Renal Insufficiency

“To be a great champion you must believe you are the best. If you’re not,

pretend you are….!”

– Muhammad Ali

TOPICS

• Introduction

• Acute renal failure

• Chronic renal failure

• Uremia

Functions of kidney

• The kidneys excrete these compounds with water to make urine.

• They also eliminate excess body water while selectively reabsorbing useful chemicals and allowing waste to pass freely into the bladder as urine.

• They allow you to continue to consume a variety of foods, drugs, vitamins and supplements, additives, and excess fluids without worry that toxic by-products will build up to harmful levels.

The kidneys are a pair of small organs that lie on either side of your spine at about waist level. They act as filters that keep your blood free of by-products and toxins.

• The kidneys play an essential role in maintaining electrolyte and acid-base balance.

• They produce some hormones including renin, prostaglandins, erythropoietin, and active vitamin D.

• So, they are crucial in the regulation of blood pressure, formation of matured red blood cells, and metabolism of calcium and phosphorus.

Functions of the Kidney

• Waste excretion • Electrolyte balance • Fluid balance• pH • Osmolality• Hormone production

Anatomy of Kidney

Manifestation of renal dysfunction

Glomerulus · decreased GFR · glomerular filtration membrane permeability alteration

Renal tubule · concentrative function decline (hyposthennuria/isosthennur

ia) · water, electrolyte, acid-base disorder · others

Endocrine disorder · hypertension · anemia · renal osteodystrophy · others

体内 VitD3 的代谢过程

紫外线 25- 羟化酶 1α- 羟化酶

7- 脱氢胆固醇 VitD3 25-(OH)VitD3 1,25-(OH) 2VitD3

（皮肤） （肝微粒体） （肾线粒体）

Acute Renal Failure, ARF

• Definition• Etiology & classification Prerenal failure Intrinsic renal failure Post(obstructive) renal failure • Pathogenesis• Clinical manifestation• Therapy

Definition

• Acute renal failure (ARF) is defined as a precipitous and significant (>50%) decrease in glomerular filtration rate (GFR) over a period of hours to days, with an accompany-ing accumulation of nitrogenous wastes in the body.

急性肾功能衰竭的定义 急性肾功能衰竭（ acute renal failure ， ARF ）是指各

种病因引起双侧肾脏在短期内泌尿功能急剧降低，导致机体内环境出现严重紊乱的病理过程和临床综合症。

肾泌尿功能障碍表现为 GFR 迅速下降，出现少尿无尿；内环境紊乱主要表现为氮质血症、高钾血症和代谢性酸中毒。

急性肾功能衰竭根据尿量减少与否，分为少尿型（成人每日尿量少于 400ml ）和非少尿型（成人每日尿量大于 400ml ）两种类型。急性肾衰病情凶险，临床较常见，但若及时诊治，预后较好。

Etiology

Pre-renal Pre-renal (~70% of cases)(~70% of cases) resulting from impaired blood flow to

or oxygenation of the kidneys.

Intrinsic-renal Intrinsic-renal (~25% of cases)(~25% of cases) resulting from injury to or malformati

on of kidney tissues.

Post-renal Post-renal (<5% of cases)(<5% of cases) resulting from obstruction of urinary f

low between the kidney and urinary meatus.

Causes

• Prerenal failure - Diseases that compromise renal perfusion

Decreased effective arterial blood volume - Hypovolemia, CH

F, liver failure, sepsis

Renal arterial disease - Renal arterial stenosis (atherosclerotic, fibromuscular dysplasia), embolic disease (septic, cholesterol)

肾前性急性肾功能衰竭的发生机制

肾前性因素 休克的原因（失血、失液、感染、急性心衰、

严重过敏反应）和其它（肝肾综合征）  ADH 有效循环血量 Ald  血压降低

肾灌流压 肾血管收缩

肾血流量

肾小球有效滤过压 

GFRGFR  尿量

• Intrinsic renal failure - Diseases of the renal parenchyma, specifically involving the renal tubules, glomeruli, interstitium

ATN, ischemia, toxins (eg, aminoglycosides, radiocontrast, heme pigments, cisplatin, myeloma light chains, ethylene glycol)

Interstitial diseases - Acute interstitial nephritis, drug reactions, autoimmune diseases (eg, systemic lupus erythematosus [SLE]), infiltrative disease (sarcoidosis, lymphoma), infectious agents (Legionnaire disease, hantavirus)

Acute glomerulonephritis

Vascular diseases - Hypertensive crisis, polyarteritis nodosa, vasculitis

• Postrenal failure - Diseases causing urinary obstruction from the level of the renal tubules to the urethra

Tubular obstruction from crystals (eg, uric acid, calcium oxalate, acyclovir, sulfonamide, methotrexate, myeloma light chains)

Ureteral obstruction - Retroperitoneal tumor, retroperitoneal fibrosis (methysergide, propranolol, hydralazine), urolithiasis, papillary necrosis

Urethral obstruction - Benign prostatic hypertrophy; prostate, cervical, bladder, colorectal carcinoma; bladder hematoma; bladder stone; obstructed Foley catheter; neurogenic bladder.

Causes of ARF in tertiary care hospital setting

急性肾功能衰竭病因与分类 • 肾前性ARF （早期为功能性 ARF  ） 有效循环血量减少有效循环血量减少引起肾血流量急剧减少肾血流量急剧减少是肾前性

ARF 发生的关键因素 。

• 肾性 ARF （亦称器质性 ARF ） 由肾脏实质病变引起。急性肾小管坏死（ acute t

ubular necrosis ， ATN ）是临床上最常见、最重要最常见、最重要的ARF 类型，约占 ARF 的 75% ～ 80% 。

• 肾后性 ARF 因双侧性尿路梗阻引起，如尿路结石、肿瘤、前

列腺疾患等。

Pathogenesis of ARF

Decreased renal blood flow Renal hypoperfusion Vasoconstriction Vascular obstruction

Redistribution of renal blood flow

I. Renal hemodynamics factors

Tubule injury Tubule obstruction Passive backflow

II. Nephronal factors

Acute Renal Failure, IntrinsicAcute Tubular Necrosis

• Renal hypoperfusion/ischemia• Nephrotoxic agents (both endogenous and exogen

ous) • Mortality 50%

Bronchopulmonary infections, sepsis, cardiovascular disease, bleeding disorders

• Complete Recovery 25%, Incomplete 20%, No Recovery 5%

Acute Tubular NecrosisNephrotoxic Agents

Exogenous• Antibiotics• Contrast• Diuretics• Chemotherapeutics• Analgesics• Solvents, metals,

chemicals

• HIV meds• Antiulcer meds• AnestheticsEndogenous• Pigment nephropathy• Crystal deposition• Tumor-specific syndromes

Acute Tubular Necrosis

Cell Hypoxia Depletion of ATP

Impaired functionOf plasma membranes

And ATPases

Ca++ imbalance Na-K imbalance

Cell SwellingDisrupt cytoskeletonActivate phospholipases

Formation of xanthine oxidaseUncoupling of oxidative phosphorylation

Hypoxanthine

Disrupt lipid bilayer

Reperfusion injuryFree radicals

Acute Tubular Necrosis

Leads to…

• Loss of cell polarity

• Brush border loss

• Impaired cell-cell adhesion

• Impaired tight junction

End results…

• Impaired solute and water transport

• Sloughing of tubule cells obstructionobstruction

• Back leakage of Back leakage of

filtratefiltrate

急性肾功能衰竭的发病机制       急性肾衰发病机制的中心环节是中心环节是 GFRGFR 的降低的降低。 

一  肾血流动力学异常肾血流急剧减少

肾灌注压下降 肾血管收缩 肾血管阻塞 肾内血流重分布

二  肾小管损伤肾小管阻塞 原尿返流

三  肾小球超滤系数降低

Characteristics & clinical courses

• Oliguric phase

• Diuretic phase

• Recovery phase

Oliguric phase Usually lasting for 1 to 6 weeks,the average durat

ion is between 7 & 10 days.• Features of urine: I. Oliguria or AnuriaOliguria or Anuria II. Hematuria and casts III. Low specific gravity and osmolality IV. Urinary [Na+] above 20mM• AzotemiaAzotemia • Metabolic acidosisMetabolic acidosis• Hyperkalemia Hyperkalemia • Hypervolemia / HypertensionHypervolemia / Hypertension• Others: edema, water intoxication ， tachypnea

Urinary Indices in ARF

Prerenal ARF ATN

Urinary [Na+], mEq/L <20 >40

Urine to plasma Cr >40 <20

Urine osmolality >500 <400

Urine specific gravity >1.020 <1.015

Renal Failure Index <1 >1

FENa <1 >1

Response to IVF Good Poor

功能性肾衰和器质性肾衰（ ATN ）的鉴别

功能性肾衰 器质性肾衰尿液性质 尿比重 尿渗透压 尿钠  尿肌酐 /血肌酐  尿常规治疗与反应

>1.020 <1.015

>500mOsm/L <400mOsm/L

<20mmol/L >40mmol/L>40 <20

正常 蛋白尿、管型、红细胞、白细胞

应迅速补充血容量 需严格控制补液量 使肾血流恢复， GFR 量出而入

补液后 尿量迅速增多 尿量持续减少 病情明显好转 甚至使病情恶化

Muddy Brown Cast

Red Cell Cast

White Cell Casts

Diuretic phase

As healing begins, improvement is reflected in the production of more than 400 ml of urine per day.

• Fluid and electrolyte abnormalities.• Cr may still rise for 1-2 more days.

Recovery phase

ARF 的主要机能代谢变化和临床表现 一 少尿期     1. 少尿、无尿     2.  氮质血症氮质血症：：指肾功能衰竭时，由于 GFR 下降，含氮的代谢产物如尿素、肌酐、尿酸等在体内蓄积，引起血中非蛋白氮的含量增加（＞ 28.6mmol/L ，或＞ 40mg/dl ）。

3. 水中毒水中毒：：当肾排水功能障碍的情况下，一旦水摄入稍多，就易造成稀释性低钠血症，大量水份进入细胞内，引起脑水肿、肺水肿、心力衰竭。因此对少尿期 ARF 患者，要严格控制摄入水量。

4. 高血钾高血钾：：主要由 GFR 降低和肾小管泌钾障碍引起，机体代谢分解增强使钾释放增多及酸中毒引起细胞内钾向细胞外转移，都能促使血钾进一步增高。严重高血钾可导致室颤和心跳骤停。高钾血症是ARF 患者第一周死亡的最常见原因。

5. 代谢性酸中毒代谢性酸中毒：：主要由 GFR 降低、肾小管排酸保碱作用减退、体内分解代谢加强使固定酸产生过多等原因引起。

二 多尿期 经过少尿期后，当每天尿量大于 400ml ，说明病人已进入多尿期。

进行性尿量增多是肾功能开始恢复的一个标志。多尿期的早期， GFR 仍较正常为低，主要因肾小管修复再通而修复的肾小管浓缩功能仍很差，一方面排出代谢产物的能力不足，一方面出现多尿。这时患者仍可存在氮质血症，也可能存在高钾血症。尿量过多常使患者发生水、电解质紊

乱，主要倾向是脱水、低血钾和低血钠，所以对这些病人要注意预防。

三 恢复期 患者自我感觉好转，逐步能自理生活和进行劳动。尿量逐渐恢复

正常，血尿素氮和肌酐也接近正常。

Nonoliguric acute renal failure非少尿型 ARF 近年来有逐渐增多的趋势；这可能与病人医

疗意识加强、医疗诊治手段提高及肾毒性抗生素广泛应用有关。其机制为：① 不同肾单位受损程度不一，小部分肾单位的肾血流量和肾小球滤过功能存在；② 肾小管重吸收功能障碍远较肾小球滤过功能降低为重；③ 肾髓质形成高渗状态的能力降低，使尿液浓缩功能下降，故发病后尿量无明显降低，在 400～ 1000 ml/d左右。非少尿型非少尿型 ARFARF 较少尿型较少尿型 ARFARF 病情轻、病情轻、预后好预后好，但因症状轻而不太明显，容易延误病人的就诊或引起医生的漏诊。非少尿型非少尿型 ARFARF 不及时治疗，则会转化为少尿型不及时治疗，则会转化为少尿型 AARFRF 。 

Management

• Renal Diet• Acidosis• Hyperuricemia• Hypertension• Volume overload• Protein Load• Newer Agents ： ANF• Dialysis• Kidney Transplantation

Hospital inpatients with ARF ~50% mortality rate

Dialysis indications

I. Serum abnormalities unresponsive to medical therapy a. Severe Acidosis b. Severe Hyperkalemia

II. Uremia a. Mental status changes (usually delirium) b. Nausea and vomiting c. Pericarditis (pericardial friction rub)

III. Volume Overload

Peritoneal Dialysis

Hemodialysis

• Blood is circulated through artificial cellophane membrane that permits a similar passage of water and solutes

Chronic Renal Failure, CRF

• Definition

• Etiology

• Pathogenesis

• Clinical manifestation

• Therapy

Definition

• Chronic renal failure (CRF) is defined as a permanent reduction in glomerular filtration rate (GFR) sufficient to produce detectable alterations in well-being and organ function. This usually occurs at GFR below 25 ml/min.

• CRF is characterized by progressive and irreversible loss of large numbers of functioning nephrons. Serious clinical symptoms often do not occur until the number of functional nephrons falls to at least 70 per cent below normal. In fact relatively normal blood concentrations of most electrolytes and normal body fluid volumes can still be maintained until the number of functioning nephrons decreases below 20-30percent of normal.

慢性肾功能衰竭的定义慢性肾功能衰竭是由于各种肾脏疾病引起肾单位进行性破坏，

以致残存的有功能的肾单位不能充分排出代谢废物和维持内环境恒定的缓慢发展的一种肾功能损害的病理过程。机体逐渐出现代谢废物和毒物的潴留，水、电解质与酸碱平衡紊乱，以及肾内分泌功能障碍，并可伴有全身各系统功能受损的临床症状。

因为肾组织的破坏是逐渐发生的，而且肾脏又有较强的代偿能力，故慢性肾衰常常是缓慢发展，病程迁延数月、数年以至更长的时间，最后常导致尿毒症而死亡。尿毒症是指急、慢性肾功能衰竭最危重的阶段。

Causes of CRF

Any disorder that permanently destroys nephrons can result in chronic renal failure. Most common causes of CRF are:

• Diabetic nephropathy• Hypertensive nephrosclerosis• Glomerulonephritis• Interstitial nephritis• Polycystic kidney disease

慢性肾功能衰竭的病因 凡能引起肾实质进行性破坏的疾患，均可引起慢性肾功能衰竭。其中以慢性肾小球肾炎为最常见慢性肾小球肾炎为最常见，约占 CRF 的 50% ～ 60%。

    （ 1 ）肾脏疾患：慢性肾小球肾炎、慢性肾盂肾炎、肾结核、肾肿瘤、全身性红斑狼疮。

    （ 2）肾血管疾患：高血压肾小动脉硬化等。

    （ 3）尿路慢性梗阻：尿路结石、前列腺肥大等。

    （ 4）全身代谢性疾病：糖尿病肾病等。

    （ 5）其他：药物性肾损伤等。 

Clinical courses of CRF

Four stages of decreased renal function may be visualized:

Silent – GFR up to 50 ml/min. Renal insufficiency – GFR 25 to 50 ml/min. Renal failure – GFR 5/10 to 25 ml/min End-stage renal failure (ESRF) – GFR less than 5/10

ml/min.

Stage Description GFR Level

Normal kidney function

Healthy kidneys 90 mL/min or more

Stage 1 Kidney damage with normal or high GFR

90 mL/min or more

Stage 2 Kidney damage and mild decrease in GFR

60 to 89 mL/min

Stage 3 Moderate decrease in GFR 30 to 59 mL/min

Stage 4 Severe decrease in GFR 15 to 29 mL/min

Stage 5 Kidney failure Less than 15 mL/min or on dialysis

Stages of Chronic Kidney Disease

慢性肾功能衰竭的发展过程和分期 内生肌酐清除率 氮质血症 临床表现 （ ml/min ）

代偿期 >50 无 无任何症状。但不能负荷额 外的水、电解质和酸碱失代偿期 肾功能不全期 20-50 轻、中度 轻度消化道症状和贫血 

肾功能衰竭期 10-20 较重 明显多尿、夜尿和水、电解 质、 酸碱紊乱

尿毒症期 <10 严重 全身中毒症状明显，各脏器 系统功能障碍

Pathogenesis

• The most intriguing aspect of CRF is that compensatory mechanisms allow loss of 90% of GFR before manifestations of the uremic syndrome are evident. Thus a variety of adaptations compensate for the decreased GFR and allow a new steady state of external balance to exist, but on the other hand contribute to the uremic syndrome. In spite of these adaptations, the hallmark of CRF is the loss of flexibility in responding to challenges to external load of solutes and water.

Intact Nephron hypothesisIntact Nephron hypothesis Tubulointerstitial cell injuryTubulointerstitial cell injury Trade-off hypothesisTrade-off hypothesis

Intact Nephron Hypothesis

• Nephrons functioning in diseased kidneys maintain glomerulo-tubular balance. That is, filtration and net excretion of various substances are coordinated. (e.g. with normal renal function, usually 50-60% of filtered urea is reabsorbed from the tubules. In CRF it may fall to 30% to maintain balance).

The Magnification Phenomenon

• although nephrons in diseased kidneys function homogeneously, they alter their handling of given solutes as needed to maintain balance of these solutes. That is, nephrons can magnify their excretion of a given solute. (e.g. tubular creatinine excretion is < 10% with normal renal function. In CRF it may increase to 30%).

Trade-off Hypothesis

• The mechanisms that are magnified to maintain individual solute control may have deleterious effects on other systems. This trade-off is seen in the increased parathyroid hormone (PTH) secretion seen in CRF which enhances renal phosphorus excretion. PTH has been implicated in the pathogenesis of many disturbances of uremia (sleep, sex, bone, disease, anemia, lipidemia, vascular disease). As renal disease progresses and GFR decreases, high level PTH no longer maintains the phosphate excretion. The excessive PTH may result in further side effects, such as osteomalacia, deposit of calcium phosphate salts into soft tissue and damage of cardiovascular, neural systems.

慢性肾功能衰竭的发病机制

• 健存肾单位进行性减少健存肾单位进行性减少

• 矫枉失衡矫枉失衡

• 肾小管 肾小管  - -  间质损害间质损害

钙磷代谢的矫枉失衡 慢性肾脏疾患

 

肾单位↓ 

GFR↓ GFR↓↓ VitD3

血磷↓ 肾排磷↓ 肾排磷↓↓ 酸中毒 肾排磷↑ 血磷↑、血钙↓ 血磷↑↑

肾小管重吸收磷↓ PTH↑ 血钙↓↓ （健存肾单位） 血钙↑ 溶骨 肾性骨营养不良

““ 矫正” “失衡”矫正” “失衡”

内生肌酐清除率 Ccr =[  尿肌酐  ]  尿量 /分

[  血肌酐  ]

*正常值： 90－ 140ml/min

* 无肌酐饮食 2－ 3天后测定。

* 无肌酐饮食：摄入蛋白质 <40g/天，禁肉食，避免剧烈运动。

Clinical manifestations of CRF

• Loss of nephron’s function to excrete water and solutes. Characteristics of urine: urine volume,osmotic & gravity, urinary sediment• Effects on body fluids. water & sodium imbalance potassium imbalance metabolic acidosis phosphate & calcium metabolism dysfunction azotemia• Other signs of CRF cardiovascular abnormalities anemia & bleeding renal osteodystrophy

Anemia

Anemia is universal as GFR falls below 25 ml/min.; in certain disorders it may occur with mild renal insufficiency. Several factors contribute:

a. Erythropoiesis is markedly depressed, mainly due to reduced erythropoietin production; in addition, there may be reduced end-organ response to erythropoietin with reduced heme synthesis.

b. Red cell survival is shortened with a mild to moderate decrease in red cell life span, possible due to a “uremic” toxin.

c. Blood loss is common in uremic patients, possibly secondary to abnormal coagulation due to decreased platelet function.

d. Marrow space fibrosis occurs with osteitis fibrosa of secondary hyperparathyroidism resulting in decreased erythropoiesis.

Hypertension

Hypertension occurs in 80% to 90% of patients with renal insufficiency. Several factors contribute:

a. Expansion of extracellular fluid volume; this may arise because of reduced ability of the kidney to excrete ingested sodium.

b. Increased activity of the renin-angiotensin system is common; many patients with advanced renal failure have renin levels that are not completely suppressed by the elevated blood pressure.

c. Dysfunction of the autonomic nervous system occurs with insensitive baroreceptor sensitive and with increased sympathetic tone.

d. Possible diminished presence of vasodilators: there may be decreased renal generation of prostaglandins or of factors in the kallikrein-kinin system.

Altered Calcium and Phosphorus Metabolism (Renal Osteodystrophy)

a. As GFR decreases there is a slight retention of phosphorus; this phosphorus retention can lead to hypocalcemia, which stimulates PTH. The latter causes phosphaturia, with restoration of serum phosphorus and calcium toward normal. However, this occurs only at the expense of elevated serum PTH levels. This cycle repeats itself in progressive renal failure with PTH levels increasing progressively. Ultimately, the renal tubule can no longer respond to higher levels of PTH with a further decrease in phosphorus reabsorption. When this occurs, hyperphosphatemia develops, hypocalcemia may become prominent and PTH level can increase to very high levels. High PTH levels cause bone disease with severe osteitis fibrosa.

b. Altered vitamin D metabolism occurs secondary to decreased renal mass or to phosphate retention, with decreased synthesis of 1,25 (OH)2 D3. This deficiency leads to: 1. Diminished intestinal absorption of calcium, 2. decreased calcemic response of the skeleton to PTH, 3. impaired suppression of PTH secretion for any increase in serum calcium level, and 4. altered collagen synthesis. With advanced renal failure, these events can lead to secondary hyperparathyroidism and osteomalacia.

c. Skeletal resistance to the calcemic action of PTH develops; thus an increased PTH is required to maintain serum calcium at any level.

d. Finally, accumulation of aluminum from aluminum binding antacids may contribute to the bone disease.

慢性肾功能衰竭的功能代谢变化 1 ．泌尿功能障碍 尿量的变化：早期：夜尿、多尿；晚期：少尿。 尿渗透压的变化：低渗尿、低比重尿→等渗尿。 尿质的变化：尿中可出现蛋白尿、红细胞、白细胞、管型等。 2 ．氮质血症 3 ．水、电解质和酸碱平衡紊乱 机体对水、钠、钾的调节能力下降，并可出现高磷、低钙血症。由于肾脏排酸保碱功能降低，可发生代谢性酸中毒。4．肾性高血压（ renal hypertension） 5．肾性贫血（ renal anemia） 6 ．出血倾向 7．肾性骨营养不良

慢性肾功能衰竭引起高血压的机制 肾脏疾病  GFR↓ 肾血液灌流量↓ 肾实质破坏 

钠水排出↓ 肾素分泌↑  钠水潴留钠水潴留 Ald↑ 血管紧张素 II↑ 肾髓质细胞 PGA2 、 PGE2 生成↓ 血容量↑ 外周阻力↑外周阻力↑ 

心输出量↑ 高血压高血压 

肾性骨营养不良的发生机制 慢性肾功能衰竭

 

1,25-(OH)2VitD3 GFR↓ 

肠钙吸收↓ 排磷↓ 

低钙血症 高磷血症 酸中毒 

骨质钙化障碍 PTH 分泌↑

骨盐溶解↑ 骨质脱钙

肾性骨营养不良肾性骨营养不良

 

Uremia

Concept

• Uremia, from the Greek “urine in the blood”, is a clinical and biochemical syndrome that occurs either abruptly or gradually as renal function decreases acutely or chronically. In its extreme expression as uremic coma, the patient behaves as if poisoned, hypothermia, intermittent seizures, a bleeding diathesis,cardiac arrhythmias, vomiting, and rapid, shallow respirations may appears.

Uremia

a. Definition: symptomatic azotemia b. Acidosis (± tachypnea) c. Mental Status changes d. Hypervolemia / Hypertension e. Hyperkalemia f. Pericarditis

尿毒症

     急性或慢性肾功能衰竭晚期，病人体内水电解质、酸碱平衡紊乱，肾脏内分泌功能失调，大量代谢产物和毒性物质蓄积，从而引起一系列全身中毒症状，称为尿毒尿毒症症（ uremia）。尿毒症是急性或慢性肾功能衰竭的最严重和最后阶段。

Clinical Manifestations

The symptoms and signs which constitute the uremic syndrome are summarized below:

• Neurological Disorders: Fatigue, lethargy, sleep disturbances, headache, seizures, encephalopathy, peripheral neuropathy including restless leg syndrome, paraesthesia, motor weakness, paralysis.

• Hematologic Disorders: Anemia, bleeding tendency – due in part to platelet dysfunction.

• Cardiovascular Disorders: Pericarditis, hypertension, congestive heart failure, coronary artery disease, myocardiopathy.

• Pulmonary Disorders: Pleuritis, uremic lung.• Gastrointestinal Disorders: Anorexia, nausea, vomiting gas

troenteritis, GI bleeding, peptic ulcer.

• Metabolic-Endocrine Disorders: Glucose intolerance, hyperllipidemia, hyperuricemia, malnutrition, sexual dysfunction and infertility.

• Bone, Calcium, Phosphorus Disorders: Hyperphosphatemia, hypocalcemia, tetany, metastatic calcification, secondary hyperparathyroidism, 1,25-dihydroxy vitamin D deficiency, osteomalacia, osteitis fibrosa, osteoporosis, osteosclerosis.

• Skin Disorders: Pruritus, pigmentation, easy bruising, uremic frost.

• Psychological Disorders: Depression, anxiety, denial, psychosis.

• Fluid and Electrolyte Disorders: Hyponatremia, hyperkalemia, hypermagnesemia, metabolic acidosis, volume expansion or depletion

Principles of treatment for CRF & Uremia

• Conservative management

• Dialysis

Peritoneal dialysis

Hemodialysis

• Renal transplantation

case

• 某 8岁患儿因感染采用磺胺嘧啶治疗，因使用剂量过大，用药 5天后，连续 3日尿量少于 100ml/d,急诊入院。经查：血肌酐 480μmol/L（正常值为＜ 178μmol/L），尿钠  100

mmol/L（正常值为＜ 20mmol/L），尿相对密度  1.008。问：该病人是否发生了肾功能衰竭？如果是，是急性肾功能衰竭，还是慢性肾功能衰竭？该病人的尿少是肾前性因素、肾性因素还是肾后性因素所致？为什么血肌酐、尿钠浓度增高？为什么尿相对密度降低？

Treatment of end stage renal failure(ESRF)

• When GFR falls below 5 ml/min, the patient usually can not live without renal replacement therapy. Renal replacement therapy includes dialysis and kidney transplantation .

• Various social or medical factors influence decisions about peritoneal or hemodialysis, and transplantation in the treatment of end-stage renal failure. It should also be noted that none of the above are panaceas and each, modality is associated with complications and failures.

1. Azotemia - elevated blood urea nitrogen (BUN >28mg/dL) and creatinine (Cr>1.5mg/dL)

2. Uremia - azotemia with symptoms or signs of renal failure

3. End Stage Renal Disease (ESRD) - uremia requiring transplantation or dialysis

4. Chronic Renal Failure (CRF) - irreversible kidney dysfunction with azotemia >3 months

5. Creatinine Clearance (CCr) - the rate of filtration of creatinine by the kidney (GFR marker)

6. Glomerular Filtration Rate (GFR) - the total rate of filtration of blood by the kidney

The EndThe End

肾小球滤过率（ glomerural filtration rate ， GFR ）

• 肾小球滤过面积

• 肾小球有效滤过压 = 肾小球毛细血管血压 – 血浆胶体渗透压 – 肾小球囊内压

• 肾血流量

Glomerular Filtration Rate

GFR = Kf [(Pgc-PB) - (Πgc-ΠB)] = Kf (ΔP-ΔΠ)

Kf = glomerular ultrafiltration coefficientPgc = glomerular capillary hydraulic pressurePB = Bowman’s space hydraulic pressureΠgc = glomerular colloid osmotic pressureΠB = Bowman’s space colloid osmotic press

ure

Estimates of GFR

• Inulin neither secreted or reabsorbed• Clearance of inulin approximates GFR

[U]inulin V [P]inulin

• Creatine is secreted, so Cr clearance overestimates GFR

GFR =

Estimates of GFR

Urinary Estimate[U]cr V

[P]cr

Cockcroft Gault Estimate[140-age (yr)][body wt (kg)]

72[Pcr]

CrCl =

CrCl =

Glomerulus

Capillary SpaceCapillary Space

EndotheliumEndothelium

Urinary SpaceUrinary Space

GBMGBM

PodocytePodocyte

Filtration Membrane – Electron Micro.

Symptoms of chronic kidney disease• Fatigue and weakness (from anemia or accumulation of wast

e products in the body) • Loss of appetite, nausea and vomiting • Need to urinate frequently, especially at night• Swelling of the legs and puffiness around the eyes (fluid rete

ntion)• Itching, easy bruising, and pale skin (from anemia) • Headaches, numbness in the feet or hands (peripheral neuro

pathy), disturbed sleep, altered mental status (encephalopathy from the accumulation of waste products or uremic poisons), and restless legs

• High blood pressure, chest pain due to pericarditis (inflammation around the heart)

• Shortness of breath from fluid in lungs • Bleeding (poor blood clotting) • Bone pain and fractures • Decreased sexual interest and erectile dysfunction