DRUGS THERAPY

FOR KIDNEY
Budi Raharjo
 Function of Kidney
• Excretion of waste product
– e.g.Hydogen ion, Water
• Biosynthesis and Metabolim of hormone
– e.g. Renin, Insulin, Erythropietin
• Regulation of homeostasis
– e.g. Fluid, Electrolyte and Acid-base
balance
Renal Function Test
 Renal Function Test
• Serum Creatinine

• Creatinine Clearance

• Urea (Blood Urea Nitrogen)

• Miscellaneous
 Serum Creatinine
(Male 0,6-1,2 mg/dL; Female 0,2-0,4 mg/dL)
• By product of muscle metabolism
• Rate of formation proportional to muscle
mass
• Freely filtered by glomerolus (little
secretion or reabsorption by tubule)
• Indicator of renal function, but…..
• Factor affecting serum creatinine:
– Diet, time of day, age, sex, exercise, drugs
• Caution in unstable renal function or
acute renal disease
 Creatinine Clearance
• Measurement of creatinine clearance
give an estimate of GFR (Glomerular
Filtration Rate)
• Creatinine clearance varies with age,
sex, and size
• Measurement:
– Urine collection
– Cockroft and Gault Equation
 Creatinine Clearance
• Normal reference = 120 ml/min
• Renal disorder if: 60 < CrCl < 120 ml/min
 symptomless
• Renal insuficiency:
– Mild  20 – 50 ml/min
– Moderate  10 – 20 ml/min
– Severe  < 10 ml/min
– ESRD  < 5 ml/min
(End State of Renal Disease)
 Urine Collection
• Accurate collection of over 24 hour periode
(note problems with patient compliance)
• Plasma sample midway through 24 hour
periode
U x V
Clcr = -------------
S
U = Urine Creatinine concentration (mg/dL)
V = Urine flow rate (ml/min)
S = Serum Creatinine concentration (mg/dL)
 Cockroft & Gault Equation
F x (140 – age) x IBW
CrCl = ml/min
Serum Cr (mg/dL) x 72
F = 1,23 (males) F = 1,04 (females)
IBW (Ideal Body Weight)
Males
– TB > 152,5 cm IBW = 50 + [(TB - 152,4) x 0,89]
– TB < 152,5 cm IBW = 50 - [(152,4 - TB) x 0,89]
Females
– TB > 152,4 cm IBW = 45,5 + [(TB - 152,4) x 0,89]
– TB < 152,4 cm IBW = 45,5 - [(152,4 - TB) x 0,89]
 Limitation of
Cockroft & Gault Equation
Cannot be used if
• Age < 15 years old or age > 90 years old
• Renal function is changing rapidly
• Pregnancy (GFR  + 20 %)
• Serum creatinine > 3 x normal range
• Amputated limb
 Blood Urea Nitrogen
(8 – 18 mg/dL)

• Urea Nitrogen is an end product of protein

metabolism
• Produced by the liver, transported in blood
and excreeted by the kidney
• Freely filtered by glomerolus, partly reab-
sorbed by the tubules
• use as a screening test for renal disfunction,
not quantify the extend of renal disease
 Blood Urea Nitrogen
BUN  in:
• Acute or chronic renal failure
• High protein intake in diet
• Increased catabolism (infection, surgery)
• Uper GI bleeding or esophageal varices
(blood converted to ammonia by bacteria)
• Dehydration or water depletion
BUN  in:
• End state of liver disease ( formation)
• Water axcess (dilution)
 Miscellaneous
• Increased potassium
• Decreased bicarbonate
• Increased phosphate
• Decreased calcium
• Altered sodium levels
• Disturbed fluid balance
 Implications for Clinical
Pharmacy Practice
• Drug choice in patient with renal disease
– Pharmacokinetics

• General guidelines regarding drug choice

in patient with renal disease

• Dosage adjusment in patient with renal

disease
 Pharmacokinetics
• Absorption
– Oral absortion reduce by vomitting, nausea,
diarrhoea, GI oedema & changes in blood pH
– Little clinical significance
• Distribution
– Volume distribution (Vd) due to oedema/ascites;
Vd  due to dehydration (Little clinical significant:
Aminoglycoside, Lithium)
– Protein binding (Pb)  due to protein loss or Pb 
due to uraemia; increase free drugs; temporary
effect; caution in interprete drug level (Clinical
Significant: Phenytoin, Warfarin)
 Pharmacokinetics
• Metabolism
– Hepatic metab. unaffected in renal impairment
– Clinical significant of impaired renal metabolism:
• Accumulation of active metabolite
• Vitamin D replacement
• Insulin requirement
• Excretion
– Elimination of drug or its metabolites may be
decreased
– Most important parameter to consider when
making dosage decissions
 General Guidelines
• Only use drugs if a definite indication
• Choose drugs with minimal nephrotoxic effect
and avoid potentially nephrotoxic drugs
• Increased sensitivity to certain drug effects
• Monitor and act on plasma levels
• Check appropriate dosage adjustment
• Avoid prolonged courses of potentially toxic
drugs
• Monitor for clinical efficacy and evidence of
toxicity
 Drugs in Renal Disease:
Clinical Pharmacy Practice Point
• Identification of patient with renal
disease (Acute/Chronic Renal
Disease)
• Monitoring of renal function
(including dose adjustment)
• Assessment of current and
proposed drug treatment
 Dosage Adjustment
• Loading dose is usually unchanged (except
for digoxin and gentamycin)
• The most common maintenance dosage
changes are to decrease the dosage or
increase the dosage interval or both
• Refference sources:
– BNF
– Data Sheet / Drugs leaflet
– Bennett: Drugs and renal desease
 Dosage Adjustment
DRrf = DRn x [(1 - Feu) + (Feu x RF)]
Patient creatinine clearance (ml/mnt)
RF =
Ideal creatinine clearance (120ml/mnt)
• DRrf = Dosing Rate in renal failure
• DRn = Dosing Rate in normal state
• RF = the extent of Renal Failure
• Feu = Fraction of drugs normally excreting unchage
in the urine
 RENAL DISEASE

• Acute Renal Failure

• Chronic Renal Failure

 Acute Renal Failure

Pre-Renal ARF Intra-Renal ARF Post-Renal ARF

•Hipovolemia  •Acute Tubular Necrosis

sweating,vomiting, (ATN) ichaemic & toxin
diarhoe,blood loss (aminoglycosid,cyclosporin,cont
•Cardiac Output  rast media)
 AMI, CHF •Interstitial nephritis drug
•Renal hypoperfu- hypersensitive: penicillin,cepha-
siondrug induce losporine,allopurinol,azathioprin
ARF:Diuretic,ACEI •Glomerular lession (glo- •Post-renal obstruc-
NSAID (PgE2D2I2) merulnephritis) tion: urinary stone,
neoplasm,BPH
 Examination of ARF
1. Full history, including medication history
2. Physically Examination:
 Postural hypotension & skin turgor   Pre-Renal
 Drug rashes / vasculitic lession  Intra-Renal
 Sizes of bladder & kidneys   Post Renal
3. Examination of The Urine:
 Concentrated urine  Pre-Renal
 Intra-Renal  Isotonic urine,Epithel cell (ATN);Protein-
uria & Haematuria (Glomerulonephritis)
4. Examination of Blood
5. Radiological Study
 Drugs that Alter Renal Hemodynamic

Glomerolus
Arteri Afferent Tekanan Arteri Efferent
Hidrostatik
Aliran Darah Aliran Darah
Glomerolus

Vasokonstriktor Afferent: Vasodilator Efferent:

Inhibitor Prostaglandin Ultrafiltrat Renin-Angiotensin Aldosteron
- NSAID - ACE Inhibitor
- COX-2 inhibitor - Angiotensin II Antagonis
Vasokonstriktor langsung Vasokonstriktor langsung
Tubulus Proximal - CCB dihydropiridin
- Cyclosporine
- Amphotericine-B - Diltiazem
- Kontras Media (ionik) - Verapamil
- Vasopresor
 Treatment of ARF
1.Early Management:
Correction of fluid & Electrolide imbalance
If not respons  Loop diuretic & Manitol; or Dopamine
2.Establish ARF:
a.Uraemia protein intake  + Fat & CH  Catabolism 
b.Hyperkalaemia (K excresion + Cell damage) Cardioto-
xic  Ca gluconate i.v.; Soluble insulin + glucose; Ca resin
ion exchange
c.Acidosis H+ excresion   Na bicarbonate
d.Hypocalcaemia (Ca malabsorption)  Ca Supplement
e.Hyperphosphataemia (retention)  Ca carbonat
3.Haemodialysis, Peritonial Dialysis
 Chronic Renal Failure
Causes of CRF:
• Chronic Glomerulonephritis (nephrotic syndro-
me): Pitting Oedema; Proteinuria 3-5 gram/day;
Hypoalbuminaemia 25-30 gr/L
• Hypertension
• Chronic Pyelonephritis
• Urinary Obstruction: BPH, Renal calculi, Veico-
ureteric reflux, indwelling urinary cathethers
• Interstitial Nephritis
• Congenital Abnormalities
• Metabolic Disease: DM, Amyloidosis can lead
to chronic glomerulonephritis
 Examination of CRF
1. Full history, including medication history
2. Physically Examination: Nocturia, Fatigue,
Breathless, Anemia, Skin coloration with
Hypertension, Oedema
3. Examination of The Urine: Proteinuria
4. Examination of Blood: Creatinine Serum
and/or Clearence, Electrolyte disturbance
(Hyperkalaemia,Serum bicarbonateAci-
dosis,Hypercalcaemia,Hyperphospataemia)
5. Radiological Study: Intravenous Urography
(IVU) with Contrast Media
 Hypertension

Sodium and Renal Paren-

fluid Retention chymal
damage

Reduce ability to
excrete Na ions

Renal Activation of
Ischaemic RAA System

Cycle of events leading to hypertension in CRF

 R.A.A. System
Perdarahan Iskhaemia
TD   Ginjal
Masif

Angiotensinogen

RENIN Juxtaglomerolus App.

Angiotensin I Stimulasi  Prostaglandin

Angiotensin Converting Enzyme (ACE)

Angiotensin II Angiotensin III

Vasopresin Vol.Cairan 
Aldosteron

TD  Retensi Air Retensi Na

 Renal Failure

1,25 dihydroxycholecalciferol  Phosphate excretion 

Serum phosphate 
Ca absorption
from GI tract.

Serum calcium 

Reduced Mineralization of bone Hyperparathyroidism

OSTEOMALACIA OSTEOSCLEROSIS

Disturbance of Calcium and Phosphate Balance in CRF

 Treatment of CRF
• Hypertention: Diuretics, Beta blocker, ACE
Inhibitor, AT II Antagonist, Vasodilators
(hydralazin, prazosin, minoxidil)
• Anaemia: Trans PRC,Erythropoietin (+Iron
supl)
• Oedema: Fluid and Sodium restriction, If
Hypoalbuminemia Albumin i.v., Diuretics
• Hyperkalaemia: Resin K binder
• Acidosis: Sodium bicarbonate
• Osteodystrophy: Phosphat binder AlOH
(toxic syst not recom.), (CaCO3); Vit.D/pro
vit.D
Terima
Kasih