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Department of Physiology and Pharmacology, College of Veterinary Medicine, The University of Georgia, Athens, GA 30602
1To whom correspondence should be addressed.
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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KEY WORDS: • glomerular filtration rate • soy protein • dogs • renal disease
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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). When these rats are fed high-protein
diets or when renal mass is surgically reduced, progression of renal
lesions in residual tissue is accelerated and conversely, progression
of renal damage is ameliorated by reducing dietary protein intake
(Brenner et al. 1982
). Studies suggest that increased
glomerular capillary hydraulic pressure, which causes an increase in
single nephron and whole animal glomerular filtration rate
(GFR)2
, is a significant factor in the genesis and progression of renal
lesions (Brenner et al. 1982
).
Although the effects of protein on renal damage in susceptible strains
of rats are well-documented, the question of protein effects on
progression of renal lesions in other species is controversial. A
multicenter study on progression of renal disease in humans concluded
that there was no beneficial effect from protein restriction
(Klahr et al. 1994
), but subgroups of data were
reanalyzed and protein effects were supported (Levey et al. 1995
). A meta-analysis of several studies on humans with
renal disease led to the conclusion that a beneficial effect of protein
restriction existed but was weak (Kassiske et al. 1998
).
Data from other species regarding protein effects on progression of
renal disease are contradictory, with some data suggesting adverse
protein effects in dogs (Polzin et al. 1988
) and cats
(Adams et al. 1993
) with remnant kidneys and other data
indicating a lack of protein effects in these species (Finco et al. 1992
, Finco et al. 1998
, Robertson et al. 1986
).
Most studies have focused on the amount of protein ingested, but have
ignored the source or degree of processing of the protein. However,
studies conducted in both healthy humans and in those with renal
disease have demonstrated differences between vegetable and animal
protein effects on renal functions (Bilo et al. 1989
,
Dhaene et al. 1987
, Kontessis et al. 1990
,Kontessis et al. 1995
, Nakamura et al. 1989
, Nakamura et al. 1991
and
1993
, Pecis et al.1994
). Generally, there
is a marked increase in GFR in response to ingestion of proteins of
animal origin, compared to only a mild or nonexistent change in GFR
with vegetable proteins such as soy protein. These results have been
interpreted to mean that glomerular capillary pressure would be
attenuated with intake of soy protein, compared to animal protein,
imparting a protective effect on the kidneys. The renal protection
hypothesis has been tested in rats and mice, and beneficial results
from feeding soy protein rather than casein have been reported
(Ogborn et al. 1998
, Tomobe et al. 1998
,
Walls and Williams 1988
, Williams and Walls 1987
, Williams et al.1987
).
Methods of processing soybeans may affect certain biologic properties
of the soy product (Anderson and Wolf 1995
), and thus
all soy products may not have the same effects. In addition, intestinal
transit and absorption of soy protein in dogs may differ from animal
proteins (Zhao et al. 1997
), which could affect renal
hemodynamics. The present study was performed to determine if
processing procedures and source of proteins have different effects on
GFR in dogs.
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MATERIALS AND METHODS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Dogs were obtained form the Animal Resources Unit, College of
Veterinary Medicine, University of Georgia, and protocols for dog use
were approved by the University of Georgia Animal Use Committee.
Management of dogs complied with the Guide for Care and Use of
Laboratory Animals (NRC 1996
). Four clinically normal
adult mongrel dogs weighing 20 to 28 kg were fed a weighed amount of
commercially available adult maintenance dogfood for 2 mo. Food
consumption was measured daily, and body weight measurements were
performed weekly. Daily protein intake during the 2-mo period was
calculated. (PMI Feeds, St. Louis, MO; protein = 210 g/kg, fat
= 80 g/kg, fiber = 55 g/kg, gross energy = 12,331
kj/kg). Corn, corn gluten feed, meat meal, soybean meal were sources of
protein.
Eight adult mongrel dogs weighing 8 to 13 kg had renal mass surgically
reduced as previously described (Finco et al. 1991
).
Dogs were fed weighed amounts of a diet prepared for dogs with renal
compromise (Iams Co., Lewisburg, OH; protein = 150 g/kg, fat = 137 g/kg, fiber = 18 g/kg, gross energy = 19094
kj/kg). Ground corn grits, soy protein isolate, chicken digest, corn
gluten meal were sources of protein for 5 mo, and during the last 2 mo
food intake was measured daily, and daily intake of protein was
computed.
Protein preparations.
Casein, soy meal, soy flakes, purified soy protein and pork liver were obtained from suppliers [Protein Technologies International, St. Louis, MO (soy flakes, purified soy protein); Sigma Co., St. Louis, MO (casein, creatinine), Clarke Co. Milling, Athens, GA (soy meal)]and analyzed for protein concentration. Calculations were performed to determine the amount of each preparation required to supply the quantity of protein consumed by each dog daily during the prior 2 mo. Normal dogs were tested with casein, soy meal, soy flakes and purified soy protein. Based on results from normal dogs, the dogs with reduced renal function were tested with casein, pork liver and purified soy protein.
Experimental protocol.
All dogs were subjected to the same protocol for measuring GFR
(Finco et al. 1991
). After 16 h without food, dogs
were placed in Pavlov slings and catheters were placed in a saphenous
vein, a jugular vein and the urinary bladder. A bolus injection of
sterile solutions of creatinine (25 g/L) was administered via the
saphenous vein catheter and followed by a constant infusion (1.0
mL/min) of a sterile mixture of saline, creatinine and mannitol. Two
protocols were employed. Group 1 (normal) dogs received bolus
injections of 55 mg/kg of creatinine followed with constant infusion of
0.33 mg-1 · kg-1 · min-1.
Group 2 dogs (reduced renal mass) received bolus injections of 45 mg/kg
of creatinine followed by constant infusion of 0.18 mg-1
· kg-1 · min.-1. Mannitol concentration
in the infused solution was 25 g/L for both groups. After a 40-min
equilibration period, the bladder was emptied and rinsed with sterile
saline (0-time), and three 20-min urine collections were made. The
bladder was emptied and rinsed thoroughly at the end of each collection
period. Blood samples were obtained from the jugular vein catheter at
0, 20, 40 and 60 min. Immediately after 60-min samples were obtained,
each dog was fed a test protein. Material not consumed voluntarily was
force-fed within 15 min to assure prompt and complete intake of the
calculated quantity of protein. Hourly collections of urine and blood
for GFR measurement were continued postprandially for 4 or 5 h.
Dogs with normal renal function were tested on d 1, 8, 15, 22 and 29, with a 7-d interval provided to prevent carryover effects. On d 1, one dog received casein, the second soy meal, the third soy flakes, and the fourth purified soy protein. Protein assignments for subsequent days were in the sequence of casein, soy meal, soy flakes and purified soy protein. On d 29 dogs had GFR measured without feeding in order to determine if renal function changed independently of protein intake during the several hours of study.
Dogs with reduced renal mass were tested on days 36, 50 and 64. Based on results from normal dogs, three soy proteins were eliminated and an additional animal-source protein was added (see Discussion section). On d 36, two dogs received casein, three dogs received purified soy protein, and two received pork liver. Protein assignments for subsequent days were in the order of casein, purified soy protein and pork liver. On each day an eighth dog had GFR measurements made without feeding, to serve as a time control.
Laboratory analyses.
Creatinine concentration in plasma and urine was determined by the Jaffe reaction using a semiautomated analyzer (Spectrum CCX, Abbot Diagnostics, Irving, TX). Protein concentration of protein sources was determined by a combustion method (CN/S Determinator, Leco Industries, St. Joseph, MI).
Computations and statistical analyses.
Creatinine clearances were calculated using the standard urinary clearance formula. For calculations, the plasma concentration of creatinine was computed as the mean of plasma concentration at the beginning and end of each urine collection period. Preprandial values for GFR for each dog were computed as the average of the three 20-min clearance measurements performed before feeding each protein. Postprandial values for GFR were computed as the average of the four or five hourly clearance measurements following the preprandial measurements.
Preprandial and postprandial measurements of GFR for each protein were compared using a paired-comparison t test. To make comparisons between protein sources for the magnitude of their effects on GFR, data from each dog for each test protein were normalized by computing the postprandial/preprandial clearance ratio. The ratios were subjected to a one-way ANOVA, and the LSD multiple comparison test was used to test differences between treatments. Means and SD values are reported, and for all statistical analysis, a P < 0.05 was considered significant.
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RESULTS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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).
Preprandial measurement of GFR in normal (group 1) dogs (2.39 ± 0.16 mL · min-1 · kg-1
body weight) was significantly greater than in dogs with reduced renal
mass (group 2) (1.00 ± 0.17 mL · min-1 ·
kg-1 body weight). Preprandial vs postprandial measurements.
In normal dogs, all soy proteins significantly increased the GFR
(Table 1
), but the effect of casein was not significant (P = 0.066). No significant change in GFR occurred when normal dogs were not
fed.
|
. In both dog groups for all
proteins tested, GFR began increasing during the first hour
postprandially, and was stable or declining by the fifth hour
postprandial. Magnitude of protein effects.
In normal dogs and those with reduced renal mass,
postprandial/preprandial ratios of GFR (Table 2
) were not significantly different among the protein types but were
significantly different from values obtained when dogs were not fed.
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Some studies in humans have suggested that the differences in
physiologic effects observed between animal and vegetable proteins
could be related to nonprotein components unique to vegetable sources.
Legumes such as soy contain trypsin inhibitors, phytic acid, saponins
and isoflavones, which could alter the digestibility of the protein or
have other physiologic effects (Anderson and Wolf 1995
,
Zhao et al. 1997
). Because various processing procedures
may change the quantity or activity of these soy constituents, we
evaluated three soy preparations in our study of normal dogs. These
preparations varied in protein concentration from 48 g/100 g in meal to
over 82 g/100 g in purified soy protein, reflecting removal of
nonprotein constituents during processing. The lack of difference in
hemodynamic effects between the least processed and the most processed
soy preparations indicated that processing did not alter protein
absorption significantly.
Because different soy preparations had similar effects in normal dogs,
a single soy preparation was used in dogs with reduced renal mass.
Another animal protein was added in this group because results with
casein in normal dogs approached but failed to reach significance. Pork
liver was chosen because severe glomerular lesions have been found to
develop in cats with reduced renal mass consuming a pork liver protein
source (Adams et al. 1993
), whereas cats with reduced
renal mass fed a diet devoid of pork liver developed only minor renal
lesions (Finco et al. 1998
). In dogs with reduced renal
mass, the three proteins tested caused a significant increase in GFR,
and no significant difference was detected among the sources of protein
in the magnitude of GFR response. These findings do not support the
hypothesis that pork liver protein causes renal hemodynamic changes
different from casein or soy protein.
Classic studies performed in normal dogs nearly 50 y ago first
demonstrated the effect of protein on GFR (Smith 1951
),
but initial studies were conducted using amounts of protein far in
excess of daily requirements. The quantity of protein administered to
dogs in the present study to measure acute hemodynamic effects was
based on daily protein intake for the preceding 2 mo. Stable body
weight in all dogs during the 2-mo pretest period indicated that energy
intakes were adequate. Since diets are formulated to provide adequate
protein when energy needs are met, the diets were probably adequate in
protein content. Some claims of different hemodynamic effects from
vegetable and animal proteins reported in humans could be related to
failure to control the quantity of protein ingested. Indeed, some
studies of humans have failed to detect a difference in hemodynamic
effects between animal and vegetable proteins (Mansey et al. 1987).
Soy protein compared to casein has been reported to slow progression of
renal failure in rats with reduced renal mass (Williams and Walls 1987
and 1988
, Williams et al.1987
) and to decrease the progression of renal disease in
mice and rats with polycystic kidneys (Ogborne et al. 1998
, Tomobe et al. 1998
). However in these
studies protein effects on GFR were not measured, and it is possible
that factors other than renal hemodynamics explain long-term renal
benefits attributed to soy proteins. Other changes attributed to soy
foods include alteration of plasma lipid profiles, (Kirk et al. 1998
, Nagata et al. 1982
, Tovar-Palacio et al. 1998
, Vahouny et al. 1984) and
prevention of peroxidation of plasma lipoproteins that could cause
glomerular injury (Grone et al. 1996
, Kanazawa et al. 1995
). Considerable attention has been focused on
isoflavones in soy as they relate to many aspects of human health
(Setchell and Cassidy 1999
), and specifically to renal
disease (Wardle 1998
). However, one isoflavone
(genistein) was not related to the beneficial effects from
long-term feeding of soy proteins to mice with renal polycystic
disease (Tomobe et al. 1998
). The
results of this study of dogs do not support the hypothesis that
proteins vary in potential renoprotective effects based on renal
hemodynamics, but benefits from other factors such as isoflavones
remain to be examined.
The authors thank David Smith and Stephen Rathbun, Department of Statistics, The University of Georgia, for assistance with statistical analysis.
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FOOTNOTES |
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Manuscript received August 27, 1999. Revision accepted December 15, 1999.
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REFERENCES |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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1. Adams L.G., Polzin D.J., Osborne C.A., O’Brien T.D. Effects of dietary protein and calorie restriction in clinically normal cats and in cats with surgically induced chronic renal failure. Am J Vet Res 1993;54:1653-1662[Medline]
2. Anderson R. L., Wolf W. F. Compositional changes in trypsin inhibitors, phytic acid, saponins, and isoflavones related to soybean processing. J. Nutr. 1995;125:581S-588S
3. Baylis C. Age-dependent glomerular damage in the rat. Dissociation between glomerular injury and both glomerular hypertension and hypertrophy. Male gender as a risk factor. J. Clin. Invest. 1994;94:1823-1829
4. Bilo H. J., Schaap G. H., Blaak E., Gans R. O., Oe P. L., Donker A. J. Effects of chronic and acute protein administration on renal function in patients with chronic renal insufficiency. Nephron 1989;53:181-187[Medline]
5. Brenner B. M., Meyer T. W., Hostetter T. H. Dietary protein intake and the progressive nature of kidney disease: The role of hemodynamically mediated glomerular injury in the pathogenesis of progressive glomerular sclerosis in aging, renal ablation, and intrinsic renal disease. N. Engl. J. Med. 1982;307:652-659[Medline]
6. Dhaene M., Sabot J.-P., Philippart Y., Doutrelepont J., Vanerweghem J. Effects of acute protein loads of different sources on glomerular filtration rate. Kidney Int 1987;32:S25-S28
7. Finco D. R., Brown S. A., Crowell W. A., Barsanti J. A . Exogenous creatinine clearance as a measure of glomerular filtration rate in dogs with reduced renal mass. Am. J. Vet. Res. 1991;52:1029-1032[Medline]
8. Finco D. R., Brown S. A., Crowell W. A., Duncan J. R., Barsanti J. A., Bennett S. E. Effects of dietary phosphorus and protein in dogs with chronic renal failure. Am. J. Vet. Res. 1992;53:2264-2271[Medline]
9. Finco D. R., Brown S. A., Brown C. A., Crowell W. A., Sunvold G., Cooper T. L. Protein and calorie effects on progression of induced chronic renal failure in cats. Am. J. Vet. Res. 1998;59:578-582
10. Grone H. J., Hohbach J., Grone E. F. Modulation of glomerular sclerosis and interstitial fibrosis by native and modified lipoproteins. Kidney Int. 1996;249(supplement 54):18-22
11. Kanazawa T., Osani T., Zhang X. S., Uemura T. Protective effect of soy proteins on the peroxidability of lipoproteins in cerebrovascular diseases. J. Nutr. 1995;125(supplement):639-646
12. Kassiske B. L., Lakutua J. D., Ma J. Z., Ma J., Louis T. A. A meta-analysis of the effects of dietary protein restriction on the rate of decline in renal function. Am. J. Kidney Dis. 1998;31:954-961[Medline]
13.
Kirk E. A., Sutherland P., Wang S. A., Chait A., LeBoeuf R. C. Dietary isoflavones reduce plasma cholesterol and atherosclerosis in C57BL/6 mice but not LDL receptor-deficient mice. J. Nutr. 1998;128:954-959
14.
Klahr S., Levey G., Beck A., Caggiula A., Hunsicker L., Kusek J., Striker G. The effects of dietary protein restriction and blood pressure control on the progression of renal insufficiency. N. Eng. J. Med. 1994;330:877-884
15. Kontessis P. S., Bossinakou I., Sarika L., Iliopoulou E., Papantoniou A., Trevisan R., Roussi D., Stipsanelli K., Grigorakis S., Souvatzoglou A. Renal, metabolic, and hormonal responses to proteins of different origin in normotensive, nonproteinuric type I diabetic patients. Diabetic Care 1995;18:1233-1240
16. Kontessis P., Jones S., Dodds R., Trevisan R., Nosadini R., Fioretto P., Borsato M., Sacerrdoti D., Viberti G. Renal, metabolic and hormonal responses to ingestion of animal and vegetable proteins. Kidney Int 1990;38:136-144[Medline]
17. Levey A., Adler S., Caggiula A., England B., Greene T., Hunsicker L., Kusek J., Rogers N., Teschan P. Effects of dietary protein restriction on the progression of advanced renal disease in the modification of diet in renal disease study. Am. J. Kidney Dis. 1995;27:652-663
18. Nagata Y., Ishiwaki N., Sugano M. Studies on the mechanism of antihyper-cholesterolemic action of soy protein and soy protein-type amino acid mixtures in relation to the casein counterparts in rats. J. Nutr. 1982;112:1614-1625
19. Nakamura H., Ito S., Ebe N., Shibata A. Renal effects of different types of protein in healthy volunteer subjects and diabetic patients. Diabetic Care 1993;16:1071-1075
20. Nakamura H., Takasawa M., Kasahara S., Tsuda A., Momotsu T., Ito S., Shibata A. Effects of acute protein loads of different sources on renal function of patients with diabetic nephropathy. Tohoku J. Exp. Med. 1989;159:153-162[Medline]
21. Nakamura H., Yamazaki M., Chiba Y., Tani N., Momotsu T., Kamoi K., Ito S., Yamaji T., Ahibata A. Acute loading with proteins from different sources in healthy volunteers and diabetic patients. J. Diabetic Complications 1991;5:140-142[Medline]
22. National Research Council, Institute of Laboratory Animal Resources, Commission on Life Sciences. National Academy Press, Washington, DC 1996
23.
Ogborn M. R., Bankovic- Calic N., Shoesmith C., Buist R., Peeling J. Soy protein modification of rat polycystic kidney disease. Am. J. Physiol. 1998;274:F541-F549
24. Pecis M., DeAzevedo M. J., Gross J. L. Chicken and fish diet reduces glomerular hyperfiltration in IDDM patients. Diabetes Care 1994;17:665-672[Abstract]
25. Polzin D. J., Leininger J. R., Osborne C. A., Jeraj K. Development of renal lesions in dogs after 11/12 reduction of renal mass. Lab Invest 1988;58:172-183[Medline]
26. Robertson J., Goldschmidt M., Kronfeld D., Tomaszewski J., Hill G., Bovee K. Long-term responses to high dietary protein in dogs with 75% nephrectomy. Kidney Int 1986;29:511-519[Medline]
27. Setchell K. D., Cassidy A. Dietary isoflavones:biologic effects and relevance to human health. J. Nutr. 1999;129:758S-767S
28. Smith H. W. The Kidney: Structure and Function in Health and Disease 1951:143–168,191,470–473 Oxford University Press New York, NY.
29. Tomobe K., Philbrick D., Ogborn M., Takahashi H., Holub B. Effect of dietary soy protein and genestein on disease progression in mice with polycystic kidney disease. Am. J. Kidney Dis. 1998;31:55-61[Medline]
30.
Tovar-Palacio C., Potter S. M., Hsafermann J. C., Shay N. F. Intake of soy protein and soy protein extracts influences lipid metabolism and hepatic gene expression in gerbils. J. Nutr. 1998;128:839-842
31.
Vahouny G. V., Chalcarz W., Satchithanandam S., Satchithanandam S., Adamson I., Klurfeld D., Kritchevsky D. Effect of soy protein and casein intake on intestinal absorption and lymphatic transport of cholesterol and oleic acid. Am. J .Clin. Nutr. 1984;40:1156-1164
32. Walls J., Williams A. J. Influence of soya protein on the natural history of a remnant kidney model in the rat. Contrib. Nephrol. 1988;60:179-187[Medline]
33. Wardle E. N. Soyprotein diet therapy in renal disease. Nephron 1998;78:328-331[Medline]
34. Williams A. J., Baker F., Walls J. Effect of varying quantity and quality of dietary protein intake in experimental renal disease in rats. Nephron 1987;46:83-90[Medline]
35. Williams A. J., Walls J. Metabolic consequences of differing protein diets in experimental renal disease. Eur. J .of Clin. Invest. 1987;17:117-122
36.
Zhao X. T., McCamish M. A., Miller R. H., Wang L., Lin H. C. Intestinal transit and absorption of soy protein in dogs depends on load and degree of protein hydrolysis. J. Nutr. 1997;127:2350-2356
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