만성콩팥병

(1)

만성콩팥병

경희대 병원 신장내과 정경환

(2)

2002

(3)

증례 1

• 40 세 남성이 건강검진상 신장이상으로 왔다 . 환자는 수년 전 부터 소변 검사상 혈뇨와 단백뇨가 있었다고 한다 . 혈압 은 130/80mmHg, 몸무게는 72kg 이었고 검사결과 다음 과 같다 .

혈액 : BUN/Cr 28/2.0 mg/dl

소변 : ACR 500mg/g, RBC many/HPF

(4)

• 환자의 만성콩팥병 병기는 ? 1) 1 기

2) 2 기

3) 3 기

4) 4 기

5) 5 기

(5)

증례 요약

• CKD is defined as abnormalities of kidney structure or function, present for ≥3 months, with implications for health

Cockcroft-Gault equation

(140 - age) x lean body weight [kg]

CCr (mL/min) = --- (여성 , X 0.85) Cr [mg/dL] x 72

NKF KDOQI CKD guideline 2002, Am J Kidney Dis 2002;

39:S1

(6)

Definition of CKD

CKD is defined as abnormalities of kidney structure or function, present for ≥3 months, with implications for health

KDIGO Guideline for the Evaluation and Management of CKD Kidney Int 2013; 3 : 1-150

(7)

NKF KDOQI CKD Classification

Am J Kidney Dis 2002; 39:S1

90 30

60

15

(8)

KDIGO staging of CKD

1.2.1: We recommend that CKD is classified based on cause, GFR category and albuminuria category (CGA) (1B)

1.2.2: Assign cause of CKD based on presence or absence of systemic disease and the location within the kidney of observed or presumed pathologic,

anatomic findings. (Not graded)

(9)

KDIGO revised classification based upon glomerular filtration rate and albuminuria

GFR stages

GFR

(mL/min/1.73

m²) Terms

G1 >90 Normal or high

G2 60 to 89 Mildly decreased

G3a 45 to 59 Mildly to moderately decreased

G3b 30 to 44 Moderately to severely decreased

G4 15 to 29 Severely decreased

G5 <15 Kidney failure (add D if treated by dialysis) Albuminuria

stages AER

(mg/day) Terms

A1 <30 Normal to mildly increased (may be subdivided

for risk prediction)

A2 30 to 300 Moderately increased

A3 >300

Severely increased (may be subdivided into nephrotic

and non-nephrotic for differential diagnosis, management, and risk prediction)

(10)

Staging of CKD

Kidney Int 2013; 3 : 1-150

(11)

Rationale for GFR categories

New Engl J Med 2004; 351:1296

(12)

Evaluation of CKD: GFR

1.4.3.1: We recommend using serum creatinine and a GFR estimating equation for initial assessment. (1A)

1.4.3.2: We suggest using additional tests (such as cystatin C or a clearance measurement) for confirmatory testing in specific circumstances

when eGFR based on serum creatinine is less accurate. (2B) 1.4.3.3: We recommend that clinicians (1B):

• use a GFR estimating equation to derive GFR from serum creatinine (eGFRcreat) rather than relying on the serum creatinine concentration alone

• understand clinical settings in which eGFRcreat is less accurate

(13)

Creatinine Based eGFR

Cockcroft-Gault equation

(140 - age) x lean body weight [kg]

CCr (mL/min) = --- ( 여성 , X 0.85) Cr [mg/dL] x 72

(14)

CKD-EPI and MDRD study equations

Ann Intern Med 2009; 150: 604

(15)

Evaluation of CKD: albuminuria

1.4.4.1: We suggest using the following measurements for initial testing of proteinuri a

(early morning urine sample is preferred) (2B);

1) urine albumin-to-creatinine ratio (ACR);

2) urine protein-to-creatinine ratio (PCR);

3) reagent strip urinalysis for total protein with automated reading;

4) reagent strip urinalysis for total protein with manual reading

1.4.4.3:

Confirm reagent strip positive albuminuria and proteinuria by quantitative

laboratory measurement and express as a ratio to creatinine wherever possible.

Confirm ACR ≥ 30 mg/g (≥ 3 mg/mmol) on a random untimed urine with a subsequent early morning urine sample

If a more accurate estimate, measure albumin excretion rate or total protein excretion rate in a timed urine sample

(16)

(17)

Etiology

신대체 요법 현황 2015, 신장학회

(18)

증례 2

• 50 세 남자가 신기능 이상으로 왔다 .

혈압은 160/90 mmHg 였고 , 검사 결과 다음과 같다 .

혈액 : Hb 10.0 g/dl, Creatinine 2.5 mg/dl Na/K 139/6.0 mEq/L, HCO₃^-13 mEq/L Ca/P 10/6.0 mg/dl

소변 : ACR 500 mg/g

(19)

• 환자의 치료로 맞는 것은 ?

1) 혈압은 120/70 mmHg 로 유지한다 2) Hb 은 13g/dl 이상으로 유지한다

3) 경구용 Bicarbonate 를 투여한다 4) 알루미늄 인 결합제를 투여한다

5) 단백질 2g/kg/day, 염분 8 g/day 로 식이조절한다

(20)

증례 요약

• Treatment Goal of CKD

BP: CKD+ 단백뇨 130/80mmHg 혈당 : DM CKD HbA1c 7.0%

Acidosis: HCO3

^-

22 mEq/L (20-23)

Diet: protein 0.8g/kg/day, salt intake to <2 g/day sodium

(21)

Prevention of CKD progression

• Traditional

– 혈압 조절 – 혈당 조절

– 단백뇨 조절 (ACE inhibitor, ARB)

• Beneficial

– 단백제한

– Hyperlipidemia 조절 – 금연

– 그밖에 anemia, acidosis, CKD-MBD 조절

(22)

Blood pressure target in CKD

Guideline Condition Goal BP Drug

JNC8 (2014) DM <140/90 Thiazide, ACEi or

ARB, CCB

CKD <140/90 ACEi or ARB

ESH/ESC (2013) DM <140/90 ACEi or ARB

CKD, no 단백뇨 <140/90 ACEi or ARB

CKD + 단백뇨 <130/80 ACEi or ARB

KDIGO (2012) CKD , no 단백뇨 <140/90 ACEi or ARB CKD + 단백뇨

(>30mg/g ACR)

<130/80 ACEi or ARB Harrison 19th CKD + 단백뇨

(>1g/day)

<130/80 ACEi or ARB

(23)

BP and RAAS interruption

3.1.4: We recommend that in both diabetic and non-diabetic adults with CKD and urine albumin excretion <30 mg/24 hours (or equivalent) whose office BP ≤ 140/90 mmHg (1B)

3.1.5: We suggest that in both diabetic and non-diabetic adults with CKD and with urine albumin excretion of ≥ 30 mg/24 hours (or equivalent) whose office BP ≤ 130/80 mm Hg (2D)

3.1.6: We suggest that an ARB or ACE-I be used in diabetic adults with CKD and urine albumin excretion 30–300 mg/24 hours (or equivalent). (2D) 3.1.7: We recommend that an ARB or ACE-I be used in both diabetic and non-diabetic adults with CKD and urine albumin excretion ≥ 300 mg/24 hours (or equivalent). (1B)

3.1.8: There is insufficient evidence to recommend combining an ACE-I with ARBs to prevent progression of CKD (Not Graded)

(24)

Glycemic Control in CKD

3.1.15: We recommend a target hemoglobin A1c (HbA1c) ~ 7.0%

to

prevent or delay progression of the microvascular

complications of diabetes, including diabetic kidney disease. (1A) 3.1.16: We recommend not treating to an HbA1c target of <7.0%

risk of hypoglycemia. (1B)

3.1.17: We suggest that target HbA1c be extended above 7.0% wit h

comorbidities or limited life expectancy and risk of hypoglycemia (2C)

(25)

Protein, Salt intake

3.1.13: We suggest lowering protein intake to

0.8g/kg/day in adults with diabetes (2C) or without diabetes (2B) and GFR <30 ml/min/1.73 m

²

3.1.14: We suggest avoiding high protein intake (>1.3g/kg/day) in adults with CKD at risk of progression. (2C)

3.1.19: We recommend lowering salt intake to <2 g/day sodium (5g/day sodium chloride) in adults, unless

contraindicated (CKD). (1C)

(26)

Acidosis

3.4.1: We suggest that in people with CKD and serum bicarbonate concentrations <22 mmol/l (20-23)

treatment with oral bicarbonate supplementation be given to maintain normal range (2B)

• Alkali supply 는 Metabolic acidosis 에 의한 catabolic s tatus 를 개선하여 CKD progression 을 slow

Harrison 19th

KDIGO Guideline for the Evaluation and Management of CKD

Kidney Int 2013; 3 : 1-150

(27)

증례 3

• 혈액 투석을 받는 50 세 여자 . 환자는 EPO 를 투 여 받고 있었으며 검사 결과 다음과 같다 .

Hb 8 g/dl, Hct 27%

ferritin 90 ug/L, transferrin saturation 15%

(28)

• 적절한 조치는 ? 1) EPO 항체 검사 2) 수혈

3) 골수 검사

4) IV iron

5) 경과 관찰

(29)

증례 요약

• Anemia investigation: CBC/DC, reticulocyte, ferritin, TSAT, VitB1 2, Folate

• Hb Target: 10-11.5 g/dl (harrison), <13 g/dl (KDIGO)

• Iron supply: TSAT ≤30% & ferritin ≤500 ng/ml (≤500 g/l) µ

(30)

Cause of anemia

Harrison 19th

(31)

Investigation of Anemia

In patients with CKD and anemia (regardless of age and CKD stage), include the following tests in initial evaluation of the anemia (Not Gr aded):

Complete blood count (CBC), which should include Hb concentration, red cell indices, white blood cell count and differential, and platelet count

Absolute reticulocyte count Serum ferritin level

Serum transferrin saturation (TSAT) Serum vitamin B12 and folate levels

(32)

Treatment of Anemia

• Recombinant human ESA (Erythropoiesis-stimulating agent)

• Iron supply: TSAT ≤30% & ferritin ≤500 ng/ml (≤500 g/l) µ

투석전 , 복막투석 경구 투여 , 위장장애 , 혈액 투석시 IV

• Vit B12, folate

• Resistant to ESA: inflammation, inadequate dialysis, severe hyper parathyroidism, blood loss, hemolysis, infection, malignancy

• Target: 10-11.5 g/dl (harrison), <13 g/dl (KDIGO)

(33)

증례 4

• 혈액 투석 중인 65 세 여자 . 혈액 검사 결과 다음과 같다 .

• 환자는 Calcitriol, Calcium acetate 를 복용하고 있었다 . BUN/Cr 70/6.5 mg/dl, Ca/P 11.5/6.0 mg/dl

PTH 450 pg/mL

(34)

• 변경 가능한 약제는 ?

1) Cinacalcet 2) Paricalcitol

3) Calcium carbonate

4) Parathyroidectomy

5) Calcium gluconate

(35)

증례 요약

• Secondary Hyperparathyroidism 의 치료

- Prevention: control of hyperphosphatemia

- Phosphate binder : Calcium based, non-calcium based

- Active vitamin D - Calcitriol ↑absorption of Ca & P, Paricalcitol

- Calcimimetics (Cinacalcet): Ca 에 대한 sensitivity 를 높임

(36)

Definition of CKD-MBD

A systemic disorder of mineral and bone metabolism due to CKD

one or a combination of the following:

- Abnormalities of calcium, phosphorus, PTH, or vitamin D metabolism

- Abnormalities in bone turnover,

mineralization, volume, linear growth, or strength

- Vascular or other soft-tissue calcification

Adapted with permission from Moe et al.

KDIGO Clinical Practice Guideline for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease–Mineral and Bone Disorder (CKD–MBD)

Kidney Int 2009: 76 (Suppl 113)

(37)

Mineral metabolism abnormalities

– Abnormalities of Ca, P, PTH, or Vit.D metabolism

Harrison 18

^th

Harrison 19

^th

Fig 333e-2

(38)

Mineral metabolism abnormalities

• FGF-23

– Family of phosphatonin, osteocyte 에서 secretion – Increase early in the course CKD

– increase renal phosphate excretion – Stimulate PTH

– Suppression of 1,25 (OH)

₂

D

₃

– Independent risk factor of LVH, mortality – FGF-23 증가시 therapeutic Ix

Harrison 19

^th

p1815

(39)

Mineral metabolism abnormalities

• 3.3.1: We recommend measuring serum levels of calcium, phosphate, PTH, and al kaline phosphatase activity at least once in adults with GFR < 45ml/min/1.73 m² (GFR categories G3b-G5) in order to determine baseline values and inform predict ion equations if used. (1C)

• 3.3.3: In people with GFR <45ml/min/1.73m² (GFR categories G3b-G5), we sugge st maintaining serum phosphate concentrations in the normal range according to l ocal laboratory reference values. (2C)

• 3.3.4: In people with GFR <45ml/min/1.73m² (GFR categories G3b-G5) the optim al PTH level is not known. We suggest that people with levels of intact PTH above the upper normal limit of the assay are rst evaluated for hyperphosphatemia, hypﬁ ocalcemia, and vitamin D de ciency. (2C)ﬁ

(40)

Mineral metabolism abnormalities

• K/DOQI™ Clinical Practice Guidelines on Bone Metabolism Target Levels

(41)

Treatment Mineral metabolism abnormalities

• Hyperphosphatemia Tx.

- Aluminum-containing phosphate binders

: excellent phosphate binding capacity and low cost

: aluminum accumulation  osteomalacia & encephalopathy

- Ca-containing phosphate binders

: slightly lower phosphate-binding capacity

: cost-effective, no risk of aluminum accumulation : increased Ca loading (hypercalcemia)

 excessive inhibition of PTH  adynamic bone disease : vascular calcification

(42)

Treatment Mineral metabolism abnormalities

• Hyperphosphatemia Tx.

- non Ca-based phosphate binders

: Sevelamer hydrochloride/Lanthanum carbonate

: relatively low phosphate binding capacity and high price

• Secondary Hyperparathyroidism Tx.

- Prevention: control of hyperphosphatemia - Phosphate binder

- Calcitriol : ↑absorption of Ca & P - Paricalcitol : less hyper Ca

- Calcimimetics (Cinacalcet): target Ca sensing receptor, Ca 에 대한 sensitivity 를 높여줌

(43)

Bone abnormalities

• High-turnover bone diseases - Osteitis fibrosa cystica

:↑P, ↓Ca, ↑PTH, ↓calcitriol : Osteoblast, osteoclast ↑

: bone pain, spontaneous Fx.

• Low-turnover bone dis- eases

- Adynamic bone disease :↓PTH (by calcitriol, Ca-P binder)

: Osteoblast, osteoclast ↓ : Fx. Risk

- Osteomalacia (renal rickets) : Vit.D deficiency, metabolic acidosis

: Osteoblast ↑

: spontaneous Fx.

(44)

Vascular calcification

• Low PTH, low turn over > advanced hyperparathyroidism

• Hyperphosphatemia, hypercalcemia

• Increased use of oral calcium

• Non calcium based phosphate binder preferred

(45)

Vascular calcification

(46)

Vascular calcification

• Calciphylaxis (calcific uremic arteriolopathy) - Rare, serious disorder

- Systemic medial calcification of arterioles  ischemia, subcutaneous necrosis

-

Risk factor: warfarin (decrease Vit K dep GLA prot. regeneration)

Early calciphylaxis Progressive calciphylaxis Advanced calciphylaxis

(47)

CKD and CVD

4.1.1: We recommend that all people with CKD be considered at increased risk for cardiovascular disease. (1A)

4.1.2: We recommend that the level of care for ischemic heart disease offered to people with CKD should

not be prejudiced by their CKD. (1A)

4.1.3: We suggest that adults with CKD at risk for atherosclerotic events be offered treatment with

antiplatelet agents unless there is an increased bleeding risk that needs to be balanced against the possible

cardiovascular benefits. (2B)

(48)

CKD and CVD

4.1.4: We suggest that the level of care for heart failure offered to people with CKD should be

the same as is offered to those without CKD. (2A) 4.1.5: In people with CKD and heart failure, any

escalation in therapy and/or clinical deterioration should prompt monitoring of eGFR and serum potassium concentration. (Not Graded)

(49)

증례 5

• 70 세 여자가 부종과 호흡곤란으로 왔다 . 환자는 20 년째 당뇨병 치료 중에 있었으며 천진상 심낭 마 찰음이 들렸다 . 검사 결과 다음과 같다 .

Hb 9.0 g/dl,

BUN/Cr 100/5.0 mg/dl, Ca/P 7.1/7.0 mg/dl K 6.0 mEq/L, HC03- 18mEq/L

(50)

• 환자에서 응급 혈액 투석을 결정하는데 중요한 요소 는 ?

1) Hb 9.0 g/dl

2) BUN/Cr 100/5.0 mg/dl 3) Ca/P 7.1/7.0 mg/dl

4) K 6.0 mEq/L

5) 심낭 마찰음

(51)

증례 요약

• Uremic pericarditis

투석전 , 투석 시작 8 주이내 주로 발생 Hemorrhagic pericardial fluid

Dialysis initiation Ix or intensification of dialysis (without hepari n)

Recurrent effusion 시 drain 고려

감별 : viral, malig, Tb, autoimmune cause, after MI , minoxidil overuse

(52)

Preparation for RRT

5.1.1: We recommend referral to specialist kidney care services for people with CKD in the following circumstances (1B):

AKI or abrupt sustained fall in GFR;

GFR < 30 ml/min/1.73 m² (GFR categories G4-G5)*;

consistent finding of significant albuminuria

(ACR≥ 300 mg/g or AER≥ 300 mg/24 hours, approximately equivalent to PCR ≥500 mg/g or PER ≥ 500 mg/24 hours);

progression of CKD urinary red cell casts

CKD and hypertension refractory to treatment with 4 or more antihypertensive persistent abnormalities of serum potassium;

recurrent or extensive nephrolithiasis;

hereditary kidney disease.

(53)

Indication of RRT

5.3.1: We suggest that dialysis be initiated when one or more of the following are present:

symptoms or signs attributable to kidney failure (serositis, acid base or electrolyte abnormalities, pruritus);

inability to control volume status or blood pressure;

progressive deterioration in nutritional status refractory to dietary intervention;

cognitive impairment.

This often but not invariably occurs in the GFR range between 5 and 10 ml/min/1.73 m². (2B)

(54)