This document provides an overview of drugs affecting the kidney including their mechanisms and common examples. It discusses kidney anatomy and outlines common drugs that can cause vasoconstriction or vasodilation in the afferent or efferent arterioles. Examples of drugs that can cause tubular epithelial cell damage through acute tubular necrosis are also provided, such as aminoglycoside antibiotics and radiographic contrast media. The document also briefly discusses chronic kidney disease, acute kidney injury, and drug-induced nephrotoxicity.

1. Drugs and Dosing in
Renal Patients
Kimberly Treier and Hannah Bond
Pharm.D. Candidates 2016
Albany College of Pharmacy- VT campus
17 September 2015

2. Outline
• Kidney Anatomy
• Common Drugs Affecting the Kidney
• Renal Dosing Calculations
• Chronic Kidney Disease – Brief Overview
• Acute Kidney Injury – Brief Overview
• Drug Induced Nephrotoxicity – Brief Overview

3. Kidney Anatomy
Hannah Bond

6. Common Drugs Acting
on the Kidneys
Kimberly Treier

8. Afferent Arteriole
NSAIDs
- Ibuprofen
- Ketoprofen
- Naproxen
- Indomethacin
- Celecoxib
- Ketorolac
- others
Vasoconstriction

9. Efferent Arteriole
ACEIs
- Lisinopril
- Enalapril
ARBs
- Losartan
- Valsartan
Aldosterone
antagonists
- Spironolactone
- Eplerenone
Vasodilation

10. BOTH Arterioles
Dopamine agonists*
- Bromocriptine
- Ropinirole
Alpha-1 blocker
- Prazosin
- Doxazosin
Vasodilation

11. BOTH Arterioles
Direct-acting
vasodilators
- Hydralazine
Nitrates
- Nitroglycerine
- Nitroprusside
- Isosorbide
dinitrate
Vasodilation

12. Proximal Tubule
Carbonic
Anhydrase
Inhibitors
- Acetazolamaide
- Methazolamide
Promotes diuresis
and urinary
alkalinization

13. Proximal Tubule +
Descending Loop
Osmotic diuretics
- Mannitol
- Isosorbide
 urine osmolarity
(unable to be
reabsorbed) 
draws H2O into
lumen

14. Ascending Loop
Loop diuretics
- Furosemide
- Torsemide
- Bumetanide
 Na+ and Cl-
reabsorption

15. Distal Tubule
Thiazide diuretics
- HCTZ
- Indapamide
- Metolazone
- Chlorthalidone
 Na+ and Cl-
excretion

16. Distal Tubule +
Collecting Duct
K+-sparing diuretics
- Spironolactone
- Eplerenone
- Triamterene
- Amiloride
 Aldosterone-
mediated Na+ and
water reabsorption,
and K+ excretion

17. Collecting Duct
ADH agonists
- Desmopressin
 Renal H2O
reabsorption
ADH antagonists
- Conivaptan
- Tolvaptan
- Oxytocin??
Renal H2O
reabsorption

18. Proximal Tubule
SGLT2 inhibitors
- Canagliflozin
- Dapagliflozin
- Empagliflozin
 reabsorption of
filtered glucose

19. Juxtaglomerular
cells
Direct renin
inhibitor
- Aliskiren
 Release of
renin
Direct-acting
vasodilators
- Hydralazine
 Release of
renin

20. Renal Dosing
Calculations
Hannah Bond

21. • Step 1: Obtain the following information
• Age
• Height
• Current weight
• Most recent SCr
• Step 2: Calculate Ideal Body Weight (IBW)
• Male: 50 + (2.3 X inches over 60 inches in
height)
• Female: 45.5 + (2.3 X inches over 60 inches in
height)
Creatine Clearance

22. • Step 3: Determine dosing weight
• Use total body weight to calculate CrCl if TBW<
IBW
• Use adjusted body weight for obese patients
• TBW > 1.3 times IBW
• AdjBW: IBW + 0.4 (TBW – IBW)
• Step 4: Calculate estimated Creatine
Clearance
• Male: [(140-age) X IBW] / (72 X SCr)
• Female: [(140-age) X IBW] / (72 X SCr) X 0.85
Creatine Clearance

23. • A 57 year old African American female with a
PMH of CKD, HTN, and DM is admitted to
ICU for IV antibiotics to treat an infected ulcer
on her right foot. Dr. Johnson has ordered
Ceftazidime 1 g every 12 hours and
vancomycin 1 g every 12 hours.
• SCr: 2.51 mg/dL
• Height: 65 inches
• Weight: 68 kg
Creatine Clearance Example

24. • Step 1: Obtain the following information
• Age: 57
• Height: 65 inches
• Actual current weight: 68 kg
• Most recent SCr: 2.51 mg/dL
• Step 2: Calculate Ideal Body Weight (IBW)
• Male: 50 + (2.3 X inches over 60 inches in
height)
• Female: 45.5 + (2.3 X inches over 60 inches in
height)
• IBW = 45.5 + (2.3 X 5) = 57 kg
Creatine Clearance Example

25. • Step 3: Determine dosing weight
• Use total body weight to calculate CrCl if TBW< IBW
• 68 kg /57 kg = 1.19
• Use adjusted body weight for obese patients
• TBW > 1.3 times IBW
• AdjBW: IBW +0.4 (TBW – IBW)
• Step 4: Calculate estimated Creatine Clearance
• Male: [(140-age) X IBW] / (72 X SCr)
• Female: [(140-age) X IBW] / (72 X SCr) X 0.85
• CrCl = [140-57) X 57 kg]/(72 X 2.51 mg/dL) X 0.85 =
26.55 mL/min
Creatine Clearance Example

26. • Ceftazidime renal dosing
• CrCl 31-50 mL/min: 1-2 g every 12 hours
• CrCl 10-30 mL/min: 1-2 g every 24 hours
• CrCl < 10 mL/min: 1-2 g every 48 hours
• Based on the above information and her CrCl
of 26.55 mL/min, did the doctor prescribe the
correct dose of ceftazidime (1 g every 12
hours)?
Creatine Clearance Example

27. • Most drug dosing recommendations are
based on CrCl
• There are many equations to calculate CrCl
• Cockcroft-Gault (adults)
• Schwartz Equation (children)
Using CrCl

28. • Limitations:
• CrCl is just an estimate (“eCrCl”)
• Creatinine levels dependent on many factors
• Age
• Sex
• Muscle mass
• Diet
• Renal creatinine secretion (overestimation of kidney function)
• Fluctuating renal function (e.g. ICU)
• Multiple equations
• Lack of standardization among manufacturers (FDA
labeling and institution-specific implementation)
Using CrCl

29. • Step 1: Obtain the following information
• Age
• Sex
• Ethnicity
• Most recent SCr
• Step 2: Calculate eGFR
• GFR (mL/min/1.73 m2) = 175 × (Scr)-1.154 ×
(Age)-0.203 × (0.742 if female) × (1.212 if African
American)
Estimated Glomerular
Filtration Rate (eGFR)

30. • A 57 year old African American female with a
PMH of CKD, HTN, and DM is admitted to
ICU for IV antibiotics to treat an infected ulcer
on her right foot. Dr. Johnson has ordered
Ceftazidime 1 g every 12 hours and
vancomycin 1 g every 12 hours.
• SCr: 2.51 mg/dL
• Weight: 68 kg
• Height: 65 inches
eGFR example

31. • Step 1: Obtain the following information
• Age: 57
• Sex: Female
• Ethnicity: African American
• Most recent SCr: 2.51 mg/dL
• Step 2: Calculate eGFR
• GFR (mL/min/1.73 m2) = 175 × (Scr)-1.154 × (Age)-0.203
× (0.742 if female) × (1.212 if African American)
• = 175 × (2.51)-1.154 × (57)-0.203 × (0.742 if female) ×
(1.212 if African American)= 25 mL/min/1.73m2
eGFR Example

32. • Some drug dosing recommendations are based
on eGFR
• Basis for chronic kidney disease staging
• Multiple equations:
• Modification of Diet in Renal Disease (MDRD)
• Chronic Kidney Disease Epidemiology Collaboration
(CKD-EPI)
• Limitations:
• Less accurate in very large/small patients
• Multiply eGFR by BSA
Using eGFR

33. Chronic Kidney
Disease
Hannah Bond

34. What is Chronic Kidney
Disease?
• Presence of kidney damage or a reduction in
glomerular filtration rate for three months or
longer
• As CKD progresses, wastes can build to high
levels in your blood.
• Complications: high blood pressure, anemia,
weak bones, poor nutritional health and nerve
damage

35. CKD staging
GFR category GFR (mL/min/1.73m2) Terms
G1 ≥90 Normal to high
G2 60-89 Mild decreased
G3a 45-59 Mild to moderate
decrease
G3b 30-44 Moderate to severe
decrease
G4 15-29 Severe decrease
G5 <15 Kidney failure

36. Acute Kidney Injury
Kimberly Treier

37. What is AKI?
• Abrupt loss of kidney function
• Accumulation of urea and nitrogenous waste
• Inability to effectively regulate fluid and electrolytes
• ICU patients considered high-risk for AKI
• Occurs in up to ⅔ ICU patients
• Consequences:
• Prolonged hospital stay
• Hospital-related adverse events
• Development of CKD
• Acute/chronic renal replacement therapy

38. What is AKI?

39. Drug-Induced
Nephrotoxicity
Kimberly Treier

40. Risk factors for drug-induced nephrotoxicity in the
ICU
Chronic risk factors
- Older age (> 65 years)
- CKD
- Diabetes mellitus
- Malignancy
- Cardiovascular disease
- Liver disease
- Chronic pulmonary disease
- HTN
- Peripheral vascular disease
Acute risk factors
- Sepsis/infection
- Volume depletion (true and effective)
- Acute decompensated heart failure
- Hypotension
- Complex/major surgery
- Trauma
- Mechanical ventilationPerazella MA. Drug use and nephrotoxicity in the intensive care unit. Kidney International (2012) 81, 1172-1178; doi:
10.1038/ki.2010.475

41. Drug-Induced Nephrotoxicity
• Tubular epithelial cell damage
• Hemodynamically-mediated kidney damage
• Obstructive nephropathy
• Glomerular disease
• Tubulointerstitial disease
• Renal vasculitis, thrombosis, and cholesterol
emboli

42. Tubular epithelial cell damage
Acute tubular necrosis **Most common in inpatient setting**
- Aminoglycoside antibiotics
- Radiographic contrast media
- Cisplatin, carboplatin
- Amphotericin B
- Cyclosporine, tacrolimus
- Adefovir, cidofovir, tenofovir
- Pentamidine
- Foscarnet
- Zoledronate
Osmotic nephrosis
- Mannitol
- Dextran
- Radiocontrast media
- IV immunoglobulin
- Drug vehicles (e.g. sucrose, polyethylene glycol)
Drug-Induced Nephrotoxicity

43. Aminiglycoside nephrotoxicity
• Gentamycin, tobramycin, streptomycin, amikacin
• 10-25% of patients treated with aminoglycoside
• Critically ill: up to 58%
• Accumulation of drug in proximal tubular epithelial
cells  reactive oxygen species  cell apoptosis
and proximal tubular necrosis
Drug-Induced Nephrotoxicity

44. Dose adjustment example:
• Gentamycin:
• Traditional dosing – increase dosing interval:
• Initial dose given every [SCr x 8] hours
• Traditional dosing – decrease dose:
• Give usual initial dose, then reduce dose: [initial dose/SCr]
and give every 8 hours
• Once-daily dosing:
• Give usual mg/kg dose and adjust initial interval based on
CrCl (i.e. CrCl > 60 mL/min: every 24 h; CrCl 40-60
mL/min: every 36 h; CrCl 20-40 mL/min: every 48 h)
Drug-Induced Nephrotoxicity

45. Thank you!
Any questions?

46. References
• Santiago C, et. al. Renal Dopamine Receptors, Oxidative Stress, and Hypertension. International Journal of Molecular
Science. 2013 Sep: 14(9): 17553-17572
• Schmitz JM, et. al. Renal alpha-1 and alpha-2 adrenergic receptors: biochemical and pharmacological correlations. J
Pharmacol Exp Ther. 1981 Nov;219(2):400-6.
• Chunling Li, et. al. Molecular Mechanisms of Antidiuretic Effect on Oxytocin. Journal of the American Society Nephrology.
2008 Feb; 19(2):225-232
• Micromedex. Truven Health Analytics Inc. (online) Available at
<http://www.micromedexsolutions.com.acphs.idm.oclc.org/micromedex2/librarian/ND_T/evidencexpert/ND_PR/evidencexpert/
CS/613E30/ND_AppProduct/evidencexpert/DUPLICATIONSHIELDSYNC/2F559D/ND_PG/evidencexpert/ND_B/evidencexpe
rt/ND_P/evidencexpert/PFActionId/pf.HomePage?navitem=Logo#> (accessed 16 Sep 2015)
• CKD and Drug Dosing: Information for Providers. National Kidney Disease Education Program. Revised Apr 2015. Available
online at: www.nkdep.nih.gov
• Perazella MA. Drug use and nephrotoxicity in the intensive care unit. Kidney International (2012) 81, 1172-1178; doi:
10.1038/ki.2010.475
• DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM: Pharmacotherapy: A Pathophysiologic Approach, Ninth
Edition: www.accesspharmacy.com
• KDIGO clinical practice guideline for the management of blood pressure in chronic kidney disease. Kidney Int Suppl. 2012
Dec;2(5):337-414.

53. Radiographic contrast media-induced nephrotoxicity
(CIN)
• 3rd leading cause of hospital-acquired AKI
• <2% in patients with normal renal function
• Up to 50% in patients with CKD or diabetes
• Systemic hypotension (i.e. renal hypoperfusion) +
acute vasoconstriction  increased contrast
media remaining in tubules  cytotoxicity
Drug-Induced Nephrotoxicity

54. Prevention of radiographic CIN:
• Minimize contrast dose
• Use non-iodinated and low-/iso-osmolar contrast
media
• Hydration! – before, during and after
• Avoid other nephrotoxic drugs
Drug-Induced Nephrotoxicity

55. Tubular epithelial cell damage
Acute tubular necrosis
- Aminoglycoside antibiotics (gentamycin, tobramycin, etc.)
- Radiographic contrast media
- Cisplatin, carboplatin
- Amphotericin B
- Cyclosporine, tacrolimus
- Adefovir, cidofovir, tenofovir
- Pentamidine
- Foscarnet
- Zoledronate
Osmotic nephrosis
- Mannitol
- Dextran
- Radiocontrast media
- IV immunoglobulin
- Drug vehicles (e.g. sucrose, polyethylene glycol)
Drug-Induced Nephrotoxicity

56. Hemodynamically-mediated kidney injury
- ARBs (lisinopril, enalopril, etc.)
- ARBs (valsartan, candesartan, etc.)
- NSAIDs
- Cyclosporine, tacrolimus
- OKT3
Drug-Induced Nephrotoxicity

57. Obstructive neuropathy
Intratubular obstruction
- Acyclovir
- Sulfonamides
- Indinavir
- Foscarnet
- Methotrexate
Nephrolithiasis
- Sulfonamide
- Triamterene
- Indinavir
Nephrocalcinosis
- Oral sodium phosphate solution
Drug-Induced Nephrotoxicity

58. Glomerular disease
- Gold
- Lithium
- NSAIDs, COX-2 inhibitors (i.e. celecoxib)
Drug-Induced Nephrotoxicity

59. Tubulointerstitial disease
Allergic interstitial nephritis
- Penicillins
- Ciprofloxacin
- NSAIDs, COX-2 inhibitors (i.e. celecoxib)
- PPIs
- Loop diuretics (furosemide, torsemide, bumetanide)
Chronic interstitial nephritis
- Cyclosporine
- Lithium
- Aristolochic acid
Papillary necrosis
- NSAIDs
- Caffeine analgesics (e.g. Fiorecet, Fiorenol, Excedrin)
Drug-Induced Nephrotoxicity

60. Renal vasculitis, thrombosis and cholesterol emboli
Vasculitis and thrombosis
- Hydralazine
- Propylthiouracil
- Allopurinol
- Penicillamine
- Gemcitabine
- Mitomycin C
- Methamphetamines
- Cyclosprine, tacrolimus
- Adalimumab
- Bevacizumab
Cholesterol emboli
- Warfarin
- Thrombolytic agents
Drug-Induced Nephrotoxicity