Cardiac health and the kidneys.
The comorbidities of cardiovascular disease and renal disease are often exacerbated by anemia. This downward spiral and the interactions of these conditions has been termed cardiorenal anemia syndrome. (2) As this situation progresses, patients often become more and more dependent on multiple pharmaceuticals; but targeted dietary changes and supplementation may improve blood markers of function and reduce the need for prescription drugs. Many botanical medicines and nutraceuticals used for renal disease may help cardiovascular health and vice versa.
With renal disease, the mechanism for anemia is clearly understood as it is often due to reduced production of erythropoietin. However, with nephrotic syndrome, urinary loss of erythropoietin along with a loss of iron and transferrin contribute to anemia. (4) Activation of the renin-angiotensin-aldosterone system (RAAS) and antidiuretic hormone cause renal vasoconstriction and reduced perfusion of the kidneys. Additionally, salt and water retention cause hemodilution. Tissue hypoxia from anemia causes peripheral dilation, which reduces blood pressure. This reduction in blood pressure activates RAAS and increases the sympathetic nervous system response, causing tachycardia to maintain adequate blood pressure. Activated sympathetic response then leads to more renal vasoconstriction. All of these factors can lead to a reduced perfusion of the kidneys, which in turn leads to reduced erythropoietin production and further anemia. Thus, the renal patient is often caught in a downward spiral if there is no intervention. (2)
With cardiac patients, the cause of anemia can also be multifactorial. Hemodilution due to right-sided heart failure, although not true anemia, is associated with adverse outcomes. Heart failure creates a state of persistent inflammation. High levels of cytokines, including tumor necrosis factor (TNF)-a and 11-6, inhibit production of erythropoietin as well as the bone marrow response to erythropoietin, reducing hematogenesis and creating the anemia of chronic disease. (5) Inflammation may inhibit the uptake of iron in the gut, however, even with adequate iron levels, inflammation may inhibit its utilization. The patient may have low hemoglobin but very high ferritin. (6)
Some of the interventions used on cardiac and renal patients may also contribute to anemia. Aspirin can contribute to anemia through blood loss in the gut. ACE inhibitors may have fewer side effects than other antihypertensive agents, but have been shown to decrease renal secretion of erythropoietin. (7) Also commonly used for these patients, proton pump inhibitors may contribute to anemia through decreased B12 absorption.
Synthetic erythropoietin injections (EPO) are often made available to patients if anemia is severe enough. In practice, however, insurance approval may be slow for this very expensive medication and out-of-pocket cost may be prohibitive. Many patients the author sees in practice also hesitate to take EPO shots after becoming aware of the side effect of increased blood clots. Although a lack of red blood cells does mean fewer chances to form blood clots, the deleterious effects of uncorrected anemia generally have far worse consequences.
There are natural agents that have the potential to increase hematocrit, which could reduce the size and frequency of prescription shots. This can also be important for some patients who are unresponsive to the shots. L-carnitine, which often runs low with advanced kidney disease, can improve hematocrit levels in patients who are poor EPO responders. (8) Also the herb Angelica sinensis (Dong quai) can stimulate hematogenesis. (9) It appears to work even better when used in combination with Astragalus membranaceus. (10)
Nutritional deficiencies can also play a role in the development of anemia for these patients. Increasing uremia is notorious for causing a lack of appetite. A lack of appetite may also be a problem among the elderly patients. Other patients are unsure of what to eat. They know the standard American diet is not working for them but need guidance on how to adopt alternatives. Also, as many renal patients opt for a vegetarian diet to decrease the stress on the kidneys, they may be lacking in B12 and iron. Dialysis patients in particular may be lacking in B-vitamins as water-soluble vitamins are washed out during their treatment. This situation could be exacerbated if poor methylation is an issue for the patient.
Chronic kidney disease patients may be supplementing with iron, and dialysis patients are often given a course of iron injections as part of their treatment. However, this intensive dose of iron may be excessive, and ferritin should be monitored. Iron overload may lead to increased oxidative stress for the heart and contribute to atherosclerosis. While correcting anemia, practitioners should be aware that a high level of iron can also increase susceptibility to infection, which may increase morbidity and mortality. Iron may not only lead to increased microbial growth but can suppress CD4+ T cells and antibody production. During acute infections, iron supplementation should be at least temporarily withheld. (11)
Besides iron, another mineral that must be closely monitored is potassium. Elevated potassium is the most immediate threat to a patient with advanced renal disease and may directly impact cardiac health. As the creatinine becomes elevated, the kidneys lose the ability to expel potassium in the urine. Hyperkalemia can cause a deadly arrhythmia in patients with marginal kidney function. Common medications that can drive up potassium include ACE inhibitors, potassium-sparing diuretics, and beta blockers. (12)
Normally beneficial supplements may become problematic in patients prone toward hyperkalemia. Among the herbs highest in potassium are parsley, hops, catnip, asparagus root, and bupleurum. (13) Unfortunately, many nutrient-dense foods are very high in potassium, and the dietary guidelines given to these patients often advise many processed foods with low nutritional value. However, it is still possible to eat a whole foods diet and still maintain a low potassium intake. Cauliflower, string beans, and zucchini would be better choices than broccoli or leafy greens. Low potassium fruits include apples, berries, plums, and grapes. (14) The potassium limited diet should only be initiated when necessary as the blood tests indicate that potassium is approaching an elevated range. In practice, it is observed that patients often initiate a low potassium diet prematurely with the intention of reducing stress on the kidneys. This, however, is not helpful as hypokalemia may also be problematic.
In addition to iron and potassium, phosphorus is problematic for renal patients. Although phosphorus is a less immediate threat than elevated potassium, elevated phosphorus can wreak havoc on the renal patient over time. Phosphorus that should be excreted in the urine becomes elevated in the blood stream. High phosphorus causes an elevation of parathyroid hormone, releasing calcium from the bones. Not only does this cause osteomalacia, but calcium binds to phosphorus deposits in soft tissue. Calcification of the blood vessels and the heart valves is yet another stressor on the cardiovascular system for the renal patient. (15)
Managing phosphorus is an ongoing struggle for patients with advanced renal disease. Some dietary phosphorus is easily avoided by eliminating soft drinks with phosphoric acid and processed foods with phosphate-based preservatives. Patients should be made aware that fast foods, in particular, have a very high content of added phosphates. Phosphorus is also present in many dietary supplements such as phosphatidylserine, phosphatidylcholine, lecithin, or calcium in the form of calcium phosphate. While fish oil usually does not contain phosphorus, krill oil may be high in phosphorus. Other dietary sources of phosphorus cannot be completely eliminated as phosphorus will always accompany protein.
Extended release niacin may be of some assistance, but for most patients with advanced renal disease, prescription phosphorus binders are usually a necessity. (16) However, even with acceptable phosphorus control, PTH may remain elevated, creating a need for intervention to lower PTH.
Although adequate vitamin D is important, appropriate levels should be adjusted for renal patients. Vitamin D increases the uptake of both calcium and phosphorus. In order to avoid phosphorus overload, vitamin D should be maintained on the lower end of the normal range. The compound fibroblast growth factor-23 (FGF23) is produced in the osteocytes in response to high phosphorus. It acts as a hormone to reduce phosphorus reabsorption in the kidney and decrease renal production of 1,25[(0H).sub.2]-D. This action of FGF23 comes at a price, however, and contributes to cardiomyocyte hypertrophy, vascular calcification, and endothelial dysfunction. High circulating phosphorus is the main force driving up FGF23, but anemia and iron deficiency can also lead to increased levels. (17)
Malignant hypertension is another cause of cardiac stress in renal patients. As the ability to filter uremic wastes declines, so does the ability to regulate blood pressure. As the patient approaches end stage renal disease (ESRD), natural interventions may be a helpful adjunct to blood pressure control; but multiple therapies are usually necessary, and it may be difficult to completely control blood pressure without pharmaceutical assistance. Practitioners should anticipate that when uncontrolled blood pressure becomes successfully managed with advanced renal disease, there is often a sudden increase in creatinine. This is not due to worsening damage to kidneys. As the filtration within the kidneys takes place across a pressure gradient, a lessening of internal pressure within the kidneys will decrease the glomerular filtration. (18) A healthy kidney would be able to continue to filter with normalized blood pressure. Patients may attribute this shift in creatinine to toxicity of medications; however, the medications did not damage the kidney but simply revealed how much damage has already taken place.
Left ventricular hypertrophy (LVH) is a common development among renal patients over time. The cumulative effect of stress on the cardiovascular system includes the fluid overload that occurs with oliguria and anuria. Diuretics will be unable to stimulate urine production if the kidneys are too far damaged. Green tea shows promise of preventing cardiac hypertrophy secondary to kidney failure. Green tea can attenuate hypertension but also was shown to prevent increases in ROS production as well as (3H) phenylalanine incorporation in cardiac myocytes. (19)
Dietary interventions can also affect the development of LVH secondary to renal failure. Hemp protein and soy both helped to normalize cardiac size with renal failure. Soy, however, is particularly high in potassium and phosphorus. There was also noted less fibrosis and hypertrophy of the kidneys. Surprisingly, although pea protein ameliorated some markers of kidney function, it worsened renal hypertrophy and increased the size of fluid-filled cysts on the kidney. No change in cardiac hypertrophy was noted with pea protein. (20)
One overlooked dietary intervention is Brazil nuts. Generally, kidney patients are advised to avoid nuts due to the potassium and phosphorus content. However, nuts are usually eaten by the handful. One single Brazil nut a day is enough to make an impact without overloading the patient with minerals. After three months of consuming a single Brazil nut per day, plasma selenium and glutathione peroxidase activity increased, while cytokines, 8-OHdG, and 8-isoprostane plasma levels decreased significantly. Also observed was an increase in HDL levels and a significant decrease in LDL. This study suggests that the consumption of only one Brazil nut per day during three months was effective in reducing inflammation, oxidative stress markers, and the atherosclerosis risk in kidney patients. (21)
Pomegranate juice is another food that might not be considered due to its high potassium content. While 8 oz. of pomegranate juice would certainly be too much potassium for many of these patients, a study looked at the effect of 100 cc or 3 oz. of pomegranate juice three times a week administered during dialysis sessions. The patients who received pomegranate juice had significantly lower levels of inflammatory markers, including 11-6 and oxidized fibrinogen, compared to the control group. The treatment group had 36% fewer first hospitalizations due to cardiovascular causes and 44% fewer second hospitalizations for the cardiovascular issues. (22)
Apart from these heart issues, specific uremic products appear to also increase stress on the heart. A healthy kidney is able to expel waste products and more than 3,000 distinct uremic products have been identified. (23) Although the cardiac effect of most of these products is unknown, a few have increased cardiovascular stress. Carbamylated albumin (C-Alb), found in high levels with uremic patients, is associated with higher mortality rates and has been shown to contribute to LVH. (24) Indoxyl sulfate (IS) has been shown to increase cardiac fibrosis and hypertrophy as well as pro-inflammatory cytokines. 8-Hydroxydeooxyguanosine (8-OHdG) and acrolein, also normally cleared by the kidneys, can be found in cardiomyocytes and contribute to myocardial and perivascular fibrosis. (25)
Interestingly, oral charcoal administration appears to lower oxidative stress and cardiac damage in kidney patients by binding to these uremic waste products. (26) Oral charcoal must be administered carefully as it can bind to nutrients and medications as well as uremic waste products and should be administered at least two hours away from anything else taken by mouth. As uremic waste products build up in the entire body, binding these waste products in the gut goes a long way to reducing the total body burden.
In practice, the author has noted that there is a great deal of overlap between supplements used for cardiac health and those used for renal health. Many common supplements for the heart ameliorate the kidneys and vice versa. Ubiquinol is a very effective tool for improving kidney function and decreasing oxidative stress within the kidney. (27) The author uses ubiquinol as a first line therapy for renal disease and as a preventative for secondary heart disease.
Hibiscus sabdariffa is well known for its anti-hypertensive effects and works well with mildly elevated blood pressure. (28) However, even if hibiscus cannot control the blood pressure completely, it can still be useful for kidney patients because it has been demonstrated to attenuate the progression of renal damage and preserve kidney function. (29) The cardiac effects of hibiscus, however, are less well known; but in an animal model, it reversed cardiac hypertrophy associated with hypertension. (30)
Cordyceps sinensis has a long history of use for kidney ailments in traditional Chinese medicine. It can help with glomerulonephritis, reducing kidney inflammation and proteinuria. It also helps preserve kidney function and reduce creatinine. Now, new evidence suggests it also helps protect the heart and even the liver from injury with chronic kidney disease. (31)
Patient A is a 33-year-old African American male who lost his kidneys to the autoimmune condition FSGS. He is unsure if he had hypertension prior to advanced kidney disease. Malignant hypertension was noted immediately prior to the initiation of dialysis and required multiple pharmaceuticals to control. Even though the blood pressure is now controlled, the resting pulse is in the 90 to 110 range.
The patient has been on dialysis four months. He has been compliant with blood pressure medications, especially after severe headaches with malignant hypertension. When it comes to taking prescription phosphorus binders, he is less compliant and has trouble remembering to do this at every meal.
Limiting fluid is rarely an issue. He continues to have some fluid output and has not become anuric. Fluid overload between dialysis sessions occurs rarely when the patient eats especially salty foods.
The patient enjoys fruit and a variety of leafy green vegetables, making potassium control difficult. After dietary indiscretions, he has experienced tachycardia, which is relieved when a dialysis session normalizes his electrolytes. Patient has also noticed restless leg syndrome, which is often an indicator of low antioxidant status among kidney patients. (32)
Treatment consisted of dietary counseling, so he could enjoy a whole foods diet without excessive potassium. The patient started 200 mg of ubiquinol TID and taurine 2000 mg BID. He realizes the necessity of always carrying his phosphorus binders with him. We have also worked into his diet 2 oz. of pomegranate juice, one Brazil nut QD, hemp protein a few times a week, green tea, and hibiscus tea daily. He also eats blueberries after each treatment. On non-dialysis days, he does activated charcoal four capsules at 560 mg each, carefully timed away from blood pressure medications. The patient has also started mild, consistent exercise with a 30-minute daily walk.
The patient noticed the tachycardia and restless leg syndrome resolved. His energy level improved, which helped him feel more optimistic about the future. When he was evaluated for a potential transplant, his cardiac stress test and EKG showed favorable results. The patient understands that he will need to be vigilant in his routine to have continued cardiac health.
Patient B was a 77-year-old diabetic male who had had a six-way bypass surgery, when his care partner sought a naturopathic approach for him. He was facing renal failure in the near future with a creatinine level of 2.49 and climbing with each subsequent blood test. Diabetic control had been poor, and he had an amputation of one leg below the knee several years prior. He refused to see a nephrologist and made it clear that he was unwilling to do dialysis. Lack of mobility curtailed many activities, and he saw food as one of the few enjoyments he has in life. He was willing to take supplements but not agreeable to give up all fast food.
The patient was hypotensive with several blood pressure medications. He complained of lightheadedness upon standing. When he was able to adjust his medications to have a blood pressure of close to 120/80, his creatinine did not improve but stopped its rapid increase and settled between 3.0 and 4.0.
Low hemoglobin and hematocrit were addressed with a combination of Angelica and Astragalus, as well as ferrochel and a B-complex. He was also willing to take several antioxidants, including ginger, green tea, curcumin, pycnogenol, resveratrol, and selenium. The ocular formula he took to prevent diabetic damage included vitamin E, lutein, astaxanthin, and zeaxanthin. He also took fish oil and hawthorne. The patient was able to keep with his goal of never succumbing to dialysis. His cardiologists were pleased with his progress and surprised by his status given his history and multiple issues. He was able to maintain a reasonable quality of life until he passed at age 82.
In conclusion, cardiac patients should take steps to ensure ongoing renal health and renal patients should actively work to reduce cardiac stress. The impact of diminished renal function on cardiovascular health is multifactorial. With early and ongoing intervention through diet and supplements, it is possible to reduce the downstream effects of these chronic conditions. The cause of mortality for most kidney patients is not kidney failure but secondary heart disease that develops over the course of many years. If patients take steps to minimize the impact of chronic kidney disease on the cardiovascular system, renal patients can avoid many of these common problems.
(1.) Bansal, N. Reducing Cardiovascular Mortality in Kidney Disease: Time to Focus on Heart Failure? Medscape Medical News. Available at: http://www.medscape.com/ viewarticle/875088. Accessed March 6, 2017.
(2.) Efstratiadis G, et al. Cardio-renal anemia syndrome. Hippokratia 2008 Jan-Mar;12(1):11-16.
(3.) Pimentel R, et al. Prognostic value of worsening renal function in outpatients with chronic heart failure. Eur J Intern Med 2014 Sep;25(7);662-8.
(4.) Vazirl N. Erythropoietin and transferrin metabolism in nephrotic syndrome. Am J Kidney Dis. 2001;38:1-8.
(5.) Voulgar P, et al. Proinflammatory cytokine levels in patients with depressed left ventricular ejection fraction: a report from the Studies of Left Ventricular Dysfunction. J Am Coll Cariol. 1996;27:1201-1206.
(6.) Inverson P, et al. Decreased hematopoiesis in bone marrow of mice with congestive heart failure. Am J Physiol. 2002;282:166-172.
(7.) Pratt M, et al. Effect of angiotensin converting enzyme inhibitors on erythropoietin concentrations in healthy volunteers. Br J Clin Pharmacol. 1992 Oct; 34(4): 363365.
(8.) Matsumoto Y, et al. Effects of L-carnitine supplementation on renal anemia in poor responders to erythropoietin. Blood Purif. 2001;19(1):24-32.
(9.) Liu P, et al. Hematopoietic effect of water-soluble polysaccharides from Angelica sinensis on mice with acute blood loss. Exp. Hematol. 2010Jun;38(6):437-45.
(10.) Chang M, et al. Treatment with Astragali radix and Angelicae radix enhances erythropoietin gene expression in the cyclophosphamide-induced anemic rat. J Med Food. 2009 Jun;12(3):637-42.
(11.) Fishbane S, et al. Iron toxicity: relevance for dialysis patients. Nephrol Dial Transplant (2014) 29 (2): 255-259.
(12.) Ehrlich S. Possible Interactions with: Potassium. University of Maryland Medical Center. Available at: http://umm.edu/health/medical/altmed/supplement-interaction/ possible-interactions-with-potassium. Accessed March 6, 2017.
(13.) Pedersen M. Nutritional Herbology. Warsaw, IN: Wendell W Whitman Company; 1987: 24-25.
(14.) Mount Carmel College of Nursing. Low Potassium Diet. Available at: http://www.mccn.edu/library/ patienteducation/patienteducatio_/dietandnutritio_/ lowpotassiumdie/LowPotassiumDiet.pdf. Accessed March 6, 2017.
(15.) Klaric D, et al. [Cardiac valves calcifications in dialysis patients]. Acta Med Croatic 2011 Oct;65(3):ll-3.
(16.) Elalat-Neijad M, et al. The effect of niacin on serum phosphorus levels in dialysis patients. Indian J Nephrol. 2012 May;22(3):174-8.
(17.) Kuczera P, et al. Fibroblast Growth Factor-23-A Potential Uremic Toxin. Toxins (Basel). 2016 Dec 8;8(12).
(18.) Sobotova D, et al. [Hypertension in hemodialyzed uremic patients], Vnitr Lek. 1999 Nov;45(ll):641-4.
(19.) Priyadarshi S, et al. Effect of green tea extract on cardiac hypertrophy following 5/6 nephrectomy in the rat. Kidney Int. 2003 May;63(5):1785-90.
(20.) Aukema H, et al. Distinctive effects of plant protein sources on renal disease progression and associated cardiac hypertrophy in experimental kidney disease. Mol Nutr Food Res. 2011 Jul;55(7):1044-51.
(21.) Stockier-Pinto M, et al. Brazil nut (Bertholletia excelsa, H.B.K.) improves oxidative stress and inflammation biomarkers in hemodialysis patients. Biol Trace Elem Res. 2014 Apr;158(1):105-12.
(22.) Schieszer J. Pomegranate Juice May Benefit Dialysis Patients. Renal & Urology News. http://www. renalandurologynews.com/renal-week-2010-general-news/ pomegranate-juice-may-benefit-dialysis-patients/ article/191344/. Accessed March 6, 2017.
(23.) Urine Metabolome website. Browsing Urine Metabolites. Available at: http://www.urinemetabolome.ca/. Accessed March 6, 2017.
(24.) Perl J, et al. Reduction of carbamylated albumin by extended hemodialysis. Hemodial Int. 2016 Oct;20(4):510-521.
(25.) Lekawanvijit S, et al. Chronic kidney disease-induced cardiac fibrosis is ameliorated by reducing circulating levels of a non-dialysable uremic toxin, indoxyl sulfate. PLoS One. 2012;7(7):41281.
(26.) Fujii H, et al. Oral charcoal adsorbent (AST-120) prevents progression of cardiac damage in chronic kidney disease through suppression of oxidative stress. Neph Dial Transplant 2009 Jul;24(7):2089-95.
(27.) Ishikawa A, et al. Renal preservation effect of ubiquinol, the reduced form of coenzyme Q10. Clin Exp Nephrol. 2011 Feb;15(1):30-3.
(28.) Serban C, et al. Effect of sour tea (Hibiscus sabdariffa L.) on arterial hypertension: a systematic review and metaanalysis of randomized controlled trials. J Hypertens. 2015 Jun;33(6):1119-27.
(29.) Seujange Y, et al. Hibiscus sabdariffa Linnaeus aqueous extracts attenuate the progression of renal injury in 5/6 nephrectomy rats. Ren Fail. 2013;35(1):118-25.
(30.) Odigie I. et al. Chronic administration of aqueous extract of Hibiscus sabdariffa attenuates hypertension and reverses cardiac hypertrophy in 2K-1C hypertensive rats. J Ethnopharmacol. 2003 Jun;86(2-3):181-5.
(31.) Liu X, et al. Cordyceps sinensis protects against liver and heart injuries in a rat model of chronic kidney disease: a metabolomic analysis. Acta Pharmacol Sin. 2014 May;35(5):697-706.
(32.) Keller D. Restless Legs Syndrome More Prevalent Among Hemodialysis Patients, Correlates With CRP Levels. Medscape Medical News. Available at: http://www. medscape.com/viewarticle/724535. Accessed March 6, 2017.
Caption: Dr. Jenna Henderson is a graduate of the University of Bridgeport College of Naturopathic Medicine. Her practice, Holistic Kidney, addresses the unique needs of renal patients at all stages, including dialysis patients and transplant recipients. Her articles have been published in Natural Medicine Journal and Naturopathic Doctors News & Reviews. She has lectured across the US to both patient groups and professional groups. She has appeared on several radio shows and cohosted the program Improve Your Kidney Health. She is currently at work on a guidebook on natural medicine for transplant patients.
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|Author:||Henderson, Dr. Jenna|
|Date:||May 1, 2017|
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