Chronic Renal Failure (CRF)reviews.berlinpharm.com/20180505/Chronic_Kidney_Disease.pdf · Chronic Renal Failure (CRF) ... โรคไตเรอื Vรงั Chronic Kidney Disease

Chronic Renal Failure (CRF)

Chronic Renal Insufficiency (CRI)

ไตวายเร ือ้รงั

โรคไตเร ือ้รงั

Chronic Kidney Disease (CKD)

End Stage Renal Disease (ESRD)

Prevalence of CKD

Ingsathit A, et al. Nephrol Dial Transplant. 2010; 25: 1567-75

Study Subject

CKD stage Total

CKD I II III IV V

Thai SEEK

project

2007-2008

3,459 General

population

Age 45.3 (15.4)

Male 45.3%

3.3% 5.6% 7.5% 0.8% 0.3% 17.5%

Est. burden in age

matched (Yr 15-59)

1.4

M

2.5

M

3.4

M

0.4

M

0.1

M

7.9

Million

Prevalence of CKD


Study Subject CKD stage Total

CKD I II III IV V

Thai SEEK

project

2007-2008

3,459 General

population

Age 45.3 (15.4)

Male 45.3%

3.3

%

5.6

%

7.5

%

0.8

%

0.3

% 17.5%

Est. burden in age

matched

(Year 15-59)

1.4

M

2.5

M

3.4

M

0.4

M

0.1

M

7.9

Million

Prevalence of CKD


Study Subject CKD stage Total

CKD I II III IV V

Thai SEEK

project

2007-2008

3,459 General

population

Age 45.3 (15.4)

Male 45.3%

3.3

%

5.6

%

7.5

%

0.8

%

0.3

% 17.5%

Est. burden in age

matched (Year 15-59)

1.4

M

2.5

M

3.4

M

0.4

M

0.1

M

7.9

Million

Etiology of dialysis incident patients in Thailand 2013

Diabetes HT nephropathy

Diabetes 40.7 %

Obstructive uropathy 3.5%

HTN 37.3 %

Chuasuwan A., Praditpornsilpa K. THAILAND RRT YEAR 2013

CGN 2.3%

Total N=7,792

Ten-year mortality in type 2 diabetes by kidney disease

4.1

17.8 23.9

47

0.

17.5

35.

52.5

70.

No kidney disease Albuminuria Impaired GFR albuminuria andimpaired GFR

Afikarian M et al. J Am Soc Nephrol 2013; 24: 302-306.

Inc

ide

nc

e o

f m

ort

ali

ty

15,064 participants in the NHANES III

Mortality

4-5 time

5-6 time

10-11 time

Contents

❖ Diagnosis of CKD

❖ CKD risk factors

❖ Slow CKD progression

❖ Treatment of CKD Complications

CKD: Signs & Symptoms

❖ Fatigue, weakness

❖ Skin: Pruritus, edema, bruit

❖ Cardiovascular: Dyspnea

❖ Gastrointestinal: Nausea and vomiting

❖ Nocturia

❖ Confusion, drowsiness

Advanced CKD Stage

Non specific signs and

symptoms

Definition: Chronic Kidney Disease

Structural or functional abnormalities of the

kidneys for >3 months, as manifested by either:

1. GFR <60 ml/min/1.73 m2, with/without kidney damage

2. Kidney damage as defined by

❖ Urinary abnormalities; Albuminuria, proteinuria

❖ Urine sediment abnormalities

❖ Electrolyte and other abnormalities due to tubular disorders

❖ Pathologic abnormalities

❖ Imaging abnormalities

❖ Kidney transplantation

Methods of estimated glomerular filtration rate

Brenner & Rector’s The Kidney 10th edition

Current diagnosis with creatinine faces limitations

Limited sensitivity of serum creatinine, creatinine level rises only -

above the normal value when about loss 50 % of renal function

6.0-

5.0-

4.0-

3.0-

2.0-

1.0-

0-

0 25 50 75 100 125

GFR (mL/min)

Creatinine blind area

Creatinine-blind area : Up to 50% renal function are already lost

Evaluation of Glomerular filtration Rate (GFR)

❖ Using serum creatinine and a GFR estimating equation

for initial assessment (1A)

2009 CKD-EPI creatinine equation

Alternative creatinine-based GFR equation

KDIGO CKD 2012. Kidney International Supplements (2013) 3, 5–14

Urinary abnormalities

❖ Hematuria

❖ Microalbuminuria

❖ Proteinuria

Relationship of albuminuria with mortality

Adjusted for age, sex, ethnic origin, history of CVD, systolic BP, diabetes,

smoking, and total cholesterol and spline eGFR

Matshushita K, et al. Lancet, 2010; 375, 2073-2081.

8-

4-

2-

1-

0.5- 2.5 5 10 30 300 1000

Cardiovascular mortality; ACR

ACR (mg/g)

HR 95% CI

Albuminuria in Diabetes

Urinary

albumin

excretion rate

(mg/day)

Urinary albumin

excretion rate

(microgram/min)

Urinary albumin

to creatinine

ratio (mg/g)

Normal <30 <20 <30

Microalbuminuria 30-300 20-200 30-300

Marcoalbuminuria >300 >200 >300

* Random (Spot) urine preferably A.M. recommended

Albuminuria in Diabetes

Urinary albumin

excretion rate

(mg/day)

Urinary albumin

excretion rate

(microgram/min)

Urinary albumin

to creatinine

ratio (mg/g)

Normal <30 <20 <30

Microalbuminuria 30-300 20-200 30-300

Marcoalbuminuria >300 >200 >300

* Random (Spot) urine preferably A.M. recommended

New Terminology for Albuminuria

GFR and Albuminuria Categories KDIGO 2012


Ultrasound

Size

Echogenicity

Cortical thickening

Contents





Clinical Practice Guidelines for the Detection, Evaluation and Management of CKD

Stage GFR Evaluation Management

At increased

risk Test for CKD

1

Kidney damage

with normal or ↑

GFR

>90

Comorbid

conditions

CVD and CVD risk

factors

Specific therapy, based on

diagnosis

Management of comorbid

conditions

Treatment of CVD and CVD

risk factors

2 Kidney damage

with mild ↓ GFR 60-89

Rate of

progression

Slowing rate of loss of kidney

function

3 Moderate ↓ GFR 30-59 Complications Prevention and treatment of

complications

4 Severe ↓ GFR 15-29 Preparation for kidney

replacement therapy

5 Kidney Failure Kidney replacement therapy

Risk Factors: Development & Progression of CKD

❖ Family history of

CKD

❖ Congenital renal

disease

❖ Renal cystic

disease

Non-Modifiable

❖Age

❖Male

❖Decreased

kidney mass

Familial Clustering of Diabetic Kidney Disease

0

20

40

60

80

5 10 15 20 >25

Proband with DN

Proband without DN

Canani LH, et al. Diabetes 1999; 48: 909–13.

Sib

lin

gs’

pre

vale

nce o

f

dia

beti

c n

ep

hro

path

y

Presence of diabetic nephropathy in probands was associated with the presence of

sibling DN (OR = 3.75, 95% CI = 1.36-10.40)

Known diabetes duration (years)

Candidate genes for DN

Freedman BI, et al. Clin J Am Soc Nephrol 2: 1306–1316, 2007


Modifiable

❖Hypertension

❖Diabetes

❖Hyperlipidemia

❖Proteinuria/albuminuria

Proteinuria is the predominant renal risk marker in patients with type 2 diabetic nephropathy: Lessons from RENAAL

de Zeeuw D, et al. Kidney Int 2004; 65(6):2309-20.


Modifiable

❖Tobacco abuse

❖Obesity

❖Atherosclerosis

❖Autoimmune disease

❖Renal calculi

❖Exposure to nephrotoxic agents:

NSAIDs

Crude tobacco-associated risk of ESRD in male patients

Pack-

year

case controls Odd ratio 95% CI P value

N%

0-5 26(36) 47(65) 1.0 - -

5-15 17(24) 11(15) 3.5 1.3-9.6 0.017

>15 29(40) 14(19) 5.8 2.0-17 0.001

Orth: Kidney Int, Volume 54(3).September 1998.926-931

Crude tobacco-associated risk of ESRD in male patients

Pack-

year

case controls Odd ratio 95% CI P value

N%

0-5 26(36) 47(65) 1.0 - -

5-15 17(24) 11(15) 3.5 1.3-9.6 0.017

>15 29(40) 14(19) 5.8 2.0-17 0.001

Orth: Kidney Int, Volume 54(3).September 1998.926-931

Smoking increases the risk of ESRD in men with

inflammatory and non-inflammatory renal disease

Contents







At increased

risk Test for CKD

1

Kidney damage

with normal or ↑

GFR

>90

Comorbid

conditions

CVD and CVD risk

factors


diagnosis


conditions


risk factors

2 Kidney damage


Rate of

progression


function


complications


replacement therapy


Reno-Cardioprotection in DKD

Intervention Therapeutic goal

Renoprotective therapy

Antihypertensive agents BP ≤130/80 mmHg for albuminuria≥ 30 mg/day

BP ≤140/90 mmHg for albuminuria< 30 mg/day

ACEi or ARB

(Avoid combining ACEi+ARB)

Urine protein <0.5-1.0 g/day

GFR decline <2 mL/min/year

Glycemic control HbA1c~7%

Dietary protein restriction 0.8 g/kg/day in GFR < 30 mL/min/1.73 m2

Adjunctive cardiorenal protective therapy

Dietary salt restriction <5 g/day

Lipid-lowering agents (statin) LDL-C <70-100 mg/dL

Anti-platelets therapy Thrombosis prophylaxis

Physical activity Aiming for at least 30 minutes 5 times per wk)

Weight control Ideal body weight

Smoking cessation Abstinence

Satirapoj B, Adler SG. Kidney Res Clin Pract. 2014; 121–131.




Antihypertensive agents?? BP ≤130/80 mmHg for albuminuria≥ 30 mg/day???

BP ≤140/90 mmHg for albuminuria< 30 mg/day????

ACEi or ARB














KDIGO Clinical Practice Guideline for the Management of BP in CKD

Albuminuria

(ACR

<30 mg/g)

Albuminuria

(ACR

30-300 mg/g)

Albuminuria

(ACR

>300mg/g)

Diabetes <140/90 (1B) <130/80 (2D) <130/80 (2D)

Non diabetes <140/90 (1B) <130/80 (2D) <130/80 (2C)

Kidney International Supplements (2012) 2, 338

Individualize BP targets and agents according to age, co-existent

cardiovascular disease and other co-morbidities, risk of progression of

CKD, presence or absence of retinopathy and tolerance of treatment


Albuminuria

(ACR

<30 mg/g)

Albuminuria

(ACR

30-300 mg/g)

Albuminuria

(ACR

>300mg/g)

Diabetes <140/90 (1B) <130/80 (2D) <130/80 (2D)

Non diabetes <140/90 (1B) <130/80 (2D) <130/80 (2C)






Albuminuria

(ACR

<30 mg/g)

Albuminuria

(ACR

30-300 mg/g)

Albuminuria

(ACR

>300mg/g)

Diabetes <140/90 (1B) <130/80 (2D) <130/80 (2D)

Non diabetes <140/90 (1B) <130/80 (2D) <130/80 (2C)





NEW

2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults

UpToDate April 2018.

<130 mmHg systolic and <80 mmHg diastolic

NEW




<140/<90 mmHg (using an average of appropriately measured office readings)

in the following groups of hypertensive patients:

?

?

?

?

NEW




<140/<90 mmHg (using an average of appropriately measured office readings)

in the following groups of hypertensive patients:

•Patients with labile blood pressure or postural hypotension

•Patients with side effects to multiple antihypertensive medications

•Patients already taking three antihypertensive medications (including a

diuretic) at or near maximal antihypertensive doses

•Patients 75 years or older with a high burden of comorbidity or a diastolic

blood pressure <55 mmHg

Lifestyle Modifications

Modification Recommendation Approximate SBP

Reduction (mm Hg)

Weight loss Maintain normal body weight (body

mass index 18.5–23 kg/m2)

5–20 per 10-kg

weight loss

DASH-type

dietary patterns

Consume a diet rich in fruits, vegetables,

and low-fat dairy products with a reduced

content of saturated and total fat

8–14

Reduced salt

intake

Reduce daily dietary sodium intake,

ideally to 100 mmol/day of sodium, or 6

g/day of sodium chloride)

2–8

Physical activity Regular aerobic physical activity (at least

30 min/day, most days of the week) 4–9

Moderation of

alcohol intake

Limit consumption to 2 drinks/day in men

and 1 drink/day in women and lighter-

weight persons

2–4



Reduction (mm Hg)



5–20 per 10-kg

weight loss

DASH-type

dietary patterns




8–14

Reduced salt

intake




2–8



Moderation of

alcohol intake



weight persons

2–4



Reduction (mm Hg)



5–20 per 10-kg

weight loss

DASH-type

dietary patterns




8–14

Reduced salt

intake




2–8



Moderation of

alcohol intake



weight persons

2–4



Reduction (mm Hg)



5–20 per 10-kg

weight loss

DASH-type

dietary patterns




8–14

Reduced salt

intake




2–8



Moderation of

alcohol intake



weight persons

2–4



Reduction (mm Hg)



5–20 per 10-kg

weight loss

DASH-type

dietary patterns




8–14

Reduced salt

intake




2–8



Moderation of

alcohol intake



weight persons

2–4



Reduction (mm Hg)



5–20 per 10-kg

weight loss

DASH-type

dietary patterns




8–14

Reduced salt

intake




2–8



Moderation of

alcohol intake



weight persons

2–4




Antihypertensive agents BP ≤130/80 mmHg

ACEi or ARB













UpToDate 2018






ACEi or ARB













UpToDate 2018


Evidence for Effects of Good Glycemic Control on Complications, Including Nephropathy

Trial

Complication

DCCT

A1C: (9 → 7%)

N = 1441

Kumamoto

(9 → 7%)

N = 110

UKPDS

(8 → 7%)

N = 5102

Retinopathy ↓ 76% ↓ 69% ↓ 17-21%

Nephropathy ↓ 54% ↓ 70% ↓ 24-33%

Neuropathy ↓ 60% – –

DCCT = The Diabetes Control and Complications Trial. DCCT Study Group. N Engl J Med.

1993;329:977-986;

Ohkubo. Diabetes Res Clin Prac. 1995;28:103-117;

UKPDS Study Group. Lancet. 1998;352:837-853.

Evidence for Effects of Good Glycemic Control on Complications, Including Nephropathy

Trial

Complication

DCCT

A1C: (9 → 7%)

N = 1441

Kumamoto

(9 → 7%)

N = 110

UKPDS

(8 → 7%)

N = 5102

Retinopathy ↓ 76% ↓ 69% ↓ 17-21%

Nephropathy ↓ 54% ↓ 70% ↓ 24-33%

Neuropathy ↓ 60% – –

DCCT = The Diabetes Control and Complications Trial.

DCCT Study Group. N Engl J Med. 1993;329:977-986; Ohkubo. Diabetes Res

Clin Prac. 1995;28:103-117;

UKPDS Study Group. Lancet. 1998;352:837-853.

Annual Rates of Severe Hypoglycemia

0.

0.25

0.5

0.75

1.

1.25

0-12 13-24 25-36 37-48 49-60

Standardtreatment

Zoungas S, et al. N Engl J Med 2010;363:14108

Severe

hypogly

cem

ia (

%)

Month

Severe Hypoglycemia and Cardiovascular Outcomes and Death

No. of patients with events (%)

Events

Severe

hypoglycaemia

(n=231)

No severe

hypoglycaemia

(n=10,909)

Hazard ratio (95% CI)

Major macrovascular events 33 (15.9) 1114 (10.2) 3.53 (2.41–5.17)

Major microvascular events 24 (11.5) 1107 (10.1) 2.19 (1.40–3.45)

Death from any cause

45 (19.5) 986 (9.0) 3.27 (2.29–4.65)

CVD 22 (9.5) 520 (4.8) 3.79 (2.36–6.08)

Non-CVD 23 (10.0) 466 (4.3) 2.80 (1.64–4.79)

The hazard ratio represents the risk of an adverse clinical outcome or death among patients reporting

severe hypoglycaemia compared with those not reporting severe hypoglycaemia.

CI, confidence interval; CVD, cardiovascular disease. Zoungas S, et al. N Engl J Med 2010;363:1410–8.

Severe Hypoglycemia and Cardiovascular Outcomes and Death

No. of patients with events (%)

Events

Severe

hypoglycaemia

(n=231)

No severe

hypoglycaemia

(n=10,909)

Hazard ratio (95% CI)

Major macrovascular events 33 (15.9) 1114 (10.2) 3.53 (2.41–5.17)

Major microvascular events 24 (11.5) 1107 (10.1) 2.19 (1.40–3.45)

Death from any cause

45 (19.5) 986 (9.0) 3.27 (2.29–4.65)

CVD 22 (9.5) 520 (4.8) 3.79 (2.36–6.08)

Non-CVD 23 (10.0) 466 (4.3) 2.80 (1.64–4.79)

The hazard ratio represents the risk of an adverse clinical outcome or death among patients reporting

severe hypoglycaemia compared with those not reporting severe hypoglycaemia.

CI, confidence interval; CVD, cardiovascular disease. Zoungas S, et al. N Engl J Med 2010;363:1410–8.

Hypoglycemia Benefit

Summary of glycemic recommendations for many nonpregnant adults with diabetes: 2018

HA1C <7%*

Preprandial capillary plasma glucose 80–130 mg/dL

Peak postprandial capillary plasma glucose <180 mg/dL

*More or less stringent glycemic goals may be appropriate for individual

patients. Goals should be individualized based on:

❖ Duration of diabetes

❖ Age/life expectancy

❖ Comorbid conditions

❖ Known CVD

❖ Advanced microvascular complications

❖ Hypoglycemia unawareness, and individual patient

ADA. Diabetes Care 2018

Individualizing Glycemic Goal Setting

Favors Intensive Therapy

HbA1c <6.5-7%

Favors Less ntensive Therapy

HbA1c <8%

Highly motivated, adherent,

excellent self-care capability Less motivated, non-adherent, poor

self-care capability

Low risks potentially associated with

hypoglycemia High risks potentially associated

with hypoglycemia

Newly diagnosed diabetes Long-standing diabetes

Long life expectancy Short life expectancy

Absent comorbidities Severe comorbidities

Absent established vascular

complications (cardiovascular

disease, stroke, advanced chronic

kidney disease)

Severe established vascular

complications

(cardiovascular disease, stroke,

advanced chronic kidney disease)




HbA1c <6.5-7%


HbA1c <8%






with hypoglycemia







kidney disease)


complications






HbA1c <6.5-7%


HbA1c <8%






with hypoglycemia







kidney disease)


complications








ACEi or ARB













UpToDate 2018


Influence of LPD on Diabetes Nephropathy

Zeller et al. 1991

Low Protein Diet (LPD)

(0.4-0.6g/kg/day)

Glo

meru

lar

Filt

ration R

ate

(m

l/m

in)

Therapeutic Periods（Months）

80

70

60

50

40

30

20

10

0

0 10 20 30 40 50

Normal Protein Diet

Dietary Protein Restriction on Prognosis in Patients with Diabetic Nephropathy

Hansen HP, et al. Kidney Int 2002 Jul;62(1):220-8.

0 1 2 3 4

Follow-up time, years

Cu

mu

lative

in

cid

en

ce

of E

SR

D o

r

de

ath

, %

Low protein diet

Usual protein diet

ESRD or death occurred in 27% of patients on a usual-protein diet as compared with 10% on a

low-protein diet (log-rank test; P = 0.042)

โปรตนี 7 กรมั/ พลงังาน 70 กโิลแคลอรี ่

2 = ชอ้นโตะ๊ 4-5 ตวั 1 ตวัเล็ก

ไข่ท ัง้ฟอง 1 ฟอง ไข่ขาว 2 ฟอง 4-5 ลูก

Protein intake

❖ Lowering protein intake to 0.8 g/kg/day in adults with

❖ Diabetes (2C) or without diabetes (2B) and

❖ GFR <30 ml/min/ 1.73 m2 (GFR categories G4-G5) with appropriate education

❖ Avoiding high protein intake (>1.3 g/kg/day) in adults with CKD at risk of progression (2C)





ACEi or ARB













UpToDate 2018


อาหารจานเดยีว ทีม่เีกลอืมากทีสุ่ด?

1

ขา้วผดัหมู

3

แกงสม้ผกัรวม

2

สม้ต า

4

บะหมีร่าดหน้า

อาหารจานเดยีว ทีม่เีกลอืมากสุด?

1

ขา้วผดัหมู

3

แกงสม้ผกัรวม

2

สม้ต า

4

บะหมีร่าดหน้า

อาหาร ปรมิาณ น ้าหนกั-กรมั ปรมิาณโซเดยีม-

มก.

น า้ปลาหวาน 1 ชอ้นโตะ๊ 10 191

ปอเปียะทอด 2 อนั 80 235

น า้พรกิเผา 1 ชอ้นโตะ๊ 16 275

ขา้วผดัหม ู 1 จาน 295 416

บะหมีแ่หง้หมู 1 หอ่ 150 460

เตา้หูย้ี ้ 2 อนั 15 560

ปอเปียะสด 1 จาน 150 562

ผดัผกับุง้ใสเ่ตา้เจีย้ว 1 จาน 150 894

สม้ต าอสีาน 1 จาน 100 1006

เนือ้ปลาททูอด ½ ตวักลาง 100 1081

น า้พรกิกะปิ 4 ชอ้นโตะ๊ 60 1100

แกงสม้ผกัรวม 1 ถว้ย 100 1130

ปลาสลดิหมกัเกลอื 1 ตวั 40 1288

กว๋ยเตีย๋วผดัซอีิว้ 1 จาน 354 1352

บะหมีน่ า้หมูแดง 1 ชาม 350 1480

บะหมีร่าดหนา้ไก ่ 1 จาน 300 1819

อาหาร ปรมิาณ น ้าหนกั-กรมั ปรมิาณโซเดยีม-

มก.

น า้ปลาหวาน 1 ชอ้นโตะ๊ 10 191

ปอเปียะทอด 2 อนั 80 235

น า้พรกิเผา 1 ชอ้นโตะ๊ 16 275

ขา้วผดัหม ู 1 จาน 295 416

บะหมีแ่หง้หมู 1 หอ่ 150 460

เตา้หูย้ี ้ 2 อนั 15 560

ปอเปียะสด 1 จาน 150 562

ผดัผกับุง้ใสเ่ตา้เจีย้ว 1 จาน 150 894

สม้ต าอสีาน 1 จาน 100 1006

เนือ้ปลาททูอด ½ ตวักลาง 100 1081

น า้พรกิกะปิ 4 ชอ้นโตะ๊ 60 1100

แกงสม้ผกัรวม 1 ถว้ย 100 1130

ปลาสลดิหมกัเกลอื 1 ตวั 40 1288

กว๋ยเตีย๋วผดัซอีิว้ 1 จาน 354 1352

บะหมีน่ า้หมูแดง 1 ชาม 350 1480

บะหมีร่าดหนา้ไก ่ 1 จาน 300 1819

High salt diet

High SALT intake

(>5 grams/day)





ACEi or ARB













UpToDate 2018


Metabolic Parameters as Predictors of ESRD

Hyperlipidemia could simply be a marker of progression to end-stage

renal disease

Appel GB, et al. Diabetes Care 2003; 26: 1402–1407.

1. 1.18

1.41

1.97

0.

0.5

1.

1.5

2.

2.5

>189 189-220 220-260 >260

1. 1.07 1.24

1.87

0.

0.48

0.95

1.43

1.9

2.38

<111 111-137 137-167 >167

Cholesterol LDL-Cholesterol

Effects of Atorvastatin on Progression of Kidney Disease

-20.

-15.

-10.

-5.

0.

-12 -6 0 3 6 9 12

Atorvastatin

Bianchi, S, et al. Am J Kidney Dis 2003; 41:565.

Months

Cre

atin

ine

cle

ara

nce,

mL/m

in

* P<0.01 vs placebo

56 patients with chronic kidney disease



ACEi or ARB














การออกก าลงักายเพือ่ป้องกนัไตเสือ่ม

Contents







At increased

risk Test for CKD

1

Kidney damage

with normal or ↑

GFR

>90

Comorbid

conditions

CVD and CVD risk

factors


diagnosis


conditions


risk factors

2 Kidney damage


Rate of

progression


function


complications


replacement therapy


Systemic Complications in CKD

❖ Anemia of CKD

❖ Malnutrition

❖ Hyperkalemia

❖ Metabolic acidosis

❖ Mineral and bone disorders (MBD)


❖ Anemia of CKD

❖ Malnutrition

❖ Hyperkalemia



Anemia of chronic kidney disease

❖Normocytic, normochromic anemia

❖GFR < 30-60 (Stage 3-4)

❖Erythropoietin deficiency

❖Chronic blood loss

❖Iron deficiency (HD patients)

KDIGO Clinical Practice Guideline for Anemia in CKD. Kidney Int. 2012; 2: 279–335.

100-

90-

80-

70-

60-

50-

40-

30-

20-

10-

0-

Hemoglobin <11 g/dL

Hemoglobin <13 g/dL

43%

8% 2%

85%

55%

31% 23%

15 30 60 90 120

Estimated GFR (mL/min/1.73 m2)

Significant anemia was noted when the GFR < 30 mL/min/1.73 m2

Adapted from KDOQI guideline. Am J Kid Dis 2002; suppl 1: 1-246

Anemia with eGFR

Adverse Consequences of anemia

❖Fatigue, dizziness, shortness of breath

❖Poor quality of life

❖ Increase hospital days

❖Left ventricular hypertrophy

❖ Increased CV morbidity and mortality

Relative risks of death and hospitalization from cardiac causes

1.57

1.25

1. 0.96 0.93

1.3 1.2

1.

0.8 0.9

0.

0.4

0.8

1.2

1.6

2.

<30 30-<33 33-<36 36-<39 ≥39

RR

Hct Level

death

hospitalization

Collin AJ et al. J Am Soc Nephrol 12:2465-75; 2001.

Anemia of chronic kidney disease

❖Normocytic, normochromic anemia

❖GFR < 30-60 (Stage 3-4)

❖Erythropoietin deficiency

❖Iron deficiency esp HD patients

❖Chronic blood loss

Prefer Hb levels 10-11.5 g/dL range for patients with CKD

KDIGO Clinical Practice Guideline for Anemia in CKD. Kidney Int. 2012; 2: 279–335.

Management of Anemia of CKD

❖Recombinant erythropoietin

❖ Iron therapy

❖Red-blood-cell transfusion

❖Severe anemia

❖Acute anemia


❖ Anemia of CKD

❖ Malnutrition

❖ Hyperkalemia



Malnutrition

❖ Advanced CKD

❖ Anorexia

❖ Decreased intestinal absorption


❖ Diet 30 to 35 kcal/kg per day and

protein 0.8-1.0 g/kg/day with high biological value protein

❖ Initiative long-term renal replacement therapy


❖ Anemia of CKD

❖ Malnutrition

❖ Hyperkalemia



Plasma potassium

❖Normal K+ 3.5-5.5 mEq/L

❖Hyperkalemia >5.5 mEq/L

ผลไมช้นิดใดทีม่ปีรมิาณโพแทสเซยีมสูงทีสุ่ด?

Potassium

❖ ผลไมท้ีม่โีพแทสเซยีมสูง

❖ กลว้ย ฝร ัง่ กระทอ้น ทเุรยีน และผลไมแ้หง้

❖ ผลไมท้ีม่โีพแทสเซยีมปานกลาง

❖ สม้เขยีวหวาน สม้เชง้ มะละกอสกุ มะม่วงสกุ มะม่วงดบิ สม้โอ

แอปเปิลแดง สตรอเบอร ี ่ลางสาด แคนตาลปู เงาะ ขนุน

❖ ผลไมท้ีม่โีพแทสเซยีมต า่

❖ แตงโม และสบัปะรด

ผลไมช้นิดใดทีม่ปีรมิาณโพแทสเซยีมสูงทีสุ่ด?

Potassium-rich foods


❖ Anemia of CKD

❖ Malnutrition

❖ Hyperkalemia



Metabolic acidosis

❖Serum bicarbonate < 22 mEq/L

❖NaHCO3: Maintain serum

bicarbonate within the normal

range (22-26 mEq/L)


❖ Anemia of CKD

❖ Malnutrition

❖ Hyperkalemia



Renal Osteodystrophy

❖ X-ray Bone:

❖ Renal osteodystrophy (rugger-jersey spine)

❖ Subperiosteal erosions on radiography

Secondary hyperparathyroidism

Normal Abnormal

Secondary hyperparathyroidism

Medial calcification in subcutaneous artery and occlusive hyperplasia of intima

Medial calcification of subcutaneous artery and occlusive fibrin thrombus

Metastatic calcification

• Calcium phosphate to precipitate in arteries, joints, soft tissues, and the

viscera

• Tissue ischemia, calciphylaxis

• Tumoral collections of calcium phosphate crystals

Clinical Manifestations, Radiographic Features, and Histologic

Characteristics of Calciphylaxis

Sagar U, et al. N Engl J Med 2018;378:1704-14

Hyperphosphatemia

25 OH D deficiency

FGF-23

Renal function

Hypocalcemia

Decreased calcitriol

Increased PTH

synthesis

and secretion CaS VDR

PO4 sensor

Inh

ibit 1

-OH

Major Targets for PTH Function

❖Extracellular phosphate sensor

❖Vitamin D receptor (VDR)

❖G-protein-coupled calcium-sensing

receptor (CaSR)

Elevated Serum Phosphorus and Mortality Risk in Dialysis Patients

*Multivariable adjusted

Block GA, et al. J Am Soc Nephrol. 2004;15:2208-2218.

Rela

tiv

e r

isk

of

dea

th*

<3 3-4 4-5 5-6 6-7 7-8 8-9 >9

Serum phosphorous concentration (mg/dL)

0.00

1.0

1.4

1.6

2.0

2.2

0.08

1.2

1.8

N = 40,538

Referent

Range

Mineral and bone disorders (MBD) in CKD

VDR expression

Phosphate retention

1,25 D production

PTH

Ca2+

Altered parathyroid gland function

Hyperplasia Secondary hyperparathyroidism

CONSEQUENCES

Renal osteodystrophy Fractures Calcification Cardiovascular disease

Morbidity and mortality

FGF-23

Renal function

CaSR

KDIGO Clinical practice guideline Target level

CKD Stage 3

(GFR 30-59

ml/min)

CKD Stage 4

(GFR 15-29

ml/min)

CKD Stage 5

(GFR <15

ml/min)

P (mg/dL) Normal Normal Toward-

Normal

Ca (mg/dL) Normal Normal Normal

Intact PTH

(pg/mL)

>upper normal

of limit

>upper normal

of limit

2-9 times

upper limit of

normal

KDIGO. Kidney Int. 2009; 76 (suppl 113):S1-S130.

Normal Ranges for Measuring Biomarkers

“Normal” Phosphorus 2.5 – 4.5 mg/dL

“Normal” Calcium 8.5 – 10 mg/dL or 10.5

mg/dL

“Normal” iPTH(varies with the assay used)

15 - 65 pg/mL

KDIGO. Kidney Int. 2009; 76 (suppl 113):S1-S130.


Kidney International Supplements (2017) 7, 1–59


CKD Stage 3 (GFR

30-59 ml/min)

CKD Stage 4 (GFR

15-29 ml/min)

CKD Stage 5 (GFR

<15 ml/min)

P (mg/dL) Toward the normal

range

Toward the normal

range

Toward the normal

range

Ca (mg/dL) Avoiding

hypercalcemia

Avoiding

hypercalcemia

Avoiding

hypercalcemia

Intact PTH (pg/mL) the optimal PTH

level is not known

the optimal PTH

level is not known

2-9 times upper

limit of normal



CKD Stage 3 (GFR

30-59 ml/min)

CKD Stage 4 (GFR

15-29 ml/min)

CKD Stage 5 (GFR

<15 ml/min)


range

Toward the normal

range

Toward the normal

range

Ca (mg/dL) Avoiding

hypercalcemia

Avoiding

hypercalcemia

Avoiding

hypercalcemia


level is not known

the optimal PTH

level is not known

2-9 times upper

limit of normal



CKD Stage 3 (GFR

30-59 ml/min)

CKD Stage 4 (GFR

15-29 ml/min)

CKD Stage 5 (GFR

<15 ml/min)


range

Toward the normal

range

Toward the normal

range

Ca (mg/dL) Avoiding

hypercalcemia

Avoiding

hypercalcemia

Avoiding

hypercalcemia


level is not known

the optimal PTH

level is not known

2-9 times upper

limit of normal


Management of Hyperphosphatemia

❖ Dietary phosphate restriction 800-1,000 mg/day

❖ Phosphate binders

❖ To minimize the rest of phosphate balance

❖ Dialysis Phosphate removal

❖ Hemodialysis 20-40 mmol/session

❖ Peritoneal dialysis 10-12 mmol/day

Phosphate Restriction

❖ 800-900 mg/day

อาหารชนิดใดทีม่ปีรมิาณฟอสฟอรสัต า่สุด?


ปรมิาณฟอสฟอรสั (มก.) ตอ่อาหาร 100 กรมั

กุง้แหง้ทอดกรอบ 703

กุง้เผา 635

ถ ัว่ 400-600

งาด า 570

ขา้วโพด 360

ปลารา้ 400

ปลาชอ่นย่าง 306

เตา้หูท้อด 522

เตา้หูข้าว ออ่น 190

เตา้หูข้าว แข็ง 62


กุง้แหง้ทอดกรอบ 703

กุง้เผา 635

ถ ัว่ 400-600

งาด า 570

ขา้วโพด 360

ปลารา้ 400

ปลาชอ่นย่าง 306

เตา้หูท้อด 522

เตา้หูข้าว ออ่น 190

เตา้หูข้าว แข็ง 62




นมขน้หวาน 205

นมววั ไม่มไีขมนั 92

นมววั 99

ยาคูลท ์ 47

นมมารดา 12

Phosphate Binders

Drug Advantages Disadvantages

Aluminum-

containing

Effective

Inexpensive

Encephalopathy

Anemia

Osteomalacia

Calcium-

containing

Effective

Inexpensive

Hypercalcemia and/or

Promote vascular

calcifications

Magnesium-

containing

Effective

Inexpensive

GI side effects (diarrhea),

Rare respiratory depression

Sevelamer and

lantanum

Effective

Less vascular

calcifications

Less hypercalcemia

Expensive

Higher pill burden

Phosphate binders


Aluminum-

containing

Effective

Inexpensive

Encephalopathy

Anemia

Osteomalacia

Calcium-

containing

Effective

Inexpensive


Promote vascular

calcifications

Magnesium-

containing

Effective

Inexpensive



Sevelamer and

lantanum

Effective

Less vascular

calcifications

Less hypercalcemia

Expensive

Higher pill burden

Phosphate binders


Aluminum-

containing

Effective

Inexpensive

Encephalopathy

Anemia

Osteomalacia

Calcium-

containing

Effective

Inexpensive


Promote vascular

calcifications

Magnesium-

containing

Effective

Inexpensive



Sevelamer and

lantanum

Effective

Less vascular

calcifications

Less hypercalcemia

Expensive

Higher pill burden

Phosphate binders


Aluminum-

containing

Effective

Inexpensive

Encephalopathy

Anemia

Osteomalacia

Calcium-

containing

Effective

Inexpensive


Promote vascular

calcifications

Magnesium-

containing

Effective

Inexpensive



Sevelamer and

lantanum

Effective

Less vascular

calcifications

Less hypercalcemia

Expensive

Higher pill burden

Phosphate Binders Comparison

Vascular

Calcification Metal

accumulation

Non-absorbed

Non-accumulated

LDL reduction*

Aluminium

Potential to Potential to

Sevelamer

Carbonate

Phosphate binders


Aluminum-

containing

Effective

Inexpensive

Encephalopathy

Anemia

Osteomalacia

Calcium-

containing

Effective

Inexpensive


Promote vascular

calcifications

Magnesium-

containing

Effective

Inexpensive



Sevelamer and

lantanum

Effective

Less vascular

calcifications

Less hypercalcemia

Expensive

Higher pill burden

Treatment of CKD-MBD: Phosphorus and Calcium

❖ 4.1.5: In patients with CKD G3a-G5D, decisions about phosphate-lowering treatment should be based on progressively or persistently elevated serum phosphate (Not Graded).

❖ 4.1.6: In adult patients with CKD G3a–G5D receiving phosphate-lowering treatment, we suggest restricting the dose of calcium-based phosphate binders (2B)


Comparison of Drugs for CKD-MBD Treatment

PTH Ca P Ca×P

P Binder

Ca

Non-Ca

Vitamin D

Cinacalcet

Parathyroidectomy

Parathyroidectomy

Severe hyperparathyroidism

(iPTH > 800 pg/ml)

❖ Gland size by Imaging study >

500 mm3

❖ Osteitis fibrosa or high bone

turn over by bone metabolic

markers

❖ Failure to medical treatment

(Hypercalcemia and

hyperphosphatemia)

Progressive tissue

calcification

❖ Deformities due to

osteitis fibrosa

❖ Progressive bone loss

❖ Calciphylaxis

❖ Anemia resistance to

EPO

Parathyroidectomy

Severe hyperparathyroidism

(iPTH > 800 pg/ml)

❖ Gland size by Imaging study >

500 mm3

❖ Osteitis fibrosa or high bone

turn over by bone metabolic

markers

❖ Failure to medical treatment

(Hypercalcemia and

hyperphosphatemia)

Progressive tissue

calcification

❖ Deformities due to

osteitis fibrosa

❖ Progressive bone loss

❖ Calciphylaxis

❖ Anemia resistance to

EPO



At increased

risk Test for CKD

1

Kidney damage

with normal or ↑

GFR

>90

Comorbid

conditions

CVD and CVD risk

factors


diagnosis


conditions


risk factors

2 Kidney damage


Rate of

progression


function


complications


replacement therapy


Timing of the Initiation of RRT

❖ Symptoms or signs attributable to kidney

failure

❖ Serositis, acid-base or electrolyte

abnormalities, pruritus

❖ Inability to control volume status or BP

❖ Deterioration in nutritional status

❖ Cognitive impairment

❖ GFR 5-10 ml/min/1.73 m2


สง่ตอ่ผูป่้วยโรคไตเร ือ้รงัพบอายุรแพทยโ์รคไต

❖ มกีารเพิม่ขึน้ของ CKD staging หรอืมคีา่

eGFR ลดลงมากกวา่รอ้ยละ 25%

❖ มคีา่ eGFR ลดลงมากกวา่

5 มล./นาท/ี1.73 ม2ตอ่ปี

❖ มคีา่ eGFR น้อยกวา่ 30 มล./นาท/ี1.73 ม2

โดยเฉพาะมขีอ้บ่งชีร้ว่มอืน่ๆ ไดแ้ก ่

การส่งตอ่ผูป่้วยทีล่่าชา้ จะมผีลตอ่ระยะเวลาทีต่อ้งนอน

โรงพยาบาลและอตัราการอยู่รอดของผูป่้วย

สง่ตอ่ผูป่้วยโรคไตเร ือ้รงัพบอายุรแพทยโ์รคไต

❖ มคีา่ eGFR น้อยกวา่ 30 มล./นาท/ี1.73 ม2

โดยเฉพาะมขีอ้บ่งชีร้ว่มอืน่ๆ ไดแ้ก ่

AKI on top CKD

ACR > 300 mg/g or PCR > 500 mg/g (หลงัคมุความดนัโลหติได้

ตามเป้าหมายแลว้)

ใชย้าลดความดนัโลหติ 4 ตวัแลว้ยงัควบคมุความดนัโลหติไม่ได ้

Urine RBC > 20 cell/HPF โดยหาสาเหตไุม่ได ้

Persistent hyperkalemia

ตรวจพบน่ิวมากกวา่ 1 คร ัง้ รว่มกบัภาวะอดุกล ัน้ทางเดนิปัสสาวะ

มโีรคไตเร ือ้รงัทีเ่กดิจากการถา่ยทอดทางพนัธุกรรม

พจิารณาเร ิม่การบ าบดัทดแทนไต

❖ ผูป่้วยโรคไตทีม่รีะดบั eGFR น้อยกวา่หรอืเท่ากบั 6 มล./

นาท/ี1.73 ม2 และไม่พบเหตทุีท่ าใหไ้ตเสือ่มช ัว่คราว

❖ ผูป่้วยโรคไตทีม่รีะดบั eGFR มากกวา่ 6 มล./นาท/ี1.73

ม2 แตม่ภีาวะแทรกซอ้นทีเ่กดิโดยตรงจากโรคไตเร ือ้รงั ซึง่

ไม่ตอบสนองตอ่การรกัษาดว้ยวธิปีกต ิ

1.Hemodialysis (HD) 2. Peritoneal Dialysis

3.Kidney transplantation

(KT) คุณภาพชีวติดีสุด

4. Palliative care

Summary





Thank You for Your Attention

Naowanit Nata, MD

Division of Nephrology

Department of Medicine

Phramongkutklao Hospital and College of Medicine

Documents

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