Pharmacotherapy

of
Chronic Kidney Diseases
Denpong Patanasethanont., Ph.D.
Division of Pharmacy Practice
Faculty of Pharmaceutical Sciences
Khon Kaen University
Advanced Pharmacotherapeutics I/ November 13th 2008
Professional education resources on
management of CKD
l National Kidney Foundation, Kidney Disease Outcome
Quality Initiative (K/DOQI)
www.kidney.org/professionals/doqi/index.cfm
l National Kidney Disease Education Program
www.nkdep.nih.gov
l Veterans Affairs/Department of Defense clinical practice
guideline on pre-ESRD care
www.oqp.med.va.gov/cpg/ESRD/ESRD-Base.htm
l Nephrology Section of Yale University of Medicine
http://kidney.med.yale.edu/pages/Entry.html
Stage of chronic kidney disease
Stage Description GFR
(ml/min/1.73m
2
)
1 Kidney damage with
normal or increase GFR
>90
2 Kidney damage with
mild decrease GFR
60-89
3 Moderate decrease GFR 30-59
4 Severe decrease GFR 15-29
5 Kidney failure <15 or dialysis
note: Chronic kidney disease is defined as the presence of kidney damage or a reduction in GFR for a
period of three months or longer.
K/DOQI = Kidney Disease Outcomes Quality Initiative; GFR = glomerular filtration rate.
National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation,
classification, and stratification. Am J Kidney Dis 2002;39(2 suppl 1):S46.
Many opportunities exist for
pharmacists who practice in the
primary care setting to improve
the care of patients with CKD.
CKD
death
Stages in Progression of Chronic Kidney
Disease and Therapeutic Strategies
Complications
Screening
for CKD
risk factors
CKD risk
reduction;
Screening for
CKD
Diagnosis
& treatment;
Treat
comorbid
conditions;
Slow
progression
Estimate
progression;
Treat
complications;
Prepare for
replacement
Replacement
by dialysis
& transplant
Normal
Increased
risk
Kidney
failure
Damage GFR
Am J Kidney Dis39:S1246, 2002
Optimal care by NKF stages of CKD
components Stage
1 2 3 4 5
Dx and Tx yes yes yes yes yes
Tx of comorbid conditions yes yes yes yes yes
Slowing progression yes yes yes yes -
CVD risk reduction yes yes yes yes yes
Estimating progression - yes yes yes yes
Evaluating and treating - - yes yes yes
complications
Preparation for RRT - - - yes -
RRT (if uremia present) - - - - yes
l preparing for end-stage renal disease (ESRD)
l initiation of renal replacement therapy (RRT)
l adequate medical and psychological preparation
Critical step in the care of patients with CKD
Timing and quality of care
prior to dialysis
morbidity and mortality of ESRD
Quality-of -life
Renal insufficiency
Acute renal failure (ARF)
Chronic kidney disease (CKD)
Drug dosing adjustment ?
Closely monitoring?
Renal excretion of drugs
Glomerular filtration
Tubular secretion
Tubular reabsorption
CASE STUDY
65 y/o male, 42 Kg, 168 cm.
CC: Short of breath, urine
l Underlying mod. MR c MS c chronic AF c CKD stage 3,
no DM, no HTN
l H/O gross hematuria from coumadin overdose last admit
14-21/11/50
l On coumadin(3) 1x1, Simvastatin(20) 1x1, moduretic 1x1
l PE: VS; PR 160, BP 98/66, BT 37.2, RR 24
crepitation both lung, active precordium, heaving thrill
positive
l Imp. 1. Mod. MR c MS c chronic AF
2. Lt. side heart failure
3. CKD stage 3
l Lab.29/11/50
BUN 42, Scr 2.2,
Na 137, K 4.8, Cl 108, Ca 8.9, PO
4
4.2, Mg 2.7
Hgb 14, Hct 43.6, PT 36.4, PTT 34.6, INR 3.05
l Medication:
One day Lasix (40) IV stat
Digoxin (0.25) IV stat.
Diltiazem (30) tab, po q 8 h
Continue Coumadin(3)1x1 po hs
Simvastatin(20) 1x1 po hs
Digoxin (0.25) po EOD
Co-morbid condition
CKD stage 3, GFR 30-59 ml/min
l Decrease in Ca absorption
l Lipoprotein activity falls
l Malnutrition
l Onset of LVH
l Onset of anemia (erythropoietin deficiency)
l Hypertension (mild)
l improve morbidity and mortality
l prevent or delay progression of
kidney disease
Current Treatment
Biologic consequences of sustained reduction in GFR
Plasma conc.
Normal range
Total GFR (%of normal)
Overt renal
failure
Zone of compensation
(adequate renal reserve)
A
B
C
A = creatinine
and urea
B = PO
4
, urate,
K
+
, H
+
C = NaCl
0 25 50 75 100
CKD and complications
l Decrease in Ca absorption
l Lipoprotein activity falls
l Malnutrition
l Onset of LVH
l Onset of anemia
(erythropoietin deficiency)
l Hypertension (mild)
30-59 3
l PTH start to rise
l Hypertension possible
60-89 2
>90 1
complications GFR Stage
CKD and complications
l Triglyceride conc. start to rise
l Hyperphosphatemia
l Metabolic acidosis
l Tendency to hyperkalemia
l Hypertension (moderate)
15-30 4
l Azotemia develops
l Hypertension (severe)
<15 5
complications GFR Stage
CASE STUDY
l 32 63 158 type
1 DM 15 1
BS > 200, A1C
>8%
l Na 143, K 5.3, Cl 106, CO
2
18, SCr 2.9 mg/dL,
BUN 63, BS 220, PO
4
7.6, Ca 8.8, Mg 2.8, uric
acid 8.8
l Hct. 26, Hgb 8.7, WBC 9600, RBC indices
normal, Plt 170000,
l UA: 4+ proteinuria, Alb 700 mg/day (normal <30
mg/day)
l BP155/102 mmHg, mild pulmonary congestion,
2+ pedal edema,
Finding
l CrCl 28 mL/min
l Stage 4 CKD
l ELyte imbalance
l Advanced glomerular damage
l Volume overload (Na ?? N/V ??)
l HT, Congestive pulmonary dz, edema
l Matabolic acidosis
l Anemia
l Azotemia
l improve morbidity and mortality
l prevent or delay progression of
kidney disease
Current Treatment
Glycemic control
l DCCT :
l intensive glycemic control reduces long-term
microvascular complications in pt with type 1
diabetes.
l Risk of microalbuminuria and albuminuria were
reduced 39%(p< 0,002) and 54%(p<0,04), respectively.
l UKPDS33 :
l intensive control achieved 25 % reduction of
microvascular complications (p<0.01),
microalbuminuria, albuminuria and doubling of Scr
were sig. lower after 9 yrs. of Tx in type 2 diabetes.
Recommendations for glycemic control in DM
Goal values
Normal
value
Glycemic
measure
American college of
Endocrinology
American Diabetes
Association
<6.5 <7 <6 HbA1c(%)
NR 100-140 <110 Bedtime
</= 140 <180 <140 Postprandial
</= 110 90- 130
a
<100 Preprandial
Blood Glucose (mg/dl)
NR = no recommendation,
a
plasma glucose values
http://www.medscapes.com/viewarticle/497758
Using of Oral hypoglycemic drugs in CKD
No adjustment needed in renal impairment Thiazolidine dione
Pioglitazone (Acttos)
Rosiglitazone (Avandia)
Excrete unchanged by renal, lactic acidosis
Avoid if GFR < 60-70 mL/min
Metformin
Safe in CKD, excrete by liver Meglitinides
Repaglinide (Novonorm)
Metabolized in liver, inactive metabolite excreted by renal
Avoid if GFR <10 mL/min
Glipizide
(Minidiab)
(CrCL>50 mg/dL) Decrease dose
Not recommend if GFR< 50ml.min or Scr>2 mg/dL
Glybenclamide
Avoid if GFR< 50 mL/min or Scr>2 mg/dL Chlorpropamide
Using in CKD Drug
Alfa-glucosidase inhibitor ???? (should not be used if GFR <10)
Dipeptidyl Peptidase-IV (DPP-IV) Inhibitors
Sitagliptin
l Usual dose: 100 mg OD
l CrCl 30-50 ml/min: 50 mg OD
l CrCl < 25 mL/min: 25 mg OD
Vildagliptin
l Not yet approved (at June 2008)
l 90% of pt. with renal failure have HTN
l Multiple Risk Factor Intervention Trial (MRFIT) confirmed
association between elevated BP and declined in GFR
16 mmHg increase in SBP => 1.8 risk of developing ESRD
compared to optimal BP
l Hypertension Detection and Follow-up Program (HDFP)
noted a 5-yr risk of elevated Scr (>2.0mg/dl) was strongly
related to baseline DBP (p<0.05)
Blood Pressure Control
Recommendations from Treatment guidelines
ACEI,ARB Proteinuria < 1 g/d:<130/80
Proteinuria >/= 1 g/d:<125/75
<140/85 UK 1999 BHS
ACEI,ARB,
Thiazide
Proteinuria < 1 g/d:<130/80
Proteinuria >/= 1 g/d:<125/75
<140/90 Canada 2002 CHWG
ACEI,ARB All diabetics: <130/80 NR USA 2003 ADA
ACEI,ARB Albuminuria or GFR<60ml/min:
<130/80
<140/90 USA 2003 JNC 7
ACEI,ARB,
Diuretic
<130/80 NR USA 2004 NKF
CKD
No
Kidney
disease
Preferred
Agent(s)
Goal BP(mmHg)
Country Year Guideline
http://www.medscapes.com/viewarticle/497758_print
Blood Pressure and Diabetic Nephropathy
l Pt with diabetes => largest group of pts to develop
diabetic nephropathy.
l Hyperglycemia; a risk factor for nephropathy.
l HTN + hyperglycemia => progressive kidney disease
JNC VII guideline
l BP < 130/85 mmHg
l BP < 125/75 mmHg if proteinuria > 1g/d
Lipid Management
No preferences are indicated for which
fibrate should be used to treat
hypertriglyceridemia
Gemfibrozil may be the fibrate of choice for Tx of high
TG in pt with CKD
Fibrates are contraindicated in stage 5
CKD.
Fibrates may be used in stage 5 CKD for pt with TG
>/= 500 mg/dl, and for pt both TG >/= 200 and non-
HDL cholesterol >/= 130 who do not tolerate statins
No recommendations are made for pt< 20
y/o
Recommendations are made for pt< 20 y/o
Initial drug therapy for high LDL level
should be with a statin, bile acid
sequestrant, or nicotinic acid
Initial drug therapy for high LDL level should be with a
statin.
Drug therapy is considered optional for
LDL level of 100-129 mg/dl
Drug therapy should be used for LDL level of 100-129
mg/dl after 3 mo of therapeutic life style change.
Evaluation of dyslipidemias should occur
every 5 yrs.
Evaluation of dyslipidemias should occur at
presentation with CKD, following a change in kidney
therapy modality, and annually.
Pt with CKD should not be managed
differently from other pts.
Pt with CKD should be considered to be in the highest
risk category
Adult Treatment Panel III Guidelines
NKF K/DOQI Guidelines
Treatment goals
l LDL level should be at least less than 130 mg/dl
l High risk pt (10-yr risk of CHD>20%) should have an
LDL target of < 100 mg/dl
l The combination of statins and fibrates should be avoided.
l Statins + bile acid sequestrants (or nicotinic acid) if TG < 400
mg/dl
l Potential benefit of combination therapy must be closely
weighed against the increased risk of adverse effects,
adherence issues, and cost.
l Consider effect of altered metabolism and elimination of lipid
lowering agents, DI, closely assess for S/S, or lab.
abnormalities associated with drug toxicity
Tobacco Cessation
l Smoking, in a dose- dependent manner,
increase urinary excretion of albumin
l There is also evidence that smoking may
accelerate a decline in GFR
l The guidelines recommended that all clinicians,
including pharmacists, provide smoking
cessation interventions
l Five As is suggested to provide smoking
cessation counseling
Anemia
l progressive erythropoietin deficiency
l Iron deficiency
l normochromic, normocytic anemia
l Early treatment of anemia
l decreased hospitalizations for CVS
complications (LVH)
l improved survival, exercise capacity,
cognitive function, quality of life
l CKD => Left ventricular hypertrophy
l 39% in GFR<25.5 ml/min
l 74% in dialysis pt.
Anemia
l Definition of anemia (K/DOQI 2006)
l Men and postmenopausal women; Hgb<13.5
l Women; Hgb<12
l Target ferritin value
l HD => 200 ng/mL
l nonHD CKD => 100 ng/mL
Pharmacists key role :
Develop administration protocol and
monitoring response
l consistent monitoring of Hb and Hct, adverse
events: HTN, seizures, hyperkalemia, and
increased risk of blood clots.
l Target Hb 11-13 g/dL
Facilitate appropriate iron therapy
according to K/DOQI guidelines
to maintain
l a transferrin saturation of 20% or greater
and
l a serum ferritin level of 100 ng/ml or greater
Erythropoiesis-stimulating agents
Recommended to read;
l Cardiovascular Risk Reduction in Early Anemia
Treatment with Epoetin Beta (CREATE)
(Dreke TB et al. N Engl J Med. 2006;355:2071-2084)
l Correction of Hemoglobin and Outcomes in
Renal Insufficiency (CHOIR) trials
(Singh AK et al. N Engl J Med. 2006;355:2085-2098)
Erythropoiesis-stimulating agents
l Epoetin alfa (EPIAO

, EPREX

, ESPOGEN

, HEMAX

)
l 25 -50 IU/kg iv. or sc. 3X/wk
l Adjust increase 25 IU/Kg q 4 wk then 75 IU/ kg 3X/wk
l Epoetin beta (RECORMON

)
l Sc. : 20 IU / kg 3x/wk, adjust increase 20 IU / kg q 4 wk.
l iv : 40 IU / kg 3x/wk for 4 wk then adjust increase 80 IU/kg
l Maximum dose : 720 IU/ kg /week
There have been no reports that epoetin alfa differs from
epoetin beta in its clinical efficacy
l Darbepoetin ARANESP

l Half-life: 3x of Epoetin alfa (i.v.)

l 0.45 g/kg once a week.
l 0.75 g/kg q 2 weeks
Administration of Epoetin
l The dosage of epoetin is individual with more than
tenfold variability among individuals
l no clinical parameters of predicting the necessary
dosage.
l Therapeutic range is very wide (up to 100.000
IU/week.)
l The HB concentration, along with the reticulocyte
count, must be checked
l Initiation: weekly
l Maintenance: monthly
l stable dose-response: every 2-3 months
l The target Hb concentration 11-12 g/dL is
maintained in 90-95% of the patients by
administering
l 1.000-30.000 IU of epoetin per week or
l 5-150 mcg darbepoetin alpha per week
in the presence of adequate reserves of iron.
l Higher dosages define a state of resistance.
Administration of Epoetin (cont.)
Erythropoiesis-stimulating agents
l For all patients:
l Adhere to dosing to maintain the recommended target
hemoglobin range of 10 to 12 g/dL.
l Measure hemoglobin twice a week for 2 to 6 weeks
after any dosage adjustment to ensure that
hemoglobin has stabilized in response to the dose
change.
l Decrease the dose of the ESA if the hemoglobin
increase exceeds 1 g/dL in any 2-week period.
l For CKD patients:
l Measure hemoglobin twice a week after initiating
treatment until hemoglobin has stabilized
US FDA Issues Safety Warning on Erythropoietin
Hyperparathyroidism
and Renal Osteodystrophy
l CKD => hypocalcemia => increase in parathyroid
hormone levels => bone metabolism abnormality
=> renal osteodystrophy
l Inability of kidney to activate vitamin D needed for
calcium absorption from the gut
=> phosphate retention
l complications ; soft tissue calcification, pruritus,
proximal myopathy, skin ulceration, soft tissue
necrosis
=> impaired pulmonary & heart
Frequency of Measurement of
PTH, Ca, PO
4
Every mo Every 3 mo <15 or dialysis 5
Every 3 mo Every 3 mo 15-29 4
Every 12 mo Every 12 mo 30-59 3
Measurement
of Ca/ PO
4
Measurement
of PHT
GFR range
(mL/min/1.73 m
2
) CKD stage
Recommended Goal Conc.
for Bone Disease in CKD
<55 <55 <55 Ca-PO
4
(mg
2
/dl
2
)
8.4-9.5 8.4- 10.2 8.4-10.2 Ca
(mg/dl)
3.5-5.5
Evidence
2.7-4.6
opinion
2.7-4.6
opinion
PO
4
(mg/dl)
150-300
[16.5-33.0]
Evidence
70-110
[7.7-12.1]
Opinion
35-70
[3.85-7.7]
Opinion
iPTH pg/mL
[pmol/L]
CKD stage 5 CKD stage 4 CKD stage 3
Lab.
parameter
Pt. information: **** Decrease phosphate intake : Legume, Beverage, etc.****
Phosphate Binder
l Calcium product
l Aluminium hydroxide
l Calcium-Aluminum free
Phosphate Binder
l Calcium carbonate (40% elemental calcium)
l
l >6 g/day
l 20-30% absorbed
l 39 mg phosphate bound per 1 g CaCO
3
l Try to limit daily intake 1.5 g of elemental Ca per day
l Calcium acetate (25% elemental calcium)
l 3 g/day
l
l Absorption with meal: 20%, between meal 40%
l
l Do not exceed 1.5 g of elemental Ca per day
l 45 mg phosphate bound per 1 g Ca acetate
l GI side effects, constipation, hypocalcaemia, extraskeletal calcification
Phosphate Binder
l Aluminium hydroxide
l Calcium-Phosphate product > 55 mg
2
/mL
2
l Reserve for short-term 4 weeks
l Do not use concurrently with citrate-containing products
l ADR:
l Constipation/fecal impaction
l Bone mineral defects
l Anemia, Dementia
l Chalky taste, GI distress, N/V
l Liquid: (6.1% suspension)
l Mean binding 22.3 mg phosphate per 5 mL(320 mg/5mL)
l Tablets (500 mg)
l Mean binding 15.3 mg per pill
Phosphate Binder
l Calcium-Aluminum free
l Sevelamer hydrochloride (Renagel)
l Sevelamer carbonate (Renvela) less GI S/E
l Poly (allylamine hydrochloride),
l a polymeric amine oral administration
l No absorption
l no hypercalcemia
l Lowers LDL cholesterols, uric acid
l more expensive
Sevelamer Hydrochloride
l Renagel
l film-coated tablet 800 mg or 400 mg
l indicated for the control of serum
phosphorus in patients with chronic kidney
disease (CKD) on dialysis
l 80 mg Phosphate bound per mg
Sevelamer (animal data only)
l Decrease bioavailability of Ciprofloxacin
50%
Sevelamer Hydrochloride
4 tablets three times
daily with meals
2 tablets three times
daily with meals
9.0 mg/dL
3 tablets three times
daily with meals
2 tablets three times
daily with meals
7.5 and
< 9.0 mg/dL
2 tablets three times
daily with meals
1 tablet three times
daily with meals
> 5.5 and
< 7.5 mg/dL
400 mg 800 mg Serum Phosphorus
Product information
Sevelamer Hydrochloride
5 tablets 3 tablets 3 tablets
3 tablets 2 tablets 2 tablets
2 tablets 1 tablet 1 tablet
400 mg
(Tablets per meal)
800 mg
(Tablets per meal)
Calcium Acetate
667 mg
(Tablets per meal)
Product information
Sevelamer Hydrochloride
Decrease 1 tablet per meal < 3.5 mg/dL
Maintain current dose 3.5 - 5.5 mg/dL
Increase 1 tablet per meal
at 2 week intervals
> 5.5 mg/dL
Dose
Serum
Phosphorus
Product information
The average dose in a Phase 3 trial designed to
lower serum phosphorus to 5.0 mg/dL or less was
approximately three of 800 mg tablets per meal.
The maximum average daily dose studied was 13 g.
Vitamin D
l PTH > 110 pg/mL
l and/or Ca < 9.5 mg/dL
l and/or PO
4
< 4.6 mg/dL
l Alfacalcidal (0.25 g, 0.5 g , 1 g)
l (Alpha D3

, One-alpha

, Bon-One

)
l 0.25-1 g OD X3/wk
l Calcitriol (0.25 g)
l (Rocaltrol

, Calcit SG

, Decostriol

, Osteo D

)
l 2-4 g OD x3/wk
Vitamin D
Dosing recommendations for calcitriol
in stage 5 CKD on hemodialysis
If Ca < 9.5 mg/dL, PO
4
< 5.5 mg/dL, Ca x PO
4
< 55 mg
2
/dL
2
3-7 oral
or 3-5 g IV
>1000
1-4 g oral
or 1-3 g IV
600-1000
0.5-1.5 g oral or IV 300-600
IV and oral Calcitriol
Dose per HD
iPTH (pg/mL)
Eknoyan G, Am J Kidney Dis 2003;42:1-201
Protein Diet
l RDA = 0.8 g/kg/day
l Thai RDA = 50 g/day
Recommended for CKD patients (USA)
l GFR > 30 mL/min/1.73 m
2
(or plus proteinurea >3g/day)
l Protein intake 0.75 g/kg/day
l ( )
l GFR < 30 mL/min/1.73 m
2
l Not more than 0.6 g/kg/day
Protein Diet (cont.)
l High biological value protein
l ,
l 60%
l
l 1 = 2 2
l 0.6-0.75 g/kg/day
1 1 (3 )
Protein Diet (cont.)

l
l
l
l
l
l () ()
l ()
l
l ()
l
l

Salt (NaCl)
According to JNC VII
l Normal BP with
l Type 2 DM, CKD, RRT, Pitting edema, including of
Nephrotic syndrome
l NaCl not more than 6 g/day
l Hypertension
l Not more than 4 g/day (or 5 g/day)
l Avoid instant food, seasoning, Food in restaurant
Salt (NaCl)
Recommend for normal people 102.54 2358.9 6
Recommended by ESH and ESC 2007
for Hypertension
85.47 1965.8 5
Recommended by JNC VII
for Hypertension
68.37 1572.6 4
Remark
Na
(mEq)
Na
(mg)
NaCl
(g)
1 5
10
MW Na = 23
Cl = 35.5
Sodium bicarbonate
l When HCO
3
-
< 17 mEq/L
l Supplement 0.5-1.0 mEq/kg/day
l Titrate to bicarbonate level 18-20 mEq/L
l !!! Sodium content!!!!
l Sodamint (Sodium bicarbonate) (Sodamint 300 mg)
l 1 mEq NaHCO
3
= 84 mg (sodium content 23 mg)
l 300 mg = HCO
3
-
~ 3.7 mEq (sodium content ~82 mg)
l 650 mg = HCO
3
-
~ 8 mEq (sodium content ~178 mg)
l Shohls solution (Sodium citrate)
l 140 g citric acid and 98 g hydrated crystalline salt of
sodium citrate, distilled water to make 1000 ml;
l 1 mL = 1 mEq
l
Renal insufficiency
Effect to Pharmacokinetics
l Absorption
l Uremic gastroparesis can alter rate of drug absorption
l Gastric pH
l Gastrointestinal tract edema
l Vomitting and diarrhea
l Antacid or cholestyramine
l Distribution
l Edema or ascites
l increase Vd of water soluble drugs
l Uremic states
l alter plasma protein binding
l Tissue protein binding is reduced decrease Vd
l Metabolism
l Hepatic biotransformation may be altered
l Excretion
l Most important pharmacokinetic parameters altered
l Creatinine clearance is the guiding factor for drug
dosage
l Clinical pharmacokinetics approach for narrow
therapeutic index may be altered
Renal insufficiency
Effect to Pharmacokinetics (cont.)
Steps to Adjust Drug Dosages
for Patients with Renal Insufficiency
Important points for patient with dialysis
Dialysis can remove drug?
Dosing supplementation is necessary?
Resources for More Information
About Dosing Adjustments
in Patients with Chronic Kidney Disease
Determination of renal function
Cl
cr
using Cockcrof&Gaults equation**
Cl
cr
= (140-age)(LBW) (0.85 if female)
72 S
cr
*Unit = mL/min/1.73 m
2
, A 70 kg/1.73 m
2
BSA is assumed
MDRD study equation**
GFR = 186 (S
cr
)
-1.154
(Age)
-0.203
(0.742 if female)
(1.210 if African-American)
l **MDRD: Modification of diet in renal disease
l Age >18 year-old
l **Unit = mL/min/1.73 m
2
, > 60 mL/min/1.73m
2
is not exact number
Equations for Predicting Creatinine Clearance
or GFR in Adults with Kidney Disease
Estimated baseline creatinine
base on MDRD formula
age male female
20-24 1.3 1.0
25-29 1.2 1.0
30-39 1.2 0.9
40-54 1.1 0.9
55-65 1.1 0.8
>65 1.0 0.8
24 hour urine collection (mL/min)
CrCl = Ucr V
Scr T
l CrCL = creatinine clearance (mL/min)
l Ucr = urinary creatinine conc. (mg%)
l V= Volume of urine during collection period (mL)
l Scr = serum creatinine concentration (mg%)
l T = collection time (min) (if 24 hr = 1440 min)
Determination of renal function (cont.)
24 hour urine collection
CrCl = Ucr(g/Vol) X Vol (L)
Scr(mg/dL) x T(day)
= Ucr(g/Vol) X Vol (L) x 10
3
Scr(g/L) x T(min) x (24x60)(10
2
)
CrCl = 6.94(U
cr
/S
cr
)
CrCl ~ 7(U
cr
/S
cr
)
l Protein report g volume (L) Urine

ACEI
25-50 50-75 100 Lisinopril
50 75-100 100 Enalapril
50 75 100 Captopril
<10 10-50 >50
25-50 50-75 100 Ramipril
75 75-100 100 Quinapril
75-100 100 100 Fosinopril
% of usual Dose
based on GFR mL/min/1.73 m
2
Drug
American Family Physician Web site at www.aafp.org/afp
Case Study
l 60 y/o male 90 kg; infected CAPD
l PDF : staphylococcus coagulase negative
sensitivity: Vancomycin
on Vancomycin 1 G + D5W 200 ml IV in 2 hr.
q 96 hr. start 25/10/50
l Vancomycin conc. on 29/10/50 = 7.19 mg/L
Target Vancomycin trough
l For MRSA with MIC 2 mcg/ml
l 50% Protein binding
l Target trough => 4-5 times the MIC
l Target trough = 15-20 mcg/ml
l 20% lower response rate in pt. who did not
achieve target trough initially(76% vs 56%,
p=.05; Hidayat et al. 2006)
l Predicted Cmax after 1
st
dose
Cmax1 = [1000mg/59.5L] x e
-0.0056x2
= 16.64 mg/L
l Cmin1 = 7.19 mg/L (measured level)
l Cmax2 = 7.19 + 16.64 = 23.83 mg/L
l Cmin2 = 23.83 x e
-0.0056x96
= 13.82 mg/L
l Cssmax = 39.62 mg/L
l Cssmin = 23.21 mg/L
16.64
7.19
23.83
13.82
39.62
23.21
30
15
Time
Conc.
40
l To help reduce drug-induced CKD in
primary care
l comprehensive drug histories
l prescribing of appropriate dosages
l avoidance of nephrotoxins in pt with underlying
renal problems
l monitoring of nephrotoxic drug therapies
Many pharmacologic agents
can cause kidney damage
Avoidance/Precaution
for patient with CKD
l Pharmacologic agents
l IV radiographic contrast agents
l selected antimicrobials : AMGs, amphotericin B
l NSAIDs (including COX-2 selective inhibitors)
l cyclosporine and tacrolimus
l Volume depletion
l Obstruction of the urinary tract
l The benefits of ACEI and ARB outweigh the
risks; titrating dosage will minimize the risk
of kidney damage
Assessment of nephrotoxicity
Identification of drug-induced nephrotoxicity
l a change in Scr of at least 0.5 mg/dL for subjects with a baseline
Scr <2 mg/dL
l an increase of about 30%for those with Scr >2 mg/dL, when
correlated temporally with the initiation of drug therapy
l Serum creatinine or BUN concentrations and urine
collection for creatinine
l intrasubject between-day variability of Scr (20% within the
normal range).
Potential roles and responsibilities
l Attainment of blood pressure goal
l Attainment of glycemic goals in those with diabetes
l Early evaluation and treatment for proteinuria
l Early evaluation and therapy for anemia
l Early evaluation and therapy for secondary
hyperparathyroidism
l Attainment of lipid goals, where appropriate
l Appropriate drug dosing adjustments
l Minimization of drug-related nephrotoxin exposure
l Provision of drug therapy instruction
l Screening for ability to afford drugs
l Education regarding smoking cessation, where
appropriate