.5% of the patients. The median duration from hospital presentation to diagnosis was 41.5 h (range: 2-552 h). Contrast-enhanced computed tomography was diagnostic in 47 (90.4%) cases. Angiography was positive in the other 5 (9.6%) cases. Anticoagulation was the most common therapy. During a mean follow-up of (39.4±35.8) months, renal functions of most patients were stable. Four patients needed permanent dialysis and one patient died of heart failure. There was no statistical significance between hematuria(+) group and hematuria(-) group for all the parameters except the level of serum lactate dehydrogenase, which was higher in hematuria(+) group [773.5 IU/L (range: 153.0-3 159.0 IU/L) vs. 488.0 IU/L (range: 137.0-3 370.0 IU/L), P=0.041].
Conclusion
Thromboembolism due to heart disease is the main etiology of ARI. Early contrast-enhanced computed tomography scan should be considered for high-risk patients with persisting abdominal or lumbar pain and elevated serum level of lactate dehydrogenase. Hematuria is not a sensitive clue for diagnosis and is not relative to prognosis. Whether it is present may be determined by the severity of infarction.
Keywords: Acute renal infarction, Thromboembolism, Hematuria, Contrast-enhanced computed tomography, Lactate dehydrogenase
急性肾梗死(acute renal infarction,ARI)是肾动脉主干或分支因栓塞或血栓形成造成血流完全中断而导致的急性坏死性肾脏病变,其在临床上相对少见且症状不特异,极易漏诊和误诊,由此延误治疗,导致不可逆的肾损害[1]。血尿对ARI的诊断有提示意义,但并不常见,其相关因素尚未见文献报道。本研究拟分析、总结ARI的临床表现、诊断、治疗和预后,并探讨ARI并发血尿的相关临床及实验室因素,以期提高临床医生对本症的认识和诊治水平。
1. 资料与方法
1.1. 对象
以1992年1月至2016年12月于北京大学第一医院住院治疗的52例ARI患者为研究对象。本研究获得北京大学第一医院伦理委员会批准(批准号:2016[1276])。
ARI的诊断基于增强计算机断层显像(contrast-enhanced computed tomography,CECT)或肾动脉造影。CECT的典型征象为尖端指向肾门的楔形无强化区。肾动脉造影的典型征象为肾动脉主干或其分支截断或腔内见充盈缺损。
1.2. 方法
回顾性分析52例ARI患者的临床病历,收集包括人口学数据、既往史、症状、体征、实验室检查、就诊至确诊时间、诊断技术、治疗及预后信息。实验室检查包括全血细胞计数、肝功能、肾功能、血脂、乳酸脱氢酶、D-二聚体、纤维蛋白原及尿沉渣镜检。通过修正的基于中国人的肾脏病膳食改良(modification of diet in renal disease,MDRD)公式[2]计算患者就诊、出院及随访期间估测的肾小球滤过率(estimated glomerular filtration rate,eGFR)。根据影像学表现将ARI分为局灶性(单一楔形病灶)、多灶性(多个楔形病灶)以及大面积(超过50%的肾脏受累)梗死[3]。
1.3. 统计学分析
应用STATA 11.0软件进行统计学分析,连续变量依据是否呈正态分布分别以均值±标准差或中位数(最小值,最大值)表示,分类变量以率或百分数表示。连续变量组间比较采用t检验或Wilcoxon-Mann-Whitney检验,分类变量组间比较采用χ2或Fisher精确概率检验,P<0.05为差异有统计学意义。
2. 结果
2.1. 临床特征
52例患者中,34例男性、18例女性,年龄21~85岁,平均(56.3±14.8)岁,其中40~60岁的患者27例(51.9%),61~80岁的19例(36.5%)。左肾梗死23例(44.2%), 右肾梗死18例(34.6%),双肾梗死11例(21.2%)。局灶性梗死19例(36.5%),多灶性梗死26例(50%),大面积梗死7例(13.5%),具体见表1。
1.
急性肾梗死患者的临床特征
Clinical characteristics of patients with acute renal infarction
| Items | Total (n=52) | Hematuria(+) (n=20) | Hematuria(-) (n=32) | Statistics | P | ||||
| Data were presented as mean±SD, or number (%), or median (range). * Fisher’s exact test. BMI, body mass index; ALT, alanine transaminase (normal: 0-40 IU/L); AST, aspartate transaminase (normal: 0-45 IU/L); LDH, lactate dehydrogenase (normal: 100-240 IU/L); Creatinine (normal: 44-133 μmol/L); eGFR, estimated glomerular filtration rate; UA, uric acid (normal: 90-360 μmol/L); TG, triglycerides (normal: 0.56-1.70 mmol/L); TCHO, total cholesterol (normal: 3.4-5.2 mmol/L); LDL-C, low density lipoprotein cholesterol (normal: 2.1-3.1 mmol/L); WBC, white blood cells [normal: (3.5-9.5)×103/μL]; Plt, platelet [normal: (10-30)×103/μL]; CRP, C-reactive protein (normal: <8 mg/dL); Fibrinogen (normal: 2-4 g/L); ARI, acute renal infarction. | |||||||||
| Age/years | 56.3±14.8 | 55.9±14.7 | 56.6±15.1 | 0.18 | 0.86 | ||||
| Male | 34 (65.4) | 13 (65.0) | 21 (65.6) | 0 | 0.96 | ||||
| BMI/(kg/m2) | 24.1±3.8 | 23.7±4.1 | 24.2±3.8 | 0.34 | 0.74 | ||||
| Time from symptom presentation to urinanalysis/h |
24 (1, 360) | 24 (1, 360) | 24 (2, 288) | 1.12 | 0.27 | ||||
| Symptoms/signs | |||||||||
| Abdominal/flank pain | 37 (71.2) | 14 (70.0) | 23 (71.9) | 0.02 | 0.89 | ||||
| Lumbar pain | 28 (53.9) | 10 (50.0) | 18 (56.3) | 0.19 | 0.66 | ||||
| No pain | 4 (7.7) | 3 (15.0) | 1 (3.1) | - | 0.29* | ||||
| Nausea | 29 (55.8) | 11 (55.0) | 18 (56.3) | 0.01 | 0.93 | ||||
| Vomiting | 25 (48.1) | 11 (55.0) | 14 (43.8) | 0.62 | 0.43 | ||||
| Fever | 25 (48.1) | 13 (65.0) | 12 (37.5) | 3.73 | 0.05 | ||||
| Diarrhea | 11 (21.2) | 3 (15.0) | 8 (25.0) | - | 0.50* | ||||
| Oliguria | 9 (17.3) | 2 (10.0) | 7 (21.9) | - | 0.45* | ||||
| Fatigue | 6 (11.5) | 2 (10.0) | 4 (12.5) | - | 1.00* | ||||
| Percussion tenderness over kidney region |
21 (40.4) | 9 (45.0) | 12 (37.5) | 0.29 | 0.59 | ||||
| Laboratory data | |||||||||
| ALT/(IU/L) | 42.0 (3.0, 201.0) | 52.5 (13.0, 201.0) | 39.5 (3.0, 127.0) | -1.76 | 0.08 | ||||
| AST/(IU/L) | 38.5 (12.0, 308.0) | 40.5 (14.0, 308.0) | 35.0 (12.0, 118.0) | 0.55 | 0.14 | ||||
| LDH/(IU/L) | 511.0 (137, 3 370) | 773.5 (153.0, 3 159.0) | 488.0 (137.0, 3 370.0) | -2.13 | 0.04 | ||||
| Creatinine/(μmol/L) | 118.0 (63.5, 824.8) | 123.5 (77.0, 526.0) | 114.5 (63.5, 824.8) | -0.56 | 0.57 | ||||
| eGFR/[mL/(min·1.73 m2)] | 56.8±27.2 | 53.1±29.5 | 59.0±26.0 | 0.74 | 0.46 | ||||
| UA/(μmol/L) | 355.8±116.3 | 351.6±105.5 | 358.1±123.7 | 0.18 | 0.86 | ||||
| TG/(mmol/L) | 1.06 (0.20, 4.08) | 1.05 (0.40, 4.08) | 1.08 (0.20, 2.56) | -0.01 | 0.99 | ||||
| TCHO/(mmol/L) | 4.15±1.05 | 4.15±1.23 | 4.15±0.94 | -0.03 | 0.98 | ||||
| LDL-C/(mmol/L) | 2.62±0.88 | 2.54±0.93 | 2.67±0.86 | 0.48 | 0.63 | ||||
| WBC/(×103/μL) | 11.9 (2.7, 32.2) | 12.3 (6.5, 25.6) | 10.8 (2.7, 32.2) | -1.60 | 0.12 | ||||
| Plt/(×104/μL) | 20.5 (7.4, 49.7) | 20.9 (10.1, 32.0) | 20.1 (7.4, 49.7) | 0.70 | 0.49 | ||||
| CRP/(mg/dL) | 30.3 (0.5, 249.0) | 69.0 (1.8, 249.0) | 5.7 (0.5, 189.4) | -1.84 | 0.07 | ||||
| Fibrinogen/(g/L) | 4.6±1.8 | 4.3±1.8 | 4.7±1.8 | 0.63 | 0.54 | ||||
| D-dimer > normal upper limit | 26/46 (56.5) | 12/17 (70.6) | 14/29 (48.3) | 2.17 | 0.14 | ||||
| Left | 23 (44.2) | 9 (45.0) | 14 (43.8) | ||||||
| Right | 18 (34.6) | 5 (25.0) | 13 (40.6) | 0.35 | |||||
| Bilateral | 11 (21.2) | 6 (30.0) | 5 (15.6) | ||||||
| Focal infarction | 19 (36.5) | 5 (25.0) | 14 (43.8) | ||||||
| Multiple infarction | 26 (50.0) | 12 (60.0) | 14 (43.8) | 0.39 | |||||
| Global ARI | 7 (13.5) | 3 (15.0) | 4 (12.5) | ||||||
| Items | Total (n=52) | Hematuria(+) (n=20) | Hematuria(-) (n=32) | Statistics | P | ||||
| Concurrent thromboembolism | 20 (38.5) | 7 (35.0) | 13 (40.6) | 0.16 | 0.69 | ||||
| Splenic infarction | 11 (21.2) | 4 (20.0) | 7 (21.9) | - | 1.00* | ||||
| Lower extremity arterial embolism | 5 (9.6) | 0 (0) | 5 (15.6) | - | 0.14* | ||||
| Mesenteric arterial embolism | 4 (7.7) | 2 (10.0) | 2 (6.3) | - | 0.63* | ||||
| Iliaic artery embolism | 1 (1.9) | 1 (5.0) | 0 (0) | - | 0.39* | ||||
| Cerebral infarction | 5 (9.6) | 3 (15.0) | 2 (6.3) | - | 0.36* | ||||
| Liver infarction | 1 (1.9) | 1 (5.0) | 0 (0) | - | 0.39* | ||||
| Pulmonary thromboembolism | 1 (1.9) | 1 (5.0) | 0 (0) | - | 0.39* | ||||
| Pancreatic infarction | 1 (1.9) | 1 (5.0) | 0 (0) | - | 0.39* | ||||
多数患者出现疼痛,包括胁腹痛(71.2%)或腰痛(53.9%),4例患者(7.7%)无疼痛症状,其他常见症状有恶心(55.8%)、呕吐(48.1%)、发热(48.1%)、腹泻(21.2%)、少尿(17.3%)和乏力(11.5%),肾区叩痛是最常见的体征(40.4%,表1)。
就诊时,20例患者(38.5%)存在肉眼或镜下血尿,45例患者(86.5%)血清乳酸脱氢酶升高,35例患者(67.3%)外周血白细胞计数升高。22例患者检测了血清C-反应蛋白(C-reactive protein, CRP)浓度,其中12例患者(54.5%)浓度升高。46例患者检测了血清D-二聚体水平,其中26例患者(56.5%)水平升高(表1)。
20例患者(38.5%)同时合并其他脏器血栓栓塞事件,包括脾梗死、下肢动脉栓塞、脑梗塞、肠系膜动脉栓塞、髂动脉栓塞、肝梗死、肺栓塞和胰腺梗死,6例患者受累脏器≥3个(表1)。
2.2. 危险因素和可能的病因
23例患者(44.2%)合并心房颤动,其中6例患有风湿性心脏病二尖瓣狭窄。12例(23.1%)患有冠状动脉粥样硬化性心脏病(简称冠心病)。20例(38.5%)有吸烟史。30例患者(57.7%)合并其他脏器血栓栓塞事件或存在明确的心源性栓子(左心房或主动脉附壁血栓),其病因考虑为肾动脉血栓栓塞。5例患者(9.6%)存在肾动脉狭窄或夹层,其病因考虑为肾动脉原位血栓形成。6例患者(11.5%)的病因考虑为高凝状态,其中3例合并高同型半胱氨酸血症,2例合并恶性肿瘤,1例合并抗磷脂综合征。其余11例患者(21.2%)因检查不充分,病因未明(表2)。
2.
急性肾梗死的危险因素和可能的病因
Risk factors and presumed etiologies of acute renal infarction
| Items | Total (n=52) | Hematuria(+) (n=20) | Hematuria(-) (n=32) | Statistics | P |
| Data were presented as number (%). *Fisher’s exact test. ARI, acute renal infarction. | |||||
| Risk factors for ARI | |||||
| Atrial fibrillation | 23 (44.2) | 9 (45.0) | 14 (43.8) | 0.01 | 0.93 |
| Malignancy | 2 (3.8) | 2 (10.0) | 0 (0) | - | 0.14* |
| Hyperlipidemia | 15 (28.8) | 5 (25.0) | 10 (31.3) | 0.23 | 0.63 |
| Homocysteinemia | 5/6 (83.3) | 3/3 (100.0) | 2/3 (66.7) | - | 1.00* |
| Diabetes mellitus | 4 (7.7) | 1 (5.0) | 3 (9.4) | - | 1.00* |
| Hypertension | 26 (50.0) | 13 (65.0) | 13 (40.6) | 2.92 | 0.09 |
| Valvular heart disease | 30 (57.7) | 12 (60.0) | 18 (56.3) | 0.07 | 0.79 |
| Aortic mural thrombus | 6 (11.5) | 2 (10.0) | 4 (12.5) | - | 1.00* |
| Aortic dissection | 2 (3.8) | 1 (5.0) | 1 (3.1) | - | 1.00* |
| Congestive heart failure | 5 (9.6) | 2 (10.0) | 3 (9.4) | - | 1.00* |
| Coronary artery disease | 12 (23.1) | 5 (25.0) | 7 (21.9) | 0.07 | 0.8 |
| Antiphospholipid syndrome | 1 (1.9) | 1 (5.0) | 0 (0) | - | 0.39* |
| Smoking (current/exsmoker) | 20 (38.5) | 9 (45.0) | 11 (34.4) | 0.59 | 0.44 |
| Renal artery stenosis | 17 (32.7) | 4 (20.0) | 13 (40.6) | 2.38 | 0.12 |
| Cerebrovascular disease | 3 (5.8) | 2 (10.0) | 1 (3.1) | - | 0.55* |
| Obesity | 6/35 (17.1) | 1/11(9.1) | 5/24 (20.8) | - | 0.64* |
| Cardiomyopathy | 3 (5.8) | 1 (5.0) | 2 (6.3) | - | 1.00* |
| Etiologies of ARI | |||||
| Thromboembolism | 30 (57.7) | 10 (50.0) | 20 (62.5) | 0.79 | 0.38 |
| In situ thrombosis | 5 (9.6) | 2 (10.0) | 3 (9.4) | - | 1.00* |
| Coagulation dysfunction | 6 (11.5) | 4 (20.0) | 2 (6.3) | - | 0.19* |
| Idiopathic | 0 (0) | 0 (0) | 0 (0) | - | - |
| Unknown | 11 (21.2) | 4 (20.0) | 7 (21.9) | - | 1.00* |
2.3. 诊断、治疗和预后
自就诊至确诊的中位时间是41.5 h。腹部CECT是最常用的诊断技术,共47例(90.4%)通过CECT明确诊断,其余5例(9.6%)通过肾动脉造影确诊。1例患者磁共振检查及3例患者超声检查提示ARI可能(表3)。
3.
急性肾梗死患者的诊断、治疗和预后
Diagnosis, treatment and prognosis of patients with acute renal infarction
| Items | Total (n=52) |
Hematuria(+) (n=20) |
Hematuria(-) (n=32) |
Statistics | P |
| Data were presented as means±SD, or number (%), or median (range). *Fisher’s exact test. CT, computed tomography; MRI, magnetic resonance imaging; eGFR, estimated glomerular filtration rate. | |||||
| Time from hospital presentation to diagnosis/h | 41.5 (2.0, 552.0) | 24.0 (2.0, 552.0) | 48.0 (2.0, 408.0) | 0.39 | 0.70 |
| Diagnostic methods | |||||
| Contrast-enhanced CT | 47 (90.4) | 19 (95.0) | 28 (87.5) | - | 0.64* |
| Ultrasound | 0 (0) | 0 (0) | 0 (0) | - | - |
| MRI | 0 (0) | 0 (0) | 0 (0) | - | - |
| Angiography | 5 (9.6) | 1 (5.0) | 4 (12.5) | - | 0.64* |
| Treatment | |||||
| Anticoagulation | 25 (48.1) | 10 (50.0) | 15 (46.9) | 0.05 | 0.83 |
| Antiplatelet | 2 (3.8) | 0 (0) | 2 (6.3) | - | 0.52* |
| Systemic thrombolysis+anticoagulation | 9 (17.3) | 6 (30.0) | 3 (9.4) | - | 0.07* |
| Catheter-directed thrombolysis+anticoagulation | 7 (13.5) | 2 (10.0) | 5 (15.6) | - | 0.69* |
| Interventional therapy+anticoagulation | 1 (1.9) | 0 (0) | 1 (3.1) | - | 1.00* |
| Interventional therapy+antiplatelet | 4 (7.7) | 1 (5.0) | 3 (9.4) | - | 1.00* |
| Surgery+anticoagulation | 0 (0) | 0 (0) | 0 (0) | - | - |
| No | 4 (7.7) | 1 (5.0) | 3 (9.4) | - | 1.00* |
| Prognosis | |||||
| Duration of symptom after treatment/d | 3 (1, 12) | 4 (1, 12) | 3 (1, 9) | -0.81 | 0.43 |
| Median time of hospital stay/d | 13 (2, 64) | 18 (3, 64) | 11 (2, 42) | -1.35 | 0.18 |
| Inhospital mortality | 0 (0) | 0 (0) | 0 (0) | - | - |
| Creatinine/(μmol/L), discharge | 102.0 (60.0, 1 043.0) | 111.0 (66.0, 896.0) | 99.0 (60.0, 1 043.0) | -1.46 | 0.15 |
| eGFR/[mL/(min·1.73 m2)], discharge | 64.6±29.3 | 57.4±30.6 | 68.8±28.2 | 1.25 | 0.22 |
| Dialysis-dependent, follow-up | 4 (7.7) | 2 (10.0) | 2 (6.3) | - | 0.63* |
| Creatinine/(μmol/L), follow-up | 116.6±20.9 | 118.8±23.4 | 113.7±18.5 | 0.47 | 0.65 |
| eGFR/[mL/(min·1.73 m2)], follow-up | 52.8±15.3 | 52.3±14.7 | 53.4±17.2 | -0.14 | 0.90 |
抗凝治疗是应用最多的治疗方法,25例患者(48.1%)直接行抗凝治疗,16例患者溶栓后序贯抗凝治疗,其中静脉溶栓9例(17.3%),经导管引导局部溶栓7例(13.5%)。5例患者(9.6%)接受介入治疗并序贯抗凝或抗血小板治疗。2例患者(3.8%)仅接受抗血小板治疗。无出血或药物过敏等严重并发症发生,4例患者(7.7%)因重要脏器出血而未接受任何治疗(表3)。
治疗开始至症状消失以及住院的中位时间分别为3 d (1~12 d)和13 d (2~64 d),所有患者无院内死亡。出院时血清肌酐水平为102.0 μmol/L [(60.0, 1 043.0) μmol/L], eGFR为(64.6±29.3) mL/(min·1.73 m2)。患者治疗后肾功能均有所好转,但组间差异无统计学意义(表3)。
所有患者平均随访(39.4±35.8)个月,最长120个月。随访期间,4例患者(7.7%)需要持续透析治疗,1例患者(1.9%)死于充血性心力衰竭。可获取检验结果的16例非透析依赖患者的血清肌酐水平为(116.6±20.9) μmol/L,eGFR为(52.8±15.3) mL/(min·1.73 m2)。患者随访期间的肾功能参数同就诊和出院时比较,差异无统计学意义(表3)。
2.4. 与血尿相关的临床及实验室因素
就诊时并发血尿患者的血清乳酸脱氢酶水平显著高于无血尿患者[773.5 (153.0, 3 159.0) IU/L vs. 488.0 (137.0, 3 370.0) IU/L,P=0.041],此外,并发血尿的患者更多合并高血压,出现发热者更多,血谷丙转氨酶(alanine transaminase,ALT)及CRP水平更高,但差异均无统计学意义。
尽管血尿患者更多接受静脉溶栓治疗,但差异无统计学意义(30.0% vs. 9.4%,P=0.070)。在近期及远期预后方面,血尿患者与无血尿患者没有明显差异。
3. 讨论
心源性血栓栓塞是ARI最重要的病因,但其在不同人群的发生率有所不同。一项日本的研究发现,73%的ARI由心源性血栓栓塞引起[4],而韩国的一项研究仅报道为38.2%[5],如此巨大的差异与不同研究在入选患者的年龄、时间以及样本量等方面存在不同有关。上述两项研究的研究对象平均年龄分别为(71.9±13.4)岁和(63.5±15.4)岁,分别有69.7%和24.7%的患者合并心房颤动。由于增龄及其相关的高血压病、冠心病和肥胖均与新发心房颤动密切相关[6,7],因而不难理解为何日本的研究中血栓栓塞性ARI会更为高发。近期,Oh等[8]的一项包括1993—2003年韩国9家医院共计438例患者、迄今最大规模的研究表明,血栓栓塞性ARI占全部ARI病例的55.7%,该研究入选患者的平均年龄为60岁,48.2%的患者合并心房颤动。本研究在入选患者的年龄以及时间方面均与Oh等[8]的研究相近,所得血栓栓塞性ARI占全部ARI的百分数(57.7%)以及心房颤动的患病率(44.2%)也与其最为接近。同以往的研究结果[8,9]一致,本研究也没有发现左、右肾发生ARI的概率存在差异。本研究中,38.5%的患者同时合并其他脏器血栓栓塞事件,最多见的为脾梗死,发生率为21.2%,该数据与多数研究[4-5,8]近似,但低于Antopolsky等[9]的研究结果(34%)。
ARI患者通常出现持续性胁腹痛或腰痛,疼痛的特点是突发、剧烈、锐痛,通常不向他处放射。本研究中4例患者无疼痛症状,此种现象既往已有报道[4-5,8],所占比例甚至更高,但其机制尚不明确。在实验室检查方面,本研究结果与既往研究类似。D-二聚体是纤维蛋白降解产物,对于血栓栓塞性疾病的诊断具有很高的敏感性及阴性预测价值[10],但在本研究中,仅56.5%的患者血清D-二聚体升高,究其原因,一方面患者可能存在纤维蛋白溶解异常,另一方面所用的检测方法可能不够敏感,由此提示D-二聚体正常并不能除外ARI。血尿是ARI常见的临床表现,结合病史对于诊断有提示意义。本研究中,多数患者就诊时无血尿表现,该现象可能是梗死肾血流减少、肾小球滤过率降低所致。有研究报道,部分就诊时血尿阴性的患者在24 h内可转为阳性[11]。本研究中,与无血尿患者相比,血尿患者血清乳酸脱氢酶水平更高,差异有统计学意义,同时出现发热者更多,血ALT及CRP水平也存在更高的趋势。上述参数,特别是血清乳酸脱氢酶水平,反映了全身炎症负荷及局部组织损伤程度,因此,本研究结果提示血尿并非ARI敏感的诊断线索,其是否出现可能取决于肾实质损伤的程度,并在一定程度上反映疾病的严重程度。
肾动脉造影是ARI诊断的金标准,典型征象包括肾动脉主干或其分支截断或见腔内充盈缺损。本研究中共5例患者进行了此项检查,均呈现阳性结果。具有创伤性是肾动脉造影的不足之处,超声检查无创伤,但敏感性差,对于ARI的诊断价值有限。本研究中所有患者均行超声检查,仅3例患者提示ARI可能。2016年的一项研究提示,应用对比剂的增强超声有助于ARI的检出[12]。CECT是包括本研究在内的多项研究中采用最多的诊断方法,通过三维重建,CECT可以显示血管病变以及病灶周围侧支循环的情况,还可探及腹腔及腹膜后的病变,同时具有便捷、无创、技术成熟等优势[9,13]。常见征象包括尖端指向肾门的楔形无强化区和被膜下皮质区强化征[3],后者是肾皮质外层由肾囊动脉穿支供血的存活肾实质[14]。肾周间隙渗出性改变及筋膜增厚更多见于急性肾盂肾炎,但在ARI也可见到,是肾实质损伤后继发的炎症反应所致[15]。
ARI的治疗原则是尽快重建血运,最大限度保留肾功能,同时进行病因治疗。治疗手段包括抗凝、溶栓、介入治疗以及手术取栓[1,13,16]。抗凝治疗既可保留肾功能,又可预防或治疗其他重要脏器血栓栓塞,已有研究证实其治疗效果与外科手术无异[8,13]。双侧肾动脉或孤立肾肾动脉血栓栓塞更适合手术取栓。ARI的治疗效果受多方面因素的影响,包括缺血时间、侧支循环情况以及已经存在的肾脏疾病。Rhee等[17]的研究中,血尿是患者ARI后短期和长期死亡的独立危险因素。本研究中,无论血尿组还是无血尿组,大多数患者均接受了抗凝和/或溶栓治疗,并经临床及影像学证实治疗有效。尽管血尿患者血清乳酸脱氢酶、ALT、CRP水平更高,组织损伤更重,但其短期和长期预后与无血尿患者无异,此结果的产生可能与治疗方法的差异有关,尽管差异无统计学意义(P=0.070),但可见更多的血尿患者接受了静脉溶栓治疗。与抗凝治疗相比,静脉溶栓能够更为快速地重建血运。
本研究存在一定的局限性,首先,这是一项回顾性研究,样本量也比较小;其次,部分患者受检查所限病因并未明确,随访数据也不够完整;第三,病例的诊治时间跨度超过20年,对该病的认识、诊断技术和治疗方法均发生了较大的变迁。未来需要进行多中心、大样本、前瞻性研究以探讨ARI的临床特征和诊治策略。
综上所述,本研究提示心源性血栓栓塞是ARI最主要的病因,相当多的患者同时合并其他脏器血栓栓塞事件,血尿不是一个敏感的诊断线索并与预后无关,是否出现血尿可能取决于肾实质损伤的程度,对于持续腰腹痛、血乳酸脱氢酶升高且具备高危因素的患者,应尽早进行CECT检查以确诊或除外ARI,抗凝治疗既可保留肾功能,又可预防或治疗其他重要脏器血栓栓塞,是最主要的治疗手段。
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