'•
CALIFORNIA STATE UNIVERSITY, NORTHRIDGE
NUTRITIONAL GUIDELINES IN EARLY CHRONIC RENAL FAILURE
A graduate project submitted in partial satisfaction of
the requirement for the degree of Master of Science in
Home Economics
by
Mary Elizabeth Polucci
May, 1986
@
The Thesis of Mary Elizabeth Polucci is approved:
- Llllle 1'1. Grossman, R. D., Ph.D.
Ann R. Stasch, Ph.D., Chair
California State University, Northridge
ii
•
ACKNOWLEDGEMENTS
I wish to express sincere thanks and appreciation
to the staff and patients of both Saint Joseph's Medical
Center and Valley Dialysis for the professionally
stimulating environment they have provided me over the
years.
I am also very thankful to the people who
participated in reviewing and evaluating this graduate
project.
I respect these people as professionals, and
their opinions and comments are very much appreciated.
I owe extreme thanks, and am particularly indebted,
to my parents for all they have done for me in the
furtherance of my education.
I am especially grateful to my close friend,
Nicolas Vasily,
for all the patience and interest he has
taken in my graduate education.
Finally, I am thankful and appreciative to my 3unt,
Rose Polucci, whose encouragement and support: were
always there.
iii
TABLE OF CONTENTS
Page
iii
ACKNOWLEDGEMENTS
vi
ABSTRACT
CHAPTER
1.
INTRODUCTION .
.
.
1
Justification
2
....
')
REVIEW OF LITERATURE
4
3.
l1ETHODOLOGY
8
Evaluation
4.
~
..)
.
8
RESULTS AND DISCUSSION
10
The Need for "Guidelines in
Early Chronic Renal
Failure"
. . . . . . . .
1_ 0
Additional Information Needed
10
Sufficient Enough Material
11
Information Current and
Up-to-Date
11
Overall Response
12
Project Rating
12
SUl'1t,Lo\RY AND CONCLUSION
iv
15
Page
APPENDICES
A.
B.
STUDY GUIDE ON THE RATIONALE
FOR DIET THERAPY IN EARLY
CHRONIC RENAL FAILURE . . .
20
EVALUATIONS AND EVALUATION
OPINIONNAIRE
84
REFERENCES
88
v
ABSTRACT
NUTRITIONAL GUIDELINES IN EARLY
CHRONIC RENAL FAILURE
by
Mary Elizabeth Polucci
Master of Science in Home Economics
The purpose of this project was to develop a
study guide of the pertinent literature concerning the
nutritional care of the individual with early chronic
renal insufficiency, and the type of nutritional support
these patients require.
The objective was to present
material that dietetic students and dietitians working
or
in health care could use in their educational svstem
-·
place of employment.
Recent clinical trials now give merit to the
protective effects of dietary manipulation in the nre'
dialysis phase of chronic renal insufficiency.
New
scientific evidence indicates that restriction of protein
and phosphorus can slow or prevent the progressive loss
of residual renal function in early stages of the
disease.
Careful attention is required to maintain the
vi
patient's nutritional status and to monitor dietary
compliance.
The role of the renal dietitian has now broadened
to include the educational and nutritional support of
this patient population.
The therapeutic goals of the
dietitian should include the following:
nutritional
assessment of the patient to fulfill energy requirements
and maintain optimal electrolyte, vitamin, nineral and
fluid levels.
The clinician must observe closely the
patient's protein status and design a diet which will
reduce the total renal solute load to the smallest
amount consistent with the nutritional welfare of the
patient.
Evaluation of the project involved a panel of five
professionals who read the study guide and answered an
opinionnaire determining the need and validity of such
a project.
vii
CHAPTER ONE
INTRODUCTION
Chronic renal failure
(CRF) of all etiologies
characteristically progresses relentlessly to end stage
renal disease until treatment by dialysis or transplantation is required.
A relationship between loss of renal
function in CRF and the diet has been suspected for many
years.
After a lapse of approximately five decades,
there is renewed interest in this topic since the course
of CRF in man mav be altered by dietary manipulation.
Increasingly,
the dietary treatment of early CRF
has become recognized by the medical community as an
integral component in managing this particular disease
state.
Therefore, a comprehensive review of the special
nutritional concerns of this patient population was
proposed.
Included were metabolic studies of low protein
diets in uremia, what its benefits are, when it is used,
and the consequences of non-intervention.
As a result,
this study guide was developed to outline the nutritional
guidelines in early chronic renal failure targeting the
metabolic effects of specific nutrients.
The project will present the special clinical
concerns of the patient in relation to specific nutrient
requirements and differing patient types.
1
The objective
2
was to present metabolic concerns of the mildly azotemic
patient, while providing the dietitian with the technical
skills and knowledge needed to implement a feasible
dietary plan with which the patient can live.
The entire study guide should be of special value to
dietitians working in the hospital setting.
A clinician
would find it most helpful to have this information
available in his daily routine for aid in assessing and
educating the patient with early CRF.
In view of the foregoing,
project,
the importance of such a
to develop a clinical study guide, justified and
established the need for this undertaking.
Justification
The nutritional management of patients with
diminished renal function represents a major challenge to
both the attending physician and the dietitian responsible
for providing nutritional support.
Dietitians play a
vital role in the education, nutritional assessment and
diet therapy which are essential for optimum care and
management of this patient population.
The dietitian's role has expanded to include the
responsibility for determining the specific metabolic
needs of a patient with early CRF.
We can now give the
patient the henefit of our nutritional knowledge which may
change the course of their disease oy 3ltering the
3
progression to end stage renal failure.
Before the renal
dietitian or student of dietetics can properly evaluate
a patient, he or she must learn how to assess a patient's
nutritional status and evaluate the results in relation
to the loss of kidney function.
Students of dietetics or dietitians who have not had
formal training in renal nutrition will find it most
valuable to read the manual, "Nutritional Guidelines in
Early Chronic Renal Failure."
The study guide is an
outlined guide demonstrating how to determine the special
metabolic needs of this particular patient population.
CHAPTER TWO
REVIEW OF
LITEP~TURE
The remarkable advances in the management of chronic
renal failure and in the efficiency of dialysis during
the past twenty years must not obscure the fact that many
patients could remain asymptomatic and prevent the rapid
loss of kidney function through proper diet therapy (5).
\mile these factors may be modified by regulation of the
dietary intake,
there are also dangers from the uncritical
application of routine diets to all patients with renal
failure under all circumstances (3).
The recognition of
the different phases of chronic renal failure in individual patients and their differentiation from secondary
nutritional disturbances forms an important part of the
assessment, both clinical and biochemical, upon whi.ch
proper management has to be based (2, 6).
Many of the
nutritional factors may appear rather obvious but are
sometimes overlooked in the technical atmosphere of a
clinical setting.
The dietary treatment of chronic renal failure was
put on a rational basis by the Italian School of
Nephrology through the scientific research of Giordano,
Giovannetti, and Maggiore (1).
They pointed out that a
diet designed to contain the minimal amount of nitrogen
4
5
consistent with the presence of the daily essential amino
acid requirements, either synthetic amino acids or in
natural foods, was beneficial in chronic renal failure,
both clinically and biochemically.
Recent clinical trials
give further merit to the protective effects of dietary
manipulation in the early stages of chronic renal
failure.
Research indicated that restriction of dietary
protein and phosphorus can slow or retard the progressive
loss of renal function early in the course of the disease
(4,
5,
6).
A comprehensive literature search was employed to
give support and validity to the role of diet therapy in
the predialysis phase of chronic renal failure.
The
product of the review of literature shall then constitute
a study course which would enable trained clinicians to
recognize the clinical and biochemical feature specific
in chronic renal failure.
normal renal anatomy,
This study course will outline
the structure of the nephron and the
pathophysiology of chronic renal failure.
Metabolic
abnormalities of chronic renal failure will be addressed,
focusing on the solute control system specific in chronic
Diagnostic tests used to assess the degree
of renal failure and the rate of progression of the
disease shall also be included within the study course.
Proposed 'TJechanisrns for the ongoing loss of renal function
6
in chronic renal failure and the impact of clinical
dietary treatment will be detailed.
Explanations of the
maladaptive mechanisms employed by the kidney during this
phase of the disease and the influence of diet on further
progression will be addressed.
Finally, nutritional
assessment parameters and recommendations for vitamin and
mineral supplementation will be outlined graphically.
REFERENCES
1.
Adler, S.G. and J.D. Kopple.
"Dietary Factors
Influencing Progression of Renal Failure." Nutrition
and the M.D., 5(4):1-3, 1984.
2.
Kark, Robert and J. Oyama.
"Nutrition, Hypertension
and Kidney Diseases," Modern Nutrition in Health and
Disease, ed. R.S. Goodhart, Philadelphia: Lea &
Febiger, 1980.
·
3.
Kopple, Joel D. The Renal Patient.
Abbott Laboratories, 1981.
4.
Maschio, G. and 0. Lamberk, N. Tessitare, and A.
D'Angelo.
"Early Dietary Protein and Phosphorus
Restriction is Effective in Delaying Progression of
Chronic Renal Failure." Kidney Int., 24(16):S273277, 1983.
5.
Mitch, \'I.E. and T.I. Steinman.
"Can the Course of
Chronic Renal Failure be Altered by Diet?" The
Kidney, 76(5):31-35, 1983.
6.
~Htch,
N. Chicago:
1.\iilliam E.
"Conservative Nanagement of Chronic
Renal Failure, 11 CC?ntemporary Issues in Neplu:~~lOf:<Y•
New York:
Churchill Livingston Publishers, 1981.
7
Q
CHAPTER THREE:
METHODOLOGY
The method employed in this project >vas to complete
a comprehensive literature search on the role of diet
therapy in the predialysis patient.
The result of the
undertaking >vas that the review of literature would then
constitute formulation of a study course which would
enable trained individuals to recognize and understand the
special nutritional concerns of this particular patient
population.
Evaluation
In order to evaluate this project, ":Nutritional
Guidelines in Early Chronic Renal Failure," a short
opinionnaire was developed (see Appendix A).
The
opinionnaire was designed to determine whether the manual
would be useful for dietetic students studying diet
therapy, dietitians in the hospital setting, or nutritional consultants who deal with these patients in private
practiceo
The opinionnaire was given to people who could have a
need for such a manual.
All were professionals, including
three registered dietitians who hold positions in
hemodialysis units and \vere responsible for the nutritional care of patients with chronic renal failure.
8
The
'
9
other two health care professionals were two physicians
who are internists with specialties in nephrology.
data was collected and summarized.
The
CHAPTER FOUR
RESULTS AND DISCUSSION
The section "Study Guide on the Rationale for Diet
Therapy in Early Chronic Renal Failure" was developed by
means of a thorough review of the literature.
The project
was presented to five professionals in the area of
nutritional support to be read and evaluated.
All five
responded and all questions were answered.
The results and comments for each question are
included below.
A determination was then made by this
author as to whether the original objectives were met.
The Need for "Guidelines in Earl_y
Chronic Renal Failure"
Question #1 determined if there is a perceived
.
Dt'('G
for this project, "!1utri tional Guide 1 ines 1.n Chronic
Renal Failure," with the "Study Guide on the Rationale
for Diet Therapy in Early Chronic Renal Failure."
All
five responded "yes" to this question; they could a}l see
a use and a need for this project.
Additional Information Needed
Question 1fo2 addressed whether additional information
need be included in a revised copy.
All evaluators
responded that the project was very thorough, but more
10
1
1
.Ll.
specific information and references regarding vitamin and
mineral requirements in chronic renal failure were
needed.
One dietitian commmented that more specific
equations for calculating nutritional parameters should
have been included.
Sufficient Enough Material
This question asked if the project included
sufficient material that a registered dietitian could
deliver optimal nutritional counseling after having read
the study course.
All five agreed that the study course
presented adequate enough material and references for a
dietitian to understand the direction her educational
efforts should be aimed.
All three dietitians commented
that the charts within the study course were easy to
read and interpret, lending to further understanding in
developing a feasible dietary protocol.
Information Curren_t and
Up-to~Dat~
Question #4 asked the evaluators whether the
information included within the project was current and
up-to-datP..
All fi.ve answered "yes" to this question;
the dietitians thought that the layout of the proposed
mechanisms for the ongoing loss of renal function were
well expla:i_ned and very current.
Two dietitians commented
that the theories behind the loss of kidney function and
dw impact of dietary treatment would be most useful in
12
a diet therapy class.
The physicians commented that the
appropriate research articles were cited.
Overall Response
The overall response to the project was very positive,
as indicated by all five evaluators.
com~ented
The physicians
that making this level of information available
to renal dietitians •vould serve to promote and elevate
the level of health care in the future.
One dietitian
commented that this was the first piece of literature she
had seen that addressed the various multifactorial aspect
of nutrition which the dietitian must have good •·mrking
knowledge.
Project Rating
The project was rated in all categories by each
evaluator as being very good to excellent.
All evaluators
stated that the organization was excellent, each section
was appropriately entitled, and provided sufficient
information to substantiate the claims.
All evaluators
expressed that the depth of research was thorough and,
therefore, vEry good.
The scientific research cited was
valid and gave appropriate merit to the protective
effects of dietary therapy.
Three evaluators rated the
"ease of :.:eading" as excellent and two rated it as very
good.
All evaluators commented on the appropriateness
13
and "ease of reading" in regards to the charts contained
within the study course.
The usefulness of the project
was rated excellent by three, and very good by two of
the evaluators.
The three dietitians gave the excellent
rating, commenting that the study cause would be useful
in an acute clinical setting as well as by a private
consultant.
Continuity was rated excellent by four and
very good by one evaluator.
Four commented that the
entire project read with continuity, as each section
followed in logical sequence.
The evaluators responded to "appropriate information
being provided for optimal nutritional care" as being
very good to excellent.
Two dietitians felt that enough
information was given to equip the nutritionist with the
educational skills she must possess to deliver optimal
care.
One dietitian asked for more references on vitamins
and minerals.
The two nephrologists felt confident that
if a nutritionist involved in health care possessed the
working knowledge contained within the study course, an
optimal level of care could be delivered.
All dietitians
felt that they could conduct a nutritional assessment with
confidPnce from the information provided within the
study guide.
Based on the above results and discussion regarding
the e\l:;luation of this project, this author believes that
the objectives in doing the research have been met.
In
addition, the project appeared to be justified since all
evaluators said they are interested in using the study
guide, "Nutritional Guidelines in Early Chronic Renal
Failure."
CHAPTER FIVE
SU1'-1HARY AND CONCLUSION··
Ji'f'
It has been more than fifty years since researchers
first discovered that a reduction in protein ingestion
helped reduce the symptoms associated with chronic renal
failure.
It was during that period of time that research-
ers suggested that the excretion of urea, sodium,
potassium, phosphate, and other catabolites increased the
renal solute load or "work load" of the kidney.
lapse of approximately five decades,
After a
there is renewed
interest in the topic of dietary intervention in early
chronic renal failure.
The clinical trials now suggest
that not only will dietary treatment maintain a patient
aE.:yrn.ptomatic, but may aid in retarding the progression of
their disease.
Scientific observations give merit to
diet:; designed to contain the minimum amounts of dietary
protein and phosphorus for the treatment of patients in
the prediaJ.ysis phase of chronic renal failure.
There-
fore, the purpose of this project was to design a study
guide documenting the rationale for diet therapy in the
treatment of chronic renal failure.
The literature documents the special metabolic
concerns of this particular patient population in regards
to specific clinical, biochemical, and nutritional
15
16
features.
Nutritional well-being and its effects on
patient outcome have been heavily researched and
documented.
The results have suggested that a patient's
nutritional status must undergo close clinical examination
by a trained nutritionist on a regular basis to ensure an
optimal level of care.
Rigid standards for patient
assessment are essential to prevent the nutritional complications that can occur in a patient following a diet
restricted in protein and phosphorus.
Recent reports,
however, show that a low protein low phosphorus diet can
be effectively utilized to offset the progression of
chronic renal failure without sacrificing nutritional
status.
It is necessarv for trained individuals (usually a
J
J
renal dietitian) to assume responsibility for the
patient's nutritional support and education by seeing that
nutritional needs are met and learning skills are adequately assessed.
The consequences of non-intervention in
regards to nutritional assessment, education, and close
follow-up is inconsistent with providing good patient
care.
A project of this sort was designed for renal
dietitians and dietetic students, and can be used in a
physician's office by a private consultant.
These pro-
fessionals will benefit from such a project as they will
17
have a comprehensive review of the special nutritional
concerns of the patient with chronic renal failure.
The study guide was designed to meet the needs of
the dietetic student or practicing clinician, whether it
be by a nutritionist in an acute care setting or a private
consultant.
In developing the study guide, this author
conducted a thorough research of the literature to
determine what the benefits of dietary intervention are,
when it is used, and the specific nutritional and metabolic profile of a patient with early chronic renal
failure.
The study guide was also designed to condense
and sum..'Tlarize the different mechanisms for the ongoing
loss of renal function and the effects of dietary
composition on the kidney, more specifically the g1ot'Jerular structure.
The study guide also capsulized the
interpretation of pertinent laboratory data and diagnostic
tests.
Presented in chart form were nutritional assess-
ment parameters and vitamin and mineral requirements for
use by the dietitian to ensure optimal nutritional
support.
An opinionnaire \vas developed so that an evaluation
of the project could be made.
This opinionnaire was
implemented to determine "l.vhether the content of the
project would be useful for renal dietitians in an acute
care facility,
dietetic students in a classroom, or
18
private nutritional consultants.
Five professionals
involved in the care of patients with chronic renal
failure evaluated the project for adequacy.
All five
responded to the opinionnaire and all indicated it would
be very useful for the patient population for which it was
designed.
Thus the results were favorable.
The evaluators were asked for suggestions as to what
else need be included in the project and subsequent study
guide.
One dietitian asked for more information on vita-
min and mineral requirements.
Another renal dietitian
asked for more specific calculations in regards to
figuring a patient's urea nitrogen appearance.
All
evaluators had a very positive response to the overall
project.
The study guide, as it appears in Appendix A, differs
slightly from that seen by the evaluators due to
C~langes
recoTTliLl.ended by the evaluators and the project graduate
committee.
It is the opinion of this author, based on the
results of the evaluation, that the original objectives
have been met.
In conclusion, the project, "Nutritional
Guidelines :Ln Early Chronic Renal Failure" ('<;vi th a
fe~,..,
additions), would be very useful for students studying
dietetics, dietitians in the acute care setting, and
private nutritional consultants who are responsible for
the nutritional support of the patient with early chronic
19
renal failure.
APPENDIX A
20
,, .
APPENDIX A
STUDY GUIDE ON THE RATIONALE
FOR DIET THERAPY IN EARLY
CHRONIC RENAL FAILURE
This study guide was prepared for persons trained
in nutritional support of the patient with chronic renal
failure and are to provide information regarding the
specific nutritional and metabolic concerns of this
patient population.
21
,, .
SUBTITLES FOR STUDY GUIDE ON THE
P~TIONALE
FOR DIET THERAPY IN
EARLY CHRONIC RENAL FAILURE
Page
Normal Renal Physiology .
25
Renal Anatomy:
26
Structure of the Nephron
Chronic Renal Failure .
28
The Solute Control System in Chronic
Renal Disease .
29
Progressive Nature of the Disease
30
Metabolic Abnormalities in Chronic
Renal Disease
33
Diagnostic Tests Specific in Chronic
Renal Failure
34
Urinalysis
34
Serum Urea Nitrogen or Blood
Urea Nitrogen
35
Serum Uric Acid
35
Serum Creatinine
36
Tests of Renal Ftmction
36
Inulin Clearance .
37
Endogenous Creatinine Clearance
38
Measuring the Rate of Progression .
40
Problems Associated with Quantitation
43
Effects of Dietary Composition and Feeding
Patterns on Renal Function
45
22
Page
Effects of Dietary Composition on
Glomerular Structure .
50
Clinical Dietetics in the Treatment of
Early Chronic Renal Failure
52
Proposed Mechanisms for the Ongoing
Loss of Renal Function in Chronic
Renal Failure .
53
Nephrotoxic Effects of Dietary Protein
53
Adaptive Hemodynamic Changes in the
Kidney
56
Precipitation of Calcium and Phosphorus
in Chronic Renal Failure
59
The Influence of Diet and Progression of
CRF in Man .
62
Combating Dietary Noncompliance
70
Protein Restricted Diets Suonlemented
Hith Essential Amino Acids
71
Supplenentation with Keto and
Hydroxy Analogues .
74
•
l
Dietary Restriction and Optimum Recommendation
for Vitamin Supplementation
REFERENCES .
23
76
LIST OF TABLES
Table
l.
2.
3.
4.
Page
Range of Serum Creatinine and
Creatinine Clearance .
39
Correlation Among Creatinine
Clearance, Serum Creatinine, and
Renal Failure
40
The Rate of Deterioration in Renal
Function with Protein Controlled
Diets vs. Unrestricted Diets .
69
Reco~~ended
Dietary Intakes for
CRF Patients .
24
80
25
Normal Renal Physiology
The physiological processes that are of major
importance in the consideration of renal diseases are
described briefly.
The kidneys regulate and are responsible for the
nutritional wealth of the body by maintaining its internal
chemistry.
tions.
Broadly, the kidney has three kinds of func-
These are:
1) the excre'tory functions, 2) their
homeostatic and metabolic functions, and 3) the endocrine
activity (28).
In addition to excretion of excess water
and electrolytes, the kidney must also excrete the waste
products of metabolism.
The elimination of the products
of nitrogen metabolism are very important.
Creatinine,
urea and uric acid are prominent among these, but there
are many others, not all of ,..,hich will be identified
(28) .
The second function, hemeostatic and metabolic, is
related to the first.
It deals with the maintenance of
normal nutrition, acid-base and electrolyte balance, and
the water economy of the body.
The kidneys play an
essential role in the maintenance of hydrogen ion homeostasis by means of their effects on secretion and
excretion or on reabsorption of hydrogen bicarbonate,
26
ammonium, and phosphate ions
(28, 69).
The third, endocrine activity, concerns hormones
secreted by the organ.
Among these are renin, which
functions in the renin-angiotensin system for control of
blood pressure (28, 69).
Another group of hormones, the
prostaglandins, are present in the medulla and also act to
preserve blood pressure and regulate sodium transport in
man (28).
Still another hormone secreted by the kidney
is erythropoietin which stimulates production of normal
red blood cells (28).
Vitamin D can also be termed a
renal hormone for the fact that the final hydroxylation of
vitamin D to the active form occurs Hithin the kidneys
(28,
69).
The kidney also influences the action of other
hormones, since it degrades and eliminates circulating
hormones including insulin, glucagon, and parathyroid
hormone (28, 69).
Rena 1 Anatomy:
Structure of the
~ephron
The functional unit of the kidney is the nephron.
It
has been estimated that each kidney contains one to one
and one-half million nephrons that carry out the ftmctions
of the kidney (64, 69).
Blood is transmitted from the aorta via the renal
artery and a series of renal arterial subdivisions to the
afferent arterioles.
Directly distal to this structure is
the glomerulus, a tuftlike network of capillaries Hhich
28
contact with the basement membrane of the capillary
endothelial cells (64, 69).
Mesangial cells, which are
part of the reticuloendothelial system, are located
between the capillaries (64).
Together, they are envel-
oped by a basement membrane (64, 69).
Chronic Renal Failure
Chronic renal failure (CRF) is the irreversible loss
of the excretory capacity of the kidney which occurs over
an extended period of time, from months to years (11,
69).
Endocrine and metabolic functions also are lost
(11, 69).
Chronic renal failure, of all etiologies,
characteristically progresses relentlessly to end-stage
renal disease until treatment by dialysis or transplantation is required (45).
In patients with CRF, nephrons
continue to be destroyed, causing progressive worsening of
kidney functions until end-stage renal failure occurs.
This progression occurs even when the disease that damaged
the kidney is no longer active.
Because of this, CRF can
be considered a separate disease entity (45).
Virtually every aspect of metabolism and nutrition
can be altered :Ln chronic renal failure.
The kidneys
continue to respond to the needs of the body insofar as
they are able to do so.
However, as the number of
functioning nephrons diminishes, there are functional
adaptations
t~at
occur in a regular sequence.
The nature
29
of the adaptive mechanisms varies with the solute that is
controlled (11, 45).
An important consideration is that
the adaptive mechanisms are not always of positive value,
and these sometimes are detrimental.
The Solute Control System in
Chronic Renal Disease
The composition of body fluids undergoes progressive
changes in advancing renal disease, but these changes
affect only some solutes and they vary widely in time of
onset and in degree.
The body employs a biological con-
trol mechanism for excretion and reabsorption of solutes.
The mechanism is solute specific and arises from individual detector elements and from the capability of each
control system to modulate the rate of excretion of its
own solute, overriding if necessary the effects of any
other control system on tubule transport (11).
In
advancing renal disease, the load of key solutes may vary
over the same predictable range, but the excretory
response per nephron must increase in inverse proportion
to the number of surviving nephrons.
perturbation of body fluids,
Thus, for any given
occasioned by the entry of
any given amount of a solute into the extracellular
fluid (ECF) , the excretory response per nephron must
increase as GFR decreases (11).
As has been discussed earlier, urea and creatinine
27
comprises the filtering unit (64).
These capillaries
combine to form the efferent arteriole, a blood vessel
with a muscular wall which is thus capable of changes in
the diameter of its lumen (64).
The efferent arteriole
immediately divides again into a second capillary network
which surrounds the remaining portions of the nephron
(64) .
The glomerulus invaginates a Bowman's capsule, a
blind-ended epithelial sac which, with the glomerulus,
forms the renal corpuscle (69).
Bm'llffian' s capsule is
continuous with a tubular system, the parts of which are,
successively, the proximal convoluted tubule, the loop of
Henle, the distal convoluted tubule, and the collecting
duct (69).
Urine flows through the collecting ducts to
an opening in the papilla (the apex of the pyramid) and
enters the pelvis of the kidney, which forms the
funnel~
shaped proximal end of the ureter through which the urine
passes into the bladder (69).
Bowman's capsule consists of an outer parietal layer,
which is continuous with the tubules.
The parietal layer
then is reflected back to forY-1 the visceral layer, which
covers the capillaries (64,
69).
The area between the
parietal and visceral layers is the capsular space (64,
69).
The visceral layer is composed of podocytes, which
have projections called foot processes.
These are in
~.
30
concentrations rise throughout the course of chronic
renal disease.
body fluids,
Many other solutes also are retained in
including certain organic acids, quanidinium,
phenolic acids and middle molecules (31).
Hydrogen ion
concentration increases and bicarbonate concentration
decreases, but values for both generally stabilize, and
progressive acidosis is not the rule (11).
However,
sodium, potassium, and magnesium concentrations typically
remain normal or close to normal, and detectable abnormalities in extracellular fluid (ECF) volume are the
exception rather than the rule in patients with early
chronic renal failure (11).
Phosphate concentrations in
plasma typically remain normal through at least the first
two-thirds of the natural history of chronic renal
disease, and increase thereafter only if phosphate intake
and absorption remain undiminished (11).
Plasma urate
levels also remain normal or only slightly increased,
until the underlying disease becomes relatively far
advanced.
Plasma calcium concentration falls, but this
also tends to be delayed and typically does not become
marked until hyperphosphatemia and/or vitamin D deficiency
occurs ( 31) .
Progressive Nature of the Disease
The progression of chronic renal failure has been
described by Zeman (69) as occurring in four stages which
31
are not sharply separated but, rather, are phases in a
continuing degenerative process with loss of more and
more functioning nephrons.
creased renal reserve,
The four phases are:
1) de-
2) renal insufficiency, 3) renal
failure, and 4) uremia or uremic syndrome (69).
Normally the kidneys have a large reserve capacity.
At least fifty-five percent of normal renal function must
be lost before blood urea increases, although there may
be some nephron hypertrophy during this first phase of
decreased renal reserve (11) .
The glomerular filtration
rate (GFR) is greater than SSml/minute, but less than the
normal 12Sml/minute (69).
At this stage the patient is
without clinical or metabolic symptoms.
In renal insufficiency, up to eighty percent of
nephron function may be lost, and the GFR is 30ml/minute
to 55ml/minute (69).
At this stage the nephrologist will
be able to quantitate excessive amounts of nitrogen
components in the blood.
azotemic.
normal.
The patient is said to be mildly
Serum urea and creatinine are thus above
The patient becomes more susceptible to the
effects of stress, including large changes in intake of
fluids, protein, and electrolytes (10,
69).
There is some
loss of concentrating ability, producing nocturia or excessive urination at night (10, 69).
The patient may
remain asymptomatic if no other overwhelming metabolic
32
stress occurs, such as the stress of infection.
It is
between this stage and the next that research has shown
the benefits of reducing protein and other nutrients in
slowing the progression of chronic renal failure to end
stage (10, 17, 39, 42, 45).
In renal failure,
ninety percent (69).
30.0ml/minute (69).
loss of nephron function may reach
The GFR is 12.5ml/minute to
The patient shows moderate to severe
azotemia and anemia, decreased concentrating ability, and
impaired ability to maintain electrolyte and acid-base
balance (69).
Loss of function in the final phase, uremia or
uremic syndrome, is ninety to one hundred percent.
GFR is less than 12.5ml/minute.
The
The patient is oliguric,
producing insufficient urine, or anuric, producing no
urine, \vith ureraic symptoms involving many organ systems
( 6 9) .
This manual will address the individual who has lost
approximately eighty percent of normal renal function and
the ability to adjust to the wide variations in fluid and
nutrient intake.
It is the patient with early chronic
renal insufficiency that research has targeted with the
attempt to shmv the benefits of proper dietary manipulation (10, 17, 39, 42, 45).
33
Hetabolic Abnormalities in
Chronic Renal Failure
Patients with chronic renal failure display various
abnormalities that dictate adjustments in their dietary
regimen.
failure,
During the slow development of chronic renal
the cells of the body are bathed in an abnormal
fluid and, in many cases, appear to have come into a ne1;.J
homeostatic equilibrium with the altered humoral environment (28).
One important biochemical abnormality is the
accumulation of toxic products that are normally excreted
by the kidney.
Host prevalent are the metabolic end-
products of amino acids and protein (31).
Although most
toxic metabolites accumulate as a result of decreased
excretion, other factors such as impaired degradation
by the diseased kidney, or enhanced synthesis, or
decreased catabolism by other organs may contribute to
the increased presence of many of these substances (31).
Possible abnormalities of chronic renal failure
include:
1. Retention of nitrogenous waste
products (azotemia).
2. A decrease in the ability to
excrete a sodium load or conserve
sodiUtll with dietary sodium restriction.
3. An increase in the renal obligatory
1 o s s of \vat e r .
4. A limitation in the ability to
handle loads of water, potassium, or
magnesium.
34
5.
Retention of phosphate.
6.
Hypocalcemia.
7. \-Jasting syndrome.
8. A decrease in the concentration of
serum albumin and total albumin pools
and in rates of synthesis and degradation of albumin.
9. A decrease in the concentration of
serum transferrin and certain proteins
of the complement systems.
(40)
Diagnostic Tests Specific in
Chronic Renal Failure
In order for the renal dietitian to maintain optimum
nutrition while minimizing the metabolic disorders of
kidney failure, he or she must understand the clinical
tests used in diagnosis of the disease.
The clinician
must be able to interpret the results of the relevant
tests in relation to severity of renal failure and degree
of dietary restrictions that are needed.
Urinalysis
In the normal adult, 600-2500cc of urine are formed
daily.
The quantity generally depends on the water
intake, the external temperature, the diet, and the
individual 9 s mental and physical state (64).
The urine
may be examined for the presence of materials not normally
seen in the urine or for abnormal quantities of substances
normally found in the urine (69).
Substances that, when
present in the urine, may indicate kidney disease include
35
erythrocytes,
(69).
leukocytes, microorganisms, and protein
Measurements of the pH and specific gravity of the
urine are sometimes of diagnostic value as well, since
they indicate the capacity of the kidneys to maintain
acid-base balance and a normal osmolality of body fluids
( 69) .
Serum Urea Nitrogen (SUN) or
Blood Urea Nitrogen (BUN)
Urea is the principal end-product of protein
metabolism in mammals (64).
Its excretion is directly
related to dietary protein intake and comprises eighty to
ninety percent of the total urinary nitrogen (64).
The
deamination of amino acids results in the product of
ammonia, a highly toxic substance (69).
In the human
liver, ammonia is converted to urea via the urea cycle and
If the kidney is
then is excreted in the urine (64).
unable to excrete nitrogenous wastes, urea, too, \vill rise
in concent:ration in the blood (69).
The ranges of normal
urea nitrogen concentration are Smg/dl to 20mg/dl of blood
and 6mg/dl to 20mg/dl of serum (69).
Serum Uric Acid
This is the most important end-product of the
oxidation of purines in the body.
It is derived not only
from dietary nucleoprotein, but also from the breakdo\m of
36
cellular nucleoprotein in the body (64).
Uric acid
appears in the serum in a concentration of 3mg/dl to
7mg/dl in men or 2mg/dl to 6mg/dl in women (69).
As with
urea, it increases in concentration as renal function
diminishes.
Serum Creatinine
Phosphocreatine in muscles is formed from glycine,
arginine, and methionine (69).
tion product of phosphocreatine.
Creatinine is a degradaIt is produced in an
amount proportionate to muscle mass and is excreted in the
urine (69).
As women have less muscle mass than men,
they usually have a lower serum creatinine.
Normal
concentration in the serum is usually 0.6mg/dl to
1. Srag/ dl ( 69) .
If the kidney is unable to excrete
nitrogenous waste products, the concentration of creatinine will increase in the blood.
Tests of Renal Function
For the purpose of expressing quantitatively the rate
of excretion of a given substance by the kidney,
11
1
II•
d
c_earance
lS f_requent 1 y measure_.
its
This is a ·Jolurrte of
blood or plasma which contains the amo1.mt of the substance
that is excreted in the urine in one minute (64).
Alternatively, the clearance of a substance may be defined
as that volume of blood or plasma cleared of the amount of
37
substance found in one minute's excretion of urine (64).
The calculation of clearance can be illustrated by
measurement of the clearance of inulin or creatinine.
Inulin Clearance
The polysaccharide inulin is filtered at the
glomerulus but neither secreted nor reabsorbed by the
tubule (64).
The clearance of inulin is therefore a
measure of glomerular filtration rate.
These clearances,
as with many other physiologic phenomena, vary with body
size; e.g., normal inulin clearance is 120mg/1.73m 2 body
surface area.
To facilitate interpretation, the results
of an actual clearance study are usually calculated on the
basis of ml/1. 73m2 (64).
This is considered the most
precise method for quantifying renal function, however
not frequently used, as the test is time-consuming, expensive and potentially hazardous in CRF patients who may
not be able to effectively excrete the water load given
during administration (45).
In measuring inulin clearance, it is desirable to
maintain a constant plasma level of the test substance
during the period of urine collections (64).
Simultane-
ous measurement of the plasma inulin level and the
quantity excreted in a given time supplies the data
necessary to calculate the clearance according to the
follmving formula:
38
\.Jhere
c
in
c
in
u
p
v
U
X
V
p
Clearance in inulin (ml/min)
Urinary inulin (mg/dl)
Plasma inulin (mg/dl)
Volume of urine (ml/min)
(64)
Endogenous Creatinine Clearance
At normal levels of creatinine in the serum, this
metabolite is filtered at the glomerulus but not
secreted or reabsorbed by the tubule
quently,
GFR.
(63).
Conse-
its clearance may also be measured to obtain the
Creatinine clearance is computed using the following
formula:
Creatinine
Clearance
(ml/mi.nute)
Urine Creatinine
(mg/lOOml)
X
Urine Flow
(ml/minute)
Serum Creatinine
(mg/lOOml)
This is a convenient clinical method for estimation of
the GFR since it does not require the intravenous
administration of a test substance as in the case with an
exogenous clearance study using inulin.
Normal values
are lOOml/minute to lSOml/minute for men and 85mg/minute
"J
L
to 125mg/minute for women when corrected to 1.73m
surface area (68).
of body
Lancaster et al. (35) shovJ the
range for serum creatinine and creatinine clearance for
men and women (Table 1).
In addition, Lancaster et al.
39
(35) also demonstrated an approximate correlation among
creatinine clearance, serum creatinine and degree of renal
failure (Table 2).
TABLE l
Range for Serum Creatinine
and Creatinine Clearance
Serum
Creatinine:
Hen
Women
0.85-l.Smg/lOOml
0. 70-l.25mg/l00ml
Creatinine
Clearance:
Hen
\\Tomen
100-lSOml/min
85-125ral/min
(35)
40
TABLE 2
Correlation Among Creatinine Clearance,
Serum Creatinine, and
Renal Failure
Creatinine
Clearance
.
m-'-, I mJ_n
Degree of
Renal Failure
1.0 - 1.4
Normal
84
1..5
~1ild
49
2.1 - 6 . .5
10
6.5
Severe
12
Anuria
(end stage)
-
150
50 10 -
8.5
Serum Creatinine
(Approximate)
mg/lOOml
0
-
2.0
~1o
derate
(35)
-----------------------
l1easuriEf~pe
Rate of Progression
An assessment of the impact of any therapy on the
progression of a disease requires a reliable method for
quantifying changes in the course of the disease (43, 47).
In CRF, emphasis is placed on assessing the rate of loss
of residual renal
~mction
in the individual since there
is considerable variability among patients afflicted with
the same disease (43, 47).
Such variabilitv
_, makes it
41
difficult to detect Hhen a therapy is truly effective in
altering the course of progressive renal insufficiency.
Moreover, the physician and dietitian need an acceptable
tool in which to determine the effects of therapy in
individual patients.
As previously mentioned, the most precise method for
quantifying the level of renal function is to measure the
glomerular filtration rate (GFR).
The standard method
is the inulin clearance usually measured during administration of a water load, but this is time-consuming,
expensive and potentially hazardous if the patient does
not excrete the water load rapidly (43, 44, 47).
To avoid
these problems, the twenty-four-hour clearance of
endogenous creatinine has been used (43, 44, 47).
How-
ever, repeated urine collections are inconvenient, and
incomplete collections constitute an important error in
calculating clearance (43, 48).
At present, the most
reliable method of estimating changes in renal function
during long-term therapy is to monitor changes in the
reciprocal of serum creatinine concentration (43, 44).
Creatinine is used rather than BUN because the latter
provides only a rough determination of renal function and
is affected by many variables.
Host patients experience a constant rate of loss of
residual renal function after the initial disease has
42
damaged the kidneys enough to initiate the characteristic
nephrotoxicity of CRF (43, 44).
Mitch et al.
(43) showed
that in thirty-one of thirty-four patients with chronic
renal insufficiency caused by various diseases, reciprocal
serum-creatinine concentration declined linearly as creatinine concentration rose from a mean of 2.6mg/dl to
14.8mg/dl over an average of seventy-one months.
Mea-
suring the rate of rise of serum creatinine is difficult
but the loss of function can be estimated easily by
plotting the reciprocal of the serum creatinine
concentration against time (43, 44, 47).
This relation-
ship is linear in most patients and the rate of
progression apparently is independent of the initial cause
of renal disease (43, 44, 47).
The simplest explanation
for this constant decrease in the reciprocal of serum
creatinine is that creatinine clearance and, hence,
residual nephrons are being lost at a constant rate (43,
44, 47).
If a clinic or hospital were to plot a graph on
individual patients, the effect of therapy on progression
of CRF could be assessed before initiation of therapy and
during therapy to assess the adequacy of a given
protocol.
Other factors in addition to decreased renal
function that may account for an elevation in BUN are:
0
•
43
(1) Exogenous protein load
(2) Endogenous protein load
a) Destruction of local tissue
b) Blood in gastrointestinal
tract
(3) Altered balance between protein
synthesis and degradation; catabolic state:
a) Glucocorticoids
b) Infection
c) Stress resulting from surgery
or injury
d) Anabolic steroids
e) Tetracycline
f) Caloric restriction
g) Previous protein depletion
h) Protein-losing syndromes
(4) Factors altering urea synthesis
a) Severe liver disease
b) Altered urea recycling in
gastrointestinal tract
(5) Decreased urinary output; urea is
filtered and absorbed in relation
to urine flow
(33)
Problems Associated with
Quantitation
One of the concerns with using serum creatinine or its
reciprocal is that changing the diet could lower the
serum creatinine concentration by reducing creatine
intake or the accumulation of compounds inhibiting renal
creatinine secretion or by reducing endogenous production
of creatinine through effects on lean body mass (43, 44,
47).
If nutritional therapy does not estimate the
patient's metabolic and caloric requirements adequately,
frank muscle wasting could be seen.
As muscle mass
p '
44
decreases, a transient decrease in serum creatinine will
be evident on a chemistry panel.
The dietitian must follow
the patient's weight and anthrooometric measurements
closely in order to assess false values which would be
suggestive of improvement in renal function.
After changes secondary to the diet have occurred, a
new steady state of creatinine production and clearance
will be established and any subsequent change in the
reciprocal of serum creatinine must, therefore, represent
a change in renal function (43, 44).
Since the half-time
to a new level of creatinine excretion following a change
in creatine intake is about forty-one days, changes in the
serum creatinine concentration cannot be ascribed with
confidence to dietary intervention unless they persist for
at least four months (46).
If after this period the
reciprocal of serum creatinine continues to decrease at a
lower rate than previously, then it should be concluded
that a significant change in progression of the disease has
occurred (43, 44).
On the other hand,
if the rate returns
to the same value as that measured before dietary intervention, then changing the diet had no significant effect
on progression (43, 44).
It is important to emphasize that this method
estimates the rate of loss of residual renal function and
cannot be considered equivalent to GFR at any point in
time (43, 48).
However,
the inulin clearance is not a
45
precise measure of the number of remaining nephrons,
either, because there are adaptive increases in the singlenephron GFR of the remaining nephrons and it is not knmm
how these adaptive responses vary with decreasing renal
function (43, 44).
Nore will be \vritten regarding the
adaptive and hemodynamic changes within the nephron in
relation to dietary intake.
In summary, repetitive measurements of inulin
clearance would give the most accurate estimate of residual
renal function but \vould not necessarily measure the true
rate of loss of residual nephrons (43, 44).
Because of
practical problems, it seems prudent to use the simpler
method of following changes in the reciprocal of serum
creatinine during long-term therapy (48).
Those patients with substantial kidney damage, e.g.,
serum creatinine above 3-4mg/dl, have the highest likelihood of progressing to end-stage renal disease and would
benefit the most from dietary intervention (43, 44).
Effects of Dietary Composition and
Feeding Pat terns on Renal Fun c.!-- ion
It has been more than thirty years since Addis (2)
suggested that the excretion of urea, sodium, potassium,
phosphate and other catabolites required "renal v-wrk."
This concept was supported by the early findings in rats
46
that renal mass increased •vith long-term feeding of
protein (37).
Changing the diet of dogs from carbohydrate
to meat was subsequently shown to increase renal blood flow
and glomerular filtration rates by as much as one hundred
percent (10).
Similarly, the average glomerular filtration
rate was approximately seventy percent higher in rats
maintained on thirty-five percent protein chow than in
rats fed a diet containing only six percent protein (55).
Striking increases in kidney size have been reported
in patients receiving large quantities of amino acids
intravenously during hyperalimentation.
Kline (29) showed,
the effects of acute protein challenges when he reported
the changes in glomerular filtration rate during cyclic
total parenteral nutrition.
The GFR, during the twelve-
hour infusion of the amino acid-rich nutrient solution
(equivalent to lSOgm of protein), increased fifty percent
over the following twelve-hour nutrient-free interval
(29).
According to Brenner et al.
(10), the changes in
renal function induced by protein intake reflect evolutionary adaptations of the kidney to meet the excretory
needs of carnivores whose protein intake was not constant
(10).
Only in the past 5,000 to 10,000 years have
agriculture and herding allowed a more continuous pattern
of food ingestion; daily intake in many Hestern countries
47
now averages approximately 3,000 calories and more than
one hundred grams of protein (10).
Unlimited intake of protein-rich food, now generally
regarded as "normal," may be responsible for dramatic
differences in renal function between modern human beings
and their remote predecessors who hunted and scavenged for
meat (10).
Hhatever its mechanism, the renal hemodynamic
response to protein consumption reflects major adaptations
of the kidney to the specific excretory needs of man.
Catabolism of such meals yields not only large quantities
of urea and other nitrogenous wastes, but of net acid
equivalents, sulfate, phosphorus, other solutes, and
water (42).
Renal vasodilator mechanisms triggered by
protein ingestion, by increasing renal blood flow and
glomerular filtration rate, should facilitate excretion of
these large solu·te loads (42).
sition, 0' Connor et aL
In support of this suppo-
(49) showed that after dogs were
fed high meat meals (lOg/kg), urine flow doubled and
excretion of urea, sodium, potassium and phosphorus
:I
increases by more than 200 percent.
The increase in
glomerular filtration rate is apparent within one hour
after ingestion of the meat meal and persists for several
hours; 3imilar changes in renal function are not found
after consumption of carbohydrate and fat meals (49).
Thus, ingestion of protein opposed to other nutrients
appears to result in a preferential increase in renal
48
perfusion that is accompanied by an increase in glomerular
filtration (42).
In contrast to the hyperexcretory pattern of renal
function in the immediate postprandial period, renal blood
flow and glomerular filtration rates are considered to fall
to low base-line levels during the relatively long
intervals, facilitating conservation of water and electrolytes Hhile intake is lmv (10).
Different nephron populations may make different
contributions to the post-prandial rise in glomerular
filtration (10).
By analogy with observation in the desert
quail, we assume that in intermittently fed mammals,
perfusion of superficial glomeruli is minimal during the
interval between meals (14).
With reduced glomerular
perfusion, low capillary-plasma flow rates and mean
transcapillary hydraulic-pressure gradients combined to
reduce superficial-nephron glomerular filtration rates to
very low levels (10).
Assumption is that the deeper
glomeruli, in contrast, remain relatively well perfused at
all times, as they do in the quail (14), and thus contribute more importantly to the low basal whole-kidney
glomerular filtration rate in the interval between
feedings
(10).
With the next meal, perfusion and filtra-
tion rates are assumed to increase more markedly in
superficial than in deep glomeruli.
Brenner et al.
(10)
49
suggest that the renal vasodilator mechanisms triggered by
protein ingestion may thus enhance excretory function in
the post-prandial period by selectively "recruiting" the
numerically predominant superficial-nephron population.
As a result of this change in renal perfusion,
the bulk of
filtrate is assumed to enter longer-looped deep nephrons
in the interfeeding interval and shorter-looped superficial
nephrons in the immediate post-prandial period (10).
To
the extent that urinary concentrating power and salt
retaining ability are greater in long-looped nephrons,
excretory losses of salt and water will be minimized
between meals and exaggerated with feeding (10).
When amount and type of food are available ad libitum,
eating patterns change, and individual meals are smaller
but more frequent, so that the aggregate amounts of food
and protein consumed are increased substantially (50).
As mentioned above, the elevations of total renal blood
flow and filtration rates are sustained at high levels.
Although basal rates of renal blood flow and filtration
are higher than they are with intermittent feeding, the
post-prandial elevations are less marked because individual
meals are relatively small (10) .
The sustained elevations
in renal blood flO\v and filtration rates can only come
about with continuous perfusion of both deep and superficial nephrons (10, 42).
In animals fed ad libitum, the
time-averaged increase in protein intake leads to
{l
'
50
unremitting filtration in superficial glomeruli at the
high rates presumably occurring in the hunter only after
ingestion of a large meal (10).
According to this formulation,
the continuous
availability of protein-rich foods obscures the large
fluctuations in renal hemodynamics that occur in wild
animals fed intermittently.
In freely fed animals, all
nephrons are continuously perfused, whereas in animals fed
intermittently, the large superficial-nephron population
provides a reserve capacity to help handle the excretory
load after occasional very large meals (10).
Accordingly,
renal perfusion and glomerular filtration are related to
the excretory demands imposed by irregular and unlimited
food intake.
Effects of Dietary Composition
on Glomerular Structure
Berg et al.
(7) have reported studies that suggest
the possibility that augmented intrarenal pressure and
flows associated with ad libitum feeding contribute to
the age-associated glomerular sclerosis repeatedly
observed in laboratory animals and in human beings.
Pro-
gressive glomerular sclerosis, evidenced by proteinuria,
involves the majority of glomeruli by the age of t\vO years
in male rats fed ad libitum (13).
Similar renal lesions
,,
'
51
were shown in mice and hamsters by Guttam et al.
experimentally fed ad libitum.
(23) when
Female animals, \vhich
eat less and have smaller kidneys, acquire renal lesions
more slowly (7).
Development of lesions in both sexes
can be delayed by
~aking
food available on alternate days
or by limiting the amount of food to one-half or two-thirds
the amount consumed by animals fed ad libitum (7).
In
rats with hereditary overeating, as in normal rats fed
ad libitum, progression of glomerular disease may be
retarded by restricting food intake (57).
Age-related studies of renal function in healthy
human beings indicate that renal blood flovl and glomerular
filtration rates decline progressively after the third
decade; values in the eighth decade are only one-half to
t\vo-thirds those measured in young adults (54).
Horpho-·
logic studies demonstrate sclerosis of ten to thirty
percent of the total glomerular population between the
fourth and eighth decades of life (7).
Alone, age-related
glomerular sclerosis poses no threat to well-being, since
renal function is not seriously compromised even in the
•
• ht y ancJ s ].lg.1r
. 1- . l y over ( .s· <+1 1I
popu.1 atlon
elg
•
If, however,
surgical loss of renal tissue or intrinsic renal disease
added to the glomerular burden imposed by eating ad
libitum,
the course of glomerular sclerosis may be
hastened appreciably (10).
52
Clinical Dietetics in the Treatment of
Early Chronic Renal Failure
As early as the 1920s, it was reported that a
reduction in protein ingestion helped reduce nausea and
vomiting in some uremic p2tients (3).
In the era before
dialysis therapy became a common mode of therapy, protein
restriction was commonly employed to alleviate uremic
toxicity and prolong life for as long as possible (63).
As uremia progressed, individuals developed nausea and
vomiting and became malnourished.
Impaired wound healing,
increased susceptibility to infection, and diminished
overall quality of life were attributed to the protein
calorie malnutrition of renal failure (12).
Therefore,
severe dietary restrictions to postpone initiation of
dialysis were not commonly implemented during the past
decade (63).
Recent reports, however, suggest that low protein/
low phosphorus diets can effectively be utilized to
offset the progression of chronic renal failure without
sacrificing nutritional status (43).
This section will
review the mechanisms that may account for the ongoing
loss of renal function and will explore the issues associated with the use of low protein/low phosphorus diets
in the nutritional management of the pre-dialysis
patient.
Proposed Mechanisms for the Ongoing Loss
of Renal Function in CRF
From studies in rats, three mechanisms have been
advanced to account for the ongoing loss of renal function
that follows an insult to the kidney:
a) uremic toxins
could cause ongoing renal damage; b) physiologic adaptations that occur in the kidney as a response to loss of
renal function could become maladaptive, in time leading
to progressive destruction of the kidney; and c) secondary
hyperparathyroidism, an inevitable consequence of renal
insufficiency, has been linked to progressive loss of renal
function (43).
Although this \vas demonstrated decades ago
in rats with CRF, and was suggested to be applicable to
patients as well by Addis in 1948 (2), only recently have
methods been available for assessing the rate of loss of
renal function so that the hypothesis could be tested.
Actually, these apparently disparate mechanisms are related
since all three can be modified by appropriately manipulating the diet.
Nephrotoxic Effects of
Dietary Protein
The first of the proposed mechanisms for this effect
states that a metabolite of dietary protein, which is
nephrotoxic, accumulates in rats (or patients) because of
54
impaired renal function (44).
Accordingly, raising dietary
protein would increase the plasma level of the toxin,
leading to progressive loss of renal function.
The
obvious conclusion would be that this vicious cycle could
be broken by feeding a low-protein diet (30, 44).
Mitch (43) reported the work of Chanutin and
Ferrin in 1932, which showed that rats \vith experimental
renal insufficiency produced by sub-total nephrectomy
developed a progressive rise in blood pressure and
proteinuria, as well as increasing histologic damage to the
kidneys.
Subsequently, they reported that raising dietary
protein in a stepwise fashion for rats with either
uninephrectomy or sub-total nephrectomy accelerated the
degree of proteinuria, azotemia, hypertension, and loss of
urea clearance; mortality was also higher (43),
In
attempting to isolate the factor(s) causing these changes,
they further examined the effects of different types of
dietary protein and calories, but no specific dietary
constituent was identified as being nephrotoxic (9, 43).
These early investigators through their studies have made
it clear that some dietary factor adversely affects the
kidney in CRF, leading to progressive glomerulosclerosis.
More recently,
these observations were confirmed by
Kleinknecht e t al.
They
t~sed
( 30) in partially nephrectomized rats.
isocaloric diets differing in protein content,
55
and therefore isolated a specific toxic effect of protein
that increased functional loss and histological damage to
the kidney (30) .
It therefore seems likely that some circulating
hormone or other intermediate effector is responsible for
the increased renal perfusion and filtration induced by
protein-rich meals.
According to Roche (53), one such
effector may be glucagon, which is known to increase renal
blood flow and glomerular filtration rates and is released
by the pancreas after both protein in2estion and amino acid
infusions.
A similar toxic effect of dietary protein occurs in
rats with immunologically induced CRF.
Hitch (43) cites
the 1940 studies of Farr and Smadel which reported that the
severity of CRF induced by administration of an anti-·
kidney antibody was augmented by a high-protein diet.
hfhen
they raised dietary protein from five to forty percent,
urea clearance and survival decreased progressively,
accompanied by increasingly severe proteinuria (43).
t·1ore
recently, an important influence of food intake on the
"lupus-like" nephropathy of NZBXNZH mice was demonstrated
by Friend,
et aL
(15).
Restriction of dietary protein or
calories markedly decreased deposition of im.'Tlune complexes
at the glomerular basement membrane and damage to the
rnesangium (15, 43).
Taken together, these reports establish that a high
56
protein diet accelerates histologic damage and the loss
of renal function in surgically or immunologically induced
CRF.
They do not, however, isolate the specific nephro-
toxin.
Adaptive Hemodynamic Changes
in the Kidney
The second proposed mechanism is actually an
extension of the nephrotoxin hypothesis, since it holds
that excessive protein ingestion causes a compensatory
increase in the GFR of remaining nephrons (43).
The factor
stimulating this "hyperfiltration" response in single
nephrons becomes maladaptive,
leading to ongoing renal
damage (10).
The glomerular hyperfiltration hypothesis is based on
observations that a high intake of protein increases overall and single nephron glomerular filtration in rats and
other animals with experimental renal failure, and that
protein restriction inhibits further nephron destruction
(8, 10).
According to the hypothesis, glomerular
hyperfiltration is harmful to the kidneys by increasing
glomerular pressure and flow, which leads to proteinuria
and progressive glomerulosclerosis (8, 10).
In the compromised individual, with a reduced number
of nephrons, such as in CRF, there is a compensatory
increase in single nephron blood in GFR (10, 42, 43).
It
57
has been noted that in
adva~ced
renal disease, a single
nephron may accomplish the excretory function of a few
dozen to as many as one hundred nephrons, as such adaptations are essential for the preservation
of life (ll) .
the rat, Hostetter, et al.
(25) noted that seven days
after subtotal nephrectomy,
there "l.vas an increase in
In
single-nephron glomerular capillary plasma flow and
pressure.
This increase depended on dietary protein since
both were virtually abolished when total dietary protein
was decreased from forty to six percent (25).
Importantly,
this also reduced structural damage to glomerular capillary,
endothelium and to the mesangium (43).
The research
suggests that the progressive loss of renal function may
be related to damage caused by compensatory increases in
renal blood flmv and filtration rate or "hyperfiltration,"
in the remaining functional glomeruli (10, 25, 42, 43).
The study also supports the theory that dietary protein
restrictions inhibit further nephron destruction by
;j
preventing compensatory increases in the single nephron
blood flow and
GF~.
therefore preventing further sclerosis
of that filtering unit (25).
As more nephrons are
obliterated, there is an increased excretory burden on the
remaining nephrons, thus providing further stimulus for
increased hyperfiltration in remnant glomerular capillaries
and for progressive glomerular sclerosis (10, 25, 42, 43).
,, .
58
Olson et al.
(50) extended these observations in a
detailed study of the mechanism of proteinuria in rats
with CRF.
They noted that lowering dietary protein did
indeed blunt the expected compensatory increase in GRF and
largely ameliorated both the degree of proteinuria and
histologic damage occurring after sub-total nephrectomy
(43, 50).
Structural damage to the glomerular capillary
\valls, mesangial accumulation of fibrin, and loss of the
normal-sized and charge-selective properties of capillaries
found in CRF rats fed a higher protein diet \vere largely
eliminated by reducing dietary protein (43, 50).
The hypothesis of hyperfiltration, caused by high
protein diets, has been extended to include the progressive
glomerulosclerosis seen in the aged kidney of senescent
rats and in the kidney of rats with hereditary hyperphagia
(10, 57).
Although the vasoactive mediator causing these
changes has not been identified, the argument that hemodynamic factors contribute to progressive function and
structural kidney damage is persuasive (10, 57) .
One might conclude that these compensatory changes are
maladaptive in the long term as it leads to capillary
damage and progressive scarring with increased loss of
renal function (?'5, 43, 50).
59
Precipitation of Calcium and
Phosphorus in CRF
The third hypothesis invokes the alterations in
calcium and phosphorus metabolism characteristic of renal
insufficiency.
In this theory, patients with CRF accumu-
late phosphates leading to secondary hyperparathyroidism
and subsequently to kidney damage (44).
This mechanism was
based on the fact that primary hyperparathyroidism can
damage the kidney and parathyroid hormone injections will
lead to deposition of calcium in the kidney and
interstitial nephritis (43).
Horeover, in the rats with
CRF, excessive calcium deposition and interstitial lesions
in
t~e
kidney could be prevented by parathyroidectomy (26,
43).
In further support of this hypothesis, a review of
the metabolic pathways involving these nutrients is
outlined below.
I
In renal disease, the alterations in
vitamin D metabolism and in calcium and phosphorus homeostasis have far-reaching consequences •vhich affect the
skeletal system (11, 64,
69).
Calcium and phosphate concentrations in the
extracellular fluid normally are close to those at which
calcium phosphate salts would precipitate out into soft
tissues
(11,
28,
69).
A serum calcium X serum phosphorus
product greater than 70mg/dl may be suggestive of metastatic calcifications occurring.
As the GRF decreases, more
60
phosphate is retained and serum phosphorus levels rise
(11, 28, 69).
Calcium phosphates are deposited both in
bone and soft tissue, e.g.,
lung and heart, reducing the
serum concentrations of phosphate and reducing serum
calcium which was depressed by virtue of the vitamin D
deficiency produced in CRF (11, 69).
The depressed serum
calcium stimulates secretion of PTH, reducing tubular
reabsorption of phosphate and restoring sermn phosphate and
calcium to normal (11, 69).
As the GFR continues to
decrease, phosphate levels increase and remain high with a
transient decrease in serum calcium (69).
In an effort to
keep serum calcium at normal levels, PTH secretion becomes
chronically increased as seen in Figure l.
Loss of Nephrons
/
\
Ca & P deposition
in renal tissue
1
Ps
/
Ca 8 X Ps
PTH
Figure 1.
The vicious cycle that may contribute to the
progression of renal failure (63).
61
Decreased renal clearance contributes to the maintenance of
the high PTH levels (69).
Serum calcium is increased
toward normal, but it remains somewhat depressed.
Impaired
calciuTI absorption from the intestine also contributes to
the deficit in serum calcium (69).
Intestinal absorption
is affected when renal hydroxylation of the 25-hydroxycholecalciferal form of vitamin D to the 1, 25 form, which
stimulates calcium absorption is depressed (69).
Ibel et al.
(26) reawakened interest in this
.mechanism with their report that, in rats with CRF,
residual renal function could be protected by restricting
dietary phosphates.
As previously shown, calcium phosphate
deposition in the kidney has been linked to a high calcium
X phosphorus product and <m excess of PTH, since both can
cause calcium deposition in tubule cell mitochondria (11,
26, 43, 69).
Using the remnants-kidney model in rats,
they found that dietary phosphate restriction prevented
proteinuria, renal calcification, histologic changes,
functional deterioration and death in uremia (26).
A
similar degree and pattern of calcification has been found
in preliminary studies of human kidneys (26).
The resulcs
suggest that the calcification produced by the altered
phosphorus metabolism present in CRF incites an inflamma··
tory and fibrotic action leading to destruction of the
remnant kidney, and that phosphate restriction prevents
62
this response.
Haut et al.
(24) found that dietary phosphate can be
injurious to the kidney of rats with partial nephrectomy,
and this effect is greater as the residual mass is reduced.
As more nephrons are destroyed,
there is an increased
phosphorus concentration in tubular fluid which may provide
a stimulus for dystrophic calcification (24).
Thus, experimental studies suggest that ad libitum
feeding of protein and possibly phosphate is deleterious
to residual renal function in animals with CRF.
However,
more 1;vork is needed to clarify which constituents of the
diet are harmful and to identify a nephrotoxin.
The fore-
going attempts to further justify dietary therapy in the
progression of CRF in man.
The Influence of Diet and Progression
of CRF in Man
Giordano and Giovannetti (18, 21), along with other
investigators, have reported the results of conservative
management of patients with advanced renal failure.
Patients were fed diets containing small quantities of
protein, often supplemented with essential amino acids,
and sometimes with ketoacids or hydroxyacid analogues (3).
The purpose of these studies was to maintain optimum
nutritional status while reducing uremic symptoms in
patients with advanced renal failure.
(l
63
Hore recently, clinicians have developed evidence
that diets low in protein and/or phosphorus may not only
eliminate uremic toxicity but also retard the progression
of renal failure.
The research suggests that dietary
manipulation produces better results in patients with mild
to moderate renal failure,
i.e., a GFR of 20-60ml per
minute.
Barsatti et al.
(5) evaluated the rate of progression
of renal failure between two homogenous groups of fiftyfive patients with early renal insufficiency.
The average
creatinine clearance was approximately 30ml/minute.
In
both groups, the diet supplied the same amount of
calories (approximately 35 Kcal/kg/day) and the protein
intake was equally restricted (approximately 0.6g/kg/day)
(5).
However, in Group 1, the phosphorus intake was
lower, 6. 5mg/kg/ day than in Group 2, 12mg/kg/ day (5).
In both groups the rate of decline of creatinine clearance
decreased when patients changed from a free mixed diet to
the specially controlled diets; however, in Group l, this
change was much more marked than in Group 2.
Elevated
mean levels of serum phosphate and of urinary output of
phosphate per unit of creatinine clearance, and elevated
mean levels of serum PTH were found in Group 2, whereas
Group 1 patients had normal mean levels of serum phosphate,
PTH and phosphaturia per unit of creatinine clearance (5).
•
64
p
These finds strongly suggest, therefore, that the
protection of renal function was exerted by the lower
dietary phosphorus, as this was the only significant difference in the dietary regime.
Further support for the value of the low protein/low
phosphorus diet comes from work originally intended for
preventing renal osteodystrophy done by Maschio in 1982
(39).
During the first five years of administration of
protein-restricted diets to prevent renal bone disease,
researchers were not specifically looking at the survival
of renal function in the patients tested.
However, a
retrospective analysis of eighteen patients with chronic
renal failure of varying etiologies, followed for five to
thirteen years, showed that their serum creatinine concentration had increased from the mean values of 4.3 to only
8.2mg/dl over a mean period of seven years, during which
good control of the serum concentrations of calcium and
phosphate also was obtained (39).
Their data suggested
that dietary p:t·otein restriction, \vith emphasis on control
of serum calcium and phosphate, was effective in preventing
secondary hyperparathyroidism and renal osteodystrophy, as
well as in delaying the progression of chronic renal
failure.
Later, in 1983, Maschio et al.
(38) showed that
early dietary restriction in protein and phosphorus was an
acceptable and effective regimen for delaying disease
'
65
progression in most patients with early to moderate renal
failure.
Their patient population was divided into four
groups, all with varying etiologies to their renal
disease.
Each patient, except those in Group 4, was fed
a diet of 40 Kcal/kg, 0.6g of protein per kilogram
(seventy-five percent of which was high biological value),
600 to 750mg phosphorus, 75mEq sodium and choride, and
1,000 to l,SOOmg of calcium.
Treatment with vitamin D or
its analogues was given for only short periods to some
patients (38).
Group 1 was composed of twenty-five
patients with serum creatinine levels of 1.55 to 2. 70mg/dl;
Group 2 was composed of twenty patients with serum
creatinine levels of 2.90 to 5.40mg/dl; Group 3 was
composed of eight patients with serum creatinine levels of
5.50 to 6.70mg/dl; Group 4 included thirty patients with
serum creatinine levels of 1. 60 to 4. 70mg per day (38).
Since the discovery of their renal failure, the patients
in Group
l+
had made no attempt to control s eruEl phosphorus,
calcium or BUN by dietary restriction and continued this
way throughout the experiment.
The results showed that
the rate of progression of renal failure was significantly
greater in Group 3 "late diet" than in Croup l "early
diet'' (38).
They showed that in patients with early renal
failure on protein restricted diets (Group 1), the average
rate of decrease in reciprocal creatinine was ten to forty
times lower than that observed in patients who were not
66
treated with dietary protein restriction (Group 4) and were
also significantly lower than those observed in patients
who started the diet late in the course of their renal
disease (38).
Maschio et al.
(38) also conducted a follow-up of the
same patients ranging from six to seventy-six months.
They found that in Group 1, twelve percent of the patients
had a significant deterioration of renal function, as
indicated by a rise of serum creatinine above twice the
mean initial values.
In Group 2, twenty percent had a
significant deterioration of renal function as determined
by a doubling of serum creatinine concentration (38).
In
Group 3, thirty-seven and a half percent had a significant
deterioration in renal function, again giving supportive
evidence to early dietary therapy (38).
Johnson et al. (38) followed twenty-seven patients
with early chronic renal failure for over two years,
during which time they were treated with protein restriction plus aluminum hydroxide and calcium supplements so as
to maintain normal serum levels of phosphorus and ionized
calcium.
The remarkable aspect of this study is that
serum creatinine concentrations remained nearly constant.
The initial serum creatinine averaged Smg/dl and twentyseven months later it had only increased an average of
lmg/dl (27,
62).
Thus, progression of renal failure in
67
these twenty-seven patients was relatively undetectable.
These results give further support to the theory that,
by restricting dietary protein and controlling serum phosphorus levels, progression of renal failure can be
markedly slowed or even stopped.
An additional study in which patients with earlier
renal failure were treated specifically to maintain low
normal serum phosphate concentrations has been reported
by Llach et al.
(36).
Again, the purpose of the study
was not to retard progression of renal failure but,
rather to attempt to prevent renal osteodystrophy and
secondary hyperparathyroidism (36).
In these patients,
serum parathyroid hormone levels fell markedly.
The
report showed that serum creatinine did not rise at all
during the three months these patients were initially
studied, nor during the ensuing two years of follow-up.
Another study of this type was reported by Maschio
et al.
'\
(63).
They showed that when phosphate restriction
was star-ted at a serum creatinine of 3rng/dl, an increase to
only 6rng/dl was seen in four years (63).
~fuen
phosphate
restriction was begun at a serum creatinine of 2mg/dl,
no progression at all was observed during one-and-a-half
years (63).
Giordano (17) reported that dietary protein
restriction can profoundly alter the course of patients
68
with early CRF with an initial serum creatinine of 2-3mg/dl.
Twelve CRF patients treated with low protein diets were
compared with thirteen patients who were believed to be
eating an unrestricted diet (17).
The average time until
dialysis or transplantation was required in the unrestricted group was sixteen months, but for patients adhering to
the diet, end stage renal
disease did not occur for an
average of 7.6 years (five to eleven years)
(17).
The
experiment reports the individual deterioration times,
given as half the value of survival time (to dialysis or
transplantation), as 240 days in the group of patients
refusing the diet and 3.8 years in the group on the low
protein diet (Table 3) (17).
The advantageous effects of a low protein/low
phosphorus diet in preserving kidney fLmctions were
documented in a report from Italy in 1982 (39).
Forty-five
patients were treated with a diet providing 40 Kcal/kg,
0.6gm/kg protein and 700mg phosphorus for a period of
eighteen to seventy--six months (39).
They were compared to
a control group of thirty patients following an ad
1~
diet providing approximately 35 Kcal/kg, 70gms protein/day
and 900mg phosphorus.
The researchers plotted the recipro-
cal of serum creatinine over time to evaluate the rate of
progression of renal disease (39).
A substantially slower
decline in kidney function was reported in patients
69
TABLE 3
The Rate of Deterioration in Renal Function with
Protein Controlled Diets vs. Unrestricted Diets
Untreated Patients n
Treated Patients n
=
Survival
(Honths)
Serum
Creatinine
at Start
2.6
14
2.5
5
2.2
21
2.4
6
3.0
14
2.3
6
2.5
16
2.8
7
2.7
24
3.0
7
2.6
15
2.2
-
2.3
12
2.5
7
3.0
16
2.8
8
2.2
20
2.2
8
2.7
1.5
2.6
9
3.0
15
2.2
10
2.8
18
2.5
11
2.6 mean
16
2.5 mean
7. 6
Serum
Creatinine
at Start
'
i
13
'
12
Time
on Diet
(Years)
I
70
receiving the experimental diet.
Skeletal muscle biopsy
and serial measurements of serum albumin and total protein
indicated there was no phosphorus or protein wasting (39).
It was recommended that dietary protein restriction be
initiated in the earlier stages of renal failure since
impaired protein synthesis, increased metabolism, and
nausea and vomiting may present later in the course of the
disease (39).
Combating Dietary Noncompliance
A major drawback to the low protein/low phosphorus
diet is poor patient acceptance over a long period of time.
The numerous dietary restrictions severely limit the
individual's ability to select a \vide variety of foods, and
the diets become monotonous.
In response to this problem, a modulated low protein
dietary regimen was tested by Giordano et al.
(18).
Six
renal patients were studied in a metabolic ward for periods
of forty-five days on each of the following dietary
protocols:
a) 0.33g protein/kg/day; b) 0.33g protein/kg/
day for five days of the week, then increased to l.Og
protein/kg for two days to alleviate boredom with the
diet; and c) a daily protein intake equal to the mean value
for period "b" (18).
Results indicated that urea
appearance in period "a" was equal to period "b," but
lower than period "c" (18).
The researchers concluded that
p '
71
the modulated low protein diet, which allowed a periodic
increase in protein intake, was superior to the other
two diets since there was improved patient compliance
without increased accumulation of urea.
The available data indicates that CRF usually
progresses at a constant rate toward end-stage renal
disease.
Because there are methods for analyzing the rate
of progression in such patient, the effects of dietary
protein and phosphate restriction on loss of residual renal
function have been tested (38, 39, 43, 44).
The therapy
was used because of the beneficial effects of dietary
manipulation on the survival, degree of proteinuria,
histologic damage and rate of loss of residual renal
function with experimental renal insufficiency (10, 39,
This manual has cited numerous research
reports that show the benefits of reducing protein and/or
phosphorus in patients with early CRF.
If these reports
are confirmed, a major therapeutic advance for patients
with CRF would be realized and the period before dialysis
or transplantation could be safely prolonged (43).
Protein Restricted Diets Supplemented
-------·-------------
with Essential Amino Acids
In 1963, Giordano reported that uremic patients on
synthetic, practically nitrogen-free diet could be brought
72
into positive nitrogen balance when given essential amino
acids, thereby apparently utilizing their own urea nitrogen
for protein synthesis (22).
He postulated that if urea,
under certain conditions, were used for protein synthesis,
the possibility would exist that patients with azotemia
could utilize their own urea for anabolic purposes (22).
To investigate the hypothesis, nitrogen balance was
studied in one volunteer and a group of eight patients
with renal disease, six of whom were uremic.
With the
use of a synthetic diet containing essential amino acids
in low quality, it is shown that urea, either if given
exogenously or if taken endogenously from waste nitrogen
retained in uremia is utilized for synthesis of nonessential amino acids (22).
The research by Giordano (22) was questioned by other
researchers since no metabolic pathway seems to exist in
mamalian cells by which urea nitrogen can be re-entered
into the amino acid pool (8).
On the other hand, it is
now agreed that utilization of endogenous urea nccurs
after hydrolysis to ammonia by bacterial urease in t:he
intestine (8).
The ammonia is taken up in the liver and
transformed into urea again or incorporated into proteins
(8).
The subjects should be on a low-protein diet with an
adequate intake of carbohydrates and calories to obtain
optimal nitrogen utilzation (52).
However, some argue
that even under the most favorable conditions, re-utilized
73
urea is of minor importance as a source of non-essential
nitrogen for protein synthesis (63).
Giovannetti and Maggiore (21) later treated uremic
patients with a calorie-rich, protein-poor diet containing
six to ten grams protein (1.0-l.SgmN) per day.
The nitro-
gen balance became positive \vhen the diet \vas supplemented
with the recommended daily intake of essential L-amino
acids according to Rose, or with proteins of high
biological values (egg protein) corresponding to 1.5-2,2
grams N per day (21).
The patients improved clinically
with the disappearance of mental, muscular, and gastrointestinal symptoms (21).
To re-test his earlier finds, Giordano et al.
(20)
later gave one normal subject and four patients with CRF
a sample of N labeled urea.
The recovery of the isotope
was attempted in all the component amino acids of plasma
albumin and was found to be maximal in glutamic acid,
alanine, aspartic acid, and serine, but negligible in
histidine, phenylalanine, methionine, threonine and
tryptophan (20).
The research showed that on a low
protein diet, renal patients utilized urea two to three
times better than the normal control.
Results also
indicated that on an essential amino acid diet, the
utilization of urea was even more pronounced (20).
The
data provides support for the recommendation of treating
74
patients with CRF with diets low in nitrogen but rich in
essential amino acids.
Supplementation with Keto- and
Hydroxy-Analogues
Keto-acid analogues were originally suggested for use
as an alternative to essential amino acids for nutrition in
renal failure (8).
This suggestion was based on the
concept that in mammals the transamination reaction is
reversible for all essential amino acids except threonine
and lysine (62).
By giving the nitrogen-free keto- or
hydroxy-analogues instead of the complete amino acid, less
nitrogen may be required to satisfy nutritional requirements.
Several studies of N incorporation into protein and
amino acids and of nitrogen balance have shown that t:he
keto- or hydroxy-analogues of isoleucine, leucine, valine,
and phenylalanine and the hydroxy-analogues of methionine
are utilized in uremic man (8, 19).
However, transamina-
tion of histidine seems to be impaired in renal failure,
suggesting that histidine cannot be substituted by the
analogue (8).
The keto analogue of tryptophan has not
been used in uremia (8).
Bergstrom et al.
(43) reported that supplementation
of an eighteen to twenty gram protein diet per day with a
mixture of essential amino acids slowed the rate of loss of
75
renal failure of four patients, compared to their
respective rates of progression determined before the diet.
Another report by Barsotti et al.
(6) examined the
course of thirty-one patients with CRF by measuring the
rate of change in creatinine clearance.
In patients with
an unrestricted diet, the decline in creatinine clearance
was virtually constant regardless of the type of initial
renal disease (6).
Twelve patients were treated for ten
to fifteen months with a diet restricted to 0.2 gram
vegetable protein per kg body weight and 300mg phosphorus
per day (6).
Nitrogen balance was maintained by providing
a supplement of nitrogen-free analogues of essential amino
acid, e.g., ketoacids (6).
Eleven of the patients
experienced a marked decrease in the rate of loss of
residual renal function; only one continued to lose
creatinine clearance at the same rate (6).
Grety et al.
(43) studied the effects of a daily
intake of thirty grams of protein supplemented with ketoacids on changes in the reciprocal of sert_un creatinine
concentration in forty-five patients; forty-five additional
patients served as a control group (43).
The median time
for the serum creatinine to increase from 6-lOmg/dl was
pro longed from twenty-five to sixty weeks by the dietary
regimen (43).
Alvestrand et al.
(4) reported that dialysis can be
successfully postponed for a number of months using
76
,, .
essential amino acids and/or keto-acids plus a diet
containing twenty grams of unselected protein (4).
The
study involved fifty patients with a mean initial
creatinine concentration of lOmg/dl and proved to successfully defer dialysis for an average of eleven months (4).
Some of the patients received N-free analogues in place of
five of the essential amino acids, and some received only
essential amino acids, but not in a randomly assigned
manner (4).
In summary, a low protein diet supplemented with
essential amino acids or their nitrogen-free analogues
can promote positive nitrogen balance, a reduction in
uremic symptoms and defer dialysis time resulting from
a decrease in the progression of CRF.
Di~_!:ary_.Restriction
an_d Optimum Nutrition
Dietary therapy in patients with CRF requires that
certain basic principles be kept in mind.
First, re-
stricting protein and phosphorus in the diet
usuall~
restricts calories, calcium, sodium potassium, vitamins
and minerals.
Patients with severe dietary restrictions
are always on the edge of a possible deficiency.
As
previously suggested, the daily protein requirement of
patients with CRF is approximately 0.6g protein/kg body
weight, of which sixty to seventy percent should be high
quality protein, i.e., rich in essential amino acids (39,
77
43, 44).
Further restriction of dietary protein
necessitates supplementation with either essential amino
acids or keto-acid analogues if protein wasting is to be
avoided (43, 44).
In addition, the diet should take into
account urinary protein losses.
Generally dietary protein
is increased by l-1.2g/day for each gram of proteinuria
(43).
Patients being treated with protein restricted diets
should be monitored closely to detect evidence of protein
malnutrition by measuring serum total protein, albumin and
transferrin (43, 44).
The clinician should strive to
provide the patient \vith a diet plan providing 35 Kcal/kg
body weight per day unless the patient is obese (31).
For
the patient who is either above or below ideal body
weight, an appropriate level of calories to support their
frame size should be established by the following
formula:
Men:
Women:
106 lbs. for 5' + 6 lbs. for each inch above
100 lbs. for 5' + 5 lbs. for each inch above
Recommendation for Vitamin Supplements_
Based on the information that is currently available,
recommendation have been made for supplementation of some
vitamins for persons vJith chronic renal failure.
Careful
consideration of the person's dietary and medicinal intake
should be given before additional recommendations for
supplementation is made.
78
All patients who follow protein and phosphorus
restricted diets should receive oral supplements which
must include calcium, vitamin B complex and vitamin C (31).
Vitamins E and K are not necessary; however, patients on
long-term antibiotic therapy may need K supplementation
( 31).
Vitamin D deficiency is common because of failure of
the diseased kidney to convert sufficient 25 (OH) vitamin D3 to 1, 25-(0H) 2-vitamin D3 (27).
Synthetic
vitamin D3 and vitamin D analogs have been administered
with beneficial results (27).
used:
Two products are currently
the metabolic end-product of vitamin D,
1, 25dihydroxy-cholecalciferal (Rocaltrol) or the synthetic
vitamin D analog, dihydrotachysterol (Hytakerol)
(31).
However, these drugs are used in patients with faradvanced renal failure, with a GFR of 15/25ml minute and,
i
therefore, are not the focus of this manual.
i
Serum retinol-binding protein and vitamin A levels
tend to be high in patients with chronic renal failure
(66).
Based on the information available, it is possible
to attribute the elevation in vitamin A concentration to
an increase in the binding protein, since it has been shown
that the catabolism of retinol binding protein is reduced
in renal failure (67).
The abnormalities of calcium
metabolism, bone mineralization, and fat metabolism that
79
occur in chronic renal failure have been linked to vitamin
A, but the exact rate of vitamin A in these changes is not
known (66).
The objective of a dietary protocol should be to
reduce dietary protein and phosphorus to a safe minimum,
leaving other constituents as much above the suggested
requirements as possible (Table 4) (31).
Nutritional Assessment Parameters
Although dietary protein restriction may aid in
eliminating many of the uremic symptoms characteristic of
CRF which may alter the course of the disease, it may also
induce malnutrition or a wasting syndrome in patients.
Rigid standards for patient monitoring are essential to
prevent the metabolic and nutritional complications that
e:an occur in any patient who follows a severely protein
restricted diet.
The nutritional metabolic profile developed by Kopple
(31), consists of the following parameters:
1.
2.
3.
4.
5.
6.
Intake of energy, protein,
carbohydrate, fat, mineral, vitamins and water.
Height in centimeters.
Weight in kilograms.
Percentage of relative body weight
or percentage of ideal body weight.
Weight change as a percentage of
usual weight.
Triceps and subscapular skinfold
thickness actual measurements and
percentages of the standard values.
80
TABLE 4
Recommended Dietary Intake for
Early CRF Patients
Quantities to be
Supplemented
Component
Protein
0.6g/day (70% HBV
protein)
35 Kcal/kg/day
(unless 120% of
IBH or 88% IBH)
Calories
Vitamins
Thiamine (mg/day)
1.5
Riboflavin (mg/day)
1.8
Niacin (mg N.E./day)
20
Vitamin B6 (mg/day)
10 (pyridoxine
hydrochloride)
Folacin (mg/day)
1
Vitamin B
(mg/day)
12
3
Biotin (mg/day)
not established
Pantothenic Acid (mg/day)
5
Vitamin C (mg/day)
100
Vitamin A (R.E./day)
not recommended
Vitamin D (I.V./day)
individualized (active
form)
Vitamin E (mg alpha T.E./day)
15
Vitamin K
not necessary
81
TABLE 4
(continued)
Minerals
Sodium (mg/day)
1,000-3,000
Potassium (ME /day)
40-70
Phosphorus (mg/day)
600
Calcium (mg/day)
1,000-1,500
Magnesium (mg/day)
200-300
q
Trace Elements
Zinc (mg/day)
15
Water
up to 3000ml/day as
tolerated
82
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
Percentage of body fat.
Hid-upper-arm muscle circumference
-- actual measurements and percentages of the standard values.
Serum albumin.
Serum total protein.
SerLE transferrin.
Creatinine/height index.
Net protein breakdown (UNA)
(Urinary Nitrogen Appearance,
UNA) .
Estimated nitrogen balance (can
be estimated from the difference
between nitrogen intake and UNA).
Creatinine and urea clearance.
Serum sodium, potassium, chloride
and bicarbonate.
Serum calcium, phosphorus and magnesium.
Fasting blood glucose, triglycerides
and cholesterol.
(31)
As a rule, any patient who has recently lost seven
pereent to ten percent of his or her body weight or has a
serum albumin concentration of less than 3.5gm/dl is at
nutritional-risk and must be monitored very closely (31).
Urea nitrogen appearance cr net protein breakdown is a
documented formula which is not a readily used parameter;
however; equations for its use can be fotmd in Kepple's
research (31).
Interested professionals need to keep abreast: of nev.7
research finds related to these issues.
Reports of
clinical trials should be carefully scrutinized as to:
a) degree of renal failure; b) diet prescribed; c) methods
of monitoring dietary compliance; d) parameters used to
83
assess changes in nutritional status; and e) the
methodology used to analyze outcome.
If future research
confirms the beneficial effects of these diets, then
dietary intervention in chronic renal insufficiency will
become an important and permanent component of medical
treatment.
This, in turn, will broaden the role of the
renal dietitian with greater emphasis placed on the provision of nutritional care to the pre-dialysis patient
population.
! :
,, .
(l
APPENDIX B
84
•
EVALUATIONS AND
EVALUATION OPINIONNAIRE
85
OPINIONNAIRE
l.
After having read "Nutritional Guidelines in Early
Chronic Renal Failure," do you see a use for this
manual in the health care field?
Yes
2.
Maybe
No
Do you believe additional information should have
been included and, if so, what?
Yes
No
Comments
3.
Is this sufficient enough material that a Registered
Dietitian could deliver optimal nutritional counseling
after having read this manual?
If not, why?
Yes
No
Comments
4.
Do you feel the information is current and up-to-date?
If not, -.;,;rhy?
No
Corrunen t s - - - - · - - - · - - - - - - - -
---·--------·------
86
87
Opinionnaire (Continued)
5.
6.
What is your overall reaction having read this
project?
Very Positive
Positive
Negative
Very Negative
Please rate the manual accordingly:
Very
Excellent Good
Good
Organization
Fair
----
Depth of Research
Easy to Read
Usefulness
-----
----
----
---
----
Continuity
Information
Appropriate for
Optimal Nutritional Care
Poor
--~--
---
------
----
---
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---------·--""-·--·-
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