1、Baxter Asia RenalHow PD works 腹透原理腹透原理 Kidney Disease肾脏病基础肾脏病基础Implications Therapy options包括治疗选择包括治疗选择Pr Max DratwaHpital BrugmannBrusselsConfidential Not for distributionLearning objectives学习目的学习目的 Understand normal kidney anatomy&functioning Understand kidney disease:acute and chronic Know the im
2、plications of kidney disease Be able to discuss the different treatment options 理解肾脏正常的解剖和功能 理解急性和慢性肾脏疾病 了解肾脏病的并发症 讨论不同的治疗方式Confidential Not for distributionThe Kidney 肾脏肾脏 肾解剖特征：肾解剖特征：1.肾外形似蚕豆，成年人肾约长肾外形似蚕豆，成年人肾约长12cm，宽，宽6cm，厚，厚3cm，重约，重约120160g；呈红褐色，质软。；呈红褐色，质软。Confidential Not for distributionThe K
3、idney 肾脏肾脏（续）（续）肾解剖特征：肾解剖特征：2.冠状面：冠状面：外外1/3皮质皮质，内，内2/3髓质髓质 肾锥体肾锥体的尖端形成的尖端形成肾乳头肾乳头，23个个肾乳头肾乳头汇入汇入肾小盏肾小盏，肾小盏肾小盏汇入汇入肾盂肾盂 肾门肾门：肾静脉肾静脉、肾动脉肾动脉、输尿管输尿管、神经结缔组织等神经结缔组织等 肾皮质肾皮质肾锥体肾锥体肾盂肾盂输尿管输尿管肾髓质肾髓质肾动脉肾动脉肾静脉肾静脉肾小盏肾小盏Confidential Not for distributionThe Kidney basic unit:the nephron肾脏基本结构：肾单位肾脏基本结构：肾单位每个肾脏由每个肾脏
4、由100万个肾单位组成万个肾单位组成肾单位肾单位肾小球肾小球肾小管肾小管血管丛血管丛血小囊血小囊关键词：关键词：原尿：原尿：终尿：终尿：Confidential Not for distributionUreter输尿管输尿管Urethra尿道尿道Calyx肾盏肾盏Bladder膀胱膀胱Renal pelvis肾盂肾盂Confidential Not for distributionFunctions of the kidney肾功能肾功能Homeostasis=maintenance of equilibrium in terms of:Salt and water(blood pressu
5、re)Electrolytes(K,Mg,)Acid-Base balance(pH)Metabolism of waste productsHormone production Active form of Vitamin D (healthy bones)Erythropoetin(RBC synthesis)Renin-Angiotensin(blood pressure)内环境稳态内环境稳态水盐平衡电解质(K,Mg,)酸碱平衡(pH)废物的代谢激素生成激素生成 活性维生素 D（健康骨）EPO(促进红细胞生成)肾素血管紧张素（调节血压）Confidential Not for distr
6、ibution The diseased kidney肾脏疾病肾脏疾病Confidential Not for distribution Two types of kidney disease Acute failureClassified according to site of problem:pre-renal renal post-renal Chronic disease Classified in 5 stages of increasing seriousness1:1:mild damage 2:mild decrease of renal function 3:moderat
7、e renal insufficiency 4:severe damage 5:end stage renal disease(ESRD)两种类型 急性急性:根据病变部位分类 肾前性（肾脏供血障碍）肾性（肾本身疾病所致）肾后性（肾的排泄系统阻塞）慢性慢性:严格按照疾病进展分5期 1:轻微损害 2:GRF轻度下降 3:GRF中度下降 4:GRF重度下降 5:终末期肾脏疾病（ESRDClassification of Kidney Disease肾脏病分类肾脏病分类1 K/DOQI Clinical Practice Guidelines for Chronic Kidney Disease:Ev
8、aluation,Classification,and Stratification;Part 4 Definition and Classification of Stages of Chronic Kidney Disease,Guideline 1:Definition and Stages of Chronic Kidney Disease,NKF,2002.Confidential Not for distribution肾功能急骤地、进行性地减退导致的临床症候群肾功能急骤地、进行性地减退导致的临床症候群急性肾衰急性肾衰Confidential Not for distributio
9、n“Pre-renal”Usually due to decreased blood flow to the kidneyshemorrhage,gastrointestinal bleeding leading to shockburnssepsisemboli,stenosis,occlusion,trauma to renal arterydecreased cardiac outputcongestive heart failure,myocardial infarctionSurgery 肾前性 通常是因为肾脏血流灌注减少 出血性疾病导致休克 创伤 败血症 肾动脉狭窄、栓塞、硬化等
10、心输出量下降 充血性心力衰竭、心肌梗塞 手术Causes of Acute Kidney Failure 急性肾功能衰竭的原因急性肾功能衰竭的原因 1 ANNA Core Curriculum for Nephrology Nursing,3rd Edition,Lancaster,L.;Section III,Causes of Renal Disease,pgs.53-62.Confidential Not for distributionCauses of Acute Kidney Failure 急性肾功能衰竭的原因急性肾功能衰竭的原因“Intra-renal”(continued)I
11、nflammation from bacteria/virusTrauma Immunological and vasculitic diseases Auto-antibodies(Goodpastures,LED,Wegeners,)Transfusion reactionsVascular disorders hypertension,diabetesPregnancy disorders pre-eclampsia,septic abortionTissue or organ transplant rejection肾性（续）细菌或病毒感染创伤自身免疫性疾病和血管疾病 自身抗体(Goo
12、dpastures,LED,Wegeners,)输血反应血管性疾病 高血压、糖尿病妊娠相关疾病 子痫,败血症流产器官移植排异Confidential Not for distributionCauses of Acute Kidney Failure 4急性肾功能衰竭的原因急性肾功能衰竭的原因 4“Post-renal”The flow of urine from the kidneys to the exterior of the body is prevented,usually due to an obstruction(stones,tumors,)肾后性 尿液从肾脏排出体外受阻，通常
13、为尿路梗阻(结石,肿瘤等)X XX XConfidential Not for distributionAcute Kidney Failure急性肾功能衰竭急性肾功能衰竭 Acute Kidney Failure Occurs over hours or few days Lasts hours to a few months,up to 1 year Can be reversible 50%mortality rate major cause of death is infection 急性肾功能衰竭急性肾功能衰竭 数小时或数天后出现 持续数小时、数日，甚至一年可逆性可逆性 死亡率高达5
14、0%通常死于感染Confidential Not for distributionDefining CKD(Guidelines 1&6 1)Kidney damage,as defined by structural or functional abnormalities of the kidney(with or without decreased GFR)as manifested by:pathological abnormalitiesmarkers of kidney damageProteinuria(can be estimated by the ratio urinary p
15、roteins/creatinine)Hematuria and RBC castsPyuria(WBCs)abnormal imaging studiesGlomerular Filtration Rate(GFR)60 ml/min/1.73m2(with or without kidney damage)Chronic Kidney Disease(CKD)慢性肾脏病（慢性肾脏病（CKD）1 K/DOQI Clinical Practice Guidelines for Chronic Kidney Disease:Evaluation,Classification,and Strati
16、fication;Part 4 Definition and Classification of Stages of Chronic Kidney Disease,Guideline 1:Definition and Stages of Chronic Kidney Disease and Part 5 Evaluation of Laboratory Measurements for Clinical Assessment of Kidney Disease,Guideline 6:Markers of Chronic Kidney Disease Other than Proteinuri
17、a,AJKD,February 2002.CKD的定义(指南 1&6 1)肾损害：肾脏结构或功能的损害(可以没有 GFR下降):病理改变 损害指标 蛋白尿 血尿 白细胞尿或脓尿 影像学检查异常GFR 60 ml/min/1.73m2(可以伴有或不伴有肾损害，持续3个月以上）Confidential Not for distributionChronic Kidney Disease 慢性肾脏病慢性肾脏病 Clinical factors associated with an increased risk for CKDDiabetesHypertensionAutoimmune disease
18、sSystemic infectionsUrinary tract infectionsUrinary stonesLower urinary tract obstructionNeoplasia(cancer)Family history of CKDRecovery from acute kidney failureReduction in kidney mass(trauma,surgery)Exposure to certain drugsLow birth weight1 K/DOQI Clinical Practice Guidelines for Chronic Kidney D
19、isease:Evaluation,Classification,and Stratification;Part 4 Definition and Classification of Stages of Chronic Kidney Disease,Guideline 3:Individuals at Increased Risk for Chronic Kidney Disease,AJKD February 2002.Individuals at Increased Risk for CKD(Guideline 3 1)CKD易患人群（指南3）临床因素临床因素 糖尿病 高血压 自身免疫性疾
20、病 系统性感染 尿路感染 尿路结石 下尿路梗阻 肿瘤 CKD家族史 急性肾功能衰竭恢复期 肾脏容积减少（创伤，手术）服用某些肾毒性药物 低出生体重Confidential Not for distributionGlomerular Filtration Rate(GFR)is an index of kidney functionMost accurate measurement is by isotopic methodsEstimating GFR is accomplished by using the patients serum creatinine value in an equ
21、ation other values used in the equation include patients age,sex,weight,race,etc.Equations include:For adults,the equation derived from the MDRD Study or the Cockcroft-Gault formula For pediatric patients,Schwartz or Counahan-Barratt No need to do a 24 hour urine collection to measure clearances(alt
22、hough a precise measurement can be made by the mean of urea and creatinine clearances)Calculators can be found on the following site:www.kidney.org/professionals/tools/肾小球滤过率（GFR）是反应肾功能的一项指标是单位时间内肾小球滤出地肾血浆流量，正常值为120160ml/min最精确的方法是应用同位素测定估计GFR的公式需要考虑血肌酐、年龄、性别、种族、体重、身高等因素的影响:成人可以运用 MDRD 研究或 Cockcroft
23、-Gault方程 儿童可以运用 Schwartz 或 Counahan-Barratt方程 无需留取24小时尿测定清除率（虽然测定尿素和肌酐清除率较准确）计算方程式可以参阅网站:www.kidney.org/professionals/tools/K/DOQI Guidelines for Classification 1 K/DOQI 指南估计指南估计GFR 11 K/DOQI Clinical Practice Guidelines for Chronic Kidney Disease:Evaluation,Classification,and Stratification;Part 5
24、Evaluation of Laboratory Measurements for Clinical Assessment of Kidney Disease,Guideline 4:Estimation of GFR,AJKD February 2002.Confidential Not for distributionCKD:Classification1 CKD分期分期StageDescriptionGFRmL/min/1.73mActions1Kidney damage with normal or increased GFR肾损害，GRF正常或增加9070%of normal fun
25、ction70%肾功能正常）Diagnose&treat cause,comorbid conditions 诊断和治疗Try to slow progression 延缓进展Reduce CKD risk 减少CKD患病因素2Kidney damage with mild decrease in GFR肾损害，GFR轻度下降60 8955 70%Estimate progression of disease 评估进展Idem Stage 1 同Stage 13Moderate decrease in GFRGFR中度下降30 5925 55%Assess anemia,nutrition a
26、nd bone status 评价贫血、营养和骨病Treat complications 治疗并发症Idem Stage 1&2 同Stage 1&24Severe decrease in GFRGFR重度下降15 2915 25%Referral to nephrologist 肾脏专科诊治Prepare for RRT(Predialysis education)准备肾脏替代治疗（透析前教育）Start RRT earlier if elderly,diabetes,CVD,other comorbid conditions 老年、糖尿病、CVD、及其他合并症者早期肾脏替代治疗5Kidne
27、y failure肾衰竭 15(dialysis)15%Uremic symptoms,marked in urea,creatinine,K+,P+&fluid 尿毒症症状，尿素，肌酐升高，高钾高磷，容量过多Start RRT 开始肾脏替代治疗1 K/DOQI Clinical Practice Guidelines for Chronic Kidney Disease:Evaluation,Classification,and Stratification;Part 4 Definition and Classification of Stages of Chronic Kidney Di
28、sease,Guideline 2:Evaluation and Treatment,AJKD February 2002.Confidential Not for distributionCauses of Chronic Kidney DiseaseCKD病因病因DiabetesHypertension/Large Vessel DiseaseRenal Artery Stenosis or OcclusionCholesterol Emboli,Renal EmboliGlomerulonephritisInterstitial Nephritis/PyelonephritisAnalg
29、esic AbuseMiscellaneous Conditions(includes unknown)Complication Post Bone Marrow or Other TransplantSickle Cell DiseaseAIDS NephropathyTraumatic/Surgical Loss of KidneyHepatorenal SyndromeTubular Necrosis with No RecoveryIncidence of Treated ESRD by Primary Disease,1999-2002Description of Diseases
30、taken from the USRDS 2004 Annual Data Report糖尿病高血压/大血管病变肾动脉狭窄或梗阻动脉粥样硬化肾小球肾炎间质性肾炎/肾盂肾炎止痛剂成瘾不明原因骨髓移植或其他器官移植后镰状细胞病AIDS 相关性肾病肾脏外伤或手术肝肾综合征肾小管不可逆性坏死Confidential Not for distribution Secondary Glomerulonephritis/Vasculitis Lupus Scleroderma Hemolytic Uremic Syndrome Nephropathy from Heroin/Related Abuse Ne
31、oplasms/Tumors Multiple Myeloma Amyloidosis 继发性肾小球肾炎/血管炎 狼疮 硬皮病 溶血尿毒综合征 海洛因或其它毒品成瘾性肾病 新生物/肿瘤 多发性骨髓瘤 淀粉样变性Causes of Chronic Kidney DiseaseCKD病因病因（续）（续）Confidential Not for distributionConsequences of CKD慢性肾脏病的预后慢性肾脏病的预后 When 75-80%of renal function is lost,every organ system is affected 1 End Stage R
32、enal Disease(ESRD)is irreversible kidney disease 10-15%of renal function remaining Patient must receive dialysis or transplant,or they will die!75-80%的肾功能丧失后，各个系统都会受到影响 ESRD是 不可逆不可逆 的肾脏疾病 残余肾功能60 mcg/dL.%Transferrin Saturationavailable Iron25-45%normalDialysis patients:25%Serum Ferritinstored Iron12
33、-300 ng/mL.NormalDialysis patients:100-600 ng/mL.Anemia Status 贫血贫血 铁铁 血清铁 正常值：25-170 mcg/dL 透析病人：60 mcg/dL.转铁蛋白饱和度 可利用的铁 正常值：25-45%透析病人：25%血清铁蛋白 储存铁 正常值：12-300 ng/mL 透析病人：100-600 ng/mL.注意：多数患者铁的指标并不低Confidential Not for distribution Indicators of Iron Deficiency 铁缺乏指标 Causes resulting decrease in H
34、b levels 导致血红蛋白下降Anemia Status 贫血贫血（续）（续）Confidential Not for distributionAnemia Treatment 贫血治疗贫血治疗 Recombinant human erythropoietin(Eprex,Neo-Recormon)or darbepoietin(Aranesp)with increased half-life and activity Given sub-cut.(pre-D and PD)or IV(HD)Stimulates RBC production by bone marrow Pt must
35、be iron repleted for these drugs to work efficiently:major cause of resistance to EPO therapy Other causes of resistance:-inflammation(infection,cancer,)-Pure Red Cell Aplasia(antibodies against EPO seen with SC Eprex)重组人红细胞生成素（EPO）皮下(透析前和 PD)或静脉(HD)刺激骨髓造血 补铁:缺铁是EPO反应不佳的主要原因 其他原因:感染、肿瘤、纯红细胞再障（EPO抗体形
36、成）Confidential Not for distributionAlterations in Body Systems 11各系统症状各系统症状 11 Fluid balance/imbalance retention of water volume overload serum albumin level is low hypertension shortness of breath edema of tissues or organs 体液平衡体液平衡 水潴留 体液过多 低蛋白血症 高血压 呼吸短促 水肿Illustration from NKF Nephrology 101 Cou
37、rse:Pathophysiology by S.Mujais,2004.Confidential Not for distributionAlterations in Body Systems 12各系统症状各系统症状 12Electrolyte balance/imbalancesodiumpotassiumcalcium/phosphorusglucosemagnesiumhydrogen/bicarbonateAluminum 电解质平衡/失衡 钠（GFR、排钠、血钠）钾 钙磷 葡萄糖 镁（GFR、排钠、血钠）H+/HCO3-铝Confidential Not for distribu
38、tionAlterations in Body Systems 13各系统症状各系统症状 13 Acid/base balance(alteration in pH)patients usually exhibit metabolic acidosis retention of hydrogen ions decreased reabsorption of bicarbonate decreased excretion of ammonium chloride retention of acid end products of metabolism Catabolism 酸碱平衡（PH改变）常
39、有代谢性酸中毒 H+潴留 HCO3-重吸收减少 泌H+减少 酸性代谢产物潴留 分解代谢Confidential Not for distributionAcid/base balance(continued)signs and symptomsincreased rate and depth of respirationsplasma bicarbonate level 22 mEq/L.arterial pH 7.4tachycardia in mild acidosis;bradycardia in severe acidosisaltered mental statuslow blood
40、 pressurehyperkalemiavarious other complaintsnausea,vomiting,headacheAlterations in Body Systems 14各系统症状各系统症状 14 酸碱平衡（续）酸碱平衡（续）症状和体征 呼吸深长 HCO3-22 mEq/L.pH 7.4 轻度酸中毒时出现心动过速;严重酸中毒时则出现心动过缓 精神症状 低血压 高钾 其他如恶心、呕吐、头痛等Confidential Not for distributionAlterations in Body Systems 15各系统症状各系统症状 15Endocrine syst
41、em(hormones)decreased somatotropin(exerts effect on growth hormone)in childrengood amounts of dietary protein,control anemia,control acidosishuman recombinant growth hormone(somatropin)decreased reproductive ability/sexual desiretestosterone,zinc for malescounselinganemia therapy 内分泌系统（激素）内分泌系统（激素）儿
42、童生长激素减少 增加膳食蛋白,纠正贫血和酸中毒 人重组生长激素 生育能力和性欲下降 男性睾丸素、锌下降 心理咨询 纠正贫血Confidential Not for distributionAlterations in Body Systems 16各系统症状各系统症状 16 Immune system suppression of immune systemhigh level of circulating uremic toxinsabnormal intake of nutrients for white blood cell(WBC)function CKD patients have
43、subnormal temperaturesurea is a known antipyretic 免疫系统免疫系统 免疫抑制（T细胞、B细胞功能均受到抑制）循环中毒素水平高 不适当的饮食影响白细胞功能 CKD 病人体温常较低 尿素氮降体温作用Confidential Not for distributionCalcium Phosphorus Imbalance and Bone Disease 钙磷平衡失调和肾性骨病钙磷平衡失调和肾性骨病 17Renal Failure/High Phosphorus Intake肾功能衰竭肾功能衰竭/高磷摄入高磷摄入 Phosphorus Increas
44、es/Vitamin D synthesis Decreases 血磷升高血磷升高/VitD合成减少合成减少 Calcium Absorbtion from Intestines Decreases/Serum Calcium and Phosphorus Bind肠道吸收钙减少肠道吸收钙减少/血钙磷乘积血钙磷乘积 Low Serum Calcium Stimulates Increased PTH Secretion低血钙刺激低血钙刺激PTH分泌分泌 Calcium is Pulled from the Bones to Increase Serum Calcium 肾钙动员以升高血钙肾钙动
45、员以升高血钙 Further Binding of Calcium and Phosphorus Forming Calcium Phosphate Complexes钙磷乘积升高钙磷乘积升高 Metastatic Calcification软组织钙化软组织钙化Alterations in Body Systems 各系统症状各系统症状17Confidential Not for distributionAlterations in Body Systems18各系统症状各系统症状 18骨病-“肾性骨病”高转运性骨病纤维性骨炎 骨痛和骨折 骨钙磷丢失血钙降低，血磷升高，血PTH升高，血维生素D
46、降低低转运性骨病 血钙正常或升高，血磷升高，PTH降低 微骨折 （可能与高钙摄入和维生素D的不适当应用有关）骨软化骨痛，骨折，畸形骨脱矿质(“woven”bone)高血铝，影响成骨细胞活性Calcium,phosphorus,PTH,Vitamin D and their contributions to bone disease are discussed in further detail in the“Blood Chemistries and Nutrition in Kidney Disease Patients”presentation Bone problems-“renal o
47、steodystrophy”Osteitis Fibrosa bone pain and fractures calcium and phosphate are removed from the bonespatient has low calcium,high phosphorus,high PTH,low vitamin D levels Adynamic bone disease patient has high normal calcium,high phosphate,low PTH microfractures,calcifications maybe due to high do
48、ses of Ca salts,inappropriate use of Vit.Osteomalaciabone pain,fractures,deformitiesdemineralization of bone(“woven”bone)high aluminum levels;altered osteoblast activityConfidential Not for distribution Disorders of mineral and bone metabolism are associated with excess morbidity and mortality The e
49、xcess mortality linked to abnormalities of mineral metabolism(Ca 10,P 5,PTH 600)(17.5%)supersedes that due to anemia Hb 11(11.3%)and to under-dialysis URR65%(5.1%)钙磷代谢紊乱和骨病的发生与死亡率相关 钙磷等矿物质代谢紊乱引起的死亡率 Ca 10,P 5,PTH 600(17.5%)要高于 贫血Hb 11(11.3%)和透析不充分 URR65%(5.1%)Block GA et al.Am J Kidney Dis 1998;31:6
50、01Block GA et al JASN 2004;15:2208Ganesh SK et al.JASN 2001;12:2131Confidential Not for distribution In fact parameters of mineral metabolism can be modulated by therapeutic interventions Hence the publication of therapeutic targets for those parameters such as the“DOQI Guidelines”The rationale for
