慢性腎臟病 腎臟內科
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慢性腎臟病
腎臟內科
學習目標
PGY UGY
知識
1.慢性腎臟病相關的影像檢查
2.腎切片檢查的照護
3.慢性腎臟病病人的處理程序
4.透析病人的照護
5.透析相關併發症的防治
知識
1.慢性腎臟病的定義
2.慢性腎臟病的臨床表現
3.慢性腎臟病的病理生理機制
4.慢性腎臟病的診斷流程
5.尿毒症的病理生理機制
6.透析的基本原理
7.慢性腎臟病相關的實驗室檢查判讀，包括BUN/Cr、Ca、P、電解質、動脈血氣體分析、尿液分析、尿鈉、血清及尿之滲透壓、計算鈉離子之fraction excretion
8. 照會做腎超音波之適應症及判讀
技能
1.慢性腎臟病相關的病史詢問
2.慢性腎臟病相關的身體檢查
2002 慢性腎臟病（CKD）的定義與分期
改Scr為estimated GFR
美國國家腎臟基金會慢性腎臟病的定義
腎絲球濾過率: >60 ml/min + 腎臟實質傷害
微蛋白尿、血尿、影像學證據、病理學證據
腎絲球濾過率: <60 ml/min
大於三個月
腎絲球濾過率的測定
MDRD-Simplified equation: GFR
(ml/min/1.73m²) =186 x Scr -1.154 x
Age -0.203 x 0.742 (if female) x 1.212
(if black)
ESRD n = 53,000
CKD
？
尿毒病患是冰山一角，慢性腎臟病者知多少？
過去混亂的名稱與所謂分期 慢性腎病 Chronic renal disease
慢性腎功能不全 Chronic renal
insufficiency
慢性腎衰竭Chronic renal failure
I. CKD定義與分期
慢性腎臟病(CKD) US-NKF的新定義與分期(2002)
只有eGFR沒有蛋白尿時，不能診斷為CKD，否則變成全部檢查對象皆是CKD。如同全民皆是CKD
*Urine albumin-to creatinine ratio (ACR) > 30 mg/g
特別注意何謂慢性腎病第一期與第二期
All-cause mortality attributable to chronic kidney disease: A prospective cohort study based on 462,293 adults in Taiwan
Wen CP et al, Lancet 2008 年紀愈大盛行率愈高
約兩百萬人 世界各國的報告，CKD的盛行率約佔全體人口之10-
14%
相關危險因子
吸菸
糖尿病
高血壓
貧血
高血脂
肥胖
中草藥
1822
34
57
78 77
10 1215
2126
20
8 9 10 1217
23
0
10
20
30
40
50
60
70
80
90
Non-
CKD
Stage
1
Stage
2
Stage
3
Stage
4
stage
5
% HTN
% high cholesterol
Chinese Herbal Medicine
% o
f popula
tion
II. 台灣CKD流行病狀況
2007年台灣地區20歲以上國人慢性腎臟病(CKD)盛行率
（ 第二波三高調查）
年齡校正盛行率 9.8％
預估人口數 約171萬人
※ 2008年20歲以上人口總計：17,525,876人。
慢性腎臟疾病之盛行率為11.3%，以2007年台灣地區人口作為標準人口進行年齡校正後之盛行率為9.8%；
追蹤個案2002~2007年罹患腎臟病之發生率與罹患腎臟病之相對危險性
台灣CKD 第1期至第5期各期盛行率
三高調查, 溫等人
第1期: 1.3%, 1.0%
第2期: 1.5%, 3.8%
第3期: 7.9%, 6.8%
第4期: 0.4%, 0.2%
第5期: 0.2%, 0.1%
全部: 9.8% 11.9%
高血壓
高血糖
高血脂
高膽固醇
高TG
低HDL
高LDL
年齡校正盛行率
24
％
7.9
％
10.1
％
14.2
％
10.2
％
7.3
％
預估
人口數
約421
萬人
約138
萬人
約177
萬人
約249
萬人
約179
萬人
約128
萬人
國民健康局2009
台灣CKD的危險因子
老年腎功能老化
慢性腎臟病
慢性腎炎(腎絲球腎間質炎)
糖尿病
高血壓
高血脂
肥胖
代謝症候群
藥物: 中草藥、西藥
透析腎臟病患家屬
抽菸、檳榔?
慢性感染
重金屬
???
III. 台灣CKD危險因子
7 基因、環境
14.14
11.36
4.76
1.080.76
012345678
910111213141516
≥60 45-59 30-44 15-29 <15
Estimated Glomerular Filtration Rate (ml/min/1.73 m2)
Ag
e-S
tan
da
rdiz
ed
Ra
te (
pe
r 1
00
pe
rso
n-y
ea
rs)
Events: 25,803 11,569 7,802 4,408 1,842
36.60
21.80
11.29
3.652.11
0
5
10
15
20
25
30
35
40
≥60 45-59 30-44 15-29 <15
Estimated Glomerular Filtration Rate (ml/min/1.73 m2)
Ag
e-S
tan
dar
diz
ed R
ate
(per
100
per
son
-yea
rs)
Events: 73,108 34,690 18,580 8,809 3,824
Go AS et al. N Engl J Med 2004;351(13):1296-1305
144.61
86.75
45.26
17.2213.54
0
10
20
30
40
50
60
70
80
90
100
110
120
130
140
150
≥60 45-59 30-44 15-29 <15
Estimated Glomerular Filtration Rate (ml/min/1.73 m2)
Ag
e-S
tan
da
rdiz
ed
Ra
te (
pe
r 1
00
pe
rso
n-y
ea
rs)
Events: 366,757 106,543 49,177 20,581 11,593
Mortality
CV events
Hospitalization
隨eGFR的減低病患死亡、心血管事件、與住院的危險
機率均增加
eGFR與死亡危險之關係 eGFR遇低死亡機會愈大，但有蛋白尿則是在高eGFR時仍有較
高之死亡危險
Wen CP et al. Lancet 2008
IV. CKD的影響
公衛流行病學：盛行率、危險族群、因子 臨床醫療預後：死亡、併發症、危險因子 醫療體系負擔：健康維護、醫療費用、照護人力
Albuminuria & Proteinuria - A index of
renal injury and CKD progression
24hr (ug/min) 24hr (mg/day) Spot (ug/mg)
Normo <20 <30 <30
Micro 20-200 30-300 30-300
Marcro >200 >300 >300
Albuminuria
Gold standard
24 hours urine collection (urine albumin, x urine amount)
Clinical practice
Morning spot urine, urine albumin and creatinine ratio (ACR)
Microalbuminuria refers to the excretion of amounts of albumin too small to detect by urinary dipstick
Proteinuria (Overt, Macro-) Use of urine dipstick for proteinuria is
convenient, but it needs to be rechecked and confirmed and quantified by Upcr or Uacr.
Gold standard
24 hours urine collection (urine total protein x urine amount)
Clinical practice
Morning spot urine, urine total protein and creatinine ratio (PCR)
> 150 (200) mg/g creatinine usually signifies chronic renal damage
If patient already has macroalbuminuria, it is not necessary to check ACR. Check PCR is cheaper.
Urine total protein (mg/dl)/urine Cr (mg/dl) x 1000 = UPCR (mg/g creatinine)
2012 KDIGO CKD Guideline
Pathophysiology and Biochemistry of Uremia
Pathophysiology of uremic symptom
1. accumulation of toxins normally undergoing renal excretion, including products of protein metabolism
2. loss of other renal functions, such as fluid and electrolyte homeostasis and hormone regulation
3. progressive systemic inflammation and its vascular and nutritional consequences.
More than 4000 uremic toxins
accumulated in uremia
Small molecule (<500 Da)
Blood urea nitrogen
(BUN), creatinine
Middle molecule (500-1500
Da)
Vitamin B12
Large molecule (>1500Da)
Beta-2
macroglobuminemia
monitoring the levels of urea and creatinine in the patient with
impaired kidney function represents a vast oversimplification
of the uremic state.
Clinical Manifestations of CKD and Uremia (1)
Fluid and electrolyte disturbances
Volume expansion (I)
Hyponatremia (I)
Hyperkalemia (I)
Hyperphosphatemia (I)
Endocrine-metabolic disturbances
Secondary hyperparathyroidism (I or P)
Adynamic bone (D)
Vitamin D–deficient osteomalacia (I)
Carbohydrate resistance (I)
Hyperuricemia (I or P)
Hypertriglyceridemia (I or P)
Increased lipoprotein A level (P)
Decreased high-density lipoprotein level
(P)
Protein-energy malnutrition (I or P)
Impaired growth and development (P)
Infertility and sexual dysfunction (P)
Amenorrhea (I/P)
Beta 2-Microglobulin associated
amyloidosis (P or D)
(I) denotes an abnormality that usually improves with an optimal program of dialysis and related therapy
(P) denotes an abnormality that tends to persist or even progress, despite an optimal program;
(D) denotes an abnormality that develops only after initiation of dialysis therapy.
Clinical Manifestations of CKD and Uremia (2)
Neuromuscular disturbances
Fatigue (I) b
Sleep disorders (P)
Headache (P)
Impaired mentation (I)b
Lethargy (I) b
Asterixis (I)
Muscular irritability
Peripheral neuropathy (I or P)
Restless legs syndrome (I or P)
Myoclonus (I)
Seizures (I or P)
Coma (I)
Muscle cramps (P or D)
Dialysis disequilibrium syndrome (D)
Myopathy (P or D)
Cardiovascular and pulmonary disturbances
Arterial hypertension (I or P)
Congestive heart failure or pulmonary edema (I)
Pericarditis (I)
Hypertrophic or dilated cardiomyopathy (I, P, or D)
Uremic lung (I)
Accelerated atherosclerosis (P or D)
Hypotension and arrhythmias (D)
Vascular calcification (P or D)
Clinical Manifestations of CKD and Uremia (3)
Dermatologic disturbances
Pallor (I)b
Hyperpigmentation (I, P, or D)
Pruritus (P)
Ecchymoses (I)
Nephrogenic fibrosing dermopathy (D)
Uremic frost (I)
Gastrointestinal disturbances
Anorexia (I)
Nausea and vomiting (I)
Gastroenteritis (I)
Peptic ulcer (I or P)
Gastrointestinal bleeding (I, P, or D)
Idiopathic ascites (D)
Peritonitis (D)
Hematologic and immunologic disturbances
Anemia (I) b
Lymphocytopenia (P)
Bleeding diathesis (I or D) b
Increased susceptibility to infection (I or P)
Leukopenia (D)
Thrombocytopenia (D)
Laboratory Manifestations of CKD and Uremia
Fluid, Electrolyte and Acid-Base Disorders
Sodium and Water Homeostasis
Potassium Homeostasis
Metabolic acidosis
Disorders of Calcium and Phosphate Metabolism
Bone disorders
Vascular calcification
Cardiovascular Abnormalities
Ischemic vascular disorders
Hematologic Abnormalities
anemia
Frequency and severity of relevant disorders increase as CKD progressing
How it happens? Mechanism
When it happens? At what level of GFR
How frequent?
How severe?
What impact?
How to manage?
Sodium and Water Homeostasis
Balance of salt and water is impaired in CKD patients, either causing salt retention or wasting.
Sodium retention and extracellular fluid volume expansion noted frequently in CKD and may contribute to hypertension. This can be treated by
Salt restriction
Diuretics, loop diuretics work efficiently than thiazides in CKD stage 3-5
Combined therapy by loop and with potassium sparing diuretics
intractable edema and hypertension in advanced CKD may serve as an indication to initiate dialysis.
Impaired renal conservation of sodium and water (sodium wasting) may be prone to ECFV depletion and easily followed by pre-renal azotemia.
Hyponatremia is not commonly seen in CKD patients but, when present, can respond to water restriction.
H2O
Potassium Homeostasis Compensation of impaired potassium secretion in CKD (which is not
necessary) includes increased secretion through GI tract Conditions in which easily developing hyperkalemia:
increased dietary potassium intake, protein catabolism, hemolysis, hemorrhage, transfusion of stored red blood cells
metabolic acidosis Use of ACE inhibitors, ARBs, and spironolactone and other potassium-sparing
diuretics. Certain renal diseases such as of diabetes, obstructive uropathy and sickle cell
nephropathy.
Hyperkalemia can be treated by avoidance of
dietary potassium potassium supplements (including occult sources, such as dietary salt substitutes) potassium-retaining medications (especially ACE inhibitors or ARBs)
use of kaliuretic diuretics. Potassium-binding resins (calcium resonium or sodium polystyrene)
Dialysis in intractable hyperkalemia
Metabolic Acidosis
Most CKD patient can acidify the urine but cannot excrete the normal quantity of protons for less production of ammonia.
Metabolic acidosis in CKD will transit from non-anion gap to anion gap as clinical course progression
Metabolic acidosis cause net protein catabolism and can be treated by
Correct hyperkalemia to increase ammonia production
Use of alkali supplement, usually sodium bicarbonate, when the serum bicarbonate concentration falls below 20–23 mmol/L
Dialysis in intractable condition
Disorders of Calcium-Phosphate Metabolism in CKD
Homeostasis of Ca and P is maintained by the hormones of vitamin D, parathyroid hormone (PTH) and, fibroblast growth factor 23 (FGF-23); involve the organs of GI tract, kidney and bone.
Calcium level sensed in Ca-sensing receptor at parathyroid gland
Phosphorus intake and level can be reflected on FGF-23, which is secreted at bone and enhance phosphorus secretion through kidney
CKD mainly causes the retention of phosphate and inadequate synthesis of active vitamin D, which further disturbs the whole Ca-P homeostasis.
Usually CKD patients will have high FGF-23, low vitamin D, high PTH, high phosphate and low calcium.
Bone turnover disorder and vascular calcification are two major complications.
J Clin Invest. 2008;118(12):3820–3828. doi:10.1172/JCI36479.
Disorders of Calcium-Phosphate Metabolism in CKD
High turnover / Secondary hyperparathyroidism
Severe form- Osteotitis fibrosa cystica
Treated by
lowering serum phosphate though diet restriction and phsphate binders
vitamin D supplement
Cinacalcet hydrochloride, an antagonist of calcium sensing receptor.
Low turnover / Adynamic Bone Disease
Usually Low iPTH, frequent noted in old age, DM and peritoneal dialysis patens
Related to the frequent use of active vitamin D and calcium-based phosphate binders
Increased risk for bone fracture and vascular calcification
Mixed
Subosteal and Peri-
osteal reabsorption
Rugger-Jersey spine Osteotitis fibrosa cystica
Disorders of Calcium-Phosphate Metabolism in CKD
Vascular calcification
Characteristics of vascular calcification
in CKD
Involvement in younger population and
systemic
More common and severe than general
population
Independent risk factor for mortality
Pathogenesis of vascular calcification
in CKD
Transformation of smooth muscle cell to
bone-like cell (media calcification) by Pi
stimulating sodium-dependent Pi
cotransporter Pit-1 channel
Calciphylaxis
Severe vascular calcification results into
patch of skin necrosis
Ectopic calcification &
Vascular calcification
Calciphylaxis
Cardiovascular abnormality
Cardiovascular disease is the leading cause of morbidity and mortality in
patients at every stage of CKD. The prevalence is 10-200-fold higher than the general population
Prevention of cardiovascular disease should be performed in very early CKD stage
Ischemic vascular disorders
Traditional risk factors include hypertension, hypervolemia, dyslipidemia, sympathetic over
activity, and hyperhomocysteinemia.
The CKD-related risk factors comprise anemia, hyperphosphatemia, hyperparathyroidism, sleep
apnea, and generalized inflammation.
Congestive heart failure – Multifactorial
hypertension/ left ventricular hypertrophy
CKD associated fluid overloading
Uremic lung- low pressure pulmonary edema
Hypertension and ventricular hypertrophy
Vicious cycle between hypertension and CKD progression
Anemia in CKD A normocytic, normochromic anemia
is almost universal by CKD stage 4.
Causes of anemia in CKD
Relative deficiency of erythropoietin
Diminished red blood cell survival
Bleeding diathesis
Iron deficiency
Hyperparathyroidism/bone marrow fibrosis
"Chronic inflammation“
Folate or vitamin B12 deficiency
Hemoglobinopathy
Comorbid conditions: hypo/hyperthyroidism, pregnancy, HIV-associated disease, autoimmune disease, immunosuppressive drugs
Treatment of anemia for CKD is to reverse all the causes above if possible
Evaluation of Patients with CKD--I HISTORY- Symptoms and overt signs of
kidney disease are often absent until
renal failure supervenes.
Past History of hypertension), diabetes
mellitus, abnormal urinalyses, problems
with pregnancy and drug history
In early CKD, noccturia and foamy urine
noted frequently
In late CKD, uremic symptoms such as
appetite, weight loss, nausea, hiccups,
peripheral edema, muscle cramps,
pruritus, and restless legs should be kept
in mind.
PHYSICAL EXAMINATION -The physical
examination should focus on blood
pressure and target organ damage from
hypertension.
Funduscopy
Volume status
VIII. Evaluation of Patients with CKD
LABORATORY INVESTIGATION - the degree of renal damage and its consequences
tests for underlying causative or aggravating disease process
systemic lupus erythematosus and vasculitis
multiple myeloma
hepatitis B and C and HIV
tests for degree and peace of renal damage
Serial measurements of renal function
tests for CKD consequences
Serum concentrations of calcium, phosphorus, and PTH
Hemoglobin concentration, iron, B12, and folate should also be evaluated.
acidosis and electrolyte disorders
IMAGING STUDIES
renal ultrasound, most important and popular small kidney suggests CKD (normal range
around 9-11cm)
The exceptions are diabetic nephropathy, amyloidosis, and HIV nephropathy, where kidney size may be normal in the face of CKD.
A discrepancy >1 cm in kidney length suggests either a unilateral developmental abnormality or disease process or renovascular disease
renal masses and obstruciton detection
Radiographic contrast imaging studies should be avoided to prevent contrast inducing nephropathy.
Evaluation of Patients with CKD--II
RENAL BIOPSY
renal biopsy is not advised In CKD patient with bilaterally small kidneys because
1. technically difficult and higher complication rate
2. less help in diagnosis
3. already pass up therapeutic opportunity
Establishing the Diagnosis and Etiology of CKD
Distinguish newly diagnosed CKD from acute or subacute renal failure
Evidences support chronicity
hyperphosphatemia, hypocalcemia, and elevated PTH and bone alkaline phosphatase
Normochromic, normocytic anemia
bilaterally reduced kidney size (<8.5 cm in all but the smallest adults)
Usually biopsy is not necessary to diagnose diabetic nephropathy
慢性腎臟病自然病程與治療策略
併發症
正常 高風險 傷害 GFR 下降
腎衰竭 死亡
CKD危險 因子篩檢
減少CKD 危險因子， 篩檢CKD
診斷與治療， 治療合併症， 阻緩腎病惡化
評估惡化速度 治療併發症， 準備替代療法
進行腎臟 替代療法
Levey AS et al, Kidney Int 2007
阻緩腎功能惡化 處理併發症 防止死亡
IX. Management of CKD
Slow progression of CKD—BP control
Control systemic blood pressure to reduce Intraglomerular Hypertension and Proteinuria
JNC 8 recommends new BP goals for persons >60: <150/90.
Under certain conditions, JNC 8 recommends new BP goals for persons >18 with CKD or diabetes: <140/90.
Initial therapy for non-black population should consist of either thiazide-type diuretic, CCB, ACEI, or ARB; and in the black population should either be a thiazide diuretic or CCB.
Avoiding further renal injury
Dehydration Renal toxic agents
NSAIDs (non-steroid anti-inflammatory drugs) Amionoglycosides Contrast medium
Slowing Progression of Diabetic Renal Disease
Treatment principle 1. Control of blood glucose
preprandial glucose kept in the 90–130 mg/dL, hemoglobin A1C < 7%.
the use and dose of oral hypoglycemics needs to be reevaluated as CKD progression.
2. Control of Blood Pressure and Proteinuria
Hypertension is found in the majority of type 2 diabetic renal disease patients.
the presence of albuminuria and is a strong predictor of cardiovascular events and nephropathy. Microalbuminuria precedes the decline in GFR Testing for microalbumin annually until established proteinuria,
In addition to treatment of hypertension in general, the use of ACE inhibitors and ARBs in particular is associated with additional renoprotection.
Why ACEIs/ARB use frequent in CKD patients
Lowering both systemic and intraglomerular hypertension to decrease proteinuria
Several controlled studies showing ACEI/ARBs are effective in slowing the progression in both diabetic and nondiabetic CKD patients, esp. with protienuria
Adverse effects
ACEIs: cough and angioedema
ACEI/ARB: anaphylaxis, and hyperkalemia
A progressive increase in plasma creatinine after the use may suggest the presence of renovascular disease within the large or small arteries.
ACEi/ARB Reduce Intraglomerular Pressure: Mechanism for Renal Protection
G. Curr Hypertension Rep. 2019;21(2):12-18. Gilbert RE. Kidney Int. 2014;86(4):693-700.
ACEi and ARB ↓ efferent arteriole tone and ↓ intraglomerular pressure
Renal protection
Initial ↓ in eGFR
followed by stabilization
↓ albuminuria
Slow progression of CKD– Protein restriction
Protein Restriction
Background
protein-mediated hyperfiltration contributes to ongoing decline in renal
function in many renal diseases.
It can slow the rate of renal decline at earlier stages of renal disease, especially
proteinuric and diabetic renal diseases
However, the Modification of Diet in Renal Disease (MDRD) study unable to
demonstrate in advanced stages of CKD patients.
Treatment Principle
KDOQI clinical practice guidelines include a daily protein intake of between 0.60
and 0.75 g/kg per day, and at least 50% of the protein intake be of high biologic
value.
Sufficient energy intake is important to prevent protein-calorie malnutrition,
and 35 kcal/kg is recommended.
Managing Other Complications of CKD
Medication Dose Adjustment
The loading dose is same but the maintenance doses for may drug may need to be adjusted
by a reduction in dosage or change in the dose interval .
Drugs that should be avoided include NSAIDs, metformin, meperidine, oral hypoglycemics
et al. each one has their different consideration to be hold in CKD patients.
Patient Education - Preparation for RRT—Integrated care
The educational programs should be commenced no later than stage 4 CKD.
Social, psychological, and physical preparation for the transition to renal replacement
therapy and the choice of the optimal initial modality are best accomplished with a gradual
approach involving a multidisciplinary team.
Advanced preparation may help to avoid problems with the dialysis process itself
provided with educational programs are more likely to choose home-based dialysis therapy.
home-based therapy is less expensive and is associated with improved quality of life.
When to start maintenance dialysis
Indications for Starting Renal Replacement therapy
Basic Principles:
Save life
Improve quality of life (QoL)
Clear indications for initiation of renal replacement therapy
encephalopathy, pulmonary edema, hyperkalemia, pericarditis, intractable muscle cramping, …
Appearance of uremic symptoms/signs refractory to medical treatment
anorexia, and nausea not attributable to reversible causes such as peptic ulcer disease,
evidence of malnutrition, and fluid and electrolyte abnormalities,
Blood urea nitrogen or creatinine level to start dialysis is individualized.
How to Treat Chronic Kidney Disease---A summary
Maintain blood pressure less than 140/90 (130/80)mmHg
Use an ACE Inhibitor or ARB, more than one drug is usually required and a
diuretic should be part of the regimen
Continue best possible glycemic control in individuals with diabetes
(HbA1c < 7%)
Refer to dietician for a reduced protein diet (0.6-0.8g/Kg/Day)
Consult a Nephrologist early
Team with the nephrologist for care if GFR is less than 30 mL/min/1.73 m2
Monitor hemoglobin and phosphorous with treatment as needed
Treat cardiovascular risk, especially quit smoking and
hypercholesterolemia
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