Effects of Hemp

Protein on the Kidneys

and the Heart
HaroId Aukema
Rotimi AIuko
Human NutritionaI Sciences
University of Manitoba
Canadian Hemp Trade AIIiance
NationaI Hemp Convention
Winnipeg, November 17, 2009
Outline
 Ìmportance of kidneys and chronic kidney
disease
 Dietary approaches to slowing kidney
disease progression
 Effects of hemp protein isolate on
progression of chronic kidney disease
Effects on the heart
Why are kidneys so important?
 They do 3 essential things:
Regulate water
Remove wastes
Produce hormones that regulate:
 the uptake of calcium from the intestine
 blood pressure
 the making of red blood cells
Chronic Kidney Disease
 Affects 2 miIIion Canadians
 Kidneys faiI in 14 more Canadians
every day
 34,000 on RRT in 2006
Expected to doubIe in 10 years
40% had transpIant
60% on diaIysis
 70% of those on transpIant waiting Iist
need kidneys (Dec 2007)
National Kidney Foundation, 2009
USRDS 2008 ADR USRDS 2008 ADR
Recognized CKD & ESRD in the NHANES &
Medicare popuIations
Figure p.1 (VoIume 1)
NHANES: NHANES 1988-1994 & 1999-2006 participants, age 20 & older. Pati ent counts from 1988-1994 survey
adjusted to 1990 U.S. population; counts from 1999-2006 survey adjusted to 2000 U.S. population. Medicare: general
Medi care patients age 65 & older, surviving entire cohort year with Medicare as primary payor (& not enrolled in an
HMO). ESRD patients excluded for CKD estimation; CKD defined by diagnosis codes.
Risks associated with CKD
 Increased risk of kidney faiIure, CVD
and death
 DiaIysis associated with:
Reduced Iifespan (10 y for 42 year oId)
4 co morbidities per year
15 hospitaI days per year
Lower quaIity of Iife
NationaI Kidney Foundation, Am J Kidney Dis 39, S1-S256.
Approaches to sIowing renaI
disease progression
 Strict bIood gIucose controI in diabetes
 BIood pressure controI
 Dietary modifications - protein, Iipid,
saIt
Dietary Intervention on Chronic
Kidney Disease
90 60 30 15
GIomeruIar FiItration Rate (GFR)
MarginaI ESRD Moderate
CKD
Severe
CKD
Stage 1 5 4 3 2
120
Early treatment can make a
difference
100
10
0
No Treatment
Current Treatment
Earl y Treatment
4 7 9 11
Time (years)
Kidney Failure
G
F
R
(
m
L
/
m
i
n
/
1
.
7
3
2
)
Dietary Soy Protein in Kidney
Disease
 Subtotally nephrectomized rats
(Williams A. et al, 1987)
 db/db mice with type ÌÌ diabetic nephropathy
(Teixeira S.R. et al, 2003)
 Aging Fischer 344 rats
(Schimokawa I. et al, 1993; Iwasaki K. et al, 1988)
 Chronic nephrotic syndrome
(Tovar et al 2002)
 pcy mice ÷ adolescent nephronophthisis
(Tomobe K. et al 1998, Aukema H. et al 1999)
Effects of Dietary Soy Protein on
Glomerular Size in Obese fa/fa Zucker Rats
In CTL In SOY
fa CTL fa SOY
6 Wk of Dietary Soy Protein in
weanling Han:SPRD-cy rats
Casein Soy Protein
Kidney Int 59: 52 Kidney Int 59: 52- -61, 2001 61, 2001
Effect of dietary soy protein on established
kidney disease in Han:SPRD-cy rats
Macrophages (ceIIs/video fieId)
0
10
20
Casein Soy Protein
PCNA (ceIIs/video fieId)
0
10
20
30
Casein Soy Protein
Oxidized LDL (fraction of section)
0
0.01
0.02
0.03
Casein Soy Protein
*Soy protein reduces
renal cell inflammation,
proliferation and
oxidative damage
*
*
*
P=0.0455
P=0.0059
0
0.005
0.01
0.015
0.02
Week 1 Week 3
MaIe
F
i
b
r
o
s
i
s

V
o
I
u
m
e

(
m
I
)
Casein
Soy
1 or 3 Wk of Dietary Soy Protein in
weanling Han:SPRD-cy rats
J Nutr 134: 1504 J Nutr 134: 1504- -1507, 2004 1507, 2004
PoIycystic Kidney Disease
PoIycystic Kidney Disease
PoIycystic Kidney Disease
Cyst growth and expansion
Fibrosis, InfIammation
Kidney faiIure
Copyright ©2009 American Society of Nephrology
Eknoyan, G. J Am Soc NephroI 2009;20:1874-1876
Age-reIated prevaIence of simpIe renaI cysts
PKD - >50,000 affected in Canada
- 12.5 miIIion worIdwide
PKD >
·Cystic fibrosis
·MuItipIe scIerosis
·MuscuIar dystrophy
·SickIe ceII anemia
·HemophiIia
What is the effect of other plant protein
sources on cystic kidney disease?
 AnimaI modeI
 WeanIing Han:SPRD- rat (=12)
 Cysts, fibrosis, infIammation
 Dietary Intervention
 AÌN 93G laboratory rodent diet
 Protein source:
 casein, hemp, pea, soy protein isolates
(HPI from SepaIIo Food Ingredients)
 supplemented with amino acids to balance
 Food and water provided ad libitum
 8 weeks of feeding
Effect of protein source on final body
weight in rats with cystic kidneys
Effect of protein source on size of
cystic rat kidneys
Effect of protein source on liver
size in rats with cystic kidneys
Effect of protein source on fluid
content in cystic rat kidneys
Kidney cortex and medulla in normal
rats and rats with cystic kidneys
Diseased MeduIIa Diseased Cortex
NormaI Cortex NormaI MeduIIa
Effect of protein source on cyst
growth in cystic rat kidneys
Effect of protein source on kidney
fibrosis in cystic rat kidneys
Effect of dietary protein source on
inflammation in cystic rat kidneys
Effect of protein source on function
of cystic rat kidneys
Effect of protein source on function
of cystic rat kidneys
CKD is prevalent in CVD
Ìx, et al., 2003; Anavekar, et al., 2004; Shlipak, et al., 2004.
0
20
40
60
CAD
CrCI =60 mL/min
AMI
GFR <60 mL/min
CHF
GFR =60 mL/min
23%
46%
33%
P
a
t
i
e
n
t
s
W
i
t
h
C
K
D
(
%
)
In addition to ESRD, CKD leads
to CVD
Go, et al., 2004
1 . 0
2 . 8
3 . 4
2 . 0
1 . 4
0 . 0
0 . 5
1 . 0
1 . 5
2 . 0
2 . 5
3 . 0
3 . 5
4 . 0
= 6 0 4 5 - 5 9 3 0 - 4 4 1 5 - 2 9 < 1 5
A
d
j
u
s
t
e
d
H
a
z
a
r
d
R
a
t
i
o
eGFR
Adjusted* hazard ratio for CVD events
NationaI Kidney Foundation, Am J Kidney Dis 39, S1-S256.
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Effect of protein source on heart
size in rats with cystic kidneys
Conclusions
 Ìn a model of chronic kidney disease, early
treatment with dietary hemp protein:
 Maintains normal growth
 Reduces kidney pathology
 Ìmproves kidney function
 Reduces enlarged heart size
 Hemp protein could be part of an overall dietary
approach to slowing down kidney disease and
associated heart disease
Acknowledgements
 Joy Gauthier
 Yong Jia
 Manon Roy
 Stephanie Caligiuri
 Eniko Kresz
 Natural Sciences and Engineering Research
Council of Canada
Effect of protein source on serum
MCP-1 in rats with cystic kidneys