(Analgesic nephropathy ) 止痛藥於慢性腎病人 使用 提醒

請慎用止痛藥！腎臟科名醫沉痛告白 發稿時間：2017/02/08「親愛的醫生：這位患者有慢性腎病（腎病期數3b、腎功能指數38ml/min/1.73㎡），請勿開立NSAIDs（非類固醇消炎止痛藥），但Aspirin及Acetaminophen可適量使用，以避免影響腎功能。誠摯感謝。」用中英文親筆手寫便條紙，是腎臟科名醫、中國醫藥大學附設醫院副院長黃秋錦最深重的託付與叮嚀。「我就這樣寫，一張張寫給非腎臟科醫生看，」黃秋錦用力地說，腎臟科醫生有責任提醒非腎臟科醫師。因為她看過太多有慢性腎臟病的人，因為感冒全身痠痛去「吊大筒（點滴）」加上打止痛針，結果腎指數變差甚至產生嚴重腎衰竭，「吃了立刻不痛的藥，有可能會害你的腎！」黃秋錦說，腎臟不好的人要慎用非類固醇類消炎止痛藥，但她憂心這類止痛藥在台灣用得太浮濫，因為對腎臟有傷害的含馬兜鈴酸中草藥早已在2003年禁止使用，「慢性腎病卻還這麼多，我們要思考其他可能的原因，」她說。無獨有偶，積極推動慢性腎病防治、高雄醫學大學附設中和紀念醫院副院長黃尚志也發現，醫界對於止痛藥的使用應更謹慎。「我們在病患健保卡上註記、有貼紙提醒，還是亂開藥⋯⋯，」說到這，他忍不住氣憤到用力重捶沙發3下。

止痛藥破壞腎臟保護機制 非類固醇消炎止痛藥（Nonsteroidal anti-inflammatory drugs，NSAIDs）因同時具有止痛及抗發炎效果而被廣泛使用於關節炎及各種疼痛上，如學名藥Ibuprofen、Naproxen、Celecoxib、Ketoprofen等，這類藥物會抑制前列腺素E合成，破壞腎臟自我保護機轉，造成腎衰竭，也會破壞腎小管，引發間質性腎炎。健康人使用它造成腎病的比例不高，但對年老或有心、腎疾病的人來說，會增加急性腎衰竭機率。《台灣慢性腎臟病臨床診療指引》指出，長期使用非類固醇消炎止痛藥比未使用者多3倍發生急性腎衰竭風險，建議謹慎使用、減少劑量並縮短使用時間。尤其點滴或直接注射傷害更大。

Analgesic nephropathy: Proper kidney function depends upon adequate blood flow to the kidney. Kidney blood flow is a complex, tightly regulated process that relies on a number of hormones and other small molecules, such as prostaglandins. Under normal circumstances, prostaglandin E2 (PGE2) produced by the kidney is necessary to support adequate blood flow to the kidney. Like all prostaglandins, PGE2 synthesis depends upon the cyclooxygenases. Aspirin and other NSAIDs are inhibitors of the cyclooxygenases. In the kidney, this inhibition results in decreased PGE2 concentration causing a reduction in blood flow. Because blood flow to the kidney first reaches the renal cortex (outside) and then the renal medulla (inside), the deeper structures of the kidney are most sensitive to decreased blood flow. Thus the innermost structures of the kidney, known as the renal papillae, are especially dependent on prostaglandin synthesis to maintain adequate blood flow. Inhibition of cyclooxygenases therefore rather selectively damages the renal papillae, increasing the risk of renal papillary necrosis. NSAIDs caused no adverse effects on renal function in healthy dogs subjected to anesthesia. Most healthy kidneys contain enough physiologic reserve to compensate for this NSAID-induced decrease in blood flow. However, those subjected to additional injury from phenacetin or paracetamol may progress to analgesic nephropathy.

Chronic kidney disease: targeting prostaglandin E2 receptors. Am J Physiol Renal Physiol. 2014 Aug 1;307(3) Chronic kidney disease is a leading cause of morbidity and mortality in the world. A better understanding of disease mechanisms has been gained in recent years, but the current management strategies are ineffective at preventing disease progression. A widespread focus of research is placed on elucidating the specific processes implicated to find more effective therapeutic options. PGE2, acting on its four EP receptors, regulates many renal disease processes; thus EP receptors could prove to be important targets for kidney disease intervention strategies. This review summarizes the major pathogenic mechanisms contributing to initiation and progression of chronic kidney disease, emphasizing the role of hyperglycemia, hypertension, inflammation, and oxidative stress. We have long recognized the multifaceted role of PGs in both the initiation and progression of chronic kidney disease, yet studies are only now seriously contemplating specific EP receptors as targets for therapy. Given the plethora of renal complications attributed to PG involvement in the kidney, this review highlights these pathogenic events and emphasizes the PGE2 receptor targets as options available to complement current therapeutic strategies.