RESEARCH BRIEFS

Foods With Added Fiber Lower Serum CreatinineLevels in Patients With Chronic Kidney DiseaseYounis A. Salmean, MS,* Mark S. Segal, MD, PhD,† Bobbi Langkamp-Henken, PhD,*

Muna T. Canales, MD,† Gordon A. Zello, PhD,‡ and Wendy J. Dahl, PhD*,‡

Objective: To determine the effect of foods with added fiber on blood urea nitrogen (BUN) and serum creatinine concentrations in

patients with chronic kidney disease (CKD).

Design: Participants were enrolled in a 6-week single-blind crossover study.

Setting: Free living with partial dietary intervention.

Patients: Thirteen CKD patients with Modification of Diet in Renal Disease formula–based estimated glomerular filtration rate (eGFR)

#50 mL/minute/1.73 m2 at the time of screening (5 men, 8 women; mean age, 67.0 6 14.8 years) completed the study.

Intervention: Patients consumed control foods (cereal, cookies, and bars) providing 1.6 g/day fiber daily for 2 weeks, followed by

similar foods providing 23 g/day fiber daily for 4 weeks, incorporated into their usual diets.

Main Outcome: The main outcome of the study was the determination of the impact of foods with added fiber on BUN and serum

creatinine levels.

Results:Consuming foods with added fiber resulted in a 10.6%decrease in mean BUN concentration (13.86 2.0 to 12.16 1.8mmol/

L or 38.56 5.6 to 34.06 5.1 mg/dL; P, .05). Serum creatinine level decreased from a baseline value of 2166 26 to 2016 23 mmol/L

(2.446 0.30 to 2.276 0.26 mg/dL; P, .05) after 2 weeks of fiber-containing food consumption, and remained significantly lower at 195

6 23 mmol/L (2.216 0.26 mg/dL) after 4 weeks of the intervention (P, .05). Calculated eGFR increased from a baseline value of 29.66

3.5 to 31.46 3.8 mL/minute/1.73 m2 at the end of 2 weeks, and remained higher at 32.56 3.6 mL/minute/1.73 m2 after 4 weeks of fiber

intervention (P , .05).

Conclusion:We conclude that increasing fiber intake in CKD patients through the consumption of foods with added fiber may reduce

serum creatinine levels and improve eGFR. Additional studies are warranted to confirm these findings and to determine whether the

changes are due to direct effects on kidney function.

� 2012 by the National Kidney Foundation, Inc. All rights reserved.

UREMIA IS A broad term to describe symptoms asso-ciated with advanced decline in kidney function that

is not due to changes in extracellular volume, inorganic ionconcentrations, or lack of known substances produced bythe kidney.1 The primary functions of the kidneys are tomaintain electrolyte and fluid homeostasis as well as filteruremic retention molecules from the blood. Declining re-nal function can result in progressive retention of uremicsolutes in the blood, which can lead to uremic symptomsand reduced health and well-being. Urea is normally

*Food Science and Human Nutrition Department, University of Florida,

Gainesville, Florida.†Division of Nephrology, Hypertension, and Renal Transplantation, Univer-

sity of Florida, Gainesville, Florida.‡College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon,

Saskatchewan, Canada.

Funding Support: This study was supported by Saskatchewan Pulse Growers.

Financial Disclosure: The authors declare that they have no relevant financial

interests.

Address reprint requests to Wendy J. Dahl, PhD, Food Science and Human

Nutrition Department, University of Florida, 359 FSHN Building, Newell

Drive, Gainesville, FL 32611. E-mail: wdahl@ufl.edu� 2012 by the National Kidney Foundation, Inc. All rights reserved.

1051-2276/$36.00

doi:10.1053/j.jrn.2012.04.002

Journal of Renal Nutrition, Vol -, No - (-), 2012: pp e1-e4

excreted to maintain a narrow blood urea nitrogen(BUN) range, but can be significantly elevated in chronickidney disease (CKD) patients. Approximately 70% of theurea produced by healthy individuals is eliminated by thekidneys, whereas most of the remaining 30% is excretedby the large intestine through fecal output.2

Both animal and human studies have shown that thesupplementation of high levels (40 to 50 g/day) of ferment-able fiber lowers BUN,3-6 decreases urinary nitrogenexcretion,3,7,8 and increases nitrogen excretion in feces.8

Fiber may provide a viable nutritional approach to alleviateuremic solute load, and may possibly reduce other uremicretention molecules that may be increasingly implicated inCKD and its symptoms.9,10 It is not known whetherreductions in BUN can be achieved through consumingcommon foods with added fiber.The objective of this studywas to determine the effects of

a moderate amount of added fiber frommixed sources, pro-vided in commercially available foods suitable for CKD pa-tients, onBUN, serumcreatinine, and estimated glomerularfiltration rate (eGFR) values in patients with CKD.

MethodsNephrology patient charts (n 5 270) were screened for

eligible participants using the following inclusion criteria:

e1

SALMEAN ET ALe2

age.18 years, eGFR#50mL/minute/1.73m2 (stage 3, 4,and 5 CKD, but not on dialysis), no diagnosis of acutekidney injury or glomerulonephritis, no prescribed immu-nosuppressant medications, and ability to understand, ver-balize, and sign the informed consent in English. Aftereligibility and willingness to participate was confirmed byphone, informed consent was obtained in person.

A 6-week, single-blind controlled study in CKD patientswith an eGFRof#50mL/minute/1.73m2 at screeningwascarried out. After consent and baseline assessment, patientswere scheduled for follow-up every 2 weeks for food pick-up, blood draw, and compliance checkup. Phase 1 (14 days)represented the control period in which participantsconsumed commercially available breakfast cereal, cookies,and cereal bars daily, providing 1.6 g/day of fiber. Phase 2(28 days) represented the treatment period in which partici-pants consumed similar foods with added fiber, providing 23g/day of fiber as pea hull fiber, corn fiber, and inulin. Table 1gives the nutrient content of the control and added fiberfoods. Participants were instructed to consume foods ona daily basis and return any unused packages to monitorcompliance. Participants were required to keep 3-day foodrecords in week 2 (control period) and week 6 (added fiber).Macronutrient intakes were analyzed using Food Processor(ESHA Research, Salem, OR, version 10.8.0.0).

Blood samples (10 mL) were taken on day 1, 14, 28, and42. BUN was assayed using the Urea Nitrogen Concen-trated Reagent method, and serum creatinine was assayedusing the ADVIA Chemistry CRE_2c method (SiemensHealthcare Diagnostics Inc., Tarrytown, NY).

Paired t tests were used to compare dietary intake and se-rum creatinine and BUN levels between baseline, control,and treatment periods, and to compare the percent changein the mean values of BUN between baseline/control andtreatment periods. Differences were considered statisticallysignificant atP,.05.Data representmean6 standard error.

ResultsSeventeen patients diagnosed with CKD with an eGFR

of,50mL/minute/1.73m2 consented to participate in the

Table 1. Nutrient Composition of Foods Provided in the Control a

Weight(g)

Energy(kcal)

Control foods

Kellogg’s Corn Pops (Battle Creek, MI) 58 220

Publix Chocolate Chip Cookies (Lakeland, FL) 24 120

Kellogg’s Special K Bar (Battle Creek, MI) 23 90Fiber treatment

Kellogg’s Corn Pops with Fiber (Battle Creek, MI) 64 240

Weight Watchers ChocolateChip Cookies (Jerico, NY)

50 180

General Mills FiberOne Bar (Minneapolis, MN) 40 140

study. One subject withdrew her consent for personal rea-sons, 1 subject dropped from the study citingmild but both-ersome abdominal side effects, and 2 patientswere excludedfrom the analysis owing to antibiotic use during the study.Thirteen patients completed the study (5 men, 8 women;mean age, 67.06 14.8 years). Compliance to study food in-take was 82% during phase 1 and 78% during phase 2.Added fiber intake averaged to 16.5 6 5.5 g/day, andmean total fiber intakes increased from 11.8 6 3.2 to 26.46 7.0 g/day (P , .001). No significant differences werefound with regard to energy (1650 6 250 to 1550 6 310kcal), protein (596 16 to 566 24 g), or carbohydrate intake(214 6 33 to 227 6 43 g), but fat intake decreased duringthe added fiber period (57 6 21 and 47 6 20 g; P , .01).Body weight remained unchanged from baseline to studyend (86.6 6 7.0 to 87.3 6 6.8 kg, not significant).The consumption of added fiber resulted in a 10.6% de-

crease in BUN from an average mean concentration of 13.86 2.0mmol/L (38.56 5.6mg/dL) in the control period to12.1 6 1.8 mmol/L (34.0 6 5.1 mg/dL) in the treatmentperiod (P , .05), with the absolute changes in BUN levelsapproaching significance (P5.058). Serum creatinine con-centration was 216 6 26 mmol/L (2.44 6 0.30 mg/dL) atthe baseline. After 2 weeks of control food consumption,there was no change in serum creatinine level, which wasat 2216 25 mmol/L (2.506 0.29 mg/dL, not significant).However, after 2 weeks of fiber-containing food consump-tion, serum creatinine concentration was significantlylower at 201 6 23 mmol/L (2.27 6 0.26 mg/dL, P ,.05). This reduction in serum creatinine concentration re-mained significantly lower at 195 6 23 mmol/L (2.21 60.26 mg/dL) after 4 weeks of fiber-containing food intake(P , .05; Fig. 1). The decrease in serum creatinine levelcorresponded to a significant improvement in eGFR calcu-lated using the Modification of Diet in Renal Disease for-mula: eGFR increased from 29.6 6 3.5 mL/minute/1.73m2 at the baseline to 31.4 6 3.8 mL/minute/1.73 m2

(P , .05) at the end of 2 weeks of fiber interventionand remained significantly improved at 32.5 6 3.6 mL/minute/1.73 m2 after 4 weeks of fiber intervention (P ,.05; Fig. 2).

nd Fiber Treatment Periods

Fiber(g)

Fat(g)

Protein(g)

Carbohydrate(g)

Source ofAdded Fiber

0 0 2 52 None

0 6 1 15 None

,1 1.5 1 17 None

6 0 2 58 Corn dextrin

8 5 2 36 Inulin, pea hull fiber

9 4 2 29 Chicory root fiber

Journal of Renal Nutrition, Vol -, No - (-), 2012: pp e1-e4

Figure 1. Baseline, control, and treatment serum creatininelevels (for baseline and 4 weeks of treatment, n5 13; control,n 5 11; 2 weeks of treatment, n 5 12). *Significant declinewas observed in serum creatinine level compared with base-line (day 1; P , .05).

FIBER-CONTAINING FOODS LOWER SERUM CREATININE e3

DiscussionProgressive decline in renal function leads to the accumu-

lation of uremic solutes, worsening of uremic symptoms,and further progression of the disease. This pilot studywas designed to determine whether a moderate intake ofadded fiber would lead to reduced BUN levels. The studywas unique because participants with more moderateeGFR than in previous works4,11 were included, and thefiber dose of the intervention was much more practicable:23 g/day from common foods versus up to 50 g/day ofsupplemental fiber. Human clinical studies, to date, haveshown reductions in the uremic solute profiles of BUNand/or p-cresol sulfate.4,5,11,12 However, lowering ofserum creatinine level has not been demonstratedpreviously. In this pilot study, we have shown that whenparticipants consumed an average of 16.5 g/day of addedfiber, serum creatinine concentrations decreased and,thus, affected eGFR. Most participants were responsive to

Figure 2. Baseline, control, and treatment estimated glomer-ular filtration rate (for baseline and 4 weeks of treatment, n513; control, n5 11; 2 weeks of treatment, n5 12). *Significantincrease was observed in estimated glomerular filtration ratecompared with baseline (day 1; P , .05).

Journal of Renal Nutrition, Vol -, No - (-), 2012: pp e1-e4

the intervention. Only 1 subject remained unchanged,whereas another participant continued to experience anincrease in serum creatinine concentration.In this study, absolute changes in BUN approached

significance. However, when compared as a percentchange, BUN level was significantly lower. The 10.6%change is comparable with the results reported by Blisset al., in which fiber intervention achieved a 12% reduc-tion in BUN levels,4 but less than the 23% reported byYounes et al.11 In both of these studies, the fiber dosewas nearly twice that used in our study, which may ex-plain the differences in outcomes. Moreover, both of theprevious studies enrolled participants with a baselineBUN concentration that was significantly elevated com-pared with that of the participants in our study. In ourstudy, the mean baseline BUN values for some partici-pants were within normal ranges. In contrast, participantsin the study by Younes et al. had a baseline BUN con-centration of 26.1 6 8.7 mmol/L (73 6 24 mg/dL),whereas those in the study by Bliss et al. had a baselineBUN concentration of 18 6 2 mmol/L (50 6 6 mg/dL). A more pronounced decline from elevated concen-trations may be expected.Participants from our pilot study had a baseline serum

creatinine concentration of 216 6 26 mmol/L (2.44 60.30 mg/dL), whereas in previous studies by Younes et al.and Bliss et al., baseline serum creatinine levels of 357 6143 mmol/L (4.03 6 1.61 mg/dL) and 390 6 70 mmol/L(4.4 6 0.8 mg/dL), respectively, were reported. Fiber in-takemay bemore effective for improving various serum pa-rameters in our sample population compared with thosewith more serious renal dysfunction.In conclusion, our pilot study suggests potential value for

the inclusion of foods with added fiber to the diet of indi-viduals exhibiting a moderate-to-severe decline in kidneyfunction. We were also able to achieve desirable outcomeswithout the potential side effects of very high supplementalfiber intakes (e.g., 40 to 50 g/day). Further studies areneeded to confirm these results, to assess uremic solutesin addition to urea, and to include direct measurement ofkidney function to determine whether the improvementis in part due to a direct effect on the kidney.

Practical ApplicationFoods with added fiber, some appropriate for individ-

uals with CKD, are now common in the marketplace.The consumption of foods with added fiber may func-tion to reduce BUN levels and may potentially affectkidney function.

References1. Meyer TW,Hostetter TH.Uremia.NEngl J Med. 2007;357:1316-1325.

2. Moran BJ, Jackson AA. 15N-urea metabolism in the functioning human

colon: luminal hydrolysis and mucosal permeability. Gut. 1990;31:454-457.

SALMEAN ET ALe4

3. Younes H, Alphonse JC, Hadj-Abdelkader M, Remesy C. Fermentable

carbohydrate and digestive nitrogen excretion. J Ren Nutr. 2001;11:139-148.

4. Bliss DZ, Stein TP, Schleifer CR, Settle RG. Supplementation with

gum arabic fiber increases fecal nitrogen excretion and lowers serum urea ni-

trogen concentration in chronic renal failure patients consuming a low-

protein diet. Am J Clin Nutr. 1996;63:392-398.

5. Rampton DS, Cohen SL, Crammond VD, et al. Treatment of chronic

renal failure with dietary fiber. Clin Nephrol. 1984;21:159-163.

6. MeijersBK,PreterVD,VerbekeK,VanrenterghemY,Evenepoel P. p-Cre-

syl sulfate serum concentrations in haemodialysis patients are reduced by the pre-

biotic oligofructose-enriched inulin.Nephrol Dial Transplant. 2010;25:219-224.

7. Zervas S, Zijlstra RT. Effects of dietary protein and fermentable fiber on

nitrogen excretion patterns and plasma urea in grower pigs. J Anim Sci.

2002;80:3247-3256.

8. Heijnen ML, Beynen AC. Consumption of retrograded (RS3) but not

uncooked (RS2) resistant starch shifts nitrogen excretion from urine to feces

in cannulated piglets. J Nutr. 1997;127:1828-1832.

9. Evenepoel P,Meijers BK, Bammens BR, Verbeke K. Uremic toxins orig-

inating from colonic microbial metabolism. Kidney Int. 2009;76(suppl 114):

S12-S19.

10. Schepers E, Glorieux G, Vanholder R. The gut: the forgotten organ in

uremia? Blood Purif. 2010;29:130-136.

11. Younes H, Egret N, Hadj-Abdelkader M, et al. Fermentable carbohy-

drate supplementation alters nitrogen excretion in chronic renal failure. J Ren

Nutr. 2006;16:67-74.

12. Meijers BK, De Loor H, Bammens B, Verbeke K, Vanrenterghem Y,

Evenepoel P. p-Cresyl sulfate and indoxyl sulfate in hemodialysis patients.

Clin J Am Soc Nephrol. 2009;4:1932-1938.

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