專題討論19:腎臟衰竭與國人常用藥物的關係

S19-5
腎臟保護藥物: 輔助性及發展中新藥物
Renoprotective Drugs : complementary alternative and potential future therapies
洪振傑 楊智偉
林口長庚醫院 腎臟科

The increasing global prevalence of chronic kidney disease (CKD) and end-stage renal disease with the associated spiraling cost has profound public health and economic implications. This has made slowing the progression of CKD, a major health-care priority. Efficient control of blood pressure (BP) and minimization of proteinuria appear as the two most important measures to preserve residual kidney function. Therapies that target the renin-angiotensin system (RAS) offer particular benefit to hypertensive, proteinuric patients with CKD because these agents reduce proteinuria as well as BP. However, because of the pathogenetic complexity of CKD, multidrug interventions with the least adverse effects should be investigated in attempts to stop CKD progression.

For many years patients with CKD have been advised to control the protein content of their diet. This advice has been given on the basis of a number of reported metabolic effects of lowering protein intake, and, more recently, ameliorating proteinuria (independent of antiproteinuric medications). The effects on the progression of kidney disease, although spectacular in experimental studies, have been less convincing in humans. Dyslipidemia is highly prevalent in patients with CKD and may contribute to the elevated cardiovascular risk as well as CKD progression. Statins are lipid-lowering drugs that appear to protect the kidneys via cholesterol reduction as well as noncholesterol-mediated mechanisms. Subgroup analyses of major clinical studies and meta-analyses of smaller trials indicate that statin therapy slows the decline of the glomerular filtration rate. Additionally, statins appear to reduce proteinuria in patients with CKD. Pentoxifylline, a non-selective phosphodiesterase inhibitor with indiscernible toxicity, exerts potent inhibitory effects against cell proliferation, inflammation, and extracellular matrix accumulation, all of which play important roles in CKD progression. Limited human studies have proven pentoxifylline efficacy in reducing proteinuria in patients with diabetes receiving angiotensin-converting enzyme inhibitors. Further clinical trials are necessary to examine whether pentoxifylline can improve renal outcomes in patients receiving interventions of proven efficacy.

Novel therapeutic approaches, focusing on experimental therapies that target the key cellular events that are central to kidney fibrosis, have the potential of being translated to the clinical arena within the foreseeable future.