Creatinine Clearance In Pregnancy Normalized To Lean Body Mass Essay

Serum creatinine (a blood measurement) is an important indicator of renal health because it is an easily measured byproduct of muscle metabolism that is excreted unchanged by the kidneys. Creatinine itself is produced via a biological system involving creatine, phosphocreatine (also known as creatine phosphate), and adenosine triphosphate (

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Creatine is synthesized primarily in the liver from the methylation of glycocyamine (guanidino acetate, synthesized in the kidney from the amino acids arginine and glycine) by S-adenosyl methionine. It is then transported through blood to the other organs, muscle, and brain, where, through phosphorylation, it becomes the high-energy compound phosphocreatine. Creatine conversion to phosphocreatine is catalyzed by creatine kinase; spontaneous formation of creatinine occurs during the reaction.Creatinine Clearance In Pregnancy Normalized To Lean Body Mass Essay

At each specified interval, subjects had 6 ml of blood drawn using standard venipucture technique with a stainless steel, 20–23 gauge needle attached to a plastic syringe. The samples were placed into plastic tubes containing solid lithium heparin, gently rotated twice and centrifuged at 800 rpm for 20 min. Using a plastic pipette, plasma was proportioned into 2 plastic cryovials and frozen at < 20°F until ready for delivery to the analytical laboratories. All urine (2-h and 22-h) was collected in plastic containers and the volumes measured. Aliquots of urine were refrigerated at 40°F in plastic tubes containing no preservatives, until ready for delivery to the analytical laboratories.Creatinine Clearance In Pregnancy Normalized To Lean Body Mass Essay

The prevalence of obesity (body mass index [BMI] $30 kg/
m2
) continues to increase in both developed and developing countries.1 Recent estimates from the National
Health and Nutrition Examination Survey (2013-2014)
report prevalence of obesity of 37.7%, and class III obesity
(BMI $40 kg/m2
) of 7.7%, up from 33.9% and 5.7% in 2007
to 2008.2,3 Among the US population with CKD, the
prevalence of obesity and class III obesity is even higher,
at 44.1% and 22.2%, respectively.4 Both kidney disease
and obesity have important implications in terms of prognosis and drug dosing; however, methods for estimating
kidney function in the setting of obesity—particularly severe obesity—remain uncertain. In this review, we
examine the rationale for indexing glomerular filtration
rate (GFR) to body surface area (BSA), methods to estimate
GFR, and the accuracy and clinical implications of these
conventions in the obese population. Finally, we highlight
areas requiring additional research in the growing population of obese individuals.Creatinine Clearance In Pregnancy Normalized To Lean Body Mass Essay
RATIONALE FOR INDEXING GFR TO BSA
To fully understand the issues inherent to the assessment
of kidney function in obesity, we must first discuss the
rationale underlying the convention of indexing GFR to
BSA. Across mammalian species, GFR increases as kidney
and body mass increases. This relationship follows the power law equation (y ¼ aXb
), where y is the GFR, a is a constant, X is the body mass, and the coefficient b is estimated
to be 0.77 to 0.79.5,6 This “3
/4 power” relationship between
GFR and body mass is similar to the relationship between
metabolic rate and body mass, suggesting that GFR
increases proportionally to metabolic needs, which
makes physiological sense. In a similar manner, higher
glomerular number (power law coefficient 0.57-0.62)
and, to a lesser extent, glomerular capillary tuft volume
(power law coefficient 0.26-0.29) are associated with
higher body mass.5
BSA provides a critical role in dissipating heat produced
through metabolic processes, although recent literature
suggests that scaling of metabolism is complicated and
that substantial variation exists in animals.6,7 Because
BSA is a 2-dimensional variable whereas volume (body
mass) is a 3-dimensional variable, smaller animals have a
higher BSA to body mass ratio than larger animals. For
example, a mouse has a relatively higher metabolic rate
and GFR per body mass (0.2 mL/min, or about 0.007 mL/
min/g body weight) than a horse (390 mL/min, or about
0.0008 mL/min/g body weight).6 Allometric scaling was
first used to standardize GFR in humans in studies published in the early 20th century, based on the observation
that correction for BSA tended to normalize rates of urea
excretion.8,9
However, there is controversy over the most appropriate
scaling variable, as physiological rationale exists for other
factors such as resting energy expenditure (REE) or total
body water (TBW) because the kidneys help excrete metabolic wastes and regulate fluid and electrolyte balance. Ellam and colleagues10 used data from the Chronic Renal
Insufficiency Cohort (CRIC) study and the Modification
of Diet in Renal Disease (MDRD) study to examine gender
differences in metabolic burden. Men had higher 24-hour
urine urea excretion and serum urea nitrogen levels than
women; indexing to BSA only slightly attenuated these
gender differences. When GFR was indexed to estimated
REE, differences between 24-hour urine urea nitrogen
and serum urea nitrogen levels were mostly abolished.
From the Kidney Health Research Institute, Geisinger Health System, Danville,
PA; Department of Epidemiology and Health Services Research, Geisinger
Health System, Danville, PA; Welch Center for Prevention, Epidemiology,Creatinine Clearance In Pregnancy Normalized To Lean Body Mass Essay
and Clinical Research, Johns Hopkins University, Baltimore, MD; and Divison
of Nephrology, Johns Hopkins University, Baltimore, MA.
Financial Disclosure: The authors declare that they have no relevant financial interests.
Address correspondence to Alex R. Chang, MD, MS, 100 N Academy
Avenue, Danville, PA 17822. E-mail: achang@geisinger.edu
2017 by the National Kidney Foundation, Inc. All rights reserved.
1548-5595/$36.00
https://doi.org/10.1053/j.ackd.2017.10.007
Adv Chronic Kidney Dis. 2018;25(1):31-40 31
When GFR was indexed to estimated TBW, serum urea nitrogen levels were similar between genders, but the relationship was reversed for 24-hour urea nitrogen (higher
in women than men). Thus, indexing to BSA results in a
greater metabolic burden in men compared with women,
whereas indexing to REE or TBW may help reduce these
differences.
Daugirdas and colleagues11 used data from 1551 potential
kidney donors evaluated between 1973 and 2005 to examine
different methods of indexing GFR measured with 125I
-iothalamate. Mean BMI was 27.2 kg/m2 for men and 26.3 kg/
m2 for women. Scaling parameters included equationbased estimates of BSA, TBW, metabolic rate, and liver
size. Mean unindexed GFR was 122 mL/min in men and
106 mL/min in women. Indexing to TBW resulted in women
having higher indexed GFR (119 mL/min) than men (105 mL/
min), whereas indexing to BSA, or liver size, resulted in
similar mean indexed GFR for men and women (113 mL/
min/1.73 m2 for men and women using both methods).
Furthermore, indexing to
BSA resulted in the most uniform indexed GFR across
quintiles of BSA (Q1-5: 107,
103, 106, 103, and 104 mL/Creatinine Clearance In Pregnancy Normalized To Lean Body Mass Essay
min/1.73 m2
, respectively).
Thus, if GFR adjusted for a
body size scaling variable
should be similar across a
population, then BSA seems
to be appropriate.
EVIDENCE FOR INDEXING
TO BSA FROM THE
DIALYSIS POPULATION
Another interesting way to
compare different methods
of indexing GFR is to
examine patient outcomes
by hemodialysis adequacy,
which is commonly assessed
as Kt/V (where K is the urea
clearance of dialyzer, t is the
dialysis time, and V is the volume of distribution of urea,
which approximates TBW). Several studies have identified
limitations of using V as an indexing variable for a given
BSA, V is lower in smaller individuals than larger individuals.6,12 This may have resulted in hemodialysis treatment
disparities for smaller individuals. For instance, V is on
average lower in women than men, and women are
often prescribed treatments of shorter duration.
Port and colleagues13 examined the association between
dialysis dose and body size with mortality in 45,967
incident hemodialysis patients. Dialysis dose was divided
into 5 groups—urea reduction ratio (URR) ,60, 60 to 65, 65
to 70, 70 to 75, and .75, corresponding to single pool Kt/V
KT/V cutpoints of ,1.1, 1.2, 1.32, 1.5, and .1.7. Lower BMI
and lower dialysis dose were both associated with
increased risk of death. When stratified by tertiles of
body size (BMI—small ,23.1 kg/m2
, medium,Creatinine Clearance In Pregnancy Normalized To Lean Body Mass Essay

NOW

Plasma and urine boron were measured at West Coast Analytical Laboratory (WCAS) using inductively coupled plasma-mass spectrometry (ICPMS). All samples were brought to room temperature and either shaken or vortexed to facilitate mixing. After preparing the dilutions, all solutions were also vortexed. The internal standard (IS) used for all samples and standards was 10B at a final concentration of 50 μg/l. Human plasma samples were prepared for testing by making 1/10 v/v dilutions in 0.05% ammonium hydroxide containing 10B internal standard. Urines were diluted 1/10 v/v in 5% nitric acid containing 10B internal standard. Samples were analyzed for 10B and 11B content by inductively coupled plasma-mass spectrometry (ICPMS), using both a VG PlasmaQuad II system and a PE/Sciex Elan 6100 system. The samples were introduced into the ICPMS by utilizing automated flow injection via either a FIAS system or by controlling the time it took the autosampler to fill the sample loop. NIST SRM 951, boric acid, which is certified for both purity and isotopic content, was used to prepare boron standards in the range of 1 μg/l to 200 μg/l. Standards were prepared in both 5% nitric acid containing 10B internal standard and 0.05% ammonium hydroxide containing 10B internal standard. Acid standards were used for acid prepared samples and the basic standards were used for the basic dilutions. Below are typical instrument parameters for data acquisition. Boron background and carryover was controlled by limiting the sample size (approximately 0.3 ml) and concentration (< 200 μg/l). For the VG PlasmaQuad (∼0.3 ml), samples were injected using a time-controlled uptake with a Gilson Model 222 autosampler. Acquisition was timed for 10 s in the middle of the 20-s sample-loop plug. The flow rate to the instrument was 1.2 ml/min delivered by a Gilson minipuls 3 peristaltic pump. Data was collected for masses of 9Be, 10B, and 11B using a dwell time of 50 ms for each selected isotope. Washout time was 60 s at 1.2 ml/min. For the ELAN 6100, a 0.2 ml sample loop was used. The sample injection timing was controlled by a PE/SCIEX FIAS 400 unit. A Gilson peristaltic pump at 1.5 ml/min controlled sample flow rates. The flow rate for the FIAS was 1.1 ml/min. Washout time was 15 s at a flow rate of 2.4 ml/min. Acquisition masses were 9Be, 10B, and 11B using a dwell time of 10 ms. All other instrument parameters were typical operating settings recommended by the manufacturers.Creatinine Clearance In Pregnancy Normalized To Lean Body Mass Essay

All urine and plasma samples were analyzed for creatinine using a quantitative, colorimetric method (Sigma Diagnostics, St. Louis, MO.). Reference samples were obtained from Sigma Diagnostics. In addition, in-house plasma and urine samples were included as reference samples in each batch of samples analyzed. Creatinine clearance was used as a measure of glomerular filtration rate (GFR). The creatinine analyses were performed at the University of California, Irvine. Creatinine Clearance In Pregnancy Normalized To Lean Body Mass Essay

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