Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_2754_Библиотеки_им_академика_М_И_Перельмана
.pdf
206 BASIC SKILLS IN INTERPRETING LABORATORY DATA
(140 age) weight(kg)
−×
1.73
BSA
20
Creatinine clearance
https://t.me/med1917
140
120
100
80
60
(mL/min)
40
20
0
0
123456
Serum creatinine (mg/dL)
78910
FIGURE 10-1. This plot represents the inverse
relationship between SCr and CrCl. Relatively small
change in kidney function as assessed by CrCl.
Because its excretion remains relatively consistent within these
ranges, UCr is oen used as a check for completion of urine collection. In adults, some clinicians discount a urine sample if it
contains <10 mg of creatinine/kg/24h and assume that the collection was incomplete. However, 8.5 mg/kg/day might be a better cuto, especially in critically ill elderly patients. UCr assays
are aected by most of the same substances that aect SCr. To
interfere signicantly, however, the substance must appear in the
urine in concentrations at least equal to those found in the blood.
Measured CrCl is calculated using the following formula:
CrCl (mL/min/1.73m)=[UCrV]/[Scr T]
where CrCl is the CrCl in mL/min/1.73 m2, UCr is urine creatinine concentration (mg/dL), V is volume of urine produced
during the collection interval (mL), SCr is serum creatinine
concentration (mg/dL), T is time of the collection interval
(minutes), and BSA is body surface area (m2).
BSA can be estimated using the standard method of Dubois
and Dubois42:
BSA(m)=0.20247 height (m)weight(kg)
BSA also can be estimated using the following equations from
Mosteller43:
BSA(m)=[height(cm)weight(kg)]/3,600
2
BSA(m)=[height(in)weight(lb)]/3,131
2
Adjustment of eGFR to a standard BSA (1.73 m2) allows
direct comparison with normal CrCl ranges because such tables
are in units of milliliters per minute per 1.73 m2. e CrCl value
adjusted for BSA is the number of milliliters cleared per minute
for each 1.73 m2 of the patient’s BSA. erefore, such adjustment
in a large person (>1.73 m2) reduces the original nonadjusted
clearance value because the assumption is that clearance would
be lower if the patient were smaller. In practice, de- indexed values in which CrCl is in millimeters per minute should be used,
and adjustment for body size is accomplished through a weightbased equation.
2
××
×××
.725 0.425
×
×
Estimation of Creatinine Clearance
In practice, dosage recommendations for medications excreted
through the kidneys have been traditionally based on the Cockcro-Gault estimation of CrCl. With the implementation of
standardized reporting of creatinine values, calculated CrCl
values may be 5% to 20% higher and may not correlate with
dosage guidelines based on renal dose adjustments on creatinine
values from older assays.
Cockcro-Gault equation. is formula provides an estima-
tion of CrCl.37 e patient’s age, body weight, and SCr concentration are necessary for the estimation. ere is some
controversy regarding which type of patient weight (total body
weight [TBW], ideal body weight [IBW], adjusted body weight
[ABW]) to use in the formula. Each weight aects the CrCl
dierently and may be preferred in certain situations over others. TBW may underestimate CrCl in underweight patients. In
contrast, IBW was more accurate than TBW in normal weight
patients. If TBW is less than IBW, use TBW to calculate CrCl.
Lastly, ABW using a factor of 0.4 was found to be the least
biased and most accurate method in patients who are obese
because TBW overestimates the CrCl in this situation.
Additional attempts to improve the Cockcro-Gault equa-
tion include rounding the SCr when values are <1.0 mg/dL. By
rounding the SCr to 1.0 mg/dL, the calculated CrCl is lower
than the value given by using the actual SCr. A lower CrCl may
lead to more conservative drug dosing. However, rounding of
SCr has resulted in signicant underestimation of CrCl.
results of a meta- analysis suggest that actual SCr most closely
(2)
estimates CrCl.47 Based on the available data, rounding of SCr
in elderly patients should be considered on a case- by- case basis
because of limited evidence that this approach improves accuracy. Conicting data exist for using lean body weight (LBW) to
improve CrCl calculation in patients who are overweight, obese,
or morbidly obese. Without clinical validation, both rounding
of SCr and using lean body weight should be used cautiously.
Additionally, this equation should be used cautiously in
patients with unstable renal function. Instead, other methods,
like cystatin C and the 6- variable MDRD equations, may provide
(3)
(4)
more accurate results in critically ill patients with uctuating
renal function, but validation is lacking.
CrCl(mL/min)=
72 SCr(mg/dL)
×
48
0.85(iffemale)
×
Body Weights Used with the Cockcro-Gault Equation
(5)
Weight (kg) Calculation
TBW Total body weight
IBW (male) (2.3 x inches > 5 feet) + 50 kg
IBW (female) (2.3 x inches > 5 feet) + 45.5 kg
ABW IBW (kg) + 0.4 x (TBW (kg) – IBW (kg))
To illustrate the variations in CrCl based on dierent weights,
consider a 50- year- old man with the following information:
height 72" (182.88 cm); weight 115 kg; BMI 34.3; SCr 1.7 mg/dL.
44
45,46
e
46
(6)
CHAPTER 10 • REnAl FunCTion And RElATEd TEsTs 207
2(
0
−−
https://t.me/med1917
e CrCl would be 84.6 mL/min with TBW, 57.1 mL/min using
IBW, and 68.1 mL/min using ABW. ese dierences may aect
diagnosis of CKD and renal dose adjustments for certain medications. Because the patient is obese, CrCl using TBW may
overestimate the CrCl, whereas using ABW may provide a more
accurate calculation.
Estimation of Glomerular Filtration Rate–Modication of
Diet in Renal Disease Equation. e MDRD equation had
been developed as a tool to identify patients at risk for complications arising from CKD.
14,49
(See Table10-2 for the stages of
CKD.) Although the CKD-EPI equation is largely considered
more accurate and less biased than the MDRD equation, some
laboratories still use the MDRD equation for reporting eGFR.
e MDRD equation provides an estimated GFR, which was
developed using measured GFR I- iothalamate reference values in patients with CKD. e abbreviated MDRD equation
has been reexpressed to include standardized SCr traceable
to IDMS values.
11,39,50-52
Patients at age extremes may be particularly vulnerable to errors of estimated GFR.
results of the MDRD equation should be interpreted cautiously
in patients with low muscle mass (eg, cachectic patients) or
those with unstable renal function.
One well- known limitation identied with the MDRD equa-
tion is underestimation of renal function for patients with eGFR
>60 mL/min/1.73 m2.53 Because this study did not include patients
with normal kidney function, the MDRD equation is considered
particularly less accurate at higher GFRs.54 is can lead to more
patients being falsely identied with CKD. In these populations,
the Kidney Disease: Improving Global Outcomes (KDIGO) working group recommends the measurement of cystatin C or direct
measurement of CrCl when SCr concentration is less accurate.
The original MDRD equation was also known as the
6- variable MDRD because it was based on six variables that
included age, sex, ethnicity, SCr, urea, and albumin.11 e
TABLE 10-2. Chronic Kidney Disease Stages
STAGE GFR (ML/MIN/1.73 M2) INTERPRETATION
*
1
*
2
>90
60–89 Mildly decreased
3 A 45–59
Normal or high GFR
Mildly to moderately
decreased
B 30–44
Moderately to
severely decreased
4 15–29
decreased
5
*In the absence of kidney damage, neither GFR category G1 nor G2
Source: Adapted with permission from Levey AS, Stevens PE, Bilous
RW, et al. KDIGO 2012 Clinical practice guideline for the evaluation
and management of chronic kidney disease. https://kdigo.org
/guidelines/ckd- evaluation- and- management.
<15
Kidney failure
9,13
In addition,
simplied 4- variable MDRD, shown below, uses four variables
that include age, sex, ethnicity, and a revised calibration for SCr:
GFR(mL/min/1.73 m)= 175 standardizedSCr
(0.203)
−
age1.212(ifAfricanAmerican)
××
0.742(iffemale)
×
×
Estimation of Glomerular Filtration Rate–
Chronic Kidney Disease Epidemiology
Collaboration Creatinine Equation 2009
Introduced in 2009, the Chronic Kidney Disease Epidemiology
Collaboration (CKD-EPI) equation is also based on standardized SCr, age, sex, and race. is equation performs with the
same degree of accuracy as the MDRD equation for patients
with eGFR <60 mL/min/1.73 m2.
55,56
However, it corrects the
inadequacy of the MDRD equation, which leads to underestimations in patients with eGFR >60 mL/min/1.73 m2. Both
the CKD-EPI and the MDRD equations account for age of the
patient. Like all SCr- based equations, the Cockcro-Gault,
MDRD, and CKD-EPI equations succumb to the same inherent
problems associated with this endogenous surrogate marker
(ie, the formula should not be used in patients with unstable
renal function). At the same SCr, younger patients who have
more muscle mass have a higher GFR than older adults with
low muscle mass. e usefulness of the CKD-EPI equation
may be particularly evident in younger patients without kidney
disease, younger patients with type 1 diabetes without microalbuminuria, or persons considering kidney donation with GFR
rates approximating normal values. Additionally, data support
5
its advantage over Cockcro-Gault and MDRD in prognostic
value in predicting cardiovascular mortality.57 KDIGO currently
recommends the CKD-EPI equation to estimate GFR.
GFR(mL/min/1.73m ) 141 min(S/ ,l)
max(S/ ,l)0.993 1.018 (iffemale)
1.159 (ifAfrican American)
κ
c
2
=× ×
−
1.209
age
×× ×
κ
c
where Sc = standardized SCr, κ = 0.7 for women and 0.9 for
men, α = −0.329 for women and −0.411 for men, min indicates
the minimum of Sc/κ or 1, and max indicates the maximum of
Sc/κ or 1.
Cystatin C Equations
Recently, there has been calibration and standardization of
traceable cystatin C concentrations to international reference
standards. e 2012 NKF KDOQI Clinical Practice Guidelines for the Evaluation and Management of CKD recommend measuring cystatin C in adults with eGFR between
45 and 59 mL/min/1.73 m2 who do not have conrmatory kidney
damage.5 e measurements of IDMS traceable cystatin C concentrations are not universally available in many community settings.
2012 Chronic Kidney Disease Epidemiology
Collaboration Cystatin C Equation
133 min(SCysC/0.8,1)max (SCysC/0.8,1)
××
0.996 0.932(iffemale)
××
0.499 .1328
age
5
:
1.154)
−
α
(7)
5,55,56
:
(8)
(9)
208 BASIC SKILLS IN INTERPRETING LABORATORY DATA
××
××
α−
−−
=×
https://t.me/med1917
where SCysC is serum cystatin C (in mg/L), min indicates the
minimum of SCysC/0.8 or 1, and max indicates the maximum
of SCysC/0.8 or 1.
2012 Chronic Kidney Disease Epidemiology
5
Collaboration Creatinine–Cystatin C Equation
135 min(SCrk,1)max (SCr /k,1)
×/
min(SCysC/0.8,1) max(SCysC/0.8,1)
age
0.995 (0.969 if female)
××
0.375 0.711
0.601
:
(1.08ifAfrican American)
where SCr is serum creatinine (in mg/dL), SCysC is serum
cystatin C (in mg/L), k is 0.7 for women and 0.9 for men,
α is −0.248 for women and −0.207 for men, min(SCr/k, 1)
indicates the minimum of SCr/k or 1, max(SCr/k, 1) indicates
the maximum of SCr/k or 1, min(SCysC/0.8, 1) indicates the
minimum of SCysC/0.8 or 1, and max(SCysC/0.8, 1) indicates
the maximum of SCysC/0.8 or 1.
Clinical controversy: Cockcro-Gault versus estimated
glomerular ltration rate equations. e appropriate dos-
ing of renally eliminated medications is necessary to prevent
overdosage or underdosage. Overdosage of a medication can
cause signicant clinical consequences and contribute to poor
patient outcomes. Similarly, underdosing medications can
lead to therapeutic failures. In both scenarios, inappropriate
medication dosing can lead to increased length of stay, higher
healthcare costs, and preventable medication- related problems. e MDRD equation provides a more accurate estimation of kidney excretory function than the Cockcro-Gault
equation.
11,58,59
At this time, the optimal single best equation
that can be used universally in all populations does not exist.
e usefulness of the MDRD equation in staging kidney
disease is indisputable. Recently, manufacturers have provided
some dosage guidance based on eGFR for patients with deteriorating kidney function. Recent studies support the agreement
of the MDRD equation with measured GFR and FDA- assigned
kidney function categories for medication dose adjustment.60
e NKDEP in 2009 suggested the use of either the CrCl as
estimated by Cockcro-Gault or the eGFR for dosing medications in CKD for most patients.61 However, this is controversial because most renal drug dosing is still based on CrCl.
An important caveat that is oen overlooked in the NKDEP
recommendation is that the eGFR needs to be individualized
in patients at the extremes in body size by multiplying the
eGFR/1.73 m2 by patient BSA to convert units to milliliters
per minute:
IndividualizedMDRDeGFR/1.73m
estimatedBSA(m )eGFRfordrugdosing
2
=
2
(11)
Alternatively, in patients who are considered to be high risk
for adverse medication events, who are taking drugs that have
a narrow therapeutic index, or in whom estimations of kidney
function vary or are inaccurate, consider measuring CrCl or
GFR using exogenous markers.5 e Nephrology Practice and
Research Network of the American College of Clinical Pharmacy
(10)
has suggested an algorithm for dosing medications eliminated
by the kidneys using SCr- based equations.62 Additionally, safety
and ecacy considerations aect decisions regarding dosing of
renally eliminated medications that include both patient factors (clinical condition, cachexia) and drug- specic properties
(therapeutic index). In summary, individualized patient characteristics and the specic clinical situation necessitate medication dosing decisions based on benets and risks rather them
numbers purely derived from generalized equations.
MEDICATION SAFETY
Pharmacists are responsible for optimizing the use of medications in their patients. Medications eliminated by the kidneys
require caution in patients with acute kidney disease and CKD
because the need for modifying the drug dose, extending the
dosing interval, discontinuing use, and totally avoiding nephrotoxic drugs must be considered. Drug manufacturers provide
drug information for use in patients with diminished renal
function. Serum levels of medications that depend on renal
elimination can be elevated, contributing to the increased likelihood of drug toxicity and subsequent adverse drug reactions.
As mentioned, the use of eGFR estimating equations or direct
measurements of CrCl, where appropriate, can provide important information for medication use and drug dosing. In situations in which SCr is not suitable, consider the use of a cystatin
C equation (Equation 14).5 Ensuring appropriate medication
use and dosing in patients with acute kidney disease and CKD
is one of the major contributions made by pharmacists. In acute
kidney disease, temporarily hold administration of drugs that
may contribute to or exacerbate kidney damage. Table10-3
identies medication safety considerations for use in patients
with acute or chronic kidney disease. However, specic medication recommendations from more than one reference should be
reviewed before committing to dosing decisions (Minicase 2).
URINALYSIS
Urinalysis is a commonly used clinical tool for the evaluation of
various renal and nonrenal problems (eg, endocrine, metabolic,
and genetic). A routine urinalysis is performed as a screening test
during many hospital admissions and initial physician visits. It
is also performed periodically in patients in nursing homes and
other settings. e most common components of the urinalysis
are discussed here.
An accurate interpretation of a urinalysis can be made only
if the urine specimen is properly collected and handled. Techniques are fairly standardized and, keeping in mind that urine
is normally sterile, aim to avoid contamination by normal ora
of the external environment (mucous membranes of the vagina
or uncircumcised penis or by microorganisms on the hands).
erefore, these areas are cleansed and physically kept away
from the urine stream. During menses or heavy vaginal secretions, a fresh tampon should be inserted before cleansing.
A rst- morning, midstream collection is customarily used as the
specimen.69 Once voided, the urine should be brought to the laboratory as soon as possible to prevent deterioration. If the sample is not
refrigerated, bacteria multiply and use glucose (if present) as a food
CHAPTER 10 • REnAl FunCTion And RElATEd TEsTs 209
https://t.me/med1917
TABLE 10-3. Medication Safety in Patients with CKD
AGENTS CAUTIONARY NOTES
Antihypertensives/cardiac medications
RAAS antagonists
(ACE-I, ARB,
aldosterone
antagonists, direct
renin inhibitors)
Digoxin
Analgesics
NSAIDs
Opioids
Antimicrobials
Penicillin
Aminoglycosides
Macrolides
Fluoroquinolones
• Avoid in people with suspected functional renal artery stenosis
• Start at lower dose in people with GFR <45 mL/min/1.73 m
2
• Assess GFR and measure serum potassium within 1 wk of starting or following any dose escalation
• Temporarily suspend during intercurrent illness, planned IV radiocontrast administration,
bowel preparation prior to colonoscopy, or before major surgery
• Do not routinely discontinue in people with GFR <30 mL/min/1.73 m2 because they remain
nephroprotective
Reduce dose by 50% in people with GFR <30 mL/min/1.73 m
•
2
• Reduce dose based on plasma concentrations
Avoid in people with GFR <30 mL/min/1.73 m
•
• Prolonged therapy is not recommended in people with GFR <60 mL/min/1.73 m
2
2
• Should not be used in people taking lithium
Avoid in people taking RAAS blocking agents
•
•
Reduce dose when GFR <60 mL/min/1.73 m
• Use with caution in people with GFR <15 mL/min/1.73 m
•
Risk of crystalluria when GFR <15 mL/min/1.73 m2 with high doses
2
2
• Neurotoxicity with benzylpenicillin when GFR <15 mL/min/1.73 m2 with high doses
(maximum 6 g/day)
•
Reduce dose and increase dosage interval when GFR <60 mL/min/1.73 m
2
• Monitor serum levels (trough and peak)
• Avoid concomitant ototoxic agents such as furosemide
•
Reduce dose by 50% when GFR <30 mL/min/1.73 m
Reduce dose by 50% when GFR <15 mL/min/1.73 m
•
2
2
Tetracyclines
Antifungals
Hypoglycemics
Sulfonylureas • Avoid agents that are mainly renally excreted (eg, glyburide/glibenclamide)
Insulin
Metformin
GLP-1 RA
1
Reduce dose when GFR <45 mL/min/1.73 m2; can exacerbate uremia
•
Avoid amphotericin unless no alternative when GFR <60 mL/min/1.73 m
•
• <45 mL/min/1.73 m
• <60 mL/min/1.73 m
2
2
2
• Other agents that are mainly metabolized in the liver may need reduced dose when
2
GFR <30 mL/min/1.73 m
• Partly renally excreted and may need reduced dose when GFR <30 mL/min/1.73 m
• Suggest avoiding when GFR <30 mL/min/1.73 m
• Review use when GFR <45 mL/min/1.73 m
•
(eg, gliclazide, gliquidone)
2
2
2
2
• Suspend in people who become acutely unwell
• Renal dose adjustment required (exenatide, lixisenatide)
• Caution when initiating or increasing dose due to potential risk of AKI
•
(continued )
210 BASIC SKILLS IN INTERPRETING LABORATORY DATA
https://t.me/med1917
TABLE 10-3. Medication Safety in Patients with CKD, cont’d
AGENTS CAUTIONARY NOTES
SGLT2i
Lipid-
1
lowering
• Renal dose adjustment required
•
• Talk about cutoffs with the four
Statins • No increase in toxicity for simvastatin dosed at 20 mg per day or simvastatin 20 mg/ezetimide
10- mg combinations per day in people with GFR <30 mL/min/1.73 m
2
or on dialysis
83
• Other trials of statins in people with GFR <15 mL/min/1.73 m2 or on dialysis also showed no
excess toxicity
•
Chemotherapeutic
Cisplatin
Melphalan
Methotrexate
Reduce dose when GFR <60 mL/min/1.73 m
•
• Avoid when GFR <30 mL/min/1.73 m
•
Reduce dose when GFR <60 mL/min/1.73 m
•
Reduce dose when GFR <60 mL/min/1.73 m
• Avoid if possible when GFR <15 mL/min/1.73 m
2
2
2
2
2
Anticoagulants
Low- molecular- weight
heparins
•
Halve the dose when GFR <30 mL/min/1.73 m
• Consider switch to conventional heparin or alternatively monitor plasma antifactor Xa in
2
persons at high risk for bleeding
Warfarin
DOAC
•
Increased risk of bleeding when GFR <30 mL/min/1.73 m
• Use lower doses and monitor closely when GFR <30 mL/min/1.73 m
Edoxaban is not approved for patients with poor renal function (CrCl <30 mL/min) or upper
•
2
2
range renal function (CrCl >95 mL/min)
•
Miscellaneous
Lithium • Nephrotoxic and may cause renal tubular dysfunction with prolonged use even at therapeutic
levels
• Monitor GFR, electrolytes, and lithium levels monthly or more frequently if the dose changes
or the patient is acutely unwell
• Avoid using concomitant NSAIDs
• Maintain hydration during intercurrent illness
•
Radiocontrast agents • Use with caution in advanced renal disease
• Iodinated and ionic iodinated contrast media may cause acute renal failure as serious adverse
effect
• Iodinated and ionic iodinated contrast media contraindicated in severe CKD
2
(GFR <30 mL/min/1.73 m
ACE-I = angiotensin- converting enzyme inhibitor; ARB = angiotensin- receptor blocker; DOAC = direct oral anticoagulant; GLP-1 RA =
glucagon- like peptide-1 receptor agonists; KDIGO = Kidney Disease: Improving Global Outcomes; RAAS = renin- angiotensin-
aldosterone system.
Data as of January 2013.
Source: Reproduced with permission from KDIGO
5
; adapted from References 63–68.
) or in AKI
CHAPTER 10 • REnAl FunCTion And RElATEd TEsTs 211
https://t.me/med1917
MINICASE 2
Heart Failure
Elle K., an 83- year- old woman with a long history of congestive
heart failure, is admitted to the hospital with reports of shortness of
breath (she has been sleeping in her recliner and is unable to sleep
in her bed despite using two pillows), a 15retention in her lower extremities. She also has anorexia, nausea,
fatigue, and weakness. All have worsened over the past 2 weeks.
Physical examination reveals a frail (5'3", 78 kg) woman in moderate
distress; heart rate 108 beats/min; BP 96/60mm Hg; S3/S4 heart sounds;
and +3 pitting edema bilateral lower extremities. Chest radiograph
reveals bilateral pleural effusions. Past medical history is significant for
hypertension, osteoarthritis of the knee, and atrial fibrillation.
Her current medications include the following:
• Lisinopril, 20 mg PO daily
• Metoprolol succinate, 100 mg PO daily
• Furosemide, 40 mg PO daily
• KCl, 10 mEq PO twice daily
• Ibuprofen, 400 mg PO four times daily PRN for knee pain
Laboratory test results are as follows:
• Sodium, 130 mEq/L (136 to 142 mEq/L)
• Potassium, 3.2 mEq/L (3.8 to 5 mEq/L)
• Chloride, 96 mEq/L (95 to 103 mEq/L)
• Carbon dioxide, 30 mEq/L (24 to 30 mEq/L or mmol/L)
• Magnesium, 1.6 mEq/L (1.3 to 2.1 mEq/L)
• Glucose, 78 mg/dL (70 to 110 mg/dL)
• Hgb, 11.5 g/dL (12.3 to 15.3 g/dL)
• BUN, 76 mg/dL (8 to 23 mg/dL)
• SCr, 2.5 mg/dL (0.6 to 1.2 mg/dL)
• BNP, 1,200 pg/mL (<100 pg/mL)
• Urinalysis, normal
Over the next 2 days, Elle K. receives aggressive diuretic therapy
(intravenous [IV] furosemide 80 mg twice a day), and all electrolyte
abnormalities were corrected. Her physical exam results were much
improved, and she was no longer short of breath.
On the morning of day4, her laboratory results were as follows:
• Sodium, 135 mEq/L
• Potassium, 3.2 mEq/L
• Chloride, 100 mEq/L
• Carbon dioxide, 34 mEq/L
• Magnesium, 1.4 mEq/L
• Glucose, 80 mg/dL
• Hgb, 11.4 g/dL
• BUN, 40 mg/dL
• SCr, 1.9 mg/dL
• BNP, 400 pg/mL
QUESTION: What type of renal dysfunction was this patient
experiencing on admission to the hospital? What are the likely
causes of her elevated BUN and SCr? Which formula would be
best to estimate CrCl or eGFR?
lb weight gain, and fluid
DISCUSSION: This is a rather complex case because of the
involvement of the kidneys in heart failure. Initially, the elevated
BUN and SCr could be attributed to a prerenal state secondary
to increased edema (hypervolemia) caused by worsening heart
failure. This is supported by her clinical presentation (weight gain,
symptoms of heart failure, chest X-ray, elevated BNP, and an
elevated BUN:SCr ratio with a ratio of >20:1). A normal urinalysis
would not reveal any cells that may indicate an intrinsic AKI (see
Urinalysis section). Additionally, diuretics may increase BUN, which
may complicate the picture, but the other evidence supports the
diagnosis of prerenal azotemia. Assessment of kidney function on
day1 is difficult because the Cockcroft-Gault, MDRD, or CKD-EPI
equation should not be used in patients with acute alterations in
kidney function. In suspected cases of AKI and when there is a
need to assess GFR, measurement of CrCl through collection of
urine may be considered; however, this technique is associated
with significant limitations in the setting of rapidly changing renal
function.
QUESTION: What factors may have contributed to this patient’s heart
failure exacerbation?
DISCUSSION: She has several risk factors that can worsen heart
failure. She has a history of hypertension and atrial fibrillation. If
her osteoarthritis has worsened, she may have been using more
ibuprofen more frequently and for an extended period of time.
Additional risk factors that could also contribute to exacerbation of
heart failure include nonadherence to medications (eg, furosemide)
and noncompliance with fluid (2 L) and diet (2g sodium/day)
restriction recommendations.
QUESTION: What other electrolyte abnormalities have resulted?
DISCUSSION: Several electrolyte abnormalities were identified
during initial presentation and subsequent laboratory analysis:
increased BUN and SCr, increased serum bicarbonate, hypokalemia,
hypomagnesemia, and hyponatremia. On admission, worsening
heart failure resulted in decreased RBF. As with creatinine, there
will be a reduction in BUN filtration at the glomerulus; however,
urea is avidly reabsorbed in the proximal tubule (following sodium
and water), resulting in an elevated ratio of BUN out of proportion
to the creatinine (>20:1). This patient also presented initially with
hypervolemic hyponatremia, most likely caused by worsening heart
failure, diminished blood flow to the kidneys, peripheral edema,
and subsequent weight gain. As she becomes euvolemic, the
hyponatremia will gradually be corrected. After aggressive diuresis
with IV furosemide, hypokalemia and hypomagnesemia require
replacement therapy. Loop diuretics can also cause metabolic
alkalosis (increased serum bicarbonate). Overaggressive diuresis
can cause elevations in BUN and SCr without evidence of overt
heart failure.
212 BASIC SKILLS IN INTERPRETING LABORATORY DATA
https://t.me/med1917
source. Subsequently, glucose concentrations decrease and ketones
may evaporate with prolonged standing. Another problem is that
formed elements (see Microscopic Analysis section) begin decomposing within 2 hours. With excessive exposure to light, bilirubin
and urobilinogen are oxidized. Unlike other substances, however,
protein is minimally aected by prolonged standing.
Aer a urine sample is collected, it may undergo three types
of testing: macroscopic, microscopic, and chemical (dipstick).
Macroscopic Analysis (General Appearance)
e color of normal urine varies greatly— from totally clear
to dark yellow or amber— depending on the concentration of
solutes. Color comes primarily from the pigments urochrome
and urobilin. Fresh normal urine is not cloudy or hazy, but urine
may become cloudy if urates (in an acid environment) or phosphates (in an alkaline environment) crystallize or precipitate out
of solution. ese salts become less soluble as the urine cools
from body temperature.
Turbidity may also occur when large numbers of RBCs or
white blood cells (WBCs) are present. An unusual amount of
foam may be from protein or bile acids. Table10-4 lists causes of
dierent urine colors. Some of the changes noted may be urine
pH– dependent. In general, drug- induced changes in urine color
are fairly rare. Drugs that cause or exacerbate any of the medical
problems listed in Table10-4 can also be considered indirect causes
of discolored urine.
Microscopic Analysis (Formed Elements)
Microscopic analysis typically involves the following steps71:
•
Centrifuging the urine (12 mL) at 2,000 revolutions per
minute for 5 minutes
• Pouring o all “loose” supernatant
• Mixing the sediment with the residual supernatant
•
Examining the resulting suspension under 400 to 440×
magnication (also described as high- power eld)
TABLE 10-4. Potential Causes of Various Urine Coloring
COLOR CAUSE POSSIBLE UNDERLYING ETIOLOGIES
Red to orange Myoglobin Crush injuries, electric shock, seizures, cocaine-
rhabdomyolysis
induced muscle damage,
Hemoglobin/
erythrocytes
Porphyrins Porphyria, lead poisoning, liver disease
Drugs/chemicals Drugs/chemicals causing previously mentioned diseases; as dyes: rifampin,
Food Beets, rhubarb, blackberries, cold drink dyes, carrots
Blue to green Biliverdin Oxidation of bilirubin (poorly preserved specimen)
Bacteria Pseudomonas or Proteus in urinary tract infections (rare), particularly in urine
Drugs/chemicals As dyes: amitriptyline, azuresin, methylene blue, Clorets abuse, Clinitest
Brown to black Myoglobin Crush injuries, electric shock, seizures, cocaine- induced muscle damage,
Bile pigments Hemolysis, bleed into tissues, liver disease
Melanin Melanoma (prolonged exposure to air)
Methemoglobin Methemoglobinemia from drugs, dyes
Hemolysis (malaria, drugs, strenuous exercise), menstrual contamination; kidney
stones
phenazopyridine, daunorubicin, doxorubicin, phenolphthalein, phenothiazines,
senna, chlorzoxazone, hydroxocobalamin
drainage bags
ingestion, mitoxantrone, triamterene, resorcinol, promethazine, cimetidine,
amitriptyline, metoclopramide, indomethacin, and propofol
rhabdomyolysis
Porphyrins Porphyria and sickle cell crisis
Drugs/chemicals As dyes: cascara, chloroquine, clofazimine, emodin, senna; as chemicals: ferrous
Source: Adapted from References 70–73.
salts, methocarbamol, metronidazole, nitrofurantoin, sulfonamides, sorbitol,
- dopa
CHAPTER 10 • REnAl FunCTion And RElATEd TEsTs 213
https://t.me/med1917
Microscopic analysis can be done either routinely or selectively. In either case, one should look for the three “Cs”— cells,
casts, and crystals.
Cells
eoretically, no cells should be seen during microscopic examination of urine. In practice, however, an occasional cell or two is
found. ese cells include microorganisms, RBCs, WBCs, and
tubular epithelial cells.
Microorganisms (normal range: zero to trace). If bacteria
are found in the urine sediment, contamination should be
the rst consideration. Of course, fungi, bacteria, and other
single- cell organisms can be seen in patients with a urinary
tract infection (UTI) or colonization. Even if ordered, some
laboratories do not perform urine cultures unless there is signicant bacteriuria. Signicant bacteriuria may be dened as
an initial positive dipstick screen for leukocyte esterase and
nitrites (Chemical Analysis section). Likewise, some laboratories do not process cultures further (eg, identication,
quantication, and susceptibility) if more than one or two different bacterial species are seen on initial plating. Additionally, some laboratories do not perform susceptibility testing
if more than one organism (some more than two) is isolated
or if <100,000 (some use 50,000 as the cuto) colony- forming
units (CFU) per milliliter per organism are measured with a
midstream, clean- catch sample. e common cuto for urine
obtained through a catheter is <10,000 CFU/mL/organism. If
multiple types of bacteria are present, contamination by ora
from vaginal, rectal, hand, skin, or other body site is assumed.
Red blood cells (erythrocytes) (normal range: one to three per
high-power eld). Hematuria is the abnormal renal excretion
of erythrocytes detected in two of three urine samples. A few
RBCs are occasionally found in the urine of a healthy man or
woman, particularly aer exertion, trauma, or fever. If persistent, even small numbers (more than two to three per highpowered eld) may reect urinary tract pathology. Increased
numbers of RBCs are seen (among others) in glomerulonephritis, infection (pyelonephritis), renal infarction or papillary
necrosis, tumors, stones, and coagulopathies. In some of these
disorders, hematuria may turn the urine pink or red (gross
hematuria). If a specimen is not collected properly, vaginal
blood may contaminate the urine.
White blood cells (leukocytes) (normal range: zero to two per
high-power eld). Potentially signicant pyuria has been dened
as three or more WBCs per high- power eld of centrifuged
urine sediment. Pyuria is usually associated with UTIs (upper or
lower). However, inammatory conditions (glomerulonephritis,
interstitial nephritis) may also lead to this nding.
Epithelial cells (normal range: zero to one per high-power
eld). Epithelial cells may be categorized as either squamous
or nonsquamous. Squamous cells originate from the surfaces
of external genitalia and the lower urinary tract. Presence of
a large number of squamous epithelial cells usually suggests
specimen contamination.
74,75
Tubular epithelial cells (normal range: zero or one per
high-power eld). One epithelial cell per high- power eld
71,72
is oen found in normal subjects. Cells originating from the
renal tubules are small, oval, and mononuclear. Nonsquamous epithelial cells include transitional cells and renal tubular epithelial cells, and their presence indicates acute tubular
necrosis, acute interstitial nephritis, and proliferative glomerulonephritis.75 eir quantity increases dramatically when the
tubules are damaged (eg, acute tubular necrosis) or when there
is inammation from interstitial nephritis or glomerulone-
71
phritis.
Casts
Casts are cylindrical masses of glycoproteins (eg, Tamm- Horsfall
mucoprotein) that form in the tubules. Casts have relatively
smooth and regular margins (as opposed to clumps of cells)
because they conform to the shape of the tubular lumen. Under
certain conditions, casts are released into the urine (called cylin-
druria). Even normal urine can contain a few clear casts. ese
formed elements are fragile and dissolve more quickly in warm,
alkaline urine. Types include hyaline, cellular, granular, and
waxy (broad); their causes are listed in Table10-5.
TABLE 10-5. Causes of Various Types of Casts in
Urine
CAST CAUSE
Red blood cell Classically seen with acute
glomerulonephritis; can be seen in patients
who play contact sports and uncommonly
with tubular interstitial disease
White blood
cell
Squamous
epithelial cell
Tubular
epithelial cell
Hyaline
Granular
Waxy (broad)
Source: Adapted with permission from References 71,72,74.
Classically seen with urinary tract
infections and cystitis; also seen with
glomerulonephritis and interstitial
nephritis
seen with perineal or vaginal specimen
contamination in females or foreskin
contamination in males
glomerulonephritis, tubulointerstitial
disease; also seen with cytomegalovirus
infection and toxicity from salicylates and
heavy metals, ethylene glycol
seen with prerenal azotemia and
strenuous exercise
acute tubular necrosis; volume depletion,
glomerulonephritis, tubulointerstitial
disease
with advanced or chronic renal failure
214 BASIC SKILLS IN INTERPRETING LABORATORY DATA
https://t.me/med1917
Hyaline casts. Being clear, hyaline casts are dicult to observe
under a microscope and are, by themselves, not indicative of
disease. Hyaline casts can be seen in concentrated urine or
with the use of diuretics.
72,75
Cellular casts. In contrast to hyaline casts, cellular casts are
seen with intrinsic renal disease. ey form when leukocytes,
RBCs, or renal tubular epithelial cells become entrapped in
the gelatinous matrix forming in the tubule. eir clinical signicance is the same as that of the cells themselves; unlike free
cells, however, cells in casts originate from within the kidneys.
e identication of a particular cast- type is oen used to
assist in diagnosis. WBC casts suggest intrarenal inammation
(eg, acute interstitial nephritis) or pyelonephritis. Epithelial
cell casts suggest tubular destruction; they may also be noted
in glomerulonephritis. RBC casts are seen in glomerulone-
71,75
phritis.
Granular and waxy casts. Granular and waxy casts are older,
degenerated forms of the other types. Granular (also called
muddy brown) casts can be seen in many conditions, such as
acute tubular necrosis, glomerulonephritis, and tubulointerstitial disease. Because waxy casts occur in many diseases, they
do not oer much diagnostic information.
71,75
Crystals
e presence of crystals in the urine depends on urinary pH, the
degree of saturation of the urine by the substance that is forming
crystals, and the presence of other substances in the urine that
may promote crystallization. Numerous types of crystals can
be detected in the urine (Figure10-2). Crystalluria, if dierentiated by type, can help identify patients with certain local
and systemic diseases. Cystine crystals occur with the condition
cystinuria, and struvite (magnesium ammonium phosphate)
crystals are seen with struvite stones. Calcium oxalate, calcium
phosphate, and uric acid crystals are also suggestive of stones.
Many crystals can be detected in otherwise healthy patients.
70,75
CHEMICAL ANALYSIS
(SEMIQUANTITATIVE TESTS,
URINE DIPSTICK TESTS)
For this discussion, biochemical analysis of urine includes protein;
pH; specic gravity; bilirubin, bile, and urobilinogen; blood and
hemoglobin; leukocyte esterase; nitrite; glucose; and ketones.
ese semiquantitative tests can be performed quickly using
modern dipsticks containing one or more reagent- impregnated
pads. When using these strips, the clinician must carefully apply
the urine to the pads as instructed and wait the designated time
before comparing pad colors to the color chart. Possible results
associated with various colors are displayed in Table10-6.
Protein
Normal range: zero to trace on dipstick or <200 mg/g (urine
protein to creatinine ratio)
e normal urinary proteins are albumin and low molecular
weight serum globulins. However, albumin has a molecular
weight of 66,000 Da and is typically restricted from passing
through the glomerulus into the urine. e smaller serum globulins that are ltered in the nephron are generally reabsorbed
in the proximal tubule. erefore, healthy individuals excrete
small amounts of protein in the urine (80 to <150 mg of protein
per day). In the presence of kidney damage, larger quantities of
protein may be excreted. Increased excretion of albumin is associated with diabetic nephropathy, glomerular disease, and uncontrolled hypertension. If low molecular globulins are detected, it
is more likely a tubulointerstitial process. e term proteinuria
is a general term that refers to the renal loss of protein (albumin
and globulins). e term albuminuria specically refers to the
abnormal renal excretion of albumin. Clinical proteinuria is
dened as the loss of >500 mg/day of protein urine. Patients with
microalbuminuria are excreting relatively small, but still pathogenic, amounts (30 to 300 mg/day) of albumin. Common causes
of proteinuria are listed in Table10-7. It should be noted that
proteinuria is sometimes intermittent and is not always pathologic (eg, aer exercise and fever).
Because of diculties with overnight and 24- hour collections, KDIGO recommends spot (untimed) urine testing. e
ACR ratio is convenient and accounts for urine volume eects on
protein concentration and standardizes the protein or albumin
excretion to creatinine excretion. e ratio of protein (or albumin) to creatinine in an untimed urine sample is an accurate esti
mate of the total amount of protein (or albumin) excreted in the
urine over 24 hours.5 e current criteria for staging and prognosis of CKD recommends testing for albuminuria. e KDIGO
working group recommends the urine ACR ratio as the preferred
method to assess for kidney damage in addition to estimation of
GFR. Like GFR, albuminuria should be assessed at least annually
in patients with CKD and more frequently in high- risk populations in whom measurements may aect clinical decisions.
5
Color indicator test strips (eg, Albustix, Multistix) used to
detect and measure protein in the urine contain a buer mixed
with a dye (usually tetrabromophenol blue). In the absence of
albumin, the buer holds the pH at 3, maintaining a yellow
color. If albumin is present, it reduces the activity coecient of
hydrogen ions (the pH rises), producing a blue color. Of note,
these tests are fairly insensitive to the presence of low molecular globulins, including the Bence-Jones protein. Results can
be aected by the urinary concentration. At both extremes of
urinary concentrations, false- positive and false- negative results
may occur. e potential for this can be easily assessed if specic
gravity is measured concomitantly. Substances that cause abnormal urine color may aect the readability of the strips, including
blood, bilirubin, phenazopyridine nitrofurantoin, and riboavin.78 Standard dipsticks do not detect microalbuminuria; however, newer dye- impregnated strips are available that can detect
lower concentrations of albumin. e KIDIGO recommends
conrming positive albuminuria test strips with quantitative
laboratory measurements as a ratio to creatinine when possible.
pH
Normal range: 4.6 to 8
Sulfuric acid, resulting from the metabolism of sulfurcontaining amino acids, is the primary acid generated by the
5
CHAPTER 10 • REnAl FunCTion And RElATEd TEsTs 215
https://t.me/med1917
Found chiefly
in alkaline
urine
Found chiefly
in acid urine
Ammonium urate
crystals
Calcium phosphate crystals
Uric acid crystals
Sodium urate crystals
Common form
Triple phosphate crystals
Amorphous phosphates
Amorphous urates
Rapidly precipitated form
Calcium
carbonate
crystals
Calcium oxalate crystals
Leucine crystals
Tyrosine
crystals
Sulfonamide crystals
Cystine crystals
FIGURE 10-2. Inorganic elements that may be found in urinary sediment. Elements founds in alkaline urine are
Source: Reprinted with permission from Runge MS, Greganti MA. Netter’s Internal Medicine. 2nd ed. Philadelphia,
PA: Saunders; 2008:766. Copyright© 2008. Netter medical illustration used with permission of Elsevier. All rights
reserved.
daily ingestion of food. e pH is usually estimated in 0.5- unit
increments by use of test strips containing methyl red and
bromthymol blue indicators. ese strips undergo a series of
color changes from orange to blue over a pH range of 5 to 8.5.
Additionally, pH can be precisely measured with electronic pH
meters. Normally, the kidneys can eliminate the acid load by
excreting acid itself and sodium hydroxide ions. In fact, healthy
persons can acidify urine to pH 4.5, although the average pH
is around 6. Any pH close to the reference range can be interpreted as normal as long as it reects the kidneys’ attempts
at regulating blood pH. Urinary pH can be aected by the
various acid–base disorders. Determination of the urinary
pH is oen used in the setting of a UTI.
(versus neutral) urine deters bacterial colonization. Alkaline
urine may be seen with either UTIs caused by urea- splitting
bacteria, such as Proteus mirabilis (via ammonia production),
or tubular defects causing decreased net tubular hydrogen ion
secretion, as in renal tubular acidosis.
By their intended or unintended pharmacological actions,
drugs can also cause true pH changes; they do not interfere with
the reagents used to estimate urine pH. Drugs that induce diseases associated with pH changes are indirect causes. ese and
other causes of acidic and alkaline urine are listed in Table10-8.
Persistent pHs >7are associated with calcium carbonate, calcium
74,75
In general, acidic
Соседние файлы в папке Библиотека им академика М.И. Перельмана