Diabetic Nephropathy
By Dr. Brian P. Jakes, Jr.
Diabetic
nephropathy is the dysfunction of the kidneys that is seen in
both types of diabetes, but seems to be more common in Type
I patients.
It is a vascular complication
that affects the tiny glomerular capillaries of the kidney thus
reducing the kidney’s filtration ability. This is first
indicated by the appearance of protein in the urine.
Typically before any signs of
nephropathy appear, retinopathy has usually been diagnosed.
Retinopathy is also a microvascular complication that causes
similar damage to the blood vessels in the retina and lens of
the eye.
There are several different theories
on the mechanisms involved in the development of these conditions,
however they all are based on chronic hyperglycemia.
The presence of glucose alone
is harmless until an enzyme called aldose reductase catalyzes
it. The result is the production of sorbitol, a converted sugar
alcohol. Sorbitol itself is not a problem but the amount of
sorbitol present in a given organ or cell is. The kidneys have
several different types of cells containing aldose reductase.
A patient with elevated serum glucose levels would likely produce
more sorbitol in these sites. This causes a fluid imbalance
within these cells and this disruption of cellular osmoregulation
might corrupt sufficient cell function to cause organ impairment
and failure.
This process is known as the
polyol pathway. The other manifestations associated with the
polyol pathway and nephropathy are increased permeability and
thickening of glomerular basement membranes that will eventually
decrease renal function.
There are a number of physiological
changes at the onset of diabetes and during the course of the
disease. These changes begin with an enlargement of the kidneys.
This may be reversible if near normal blood glucose values are
restored promptly and then maintained. Also, an increase in
glomerular filtration rate and renal plasma flow are common
in almost half of patients, signaling some of the indications
of altered renal function. These signs will go unnoticed for
years while the kidneys’ efficiency continuously decreases
and then dramatically declines towards end stage renal failure.
Screening for elevated levels
of protein seepage in the form of albumin or more specifically
micro albumin in the urine will confirm renal involvement. Routine
diagnostic micro albumin Testing is the best way to monitor
and identify renal problems.
It appears that the damage incurred
in the kidneys from the effects of sustained hyperglycemia is
cumulative throughout the duration of diabetes. Improvements
in blood sugar control at anytime will help to slow or even
prevent this complication from occurring. The strategies outlined
in this article to reduce glycosylation and support blood vessel
integrity and flow may be some of the best defenses.
There are a large number of studies
that suggest the use of antioxidants indirectly helps in the
prevention or improvement of diabetic nephropathy.[i]
Although there are a number of
supplements that may improve nephropathy, inositol has shown
direct benefits.
There is a depletion of intracellular
inositol during hyperglycemia possibly leading to cell corruption.
Oral supplementation of inositol, a member of the B vitamin
group, may help correct this situation.[ii] As mentioned earlier,
there are similarities between retinopathy and nephropathy in
the case of diabetes. The common feature of both conditions
is damage to the tiny blood vessels located in the eyes and
the kidneys. An extract of the bilberry plant has been studied
in-depth for well over half a century and has proven its ability
to increase vascular integrity within the eye, so it use as
a prophylactic agent in nephropathy should be strongly considered.
Animal research with bilberry
and its effect in the kidneys as well as for hypertension, give
cause to believe that it will be equally effective in treating
nephropathy.
Vitamin C may also be beneficial
in the treatment and prevention of nephropathy through several
pathways.
Vitamin C acts as an aldose reductase
inhibitor reducing sorbitol conversion and decreasing cellular
damage in the kidneys.
Vitamin C may also be helpful
is this role as an antioxidant. Hyperglycemia induces oxidative
stress that negatively effects the vascular system and can lead
to the development of atherosclerosis. Patients with nephropathy
show lower serum levels of vitamin C due to increased renal
clearance of vitamin C.[iii] This reduction may allow more oxidant
damage to occur to the vascular system and kidneys thus perpetrating
the cycle.
Animal studies with vitamin E
have been used with success in preventing glomerular dysfunction.[iv]
Recent studies with diabetes patients show a significant improvement
in renal function with high dose vitamin E.
Normalization of blood lipids
and cholesterol are important in the prevention of diabetic
nephropathy.[v]
Reducing high blood pressure
will aid in preservation of renal function.[vi]
Diet and exercise must not be
excluded in the treatment of nephropathy. Dietary restriction,
but not exclusion of, protein, sodium and some types of fats
may also help delay renal failure.
The reduction of dietary protein
will also cause a similar decrease in amino acid intake and
conversion.[vii] This may facilitate the need for oral amino
acid supplements. Saturated fats should be replaced ideally
with monounsaturated fats like those in fish or chicken.[viii]
[ix]
Angiotensin converting enzyme
(ACE) inhibitors are drugs used after the diagnosis of nephropathy.
Some recent studies have shown the benefit of starting all diabetes
patients on these types of drugs.
They treat some of the symptoms
of nephropathy, but like all drugs of this nature they have
significant side effects that must be monitored closely especially
if the patient is close to end stage renal failure.
Dr. Brian P. Jakes, Jr., N.D.,
C.N.C. is a Board Certified Doctor of Naturopathy as well as
a Certified Nutritional Consultant. In his practice, in Mandeville,
LA, Dr. Jakes works with physicians to treat a large number
of diabetes patients. This is an excerpt from his upcoming book;
"Diabetes: The Essence Of A Cure”
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References:
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[i] Kakkar R, Mantha SV, Radhi
J, Prasad K, Kalra J. Antioxidant defense system in diabetic
kidney: a time course study. Life Sci 1997;60(9):667-79.
[ii] Goldfarb S, Simmons DA,
Kern EFO. Amelioration of glomerular heperfiltration in cute
experimental diabetes mellitus by dietary myo-inositol supplementaion
and aldose reductase inhibitation. Trans Assoc Am Physicians
1986;99:67-72.
[iii] Dirsch IB, Archley SH,
Tsai E, Labbe RF, Chait A. Ascorbic acid clearance in diabetic
nephropathy. J Diabetes Complications 1998 Sep-Oct;12(5):259-63.
[iv] Koya D, Lee IK, Ishii H,
Kanoh H, King GL. Prevention of glomerular dysfunction in diabetic
rats by treatment with d-alpha-tocopherol. J AM Soc Nephrol
1997 Mar;8(3):426-35.
[v] Lam KS, Cheng IK, Janus ED,
Pang RW. Cholesterol-lowering therapy may retard the progression
of diabetic nephropathy. Diabetologia 1995 May;38(5):604-9.
[vi] Jerums G, Cooper ME, Seeman
E, Murray RM, McNeil JJ. Spectrum of proteinuria in type I and
type II diabetes. Diabetes Care 1987 Jul-Aug;10(4):419-27.
[vii] Brodsky IG, Robbins DC,
Hiser E, Fuller SP, et al. Effects of low-protein diets on protein
metabolism in insulin-dependent diabetes mellitus patients with
early nephropathy. J Clin Endocrinol Metab 1992 Aug;75(2):351-7.
[viii] Malcolm D Riley and Terence
Dwyer. Microalbuminuria is positively associated with usual
dietary saturated fat intake and negatively associated with
usual dietary protein intake in people with insulin dependent
diabetes mellitus. American Journal of Clinical Nutrition, Jan
1998 v67 n1 p50(8).
[ix] Pecis M, de Azevedo MJ,
Gross JL. Chicken and fish diet reduces glomerular hyperfiltration
in IDDM Patients. Diabetes Care 1994 Jul;17(7):665-72.
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