A Review of Dietary Supplement–Induced Renal Dysfunction

Clin J Am Soc Nephrol 2: 757–765, 2007. doi: 10.2215/CJN.00500107

A Review of Dietary Supplement–Induced Renal Dysfunction
Steven Gabardi,*†‡ Kristin Munz,* and Catherine Ulbricht§
*Department of Pharmacy Services, †Renal Division, Brigham and Women’s Hospital, ‡Harvard Medical School, and
§Natural Standard and Department of Pharmacy Services, Massachusetts General Hospital, Boston, Massachusetts

Complementary and alternative medicine (CAM) is a multibillion-dollar industry. Almost half of the American population
uses some form of CAM, with many using them in addition to prescription medications. Most patients fail to
inform their health care providers of their CAM use, and physicians rarely inquire. Annually, thousands of dietary
supplement–induced adverse events are reported to Poison Control Centers nationwide. CAM manufacturers are not
responsible for proving safety and efficacy, because the Food and Drug Administration does not regulate them. However,
concern exists surrounding the safety of CAM. A literature search using MEDLINE and EMBASE was undertaken to
explore the impact of CAM on renal function. English-language studies and case reports were selected for inclusion but
were limited to those that consisted of human subjects, both adult and pediatric. This review provides details on dietary
supplements that have been associated with renal dysfunction and focuses on 17 dietary supplements that have been
associated with direct renal injury, CAM-induced immune-mediated nephrotoxicity, nephrolithiasis, rhabdomyolysis
with acute renal injury, and hepatorenal syndrome. It is concluded that it is imperative that use of dietary supplements
be monitored closely in all patients. Health care practitioners must take an active role in identifying patients who are
using CAM and provide appropriate patient education.

"This review focuses
only on supplements that commonly are available in the
US market (Table 1). A variety of foods that are ingested for
medicinal purposes have been associated with nephrotoxicity.
A discussion of these medicinal foodstuffs (e.g., star fruit, Jehring-
fruit, Djenkol beans, Cape aloes) and their risk for nephrotoxicity
is beyond the scope of this article."

Table 1. Review of nephrotoxic dietary supplementsa
Common Name
Familiar Indications
Nephrotoxic Manifestations
(AKI, acute kidney injury; ATN, acute tubular necrosis; GI, gastrointestinal; SLE, systemic lupus erythematosus)

Cat’s claw
Anti-inflammatory GI disorder
Acute allergic interstitial nephritis

Chaparral
Antibiotic Anti-inflammatory Antioxidant
Renal cystic disease and low-grade cystic renal cell carcinoma

Chromium
Glucose control Lipid lowering Weight loss
ATN Interstitial nephritis

Cranberry
Antibiotic Urinary acidifier and deodorizer
Nephrolithiasis secondary to oxaluria

Creatine
Enhancement of muscle performance during brief, high-intensity exercise
Acute focal interstitial nephritis and focal tubular injury Nonspecific renal dysfunction AKI secondary to rhabdomyolysis

Ephedra
Allergic rhinitis Asthma Hypotension Sexual arousal Weight loss
Nephrolithiasis secondary to ephedrine, norephedrine, and pseudoephedrine stone formation

Germanium
Anti-inflammatory Immunostimulant
Tubular degeneration with minor glomerular abnormalities

Hydrazine
Anorexia and cachexia Chemotherapeutic
Autolysis of the kidneys in the setting of hepatorenal syndrome

Licorice
Antibiotic Anti-inflammatory GI disorders
Renal tubular injury secondary to prolonged hypokalemia AKI secondary to hypokalemic rhabdomyolysis in the setting of pseudoaldosteronism

l-Lysine
Antiviral Wound healing
Fanconi syndrome and tubulointerstitial nephritis

Pennyroyal
Abortifacient Menstrual stimulant
Edematous hemorrhagic kidneys with ATN and proximal tubular degeneration in the setting of hepatorenal syndrome

Thunder god vine
Immunosuppressant Unknown supplement effects in conjunction with prolonged shock

Vitamin C
Enhance iron absorption Prevention of cancer and heart disease Wound healing
Nephrolithiasis secondary to oxaluria

Willow bark
Analgesic Anti-inflammatory
Necrotic papillae consistent with analgesic nephropathy

Wormwood oil
Anemia Antipyretic Appetite stimulant Asthma GI disorders
AKI secondary to rhabdomyolysis in the setting of supplement-induced tonic-clonic seizures

Yellow oleander
Anti-inflammatory
Renal tubular necrosis with vacuolated areas in the glomerular spaces in the setting of hepatorenal syndrome

Yohimbe
Erectile dysfunction Sexual arousal
SLE with resultant renal dysfunction

Table 2. Dietary supplements (common names)
associated with seizures (97)
Aspartamine
Bearberry
Black cohosh
Ephedra
Guarana
Kava kava
Monkshood
Water-hemlock
Wormwood oil
Yohimbe

Table 3. Dietary supplements (common names) with
known or potential diuretic properties
Aloe vera
Antineoplaston
Artichoke
Asparagus
Astragalus
Birch
Bladderwrack
Bupleurum
Burdock
Copper
Corn silk
Couch grass
Creatine
Dandelion
Elder flower
Ephedra
Gingko
Glucosamine
Goldenrod
Gotu kola
Green tea
Horsetail
Juniper berry
Kava
l-Arginine
Lovage
Meadowsweet
Mistletoe
Oleander
Shepherd’s purse
Sorrel
Uva ursi
White horehound
Yarrow flowers

Table 4. Hepatotoxic dietary supplements (common names)
Bee pollen
Birch oil
Blessed thistle
Borage
Bush tea
Butterbur
Cascara Sagrada
Celandine
Chaparral
Coltsfoot
Comfrey
DHEA
Echinacea
Ephedra
Germander
Green tea
Kava
Lobelia
Mistletoe
Periwinkle
Sassafras
Turmeric
Uva ursi
Valerian
White chameleon

Table 5. Dietary supplements with theoretic nephrotoxic potential
-> Potential Mechanism
Complementary and alternative medicine: Scientific Name (Common Name)
Cyclooxygenase inhibition (altered renal hemodynamics)
Curcuma longa (turmeric)
Filipendula ulmaria (meadowsweet)
Tanacetum parthenium (feverfew)
Zingiber officinale (ginger)
Boswellia serrata (frankincense)
Camelia sinensis (green tea)
Aesculus hippocastanum (horse chestnut) (Case report of intravenous horse chestnut–induced nephrotoxicity, presumably secondary to vasoconstriction from a high aescin content (no reports linked to oral formulations, which have a much lower aescin content))

-> Nephrolithiasis
Rheum officinale (rhubarb)
Rumex acetosa (sorrel)(One case report of sorrel-induced nephrolithiasis when consumed as a foodstuff and not as a dietary supplement)
Rumex crispus (yellow dock)

-> Rhabdomyolysis
Cannabis sativa (marijuana) (Case report of rhabdomyolysis was with the use of intravenous marijuana)
Colchicum autumnale (autumn crocus)
Commiphora mukul (guggul)
Coutarea latiflora (copalchi)
Monascus purpureus (red yeast)

Conclusion
Dietary supplements are a significant component of the overthe-
counter market. Consumers generally view these products
as safe and effective alternatives to conventional therapies, and
most users include these products in their therapeutic regimens
without consulting health care providers. Patients do not always
comprehend the potential dangers of consuming these
products. The current lack of supplement standardization further
complicates CAM use. Additional information is needed
regarding dietary supplement safety and efficacy, especially in
the settings of underlying illness and concomitant prescription
medication use.
Most relevant data on CAM-induced nephrotoxicity come
from individual case reports, and it is often impossible to prove
a definitive cause-and-effect relationship. These reports are not
to be considered conclusive evidence. However, circumstantial
evidence, in some cases, is strong and warrants caution. Dietary
supplement use should be monitored closely in patients who
have or at risk for renal dysfunction. It is imperative that health
care practitioners take an active role in identifying CAM use
among their patients, are aware of possible complications, report
any drug misadventures, and educate their patients on the
need for open communication regarding CAM.

http://cjasn.asnjournals.org/cgi/reprint/2/4/757.pdf