肾功能不全是肝硬化的一个常见并发症，常在中晚期肝硬化及腹水患者观察到。加拿大多伦多大学医学博士Florence Wong教授在第24届亚太地区肝脏研究协会年会上的报告总结了若干评估肝硬化患者肾功能的研究。
 

Florence Wong教授
 

据估计，住院肝硬化患者的肾功能不全发生率约占20％。这些病例大多数是肾功能不全急性发作，通常称为AKI 。三分之二的AKI发作属于功能性，与肝硬化血流动力学变化有关，包括内脏和全身动脉血管扩张以及有效动脉血容量减少，而其余的AKI部分与肾结构损害有关，肾小管损害多于肾小球。不到1％的肝硬化和AKI患者有肾后性梗阻，是其AKI的一个病因。
 

功能性AKI最严重的类型是1型肝肾综合征（HRS-1），这往往是由感染或容积改变造成的。如果不进行治疗，HRS-1的中位存活时间为7-10天。使用血管收缩剂进行HRS-1药物治疗，可改善约三分之一患者的肾功能。血管收缩剂的治疗应答率较低的原因不详。许多医生认为，血管收缩剂治疗HRS-1治疗可能开始的太晚，因此，许多患者可能已经越过了“无法挽救”的门槛。这可能与血清肌酐（肾功能的常用指标），往往过高估计失代偿性肝硬化患者的肾小球滤过率这一事实有关，这可能又引起HRS -1开始治疗延迟。晚期表现HRS- 1患者肾缺血延长也可导致结构损坏，例如急性肾小管坏死（ATN），最近的数据表明，即使不正常的血流动力学得以纠正，结果也将不可逆。
 

为了克服这些问题，国际腹水协会和急性透析品质倡议最近修改了肝硬化人群急性肾损伤网络（ AKIN ）的AKI诊断标准，即48小时内血清肌酐急性升高26.4μmol/L（0.3mg/dl）或比基线增加50％，而与最终血清肌酐水平无关。采用新诊断标准诊断为AKI的患者有着相同的诱发事件，与门诊或住院部患者的生存时间较差有关，尽管血肌酐也有小幅升高。肌酐升高水平较低时的治疗干预可能会导致肾功能障碍逆转率较高，从而改善患者预后。但是，AKIN的诊断标准，还能为定义AKI分期和进展提供指南。从任何起点到下一分期的AKI的生存时间明显较差。
 

目前正在努力确定可预测AKI进展的肾功能生物标志物，所以实施了预防策略。因此，肾功能不全甚至较十年前有很大的增加。患者现在已经不再分为HRS-1或无HRS-1，目前轻度肾功能不全的肝硬化患者还占相当比例，现在将对这些患者进行研究，以确定他们的自然史，病理生理学，治疗方案和预防措施。
 

原文阅读》》》Clinical Spectrum of Acute Kidney Injury in Patients with Liver Disease
 

Renal dysfunction is a common complication of liver cirrhosis, frequently observed in patients with advanced cirrhosis and ascites. In a report that summarises several studies assessing renal function in cirrhosis, it has been estimated that renal dysfunction occurs in approximately 20% of hospitalised cirrhotic patients. The majority of these cases are acute episodes of renal dysfunction, more commonly known as AKI. Two-thirds of these AKI episodes are functional in nature, related to haemodynamic changes in cirrhosis, consisting of splanchnic and systemic arterial vasodilatation with resultant reduction in effective arterial blood volume, while the remainder of AKI episodes are related to renal structural damage, more commonly tubular than glomerular. Less than 1% of patients with cirrhosis and AKI have post-renal obstruction as a cause of their AKI. 
 

The most severe form of functional AKI is type 1 hepatorenal syndrome (HRS-1),which frequently is precipitated by either infection or volume changes. HRS-1, if left untreated, has a median survival of 7-10 days. Pharmacotherapy using vasoconstrictors for HRS-1 has led to improvement in renal function in approximately one-third of patients. The reasons for this low response rate to vasoconstrictor therapy are unclear. Many clinicians believe that treatment for HRS-1 with vasoconstrictor therapy may be started too late in the course of the natural history of renal dysfunction, and therefore many patients may have crossed the threshold of “no return”. This may be related to the fact that serum creatinine, the commonly used index of renal function, tends to overestimate the glomerular filtration rate in decompensated cirrhosis, and this may contribute to a delay in initiating treatment for HRS-1. Prolonged renal ischaemia in late-presenting HRS-1 can also lead to structural damage such as acute tubular necrosis(ATN), as recent data have suggested, and therefore will not be reversible even if the abnormal haemodynamics are corrected.
 

To overcome some of these issues, the International Ascites Club and the Acute Dialysis Quality Init iative recently modified the AKI diagnostic criteria of the Acute Kidney Injury Network (AKIN) for the cirrhotic population as an acute rise in serum creatinine by 26.4µmol/L(0.3 mg/dL) in <48 hours or a 50% increase from baseline irrespective of the final serum creatinine level. Patients diagnosed with AKI with these new diagnostic criteria also have the same precipitating events, associated with a worse survival, whether in an outpatient or inpatient setting, despite a smaller increase in serum creatinine. Treatment intervent ion at a lower level of creatinine increase could potentially lead to a higher rate of reversal of renal dysfunction, leading to improved patient outcomes. The AKIN diagnostic criteria, however, also provide guidelines to define staging and progression of AKI. The progression of AKI from any starting point to the next stages is associated with markedly worse survival. 
 

Efforts are now being made to identify renal biomarkers that can predict progression of AKI, so to implement prevention strategies. Therefore, the spectrum of renal dysfunction has greatly expanded from even a decade ago. Patients are now no longer classified as either having HRS-1 or no HRS-1, rather, there is a substantial population of cirrhotic patients with milder degrees of renal dysfunction, who will now be studied to determine their natural history, pathophysiology, treatment options and preventative measures.