early detection & prevention of chronic kidney disease
DESCRIPTION
Early Detection & Prevention of Chronic Kidney Disease. Dhavee Sirivongs, M.D. August 5, 2005. 30 บาทรักษาทุกโรค. 30 บาท ช่วยคนไทยห่างไกลโรค. Prevention is better than treatment Prevention is the best policy Prevention forever. - PowerPoint PPT PresentationTRANSCRIPT
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Early Detection & Prevention of Chronic Kidney Disease
Dhavee Sirivongs, M.D.
August 5, 2005
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30 บาทรั�กษาท�กโรัค 30 บาท ช่�วยคนไทยห่�างไกล
โรคTreatment Treatment Treatment Treatment Treatment Treatment Treatment Treatment Treatment Treatment Treatment Treatment Treatment Treatment Treatment Treatment Treatment Treatment Treatment Treatment Treatment Treatment Treatment Treatment Treatment Treatment Treatment Treatment Treatment Treatment
Prevention is better than treatment
Prevention is the best policy
Prevention forever
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normalkidneyfailure
increaserisk
decreaseGFR
damage
complications
Screening for CKD riskfactor
Risk factorreduction,screening
Dx & Rx treat comorbid
slow progression
Estimateprogression
prepare RRT
Dialysistransplantation
Stages in Progression of CKD and Therapeutic Strategies
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นิ ยามของ โรัคไตเรั��อรั�ง ใช้�“ ”หนิ��งในิ 2 ข�อ
1) ไตผิ ดปกต อย!างนิ�อย 3 เด�อนิ ความผิ ดปกต นิ��นิอาจเป$นิโครังสรั�างหรั�อในิหนิ�าท&�ของไต อาจม&หรั�อไม!ม&การัลดลงของ GFR โดยม&รั!องรัอยความผิ ดปกต ข�อใดข�อหนิ��งต!อไปนิ&�–ทางพยาธิ ว ทยา หรั�อ- ผิ ดปกต : ในิเล�อด/ป*สสาวะ/ทางรั�งส&ว ทยา 2) GFR < 60 173ml/min/ . m2 เป$นิ
เวลาอย!างนิ�อย 3 เด�อนิ โดยไม!ม&ความผิ ดปกต ของไต
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รัะยะ ค,าจ,าก�ดความ GFR (มล./นิาท&)
0ไตผิ ดปกต ป*จจ�ยเส&�ยงต!อโรัค
ไตเรั��อรั�ง> 90 (รั!วมก�บม&ป*จจ�ย
เส&�ยง)
1ไตผิ ดปกต และ GFR ปกต หรั�อ
เพ �มข��นิ > 90
2 GFR ลดลงเล.กนิ�อย 60 – 89
3 GFR ลดลงปานิกลาง 30 – 59
4 GFR ลดลงมาก 15 – 29
5 ไตวายรัะยะส�ดท�าย < 15 (หรั�อต�องล�างไต)
รัะยะต!างๆของ “โรัคไตเรั��อรั�ง”
Cr 1.2
Cr 1.8
Cr 3.6
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Burden of ESRD in Thailand
30
15
10฿1
00 m
illio
n)
2000 2005 2010
Costs
20
25
$
$
$
Growth to year 2010 projected on the basis of historical data (1996-2000) from TRT
Dialysis 12000 cases in 2004
ป0 2547 ปรัะเทศไทยใช้�เง นิ 2400 ล�านิบาท 100(
00 ล�านิบาท)
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Lysaght, J Am Soc Nephrol, 2002
GLOBAL MAINTENANCE DIALYSIS POPULATION FROM 1990 TO 2010
1990 2000 2010
426,000
1,065,000
2,095,000
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8ประเมิ�นการเก�ดผู้��ป�วยไตวายเร��อร ง
ใน 10 ป"
ปรัะช้ากรั 66 ล�านิ
เบาห่วาน 2 ล�าน
ความิด นโลห่�ตสู�ง 4 ล�าน
โรคไตอ�$นๆ 0.5 ล�าน
5 %ไตวายใน10 ป"
1% ไตวายใน 10 ป"
1% ไตวายใน 10 ป"
10000 ราย ไตวาย/ป"
4000 ราย ไตวาย/ป"
500 ราย ไตวาย/ป"
ม&ผิ2�ป3วยไตวายใหม! 14500 รัาย/ป0
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At prsent, treatment of renal patients has been pointed to retard or prevent progression to ESRD
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Renal injury
Glomerular-capillary hypertension
Increased filtration of plasma proteins
Excessive tubular reabsorption
Nuclear signals for NF-kB-dependent and independent vasoactive and inflammatory genes. Corresponding protein products then released
into interstitium
Tubular cell transdifferentiation
Fibroblast proliferation
Fibrogenesis
Increased glomerular permeability to macromolecules
Proteinuria
Renal scarring
Reduction of nephron numbers
PATHOPHYSIOLOGY OF PROGRESSIVE NEPHROPATHIES
1998 concept1998 conceptRemuzzi and Bertani,N Engl J Med
Tubular damage
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Mechanisms of Progressive Loss of Renal function
Proteinuria Hypertension
Initial insult
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Relationship between achieved BP control and rate of renal function decline in 9 clinical trials (DM & non-DM)
Adapted from Bakris GL, William M, Dworkin L et al: NKF Hypertension and Diabetes executive committee Working group. Am J Kidney Dis 36:646-61, 2000
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NEPHRON NUMBER IN 10 MIDDLE-AGED WHITE HYPERTENSIVES AND 10 MATCHED NORMOTENSIVES
Keller et al., N Engl J Med, 2003
Mean glomerular volume (10-3/mm3)
Nephron number per kidney
(x 1
,000
)
Ht0
1,000
1,500
2,000
2,500
500
N
6.5 2.8
706 (626-802)
1,429 (1,130-1,627)
*
* p < 0.001
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Risk factors & Targets for Renoprotection
• Hypertension < 130/80 • Hyperglycemia HbA1c < 7• Smoking Stop• Hyperlipidemia LDL-c <
100• Drug(s) Avoid
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Markers/Indicies for Early Detection of Renal Deterioration
•Proteinuria***** (microalbuminuria)
•?? FE Mg < 2.2% (detect Tubulo-interstitial damage)
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รัะด�บโปรัต&นิ , อ�ลบ2ม นิในิป*สสาวะและนิ ยาม
Staging Random urine
Morning urine
24 hour urine
Timed urine
UAC mg/L Alb/Cr ratio, mg/g
UAE mg/day
UAE ug/min
Normal < 10 F <10, M <15 < 15 < 10
Borderline or high normal
10-20 F 10-17 M 15-25
15-30 10-20
Micro-albuminuria
20-200 F 17-170 M 25-250
30-300 20-200
Macro-albuminuria
> 200 F >170 M >250
> 300 > 200
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Albuminuria
• Reflects endothelial damage • Associated with myocardial infarction
and stroke• Part of cardiometabolic syndrome• Progression of Micro-* to
macroalbuminuria predicts progression of renal disease
* Microalbuminuria 30-300 mg/day
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Adapted from Peterson JC, Adler S, Burkart JM el Ann Intern Med 123:758-62, 1995
Decreased GFR due to blood pressure & proteinuria from MDRD study
Proteinuria, g/day
0 - 0.25
0.25 - 1
1 - 3
> 3 g/day
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Microalbuminuria and Ischemic Heart Disease Risk
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How to screen ?
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การัตรัวจค�ดกรัองไต “ช้�ดพ��นิฐานิ”
• Blood pressure
• Urinalysis for protein
• Serum creatinine
Microalbuminuria
ASN 2003
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Tests & frequency for Screening in certain population
กล�!ม ส �งท&�ต�องตรัวจ ความถี่&�การัตรัวจ
ประช่ากรท&$ไมิ�มิ&อาการใดๆ
ช่'ดพื้��นฐาน: BP, UA, Scr
ป"ละ 1 คร �ง กรณี&ได�ผู้ลลบ
ประช่ากรสู ญญาณีบอกโรคไต
ช่'ดพื้��นฐาน + การตรวจเฉพื้าะ
ป"ละ 2 คร �ง กรณี&ได�ผู้ลลบ
ผู้��ป�วยท&$มิ&โรคท&$เสู&$ยงต�อโรคไต
เบาห่วาน ความิด นโลห่�ตสู�ง
ช่'ดพื้��นฐาน + การตรวจเฉพื้าะ
ป"ละ > 2 คร �ง กรณี&ผู้ลลบ
ผู้��ป�วยท&$มิ&โรคไตเร��อร งระยะ1-2
ช่'ดพื้��นฐาน + การตรวจเพื้�$มิเต�มิ
อย�างน�อยป"ละ 2 คร �ง
ผู้��ป�วยท&$มิ&โรคไตเร��อร งระยะ 3
ช่'ดพื้��นฐาน + การตรวจเพื้�$มิเต�มิ
อย�างน�อยป"ละ 3 คร �ง
ปรัะช้ากรัม&ส�ญญาณบอกโรัคไต
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6 ส�ญญาณบอกโรัคไต• ป*สสาวะข�ด• บวมรัอบตา บวมเท�า• ป*สสาวะบ!อย ป*สสาวะกลางค�นิ • ป*สสาวะส&นิ,�าล�างเนิ��อ • ปวดหล�งใต�ช้ายโครัง ปวดเอว• ความด�นิโลห ตส2ง
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Tests & frequency for Screening in certain population
กล�!ม ส �งท&�ต�องตรัวจ ความถี่&�การัตรัวจ
ประช่ากรท&$ไมิ�มิ&อาการใดๆ
ช่'ดพื้��นฐาน: BP, UA, Scr
ป"ละ 1 คร �ง กรณี&ได�ผู้ลลบ
ประช่ากรสู ญญาณีบอกโรคไต
ช่'ดพื้��นฐาน + การตรวจเฉพื้าะ
ป"ละ 2 คร �ง กรณี&ได�ผู้ลลบ
ผู้��ป�วยท&$มิ&โรคท&$เสู&$ยงต�อโรคไต
เบาห่วาน ความิด นโลห่�ตสู�ง
ช่'ดพื้��นฐาน + การตรวจเฉพื้าะ
ป"ละ > 2 คร �ง กรณี&ผู้ลลบ
ผู้��ป�วยท&$มิ&โรคไตเร��อร งระยะ1-2
ช่'ดพื้��นฐาน + การตรวจเพื้�$มิเต�มิ
อย�างน�อยป"ละ 2 คร �ง
ผู้��ป�วยท&$มิ&โรคไตเร��อร งระยะ 3
ช่'ดพื้��นฐาน + การตรวจเพื้�$มิเต�มิ
อย�างน�อยป"ละ 3 คร �ง
ผิ2�ป3วยท&�ม&โรัคท&�เส&�ยงต!อโรัคไตเบาหวานิ ความด�นิโลห ตส2ง
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ป*จจ�ยเส&�ยงต!อการัเก ด “โรัคไตเรั��อรั�ง” และนิ ยาม
ช้นิ ด นิ ยาม ต�วอย!างป.จจ ยท&$
เสู&$ยงต�อการเก�ดโรค
เพื้�$มิโอกาสูท&$จะมิ&การ
ท/าลายไต
Old age, Family Hx,
low birth weight
ป.จจ ยท&$ท/าให่�เก�ดโรค
ท/าลายไตโดยตรง
DM, HT, autoimmune diseases,
Systemic infection, UTI, KUB
stone, Toxins, KUB obstruction
ป.จจ ยท&$เร�งการด/าเน�นโรค
ท/าให่�ไตท&$เก�ดโรคอย��
แล�วเลวลง/ท/างานน�อยลง
High proteinuria, uncontrolled BP,
poor control BS, smoking
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How to Retard the Progression: Evidence ?
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Goal BP Recommendations for Patients with DM or Renal Disease
Organization Year Systolic BP
Diastolic BP
American diabetes Association 2004 <130 <80
KDOQI (NKF) 2004 <130 <80
JNC 7 2003 <130 <80
Canadian Hypertension Society 2002 <130 <80
British HTN Soc 1999 <130 <80
WHO/ISH 1999 <130 <80
For CKD
BP < 130/80
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Proteinuria/Microalbinuria• Microalbuminuria
30-300 < 30 < 15 mg/d
• Proteinuria > 3 2.5 1.0 0.5 g/d
Needs ACE-I, ARB (with or w/o Ht)
non-DHP CCB (for Ht)
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3 4 5 years-2 - 1 0 1 2
Mogensen et al., 1976* PA 200/120 mmHg
Glo
me
rula
r F
iltra
tion
Ra
te
(ml/m
in/1
.73
sqm
)
treatment *
GFR 20 ml/year
GFR 2 ml/year40
60
80
100
20
0DYALISISDialysis
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95
105
115
125
- 2 - 1 0 1 2 3 4 5 6years
55
65
75
85
95
105
- 2 - 1 0 1 2 3 4 5 6years
250
750
1205
- 2 - 1 0 1 2 3 4 5 6
ANTIHYPERTENSIVE THERAPY
GFR: 0.10(ml/min/month)
Glo
mer
ula
r F
iltra
tio
n R
ate
(ml/
min
/mo
nth
)M
ean
Art
eria
l Blo
od
Pre
ssu
re(m
mH
g)
Alb
um
inu
ria
(µg
/min
)
Parving et al., Br J Med, 1987Years
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A META-ANALYSIS IN 840 TYPE 1 AND TYPE 2 DIABETIC PATIENTS WITH INCIPIENT AND OVERT NEPHROPATHY AND PRESERVED RENAL FUNCTION
Cha
nge
in p
rote
inur
ia (
%)
Change in GFR (%/year)
Modified from Weidmann et al., Nephrol Dial Transpl, 1995
0
- 20
- 40
- 60
- 80
- 100
+ 20
-20 0-16 -12 -8 -4 +4 +8 +12 +16-100 -50
Nifedipine (n=75)
Diuretics and/or beta-blockers
(n=213)
CCBs, except nifedipine
(n=63)
ACE inhibitors (n=489)
Baseline parameters:
- mean GFR: 83 ml/min
- mean proteinuria: 2.4 g/24 h
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ACE-I Non DHP CCB ACE-I + CCB
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Decrease in Mean Blood
Pressure (mm Hg)
- 2 –
0 –
- 2 –
- 4 –
- 6 –
- 8 –
- 40 –
- 20 –
0 –
- 20 –
- 40 –
- 60 –
% Reduction in
Proteinuria
P <.001
% with Doubling of
Baseline Creatinine
Baseline creatinine > 1.5 mg/dl
0
25
50
75
100
0 1 2 3 4
Captopril
Conventional therapy
Lewis et al. N Engl J Med. 1993;329:1456-1462.
NS
ACEI IS BETTER THAN non-ACEI THERAPY IN TYPE 1 DIABETES
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45
30
25
40
35GF
R(m
l/min
/mon
th)
RamiprilRamipril
GFR = -0.44 ± 0.54
GFR = -0.10 ± 0.50
GFR = -0.81 ± 1.12 GFR = -0.14 ± 0.87
RamiprilConventional
CORE FOLLOW-UP
Ruggenenti et al., Lancet, 1998
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COOPERATE study: results
Nakao et al., Lancet, 2003
Pa
tient
s w
ithou
t eve
nts
* (%
)
Months after randomisation0 6 12 18 24 30 36
CombinationLosartanTrandolapril
40
80
100
60
20
0
* ESRD and doubling of serum creatinine
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REIN: ACEI IS MORE RENOPROTECTIVE THAN
CONVENTIONAL Rx IN NON-DIABETIC RENAL DISEASE
% of patients without doubling of baseline creatinine or ESRF
60
40
20
00 6 12 18 24 30
80
100
36Follow-up
P=0.02
- 40 –
- 20 –
0 –
20 –
40 –
60 –
% Reduction in
Proteinuria
Diastolic Blood Pressure (mm Hg)
100 –
90 –
80 –
70 –
60 –
Ramipril
Conventional therapy
Gisen group; Lancet 1997
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Targets of Management
Blood pressure < 120/80 mmHgProteinuria < 0.3 g/24 hLDL < 100 mg/dlHDL > 40 (60) mg/dlHbA1c < 7.0 % (DM)
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Take home message
• Identify the patients
• Check risk factors
• Interventions
• Monitoring
• Optimize the treatment
• (Reconsider on cause & Rx, in case)
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Take home message• BP controlled (120/80) with any
drugs + ACEI/ARB• Keep Proteinuria (< 3 g/d),
controlled with ACEI + ARB• HbA1C < 7.0 %• Low LDL-c (< 100) and/or
High HDL-c (> 40)• Stop smoking
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Acknowledgement
Giuseppe Remuzzi, M.D.
Mario Negri Institute for Pharmacological Research, Bergamo, Italy
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You all are invited to attend “Update on Prevention of CKD
in Thailand”in 5 areas around the country
• September 22, 2005 for Doctors
• September 23, 2005 for Nurses
• Venue in the Northeast: Chareonsri Grand, Udorn
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Thank You for
Your Attention