Because of the tremendous blood flow and high concentration of metabolic toxins continuously circulating through the kidneys, they are the site of extraordinary oxidative stress, which is known to contribute to progressive kidney damage and its complications (i.e., high LDL and increased cardiovascular disease risk) (Gazdikova 2000).
Coenzyme Q10 (CoQ10) fortifies the body’s natural antioxidant capacity and reduces levels of oxygen free radicals, indicating an important defense against CKD. As it happens, CoQ10 has been used experimentally to control hypertension and kidney disease in laboratory animals since the early 1970s (Igarashi 1974; Morotomi 1975).
Human studies have shown that CoQ10 levels substantially decline, while markers of oxidation such as malondialdehyde are dramatically elevated in kidney disease patients with even mild renal dysfunction (Yao 2007). These decreased CoQ10 levels make circulating lipoproteins (such as LDL) more vulnerable to oxidative damage. This in turn increases risk for further cardiovascular damage, adding to the renal burden and substantially increasing the risk of kidney disease (Lippa 2000).
In 2001, a team of European researchers published compelling evidence for how effective nutritional intervention can be in patients with established kidney disease (Gazdikova 2001). Subjects received antioxidant therapy with vitamins C, E, and riboflavin (vitamin B2) for one month preceding the addition of CoQ10 therapy for 2 months. Following supplementation, CoQ10 levels in the blood increased from just one-quarter to nearly four times the normal reference levels. The study was too brief to demonstrate any change in kidney function. However, evidence from animal trials the same year showed that increasing CoQ10 levels in tissues of diabetic rats resulted in a reversal of oxidative stress markers in the kidney, heart, and liver (Rauscher 2001).
By 2004, definitive evidence of the benefits of CoQ10 in human kidney disease patients was demonstrated by European researchers working with transplant recipients. Transplant recipients undergo tremendous oxidative stress and as a result, typically have marked disturbances in lipid profiles. The researchers provided their patients with 30 mg of CoQ10 three times daily for four weeks, and monitored levels of oxidation factors (such as malondialdehyde), natural antioxidant enzymes in the body, and lipid profiles (Dlugosz 2004).
Significant improvements were seen after just four weeks, with reduction in LDL, increase in beneficial HDL, and a decrease in presence of inflammatory cells noted. These results suggest a potentially dramatic improvement in both quality of life and survival rates for patients with early-stage kidney disease as well as those requiring dialysis or transplantation.
Animal studies have also shown that CoQ10 can protect kidney tissue from numerous nephrotoxic drugs, including gentamicin, a powerful antibiotic with a notorious propensity for causing kidney damage (Farswan 2005; Upaganlawar 2006). These findings are significant not only because they offer protection in patients who might be exposed to such drugs, but they teach us about CoQ10’s potent ability to combat the extreme oxidant stress that the kidney faces as it deals with a variety of foreign chemicals.
Silymarin
Silymarin is extracted from milk thistle (Silybum marianum), a plant rich in the following flavonolignans (natural phenols composed of flavonoid and lignin): silychristin, silydianin, silybin A, silybin B, isosilybin A and isosilybin B -- collectively known as the silymarin complex.
This safe, natural compound has a long history as a traditional therapy for liver and kidney conditions (Post-White 2007; Wojcikowski 2007). It has been used in Western medicine for more than a quarter of a century, owing to its potent antioxidant and nephron-protective effects, as the treatment of choice for kidney injury resulting from severe mushroom poisoning (Floersheim 1978). In fact, we’ve known since 1979 that kidney injury (via mushroom poisoning) in animals who are pre-treated with silymarin can be almost entirely preventable (Vogel 1979). This makes it a natural choice for protection against drug-induced kidney damage since so many drugs can act like poisons, exerting extreme oxidant stress on kidney tissue.
Mushroom poisons (mycotoxins) are among the most deadly natural toxins known. Their kidney toxicity is surpassed only by some of the most aggressive chemotherapy agents. Physicians have therefore looked to silymarin as a potential “renoprotective” agent for patients undergoing chemotherapy.
Silymarin is also protective against several classes of nephrotoxic drugs, in particular cisplatin and Adriamycin®, two of the most potent and damaging (owing to oxidative damage and severe inflammation) chemotherapeutic drugs (Launay-Vacher 2008; Machado 2008; Yao 2007). Researchers around the world have found that silymarin and its components reduce and often prevent the kidney damage caused by these drugs (Bokemeyer 1996; Gaedeke 1996; Karimi 2005; El-Shitany 2008).
Silymarin’s ability to protect against the oxidative stress produced by potent drugs suggests that it may be useful in protecting against more subtle, chronic injury by free radicals -- particularly those generated by chronic blood glucose elevations. German researchers, for instance, have found that silymarin could prevent injury to renal cells incubated with elevated glucose concentrations while blocking production of oxidative stress markers (Wenzel 1996).
Silymarin’s protective power also extends to ischemia/reperfusion injury (restoration of blood supply following restriction of blood flow). Turkish researchers demonstrated that by pre-treating animals with silymarin, they could completely prevent visible and functional damage to kidney structures exposed to this kind of injury (Senturk 2008; Turgut 2008). Studies such as these suggest that by maintaining optimal antioxidant function through supplementation, we may be able to prevent much (if not most) of the chronic oxidative damage to which our kidneys are exposed on a daily basis. As a result, they have huge implications for the general population.
Resveratrol
The considerable advance in our understanding of the cyclical relationships between oxidative stress, endothelial dysfunction, inflammation, atherosclerosis, and chronic kidney disease points to resveratrol as an intervention in the chain of events that ultimately lead to renal failure (Caimi 2004).
Italian researchers are among the leaders in resveratrol research. Early in this century, one group published research demonstrating the impact of resveratrol on preserving kidney structure and function in rats exposed to ischemia/reperfusion injury (Bertelli 2002; Giovannini 2001).
Japanese and Indian urologists followed that up with reports detailing the mechanisms by which resveratrol combats oxidative damage following reperfusion, markedly reducing kidney dysfunction (Saito 2005; Chander 2006(a,b); Chander 2005(a,b)). Bacterial infection (sepsis) is a common cause of kidney failure in the intensive care unit and following surgery or trauma. Turkish physiologists demonstrated that resveratrol can reduce or prevent both kidney and lung injury in septic rats (Kolgazi 2006).
Resveratrol, due to its antioxidant and anti-inflammatory potential, has been utilized in studies to prevent drug-induced kidney damage. The following results were noted when rats, exposed to antibiotic gentamicin, were treated with resveratrol: 1) nephrotoxicity was significantly reduced, 2) more rapid healing of injured kidney tissue was attained, and 3) a dramatic reduction in markers of oxidant injury was observed (Silan 2007). A team of toxicologists in Brazil demonstrated its protective power against cisplatin, the powerful chemotherapy agent responsible for so much drug-induced kidney damage (Do Amaral 2008). Finally, Indian pharmacologists were successful in protecting animal kidneys from damage caused by cyclosporine A (another common chemotherapy and immune suppressant drug) by pre-treating the animals with resveratrol (Chander 2005(b)).
Since diabetes is the leading cause of kidney disease—and because the damage it inflicts is largely mediated by free radical production resulting from destructive alteration of proteins by glucose (glycation)—researchers have explored resveratrol as a preventive in diabetic kidney damage. Promising results have come from Indian pharmacologists who significantly attenuated kidney damage in rats with experimentally induced diabetes, even 4 weeks after the diabetes was induced (Sharma 2006).
In the researchers’ own words, “The present study reinforces the important role of oxidative stress in diabetic kidney disease and points towards the possible antioxidative mechanism being responsible for the renoprotective action of resveratrol.”
Lipoic Acid
Like resveratrol, lipoic acid is a powerful antioxidant with few known side effects (Amudha 2006). Lipoic acid has been successfully employed in the laboratory to block the oxidative damage caused by ischemia/reperfusion injury, thereby opening the door to another effective treatment for this common cause of acute kidney failure (Takaoka 2002). In 2008, researchers showed that they could reverse all adverse effects on renal function and lab abnormalities following experimental ischemia/reperfusion injury in animals (Sehirli 2008).
Lipoic acid has been comprehensively studied worldwide for its power to prevent or mitigate drug-induced kidney damage. We know that lipoic acid is an effective kidney-protective agent against damage inflicted by Adriamycin® (Malarkodi 2003(a,b)), the immunosuppressive drug cyclosporine A (Amudha 2006; Amudha 2007(a,b)), and even against acute toxic doses of the pain reliever acetaminophen (Abdel-Zaher 2008). In studies examining the protective benefits of lipoic acid against cyclosporine toxicity, it helped to normalize blood lipid abnormalities (Amudha 2007b).
Nephrologists at Georgetown University examined lipoic acid in the context of diabetic kidney disease. Their results showed that it can improve renal function in diabetes by lowering sugar levels (Bhatti 2005).
They also demonstrated that lipoic acid lowers protein loss in urine and improves kidney structure and function by reducing oxidative stress in diabetic laboratory animals (Bhatti 2005).
In yet another compelling study, Korean researchers showed that they could improve kidney patients’ responses to the vasodilator (blood vessel relaxer) nitric oxide (NO) by supplementing them with lipoic acid (Chang 2007). Loss of endothelial responsiveness to NO is a cause of vascular disease in diabetics. A chemical called asymmetric dimethylarginine (ADMA) is a sensitive marker and predictor of cardiovascular outcome in patients with end-stage renal disease. Fifty patients on hemodialysis were treated with 600 mg lipoic acid daily for 12 weeks. ADMA levels remained unchanged in the control group but fell significantly in the treatment group, suggesting that lipoic acid may reduce the risk of cardiovascular complications in this group of patients.
http://www.lef.org/protocols/kidney_urinary/kidney_disease_03.htm?source=search&key=kidney
