4/9/06njm

**Q. Can we use a protein to creatinine ratio instead of a 24 urine
protein in preeclampsia?**

A. P:C is a standard metric for chronic renal disease. Here are the
details in the OB setting

What would you do if you worked in an Indian Health facility that was 2
hours away from a Level III nursery and a 30 week EGA patient presented
with a blood pressure of slightly greater than 140 / 90 on two occasions
separated by 6 hours, a clean catch urine dipstick of 1+, and a mild
headache?

One of the possible scenarios would include hospitalizing the patient in
your facility and beginning a 24 hour urine collection for protein.
Unfortunately the 24 hour urine collection is one of the most
notoriously incomplete samples that we routinely encounter. It is
estimated that 10-20% of specimens are incomplete and should be
discarded because of the difficulties associated with obtaining a
complete collection, particularly in the outpatient setting.

The second issue is that pre-eclampsia can have a rapidly progressive
course and waiting 24-36 hours for a diagnosis. In this case definitive
neonatal care is a 2 hour transport time away and can mean the
difference between an orderly maternal / fetal transport of a stable
patient versus the emergent delivery of significantly preterm infant in
a remote facility without adequate neonatal support.

Another scenario for the same patient would include performing a random
spot urine protein to creatinine ratio and triaging based on that
estimate. Price et al's systematic literature review documents that "the
protein:creatinine ratio on a random urine specimen provides evidence to
\"rule out\" the presence of significant proteinuria as defined by a
24-h urine excretion measurement."

In this clinical situation the international community and the data has
preceded the U.S. national benchmark organizations' recommendations. The
International Society for the Study of Hypertension in Pregnancy
Statement on the classification and diagnosis of the hypertensive
disorders of pregnancy recommends either a P:C of \> 30 mg / mmol
(calculates to 0.26 mg/mg creatinine), or a 24 hour urine value of 300
mg/ day for the baseline diagnosis of pre-eclampsia.

On the other hand, neither the National Kidney Foundation, nor the
American College of Obstetricians and Gynecologists recommends the use
of the protein to creatinine ratio in pregnancy. Perhaps after these two
U.S. groups re-examine the data, including the Price et al systematic
literature review, and the international acceptance of P:C the U.S.
recommendations may change.

Another disadvantage is that there is not complete agreement in the
nephrology community on how to convert the protein to creatinine ratio
to a similar 24 hour urine protein result. The prevailing view is that
the P:C roughly correlates on a one for one basis with a 24 hour
specimen, e. g., a P:C of 3.5 roughly correlates to a 24 hour urine
protein of 3.5 grams. On the other hand, other nephrologists feel the
ratio on a random urine specimen correlates closely with daily protein
excretion in g/1.73 m2 of body surface area, when used in mild to
moderate pre-eclampsia.

On balance as the urine protein to creatinine ratio is a
unit-less measure (mg/dl divided by mg/dl causes the units to cancel
out) usually expressed as mg of protein per mg of creatinine.  Hence if
one knows the total amount of creatinine that a pregnant excretes per
day, then one can estimate the 24 hour urine protein excretion. The
minimum diagnosis of pre-eclampsia, based on proteinuria, can be made at
a P:C of 0.2 and further conversions can be made on a 1:1 basis, e. g.,
a P:C of 5.0 correlates to a 24 hour protein of 5.0 grams.

In summary, the use of the spot urine protein to creatinine ratio has
supplanted most of the 24 hour urine estimations done in both pediatric
and adult nephrologist's clinical practice.  Yet, the practice is not
endorsed for use in pregnancy by the National Kidney Foundation, ACOG,
or any U.S. national benchmark organization. This mismatch of U.S.
benchmarks and clinical recommendations leads to confusion in the
clinical care of U.S. pregnant women.

The protein to creatinine ratio offers significant advantages to
pregnant Indian Health patients and should be explored for use at your
facility. Considering the long track record of successful use of the
protein to creatinine ratio in adults with chronic renal disease, the
endorsement the International Society for the Study of Hypertension in
Pregnancy, plus Price et al systematic literature review, the time may
have come for our clinical practice to precede the U.S. national
benchmark recommendations.

After discussion among your medical staff, plus local maternal fetal
medicine and nephrology consultants, the protein to creatinine ratio
will offer significant advantages in the triage of American Indian /
Alaska Native women with hypertensive disorders of pregnancy.

**Background**

While the use of the P:C ratio is a standard of care to determine the
extent of proteinuria in the chronic renal patients, should it be
applied universally to an acute obstetric setting whose hallmark is
intense vasoconstriction with rapid swings in fluid balance?

To decide, let's do the following....

1.) Review advantages / disadvantages of a random P:C vs 24 hour PROT
sample

2.) Review the national benchmark recommendations

3.) Review the literature in pregnancy to put those recommendations into
perspective

4.) Review how the P:C could be used in pregnancy with examples

5.) Other discussion

6.) Summarize what we know so far

7.) References

**#1 Sample collection advantages and disadvantages**

The 24 hour urine collection technique is fraught with difficulties.
Unless the patient has an indwelling catheter, the specimen is likely to
be in complete. It is estimated that 10-20% of specimens are incomplete
and should be discarded because of the difficulties associated with
obtaining a complete collection, particularly in the outpatient setting.

On the other hand, a random spot urine is easy to obtain. The spot urine
is still subject to contamination that might increase the protein
content of the specimen.

+-----------------------------------+-----------------------------------+
| **Timed 24 hour protein sample**  | **Random Spot P:C Urine sample**  |
+-----------------------------------+-----------------------------------+
| **Advantages**                    | **Advantages**                    |
+-----------------------------------+-----------------------------------+
| Directly relates to published     | Easy to collect                   |
| results of published 24 hour      |                                   |
| protein excretion                 |                                   |
+-----------------------------------+-----------------------------------+
| Easy assay for most laboratories  | Easy assay for most laboratories  |
| to perform                        | to perform                        |
+-----------------------------------+-----------------------------------+
| Defines protein over 24 hours     | Directly relates to published     |
|                                   | results of random                 |
|                                   |                                   |
|                                   | P:C                               |
+-----------------------------------+-----------------------------------+
|                                   | Good estimate of protein          |
|                                   | excretion over 24 hrs             |
+-----------------------------------+-----------------------------------+
| **Disadvantages**                 | **Disadvantages**                 |
+-----------------------------------+-----------------------------------+
| Most complex of samples           | Lower creatinine excretion in     |
|                                   | women:                            |
+-----------------------------------+-----------------------------------+
| Frequent incomplete specimens     |                                   |
+-----------------------------------+-----------------------------------+

Modified from The National Kidney Foundation and American Diabetes
Association list these advantages and disadvantages, Table 60

<http://www.kidney.org/professionals/kdoqi/guidelines_ckd/Gif_File/kck_t60.gif>

**#2 U.S. National Benchmark Recommendations**

Neither the National Kidney Foundation, nor the American College of
Obstetricians and Gynecologists recommends the use of the protein to
creatinine ratio in pregnancy. Perhaps after these two groups re-examine
the data, including the Price et al systematic literature review, their
recommendations may change. The Strength of Recommendation Taxonomy
(SORT) evidence based review recommends the P:C in adult patients, but
recommends the 24 hour specimen in pregnancy.

The International Society for the Study of Hypertension in Pregnancy
Statement on the classification and diagnosis of the hypertensive
disorders of pregnancy recommends either a P:C of \> 30 mg / mmol
(calculates to 0.26 mg/mg creatinine, or 24 hour urine value of 300 mg/
d for the baseline diagnosis of pre-eclampsia.

**#3 Literature review**

Price et al published a systematic literature review of data extracted
from 16 studies investigating proteinuria in several settings; patient
groups studied were primarily those with preeclampsia or renal disease.
Price et al concluded that the protein:creatinine ratio on a random
urine specimen provides evidence to \"rule out\" the presence of
significant proteinuria as defined by a 24-h urine excretion
measurement.

A summary of a review of over 160 abstracts on PubMed using these
keywords pregnancy, protein creatinine ratio, and pre-eclampsia is
presented in the reference section below.

The individual authors used a variety of methods to evaluate the
accuracy and precision of this test. In those studies that investigated
the P:C versus a 24 hour protein in pregnancy, a tally of just the
sample size of patients in those articles in which the authors concluded
support for the use of the P:C in pregnancy involved 779 patients. In
contrast, there were 696 patients in those articles in which the
author's conclusions that did not support the use of the P:C in
pregnancy in their individual study.

Please note that a variety of different methods were used to support
each separate author's conclusions on the utility of the P:C, e. g., not
a unified approach like the Price et al systematic literature review.

**#4 How the P:C could be used in pregnancy with examples**

**From UpToDate**

**A. Evaluation of proteinuria in pregnant women**

<http://www.uptodateonline.com/application/topic.asp?file=maternal/8748>

[Editorial Comment:]{.underline} Please note the study directly below
that is referred to as 'large' studied 138 patients and the report about
use of P:C in hospitalized patients studied 30 patients.

**Quantitation of daily excretion** --- There are two methods for
quantitating 24 hour protein excretion. The most accurate means of
quantitation of proteinuria is the 24 hour urine collection.

**Urine protein to creatinine ratio** --- Proteinuria can also be
measured by calculating the protein-to creatinine (P:C) ratio in a
random urine sample
\[[10,11](http://www.uptodateonline.com/application/abstract.asp?TR=maternal/8748&viewAbs=10~11&title=10,11)\].
This minimizes collection and laboratory errors, saves time in obtaining
results, and is far more convenient for the patient. However, there is
no consensus on the best threshold for identifying pregnant women with
significant proteinuria
\[[12-19](http://www.uptodateonline.com/application/abstract.asp?TR=maternal/8748&viewAbs=12~13~14~15~16~17~18~19&title=12-19)\].
([See \"Measurement of urinary protein
excretion\"](http://www.uptodateonline.com/application/topic.asp?file=glomrdis/5359)).

One large study concluded that in the presence of stable renal function,
a P:C ratio ![](media/image1.png){width="8.333333333333333e-2in"
height="9.236111111111112e-2in"}0.19 optimally predicted protein
excretion ![](media/image1.png){width="8.333333333333333e-2in"
height="9.236111111111112e-2in"}300 mg per day (sensitivity,
specificity, positive predictive value, negative predictive value: 90,
70, 75, and 87 percent, respectively)
\[[12](http://www.uptodateonline.com/application/abstract.asp?TR=maternal/8748&viewAbs=12&title=12)\].
Fifty percent of this population had significant proteinuria and most of
the false-negative and false-positive test results were within 50 mg of
the cutoff of 300 mg for a 24-hour urine. A cut-off of 0.14 had
sensitivity and negative predictive values of 100 percent, but
specificity dropped to 51 percent.

The P:C ratio appears to be most useful when quantitation of proteinuria
is desired quickly and in ambulatory patients with hypertension and very
low P:C values in whom the presence of significant proteinuria (and thus
preeclampsia) can be excluded confidently.

In another report in which hospitalized patients were followed with
serial tests, the P:C ratio correlated with changes in 24-hour protein
excretion over time
\[[17](http://www.uptodateonline.com/application/abstract.asp?TR=maternal/8748&viewAbs=17&title=17)\].
Therefore, the test could be used to evaluate for progression of
preeclampsia, along with other clinical parameters.

**24 hour urine collection** --- The most accurate means of quantitation
of proteinuria is the 24 hour urine collection. The collection is begun
at the usual time that the patient awakens. At that time, the first void
is discarded and the exact time noted. Subsequently, all urine voids are
collected with the last void timed to finish the collection at exactly
the same time the next morning. The time of the final urine specimen
should vary by no more than 5 or 10 minutes from the time of starting
the collection the previous morning. An inexpensive basin urinal that
fits into the toilet bowl facilitates collection.

The bottle(s) may be kept at normal room temperature for a day or two,
but should be kept cool or refrigerated for longer periods of time. No
preservatives are needed.

**[CCC Editorial Comment:]{.underline}**

The urine protein to creatinine ratio is a unit-less measure (mg/dl
divided by mg/dl causes the units to cancel out) usually expressed as mg
of protein per mg of creatinine.  Hence if one knows the total amount of
creatinine that a pregnant excretes per day, then one can estimate the
24 hour urine protein excretion. Others express the P:C as mg/mmol, e.
g., 30 mg/mmol calculates to 0.26 mg/mg creatinine.

On the other hand, other nephrologists feel the ratio on a random urine
specimen correlates closely with daily protein excretion in g/1.73 m2 of
body surface area, when used in mild to moderate preeclampsia. (see
UpToDate below)

Controversy exists on how to best interpret the P:C in comparison to a
24 urine specimen. Most nephrologists roughly correlate the P:C and the
two measurements on a one for one basis, e. g., a P:C of 9.0 is
approximately 9 g/day, or 5.0 is approximately 5 g/day.

The minimum diagnosis of pre-eclampsia, based on proteinuria, can be
made at a P:C of 0.2 and further conversions can be made on a 1:1 basis,
e. g., a P:C of 5.0 correlates to a 24 hour protein of 5.0 grams, which
is one of the criteria for severe pre-eclampsia.

**#5 Other Discussion**

-The pathophysiology of proteinuria may occur as a result of two
mechanisms. Proteinuria can result from tubular proteinuria whereby
there is a failure to reabsorb normally filtered proteins or there is an
increase in tubular secretion of protein such as alpha-2-microglobulin
(used to be called Tamm-Horsfall protein). This usually results in less
than 1 gram of proteinuria per 24 hours. The more common mechanism of
proteinuria is via increased glomerular permeability and increased
proteinuria that is usually greater than 1 gram per 24 hours.
Proteinuria greater than 3.5 grams per 24 hours is always due to
glomerular disease and increased glomerular permeability. With increased
glomerular permeability, the protein loss can be viewed in terms of
glomerular filtrate and thus the creatinine filtered at the glomerulus
and the protein filtered at the glomerulus would then be passed through
the tubule where very little creatinine would be secreted or absorbed.
Hence, we frequently talk in terms of fractional excretion by comparing
the concentration of something in the urine (i.e. sodium) to creatinine
(i.e. fractional excretion of sodium). The final protein concentration
in the urine would be no different. Pre-eclampsia is associated with
increased glomerular permeability as a result of glomerular
endotheliosis.

-Most diseases, except diabetes, have declining proteinuria as GFR
declines (this is typically seen in glomerulonephritis). Diabetic
nephropathy is the exception to this rule, where as the disease
progresses, proteinuria tends to be greater with declines in GFR.
Amyloidosis is another example of a disease that causes increasing
proteinuria with declining GFR. In pre-eclampsia, you would have two
opposing situations. As glomerular endotheliosis worsens, greater
glomerular permeability would result in greater protein excretion, but
as GFR declines, this would result in a decreasing filtered load of
protein and decreasing proteinuria. Hence, one would have to interpret
proteinuria in this relative context. However, in a given individual,
this could be followed over time by using the protein to creatinine
ratio on a spot specimen, and compare to the calculated GFR (eGFR).

-The urine protein to creatinine ratio is a unit-less measure (mg/dl
divided by mg/dl causes the units to cancel out) usually expressed as mg
of protein per mg of creatinine.  Hence if one knows the total amount of
creatinine that a pregnant excretes per day, then one can estimate the
24 hour urine protein excretion.  Creatinine excretion is a function of
muscle mass and not a function of surface area, hence, relating it to
surface area may not be appropriate.  If one has a prior 24 hour
urine that is reliable, then one can use that number for calculating
total mg of protein excretion per day.  In pregnancy, the creatinine
excretion would be a function of the mother\'s muscle mass as well as
the baby\'s and would change with progressive growth of the fetus.  The
ratio roughly correlates to grams of protein excreted per day and was
validated in a linear correlation coefficient with 24 hour urine
protein.  It was not normalized to 1.73 m2. 

-Some nephrologists question the value of comparing the degree of
proteinuria in one pre-eclamptic to another pre-eclamptic. For example,
if one patient has a protein:creatinine ratio of 0.6 and another has a
protein:creatinine ratio of 3.5, is one worse than the other? But if one
day a pre-eclamptic has a ratio of 0.6 and the next day has a ratio of
3.5 with the same GFR, then this is worse from a kidney pathophysiologic
point of view.

On the other hand, obstetricians base their clinical management on the
principle that if a pregnant patient has a 24 urine protein of 350
mg/day one week that that patient has mild pre-eclampsia and if another
patient has over 5 grams of proteinuria that the second patient has
severe pre-eclampsia. The obstetrical management of the two patients
would be very different.

**#6 Summary**

The 24 hour urine protein is the gold standard for measurement of
protein during pregnancy in a controlled setting. On the other hand, the
24 hour collection method is logistically complex and tends toward
incomplete specimens in direct patient use. It is estimated that 10-20%
of specimens are incomplete and should be discarded because of the
difficulties associated with obtaining a complete collection,
particularly in the outpatient setting.

Use of the P:C is the standard of care in chronic renal failure. Taken
individually the available literature for use of the P:C in pregnancy is
not black and white. Yet, in a systematic literature review of pregnant
and non-pregnant patients, Price et al concluded that "the
protein:creatinine ratio on a random urine specimen provides evidence to
\"rule out\" the presence of significant proteinuria as defined by a
24-h urine excretion measurement."

If one just uses each individual study author's own conclusions on the
value a screening P:C, then the literature appears decidedly mixed.
There was not a unified methodology utilized by the wide gamut of
individual study authors. Among the individual study authors there is
essentially an equal distribution of patients in whom the P:C accurately
and precisely reproduced a 24 hour specimen, versus in those samples in
which the P:C did not accurately or precisely reproduce the 24 hour
specimen.

Spot specimens are now easily corrected for creatinine excretion and are
part of the

routine in most nephrology practices.  Most nephrologists do not rely on
semiquantitativie estimation of a dipstick, but rather actual
measurement of protein to creatinine ratios that are easily reproducible
in individual patients. 

Most nephrologists use the P:C in preference to 24-hour collections
because nursing and patient errors in the timing of the 24-hour
collection are eliminated. All of the dipsticks still use an
approximation that gives general ranges and are highly sensitive but not
specific or reproducible in comparative studies.

The P:C ratio appears to be most useful when quantitation of proteinuria
is desired quickly and in ambulatory patients with hypertension and very
low P:C values in whom the presence of significant proteinuria (and thus
preeclampsia) can be excluded confidently. A useful cut-off in the
United States is 0.2. The international cut-off is 30 mg/mmol
(calculates to 0.26 mg/mg creatinine).

Controversy also exists on how to interpret the P:C in comparison to a
24 urine specimen. Most nephrologists roughly correlate the P:C and the
two measurements on a one for one basis, e. g., a P:C of 3.5 roughly
correlates to a 24 hour urine protein of 3.5 grams. On the other hand,
other nephrologists feel the ratio on a random urine specimen correlates
closely with daily protein excretion in g/1.73 m2 of body surface area,
when used in mild to moderate preeclampsia.

On balance as the urine protein to creatinine ratio should be considered
a unit-less measure (mg/dl divided by mg/dl causes the units to cancel
out) usually expressed as mg of protein per mg of creatinine.  Hence if
one knows the total amount of creatinine that a pregnant excretes per
day, then one can estimate the 24 hour urine protein excretion. The
minimum diagnosis of pre-eclampsia, based on proteinuria, can be made at
a P:C of 0.2 and further conversions can be made on a 1:1 basis, e. g.,
a P:C of 5.0 correlates to a 24 hour protein of 5.0 grams.

There is very limited data in which hospitalized pregnant patients were
followed with serial tests, the P:C ratio correlated with changes in
24-hour protein excretion over time. Therefore, the test could be used
to evaluate for progression of preeclampsia, along with other clinical
parameters.

In the section of the 2001 REPORT of the WORKING GROUP on RESEARCH on
HYPERTENSION DURING PREGNANCY discussing \"Future Research\" (pages 25
and 26), the observation is made that \"Use of current estimates of
qualitative and quantitative protein excretion should be analyzed.\" 

Three issues for future study may be:

A.) the accuracy and precision of P:C as a screening technique for
proteinuria in pregnancy

B.) can the P:C be used as a method to monitor the ongoing course
proteinuria in pre-eclampsia

C.) " patients who are rapidly progressing from mild to severe
pre-eclampsia.

Finally, the use of the spot urine protein to creatinine ratio has
supplanted most of the 24 hour urine estimations done in both pediatric
and adult nephrologist's clinical practice.  Yet, the practice is not
endorsed for use in pregnancy by the National Kidney Foundation, ACOG,
or any U.S. national benchmark organization. This mismatch of U. S.
benchmark clinical recommendations leads to confusion in the clinical
care of U.S. pregnant women.

This confusion exists because of mismatch between the U.S. benchmark
recommendations and the recommendation of the International Society for
the Study of Hypertension for the use of the P:C, combined with a
systematic literature review that "the protein:creatinine ratio on a
random urine specimen provides evidence to \"rule out\" the presence of
significant proteinuria as defined by a 24-h urine excretion
measurement."

In the meantime, the protein to creatinine ratio offers significant
advantages to pregnant Indian Health patients and should be explored for
use at your facility. Considering the long track record of successful
use of the protein to creatinine ratio in adults with chronic renal
disease, and Price et al, the time has come for our clinical practice to
precede the U.S. national benchmark recommendations.

After discussion among your medical staff, plus local maternal fetal
medicine and nephrology consultants, the protein to creatinine ratio
will offer significant advantages in the triage of American Indian /
Alaska Native women with hypertensive disorders of pregnancy.

**Multiple Resources Below:**

U.S. National benchmark summary

Indvidual benchmark(s)

ACOG

National Kidney Foundation

Strength of Recommendation Taxonomy (SORT) Evidence based system

UpToDate Summary

Article references

**U.S. National Benchmark Summary**

**A.)** **Consensus Working Group**

The latest National Kidney Foundation endorsement was of the 24 hour
urine, not of the P:C in pregnancy, e.g., 2001 REPORT of the WORKING
GROUP on RESEARCH on HYPERTENSION DURING PREGNANCY.

This consensus document is a supplement to the regularly updated
positions of the Joint National Committee on Detection, Prevention,
Evaluation and Treatment of High Blood Pressure. These reports are
produced in conjunction with the National Institutes of Health. This
consensus process is widely endorsed by many nephrologists. 

**B.)** **The National Kidney Foundation and American Diabetes
Association**

The National Kidney Foundation\'s Kidney Disease Outcomes Quality
Initiative (KDOQI) guidelines and the American Diabetes Association
(ADA) guidelines recommend screening for microalbuminuria in all
patients at risk for kidney disease. Screening can be performed using a
microalbumin-sensitive dipstick or analysis of a random morning urine
sample to determine the microalbumin-creatinine ratio.

[Normal protein excretion (S, R).]{.underline} Normal mean value for
urine albumin excretion in adults is approximately 10 mg/d. Albumin
excretion is increased by physiological variables, such as upright
posture, exercise, pregnancy, and fever. Normal mean value for urine
total protein is approximately 50 mg/d. Major constituents of normal
urine protein are albumin, LMW proteins filtered from the blood, and
proteins derived from the urinary tract.

Pregnancy has a major effect on GFR, with GFR reaching values of 140% of
normal during the end of the second trimester.

**C.) American College of Obstretricians and Gynecologists (ACOG)**

While ACOG lists the 24 hour urine protein collection as a gold standard
diagnostic criteria, ACOG does acknowledge:

"The correlation coefficient between this ratio and the 24-hour urine
total protein was 0.94. Investigators also reported high sensitivity and
specificity between the protein/creatinine ratio from a single urine
sample and proteinuria of 300 mg or greater in a 24-hour specimen....."

(Chronic Hypertension in Pregnancy. ACOG Practice Bulletin No. 29.)

**D.) What does the Strength of Recommendation Taxonomy (SORT) evidence
based review say?**

The SORT review recommends the random P:C in adults medical patients,
but Table 4 recommends the 24 hour urine in pregnancy to determine GFR.

+---------------------------------------------------+--------+---------+
| sort: kEy Recommendations for practice            |        |         |
+---------------------------------------------------+--------+---------+
| Clinical recommendation                           | Ev     | Ref     |
|                                                   | idence | erences |
|                                                   | rating |         |
+---------------------------------------------------+--------+---------+
| All adults with risk factors for chronic kidney   | C      | 1, 5, 6 |
| disease should be screened with a serum           |        |         |
| creatinine determination for GFR estimation and   |        |         |
| analysis of a random urine sample for             |        |         |
| proteinuria.                                      |        |         |
+---------------------------------------------------+--------+---------+
| [Instead of a timed urine collection, a random    | [C]{   | 1, 24,  |
| urine sample for the microalbumin-creatinine or   | .mark} | 25      |
| protein-creatinine ratio should be used to        |        |         |
| quantify proteinuria.]{.mark}                     |        |         |
+---------------------------------------------------+--------+---------+
| Interventions proved to slow the progression of   | A      | 1, 24,  |
| chronic kidney disease include blood pressure     |        | 33,\    |
| control, glycemic control, and reduction of       |        | 34, 37  |
| proteinuria with an angiotensin-converting enzyme |        |         |
| inhibitor or angiotensin-II receptor blocker.     |        |         |
+---------------------------------------------------+--------+---------+
| A low-density lipoprotein goal of less than 100   | C      | 37      |
| mg per dL (2.60 mmol per L) is recommended for    |        |         |
| patients with chronic kidney disease, because     |        |         |
| these patients are statistically at highest risk  |        |         |
| for cardiovascular disease.                       |        |         |
+---------------------------------------------------+--------+---------+
| A blood pressure goal of 130/80 mm Hg is          | B      | 1, 30   |
| recommended in patients with normal urinary       |        |         |
| albumin concentrations, and a blood pressure goal |        |         |
| of 125/75 mm Hg is recommended in patients with   |        |         |
| proteinuria equal to or greater than 1 g per 24   |        |         |
| hours.                                            |        |         |
+---------------------------------------------------+--------+---------+
| GFR = glomerular filtration rate.                 |        |         |
|                                                   |        |         |
| A = consistent, good-quality patient-oriented     |        |         |
| evidence; B = inconsistent or limited-quality     |        |         |
| patient-oriented evidence; C = consensus,         |        |         |
| disease-oriented evidence, usual practice, expert |        |         |
| opinion, or case series. For information about    |        |         |
| the SORT evidence rating system, see page 1639 or |        |         |
| <http://www.aafp.org/afpsort.xml>.                |        |         |
+---------------------------------------------------+--------+---------+

+---------------------------+------------------------------------------+
| table 4                   |                                          |
|                           |                                          |
| Preferred Methods for     |                                          |
| Assessing Kidney Function |                                          |
+---------------------------+------------------------------------------+
| Method                    | Situations for use                       |
+---------------------------+------------------------------------------+
| MDRD study equation for   | Patients with diabetic kidney disease†   |
| estimating GFR\*          |                                          |
|                           | Patients with chronic kidney disease in  |
|                           | middle-age (average age: 51 years)†      |
|                           |                                          |
|                           | Black patients with hypertensive chronic |
|                           | kidney disease†                          |
|                           |                                          |
|                           | Patients with a kidney transplant†       |
+---------------------------+------------------------------------------+
| Cockcroft-Gault equation\ | Older patients (performs better than the |
| for estimating creatinine | MDRD study equation)                     |
| clearance\*               |                                          |
+---------------------------+------------------------------------------+
| [24-hour urine collection | [Pregnant women]{.mark}                  |
| for creatinine            |                                          |
| clearance]{.mark}         | Patients with extremes of age and weight |
|                           |                                          |
|                           | Patients with malnutrition               |
|                           |                                          |
|                           | Patients with skeletal muscle diseases   |
|                           |                                          |
|                           | Patients with paraplegia or quadriplegia |
|                           |                                          |
|                           | Patients with a vegetarian diet and      |
|                           | rapidly changing kidney function         |
+---------------------------+------------------------------------------+
| MDRD = Modification of    |                                          |
| Diet in Renal Disease;    |                                          |
| GFR = glomerular          |                                          |
| filtration rate.          |                                          |
|                           |                                          |
| \*-Requires stable kidney |                                          |
| function.                 |                                          |
|                           |                                          |
| †-Validated for use in    |                                          |
| these patients.           |                                          |
|                           |                                          |
| Based on information from |                                          |
| references 3 and 12       |                                          |
| through 17.               |                                          |
+---------------------------+------------------------------------------+

**Individual U.S. Benchmark Background**

**ACOG**

A. Chronic Hypertension in Pregnancy. ACOG Practice Bulletin No. 29.

**#1**

**Are laboratory tests useful in evaluating a pregnant woman with
essential hypertension?**

In pregnant women with known essential hypertension (primary
hypertension or hypertension not secondary to underlying renal or
adrenal disease), baseline laboratory evaluations that may prove
clinically useful include tests of renal function such as serum
creatinine, blood urea nitrogen, and 24-hour urine evaluation for total
protein and creatinine clearance . This initial laboratory assessment is
important in identifying women with underlying renal disease because
this complication may adversely affect pregnancy outcome. The subsequent
development of proteinuria in a woman with essential hypertension also
may be helpful in identifying the development of superimposed
preeclampsia.

As pregnancy progresses, other laboratory tests---in addition to
repeating those mentioned previously---may be clinically useful in
evaluating worsening renal disease and in diagnosing superimposed
preeclampsia. These include liver function tests, hemoglobin/hematocrit
evaluation, and platelet count. Periodic measurement of urine protein
may be useful in detecting worsening renal disease or the development of
superimposed preeclampsia. It has been reported that the random protein-
creatinine ratio may be useful for the quantitation of proteinuria
during pregnancy. [The correlation coefficient between this ratio and
the 24-hour urine total protein was 0.94. Investigators also reported
high sensitivity and specificity between the protein/creatinine ratio
from a single urine sample and proteinuria of 300 mg or greater in a
24-hour specimen.]{.underline}

B. Diagnosis and management of preeclampsia and eclampsia. ACOG Practice
Bulletin No. 33.

#1

**Criteria for Diagnosis of Preeclampsia\***

-   Blood pressure of 140 mm Hg systolic or higher or 90 mm Hg diastolic
    or higher that occurs after 20 weeks of gestation in a woman with
    previously normal blood pressure

-   Proteinuria, defined as urinary excretion of 0.3 g protein or higher
    in a 24-hour urine specimen

\*Preeclampsia is a pregnancy-specific syndrome that usually occurs
after 20 weeks of gestation.

#2

**The following recommendations are based primarily on consensus and
expert opinion (Level C):**

-   Women should be considered as having severe preeclampsia if they
    have blood pressure levels of 160 mm Hg systolic or higher or 110 mm
    Hg diastolic or higher on two occasions at least 6 hours apart while
    the patient is on bed rest, proteinuria of 5 g or higher in a
    24-hour urine specimen or 3+ or greater on two random urine samples
    collected at least 4 hours apart, oliguria of less than 500 mL in 24
    hours, cerebral or visual disturbances, pulmonary edema or cyanosis,
    epigastric or right upper-quadrant pain, elevated liver enzymes,
    thrombocytopenia, or fetal growth restriction.

#3

**Renal Changes**

As a result of vasospasm, the normal expected increase in glomerular
filtration rate and renal blood flow and the expected decrease in serum
creatinine may not occur in women with preeclampsia, especially if the
disease is severe. Oliguria, commonly (albeit arbitrarily) defined as
less than 500 mL in 24 hours, also may occur secondary to the
hemoconcentration and decreased renal blood flow. Rarely, persistent
oliguria may reflect acute tubular necrosis, which may lead to acute
renal failure

#4

**Maternal evaluation**

What is the optimal treatment for preeclampsia? The decision to deliver
a patient with preeclampsia must balance both the maternal and fetal
risks. Continued observation is appropriate for the woman with a preterm
fetus only if she has mild preeclampsia (4). Such therapy consists of
fetal and maternal evaluation. No randomized trials have determined the
best tests for fetal evaluation. The Working Group recommends weekly
nonstress tests, biophysical profiles, or both, which should be repeated
as indicated according to maternal condition. Testing is recommended
twice weekly for suspected fetal growth restriction or oligohydramnios.
Daily fetal movement assessment also may prove useful. The Working Group
also recommends ultrasound examination for fetal growth and amniotic
fluid assessment every 3 weeks (4).

[Maternal evaluation consists primarily of frequent evaluation for
worsening preeclampsia. Initial laboratory tests consist of evaluation
of platelet count, liver enzymes, and renal function and a 12-hour to
24-hour urine collection for protein.]{.underline} With mild disease and
no progression, these tests can be repeated weekly. The tests should be
repeated sooner if disease progression is questionable.......

Chronic Hypertension in Pregnancy. ACOG Practice Bulletin No. 29.
American College of Obstetricians and Gynecologists. Obstet Gynecol
2001; 98:177-185

Data from Report of the National High Blood Pressure Education Program
Working Group Report on High Blood Pressure in Pregnancy. Am J Obstet
Gynecol 2000;183:S1--S22

Diagnosis and management of preeclampsia and eclampsia. ACOG Practice
Bulletin No. 33. American College of Obstetricians and Gynecologists.
Obstet Gynecol 2002;99:159--167

**National Kidney Foundation**

2001 REPORT of the WORKING GROUP on RESEARCH on HYPERTENSION DURING
PREGNANCY

(The National Kidney Foundation endorsement is on page vii of the pdf)

<http://www.nhlbi.nih.gov/health/prof/heart/hbp/hbp_preg.pdf>

or

<http://www.nhlbi.nih.gov/health/prof/heart/hbp/hbp_preg.htm>

or

<http://www.nhlbi.nih.gov/resources/hyperten_preg/>

**K/DOQI Clinical Practice Guidelines for Chronic Kidney Disease:
Evaluation, Classification, and Stratification**

**PART 4.  DEFINITION AND CLASSIFICATION OF STAGES OF CHRONIC KIDNEY
DISEASE**

GUIDELINE 1. DEFINITION AND STAGES OF CHRONIC KIDNEY DISEASE

***Normal protein excretion (S, R).*** Normal mean value for urine
albumin excretion in adults is approximately 10 mg/d. Albumin excretion
is increased by physiological variables, such as upright posture,
exercise, pregnancy, and fever. Normal mean value for urine total
protein is approximately 50 mg/d. Major constituents of normal urine
protein are albumin, LMW proteins filtered from the blood, and proteins
derived from the urinary tract.

Pregnancy has a major effect on GFR, with GFR reaching values of 140% of
normal during the end of the second trimester.

<http://www.kidney.org/professionals/kdoqi/gfr_calculator.cfm>

**The K/DOQI Clinical Practice Guidelines for Chronic Kidney Disease:
Evaluation, Classification, and Stratification**

Spot Urine Protein vs. Timed Urine Protein in Adults

<http://www.kidney.org/professionals/kdoqi/guidelines_ckd/Gif_File/kck_t53.gif>

Spot Urine Albumin vs. Timed Urine Albumin in Adults

<http://www.kidney.org/professionals/kdoqi/guidelines_ckd/Gif_File/kck_t54.gif>

Spot Urine Dipstick Albumin vs. Timed Urine Albumin in Adults

<http://www.kidney.org/professionals/kdoqi/guidelines_ckd/Gif_File/kck_t55.gif>

Spot Urine Protein-to-Creatinine Ratio vs. Timed Urine Protein in Adults

<http://www.kidney.org/professionals/kdoqi/guidelines_ckd/Gif_File/kck_t56.gif>

Spot Urine Albumin-to-Creatinine Ratio vs. Timed Urine Albumin in Adults

<http://www.kidney.org/professionals/kdoqi/guidelines_ckd/Gif_File/kck_t57.gif>

## National Kidney Foundation Seventh Annual Spring Clinical Nephrology Meetings Audiotapes

### Nashville, TN       March 26-29, 1998

The National Kidney Foundation, in conjunction with Conference Copy
Incorporated presents professional recordings of the actual sessions
from the program. For ordering information [click
here](http://www.kidney.org/news/audiotapesCM98.cfm#order%23order). For
a list of other meetings and session recordings available, [click
here](http://www.kidney.org/news/index.cfm).

**22 THE MANAGEMENT OF HYPERTENSION IN PREGNANCY**\
      - Co-chairs: Susan P. Bagby, MD, Susan H. Bray, MD

-   Evolving Concepts In Pathogenesis, Treatment And Prevention Of
    Pre-Eclampsia\
          - James M. Roberts, MD

-   Pharmacologic Management Of Pregnancy-Associated Hypertension\
          - Professor Judith Whitworth

<http://www.kidney.org/professionals/kdoqi/gfr_calculator.cfm>

K/DOQI Clinical Practice Guidelines for Cardiovascular Disease in
Dialysis Patients

References

532\. Marin R, Gorostidi M, Portal CG, Sanchez M, Sanchez E, Alvarez J:
Long-term prognosis of hypertension in pregnancy. [Hypertens Pregnancy
19:199-209,
2000](https://webmail.ualberta.ca/redirect?http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10877988)

National Kidney Foundation. K/DOQI, clinical practice guidelines for
chronic kidney disease: evaluation, classification, and stratification.
Am J Kidney Dis 2002;39 (2 suppl 1):S1-266.
<http://www.kidney.org/professionals/kdoqi/guidelines_ckd/toc.htm>.

Molitch ME, DeFronzo RA, Franz MJ, Keane WF, Mogensen CE, Parving HH, et
al. American Diabetes Association. Nephropathy in diabetes. Diabetes
Care 2004;29(suppl 1):S79-83.

The K/DOQI Clinical Practice Guidelines for Chronic Kidney Disease:
Evaluation, Classification, and Stratification

Comparison of Methods for Urine Collection for Assessment of Proteinuria

<http://www.kidney.org/professionals/kdoqi/guidelines_ckd/Gif_File/kck_t60.gif>

Common Causes of False Results in Routine Measurements of Urinary
Albumin or Total Protein

<http://www.kidney.org/professionals/kdoqi/guidelines_ckd/Gif_File/kck_t61.gif>

Definitions of Proteinuria and Albuminuria

<http://www.kidney.org/professionals/kdoqi/guidelines_ckd/Gif_File/kck_t15.gif>

A user-friendly GFR calculator is available online at
<http://www.kidney.org/professionals/kdoqi/gfr_page.cfm>

**Strength of Recommendation Taxonomy (SORT)**

SNYDER S, PENDERGRAPH B Detection and Evaluation of Chronic Kidney
Disease. Am Fam Physician 2005;72:1723-32, 1733-4.
<http://www.aafp.org/afp/20051101/1723.html>

**UpToDate**

This online resource is widely used by many health care providers. It
also uses an alternative approach with the estimation of proteinuria per
day per 1.73 m2. (See below)

UpToDate's use of proteinuria per day per 1.73 m2 is unfamiliar to some
nephrologists. Proteinuria is usually expressed per unit of GFR, or per
day, but some nephrologists do not relate a spot specimen to the
standard of 1.73 m2. Creatinine clearance, urea clearance and GFR is
normalized per 1.73 m2 because size does make a difference in GFR
(larger people have a higher GFR than do small people) and this will
have some effect on the filtered load of protein, but some neprhologists
do not normalized proteinuria to body surface area. Creatinine excretion
in a large but obese white male will be less than in a black football
player with the same body surface area. This makes proteinuria difficult
to compare, unless one normalizes to filtered load. Hence it is more
important to normalize to GFR and by inference filtered load of
creatinine. The relevance of body surface area is not apparent to some
nephrologists.

**From UpToDate**

**Measurement of urinary protein excretion outside of pregnancy**

<http://www.uptodateonline.com/application/topic.asp?file=glomrdis/5359&type=A&selectedTitle=1~7>

**Protein-to-creatinine and albumin-to-creatinine ratio** ---
Measurement of protein excretion in the urine can be performed by
several different techniques. Previously, protein excretion was measured
on a 24 hour urine collection (which remains the gold standard), with
the normal value being less than 150 mg/day.

Currently, the preferred method of estimating urinary protein excretion
is the total protein-to-creatinine ratio (mg/mg) or total
albumin-to-creatinine ratio on a random urine specimen
\[[12,13](http://www.uptodateonline.com/application/abstract.asp?TR=glomrdis/5359&viewAbs=12~13&title=12,13)\].
This ratio on a random urine specimen correlates closely with daily
protein excretion in g/1.73 m2 of body surface area ([show
figure](http://www.uptodateonline.com/application/image.asp?file=neph_pix/urincrea.gif))
\[[2-6](http://www.uptodateonline.com/application/abstract.asp?TR=glomrdis/5359&viewAbs=2~3~4~5~6&title=2-6)\].
Thus, a ratio of 4.9 (as with respective urinary protein and creatinine
concentrations of 210 and 43 mg/dL) represents daily protein excretion
of approximately 4.9 g/1.73 m2.

The accuracy of the total protein-to-creatinine ratio is related to the
fortuitous occurrence that daily creatinine excretion is only slightly
greater than 1000 mg (8.8 mmol)/day per 1.73 m2. However, the formula
must be amended when the urinary creatinine concentration is measured in
mmol/L (1 mg/dL equals 0.088 mmol/L). In this setting, protein excretion
in g/1.73 m2 per day can be estimated from:

  Protein excretion  
![](media/image2.png){width="8.333333333333333e-2in"
height="7.152777777777777e-2in"}   (Urine
\[protein\]  x  0.088)  ÷  Urine \[creatinine\]

([See \"Estimation of protein
excretion\"](http://www.uptodateonline.com/application/topic.asp?file=calculat/2343)
to automatically make this calculation from values obtained in a given
patient).

The K/DOQI guidelines note that the relative merits of measuring total
protein versus albumin to detect and monitor kidney damage are unclear.
Despite this, they recommend, in adults, that the protein-to-creatinine
ratio in spot urine samples should be measured with the following:

  ![](media/image3.png){width="6.25e-2in"
height="7.152777777777777e-2in"} Albumin-to-creatinine ratio\
\
  ![](media/image3.png){width="6.25e-2in"
height="7.152777777777777e-2in"} The total protein-to-creatinine ratio
is acceptable, if the albumin-to-creatinine ratio is high (\>500 to
1,000 mg/g)

Thus, with dipstick positive proteinuria (greater than 500 mg/day),
either the total protein-to-creatinine ratio or albumin-to-creatinine
ratio provides similar information, given that proteinuria in this
setting consists primarily of albumin. By comparison, the detection and
monitoring of patients for microalbuminuria can only be performed with
the urinary albumin-to-creatinine ratio. ([See \"K/DOQI Clinical
practice guidelines for CKD. V. Evaluation of laboratory measurements
for clinical assessment of kidney disease. Guideline
5\"](http://www.uptodateonline.com/application/topic.asp?file=nkf_doqi/28222)).

**Limitations** --- The accuracy of estimating proteinuria from a random
urine specimen is diminished if creatinine excretion is substantially
different from the expected value. Thus, the total protein-to-creatinine
ratio will underestimate protein excretion in a muscular man with a high
rate of creatinine excretion and will overestimate the degree of
proteinuria in a cachectic patient in whom muscle mass and creatinine
excretion may be markedly reduced. This ratio also varies with
race/ethnicity in the United States
\[[1](http://www.uptodateonline.com/application/abstract.asp?TR=glomrdis/5359&viewAbs=1&title=1)\],
as creatinine excretion is significantly higher among non-Hispanic
blacks and Mexican Americans than among non-Hispanic whites
\[[7](http://www.uptodateonline.com/application/abstract.asp?TR=glomrdis/5359&viewAbs=7&title=7)\].

These limitations are not necessarily clinically important since the
exact degree of protein excretion (eg, 2 versus 3 g/day) is less
important than the reproducibility of the test and changes with therapy.
In patients with chronic kidney disease, the administration of
angiotensin converting enzyme inhibitors and/or angiotensin II receptor
blockers is aimed at reducing the degree of proteinuria. Similar
considerations apply to patients with nephrotic syndrome treated with
immunosuppressive therapy. In these settings, assuming that one has
verified the reproducibility of the protein-to-creatinine ratio at
baseline, marked reductions in the ratio represent marked reductions in
proteinuria even though the absolute values may not be accurately
estimated. ([See \"Antihypertensive therapy and progression of chronic
kidney
disease\"](http://www.uptodateonline.com/application/topic.asp?file=renlfail/12413)).

Another potential limitation of the total protein-to-creatinine ratio is
that values from a random urine specimen cannot be used to diagnose the
benign condition, orthostatic or postural proteinuria
\[[8](http://www.uptodateonline.com/application/abstract.asp?TR=glomrdis/5359&viewAbs=8&title=8)\].
In this disorder, which is primarily a disease of adolescents, protein
excretion is increased in the upright position but is normal when the
patient is supine. Thus, since the results of a random specimen vary
markedly with posture, a first morning spot urine can be obtained to
help avoid this confounding effect. A normal value in the first morning
spot urine and dipstick-positive proteinuria on an upright specimen is
strongly suggestive of orthostatic proteinuria
\[[9](http://www.uptodateonline.com/application/abstract.asp?TR=glomrdis/5359&viewAbs=9&title=9)\].
([See \"Orthostatic or postural
proteinuria\"](http://www.uptodateonline.com/application/topic.asp?file=glomrdis/7735)).

**Estimation of protein excretion online tool**

Daily protein excretion (in g/day per 1.73 m2 body surface area) can be
estimated from the values on a random urine specimen ([see \"Measurement
of urinary protein
excretion\"](http://www.uptodateonline.com/application/topic.asp?file=glomrdis/5359))
\[[1-3](http://www.uptodateonline.com/application/abstract.asp?TR=calculat/2343&viewAbs=1~2~3&title=1-3)\].
Press the TAB key to move through the different data fields, then press
the RETURN or ENTER key to perform the calculation. Go here
<http://www.uptodateonline.com/application/topic.asp?file=calculat/2343>

**Examples:**

-A ratio of 0.2 is widely accepted as cut-off for 300 mg protein / day.
When combined with a BP \> 140 / 90 mmHg a ratio of 0.2 would establish
a diagnosis of mild pre-eclampsia.

-A ratio of 4.9 (as with respective urinary protein and creatinine
concentrations of 210 and 43 mg/dL) represents daily protein excretion
of approximately 4.9 g/1.73 m2

How to estimate body surface area in m^2^ ?

Go here: <http://www.halls.md/body-surface-area/bsa.htm>

-To be exact, a pregnant patient that weighs 195 lbs. and is 64 inches
tall has body surface area of 2.00 m^2^

If her ratio was 4.9 g/1.73 m^2^, then her estimated daily protein
excretion would actually be....

[4.9]{.underline} is equivalent to [XXX]{.underline} which equals 1.15 x
4.9, or 5.6 g/day

1.73 2.00

**Article References:**

The following table includes those articles that compare P:C directly to
a 24 hour urine specimen. Please note that a variety of different
methods were used to support the authors conclusions on the utility of
the P:C, e. g., not a unified approach.

[Literature favorable to the use of P:C in pregnancy]{.underline} (on
separate criteria by each author)

  -------------- -------------- -------------- -------------- --------------
  **Author**     **Year**       **Sample       **Study        **Comments**
                                size**         Method**       

  Boler          1987           54             Ambulatory     

  Gonsales       2005           75             Ambulatory     

  Jaschevatzky   1990           35 / 70        PEC / controls Random

  Neithardt      2000           30             Inpatient      

  Ramos          1999           47             Cross          Random
                                               sectional      

  Risberg        2004           19 / 46        PEC / controls Random

  Robert         1997           71             Inpatient      

  Rodriguez      2001           138                           Random

  Saudan         1997           100            Inpatient      Random

  Uttendorfsky   1988           112            Ambulatory     

  Yamasmit       2004           42             Inpatient      Random

  Young          1996           66             Inpatient      

                                                              

  Total                         779                           
  -------------- -------------- -------------- -------------- --------------

[Literature not favorable to the use of P:C in pregnancy]{.underline}
(on separate criteria by each author)

  -------------- -------------- -------------- -------------- --------------
  **Author**     **Year**       **Sample       **Study        **Comments**
                                size**         Method**       

  Al             2004           185            Inpatient      

  Combs          2005           133            Ambulatory     

  Durnwald       2003           220            Ambulatory     Random

  Hass           2003           58             Ambulatory     All trimesters
                                                              / pp

                                                              

  Total                         696                           
  -------------- -------------- -------------- -------------- --------------

**References:** Literature favorable to the use of P:C in pregnancy
(alpha order)

[Boler
L](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term="Boler+L"%5BAuthor%5D),
et al Quantitation of proteinuria in pregnancy by the use of single
voided urine samples. [Obstet
Gynecol.](javascript:AL_get(this, 'jour', 'Obstet Gynecol.');) 1987
Jul;70(1):99-100.\
<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=3601274>

We conclude that the protein/creatinine ratio of a single urine specimen
represents a highly accurate method to assess renal function in the
pregnant patient, and seems clearly more practical than the 24-hour
urine collection.

[Gonsales Valerio
E](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term="Gonsales+Valerio+E"%5BAuthor%5D),
et alVariation in the urinary protein/creatinine ratio at four different
periods of the day in hypertensive pregnant women. [Hypertens
Pregnancy.](javascript:AL_get(this, 'jour', 'Hypertens Pregnancy.');)
2005;24(3):213-21.

<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16263594>

Conclusion. In hypertensive pregnant women, the single voided urine
sample protein/creatinine ratio, irrespective of sampling time, is
strongly correlated with the 24-hour proteinuria, as is the sample
obtained on arrival.

Jaschevatzky OE; Rosenberg RP; Shalit A; Zonder HB; Grunstein S
Protein/creatinine ratio in random urine specimens for quantitation of
proteinuria in preeclampsia. Obstet Gynecol 1990 Apr;75(4):604-6.\
<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=2314778&query_hl=10>

We conclude that determination of the protein/creatinine ratio in random
urine specimens may be a simple method for quantitation of proteinuria
in preeclampsia

Neithardt AB; Dooley SL; Borensztajn J Prediction of 24-hour protein
excretion in pregnancy with a single voided urine protein-to-creatinine
ratio. Am J Obstet Gynecol 2002 May;186(5):883-6.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve

<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12015502&query_hl=8>

CONCLUSION: Our data support the use of single voided P:C ratio in
hospitalized pregnant patients to predict the 24-hour urine result. In
addition, the P:C ratio appears to predict trends in protein excretion
over time.

Ramos JG, Martins-Costa SH, Mathias MM, Guerin YL, Barros EG. Urinary
protein/creatinine ratio in hypertensive pregnant women. Hypertens
Pregnancy 1999;18: 209--218 (Level II-3)

<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10586524&query_hl=1>

CONCLUSION: The protein/creatinine ratio measured in a single urine
sample taken at random from hypertensive pregnant women showed good
sensitivity and specificity for the diagnosis of 24-h proteinuria \> or
= 300 mg and was strongly correlated with 24-h proteinuria. A ratio of
0.5 mg/mg is predictive of significant proteinuria and can be used for
the diagnosis and follow-up of hypertensive pregnant women.

[Risberg
A](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&term="Risberg+A"%5BAuthor%5D),
et al Relationship between urinary albumin and albumin/creatinine ratio
during normal pregnancy and pre-eclampsia. [Scand J Clin Lab
Invest.](javascript:AL_get(this, 'jour', 'Scand J Clin Lab Invest.');)
2004;64(1):17-23.\
<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15025425&query_hl=14>

In conclusion, it has been found that the albumin excretion in urine
correlates significantly to the albumin/creatinine ratio during
pregnancy. The urinary albumin/creatinine ratio appears to be a good
alternative to the dipstick method and to 24-h urine collections

Robert M, Sepandj F, Liston RM, Dooley KC. Random protein-creatinine
ratio for the quantitation of proteinuria in pregnancy. Obstet Gynecol
1997;90:893--895 (Level II-2)

CONCLUSION: In nonambulatory hypertensive pregnant patients, there is a
strong correlation between random voided protein-creatinine ratios and
24-hour urine protein

<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=9397097&query_hl=3>

Rodriguez-Thompson D; Lieberman ES Use of a random urinary
protein-to-creatinine ratio for the diagnosis of significant proteinuria
during pregnancy. Am J Obstet Gynecol 2001 Oct;185(4):808

<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11641656&query_hl=4>

CONCLUSION: The random urinary protein-to-creatinine ratio is strongly
associated with the 24-hour total protein excretion. A level below 0.14
can rule out significant proteinuria. A best cutoff of \> or = 0.19 is a
good predictor of significant proteinuria. With further study, the
random urinary protein-to-creatinine ratio could replace the 24-hour
urine collection as a simpler, faster, more useful method for the
diagnosis of significant proteinuria.

Saudan PJ; Brown MA; Farrell T; Shaw L Improved methods of assessing
proteinuria in hypertensive pregnancy. Br J Obstet Gynaecol 1997
Oct;104(10):1159-64.

<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=9332994&query_hl=8>

CONCLUSIONS: Use of an automated urinalysis device improved accurate
detection of proteinuria, particularly reducing false positive tests. A
random urine protein:creatinine ratio provides an accurate and rapid
quantitation of proteinuria in hypertensive pregnant women. This should
improve clinical care, especially when managing hypertensive pregnant
women as outpatients.

[Uttendorfsky
OT](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term="Uttendorfsky+OT"%5BAuthor%5D),
et al Protein/creatinine ratio in the assessment of proteinuria during
pregnancy. [Eur J Obstet Gynecol Reprod
Biol.](javascript:AL_get(this, 'jour', 'Eur J Obstet Gynecol Reprod Biol.');)
1988 Mar;27(3):221-6.\
<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=3350195>

In this study, therefore, we propose the determination of the
protein/creatinine ratio in a single voided urine sample, obtained
during normal daylight activity, as a screening test for
hyperproteinuria during pregnancy which can replace the quantitation of
24-h urinary protein excretion.

[Yamasmit
W](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&term="Yamasmit+W"%5BAuthor%5D),
et al Random urinary protein-to-creatinine ratio for prediction of
significant proteinuria in women with preeclampsia. [J Matern Fetal
Neonatal
Med.](javascript:AL_get(this, 'jour', 'J Matern Fetal Neonatal Med.');)
2004 Nov;16(5):275-9.\
<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15621543&query_hl=14>

CONCLUSION: In hospitalized preeclamptic patients, the random urinary
protein-to-creatinine ratio at a cutoff of \> or = 0.25 revealed a
highly accurate prediction of significant proteinuria and could be a
more practical alternative for assessment of proteinuria

Young RA; Buchanan RJ; Kinch RA Use of the protein/creatinine ratio of a
single voided urine specimen in the evaluation of suspected
pregnancy-induced hypertension. J Fam Pract 1996 Apr;42(4):385-9

<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=8627207&query_hl=6>

CONCLUSIONS: We conclude that the protein/creatinine ratio of a single
voided urine specimen may have a role in the management of ambulatory
women with suspected PIH, although further study is needed. The main
potential benefit of this method is that in institutions where women
with suspected PIH are hospitalized, women with insignificant
proteinuria may be identified within a matter of hours and their
follow-up care handled on an outpatient basis.

**References:** Literature not favorable to the use of P:C in pregnancy
(alpha order)

Al RA; Baykal C; Karacay O; Geyik PO; Altun S; Dolen I Random urine
protein-creatinine ratio to predict proteinuria in new-onset mild
hypertension in late pregnancy. Obstet Gynecol 2004 Aug;104(2):367-71.

<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15292013&query_hl=12>

CONCLUSION: The random urine protein-creatinine ratio was a poor
predictor for significant proteinuria in patients with new-onset mild
hypertension in late pregnancy

[Combs
CA](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term="Combs+CA"%5BAuthor%5D),
et al Urinary protein/creatinine ratio before and during pregnancy in
women with diabetes mellitus. [Am J Obstet
Gynecol.](javascript:AL_get(this, 'jour', 'Am J Obstet Gynecol.');) 1991
Oct;165(4 Pt 1):920-3.\
<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=1951554>

Compared with actual protein excretion, predicted values had mean errors
of 19% to 27%; 6% to 13% of predictions were in error by greater than or
equal to 50%. Because of these large errors, we conclude that this
method of estimating protein excretion has limited value in pregnant
women with diabetes.

Durnwald C; Mercer B A prospective comparison of total
protein/creatinine ratio versus 24-hour urine protein in women with
suspected preeclampsia. Am J Obstet Gynecol 2003 Sep;189(3):848-52.

<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14526328&query_hl=10>

CONCLUSION: Protein/creatinine ratio does not exclude adequately the
presence of significant proteinuria or predict severe proteinuria and
should not be used as an alternative to 24-hour total protein
evaluation.

[Haas
DM](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&term="Haas+DM"%5BAuthor%5D),
et al Comparing ambulatory spot urine protein/creatinine ratios and 24-h
urine protein measurements in normal pregnancies.\
<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14738168&query_hl=14>

CONCLUSION: In this population, the protein/creatinine ratio correlated
only with the 24-h urine protein measurement in the first trimester and
postpartum periods. In the periods of pregnancy where physiological
changes are most prevalent, the ratio does not predict total urinary
protein reliably.

**Other References**

Brown M et al. The classification and diagnosis of the hypertensive
disorders of pregnancy: Statement from the International Society for the
Study of Hypertension in Pregnancy. Hypertens Pregnancy 2001:20(1)ix --
xiv

<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12044323>

[Price
CP](http://ezproxyhhs.nihlibrary.nih.gov:2067/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term="Price+CP"%5BAuthor%5D),
[Newall
RG](http://ezproxyhhs.nihlibrary.nih.gov:2067/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term="Newall+RG"%5BAuthor%5D),
[Boyd
JC](http://ezproxyhhs.nihlibrary.nih.gov:2067/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term="Boyd+JC"%5BAuthor%5D).
Use of protein:creatinine ratio measurements on random urine samples for
prediction of significant proteinuria: a systematic review. [Clin
Chem.](javascript:AL_get(this, 'jour', 'Clin Chem.');) 2005
Sep;51(9):1577-86.

<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16020501>

CONCLUSION: The protein:creatinine ratio on a random urine specimen
provides evidence to \"rule out\" the presence of significant
proteinuria as defined by a 24-h urine excretion measurement.

Chan P., Brown M., Simpson J.M., Davis G. Proteinuria in pre-eclampsia:
How much matters? BJOG: An International Journal of Obstetrics and
Gynaecology, 2005:112 (3), 280-285.

<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15713140>

CONCLUSIONS: With increasing proteinuria, there is increased risk of
adverse maternal and fetal outcomes. Although we did not identify a
specific spot protein/creatinine ratio that could be used as a
definitive screening value for adverse outcomes, it is possible to
utilise data from this study to predict the likelihood of adverse
maternal and fetal outcomes. A high spot urine protein/creatinine ratio
in pre-eclamptic women of greater than 900 mg/mmol ( approximately 9
g/day), or greater than 500 mg/mmol (approximately 5 g/day) in women
over 35 years, is associated with a greatly increased likelihood of
adverse maternal outcomes

Laboratory Technique (100 patients, 91 controls)

[Waugh
J](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&term="Waugh+J"%5BAuthor%5D),
et al Validation of the DCA 2000 microalbumin:creatinine ratio
urinanalyzer for its use in pregnancy and preeclampsia. [Hypertens
Pregnancy.](javascript:AL_get(this, 'jour', 'Hypertens Pregnancy.');)
2003;22(1):77-92.

<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12648445&query_hl=14>

CONCLUSIONS: The DCA 2000 is accurate for the measurement of albumin
creatinine ratios in the uncomplicated pregnant population. In the
hypertensive population the DCA 2000 remains accurate though when the
albumin concentration is greater than 40 mg/L the 95% limits of
agreement are broader. We would recommend that all other automated
urinalysis devices be validated by similar protocols to allow meaningful
comparisons of accuracy.

Rinehart B.K., Terrone D.A., Larmon J.E., Perry Jr. K.G., Martin R.W.,
Martin Jr. J.N.

A 12-hour urine collection accurately assesses proteinuria in the
hospitalized hypertensive gravida Journal of Perinatology 1999 19 (8
PART. 1):556-558

<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10645518>

RESULTS: A total of 25 patients (86%) were preeclamptic. Total protein,
the protein: creatinine ratio, and serum creatinine were significantly
correlated between the first and second urine collection. The
sensitivity and specificity of the 12-hour urine collection was 96% and
100%, respectively. CONCLUSION: A 12-hour urine collection accurately
depicts the amount of proteinuria in hospitalized gravidas being
evaluated for preeclampsia.

[Gaspari
F](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term="Gaspari+F"%5BAuthor%5D),
[Perico
N](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term="Perico+N"%5BAuthor%5D),
[Remuzzi
G](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term="Remuzzi+G"%5BAuthor%5D).
Timed urine collections are not needed to measure urine protein
excretion in clinical practice. [Am J Kidney
Dis.](javascript:AL_get(this, 'jour', 'Am J Kidney Dis.');) 2006
Jan;47(1):1-7.\
<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16377379>

### SUMMARY

Spot urine testing is an acceptable practice. It is better than nothing.
However, 24-hour testing is the gold standard, certainly for
nephrologists who maintain a referral practice in which many of the
referring physicians are nephrologists. The referring nephrologists want
and deserve the best management information available. So do their
patients. Twenty-four--hour urine testing is an important part of "best"
nephrology practices. We should not allow the regular use of such an
important practice to erode, particularly in academic centers, which
bear a special responsibility to maintain the highest clinical
standards.

[Baker
PN](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term="Baker+PN"%5BAuthor%5D),
[Hackett
GA](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term="Hackett+GA"%5BAuthor%5D).The
use of urinary albumin-creatinine ratios and calcium-creatinine ratios
as screening tests for pregnancy-induced hypertension. [Obstet
Gynecol.](javascript:AL_get(this, 'jour', 'Obstet Gynecol.');) 1994
May;83(5 Pt 1):745-9\
<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=8164937>

CONCLUSIONS: This study suggests that neither urinary ratio is a
potential screening test for pregnancy-induced hypertension. The
increased urinary creatinine concentration in patients who subsequently
developed pregnancy-induced hypertension has not previously been
reported and merits further investigation.