Update in Delaying Progression of Chronic Kidney Disease

Update in Delaying Progression of Chronic Kidney Disease

Scope of Presentation

แผ่นแปะเท้า

1. ESRD : epidemiology
2. CKD – definition & classification
– prevalence
3. Serum creatinine and GFR equation
4. Risk factors for CKD
5. Intervention to delay CKD progression

Yearly prevalence trend of renal replacement
therapy, Thailand 1997-2009 พ!L,J
Patient per millions population (pmp)
600
500
400
300
200
100
0
1997 1998 1999 2000 2001 2003 2004 2005 2006 2007 2008 2009 *Missing data in 2002
3
Thailand Renal Replacement Report 20099 Nephrology Society of Thailand

Prevalence of ESRD – World wide

Etiology of ESRD by RRT prevalence L.L J
in 2007-2009
2007 2008 2009
Diabetic nephropathy 4,965 (34.6%) 7,000 (36.9%) 9,487 (47.6%)
Obstructive nephropathy 626 (4.4%) 1,020 (5.4%) 1,036 (5.2%)
Glomerulonephritis 965 (6.8%) 951 (5.2%) 775 (3.9%)
Chronic rate nephropathy 373 (2.6%) 437 (2.3%) 295 (1.5%)
Lupus nephritis 178 (1.2%) 240(1.3%) 236(1.2%)
Polycystic kidney disease 229 (1.6%) 298(1.6%) 257 (1.3%)
Thailand Renat Replacement Report 2009, Nephrology Society of Thailand
65

Unique causes of CKD in Thailand
1. RTA (Nephrocalcinosis, renal stone)
2. Nephrolithiasis (obstruction infection, CKD)
3. Cadmium (แม่สอด) B2G’ uria, RTA, CKD
4. Lead poisoning (คลีต, กาญจนบุรี)
5. Fluorosis
6. Herbal medicine (Aristolochic acid, etc.)

Creatinine measurement
– Modified Jaffe’s method
(10 – 20% ever estimation )
– Enzymatic method

S.Cr is ล ( poor representative of GFR )

1. Creatinine clearance
– 24h urine coll^ Ccr = uv / p
– Cockroft & Gault. Ccr = (140 – Age) ■ BW
72 s.cr (x 0.85 if female)
2. Isotope clearance
– Plasma clearance : lothalamate, DTPA-
plasma clearance
– Calibrated with serum creatinine [ eGFR ]

Abbreviated MDRD-GFR equations
Re-expressed IDMS – traceable 1
= 175 X s.cr”1’154 X Age’0’203 X 0.742 ( female )
MDRD2 = 186 X S.cr’1154 X Age’0-203 X 0.742 ( female ) X 1.212 (black) Japanese 3 = 168 X s.cr’1’044 X Age’0’274 X 0.775 ( female )
Chinese 4 = 175 X s.cr”1’234 X Age’0’179 X 0.79 ( female )
Thai5 re-expressed IDMS traceable MDRD equation.
= 175 x CrEnz’1154 x Age’0’203 X 0.742 ( female ) X 1.129 ( Thai) or = 375.5 X CrF117’°’848 X Age’0’364 X 0.712 ( female ) ■ร
1. AJKD 2007; 50: 927-37.
ร. Clin Chem 2007; 53: 766-72.
5. Praditpornsilpa K, WCN May 2008.
2. Ann Intern Med 1999; 130: 461-70. 4. JASN 2006; 17: 2937-44.

A New Equation to Estimate Glomerular Filtration Rate
Table2. TheCKD-EPI Equation for Estimating GFR on the Natural Scale*
s.cr |amol/L ( mg/dL)
Fe male <62 {<0.7) >62 (>0.7) GFR = GFR = 166 X (Scr/0,7)-0329 166 X (Scr/O.7)-1-20* X (O.993)A&0 X (0.993)A&e
Male <80 (<0.9) >80 (>0.9) GFR = GFR = 163 X (Scr/0,9)-0-411 163 X (Scr/O.9)-1-209 X (0.993)Aee X (0.993)A&e
White or other
Fe male <62 (<0.7) >62 (>0.7) GFR = GFR = 144 X (Scr/0,7)-0-329 144 X (Scr/0,7)-1–209 X <O.993)A£f0 X (0.993)A^
Male <80 (<0.9) >80 (>0.9) GFR = GFR = 141 X (Scr/0,9)-0-411 141 X (Scr/0.9)-1 209 X (0.993)Aร0 X (0.993)A&e
CKD-EPI = Chronic Kidney Disease Epidemiology Collaboration; GFR = glo¬merular filtration rate.
Levey AS, etal. Ann Intern Med 2009; 150: 604.

+
Definition of Chronic Kidney Disease
1. Kidney damage >3 months, ( +/- \ GFR ) defined by
a. Pathological abnormalities; or
b. Functional abnormalities Markers of kidney damage include
– abnormal blood or urine composition
– abnormal imaging tests
2. GFR <60 mL/min/1.73 m2 for >3 months,
( +/- kidney damage )
AJKD 2002; 39 (Suppl 1): S17

Stages of Chronic Kidney Disease
stage Prevalence *
Glomerular Filtration Rate ml I min 11.73 เท2
Kidney Damage with Normal Filtration
>90
Kidney Damage with Mildly Decreased Filtration
60-89
Moderately Decreased Filtration
30-59
0.2%
Severely Decreased Filtration
15-29
0.2%
ESRD Kidney Failure
< 15
> stage 3 = 4,700 PMP
RRT V แอ, CAPD
Prevalence per adult population age > 20
AMD 2002; 39 ( Suppl 1) : ร49.
1
2
3
4
5
*

NDT Advance Access published January 22, 2010
Nephrol Dial Transplant (2009) l of 9 _
I0.l093.tadt.gfp669
Oi l Ji
Original Article HctrtwoloqY Ototyrti Ifantptentatwn
Prevalence and risk factors of chronic kidney disease in the Thai adult population: Thai SEEK study
NDI
ฯ cptirolMjy Watyjb Iransptontatk
Atiporn Ingsathit1, Ammarin Thakkinstian1, Amnart Chaiprascrt2, Pornpcn Sangthawan3,
Pongsathom Gojascni4, Kriwiporn Kiattisunthorn5, Lccna Ongaiyooth 5, Somlak Vanavanan6,
Dhavoc Sirivones7, Prapaipim Thirakhupt8, Bharati Mittal9, Ajay K, Singh1′ and the Thai-SEEK Group

Prevalence studies in Thailand
Author, year Subject Number CKD stage (%] MDRD
1 II III IV V
Domrongkitchaiporn ร et al,
1997 EGAT
Age 55(5.1) Male 75.9% 2,967 NA NA 6.4 0.2 0.2
Chittinandana A et al,
2002 RTAF
Age 45.7(8) Male 82% 15,612 0.8 0.7 2.9 0.1 0.06
Inter ASIA,
2000 General population Age 50.5(1.5) Male 48% 5,146 NA NA 13.2 0.61 NA
Thai SEEK project, Ingsathit A, et al, 2009 General
population
Age 45.3 (15.4) Male 45.3% 3,459 3.3 5.6 f 7.5 0.8
8.6 0.3\
CKD awareness = 1.9% among stages 1-4

NORMAL
Presence of risk factor
I*
Primary prevention
Renal Damage ( Nephropathy)
I— IVI
“L *
Microalbuminuria / proteinuria
GFR
Secondary prevention
Progressive Renal Damage (CKD progression )
ESRD ( pre-dialysis ) _► RRT ( HD, PD, KTx )

Conceptual model of the
course of chronic kidney
disease (CKD)
Screening for CKD risk factors
CKD risk factor reduction. Screening for CKD.
Dx + Rx of comorbid conditions. Rx to slow Progression.
Estimate Replacement rate of by dialysis progression. & transplant Treat complications.
Prepare for replacement.
Levey AS, etal. Kl 2005; 67: 2089-100.
– Glycemic control in DM
– Blood pressure control in hypertensive pts.
-Relieving obstruction
– Rx of glomerulonephritis
– iQnmunologic damage
– i proteinuria
– Rx of infection

Overall Risk Factors for CKD Progression
1. Poor glycemic control
2. Albuminuria & Proteinuria
3. BP control & RAAS inhibition
4. Baseline kidney function
5. Drugs (ASA, NSAID) & radio-contrast,
6. Metabolic acidosis
7. Acute kidney injury
8. Diet
9. Infection (local & systemic)
10. Kidney stones
11. Genetics & Races

The NEW ENGLAND JOURNAL of MEDICINE
EStA0L[SH££i [ร’ lSli DECEiVlflHft. 22> 20บ5 VOL. 3S3 S’O. i*
Intensive Diabetes Treatment and Cardiovascular Disease
ill Patients with Type 1 Diabetes
The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC} Study Research Group*
DCCT / EDIC Group 1441 T1DM F/U 17 yrs. HbA-iC : Intensive = 7.4% Conventional = 9.1%

Table 1. Clinical! Characteristics of the วCCT/ED c Cohort ± (10 yrs.) (17 yrs.)
Character Stic. DCCT at Baseline (19S3-19B9) End of DCCT (1993) Year 11 oFEDIC (20D4)j-
Intensive Corventional Intensive Conventional Inrtenrsive Convisntiorsl
Trea:rren: Treatment Trea:rren: Treatment Trea:rren: TreaTrrent
(N-711) (N = 730) {N=G9&) (N = 723) {N = 593) {N = 559)
Age (yr) 27±7 27±7 34i7 33-7 4 5 ±7 45±7
Fa-ria e sax {%) 49 46 43 46 43 46
Re:’ทะ;วa:hy a: tas-E -le fK) 51 43 — — — —
Dura:’□า cf ciaDetes tyr) bi4 5±A 12±5 1Z±5 24*5 2 3 ±5
Cjrre’ไt cigararte smoker 19 19 20 20 14 11
XTjrnin excreti □า ra:-e (mg/^4~h7r^ > 16.4±19.ร 15-5*17.9 c^£s±197.6 75.4±44lTrj^; ><^54^±375.9 llE.4±57Ea^
A ะ; jmin excreticn ra:e
ร4C mg/24 hr 5 5 7 1 ท 9 17*
23CO mg/24 hr c 0 : ท 2 *+
Serumcreatiาhea2 Tig;’c c 0 0 0 c 25
{177f/rral/liter) (%)
D al;rไsi5 nr t’anspla า tat on ever {%) c 0 0 0 1 1

Intensive Blood Glucose Control and Vascular
Outcomes in Patients with Type 2 Diabetes
The ADVANCE Call .a bo rat ive Group* _ _1 _10 _ _
NEJM 2008; 358: 2560.

11,140 T2DM : intensive vs. std. BS control, HbA.,C 6.5 vs. 7.3%,
F/U 5 yrs.
Subgroup
I liter 5 ve รใรเา da rd
Control Cc-‘tnil
(N=S571) {N = HS9;
rturttbt? pStlMii (โ] Tic ft!
Cambinfe: major muowUAdir
ari miSravaSiiJulariYPrti 16.1} Ilia (10.0)
Mijdr โ-ทatrijvasdj ar ivprti 5 57 100) 590 (lO.fi)
\Dr”ata Ml 153 2.7) 156 (l.i|
‘ฯ Dnfalal ilrcki 214 3.3) 255 (3.i|
2sarh โทว -๚ iirdi.ivaSijISr’.ia Jj=i 253 |4.5) 2i9 (5.1|
Major โ-ทieravaseular ivenu 526(5.*) 6D5 (10.9)
%EW Dr wariE- rj repnm:athy 230 |4.1) 292 เ๚.2.1
\EW Dr wariE1- rg rer -apathy 331 |6.a; 349 (6.31
SiCondar? End Pairtl
Death torn J.r> ;a-i: «94 1*9) 533 (9.6|
Major coronal-.- E’.er 11 310 ]5.6) 337 (6.11
All cororjr^ £v4rtl 560 11D.11 572 (10.3)
Major CenebrouJSiLljr Events US [4.3) 2-1: f4.4|
h| CErtbrovaiiular Evints 352 |6.3) 317 (5.&I
h=jrL’ ji Lr* 220 p.9) 231 (4.1)
-ar pheral Yilcular is1:■ไร 343 6.2) 365 (6.61
^L-ca*“iuvai:Lldf B’r-I’ti— 1231 21.1} 1249 (22.4)
^M<io«SrSei [ฯ iiroj bLi’iirur 1312. 23.71 1434 (15.7)
3C33 54-4) 3G15 |54 lj
N ะfir AC’!:ni”j ๆ■iurDpany 1353 41.11 2311 (41.5)
Cafrtirivi drilini S95 16.11 911 (15.4)
Ccnirtii 61 11) 4 ร (D.9|
Haipi:a iiation 1501. 44.&I 23S1 (4li)
hazard Ratio (95% q;
Intensive better
รุ^
Setts’
Re ativ-e Hisk Reduction pSft’EI)
£ircfni
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Standard
Better
Effect of intensive treatment of hyperglycaemia on
microvascular outcomes in type 2 diabetes: an analysis
of the ACCORD randomised trial Lancet 2010; 376:419.
10,251 T2DM ะ intensive vs. std. BS control, HbA.,C 6.3 vs. 7.2%,
F/U 8 yrs.

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Trials of glucose control on renal outcome in DM
DM
duration Archived Microalb. duration (MA) eGFR or S.cr
T,DM
DCCT 1-5 yr 7.2 vs. 9.1% 1 risk in IC No. diff.
AER < 40 mg/d
T?DM
Advance 8 6.5 vs. 7.3%
Accord 10 6.4 vs. 7.5% risk of MA No. diff.
& Mac. A.
VADT 11.5 6.9 vs. 8.4% -J
IC = Intensive blood sugar control
= Early termination of the study due to inc. MR in the arm

Guideline ๐ท glvcemic control in DM-CKD (NST – CKD guideline. 2552)
– Target FBS = 90-130, A1C < 7.0%
– If S.cr > 1.4 mg/dl No. = Metformin, &
chlorpropamide
– If s.cr > 3, eGFR < 30 ml / min /1.73 m2
no glybenclamide, no alpha-glucosidase inhibitor no nateglimide
– If s.cr > 5, eGFR < 10 ml / min /1.73 m2
prefer insulin

Overall Risk Factors for CKD Progression
1. Poor glycemic control
2. Albuminuria & Proteinuria
3. BP control & RAAS inhibition
4. Baseline kidney function
5. Drugs (ASA, NSAID) & radio-contrast,
5. Metabolic acidosis
6. Acute kidney injury
7. Diet
8. Infection (local & systemic)
9. Kidney stones
10. Genetics & Races

Cumulative incidence of ESKD in CKD patients
15 –
10 –
5 –

0 1 a 3 4 & 6 7 ร 3 10 11 12 13 14 15 16 17
Time after screering1 yrs
Clin Exp Nephrol 2009; 13: 203-204.

Lower estimated GFR and higher albuminuria are associated with adverse kidney outcomes.
A collaborative meta-analysis of general
and high-risk population cohorts Kl 2011; 80:93.
Ron T, Gansevoort1. Kunihiro Matsushita2, Marlje van der Velde1, Brad c. Astor2. Mark Woodward3,
Andrew ร. Levey4, Paul E. de Jong . Josef Coresh2 and the Chronic Kidney Disease
ระ: pop (0P, = 845,125 High risk (HR) -173,892
ESF c in GP conn-la ESFC in HR coficla

eGFR. mv’mir pe_ 1 73 1-2 eGFR, m/min EB” 1.73 ms
ES RD เา GP cohortE ESRD า HP. CDrertE

Proteinuria Reduction and Progression to Renal Failure in Patients With Type 2 Diabetes Mellitus and Overt Nephropathy
Atkins RC, et al. AJKD 2005; 45: 281
Proportion with renal outcome

months

Proteinuria in diabetic kidney disease: A mechanistic viewpoint
Lyzosome Amino acids
‘”” ‘ neabsortied
Iff Cl [ptt พ
— 0 i ‘***•+ Albumin
rtv }าIพ)JifnQjji plfyf
0 ■> ^ ^ 0 เ^
Parietal epithelial cell
Proxiimal tLibulsr cell
Glomerular endothelial cell
Glomerular basemen membrane
Jefferson JA, et al. Kl 2008; 74: 22-36.

Schematic summary of some of the pathways and mediators that are believed to be involved in proteinuria-induced tubulointerstitial injury.
Zandi-Nejad K, et al. Kl 2004; 66 (Suppl 92): S80.

Overall Risk Factors for CKD Progression
1. Poor glycemic control
2. Albuminuria & Proteinuria
3. BP control & RAAS inhibition
4. Baseline kidney function
5. Drugs (ASA, NSAID) & radio-contrast,
6. Metabolic acidosis
7. Acute kidney injury
8. Diet
9. Infection (local & systemic)
10. Kidney stones
11. Genetics & Races

Intensive Blood’Pressure Control in Hypertensive Chronic Kidney Disease
£

I
1
3
Trial Phase
Trial and Cohort Phases
Cohort Phase
Standard control Intensive control
P:C Ratio >0.22
Standard control 176
เทtensive control 181
P:C Ratio sO.22
Standard control 376
Intensive control 357
Standard
Uprot./Ucr >022
Intensive
Composite เ๐ outcome
(Scr X 2, ESRD or Death)
L^n^’uprot./ucr < 0.22
10
Follow-up Year
16 ร
172
134
151
113
128
81
109
66
87
45
67
32
56
26
47
22
40
13
25
373 362 353 332 302 267 234 214 196 128 350 335 321 306 282 254 228 206 189 128
Standard control BP = 140/90 MAP = 105 Appel LJ, etal. NEJM 2010: 363: 918. Intensive control BP = <125/75 MAP = 92 ‘ ’

Systematic Review: Blood Pressure Target in Chronic Kidney Disease and Proteinuria as an Effect Modifier
Aihlsh Upadhyay. MD; Amy EaHey. BS; shana M. Haynes. DWSc: and katrln uhllg. MD. MS
Conclusion: Available evidence is inconclusive but dose not prove that a blood pressure target of less than 130/80 mm Hg improves clinical outcomes more than a target of less than 140/90 mm Hg in adults with CKD. Whether a lower target benefits patients with proteinuria greater than 300 to 1000 mg/d requires further study.
Ann Intern Med 2011; 154: 541.

Hemodynamic changes in Diabetic Nephropathy
iEffectofRAS
1 Blockade
– Systemic hypertension
– Glomerular hyperfiltration
– Mechanical stretch of GBM &
Mesangial structure
– Tubulo-interstitial hypoperfusion
& ischemia
Kl 1997; 52: 985.
J Pharmacol Sci 2009; 109:24.

Metabolic deranaement in diabetic nephropath
Podocytes :
– effacement
– apoptosis
– IHSPG
– loss of -ve
charge at GBM
– Ja3pi integrin
– loss of nephrin
– Detachment

ACEI/ARB
T-I fibrosis
Glomerular
sclerosis
Proteinuria
GBM thickening
& adhesion to
Bowman’s capsule
Slit diaphragm widening
Mesang. Matrix deposition
Am J Physiol Renal Physiol 2006; 291: F1308.
Semin Nephron 2003: 23: 532.

Progression Risk, Urinary Protein Excretion, and Treatment Effects of Angiotensin-Converting Enzyme Inhibitors in Nondiabetic Kidney Disease
Rate of combined outcome (kidney failure or s.cr X 2) per year
Risk profiles
1. Age
2. Genger
3. S.cr
4. SBP
5. Proteinuria
Outcomes by Treatment in Risk Quartiles
30% reduction

12 3 4
Risk Quartilos
Figure ใ. Risk-stratified oiitcome rates (doubling of baseline plasma creatinine or kidney failure with need for dialysis). This graph depicts outcome rates in equal-sized quartiles of pre¬dicted risk on the basis of the multivariable model, from low- risk patients (quartile 1) to high-risk patients (quartile 4), in patients randomly assigned to control therapy (□) and angio- tens in-converting enzyme inhibitor (ACEI) therapy (■).
Kent DM, et al. JASN 2007; 18:1959 – 1965.

020-1
0
0 0.15
‘ร


01
1
1
0 10-
005-
000
No. at Risk
Telmisdrtan Ramipril Telmisjrtan plus ramipril
■Telmisarun 80 ทา9 I day Ramipril 10 mg/ day
Teimisarttrt plus ramipril
0 1 2 3 4 5
Years of FolloW’Up
«542 8177 7778 7420 7051 1687
ร 576 8214 7832 7472 7093 1703
8502 8133 7738 7375 7022 1718
Figure 1. Kaplan-Meier Curves for the Primary Outcome in the Three Study Groups.
The composite primary outcome was death from cardiovascular causes, myocardial infarction, stroke, or hospitalization for heart failure.
NEJM 2008; 358:1547 – 1559.

Renal outcomes with telmisartan, ramipril, or both, in people at high vascular risk (the ONTARGET study): a multicentre, randomised, double-blind, controlled trial

Time period
Johannes F E Mann, et al. Lancet 2008; 372:547 – 553.

Aldosterone Antagonists for Preventing the Progression of Chronic Kidney Disease: A Systematic Review and Meta-analysis
Study or $JbcrouP Ajdoitcrooc antafoniit M«r 50 Tot* Mean Ffacebo
50 ToUl Wci*N 1,™“ใ, Mean MltftiKt IV, Random. 95% a
Bianchi 2006 0-89 0.54 83 2.11 0.72 82 27.8% •1.22 l-Ml, *1.031 -•-
Ch-vsolonroj 2006 2J04 1.9 น 2.97 3.7 10 3.1% -0.93 1-3.48. 1.621 —
Furamitjj 2008 0.6 0.38 16 1.39 2.3 16 10.3% -0.79 [*1.97 0.39J ..
Roswng 2005 1JQ6 0 20 1.56 0 20 Net«’รใเททatfte
Sc^ijoed: 2005 0.7? 0.54 20 1J02 0.73 20 24.2% -075 a 15]
ScftfOed: 2006 3.06 1.74 20 4.2 1.82 20 11.2% •1.14 1-2.24. -0.041
Tyt>c4 2008 0.51 0.42 28 1.21 0.84 18 2.4% -0.701-1.13 -0.27]
Total (95% Cl) 187 185 100,0 -0^0 1-1,27, -0,331
Heto’ogtneity: r»u* • 0.20. CM – 20.56. ๙» • (P-O.OOIO);!’ – 76% 1 1 1 1
T*u ttt wtrill ๙‘พ 2 – 3.33 (p- 0.0009} J •2 3 2 4
Favour* atdo ฬนเernt
Favour* ffecrbo
Study or Subcroup Mean erone ant amount
SD Total Mean Placebo
SO Total Weight Mean Difference IV. Ran<km, 95% Cl
9’anchi 2006 58 J6 23.68 83 56.4 2082 82 35.2% 2.20 [-4.60. 90)0]
Chry*o«omou 2006 &9.7 0 11 65.2 0 10 NOT es.timatlt>
Rossing ?005 71 26.82 20 74 26.82 20 5.9% -3.00[-19.fi?. 13.6?]
Schjowil 2005 81 26.82 20 85 26.82 20 5.9% -1.00 -20X2. 12X2
Schjoedt 2006 62 8.94 20 64 SL94 20 53.0% -2.00 [7.54, 3.54]
Total (95% Cl) 154 152 100.0% -0.70 1-4.73, 3.341
Heterogeneity: Tan’ – 0,00. ChiJ = 1.13, dt = (P=Q.77);r > 0%
lest Id’ ovf’all cflad z – 0.34 (p- 0.73)
Mean Difference IV, Random. 95% a
r
T
T

-20 -10 0 Favour* aide *(iUfooi>t
10 20 Favour* pjaccbo
Navaneethan SD, et al. CJASN 2009; 4: 542 – 551.

Overall Risk Factors for CKD Progression
1. Poor glycemic control
2. Albuminuria & Proteinuria
3. BP control & RAAS inhibition
4. Baseline kidney function
5. Drugs (ASA, NSAID) & radio-contrast,
6. Metabolic acidosis
7. Acute kidney injury
8. Diet
9. Infection (local & systemic)
10. Kidney stones
11. Genetics & Races

Lower estimated GFR and higher albuminuria are associated with adverse kidney outcomes.
A collaborative meta-analysis of general
and high-risk population cohorts Kl 2011; 80:93.
Ron T, Gansevoort1. Kunihiro Matsushita2, Marlje van der Velde1, Brad c. Astor2. Mark Woodward3,
Andrew ร. Levey4, Paul E. de Jong . Josef Coresh2 and the Chronic Kidney Disease
ระ: pop (0P, = 845,125 High risk (HR) -173,892
ESF c in GP conn-la ESFC in HR coficla

eGFR. mv’mir pa -1 73 1-2 eGFR, m/min EB” 1.73 ms
ES RD เา GP cohortE ESRD า HF. CDrertE

Percentage 60- Not Reaching the Primary End point 40
20-
Scr❤
Group 1, benazepril 20 ทาฐ
Group 2, benazepnl 20 ทาฐ
ScF3-5
Group 2, placebo
6 -_2 1 24 Months 36
No. at Risk
Gnoup 1, benazepril ‘.02 96 84 40
Group 2, benazepril 107 96 73 32
Gnoup 2, placebo ‘.OS ss 59 22
Fie lire 2. Kaplan-Meier Estimates of the Percentage of Patients Not Reach¬ing the Primary Composite End Point of a Doubling of the Serum Creatinine Level, End-Stage Renal Disease, or Death.
Group 1 had 5 serum crearimne level of 1.5 to 3.0 mg per deciliter, and group 2 had J serum creatinine level <-/ 3.1 70 5.0 ms per deciliter at basel ine.
NEJM 2006; 354: 131-40.

Overall Risk Factors for CKD Progression
1. Poor glycemic control
2. Albuminuria & Proteinuria
3. BP control & RAAS inhibition
4. Baseline kidney function
5. Drugs (ASA, NSAID) & radio-contrast,
6. Metabolic acidosis
7. Acute kidney injury
8. Diet
9. Infection (local & systemic)
10. Kidney stones
11. Genetics & Races

Daily oral sodium bicarbonate preserves glomerular filtration rate by slowing its decline in early hypertensive nephropathy
Mahajan A, et al. Kl 2010; 78:303.
1.15
Per 105
70 –

Year

Serum Bicarbonate and Mortality in
Stage 3 and Stage 4 Chronic Kidney
Disease Navaneethan SD, etal. CJASN 2011; 6: 2395.

Bicarbonate
23-32
<23
>32
0
1 2 3
Years of Follow Up
4

Men ft eGFR
Acute kidney injury predicts CKD
progression
Chawla, et al. Kl2011; 79:1361
100. Mean eGFR
90
J
Mean eGFR
A <61
// \Nt- 61-79
Vulfltf
/ \
r \
Tfrftiiat >79
A
Time
Jp Jt
/ ^VV-‘V
Time

Overall Risk Factors for CKD Progression
1. Poor glycemic control
2. Albuminuria & Proteinuria
3. BP control & RAAS inhibition
4. Baseline kidney function
5. Drugs (ASA, NSAID) & radio-contrast,
6. Metabolic acidosis
7. Acute kidney injury
8. Diet ( protein, salt, phosphate )
9. Infection (local & systemic)
10. Kidney stones
11. Genetics & Races

Recommend lifestyle modificationร
1. I Salt intake 6 g / day
2. t Vegetables & fruits
3. I Cholesterol & saturated fatty acid
4. BMI <25
5. Exercise
6. I Alcohol
7. No smoking
Clin Exp Nephrol 2009; 13: 231-233.

E 111!CL of Modest Suit Kcductiun (in Bluud Pressure Urlnmy Albumin, and Pulse Wave Velocity in พ hite, Black, and Asiiln Mild Hypertensives
Feng J. He, Vlaciei Marciniak, Elisabeth Visagie, Nirmaki D. Mcirkandu, Vidya Anand, R. Neil Dalton and Graham A. MacGregor

Hypertension 2009; 54. 482-8.

Cumulative Incidence of Renal Failure or Death
80
60
Mean Total Protein Intake During Follow-Up
— <.62 g/kg/d
— .62-.68 g/kg/d
— .68-.75 g/kg/d i .75 g/kg/d
12 16 20 24 28
Follow-Up Time (months)
32 36
> .75 g/Kg/d
< .62
.62 – .68
.68 – .75
Fig 3. Relationship of
achieved protein intake to
the risk of renal failure or
death. Each curve is the cu-
mulative incidence of renal
failure or death for sub-
groups of patients with dif-
40 ferent values for follow-up
total protein intake.

Low protein diets for chronic kidney disease in non diabetic
adults (Review)
0.6
0.3-0.6
FOLIC|LIC I>, Lavillc M, Rois.se! JP
Study or iubsroup
Low protein n/N
Higher protein
FL’N
Piisk Ratio M-HRandofu95K Cl
”Afe i^-.t
Risk Ratio M-H.Random.95% Cl
I 0.6 £,■’k£..’id versus higher protein det
*๗! 991
MDRD 1994
Williams 199 I
Subtotal (95% Cl j
Total events: 5-1 (J-OW FHTOtfiin;, 70 (Hijhsr proten)
Heterogeneity: TauJ = 0.0 Chi- = I 37, df= 2 CP = ‘ว.5อ;:r; p =0.096
TesrfTF^iratMfect z = 1.65 (P = 0.099)
‘ 0.1 – o.t g/kg/d versus highei7’fi=e protein diets
21/230 32/236 157% 0.67 [ 040. บ 3
10/291 27/294 129% 0.67 [ 0.18. 1.20
12^31 11/32 95% I.C6 [ 0.55. 204
554 >62 ♦ 38.3 % 0.76 [ 0->4, 1.05
T5iafiriap=terr£i05 9/212 11/211
■di lorio 2C03 iio 7/10
Ihle 1909 4/34 11/30
Jungei-S 1 957 5/10 7/9
Mlk.y 1 997 11/25 17/25
Mire MU 2007 1/27 7/2 b
Rz-sman 1’^0’V 30/130 34/117
ibtotjl (95% Cl) 44S 436
Total events: 62 Q-OW protein), ,ไ?0 (Higher proten]
Heterogene iti-ไ TauJ =0.01; ChiJ = i ll, df = 6 (P = 0.19); lJ =4%
T«t ■fz-r oderail effect z = 3 31 ;p = 0.00092)
Total (95% Cl) 1002 90S
Total-events: I 13 (I-OLV pnot-Eri), 168 (Higher protein)
Heterogeneity TauJ = 0.0 Chi1 = a20. df = 9 CP = 0.5 I); lJ =0.0?i Test for o-^i-all effect z = 2 68 yp = 000024)

6 2% 25% 4 1 % ■54% I5.fi %
1.0 St
23 7%
61.7%
100.0 %
Q69 [ 0.30, 1.55 ]
Q29 [ บิ, 06. 1.05 ]
0.34 [0 12. 095 ]
Q64 [ 0 32, 1.31 ]
Q65 [ 0.3.9, 1.09 ]
0.14 [ 002, 1.04 ] 0.79 [ 0 52. 1.21 ]
0.63 [ 0.4S, 0.S3 ]
0.6s [ 0.>5, 0.S4 ]
Less renal death on low protein โ!Le^hsonhsh The Cochrane 2009, Issue 3
GUIDELINE 5: NUTRITIONAL MANAGEMENT IN DIABETES AND CHRONIC KIDNEY DISEASE
+
IStnttHMItn’เพ MdllSIU nnwiwwlnn

r
National Kidney Foundation
KDOQI
KIDNEY DISEASE
OUTCOMES
QUALITY INITIATIVE
Clinical Practice Guidelines and Clinical Practice Recommendations for DIABETES AND CHRONIC KIDNEY DISEASE
VOL 49, NO 2, SUPPL 2 FEBRUARY 2007
Notional Kidney Foundation’
Management of diabetes and CKD should include nutritional intervention. Dietary modi-fications may reduce progression of CKD.
5.1 Target dietary protein intake for people with diabetes and CKD stages 1-4 should be the RDA of 0.8 g/kg body weight per day. (B)
RATIONALE
A dietary protein intake of 0.8 g/kg body weight per day, the RDA for this macronutrient, is a level that has been achieved in studies of diabetes and CKD. Reduction in albuminuria and stabilization of kidney function have been reported with dietary protein intake at the RDA level. Nutrition surveys indicate that most people eat in excess of the RDA for dietary protein. (Moderate)
W.B. Saunders an Imprint of Elsevier

Lower estimated glomerular filtration rate and higher albuminuria are associated with all-cause and cardiovascular mortality. A collaborative meta-analysis of high-risk population cohorts
Marije van der Velde1, Kunihiro Matsushita2, Josef Coresh2, Brad c. Astor2, Mark Woodward3,
Andrew ร. Levey4, Paul E. de Jong’, Ron T. Gansevoort1 and the Chronic Kidney Disease
Prognosis Consortium 1^1 2011′ 79′ 1341
All-cause mortality in high-risk cohorts พrth ACR data

All-cause mortality in high-risk cohorts with ACR data

eGFR ทา[■”ทาin per 1.73 ทาs
ACR: mg/g
Cardiovascular mortality in high-risk cohorts with ACR data

Cardiovascular mortality in high-risk cohorts with ACR data

eGFR, ml/min per 1.73 m£
ACR, mg/g

AMI
Effect of calcium supplements on risk of myocardial
infarction and cardiovascular events: meta-analysis
Stroke
1 ร
2
c 4
® 3
I
Hazard ratio 1,31 (9S%CI 1.0? to 1.6 โ), FM).03&
Calcium
Placebo
.r
Placebo
No at risk
Cald แทๆ
Placebo
4097 3870 3539 2670 12 9 4 373 4054 3B65 35B8 2728 1320 388
Com p D รโน ๙ myocard ๒ LI nf arc tlo n, ร troka 10 r ร udd« ท death


9
a
I

No at risk
Calcium
Placcbo
4097
4054
3648 3S17 5846 3566
263S
2692
1271
1292
Years
360
176
Hazard ratio 1.20 (?$■%Cl 0.96 to 1.so),P=0.11

DCiith
1 แ
15¬
12
9
6
3
0

4 ร
Years
Bolland MJ, et al. BMJ 2010; 341: 3691.
409? 3865 3541 2659 1294 171 40 S4 3859 3589 2730 1312 366
4097 3889 3560 2699 1322 369 4054 3875 3618 2767 1340 399

Novel risk factors for CKD (2)
– Obesity ( + ), obstructive sleep apnea
– Periodontal disease
– Low birth weight and nephron numbers.
– Low nephron no. —► salt-sensitive HT
– Low birth weight and CKD

TGF-61
I
Whtl/p-cafenin
Podocyte
stress
Progen ftor-cei I activation
Glomerular
injury
Glomerular
regeneration
Writ = Wingless + Integrin 1
Kl 2011; 80: 1117.

^ Pericyte shedding
\ \
Kl 2011; 80: 1119.
%
%
BM~denved

EndMT
VJ

Myofibro blasts in renal interstitium
Vi

o
o
จ’
fS
Prolifer at ion (resident fibroblasts)
EMT
(epithelial-to-mesenchymal transdifferentiation )

Promising intervention to delay CKD
– Renin inhibitor (ariskiren) ะ i RAS, I U.Alb / cr ratio
– Pirfenidone : I TGF-beta synthesis,
I TNG-alpha signals, ROS scavenger
– Low MW heparin ะ restore negative charge on cell
surfaces
I proteininuria, anti-prolife
– Pentoxifylline ะ I proteinuria, I urine TNF-alpha
– Ruboxistaurine mesylate ะ protein kinase c (PKC) –
beta inhibitor
– AVP-receptor antagonists in ADPKD
– Sulodexide

CKD svstem เทลทลqement
1. Create awareness (Preventive > Curative)
– health care personnel ? weak
– public ? weak
2. Screening
– high nsk ? late referral
– tool ? s.cr
? eGFR ? IT
3. Patient counseling & Empowerment
– allied personnel ? who ? when
? where ? how ? work load
4. Direct clinical care
– MD vs. allied personnel
5. Research
– IT, Registry

Effectiveness of community-based integrated CKD care program versus standard care program in Thailand.
Teerayut Jiamjariyaporn,
Bhumirajanagarindra Kidney Institute, Bangkok.
Study design and enrollment
This is a community-based cluster randomized controlled trial to be conducted at 2 districts ofKamphaenjs Phet province, which is about 400 kilometers north of Bangkok.
WvVvVv^WvWvWvW- VAAAAAA^ 1 ‘—1
นพทย
พยาบาล
โภซนาก%
เภลิชกร
นกกาย/ทพ
ทมปฎิบตงาน CKD clinic

อบรม CKD guid

elines

^ c-
ทซน
โ o
ร่ร่ะร่^ C พร^.”■?*

อบรมผู้ป้วฮเ

เละผู้ปรุงอาทาร

อบรมผู้ป่วยและผู้ปรุงอาหาร

, -1 * ■*

Knowledge
Budget
Personnel

power
KD Team
Awareness Screening Counseling Direct care Research

Home care

 Foot Patch มีอย.ต้อง Mamae

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