Integrative Management of Renal Failure: halting progression
by manipulating renal blood flow
Steve Marsden
DVM ND MSOM LAc Dipl.CH CVA
Chinese herbal medicine appears powerful in slowing or halting the progression of renal
disease in small animals, at multiple stages. We now know enough about how these
formulas probably work to be able to use them effectively without having to be
conversant in Chinese medical theory. The formulas can now be prescribed based on the
clinical presentation of the patient in western terms, and thus safely integrated into
conventional medical protocols. In short, they allow a practitioner to begin delivering ‘the
best of all worlds’ to their patients. As a bonus to their apparent efficacy, the formulas are
teaching us a lot about the pathogenesis of renal disease.
Most veterinarians are familiar with IRIS (International Renal Interest Society) staging of
renal disease as a guide to optimal treatment of renal disease. The use of a staging system
reflects an understanding that all renal disease, regardless of cause, progresses in
fundamentally the same way. In particular, the implication is that animals in renal failure
will move from Stage I to Stage IV, with the practitioner’s goal simply being the slowing
of their passage through these stages, and of delaying their decline clinically. Therapeutic
efforts, regardless of stage, generally consist of:
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Supporting hydration
Reducing phosphorus intake and serum phosphorus levels, usually through
protein restriction
Regulating (usually by lowering) blood pressure
Controlling serum calcium levels
Treatment recommendations for the various stages of renal failure differ chiefly in the
intensity with which these objectives are pursued.
As it turns out, passage through the stages of renal failure is not necessarily a one-way
trip. Animals may be moved from Stage III to Stage I, and kept stable in Stage I for an
extended period. To achieve this feat requires an additional consideration in the
management of renal disease that must be held as the pre-eminent goal – the optimization
of renal blood flow.
Certainly fluid therapy and the use of hypotensive drugs are intended to have an influence
on renal blood flow, but their impact is somewhat indirect. Therapeutics that target
circulation within the glomerulus itself don’t exist in the conventional medical
armamentarium. By integrating select Chinese herbal therapies into renal failure
protocols, blood flow within the kidney itself can now be strongly and specifically
controlled.
Integration of Chinese medicine into conventional protocols is bringing a welcome clarity
to the sometimes muddy waters of renal disease outcomes under conventional
management. Blood pressure regulation is not always helpful in improving longevity in
renal disease patients. Some are highly responsive to intravenous fluid therapy and its
effects on increasing renal blood flow, whereas others seem to benefit only fleetingly, or
not at all. Further confusion arises from variations in efficacy of conventional therapies
over time, with fluids or hypotensive drugs being helpful one month, and deleterious the
next.
Investigation of how different Chinese medical therapies help renal disease explains these
conflicting outcomes in the process. It has taught us that the key consideration in
management of renal disease is the type of vascular state that is present. All efforts at
successful management of renal disease, whether or not they include herbal treatments,
must begin with an understanding of how blood is flowing through the kidneys.
The Two Vascular States of Renal Disease
The ability of animals to be reversed from, for example, Stage III to Stage I renal failure,
tells us that the loss of functional renal mass required to produce renal insufficiency and
renal failure is not permanent. Rather, many affected nephrons are not dead, but merely
hypoxic and hypo-functioning..
The goal of treatment, then, in renal failure is to rally these hypoxic nephrons by
optimizing circulation through the kidney. There are two main methods to do so:
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Increase blood flow to the kidney
Decrease blood flow to the kidney
The second option certainly sounds counter-intuitive, but is extremely valuable when the
glomerulus is congested to the point of being obstructed. The practitioner has no option
in these cases but to decrease congestion using anti-inflammatory strategies that reduce
the crowding of blood cells into the glomerulus, as well as the thickness of mesangial
cells and fibrosis that surround the glomerulus and place limits on its capacity.
Once the glomerulus is decongested, the way is clear for a second phase of therapy, in
which renal blood flow is increased. Chinese herbal therapies used to achieve this effect
are still anti-inflammatory and anti-fibrotic, but to a much lesser degree than the formulas
used in the decongestion phase of treatment. With mesangial cells and fibrosis subdued,
the full benefits of these renal blood flow enhancing herbs can be felt, reversing hypoxia
further and helping to restore dormant or struggling nephrons to a fuller level of function.
Not all animals will need both phases of treatment. Many cats will only need an
enhancement of their renal blood flow. Dogs, however, will frequently need an antiinflammatory phase of treatment.
Sourcing Herbs
The source of herbs used for treating renal failure in small animals must be chosen
carefully. This is particularly true of formulas that have an anti-inflammatory and
decongesting effect on the glomerulus, namely Minor Bupleurum Combination and Three
Seeds Combination. These formula names are generic and brand-independent, falsely
suggesting equivalency amongst different versions of the products. Versions of these
formulas that are designed and intended for human use have ingredient ratios that
compromise renal blood flow too severely, worsening azotemia in animals rather than
improving it. Veterinary versions of these formulas should be sought. The comments in
this paper reliably reflect experiences obtained using Natural Path Herb Company
formulas.
Natural Path formulas are available as granular extracts that can be mixed into food. They
can be sourced through All Natural Veterinary Care in Sydney Australia
(www.naturalvet.com.au)
Herbs to Increase Renal Blood Flow
Rehmannia glutinosa (Chinese Foxglove) root is used in many Chinese herbal formulas,
most commonly Rehmannia Eight Combination (Shen Qi Wan, Jin Gui Shen Qi Wan, Ba
Wei Di Huang Wan). Rehmannia has found use as a highly effective treatment for
chronic renal failure in both animals and humans. One study of its use in 100 cases of
human nephritis showed a 91% efficacy in reducing renal damage and sequela. Proposed
mechanisms of action included especially the enhancement of renal blood flow and
glomerular filtration (Su et al, 1993).
In another study, renal arteries of rats were partially ligated to provoke secondary renal
hypertension and a resultant fatal renal ischemia. Ligated rats that received Rehmannia
extract experienced reduced hypertension and mortality, and even an enhancement of
renal blood flow to near normal levels, through either ACE inhibition or juxtaglomerular
de-sensitization (Yi et al, 1965). Instead of renal blood flow being constricted, the vessels
within the glomeruli remained dilated to near normal levels.
Recent studies have confirmed Rehmannia’s ability to preserve renal function even when
the kidney is severely compromised. Following surgical ablation of the kidney,
Rehmannia glutinosa reduced serum creatinine level, 24-h urinary protein excretion, and
glomerulosclerosis. It also inhibited the expression of angiotensin II, AT(1) receptor,
TGF-beta1 and type IV collagen in the renal cortex (Lee et al, 2009).
The more studies that are done, the more mechanisms are discovered behind
Rehmannia’s efficacy in treating, preventing, and compensating for renal failure.
Rehmannia has been show to reduce oxidative stress in the kidneys and even promote red
blood cell synthesis through bone marrow stimulation (Yuan et al, 1992). Induction of
renal failure through first inducing ischemia then allowing reperfusion in rats resulted in
urine osmolality and creatinine clearance being ‘markedly restored’ compared to the
control group, when Rehmannia glutinosa was also administered. (Liu et al, 2005).
Rehmannia Eight Combination
(Ba Wei Di Huang Wan; Jin Gui Shen Qi Wan; Shen Qi Wan).
This is the default formula for renal disease in cats. It is also the formula most dogs will
end up on once the glomerulus has been decongested. It contains:
Shu Di Huang
Shan Yao
Shan Zhu Yu
Fu Ling
Ze Xie
Mu Dan Pi
Rou Gui
Fu Zi
Prepared Rehmannia root
Chinese Yam rhizome
Cornus fruit
Poria
Alisma tuber
Moutan bark
Cinnamon bark
Prepared Aconite root
Specific indications describe the ‘typical renal failure cat’:
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Prompt response to intravenous fluid infusion
Chilliness
Weak pulse
Lavender or purple and swollen tongue
Constipation
Coat dryness
Inappetance
Chronic weight loss
Polyuria
Polydipsia
Urine protein creatinine (UPC) ratios of less than 2-3
o Indicates a glomerulus that is hypofunctioning because of hypoxia alone,
rather than active inflammation
Dose (BID):
Weight (lbs)
10 - 25
25 - 60
60 - 150
NPHC (tsps)
¼
½
1
Herb drug interactions are not reported although concomitant use of systemically acting
hypotensive drugs may interfere with renal perfusion and are unnecessary given
Rehmannia’s specific ability to reduce reduce renal hypertension.
If vomiting occurs on the formula, consider use of San Ren Tang (below) or an antiinflammatory approach. Start with concomitant use of both Rehmannia Eight and San
Ren Tang if uncertain.
Herbs to Decongest the Glomerulus
Two formulas are discussed below that have an anti-inflammatory effect on the
glomerulus. Often practitioners use the two formulas simultaneously, rather than choose
one or the other. Both formulas will work well when used independently and according to
their specific indications.
Animals benefiting from these formulas often do not improve following aggressive fluid
therapy, except transiently for the first few hours when any dehydration states are
corrected. Animals receiving subcutaneous fluids may appear at their best the day after
treatment rather than the day of. In these patients, fluid therapy goals should be to
preserve hydration, rather than aggressively promote diuresis.
Xiao Chai Hu Tang (Minor Bupleurum Combination)
Figure 1. Xiao Chai Hu Tang (Minor Bupleurum Combination)
Chai Hu
Ban Xia
Gan Cao
Sheng Jiang
Da Zao
Ren Shen
Huang Qin
Bupleurum root
Pinellia rhizome
Licorice root
Ginger rhizome
Jujube
Ginseng root
Scutellaria root
Various species of Bupleurum possess compounds showing a strong anti-inflammatory
and anti-oxidant effect on the kidney (Chen et al, 2008). This effect appears due in part to
an ability of Bupleurum to inhibit nitric oxide synthase, a potent mediator of vascular
congestion and inflammation (Cheng et al, 2010). Addition of Qin Jiao (Large-leafed
Gentian Root) appears to augment this activity even further. Laboratory research confers
this plant with potent anti-inflammatory action, although its ability to treat renal disease
appears as yet unrecorded in the medical literature.
Indications
 A highly toned femoral pulse
 Concomitant liver enzyme elevations
 Light purple or normal tongue
 Hyperactivity and excitability
 Panting, restlessness, agitation
 Fatigue
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
Insomnia
Urine protein creatinine (UPC) ratios of greater than 3 (usually they are 5 to 6)
o Often indicative of glomerular damage from inflammation
Dose (BID):
Weight (lbs) NPHC (tsps)
10 - 25
¼
25 - 60
½
60 - 150
1
Adverse effects include rare transient nausea that ceases immediately following
discontinuation of herb use. Herb drug interactions are not reported.
San Ren Tang (Three Seeds Decoction)
Figure 2. San Ren Tang (Three Seeds Decoction)
Xing Ren
Yi Yi Ren
Hua Shi
Ban Xia
Bai Dou Kou
Dan Zhu Ye
Hou Po
Tong Cao
Apricot seed
Coix seed
Talc
Pinellia rhizome
Round Cardamon
Lopatherum
Magnolia bark
Rice Paper pith
Coix, one of key ingredients of San Ren Tang, has a pronounced anti-inflammatory effect
through nitric oxide (iNO) synthase inhibition (Seo et al, 2000). At the same time,
however, Coix has a clinical reputation for promoting renal filtration, such that it is
supported while inflammation is suppressed.
Although Coix is one of the main active ingredients, other ingredients appear to play a
role, yet are under-represented in most commercial versions of the formula. Versions
from Natural Path Herb Company and Kan Herb Company employ ratios that appear to
allow their formulations to work more effectively.
An added benefit of San Ren Tang may be a countering of tendencies toward
inflammation secondary to metabolic syndrome (Ha do et al, 2010). Renal inflammation
is one of the first manifestations of inflammation secondary to overnutrition (e.g. from
processed diets) in dogs (Henegar, 2001). A hallmark trait of inflammation due to
metabolic syndrome, which thus serves as an added indicator for the use of San Ren
Tang, is the previous or concomitant occurrence of inflammation at multiple epithelial
surfaces. Symptom indications include:
 Nasal congestion, wheezing, or snoring
 Constipation
 Colitis
 Seborrhea oleosa
 Recurrent cystitis
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Reverse sneezing (dogs)
Abundant nose and especially eye discharge
Weight gains
Chronic vomiting not necessarily ascribed to renal azotemia
Crystalluria
Purplish, slightly swollen and moist tongue
Toned or weak pulse
Dose (BID):
Weight (lbs)
10 - 25
25 - 60
60 - 150
NPHC (tsps)
¼
½
1
Naturally there are other herbs and herbal formulas that can manipulate or enhance renal
blood flow, including other formulas containing Rehmannia as a key ingredient; Rhubarb
root; and the formula known as Wei Ling Tang (Harmonize the Stomach with Five Herbs
and Poria Combination). The number of cases requiring these other interventions,
however, represents a minority of the total incidence of renal disease. The formulas
discussed above will easily benefit the majority of renal disease patients encountered in
small animal practice.
LONG TERM MANAGEMENT
Anti-inflammatory formulas will need to be used for usually at least four to eight weeks,
if not longer. At that point, some animals will require a restoration of renal blood flow
using Rehmannia-based formulas. If unsure if Rehmannia is appropriate yet, use the
formula concomitantly for a couple of weeks and reassess azotemia levels. If reducing the
anti-inflammatory formulas and increasing Rehmannia Eight improves azotemia, then the
transition to Rehmannia Eight can be continued.
Some animals will not thrive solely on Rehmannia Eight and will need some continuation
of an anti-inflammatory formula, usually San Ren Tang, to keep azotemia at a minimum.
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