Correspondence

incident hemodialysis patients: the Choices for Healthy Outcomesin Caring for End-Stage Renal Disease (CHOICE) Study. Am JKidney Dis. 2010;56(2):348-358.

© 2010 by the National Kidney Foundation, Inc.doi:10.1053/j.ajkd.2010.10.006

Measured GFR Has Limited Clinical UtilityTo the Editor:

Kwong et al1 provide important insights regarding the limitedclinical utility of measured glomerular filtration rate (mGFR),suggesting that a single mGFR is of little value in determiningwhether actual GFR is within the reference range, particularly inborderline cases identified using creatinine-based methods. This isparticularly relevant when evaluating living kidney donors,2,3 forwhom a more reliable, inexpensive, and simpler approach to GFRassessment is the Cockcroft-Gault formula, which appears to havebeen discounted because it did not correlate strongly with mGFR.In retrospect, the fault may lie with mGFR.1

The strength of the Cockcroft-Gault formula is that it accountsfor creatinine production related to body weight, the most impor-tant determinant of serum creatinine level at any given actual GFR,whereas the 4-variable Modification of Diet in Renal Disease(MDRD) Study and Chronic Kidney Disease Epidemiology Col-laboration (CKD-EPI) equations do not adequately adjust for bodyweight. This can lead to substantial error in estimating actual GFRin individual patients.4 Although the MDRD Study and CKD-EPIequations can be adjusted for body surface area (BSA), BSA is notan adequate substitute for body weight. For example, a 35%difference in body weight is only a 14% difference in BSA.5 Inindividuals in whom actual body weight is not within 10% of idealbody weight, those who are habitual vegetarians or “meatatarians,”those of African ancestry, or those who have atypical muscle mass,we recommend assessment of creatinine clearance using accurate24-hour urine collections, rather than the Cockcroft-Gault formula.Fasting serum creatinine is recommended for the clearance mea-surements and estimates.

For comparison with published mGFR norms, which are strati-fied by age and sex and expressed in milliliters per minute per1.73 m2 BSA,6 Cockcroft-Gault and 24-hour creatinine clearancesneed to be adjusted for BSA. To account for creatinine secretion, inindividuals with normal or near normal clearance, we recommendthat only 90% of these clearances be attributed to actual GFR.

Uday S. Nori, MDTodd E. Pesavento, MD

Lee A. Hebert, MDThe Ohio State University Medical Center

Columbus, Ohio

AcknowledgementsFinancial Disclosure: The authors declare that they have no

relevant financial interests.

References1. Kwong Y-T, Stevens LA, Selvin E, et al. Imprecision of

urinary iothalamate clearance as a gold-standard measure of GFRdecreases the diagnostic accuracy of kidney function estimatingequations. Am J Kidney Dis. 2010;56(1):39-49.

2. Rook M, Hofker HS, van Son WJ, van der Heide JJH, PloegRJ, Navis CJ. Predictive capacity of pre-donation GFR and renalreserve capacity for donor renal function after living kidney

donation. Am J Transplant. 2006:6:1653-1659.

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3. Issa N, Stephany B, Fatica R, et al. Donor factors influencinggraft outcomes in live donor kidney transplantation. Transplanta-tion. 2007:83;593-599.

4. Hebert LA, Nori U, Hebert PL. Measured and estimatedglomerular filtration rate. N Engl J Med. 2006;355(10):1068.

5. Levey AS, Kramer H. Obesity, glomerular hyperfiltration,and the surface area correction. Am J Kidney Dis. 2010;56(2):255-258.

6. Stevens LA, Coresh J, Greene T, Levey AS. Assessingkidney function—measured and estimated glomerular filtrationrate. N Engl J Med. 2006;354:2473-2483.

© 2010 by the National Kidney Foundation, Inc.doi:10.1053/j.ajkd.2010.08.035

In Reply to ‘Measured GFR Has LimitedClinical Utility’

We thank Drs Nori, Pesavento, and Hebert for their interest inour report.1 We agree that one cause of poor performance of anyestimating equation may be error in the actual measurement ofglomerular filtration rate (GFR).2 However, we disagree with theirrecommendation to use the Cockcroft-Gault equation as “a morereliable” method to assess GFR. Multiple previous studies havecompared the Modification of Diet in Renal Disease (MDRD)Study and Cockcroft-Gault equations, with most favoring theformer.3-6 Although the MDRD Study equation and the morerecently developed Chronic Kidney Disease Epidemiology Collabo-ration (CKD-EPI) equation do not explicitly use weight or bodymass index (BMI) in the calculation of GFR standardized to bodysurface area, the equations perform well.7 Rigorous evaluation ofweight as a potential variable during the development of theCKD-EPI equation showed that the addition of weight results inonly a small improvement in the subgroups with BMI �20 kg/m2

and in worse performance for people with higher levels of BMI.8

The recommendation to adjust the Cockcroft-Gault or measuredcreatinine clearance by a factor of 0.9 to account for creatininesecretion is not consistent with data showing wide variability increatinine secretion in the MDRD Study.9 In addition, adjustmentof GFR for body surface area is to provide comparable GFRsacross a range of body and kidney sizes, not to account forvariation in creatinine production for individuals of different bodysizes.10 Finally, we disagree that measured GFR has no clinicalutility. All current estimated GFRs are limited by imprecision andbias in some groups, and in those populations, measured GFR hasan important role.11

Lesley Stevens, MD, MSTufts Medical Center

Boston, Massachusetts

Josef Coresh, MD, PhDJohns Hopkins University

Baltimore, Maryland

AcknowledgementsFinancial Disclosure: The authors declare that they have no

relevant financial interests.

References1. Nori US, Pesavento TE, Hebert LA. Measured GFR has

limited clinical utility. Am J Kidney Dis. 2011;57(1):180.2. Kwong YT, Stevens LA, Selvin E, et al. Imprecision of

urinary iothalamate clearance as a gold-standard measure of GFRdecreases the diagnostic accuracy of kidney function estimating

equations. Am J Kidney Dis. 2010;56(1):39-49.

Am J Kidney Dis. 2011;57(1):179-182

Correspondence

3. Coresh J, Stevens LA. Kidney function estimating equations:where do we stand? Curr Opin Nephrol Hypertens. 2006;15(3):276-284.

4. Stevens LA, Padala S, Levey AS. Advances in glomerularfiltration rate-estimating equations. Curr Opin Nephrol Hypertens.2010;19(3):298-307.

5. Coresh J, Auguste P. Reliability of GFR formulas based onserum creatinine, with special reference to the MDRD Studyequation. Scand J Clin Lab Invest Suppl. 2008;241:30-38.

6. Stevens LA, Manzi J, Levey AS, et al. Impact of creatininecalibration on performance of GFR estimating equations in a pooledindividual patient database. Am J Kidney Dis. 2007;50(1):21-35.

7. Levey AS, Stevens LA, Schmid CH, et al. A new equation toestimate glomerular filtration rate. Ann Intern Med. 2009;150(9):604-612.

8. Stevens LA, Schmid CH, Zhang YL, et al. Development andvalidation of GFR-estimating equations using diabetes, transplantand weight. Nephrol Dial Transplant. 2010;25(2):449-457.

9. Levey AS, Berg RL, Gassman JJ, Hall PM, Walker WG.Creatinine filtration, secretion and excretion during progressiverenal disease. Modification of Diet in Renal Disease (MDRD)Study Group. Kidney Int Suppl. 1989;27:S73-S80.

10. Levey AS, Kramer H. Obesity, glomerular hyperfiltration, andthe surface area correction. Am J Kidney Dis. 2010;56(2):255-258.

11. Stevens LA, Levey AS. Measured GFR as a confirmatory testfor estimated GFR. J Am Soc Nephrol. 2009;20(11):2305-2313.

© 2010 by the National Kidney Foundation, Inc.doi:10.1053/j.ajkd.2010.10.004

RESEARCH LETTER

Once-Daily Extended-Release Niacin Lowers SerumPhosphorus Concentrations in Patients WithMetabolic Syndrome DyslipidemiaTo the Editor:

Hyperphosphatemia is associated with increased cardiovasculardisease (CVD) risk in patients across the spectrum of kidney func-tion,1,2 from end-stage renal disease (ESRD) to normal glomerularfiltration rates (GFRs). For example, the ABCD (Appropriate BloodPressure Control in Diabetes) trial investigators reported that in 950individuals with type 2 diabetes but normal kidney function, phospho-rus concentrations were an independent predictor of CVD mortality.2

Niacin decreases serum phosphorus concentrations in patients withESRD.1 Recently, we found in more than 1,500 dyslipidemic patientswithout stage 4 or 5 chronic kidney disease (CKD; GFR �30mL/min/1.73 m2) that niacin’s phosphorus-lowering effects appear to

Table 1. Baseline Characterist

Group Placebo (n

Phosphorus (mg/dL) 3.01 � 0.63 (2Calcium (mg/dL) 9.22 � 0.41 (8Ca � P (mg2/mL2) 27.85 � 6.32 (1Albumin (g/dL) 4.18 � 0.25 (3Age (y) 47 � 11 (24eGFR (mL/min/1.73 m2) 93.2 � 15.7 (6BMI (kg/m2) 32.2 � 3.5 (26Men 18 (58

Note: Values shown are mean � standard deviation (range)participants with metabolic syndrome dyslipidemia and eGFR ofmg/dL to mmol/L, �0.3229; calcium in mg/dL to mmol/L, �0.249

2

Abbreviations: BMI, body mass index; Ca � P, calcium-phosphorus

Am J Kidney Dis. 2011;57(1):179-182

extend across a broad range of kidney function.3 We sought to confirmthe external validity of these findings by determining phosphorus andcalcium concentrations and calcium-phosphorus product levels inpatients with metabolic syndrome dyslipidemia without decreasedkidney function who completed an 8-week trial assessing the effect ofa different niacin preparation on lipid and lipoprotein levels.

We selected 60 participants, using the National CholesterolEducation Program Adult Treatment Panel III definition of meta-bolic syndrome modified to target those with dyslipidemia, ie,fasting serum triglyceride levels �150-�750 mg/dL, a triglycer-ide to HDL (high-density lipoprotein) cholesterol ratio �3.5, andminimum HDL level �10 mg/dL. After 6 weeks of placebo run-in,participants were randomly assigned using a 2 � 2 factorial designto 8 weeks of treatment with dual placebo, 4 g/d of an omega-3fatty acid ethyl ester preparation (Lovaza; GlaxoSmithKline,www.gsk.com), 2 g/d of once-daily extended-release niacin (Nias-pan; Abbott Laboratories, www.abbott.com), or the 2 drugs com-bined. Lipid and lipoprotein end points have been reported else-where.4 Serum aliquots stored at �70°C by the parent study wereshipped to a central laboratory for determination of baseline and8-week phosphorus concentrations. These data were combinedwith serum calcium, albumin (for albumin-adjusted calcium level3),and creatinine (for estimating GFR using the CKD EpidemiologyCollaboration [CKD-EPI] equation)5 data made available from theparent study. We evaluated the 8-week change in phosphorus,calcium, and calcium-phosphorus product levels using analysis ofvariance (ANOVA). There was no evidence of an effect onphosphorus concentration by omega-3 fatty acid alone or ininteraction with niacin (test for interaction by ANOVA, P � 0.3);thus, we present baseline (Table 1) and follow-up (Table 2) data foractive versus placebo niacin only.

After 8 weeks of treatment, niacin (n � 29) decreased meanbaseline phosphorus levels (3.22 � 0.51 [SD] mg/dL) by an averageof �0.48 � 0.48 mg/dL. Placebo niacin (n � 31) did not decreasemean phosphorus levels from baseline (3.01 � 0.63 mg/dL; change,�0.02 � 0.64 mg/dL). A between-groups effect difference (P �0.003 by ANOVA) persisted after analysis of covariance (ANCOVA)-adjustment for baseline phosphorus levels (�0.40 � 0.43 mg/dL; P �0.007). Relative to placebo, niacin had no significant effect on serumcalcium concentrations. Consistent with these effects, niacin treat-ment was associated with significant decreases in calcium-phospho-rus product levels relative to placebo (P � 0.009 by ANCOVA,adjusted for baseline level).

Unlike calcium- and non–calcium-containing phosphorus bind-ers, which simply trap meal-related phosphorus liberated in thegut, the hypophosphatemic effect of niacin compounds resultsfrom specific inhibition of active transport-mediated intestinal

Treatment Group Assignment

) Extended-Release Niacin (n � 29)

.20) 3.22 � 0.51 (2.30-4.60)0.00) 9.39 � 0.30 (8.40-9.90)

-47.32) 30.27 � 4.82 (21.16-41.86).60) 4.22 � 0.28 (3.50-4.70)

49 � 10 (20-65)21.0) 91.8 � 15.6 (62.0-123.0).3) 32.0 � 4.2 (24.9-39.9)

18 (62.1)

mber (percentage). The study population consisted of 60 white23 mL/min/1.73 m2. Conversion factors for units: phosphorus inumin in g/dL to g/L, �10; eGFR in mL/min/1.73 m2 to mL/s/1.73

ics by

� 31

.00-5

.20-16.40.30-4

-69)2.0-1.6-39.1)

or nu62-15; alb

m , �0.01667.

product; eGFR, estimated glomerular filtration rate.

181