THE PATH AHEAD
The Kidney Dysfunction Epidemic,
Part 2: Intervention
Joseph Pizzorno, ND, Editor in Chief
I
n my last editorial, “The Kidney Dysfunction
Epidemic: Part 1, Causes,” I reviewed the key
environmental, dietary, and endogenous toxins that
appear to be the primary causes of the epidemic of kidney
dysfunction and failure. Heavy metals (cadmium and
mercury); persistent organic pollutants (halogenated
hydrocarbons—especially those that are fluorinated and
released when nonstick pans are heated to typical cooking
temperatures—glyphosates, etc); smoking; nonsteroidal
anti-inflammatory drugs (especially acetaminophen);
lipopolysaccharides from a leaky, toxic gut; and excessive
dietary salt and phosphates all add up to a heavy and
damaging load on the kidneys.
The scope of kidney failure was really brought home
to me while I was writing this editorial. I met with an
insurance broker interested in natural/integrative medicine
solutions for her client corporations. Her story of why she
was interested was quite illustrative of the problem. Fifteen
years ago, when she first started working in health care
insurance, she was seeing approximately 1 new claim per
year for dialysis. When after a dozen years it had burgeoned
to 10 per month, she realized something was wrong. She
then started seeking solutions, as the conventional
interventions not only were very expensive, but did not
seem to be dealing with the underlying causes of the
epidemic. As we were talking in a Starbucks near my
home, I looked thoughtfully at the kidney dialysis center
across the street. When it opened 5 years ago, I simply
thought, “How nice, now kidney failure patients no longer
have to drive downtown to ‘pill hill’ to get treated.”
Hmmm. An Internet search quickly showed more than
10 centers within 3 miles of my home. Sure makes this real.
Protecting and Regenerating the Kidneys
First, of course, we need to advise our patients on the
causes of their kidney damage. Basically, inadequate blood
supply to the kidneys, inadequate water consumption, and
excessive toxic load. Almost all the causes of kidney
damage can be controlled by helping our patients make
better choices. Keys for the most immediate benefit are
decreasing obvious toxins of choice, such as excessive
dietary salt and phosphates, and drugs such as the
NSAIDS.
Foundational to kidney function is simply the quantity
of their blood supply. Much of the loss of glomerular
filtration rate (GFR) is determined by the loss in quality
and quantity of the microcirculation of the kidneys.
8 Integrative Medicine • Vol. 15, No. 1 • February 2016
Interestingly, many of the factors known to increase
risk of most chronic diseases have as part of the mechanism
damage to the microcirculation. Obvious examples include
smoking, poor blood sugar control (loss of microcirculation
underlies the serious sequelae of diabetes such as loss of
vision, loss of toes, and, appropriately, accelerated decline in
kidney function), elevated blood pressure, oxidative stress,
elevated homocysteine, obesity, and even high-fat meals
(which increase absorption of endotoxins from the gut).
Some research suggests that impaired microcirculation
in the kidneys, not only glomerular damage, may be the
primary reason function declines with aging, as well as the
factors mentioned above.1 A significant number of the elderly
have enough atherosclerosis in the arteries leading to the
kidneys to cause measureable loss of kidney function.
Catherization to remove the blockage significantly increases
kidney function strongly supporting the concept that the
glomerular dysfunction may be as much due to poor blood
flow as cellular death.2 This decreased circulation also
facilitates the accumulation of extracellular matrix around
the kidney, which not only causes a buildup of scar tissue, but
also impairs vascular endothelial growth factor (VEGF) from
helping restore blood flow. This is modeled in Figure 1.
Figure 1. Model for the Development of Kidney Fibrosis1
Renal MV endothelial dysfunction
Vasoconstriction
TGF-β
CTGF
Mild tissue MMPs
ischemia HGF
ECM accumulation
Fibrosis
MV repair and VEGF
proliferation TSP, Angio
MV remodeling,
damage, and loss
Severe tissue
ischemia
Progressive renal injury
Pizzorno—The Path Ahead
This all leads me to recommend the following foundational
strategies:
1. Decrease total toxic load on the kidneys.
2. Aggressively reduce exposure to nephrotoxins.
3. Increase microcirculation of kidneys.
4. Protect the kidneys from oxidative stress.
Claudication Onset Time (s)
Decrease Total Toxic Load
Exogenous toxins, endogenous toxins, and toxins of
choice have been discussed in many of my editorials and
articles I have recruited for IMCJ. Mercury, persistent
organic pollutants, excessive salt and phosphates—the list is
long. No, I am not saying we need to give up on our more
comfortable industrialized life, but we most certainly need
to stop being so cavalier about letting all these undesirable
elements and molecules into our food, water, and air.
Aggressively Decrease Exposure to Nephrotoxins
The key nephrotoxic agents were discussed in “The
Kidney Dysfunction Epidemic: Part 1, Causes.” By far the
worst is cadmium. Although some chemicals are more toxic,
we are exposed to a lot more cadmium, especially those who
smoke or eat conventionally grown foods. With a half-life of
10 years and 50% of total body load in the kidneys, the
challenge presented by cadmium is serious. I will write an
editorial on cadmium in the future. In the meantime, I think
the work of Stephen Genuis, MD, in Edmonton, Alberta,
Canada, is very encouraging. Specifically, he has shown that
sweating helps excrete cadmium through the skin.
Improve Microcirculation of Kidneys
Beetroot Juice Increases Blood Flow to the Kidneys
Increasing blood flow to the kidneys has a huge impact
on improving detoxification and decreasing oxidative stress.
The research process looking at the benefits of foods and
nutrients that increase production of nitrogen oxides in
dilating peripheral blood vessels to increase blood flow to
the tissues is in the early stages, but encouraging. A study in
rats showed an impressive, dose-dependent increase in
blood flow to the kidneys up to 26% as shown in Table 1.3
There is growing research on the health benefits of
beetroot juice for humans, although I could not find any
that specifically looked at effects on kidney function. A
relevant study in adults with peripheral vascular disease
found, as shown in Figure 2, that beetroot juice clearly
improved microcirculation resulting in improved walking
distance. This 18% increase in walking time certainly
supports a significant improvement in blood flow.
Table 1. Beetroot Juice Increases Blood Flow to Kidneys
Control BRLD BRHD
BF
Kidney 414 ± 29 447 ± 32 521 ± 32
Abbreviations: BF, blood flow; BRLD, beetroot low dose;
BRHD, beetroot high dose.
Pizzorno—The Path Ahead
Figure 2. Beetroot Juice Improves Peripheral Blood
Supply4
425
350
250
225 a
200
175
150
125
100
75
Placebo Beetroot
Juice
a
Significantly different from placebo group, P ≤ .01.
Centella asiatica Improves Blood Flow to the Kidneys
Traditional Chinese medicine has used Gotu kola
(Centella asiatica) to treat kidney diseases for centuries.
Asiaticoside has been shown to improve in
microcirculation and reverse fibrosis in humans with
varicose veins. Its direct benefits for the kidneys have
only been shown in animals but are encouraging. One
found Gotu kola very effectively protected rats from
adriamycin-induced nephropathy resulting in
dramatically improved kidney function compared with
the untreated rats.5 Another study combined Gotu kola
in conjunction with naringenin and showed decreased
fibrosis formation in the kidneys.6
Chocolate Improves Blood Flow to Kidneys
Dark chocolate consumption improves oxygenation
of the kidneys, even in healthy people. The benefit is
directly proportional to catechin levels.7 Animal research
has shown that these substances also protect the kidneys
from oxidative stress from toxic drugs such as cyclosporine,8
which is a good segue into our final strategy.
Protect the Kidneys From Oxidative Stress
Blueberries Protect the Kidneys From Oxidative Stress
Every time I write about the remarkable health
benefits of blueberries, I think of insightful researcher and
compelling lecturer, James Joseph, PhD. I vividly remember
the first time we spoke at the same conference some
15 years ago and being so impressed by his deep
understanding of the healing effects of colorful foods. His
untimely death in 2010 was a shock and undoubtedly
slowed discovery in this important field.
Integrative Medicine • Vol. 15, No. 1 • February 2016 9
 Figure 3. Blueberries Protect the Kidneys from Gut- improved kidney blood flow and function in hypertensive
derived Toxins9 rats.11
GFR The protective effects of Ginkgo have been shown in
2.0 many tissues. One especially relevant study found that Ginkgo
protects the kidneys from glyphosate.12 Other animal studies
mL/min/g kidney wt

have shown protection of the kidneys from mercury, uranium,

1.5
naphthalene, and many other toxins.13,14,15 Ginkgo also
protects the kidneys from gut-derived endotoxins.16
1.0
Ginger Protects Kidney Function
0.5 Although human studies have not caught up with the
animal studies on the kidneys, there is now enough animal
0 research showing that Zingiber officinale not only improves
SAL BB SAL BB kidney function but is especially beneficial protecting the
Control LPS kidney from cadmium. The primary mechanism of
protection appears to be ginger’s ability to decrease
Abbreviations: GFR, glomerular filtration rate; inflammation and oxidative damage to kidney tissue
SAL, saline; BB, blueberries; LPS, lipopolysaccharide. exposed to a wide variety of toxins. The anti-inflammatory
benefits of ginger in the kidney are due to not only its
A benefit that surprised me was that blueberry antioxidant properties, but epigenetic downregulation of
anthocyanins specifically protect the kidneys from bowel- proinflammatory genes.17 (On a side note, I am beginning
derived entoxins. This is well demonstrated in Figure 3, to wonder what proportion of the beneficial effects of
which shows how blueberries increase GFR in normal botanical medicine is due their epigenetic effects. Which
kidneys (but the increase is not statistically significant) but then brings up the question of why. Why does consumption
far more importantly completely protects the kidneys of herbs result so often in desirable epigenetic effects? I
from the dramatic lowering of GFR caused by gut toxins wonder if this is in response to potentially toxic constituents
in those with impaired function. in herbs [and foods] that we evolved mechanisms to
detoxify, which then has unexpected benefits elsewhere.)
Curcumin (Turmeric) Protects the Kidneys One study, as shown in Table 4, found that ginger
Seems whenever I write an editorial like this, specifically increases activity of kidney antioxidant
curcumin shows up. Curcumin has shown renoprotective enzymes in obese and diabetic rats.18 Seems especially
benefit in diabetic nephropathy, chronic renal failure, relevant considering that one-third of our population is
ischemia, and nephrotoxicity induced by cadmium, obese and if not already diabetic are well on their way.
gentamicin, adriamycin, chloroquine,
iron nitrilotriacetate, sodium fluoride, Table 4. Ginger Increases Production of Kidney Antioxidant Enzymes
hexavalent chromium, and cisplatin.10 In
fact, it not only protects from damage but SOD GPx (mM/ CAT (mM/
also maintains GFR despite the toxins. (U/mg min/mg min/mg
I am especially intrigued by its protective Parameters protein) protein) protein)
effects against cadmium.
Group 1: Negative control 58.70 ± 2.2 69.0 ± 2.1
a a
18.5 ± 0.1a
Ginkgo biloba Improves Kidney Function Group 2: Positive control 36.50 ± 2.3d 38.0 ± 1.4d 13.8 ± 0.2d
This will come as no surprise Group 3: CAE (200 mg/kg) 47.24 ± 3.4 c
22.0 ± 1.3b
14.5 ± 0.1b
considering how most of us prescribe this Group 4: CAE (400 mg/kg) 48.15 ± 2.5c 23.0 ± 2.1b 15.8 ± 0.1b
ancient herbal medicine to improve
circulation in many chronic diseases. Group 5: GAE (200 mg/kg) 55.15 ± 2.6b 0.49 ± 1.5c 17.5 ± 0.2c
Ginkgo has been shown to improve blood Group 6: GAE (400 mg/kg) 57.17 ± 2.3b 0.47 ± 1.6c 17.8 ± 0.2c
supply to the brain and in other critical
tissues. Also of great importance is its Note: Means ± SE with different letter superscripts (a, b, c, d) in the
ability to protect against numerous same column are significant at P < .05 using 1-way ANOVA test. Unit of
mitochondrial toxins. As discussed in my GPx = mM of GSH utilized/min/mg protein. Unit of CAT = mM of
last editorial, mitochondrial damage in H2O2 utilized/min/mg protein.
the kidneys mediate much of the
nephrotoxicity. I could not find human Abbreviations: CAE, cinnamon aqueous extract; GAE, ginger aqueous
studies on Ginkgo specifically for the extract; SOD, superoxide dismutase; GPx, glutathione peroxidase;
kidneys, but one animal study showed CAT, catalase; SE, standard error; ANOVA, analysis of variance.

10 Integrative Medicine • Vol. 15, No. 1 • February 2016 Pizzorno—The Path Ahead

Figure 5. Ginger Partially Restores Kidney Function in
Diabetic Rats
55
50
45
40
Blood Urea (mg/dL)
35
30
25
20
15
10
5 Jennifer C. Blair, LAc, MaOM; Seroya Crouch, ND; William
0 Meeker, DC, MPH; Scott Shannon, MD, ABIHM; Nancy
Control Diabetic Diabetic Diabetic Diabetic +
Untreated + Free + Bound Gluben-
clamide
Note: Values are mean ± SEM of 8 rats per group. All
values are significantly different (P < .05).
Abbreviation: Free, free phenolic extract; Bound, bound
phenolic extract; SEM, standard error of the mean.
Several animal studies have also shown that ginger
can protect kidneys from cadmium. One study found that
the anti-inflammatory effects of ginger were so strong it
was able to prevent most of the kidney damage from
cadmium.19 Another found almost no histological kidney
damage when ginger was fed along with cadmium.20 This
makes sense as much of the damage from cadmium is
caused by increased oxidation.
Animal research has also shown kidney protection
from alcohol, malathion, carbon tetrachloride, chromates,
fructose, gentamycin, ischemia, lead, cancer drugs,
etc.21,22 Another study found that in a rat model of
rheumatoid arthritis induced by injection of Complete
Freund’s adjuvant that ginger prevented damage to the
kidneys.23
One especially encouraging animal study showed
restoration of kidney function in rats that already had
diabetes as shown in Figure 4.24
Summary
Loss of kidney function and outright failure are an
expensive and progressively more common problem. The
causes are clear: toxins from the environment, from
within, and by choice. Fortunately, several of our core
nutritional and botanical medicines have been shown in
animal and ever more human studies to not only help
protect the kidneys from damage but to actually improve
microcirculation and at least partially restore function. I
would like to acknowledge and thank Australian master
Pizzorno—The Path Ahead
herbalist Kerry Bone for many of the kidney function
restoration ideas in this editorial.)
In This Issue
Associate editor, Jeffery Bland, PhD, leads this issue
from his remarkable perspective of decades of deep study
of nutrition research and biochemical individuality. I
think his discussion is important to better understand the
clinical implications of phenotypes existing in not only
severe but also mild and moderate forms. Although the
severely dysfunctional phenotypes are well recognized by
conventional medicine, we clinicians must deal regularly
with the much more common milder forms that are not
nearly as well studied.
Associate editor, David S. Riley, MD, leads a team of
integrative medicine doctors—Robert Anderson, MD;
Sudak, MD, ABIHM; Lucia Thornton, RN, MSN, AHN-BC; and
Tieraona Low Dog, MD—who have worked together to
compile the history of integrative medicine. I find quite
fascinating how so many different areas of the country and
diverse health professions seem to be arriving at similar
perspectives on the causes of the health care crisis and best
practices for restoring health. I also have come to wonder
why orthomolecular medicine, which seems to be the first
organization to apply rigorous science to this way of
thinking about patients, did not evolve further.
As usual, John Weeks keeps us apprised of the
evolving political, economic, and structural environment
in which we practice our patient-centered curative
medicine. I have often thought that the key reason the
many efforts for health care reform have been almost
universally disappointing is that the core practitioners in
the various settings did not have the right training. No, I
am not saying diagnosis and treatment of disease are not
important, but rather the disease treatment model that has
dominated the past century fundamentally fails at core
primary care. Very encouraging to see emerging
demonstration models with our doctors at the core now
showing what a real HEALTH CARE system looks like.
We welcome with this issue a new associate editor,
Tim Birdsall, ND. Most of IMCJ’s readers will be aware of
his excellent research and leadership in integrative cancer
care. As this is a challenge frequently facing most
integrative medicine practitioners, I am very excited he is
bringing us his welcome expertise. For his first
commentary, he addresses the recently widely publicized
reports downplaying the role of diet and lifestyle as causes
of cancer.
I am very pleased that we are able to publish abstracts
from the Academy of Integrative Health & Medicine
(AIHM) 2015 annual conference. Reviewing the summaries
of these many dedicated researchers and clinicians, I am
starting to see us build the necessary infrastructure of
understanding and rigor necessary for this field to advance.
Integrative Medicine • Vol. 15, No. 1 • February 2016 11
 My dear spouse Lara Pizzorno, MDiv, MA, LMT, provides
us a 2-part series on the many underrecognized nutritional
problems caused by bariatric surgery. As the population
becomes ever-more obese, we will see more and more
patients trying to deal with the aftermath of these
procedures. As Lara and I reviewed the research, we were
both quite surprised by how little awareness most clinicians
have about how this procedure disrupts nutritional status
and the dearth of studies on how to take care of these
patients.
I very much appreciate the rigorous case histories
associate editor, David Riley, MD, has brought to IMCJ.
Elliot T. Taxman, BA; Erin D. Conlon, BS; Alex Speers, BA;
Kristin L. Dismuke, BS; Tonya S. Heyman, MD, FACOG; and
Thomas L. Taxman, MD, FAAP, point out that one-half of
cancer patients use integrative medicine, whether or not
their oncologist is aware of their … dallying. Clearly, this
is an area where astute and comprehensive integration and
communication are critical for these patients—as well
demonstrated by these expert clinicians. BTW, love the
timeline, David. 14. Yapar K, Cavuşoğlu K, Oruç E, Yalçin E. Protective role of Ginkgo biloba
I don’t think we can adequately recognize and honor
pioneer William Rea, MD, for his seminal work in
environmental toxicity. He will be a keynote speaker on
endocrine disrupting toxins at the upcoming
Environmental Health Symposium, March 4 through 6,
2016, in San Diego, California. Managing editor, Craig
Gustafson, interviewed him for this issue.
This month, our clinician interview is with Karen
Mercereau, RN. I was quite intrigued when I met her and
learned of the network of nurses she and her team have
created to provide greatly needed guidance for patients. I
have always thought nurses with their extensive training
are seriously underutilized. I think you will find this
interview by Craig Gustafson quite encouraging.
Associate editor, Bill Benda, MD, channels the famous
philosopher, Pogo. In response, I assert, “Laughter is the
best medicine,” the origin of which is apparently Proverbs
17:22: “A merry heart doeth good like a medicine: But a
broken spirit drieth the bones.”
Joseph Pizzorno, ND, Editor in Chief
drpizzorno@innovisionhm.com
http://twitter.com/drpizzorno
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Pizzorno—The Path Ahead