Learning Objectives

After completing this case study, students should be able to:

Calculate and interpret various markers for proteinuria

Understand various methods for estimating creatinine clearance and glomerular filtration rate.
Discuss the effects of CKD on drug absorption, distribution, metabolism, and excretion.
Dose a medication according to a patients renal function

Patient Presentation
Chief Complaint
I'm here to check the results of my labs.
HPI
Christine Karter-Davis is a 35-year-old African-American woman with type 2 diabetes mellitus who returns to her PCP
for a follow-up visit.
Last year's screening revealed SCr elevation to 1.2 mg/dL and albumin in the urine. Her last visit was 3 months ago for
a routine physical examination and her annual kidney screening. At that visit, a spot urine conducted at that time
revealed 3+ protein and Alb: Cr was 659 mcg/mg. A follow-up appointment was scheduled 6 weeks ago, and a second
spot urine test showed persistent elevation of Alb:Cr 615 mcg/mg. Complete laboratory workup was scheduled at that
time along with a 24-hour urine collection; this was completed last week. She has returned to the office today to
review the results of this testing.
PMH
Type 2 DM 8 years (history of gestational diabetes with use of insulin required)
HTN 6 years
Dyslipidemia 5 years
Gastric ulcer treated several years ago with H. pylori regimen (antibiotics and PPI)
Appendectomy at age 16
FH
Father had DM and CAD and died at age 50 secondary to MI; mother (age 62) has HTN and dyslipidemia. Brother (age
31) has DM, and two sisters (age 27 and 29) have no known medical problems other than obesity.
SH
She reports occasional alcohol consumption on weekends or when out with friends (one to two alcoholic beverages per
month). She is a one-ppd smoker; this is a decrease from her reported use of two ppd last year. No history of illicit
drug use.
All
NKDA, seasonal allergies to grass and pollen
Meds
Metformin 500 mg po TID
Hydrochlorothiazide 50 mg po daily
Atorvastatin 10 mg po at bedtime
Nasonex two sprays in each nostril BID (seasonalnot using currently)
Cetirizine 10 mg po daily PRN allergies
Aleve po PRN headaches
Omeprazole OTC 20 mg po PRN indigestion
Multivitamin po daily
Vitamin D3 1,000 IU po daily
ASA 325 mg po daily
Maalox 10ml PO TID PRN for indigestion
ROS
Occasional headaches, generally associated with menstruation; no c/o polyuria, polydipsia, polyphagia, sensory loss, or
visual changes
No dysuria, flank pain, hematuria, pedal edema, chest pain, or SOB
Physical Examination

Gen
The patient is a moderately obese African-American woman in NAD.
VS
BP 162/94 mmHg, HR 82 bpm, RR 18 breaths/min, T 37.5C; Wt 93 kg, Ht 56 BMI=33 kg/m2
Skin
Warm, dry, no rashes
HEENT
PERRLA, EOMI, fundi have microaneurysms consistent with diabetic retinopathy; no retinal edema or vitreous
hemorrhage. TMs intact. Oral mucosa moist with no lesions.
Neck/Lymph Nodes
Supple without adenopathy or thyromegaly
Lungs/Thorax
Clear, breath sounds normal
Cv
Heart sounds normal, no murmurs, no bruits
Abd
Soft NT/ND
Genit/Rect
Rectal exam deferred; recent Pap smear negative
MS/Ext
No CCE, normal ROM
Neuro
A & O 3; CNs intact; normal DTRs
Labs (1 Week Ago, Fasting)
Na 140 mEq/L
Hgb 12.2 g/dL
K 3.5 mEq/L
Hct 36.1%
Cl 107 mEq/L
WBC 9.5 103/mm3
CO2 26 mEq/L
Plt 199 103/mm3
BUN 29 mg/dL
Ca 9.4 mg/dL
SCr 1.4 mg/dL
Phos 3.5 mg/dL
Glu 196 mg/dL
A1C 10.4%

Fasting lipid profile:

T. chol 213 mg/dL
Trig 149 mg/dL
LDL 141 mg/dL
HDL 42 mg/dL
Alb 3.4 g/dL

UA (1 Week Ago)
Yellow, clear, pH 5.2, specific gravity, 1.010, 1+ glucose, (-) ketones, 3+ protein, (-) leukocyte esterase and nitrite; (-)
RBC; 3-4 WBC/hpf,
Spot Alb:Cr 673 mcg/mg
24-Hour Urine Collection
Total urine volume 2.2 L, urine creatinine 66 mg/dL, urine albumin: 873 mg/24 hours
Assessment
A 35-year-old woman recently diagnosed with diabetic nephropathy and overt albuminuria complicated by inadequately
controlled comorbid conditions
1. Identify any signs or symptoms of renal disease in this patient.
Elevated SCr (1.4 mg/dL, normal 0.6-1.1 mg/dL). Other electrolytes are still within normal limits, BUN slightly
elevated.
Proteinuria as evidenced by:
- dipstick with 3+ protein on 2 visits
- three spot Alb:Cr >300 mcg/mg (normal <30 mcg/mg)
- 24-hour urine collection (>300 mg albumin/24 hours, normal <30 mg/24 hours). (See page 6 of Assessment of Renal
Fxn handout, middle slide)
No symptoms of renal disease currently observed in this patient (edema, uremic symptoms such as n/v)

2. Could this patients renal disease have an etiology other than diabetes? What are some tests that can be
performed to further assess this patients renal disease?
While DM and HTN are leading causes of CKD, it is also possible that the renal disease could have a separate etiology. A
proper family history should be taken to determine if there is a history of inheritable renal disease i.e. polycystic
kidney disease. Review meds for drug-induced causes (i.e. heavy NSAID use)
Based on the National Kidney Foundation guidelines, ultrasound evaluation of the kidneys or other imaging studies may
be undertaken to eliminate nondiabetic causes of GFR decline. Biopsy is not required but may be performed if other
etiology is suspected.
3. Discuss the different markers of proteinuria collected for this patient and the degree of proteinuria associated
with each result. Discuss the limitations with each type of test.
Dipstick: 3+ protein. False negatives and positives possible, affected by urine concentration. Further testing necessary
to differentiate between microalbuminuria and clinical proteinuria.
Unlike the dipstick test for albumin alone, the Alb:Cr is not affected by urine concentration because it represents a
ratio between two measured substances (albumin and creatinine) in a urine sample. Alb:Cr < 30 mcg/mg is normal, 30299 mcg/mg = microalbuminuria, and > 300 mcg/mg = clinical proteinuria. Not tested for this patient but a prot:SCr >
200mg/g = clinical proteinuria. Albumin:Cr is usually tested for before Prot:Cr as microalbuminuria is detected before
proteinuria. All 3 of her Alb:Cr ratios suggest clinical proteinuria as they are all over 300 mcg/mg.
In addition to the spot Alb:Cr ratios, one can obtain a 24-hour urine collection to assess proteinuria. Some used to
consider the 24hr collection to be the gold standard for quantitative evaluation of albuminuria however improper
timing or missed samples may lead to significant overestimation and underestimation of albuminuria. In a 24-hr
collection, > 300 mg of albumin or total protein is clinical proteinuria. 873mg albumin was collected in this patients
24-hr collection indicating clinical proteinuria.
You can also calculate an alb:cr ratio from the 24 hr collection
66mg/dL CR x 10dL/L x 2.2L urine = 1452mg CR
873mg albumin/1452mg Cr x 1000mcg/mg = 601mcg/mg
The Alb:Cr estimates 24-hour urine albumin excretion without the inconvenience of a 24-hour collection and is
considered both a cost-effective and an efficient method to detect abnormalities in albumin excretion. Diagnosis of
albuminuria may be made if two of three spot urine ACRs collected over a 3- to 6-month period (taken at 1- to 8-week
intervals) are positive (microalbuminuria 30-299 mcg/mg; proteinuria more than 300 mcg/mg).
Day-to-day variation in creatinine excretion exhibits a coefficient of variation of 3-14%, and it is common for spot urine
Alb:Cr to vary from 24-hour. Spot urine Alb:Cr in this patient were 659, 615, and 673 mg/g, closely approximating the
values obtained in the 24-hour urine collection. It was not necessary to collect a 24-hour urine in this patient because
at least two of three spot urine samples (all three in this case) showed an Alb:Cr greater than 300 mcg/mg, which is
considered sufficient for diagnosis of proteinuria according to the National Kidney Disease Education Program (NKDEP),
the ADA, and the Canadian Diabetes Association (CDA) guidelines. The 24-hr collection is an additional available test
when assessing proteinuria (especially useful with variable Alb:Cr ratios).
4. Using most recent labs, what is the CrCl for this patient using the Cockcroft-Gault equation? Use actual weight,
IBW, and adjusted body weight and compare calculated CrCl values-which weight is most appropriate to use for
this patient?
Calculating CrCl from 24-Hour urine collections also a way to calculate CrCl however this is prone to error in collection
technique, etc.
Cockcroft-Gault equation:
The Cockcroft-Gault equation was designed to predict CrCl rather than GFR; it considers the effects of age, gender,
and body weight on SCr. As SCr increases, variability increases and the equation tends to overestimate GFR because of
tubular secretion. It also consistently overestimates GFR in healthy individuals. Despite these limitations, the
Cockcroft-Gault equation provides a sufficient estimation of GFR when GFR is above 25 mL/min. The most common use
of the Cockcroft-Gault equation is in drug dosing in renal impairment because it provides an easy method for
estimation of CrCl.

CrCl based on Cockcroft-Gault equation = (140 age) x weight (kg) x 0.85 for females/ (Scr x 72)
What weight to use for Cockcroft-Gault equation? Study from which Cockcroft-gault was derived was mostly normal
weight subjects but suggested a correction factor for obese. The weight used In clinical practice when calculating CG
varies however the largest study to date on this topic discussed in class (Pharmacotherapy. 2012 Jul;32(7):604-12)
suggests the following:
Actual body weight for those UNDER their IBW, BMI < 18.5
IBW for normal weight BMI 18.6 24.9
adjusted body weight for BMI > 25
IBW equations:
- Female: 45.5kg + 2.3kg for each inch over 5 ft
- Male: 50kg + 2.3kg for each inch over 5 ft Adjusted body weight for overweight and obese (BMI > 25). Adjusted BW =
IBW + 0.4(TBW IBW)
Adjusted body weight equation:
Adj BW = IBW + 0.4(actual BW IBW)
Salazar-Corcoran equation was developed for calculating CrCl in obese however has been phased out by using
Cockcroft-Gault with adjusted body weight as calculated with above equation. (71.4 ml/min using this calculator)
CrCl (actual body weight = 93kg) = 82.3 ml/mn
CrCl (IBW= 59.3) = 52.5 ml/min
CrCl (adjusted body weight=72.78) = 64.4 ml/min

most appropriate weight to use for this obese patient.

5. What equations are available to calculate an estimated GFR for this patient? Compare and contrast the
components and utility of these equations.
MDRD-6
MDRD-4
MDRD-IDMS
CKD-EPI
Components:
MDRD-6
GFR = 170 x (SCr)-0.999 x [age]-0.176 x [0.762 if patient is female] x [1.180 if patient is black] x [SUN]-0.170 x
[Alb]0.318 = SCR, Age, Gender, Race, BUN, Alb
MDRD-4
GFR = 186 x (SCr)-1.154 x [age] -0.203 x [0.742 if patient is female] x [1.210 if patient is black]
= SCR, Age, Gender, Race
MDRD-IDMS
GFR = 175 x (SCr)-1.154 x [age] -0.203 x [0.742 if patient is female] x [1.210 if patient is black]
Adjusted for SCr-IDMS assay
CKD-EPI (equation not in lecture slides)
GFR(mL/min/1.73m2)=
Blackfemales,SCr0.7mg/dL:166(SCr/0.7)0.329(0.993)Age
Blackfemales,SCr>0.7mg/dL:166(SCr/0.7)1.209(0.993)Age
Blackmales,SCr0.9mg/dL:163(SCr/0.9)0.411(0.993)Age
Blackmales,SCr>0.9mg/dL:163(SCr/0.9)1.209(0.993)Age
Nonblackfemales,SCr0.7mg/dL:144(SCr/0.7)0.329(0.993)Age
Nonblackfemales,SCr>0.7mg/dL:144(SCr/0.7)1.209(0.993)Age
Nonblackmales,SCr0.9mg/dL:141(SCr/0.9)0.411(0.993)Age
Nonblackmales,SCr>0.9mg/dL:141(SCr/0.9)1.209(0.993)Age
= SCR, Age, Gender, Race

Utility:
GFR was measured by measuring clearance of exogenous substances i.e. iothalamate. MDRD-6 equation was more
accurate than Cockcroft-Gault equation is estimating this GFR. MDRD-4 was found to be as accurate as MDRD-6 as is
simpler. MDRD-IDMS has an adjustment for the SCr-IDMS assay. CKD-EPI is better at estimating GFR in those with normal
renal fxn (GFR > 60 ml/min) and just as accurate for GFR < 60m/min and is already adjusted for use with the Scr-IDMS.
The CKD-EPI is not widely implemented yet i.e. not reported in our electronic medical record yet.
Note: This recitation is intended to give you additional background on the calculations used for proteinuria, CrCl, and
GFR. You do not need to memorize the MDRD or CKD-EPI equations; these are complicated equations and can also refer
to the online calculators when calculating them. You should know the Cockcroft-gault equation but there will be NO
calculations on the exam as you will not have calculators. Know when to use which weight (IBW vs. actual BW vs.
adjusted body weight and how to calculate these) and when to use which equation (Cockroft-Gault vs. MDRD vs. CKDEPI).
6. Based on values provided in table below, what stage of CKD does this patient have?

Cockcroft-Gault CrCl

64.4 ml/min

MDRD-4 (adjusted for IDMS)

52 ml/min/1.73m2

CKD-EPI

56 ml/min/1.73m2

Stage 1 CKD: 90 ml/min +

Stage 2 CKD: 60-89 ml/min
Stage 3 CKD: 30-59 ml/min
Stage 4 CKD: 15 30 ml/min
Stage 5 CKD: < 15 ml/min
CrCl = 64ml/min and GFR estimated by MDRD4 and CKD-EPI = 52 ml/min/1.73m2 and 56 ml/min/1.73m2. When staging
CKD, estimated GFR by MDRD-4 or CKD-EPI to be used rather than CrCl calculated by Cockcroft-gault as CG was shown
to be less accurate at estimating GFR compared to MDRD or CKD-EPI equations. For GFR > 60ml/min, CKD-EPI has been
shown to be more accurate than MDRD and for GFR < 60ml/min, it has been shown to be just as accurate. CrCl to be
used primarily for drug dosing, According to eGFR 52 - 56ml/min/1.73m2 (either MDRD or CKD-EPI is acceptable for this
pt with GFR < 60ml/min), this patient has Stage 3 CKD.
1 day later, Christine presents to the clinic with the chief complaint It burns when I urinate and Im urinating very
frequently.
ROS: urethral pain and burning with urination, as well as mild suprapubic tenderness. Patient denies systemic
symptoms such as fever, chills, vomiting, or back pain, and does not report any urethral or vaginal discharge.
UA: Yellow, cloudy; pH 5.0; WBC 10-15 cells/hpf; RBC 1-5 cells/hpf; protein 3+; trace blood; glucose 1+; leukocyte
esterase (+); nitrite (+); many bacteria
Urine culture: pending
Assessment: 35 year old woman with diabetic nephropathy presenting to clinic with dysuria, urinary frequency and UA
suggestive of acute uncomplicated cystitis (lower urinary tract infection).
Plan: The doctor plans to start levofloxacin for UTI treatment and asks you about the use of levofloxacin in CKD.
7. How will the ADME of levofloxacin be affected in this patient?
Factors from lecture that could affect ADME in CKD
Absorption:

Factors that decrease absorption: - gastroparesis (moreso time to Cmax rather than overall absorption), - increased
gastric pH from antacids, etc = decreased absorption of drugs that require acidic environment - Vomiting and
diarrhea - Chelate formation since many CKD-drugs with cations i.e antacids, ferrous sulfate - bowel wall edema
Factors that increase absorption: - Magnesium hydroxide and sodium bicarbonate may increase absorption of weakly
acidic drugs i.e. glipizide, glyburide, ibuprofen - decreased intestinal metabolism and p-gp transport
Distribution:
- less protein binding = increased [drug] especially acidic drugs
- more protein binding with alkaline drug b/c they bind to proteins that are present in higher amts in CKD - altered
tissue binding with digoxin = reduced Vd - increased Vd with fluid overload, edema
Metabolism: - Decreased hepatic and renal metabolism
Excretion: - decreased elimination of drugs that are primarily filtered - for drugs primarily secreted, decreased GFR
has less of on effect but secretion process also slowed in CKD
Excerpts from levofloxacins ADME:
Absorption:
Antacids containing magnesium or aluminum, sucralfate, metal cations such as iron or zinc, and buffered didanosine
may interfere with oral absorption of levofloxacin resulting in subtherapeutic systemic concentrations of the
quinolone. To minimize the possibility of an interaction, patients should be instructed not to ingest antacids containing
magnesium or aluminum, sucralfate, metal cations such as iron or zinc (including multivitamin preparations containing
zinc), or buffered didanosine (pediatric oral solution admixed with antacids) concomitantly with or within 2 hours of
levofloxacin oral dose.
Patient is taking Maalox which is an antacid containing magnesium and aluminum (caution: may accumulate in renal
impairment) and therefore must be separated by 2 hrs from levofloxacin dose to avoid chelate formation.
Distribution:
Widely distributed into body tissues and fluids, including skin, blister fluid, and lungs. Distributed into CSF.
Plasma Protein Binding of levofloxacin: 24-38% bound to serum proteins, principally albumin
Vd may further increase in CKD due to volume expansion, fluid overload
protein binding likely to decrease in CKD due to albuminuria, increasing Vd
Metabolism:
Undergoes limited metabolism to inactive metabolites. Not metabolized by CYP isoenzymes.
levofloxacin undergoes minimal metabolism and therefore is not greatly affected.
Elimination:
Eliminated principally as unchanged drug in urine by glomerular filtration and active tubular secretion. Approximately
87% of an oral dose eliminated in urine and <4% eliminated in feces.
Half-life:
Terminal elimination half-life approximately 6-8 hours after oral or IV administration. Decreased clearance and
prolonged half-life in patients with impaired renal function. Half-life may be 27 hours in those with Clcr 20-49
mL/minute and 35 hours in those with Clcr <20 mL/minute.
Decreased filtration and secretion in CKD, decreased elimination of drug, prolonged half-life. Thus, package insert
recommends dose adjustment in renal dysfunction.
Levofloxacin drug info:
For the treatment of urinary tract infection (UTI):
for mild to moderate complicated UTI or acute pyelonephritis:
Oral dosage:
Adults: 750 mg PO every 24 hours for 5 days or 250 mg PO every 24 hours for 10 days.
Intravenous dosage:
Adults: 750 mg IV every 24 hours for 5 days or 250 mg IV every 24 hours for 10 days.
for uncomplicated UTI (mild to moderate acute cystitis):

Oral dosage:
Adults: 250 mg PO every 24 hours for 3 days.
Patients with Renal Impairment Dosing
CrCl >= 50 ml/min: No dosage adjustment needed.
CrCl 2049 ml/min: For 750 mg doses, give 750 mg PO/IV every 48 hours; for 500 mg doses, 500 mg
PO/IV once, then 250 mg PO/IV every 24 hours; for 250 mg doses, no dose adjustments necessary.
CrCl 1019 ml/min: For 750 mg doses, give 750 mg PO/IV once then 500 mg PO/IV every 48 hours; for
500 mg doses, give 500 mg PO/IV once, then 250 mg PO/IV every 48 hours; for 250 mg doses, give 250
mg PO/IV every 48 hours except when treating uncomplicated UTI, then no dosage adjustment
necessary.
Levofloxacin 250mg po qhs x 3 days, no dose adjustment needed for this dose and for her current
renal function.
References:
Furler, Michelle D.. Renal Disorders: Case 54. Pharmacotherapy Casebook and Care Plans. 8th Ed. Ed. Terry
Schwinghammer, Ed. Julia Koehler.
Gerald K. McEvoy, Pharm.D., ed. 2014. AHFS Drug Information - 56th Ed. Bethesda, MD. American Society of HealthSystem Pharmacists, Inc. ISBN-10: 1-58528-380-0, ISBN-13: 978-1-58528-380-4. STAT!Ref Online Electronic Medical
Library. http://online.statref.com.proxy.cc.uic.edu/Document.aspx?fxId=1&docId=114. 9/7/2014 5:28:09 AM CDT (UTC
-05:00).