Heavy metal toxicity and chronic renal failure in horses
Chronic renal failure features a progressive loss of renal function. It results in decreased urinary concentration, retention of nitrogenous and other metabolic end products, alterations in electrolyte and acid-base balance, and dysfunction of several hormone systems.
There are several causes of chronic renal failure in horses. Often, however, renal dysfunction is diagnosed as idiopathic chronic renal failure. This article will include a brief review of kidney physiology, a discussion of chronic renal failure related to lead toxicity, and a case study of holistic treatment for a horse with this condition.
BRIEF REVIEW OF RENAL PHYSIOLOGY
Body fluids circulate through the kidneys 15 times a day and are continually being filtered by the two million nephrons contained within the kidneys. The afferent renal arteriole delivers blood into a capillary bed called a glomerulus, which lies within Bowman’s capsule contained in the cortex of the kidney. The fluid from blood filters through the glomerulus within Bowman’s capsule, continues through the proximal tubule and into the loop of Henle located in the renal medulla. The loops of Henle coalesce with the distal tubules, finally delivering the fl uid into a collecting duct. Individual collecting ducts converge and empty into a funnel-like structure called the renal pelvis, which then empties the fluid into the ureters during micturition.
The kidneys serve homeostatic functions such as regulating electrolytes, maintaining acid–base balance, regulating blood pressure, and producing the hormones calcitriol and erythropoietin, and the enzyme renin. The kidneys also filter blood to rid the body of toxic wastes such as urea and ammonium. These functions are accomplished by the actions of filtration, reabsorption and secretion within the nephrons. The cells and proteins are separated from the plasma at the level of the glomerulus by a passive filtration process. Tubular reabsorption is the process by which solutes and water are removed from the tubular fl uid and transported across the renal interstitium back into the bloodstream. Tubular secretion is the transfer of materials from peritubular capillaries to renal tubular lumen.
Sources of lead ingestion in the equine are varied. Human activities have spread lead widely throughout the environment – in the air, water, soil, plants, animals and manmade constructions. Once lead falls onto the earth, it adheres to the particles there and remains in the upper layer of soil. Soil erosion or environmental lead may cause contamination of rivers, lakes and streams as well as drinking water sources.1 Acute exposure to lead has deleterious effects on all organ systems, but the most profound effects are seen in the nervous, digestive and circulatory systems.
MECHANISMS OF LEAD1,2,3,4
• Substitutes for and competes with Ca++
• Disrupts Ca++ homeostasis
• Binds with sulfhydryl groups
• Stimulates release of Ca++ from mitochondria
• Damages mitochondria and mitochondrial membranes
• Substitutes for Zn in zinc-mediated processes
• Increases oxidative stress
• Inhibits antioxidative enzymes
• Alters lipid metabolism
RESULTS OF LEAD TOXICITY1,2,3,4
• Abnormal myelin formation
• Altered neurotransmitter density
• Altered neurotransmitter release
• Increase in lipid peroxidation
• Impaired heme biosynthesis leading to anemia
• Decreased cellular energy metabolism (ATP)
• Altered apoptosis
Kidney damage occurs with exposure to high levels of lead, and evidence suggests that lower levels can also damage kidneys.5 This author believes that a very low dose of lead exposure may cause subclinical renal disease. The main body compartments that store lead are the blood, soft tissues and bone. The half-life of lead in these tissues is measured in weeks for blood, months for soft tissues, and years for bone.6 The estimated half-life of lead in a human bone is 20 to 30 years. Bone deposits lead back into the bloodstream long after the initial exposure is gone as a consequence of natural cell turnover, bone remodeling and degeneration.7 Lead is predominantly cleared from the body through the kidneys, causing a subclinical tubulointerstitial nephritis which may progress to chronic renal failure. 8
Lead is absorbed by the proximal tubular cells, where it binds to specific lead-binding proteins and forms lead-protein complexes that are postulated to facilitate the movement of lead across the mitochondrial membranes of the renal tubular cells.9 Accumulation of lead in the mitochondria of the proximal nephron tubules results in mitochondrial swelling and inhibition of respiratory function and adenosine triphosphate (ATP) production.8 The tubulointerstitial structures of the kidney are very susceptible to the toxic effects of lead due to the reabsorptive function of the tubules.
Clinical signs of diarrhea, weight loss and an unthrifty hair coat are nonspecific for lead toxicosis, since these signs can be attributed to many other disease processes. However, when encountering a geriatric horse with these clinical signs, blood tests being within normal limits, and urine and fecal samples being negative for immune challenges, the veterinarian should consider testing for lead toxicity. Maximum lead blood levels in horses should not exceed 0.25 mg/dl. For suspected cases of chronic lead exposure, however, a hair analysis may be more beneficial since lead is stored in bone and soft tissue. Hair is used as one of the tissues of choice by the Environmental Protection Agency to determine toxic exposure to metals.
Lead toxicity causes impaired heme biosynthesis, which results in anemia, disrupts calcium homeostasis, causes digestive inflammation, myelin sheath degeneration and nephropathy. All these signs were evident in Hajji’s case (see previous page). Although his owner could not recall an incident when her horse was exposed to lead, she could remember him having intermittent diarrhea over a long period earlier in his life. Though he may have cleared the acute stages of lead exposure from his body, he may have had chronic exposure throughout his life due to bone remodeling, natural cell turnover and bone degeneration. It is important to use supplements that support bone integrity to slow the progress of bone deterioration and the release of lead back into the blood supply. Horses may have to be detoxified several times throughout their lives to avoid the effects of chronic lead toxicity.
Hajji is a 21-year-old gelding that presented to Michigan State University Veterinary Teaching Hospital (MSU VTH) on September 3, 2012 for severe weight loss since April of the same year. His appetite, thirst, urination and defecation were normal. He was on free choice, first cutting hay, seven pounds of grain, a double dose of Smart Gain and one pound of Natures Essential 32. Hajji had colicked three times within the previous 12 months and received fluids during the fi rst episode. Fecal fl oats for parasites performed by the referring veterinarian were negative.
Endoscopy revealed a small number of gastric ulcers within the stomach wall. Ultrasound revealed focally thickened small and large intestinal walls, while the right kidney had a mixed “moth-eaten” appearance with a loss of corticomedullary junction along with a small amount of free abdominal fl uid within the peritoneum. Blood analysis results were slightly elevated with a blood urea nitrogen (BUN) of 32 mg/dL, mild hypokalemia (9.9 mg/ dL), mild hypoalbuminemia (5.5 g/dL), mild hypoproteinemia (5.5 g/dL) and a low red blood cell count, with hemoglobin and hematocrit levels indicative of anemia. A rectal biopsy revealed minimal mucosal eosinophilic infiltrates with no signs of neoplasia. Hajji was released from MSU VTH with instructions for tapering the dose of oral dexamethasone over a 15-day period from the initial dosage of 40 mg/day. Due to the diagnosis of idiopathic chronic renal failure and the accompanying poor prognosis, Hajji’s owner sadly decided to retire him.
Hajji was presented to London Veterinary Energy Medicine on September 24 for nutritional response testing (NRT) to address metabolic concerns. The NRT revealed renal congestion due to a heavy metal toxicity. Hair analysis (Uckele) results indicated elevated levels of lead. Hajji was treated with a homeopathic remedy for heavy metals and Arginex® at 8/day for the first five weeks. The homeopathic remedy was discontinued after fi ve weeks and Renafood® was added at 6/day. Two weeks later, Renatrophin PMG™ was added at 4/ day. Two weeks after that, Super EFF was added at 8/day for six weeks, at which time all supplements were discontinued.
Arginex acts as a kidney detoxifier or decongestant by supplying the enzyme arginase to break down arginine that may have accumulated during protein metabolism. Renafood provides functional support for the kidneys by promoting filtration and reabsorption of wastes. Renatrophin PMG™ helps rebuild the kidneys by providing uniquely derived nucleoprotein-mineral extracts that support cellular health. Super EFF provides a readily available source of arachidonic acid to help rebuild the myelin sheath destroyed by heavy metals, such as aluminum and lead, or during other disease processes.
Hajji gained approximately 50 pounds during the treatment period and continues to do well on a bone/rheumatid homeopathic remedy, probiotics and a joint supplement. His owner happily decided he was doing well enough to resume participation in his therapeutic riding program.
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2 Needleman HL, Reiss JA, Tobin, MJ, Biesecker GE, Greenouse JB. “Bone lead levels and delinquent behavior”. Journal of the American Medical Association, 1997; 275:363–369.
3 Casas JS, Sordo J. Lead: chemistry, analytical aspects, environmental impact and health effects. Elsevier Sciences, 2006, New York, USA.
4 Ahameda M, Siddiqui MKJ. “Low level lead exposure and oxidative stress: current opinions”. Clinica Chimica Acta, 2007; 383:57–64.
5 Grant LD L.D. “Lead and compounds” in Lippmann M. Environmental Toxicants: Human Exposures and Their Health Effects (3rd ed), Wiley-Interscience, 2009; 789.
6 Karri, SK, Saper RB, Kales SN. “Lead Encephalopathy Due to Traditional Medicine”. Current Drug Safety, 2008; 3 (1): 54–9.
7 Patrick, L. “Lead toxicity, a review of the literature. Part 1: Exposure, evaluation, and treatment”. Alternative Medicine Review: A Journal of Clinical Therapeutic, 2006; 11 (1): 2–22.
8 Kathuria P, Jaday P. “Lead Nephropathy. eMedicine specialities”. Nephrology:eMedicine Journal, 2008; February. December Vol 2:(12).
9 “Low Level Lead Exposure Harms Children: A Renewed Call for Primary Prevention”. Centers for Disease Control and Prevention, January 2012.