Text B Chronic Kidney Disease:Treatment
Treatments aimed at specific causes of chronic kidney disease（CKD）are discussed elsewhere．The optimal timing of therapy is usually well before there has been a measurable decline in glomerular filtration rate（GFR）and certainly before CKD is established．It is helpful to sequentially measure and plot the rate of decline of GFR in all patients．Any acceleration in the rate of decline should prompt a search for superimposed acute or subacute processes that may be reversible．These include extracellular fluid volume（ECFV）depletion， uncontrolled hypertension，urinary tract infection，new obstructive uropathy，exposure to nephrotoxic agents（such as NSAIDs or radiographic dye），and reactivation or flare of the original disease，such as lupus or vasculitis．
Slowing the Progression of CKD
There is variation in the rate of decline of GFR among patients with CKD． However，the following interventions should be considered in an effort to stabilize or slow the decline of renal function．
Protein Restriction
While protein restriction has been advocated to reduce symptoms associated with uremia，it may also slow the rate of renal decline at earlier stages of renal disease．This concept is based on clinical and experimental evidence that protein－mediated hyperfiltration contributes to ongoing decline in renal function in many different forms of renal disease1．A number of studies have shown that protein restriction may be effective in slowing the progression of CKD，especially proteinuric nephritis and diabetic renal diseases．However，the Modification of Diet in Renal Disease Study was unable to demonstrate a robust benefit in delaying progression to advanced stages of CKD with dietary restriction of protein intake．Nonetheless，restriction of dietary protein intake has been recommended for CKD patients．Kidney Disease Outcomes Quality Initiative（KDOQI）clinical practice guidelines include a daily protein intake of between 0．60 and 0．75 g／kg per day，depending upon patient adherence， comorbid disease，presence of proteinuria，and nutritional status．It is further advised that at least 50％of the protein intake be of high biologic value2．As patients approach stage 5 CKD，spontaneous protein intake tends to decrease， and patients may enter a state of protein－energy malnutrition．In these circumstances，aprotein intake of up to 0．90 g／kg per day might be recommended， again，with an emphasis on proteins of high biologic value．
Reducing Intraglomerular Hypertension and Proteinuria
Increased intraglomerular filtration pressures and glomerular hypertrophy develop as a response to loss of nephron number from different kidney diseases． This response is maladaptive，as it promotes the ongoing decline of kidney function even if the inciting process has been treated or spontaneously resolved． Control of systemic and glomerular hypertension is at least as important as dietary protein restriction in slowing the progression of CKD．Therefore，in addition to reduction of cardiovascular disease risk，antihypertensive therapy in patients with CKD also aims to slow the progression of nephron injury by reducing intraglomerular hypertension．Elevated blood pressure increases proteinuria through its transmission to the glomerulus．Conversely，the renoprotective effect of anti－hypertensive medications is gauged through the consequent reduction of proteinuria．Thus，the more effective a given treatment is in lowering protein excretion，the greater the subsequent impact on protection from decline in GFR3．This observation is the basis for the treatment guideline establishing 125／75 mm Hg as the target blood pressure in proteinuric nephritis CKD patients．
ACE inhibitors and ARBs inhibit the angiotensin－induced vasoconstriction of the efferent arterioles of the glomerular microcirculation．This inhibition leads to a reduction in both intraglomerular filtration pressure and proteinuria． Several controlled studies have shown that these drugs are effective in slowing the progression of renal failure in patients with both diabetic and nondiabetic renal failure．This slowing in progression of CKD is strongly associated with their proteinuria－lowering effect．In the absence of an anti－proteinuric nephritis response with either agent alone，combined treatment with both ACE inhibitors and ARBs can be tried．Adverse effects from these agents include cough and angioedema with ACE inhibitors，anaphylaxis，and hyperkalemia with either class．A progressive increase in plasma creatinine concentration may suggest the presence of renovascular disease within the large or small arteries． Development of these side effects may mandate the use of second－line antihypertensive agents instead of the ACE inhibitors or ARBs．Among the calcium channel blockers，diltiazem and verapamil may exhibit superior anti－proteinuric and renoprotective effects compared to the dihydropyrimidines．At least two different categories of response can be considered：one in which progression is strongly associated with systemic and intraglomerular hypertension and proteinuria（e．g．diabetic nephropathy，glomerular diseases）and in which ACE inhibitors and ARBs are likely to be the first choice；and another in which proteinuria is mild or absent initially（e．g．adult polycystic kidney disease and other tubulointerstitial diseases）and hence the contribution of intraglomerular hypertension less prominent，for which reason other anti－hypertensive agents can be useful for control of systemic hypertension4．
Slowing Progression of Diabetic Renal Disease
Diabetic nephropathy is now the leading cause of CKD requiring renal replacement therapy in many parts of the world，and its prevalence is increasing disproportionately in the developing world．Furthermore，the prognosis of diabetic patients on dialysis is poor，with survival comparable to many forms of cancer．Accordingly，it is mandatory to develop strategies whose aim is to prevent or slow the progression of diabetic nephropathy in these patients5．
Control of Blood Glucose
Excellent glycemic control reduces the risk of kidney disease and its progression in both type 1 and type 2 diabetes mellitus．It is recommended that plasma values for preprandial glucose be kept in the 5．0—7．2 mmol／L（90—130 mg／d L）range and hemoglobin A1c（Hb A1c）should be＜7％6．As the GFR decreases with progressive nephropathy，the use and dose of oral hypoglycemics needs to be reevaluated．For example，chlorpropamide may be associated with prolonged hypoglycemia in patients with decreased renal function；metformin has been reported to cause lactic acidosis in the patient with renal impairment and should be discontinued when the GFR is reduced；and the thiazolidinediones （e．g．rosiglitazone，pioglitazone，and others），may increase renal salt and water absorption and aggravate volume－overloaded states．Finally，as renal function declines，renal degradation of administered insulin will also decline， so that less insulin may be required for glycemic control．
Control of Blood Pressure and Proteinuria
Hypertension is found in the majority of type 2 diabetic patients at diagnosis． This finding correlates with the presence of albuminuria and is a strong predictor of cardiovascular events and nephropathy．Microalbuminuria，the finding of albumin in the urine not detectable by the urine dipstick，precedes the decline in GFR and heralds renal and cardiovascular complications．Testing for microalbumin is recommended in all diabetic patients，at least annually．If the patient already has established proteinuria，then testing for microalbumin is not necessary．Anti－hypertensive treatment reduces albuminuria and diminishes its progression even in normotensive diabetic patients．In addition to treatment of hypertension in general，the use of ACE inhibitors and ARBs in particular is associated with additional renoprotection．These salutary effects are mediated by reducing intraglomerular pressure and inhibition of angiotensin－driven sclerosing pathways，in part through inhibition of transforming growth factor（TGF）—mediated pathways．
Implications for Global Health
In distinction to the natural decline and successful eradication of many devastating infectious diseases，there is rapid growth in the prevalence of hypertension and vascular disease in developing countries．Diabetes mellitus is becoming increasingly prevalent in these countries，perhaps due in part to change in dietary habits，diminished physical activity，and weight gain． Therefore，it follows that there will be a proportionate increase in vascular and renal disease．Health care agencies must plan for improved screening for early detection，prevention，and treatment plans in these nations and must start considering options for improved availability of renal replacement therapies．
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New Words and Phrases
superimposed［,sjuːpəɪm'pəʊzd］a． 叠加的，重叠的
subacute［,sʌbə'kjuːt］a． 亚急性的
depletion［dɪ'pliːʃən］n． 减液（如放血）；耗尽
uropathy［juː'rɑːpəθɪ］n． 尿路
nephrotoxic［nefrə'tɔksɪk］a． 对肾脏有害处的；足以危害肾脏的
reactivation［rɪ（ː）æktɪ'veɪʃən］n． 再生（作用）；再激活；再活化
radiographic［,reɪdɪəʊ'ɡræfɪk］a． 放射光线照相术的
flare［fleə］n． （皮肤的）红肿块
lupus［'luːpəs］n． 狼疮
vasculitis［,væskjʊ'laɪtɪs］n． 脉管炎，血管炎
uremia［jʊə'riːmɪə］n． 尿毒症
hyperfiltration［,haɪpəfɪl'treɪʃən］n． 超（过）滤
proteinuric nephritis［ne'fraɪtɪs］ 蛋白尿性肾炎
diabetic［daɪə'betɪk］a． 糖尿病的
comorbid［kəʊ'mɔːbɪd］a． 并存的；与另一疾病同时存在的
proteinuria［,prəʊtiː'njʊərɪə］n． 蛋白尿（症）
malnutrition［,mælnjʊ'trɪʃən］n． 营养不良
hypertrophy［haɪ'pзːtrəʊfɪ］n． 肥大；过度增大
nephron［'nefrɒn］n． 肾单位
maladaptive［,mælə'dæptɪv］a． （个体、物种等）不适应的；适应不良的
renoprotective［,riːnəʊprəʊ'tektɪv］a． 保护肾脏的
excretion［ek'skriːʃən］n． 排泄，分泌；排泄物，分泌物
angiotensin［,ændʒɪəʊ'tensɪn］n． 血管紧张素
efferent［'efərənt］a． 传出的，输出的
arteriole［ɑː'tɪərɪəʊl］n． 小动脉
anti－proteinuric［'æntɪ,prəʊtiːn'jʊərɪk］a． 抗蛋白尿的
angioedema［,ændʒiːəʊə'diːmə］n． 血管性水肿
anaphylaxis［,ænəfɪ'læksɪs］n． 过敏性；过敏反应
hyperkalemia［,haɪpəkə'liːmɪə］n． 高钾血症
blocker［'blɒkə］n． 阻滞剂；阻断药
diltiazem［dɪl'tɪəzem］n． 地尔硫䓬（一种钙离子拮抗剂）
verapamil［və'ræpəmɪl］n． 维拉帕米（一种冠状动脉扩张药）
dihydropyrimidine［daɪ,haɪdrəʊpə'rɪmɪdiːn］n．二氢嘧啶
polycystic［,pɒlɪ'sɪstɪk］n． 多囊的
tubulointerstitial［,tuːbjuːloʊ,ɪntə'stɪʃəl］a． 肾小管间质的
glycemic［ɡlɪ'semɪk］a． 血糖的
prognosis［prɒɡ'nəʊsɪs］（［复］prognoses）n．预后
diabetes mellitus［,daɪə'biːtɪs,－tiːz mə'laɪtəs］ 糖尿病
preprandial［priː'prændɪəl］a． 餐前的
glucose［'ɡluːkəʊs］n． 葡萄糖
hemoglobin［,hiːməʊ'ɡləʊbɪn］n． 血红蛋白
hypoglycemics［,haɪpəʊɡlaɪ'siːmɪks］n． 降血糖剂
chlorpropamide［klɔː'prəʊpəmaɪd］n． 氯磺丙脲（一种降血糖药）
metformin［met'fɔːmɪn］n． 二甲双胍（一种降血糖药）
lactic acidosis［'læktɪk,æsɪ'dəʊsɪs］n． 乳酸性酸中毒
impairment［ɪm'peəmənt］n． 损伤，损害
thiazolidinediones n． 噻唑烷二酮类
rosiglitazone n． 罗西格列酮，罗格列酮（一种降血糖药）
pioglitazone n． 匹格列酮
insulin［'ɪnsəlɪn］n． 胰岛素
albuminuria［,ælbjuːmɪ'njʊərɪə］n． 蛋白尿
albumin［'ælbjʊmɪn］n． 清蛋白，白蛋白
normotensive［,nɔːməʊ'tensɪv］a． 血压正常的
salutary［'sæljʊtərɪ］a． 效果好的；有用的；有益健康的
intraglomerular［,ɪntrə'ɡlɒmərjʊlə］a． 肾小球内的
sclerosing［sklɪə'rəʊsɪŋ］a． 致硬化的；硬化性的
Notes
1．This concept is based on clinical and experimental evidence that protein－mediated hyperfiltration contributes to ongoing decline in renal function in many different forms of renal disease．
参考译文：这一概念是基于临床和实验证据的。在许多不同形式的肾脏疾病中，蛋白质介导的超滤过会促使各种肾病患者的肾功能持续下降。
be based on意为“基于……，根据……”；contribute to意为“促使，引起”。that引导同位语从句，修饰evidence；in renal function in many different forms of renal disease是介词短语，作后置定语，修饰decline。
2．It is further advised that at least 50％of the protein intake be of high biologic value．
参考译文：该指南还建议摄入的蛋白至少有50％是高生物效价蛋白。
It为形式主语，真正的主语是that引导的主语从句，谓语是is further advised。另外，advise后面的that从句是虚拟语气，be前省略了should。
3．Thus，the more effective a given treatment is in lowering protein excretion，the greater the subsequent impact on protection from decline in GFR．
参考译文：因此，降低蛋白排泄的特定治疗越有效，其随后防止肾小球滤过率下降的作用也就越大。
本句为the more．．．the more句型，译为“越……越……”。
4．At least two different categories of response can be considered：one in which progression is strongly associated with systemic and intraglomerular hypertension and proteinuria（e．g．diabetic nephropathy and glomerular diseases）and in which ACE inhibitors and ARBs are likely to be the first choice；and another in which proteinuria is mild or absent initially（e．g． adult polycystic kidney disease and other tubulointerstitial diseases）and hence the contribution of intraglomerular hypertension less prominent，for which reason other anti－hypertensive agents can be useful for control of systemic hypertension．
参考译文：至少可以考虑有两种不同反应：一种反应是，肾病的进一步发展与全身性和肾小球内高血压及蛋白尿（例如，糖尿病肾病和肾小球性疾病）的相关性极强，因而血管紧张素转换酶抑制剂或血管紧张素受体阻断剂可能是首选药物；另一种反应是，初始阶段有轻微的蛋白尿或无蛋白尿（例如，成人多囊肾病和其他肾小管间质性疾病），肾小球内高血压作用并不明显，因而对于控制全身性高血压，其他降压药物也是有效的。
one in which．．．and another in which．．．是两个in which引导的定语从句，前一个修饰one，后一个修饰another。one和another指代two different categories（两种肾病反应）。for which reason引导非限制性定语从句， which指代前面的内容，即“另一个反应”。
5．Accordingly，it is mandatory to develop strategies whose aim is to prevent or slow the progression of diabetic nephropathy in these patients．
参考译文：因此，研究制订旨在预防或延缓这些糖尿病肾病患者病情渐进性发展的治疗措施就十分必要。
本句中it为形式主语，真正的主语是后面的不定式结构to develop．．．；whose引导限定性定语从句，whose＝strategies'。
6．It is recommended that plasma values for preprandial glucose be kept in the 5．0—7．2 mmol／L（90—130 mg／d L）range and hemoglobin A1c should be＜7％．
参考译文：建议餐前血浆葡萄糖值保持在5．0～7．2 mmol／L（90～130 mg／d L）这一区间，糖化血红蛋白（Hb A1c）应该小于7％。
It是形式主语，真正的主语是that引导的主语从句，谓语是is recommended。另外，recommend后面的主语从句为虚拟语气，谓语be kept前面省略了should。
Exercises
Ⅰ．Answer the following questions．
1．When is the best time for the therapy of CKD？
2．What interventions should be considered in an effort to stabilize or slow the decline of renal function？
3．Why is it mandatory for doctors to develop strategies to prevent or slow the progression of diabetic nephropathy？
4．How can patients reduce the risk of kidney disease and its progression in both type 1 and type 2 diabetes mellitus？
5．What kind of testing is recommended annually in all diabetic patients？
Ⅱ．Decide whether the following statements are True or False．
1．There is no change in the rate of decline of GFR among patients with CKD．
2．Restriction of dietary protein intake has been recommended for CKD patients．
3．Control of systemic and glomerular hypertension is not important in slowing the progression of CKD．
4．Several controlled studies have shown that ACE inhibitors and ARBs are effective in slowing the progression of renal failure in patients with both diabetic and nondiabetic renal failure．
5．Testing for microalbumin is recommended in all diabetic patients annually．