การใชย้าเพอื่รกัษาและ...
TRANSCRIPT
-
1
:
2
-
,
(metabolic
acidosis) (hyperK,
hypocalcemia & hyperphosphatemia
hyperparathyroidism)
3
Confusion, Insomnia, Depression
CVD
Anemia Hyperpigment, Pruritus
Bone disease
Infertile, loss of libido
N/V, Anorexia
Polyneuropathy
Acid/base, , Fluid- imbalance
-
,
HCTZ, furosemide, spironolactone
5
> 100
6
-
(metabolic acidosis)
parathyoid hormone (PTH)
7
8
-
(metabolic acidosis)
sodium
bicarbonate
9
Sodium bicarbonate
GI pH
enteric coated formulation
10
-
Hyperkalemia
ion exchange resin potassium
Calcium polystyrene (Kalimate
-
-
11
Hyperphosphatemia
2 hyperparathyroidism
osteodystrophy
anemia
HTN
calcification in vascular or soft tissue
CVD
12
-
13
Bone marrow fibrosis decreased erythropoiesis
14
Aluminium-based : aluminium hydroxide
Calcium-based : calcium carbonate, calcium acetate, calcium
citrate
Aluminium- and calcium-free phosphate binders
: sevelamer, lanthanum
-
15
PTH
calcification
16
calcium level mg dL calcium based phosphate binder
noncalcium nonaluminium based
phosphate binder
calcium level mg dL
PTH pg mL
Ca x PO > 55 mg2/dl2
vascular
calcification
soft tissue calcification
calcium based phosphate
binder
phosphate level
mg dL
Ca x PO > 55 mg2/dl2
aluminium based phosphate binder
-
17
Hyperparathyroidism ( iPTH > 300 (500) pg/ mL)
1. Correct calcium and phosphate level
2. Vitamin D or vitamin D analogue
- 1,25- -dihydroxyvitamin D3 (Calcitriol)
- vitamin D analogue: 1- -hydroxyvitamin D3
(alfacalcidol)
- iPTH
- Adverse effect: hypercalcemia, hyperphosphatemia
( ./ . *
( ./ .
( .2/ .2
(
/
K/DOQI
CKD 3 2.7 4.6 8.4 10.2 - 35 - 70
CKD 4 - 70 110
CKD
/dialysis
3.5 5.5 8.4 9.5 < 55 150 300
KDIGO
CKD G5/G5D Normal range Normal
range
- 2-9 * Normal
range
150 600 18
-
19
20
-
21
Conclusion: Alfacalcidol can be used to control secondary hyperparathyroidism at doses of 1.5 2.0 times that of calcitriol.
The two drugs are equally and lead to similar changes in calcium and phosphorus.
Nephrology 16 (2011) 277 284
22
Insufficient EPO
Iron deficiency
Hyperparathyroidism
Inflammation or
infection
Inadequate dialysis
Aluminium toxicity
Vitamin B12 or folate def.
Shortened red cell survival
Carnitine deficiency
ACEI
Hyporesponse to EPO
-
Erythropoietin
24
Prim Care Clin Office Pract 2008;35:329 44. Semin Nephrol 2006; 26:313-8.
Continuous Erythropoietin Receptor Activator
Erythropoiesis stimulating agents: ESAs
-
Continuous Erythropoietin Receptor Activator(CERA)
26
Hgb
20-50 IU
- EPO-alfa
EPO-beta)
IV SC
erythropoietin
-
ESA dose > IU/
Hgb
ESA
28
Adverse Effects of ESAs:
Flu like symptom (first use)
Hypertension
Increased risk of cardiovascular events;
heart attack, HF, blood clots, stroke and
death.
Pure red cell aplasia (PRCA)
Seizure
Kidney International 2008;74(Suppl 110):S12 S18.
-
29
ESAs:
30
-
: ferrous sulfate, ferrous fumarate
- elemental iron 200 mg/d
- malabsorption, intolerance (N/V, constipation),
noncompliance, excessive blood loss
31
32
Composition
Molecular size
Degradation Kinetics (rate of iron dissociation from
the complex)
Side effect profiles
anaphylaxis, anaphylactoid (iron dextran)
Test dose (25 mg IV infusion)
-
33
Comparison of intravenous iron products
Products
Properties
Iron Dextran
Sodium Ferric Guconate Complex (SFGC)
Iron Sucrose
Molecular size
(Kilodaltons) Low MW ~ 96
High MW ~ 267 ~ 38 ~ 43
rate of iron
dissociation from the complex
slow rapid
intermediate
Bloodstream t1/2
(hr) 40-60 1 6
Modified from Yee and Besarb AJKD 2002; vol 40 (6): 1111-1121
and P&T News September/October 2001 Virtual Hospital
34
-
traditional risk factor
nontraditional -related risk factor
Risk factors of CVD in CKD
Share etiology
-
Prevention and Treatment
BP < 140/90
BP < 1 / 0
nondipping
Noctural long acting Anti-HTN
PREFER RAS inhibitors
-
Anti-HTN drugs
ACEI: captopril, enalapril, ramipril
ARB: losartan, valsartan
Beta-blocker: propranolol, atenolol (unchanged renal
excreted ~ 40 %) metoprolol, carvedilol
CCB: nifedipine, amlodipine, felodipine
Alpha-blocker: prazosin, doxazosin
Vasodilator: hydralazine, minoxidil
39
statin HD patients 4D
AURORA
Subgroup analysis non-dialysis
patients JUPITER, ASCOT-LLA, CARE
HPS
-
Participants: NondialysisCKD (M: Scr > 1.7 mg%; F Scr > 1.3 mg%,
HD, PD patients Beneficial for nondialysis patients only
Statins
(primary prophylaxis)
50
50
42
-
:
43
44
-
45
:
46
-
47
Susceptibility Increased susceptibility to kidney damage
Advanced age
Reduced kidney mass and low birth weight
Racial/ethnic minority
Family history
Initiation Directly initiate kidney damage
Diabetes mellitus
Hypertension
Glomerulonephritis
Drug toxicity
Urinary stone
Autoimmune disease
Progression Cause worsening kidney damage and faster decline in
kidney function after initiation of kidney damage
Glycemia (among diabetic patients)
Hypertension
Proteinuria
Smoking
Obesity
47
CKD Risk Factors
Service plan
-
50
BP Control Prevents CKD Progression
GFR Decline
(mL/min/y)
0
-2
-4
-6
-8
-10
-12
-14
MAP (mm Hg)
95 98 101 107 104 110 113 116 119
r=0.69; P
-
Proteinuria Dipstick: Semi-quantitative testing
52
Definition of Albuminuria
Normoalbuminuria Moderately increase
albuminuria (Microalbuminuria)
Macroalbuminuria
(Nephropathy)
Detected by
dipstick
No No
(Yes, new
dipstick)
Yes
Urine Albumin
(mg/day)
< 30 30-300 > 300
Urine
Albumin-to-
creatinine
ratio, ACR
(mg/g Cr)
< 30 30 299 > 300 mg
Renal Risk No Marker of future nephropathy
Marker of
progressive
renal disease
-
53
Development of Macroalbuminuria Heralds Rapid
Decline in Glomerular Filtration in Type II Diabetes
-50
-40
-30
-20
-10
0
1 1.5 2 2.5 3 3.5 4
Time years
Ch
an
ge
in
GF
R m
l/m
in
Microalbuminuria
Macroalbuminuria
Nelson RG. et al NEJM, 1996
54
Proteinuria Dual Significance
Proteinuria results from injury to glomerular
circulation
Increased proteinuria is associated with
progressive CKD
In diabetes and hypertension, proteinuria
signifies injury to the systemic circulation
Proteinuria is associated with increased CV risk
-
55
Development of Nephropathy
Jamison, Wilkinson. Nephrology, 1997.
TGF- : transforming growth factor TIMP: tissue inhibitors of metalloproteinases PAI plasminogen activator inhibitor
TGF- 1, TIMP-1, TIMP-2, PAI-1
Modification of CKD progression factors
MODIFICATION of RISK FACTORS
INTERVENSION GOAL
1. Hypertension Anti-HTN (prefer ACEI or ARB) albuminuria
mg/day
albuminuria < 30 mg/day
(need more data from SPRINT; be expected 2018)
Salt restriction < 1.5 g/day
2. Proteinuria Anti-HTN (prefer ACEI or ARB)
< 0.5 g/day
3. Hyperglycemia Tight glycemic control HgbA1C < 7 % CKD stage 4/5 < 8 %
-
Modification of CKD progression factors
MODIFICATION of RISK FACTORS
INTERVENSION GOAL
4. Dyslipidemia lipid lowering Therapy
LDL < 100 mg/dL
5. Protein load Protein restriction 0.8 g/kg/day in GFR < 30 mL/min/1.73 m2
6. Others:
smoking cessation, weight loss (if obese), sleep apnea, correction
or prevention of metabolic acidosis, nephrotoxic drug
avoidance esp. NSAIDs, prevent CVD, AKI
Ongoing or Further Studies
Endothelin anatagonists (avosentan, atrasentan)
Lowering serum uric acid level (uric acid
promote interstitial inflammation, inhibit endothelial nitric
oxide release, stimulate RAAS)
Anti-fibrotic agent
Pirfenidone interrupt transforming growth factor -B pathway
Doxycycline inhibit matrix metalloproteinases
Vitamin B target advanced glycation end products
-
59
Renin-Angiotensin System (RAS)
CAGE
Cathepsin G
Chymase
adapted from: Chung, Unger., Am J Hypertens 1999;12:150S 156S
CAGE: chymostatin sensitive AngII - generating enzyme
ONTARGET: The ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial
Will an ARB (telmisartan) be as effective and better tolerated?
Is the combination superior?
N Engl J Med 2008; 358:1547-1559
-
Reasons for Permanently Stopping Study Medications
Ram
N=8576
Ram + Tel
N=8502
Ram + Tel vs. Ram
RR P
Hypotension 149 406 2.75
-
Summary for RAS inhibitor
Normotensive DM patients
macroalbuminuria or microalbuminuria
should be treated with ACEI or ARB.
normoalbuminuria: ACEI/ARB not recommended
Combined RAAS blockade therapy not
recommended
AJKD 2012; 60(5): 850-866
-
ACEI/ARB
Evidence-Practice GAP undertreated
66
ACE/ARB
Check Cr and K+ within 7-14 days
Cr rise < 30% BP not achieved
No hyper K
Cr rise > 30%
STOP drugs
assess for bilateral RAS
Increase ACEI dose
Hyper K+
mild severe
Low K+ diet
Initiation of ACEI/ARB treatment
-
67
AKI (ARF) Prevention
Rationale
CKD pts at higher risk for AKI
AKI produces residual kidney damage
AKI often preventable
e.g. vol depletion, drug induced
nephropathy
PA McCullough, et al. Am J Med. 1997;103:368 375
L Gruberg, et al. J Am Coll Cardiol 2000;36:1542 1548
1. 25 %
cardiac output
ischemia
2.
3. 68
-
Nephrotoxicity from NSIADs
Acute or chronic renal impairment
Incidence of renal side effects - around 1 5 %1
1 Am J Med. 1999;106(5B):13S24S.
Clinical manifestations
Acute Kidney Injury (AKI)
Tubulointerstitial nephritis
TIN
Renal papillary necrosis
Salt Retention and Edema
Hyperkalemia
Hypertension
Worsening of Chronic
Kidney Disease (Acute on
CKD)
70
-
71 TAL: Thick ascending limb of Henle
- Renal
hypoperfusion
- Salt and water
retention
- Hyperkalemia
PGE2: Afferent arteriolar
Vasodilatation Increased GFR
Inhibition of TAL Na+, K+-ATPase
Inhibition of ADH in the collecting duct
PGI2: Afferent arteriolar
vasodilatation Efferent arteriolar
vasodilatation Increased GFR Release of renin
72
renal cortex
- mononuclear
infiltrate
tubules
- inflammation and
edema
-
Acute reversible pre-renal failure
(inhibition of renal vasodilatatory PGS)
Risk factors
History
HF (3.37: 2.04-5.58), hypertension (1.94: 1.2-3.13),
diabetes (2.22: 1.31-3.78), hospitalizations in the
previous year (1.61: 1.01-2.57) and consultant visits in
the previous year (3.00: 1.8-4.99)
Current medication
Antihypertensive drugs (5.16: 2.36-11.25), diuretics
(2.77: 1.49-5.12), ACEI (3.46: 2.05-5.85), oral steroids
(2.67: 1.25-5.67) Am J Kidney Dis 45:531-539.
NSAIDs cardiovascular risk
Hypertension (increase mean BP 5 mmHg1, increase mean BP 14 mmHg in hypertensive patients2)
Hypertension stroke, MI, heart failure,
Hypertension, heart failure renal impairment
Diclofenac threefold increase in cardiovascular risk3
1 Drug Saf 17:277 289, 2 Cardiol Rev 19: 184 91, 3 BMJ 342:c7086
-
www.cdc.gov/pcd/issues/2014/14_0298.htm
www.cdc.gov/pcd/issues/2014/14
_0298.htm
www.cdc.gov/pc
d/issues/2014/
14_0298.htm
-
www.cdc.gov/pcd/issues/2014/14
_0298.htm