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An integrative approach to chronic kidney disease (CKD) in cats

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CKD is a common but manageable condition in feline patients, and responds well to integrative medicine. Herbs and acupuncture are key therapies.

Chronic kidney disease (CKD) is a common problem in cats, and one which all veterinarians encounter in practice. An integrative approach that includes herbs and acupuncture can help treat and even reverse this condition in feline patients.

CKD can be detected early through careful monitoring at annual wellness programs. IRIS (International Renal Interest Society) staging allows for the conventional staging of treatment, including any dietary changes. Key treatment strategies for feline CKD include supporting hydration, reducing phosphorus (usually through protein restriction), regulating blood pressure and controlling calcium levels. The intensity of intervention increases with disease progression.

Integrative treatment goals

Using integrative approaches to CKD, we have observed cats moving from IRIS Stages 2 and 3 to Stage 1, and remaining there for years. This reversal implies that nephrons are hypoxic and under-functioning, and that improving their functional capacity is a key goal. See below for integrative treatment goals for CKD.

Herbs can optimise kidney cell function by reducing oxidative stress, improving renal blood flow and mitigating fibrosis, thereby maintaining patients in early stages for extended periods. Acupuncture, manipulative therapies and other modalities can also be a part of the integrative approach.

With acute renal disease, the goals are modified to regulate/decongest the kidneys by reducing blood flow, and provide anti-inflammatory support to inflamed glomeruli. This may be a starting point with pyelonephritis, for example. Most cats, however, benefit from increased perfusion unless the renal disease is acute in onset (inflammatory).

Dietary considerations

Despite numerous experimental studies and clinical trials, questions about feeding protein to cats with chronic kidney disease (CKD) remain. What is the optimal amount of protein for a cat with CKD? How much restriction is necessary? Do different types of kidney disease require different dietary therapies? At what point in disease progression should protein restriction be implemented? Does the type of protein make a difference? Does every meal have to be restricted? Will a cat in IRIS Stage 3 or 4 benefit if phosphorus is restricted by other means? Might some cats with advanced disease benefit from increased protein levels?1 These concerns remain despite the common practice of prescribing therapeutic renal diets to cats in any stage of CKD.

Integrative practitioners provide, or are requested to provide, natural feeding advice to cat owners. Excellent resources include the veterinary Diplomats in Nutrition; Balance It and several software programs that can be used for formulating diets while taking feline preferences into account. See page xx for an example of a low-phosphorus diet for cats with CKD.

From an integrative perspective, real food is considered to have many benefits, including palatability for ill cats, and these benefits may outweigh those offered by processed foods. In IRIS Stage 1 and early Stage 2, the diet may not need to be modified, although serum phosphorus and the phosphorus content of the diet should be evaluated. From late Stage 2 onwards, consideration may be given to reducing protein by diluting with fat and carbohydrates.

Herbal help

Herbs can delay the onset and progression of CKD in cats by improving mitochondrial function, and providing antioxidant protection and ACE-inhibiting effects. Many herbs are anti-inflammatory, anti-fibrotic and nephroprotective, and several improve renal blood flow. A principle of herbal medicine is that formulations containing multiple plants can have greater effects than the same herbs taken separately. These synergistic effects enhance the desired action.2

Following are several herbs to be considered and included in formulas for renal treatments.

1. Rehmannia glutinosa

Rehmannia glutinosa occurs in many Chinese herbal formulas, including Rehmannia Eight Combination (Shen Qi Wan, Jin Gui Shen Qi Wan, Ba Wei Di Huang Wan), which is very useful for cats with CKD and weight loss, loss of strength, polyuria, polydipsia, and that are seeking warmth. It is also included in Zhi Bai Di Huang Wan, which is useful in cats with CKD and hyperthyroidism, particularly in those tending towards constipation, agitation and weight loss, along with polydipsia and polyuria.

Rehmannia has a long history of research and effective use in CKD. In humans, studies have found that it has a 91% efficacy in reducing renal damage from nephritis, due to the enhancement of renal blood flow and glomerular filtration.3 In a model of renal ischemia, ligated rats that received Rehmannia extract showed improved renal blood flow (to near normal levels) and reduced mortality and hypertension compared to controls, through either ACE inhibition or juxtaglomerular desensitization.4 Rehmannia reduces oxidative stress and can promote red blood cell production through bone marrow stimulation; reduce serum creatinine and urinary protein excretion and glomerulosclerosis in compromised patients; and inhibit the expression of Angiotensin II as well as Type IV collagen in the renal cortex.5, 6

Fresh Rehmannia is utilised in Ba Wei Di Huang Wan and Zhi Bai Di Huang Wan. Interestingly, a recent study supports the use of fresh over prepared Rehmannia; the former acts more powerfully on attenuating interstitial fibrosis by downregulating the expressions of transforming growth factor, a smooth muscle actin, and Type 1 collagen.7

2. Astragalus membranaceus

Astragalus membranaceus is known as a Qi tonic in Chinese medicine, and as a major immune-modulating herb in Western herbal medicine. It should also be known as a major kidney herb. Its major constituent, astragaloside, ameliorates renal interstitial fibrosis in vivo by inhibiting inflammation.8 It has major antioxidant effects.9 Astragalus has been reviewed by Cochrane and was found to offer some promising effects in reducing proteinuria and increasing haemoglobin.10 Its nephroprotective effects against oxidative stress include anti-inflammatory and anti-apoptotic mechanisms.11 In a systematic review of Astragalus on diabetic nephropathy in animal models, this herb was able to reduce blood glucose and albuminuria levels and reverse the glomerular hyperfiltration state, thus ameliorating pathologic changes.12

3. Angelica sinensis

Angelica sinensis contains polysaccharides that inhibit oxidative stress injury in mouse kidneys.13 Like Astragalus, its nephroprotective effects include anti-inflammatory and anti-apoptotic mechanisms.11 Renal microvascular lesions can contribute to the progression of glomerular sclerosis and tubulo-interstitial fibrosis in chronic kidney Both Astragalus and Angelica can improve microvascular lesions by increasing local renal blood flow to lessen hypoxic renal injury, promoting the recovery of renal blood flow and glomerular filtration rate after ischemia-reperfusion; modulating the imbalance of vaso-activators such as nitric oxide and angiotensin; increasing the expression of vascular epithelial growth factor; inhibiting the release of the intracellular calcium ion; and promoting DNA synthesis in endothelial cells to improve the function of endothelial cells. The evidence suggests that both herbs may retard the progress of renal diseases through the above-mentioned mechanisms.14

In one study involving rats with an obstructive uropathy, Astragalus and Angelica were administered with Enalapril and compared to monotherapy. Enalapril with Astragalus and Angelica decreased tubulointerstitial fibrosis to a significantly greater extent than did treatment with Enalapril alone.15

4. Cinnamon

Cinnamon is readily accepted by cats and offers a mono-herbal treatment for fussy felines. It occurs in the Wei Ling Tang formula, which is useful for overweight CKD cats with proteinuria, hematuria, urolithiasis, azotemia, glomerulonephritis and pyelonephritis. Cinnamon can inhibit advanced glycation end products (AGE) and can ameliorate AGE-mediated pathogenesis in diabetic nephropathy.16 Cinnamon is a major antioxidant and anti-inflammatory spice, and has had over 178 papers published on it from 1995 to 2015.17 Cinnamon at a dose of 50 mg/kg for two weeks was given to dogs; the systolic blood pressure and heart rate in the treated dogs was significantly lower than in the normal group.18

5. Silybum marianum

Silybum marianum is one of our preeminent nephron-protective herbs. It should be considered an adjunct to ameliorative potential effects against drug-induced kidney disease, particularly in chemotherapy.19 It is also an herb that could be considered for CKD support. It is a potent antioxidant and free radical scavenger that inhibits lipid peroxidation and stabilizes cell membranes. It also increases intracellular glutathione, which plays a crucial role in the body’s antioxidant capacity, and it has anti-inflammatory properties inhibiting T-cell proliferation and cytokine secretion.20 There is also evidence that Silybum has a regenerative effect on renal tissue after injury.21

Mushrooms — Ganoderma and Cordyceps

Mushrooms are well tolerated by cats when given in the form of powders or concentrated tinctures added to food. Ganoderma lucidum is a medicinal mushroom that has been widely used in China and Japan for hundreds of years for its immune-modulating, anti-inflammatory and anti-tumor effects. Ganoderma compounds are renoprotective.22.The active peptide in Ganoderma counteracts oxidative stress from renal ischemia, and in an animal model of diabetic nephropathies has renal protective effects.23

Likewise, Cordyceps sinensis is extensively used by Chinese physicians to treat chronic renal diseases and to stimulate the immune system. It also displays anti-oxidative activities. It is commonly used in renal transplant patients; it has been shown to significantly improve renal fibrosis.24

Acupuncture and moxibustion

A recent single blinded randomized controlled study in patients with CKD showed that acupuncture at bilateral LI4, ST36 and KI3, and electroacupuncture to right ST36 and KI3 and left ST36 and KI3, once a week for 12 weeks, led to reduced creatinine levels and increased glomerular filtration rates.25 Moxibustion at Bl 23 in patients with CKD reduced renal vascular resistance.26

Most of the benefits that acupuncture offers in renal failure are undoubtedly due to the ability of these points to manipulate blood flow. Local blood flow is manipulated using BL23, BL22 and GB25, while systemic blood flow is manipulated with GB34, BL40 and KI3. Systemic blood flow greatly impacts renal function. Peripheral vasoconstriction can be induced to drive more blood to the kidneys. Peripheral vaso-relaxation can be induced to decongest the kidneys.

For animals in Stage II renal failure (using the IRIS classification system), and particularly where UPC ratios are greater than 2.5, use GB25, BL22 and GB34. These animals will typically have benefited from hypotensive drugs and low-protein diets, but won’t show an immediate improvement from fluid therapy. For animals in Stage I renal failure, or where UPC ratios are less than 2 to 2.5, use KI3, BL40 and BL23. These animals will typically not benefit from low-protein diets and hypotensive drugs, but will show an overt improvement from fluids.27

Integrative treatment goals for feline CKD

  • Mitigate oxidative stress by using antioxidant herbs
  • Improve renal perfusion (in most cases)
  • Prevent fibrosis, which is a natural consequence of renal disease
  • Optimise systemic health and well-being

Example of a low-phosphorus diet for cats with CKD

  • 50 grams or ¼ cup pearl barley
  • 200 grams raw chicken breast meat
  • 10 grams chicken liver
  • 1 large egg yolk
  • 2 cups raw sweet potato
  • 4 teaspoons salmon oil plus 4 teaspoons flaxseed oil

Cook barley, sweet potato, chicken and liver are on low heat with water. When warm, mix in egg yolk to lightly cook it (and preserve the choline). When cool, the recipe is divided into four meals (average 250 kcals) with the addition of 1 teaspoon of salmon oil and 1 teaspoon of flaxseed oil daily. The meals are divided.

The whole recipe provides 1,029 kcal, 36% carb, 40% fat, 24% protein and 724 mg of phosphorus. It needs to be supplemented as it is low in a number of minerals and vitamins, and is still low in choline. Any supplement added should be evaluated for its phosphorus content. This should demonstrate the complexity of balancing diets. Another excellent strategy is to have several recipes and vary the composition of diets over time. More protein can be utilised alongside phosphorus binders in later stages of kidney disease.

Conclusion

Chronic kidney disease in cats is a manageable condition that responds well to integrative medicine. In the author’s experience herbal medicine and acupuncture are key. Many integrative practitioners have reported success with other additional therapies, including homeopathy, cell salts, flower essences and osteopathy.

References

1Larsen JA. “Controversies in Veterinary Nephrology: Differing Viewpoints: Role of Dietary Protein in the Management of Feline Chronic Kidney Disease”. Vet Clin North Am Small Anim Pract. 2016 Nov;46(6):1095-8.

2Bangar OP, Jarald EE, Asghar S, Ahmad S. “Antidiabetic activity of a polyherbal formulation (Karnim Plus)[J]”. Int J Green Pharm, 2009, 3(3) : 211-214.

3Su ZZ, He YY, Chen G. “Clinical and experimental study on effects of man-shen-ling oral liquid in the treatment of 100 cases of chronic nephritis”. Chung Kuo Chung Hsi I Chieh Ho Tsa Chih. 1993;13(5): 259–260,269–272.

4Yi NY, Chu W, Koang NK. “Pharmacologic studies on Liu Wei Di Huang Wan: its action on kidney function and blood pressure of rats with renal hypertension”. Chin Med J-Peking. 1965;84(7):433–436.

5Yuan Y, Hou S, Lian T, Han Y. “Rehmannia glutinosa promotes the recovery of RBC and Hb levels in hemorrhagic anemia by promoting multiplication and differentiation of CFU-S and CFU-E bone marrow cell line”. Chung Kuo Chung Yao Tsa Chih. 1992;17(6):366–368.

6Lee BC, Choi JB, Cho HJ, Kim YS. “Rehmannia glutinosa ameliorates the progressive renal failure induced by 5/6 nephrectomy”. J Ethnopharmacol. 2009;122(1):131–135.

7Liu DG, Zeng M, Gao HY, et al. “Rehmanniae Radix and Rehmanniae Radix Praeparata Ameliorates Renal Interstitial Fibrosis Induced by Unilateral Ureteral Occlusion in Rats and Their Mechanism”. Zhong Yao Cai. 2015 Dec;38(12):2507-10.

8Zhou X1, Sun X1, Gong X1. “Astragaloside IV from Astragalus membranaceus ameliorates renal interstitial fibrosis by inhibiting inflammation via TLR4/NF-кB in vivo and in vitro”. Int Immunopharmacol. 2017 Jan;42:18-24.

9Shahzad M, Shabbir A, Wojcikowski K. “The Antioxidant Effects of Radix Astragali (Astragalus membranaceus and Related Species) in Protecting Tissues from Injury and Disease”. Curr Drug Targets. 2016;17(12):1331-40.

10Zhang HW1, Lin ZX, Xu C, et al. “Astragalus (a traditional Chinese medicine) for treating chronic kidney disease”. Cochrane Database Syst Rev. 2014 Oct 22;(10):CD008369.

11Shahzad M1, Small DM2, Morais C. “Protection against oxidative stress-induced apoptosis in kidney epithelium by Angelica and Astragalus”. J Ethnopharmacol. 2016 Feb 17;179:412-9.

12Zhang J1, Xie X, Li C, et al. “Systematic review of the renal protective effect of Astragalus membranaceus (root) on diabetic nephropathy in animal models”. J Ethnopharmacol. 2009 Nov 12;126(2):189-96.

13Fan YL, Xia JY, Jia DY. “Protective effect of Angelica sinensis polysaccharides on subacute renal damages induced by D-galactose in mice and its mechanism”. Zhongguo Zhong Yao Za Zhi. 2015 Nov;40(21):4229-33. [Article in Chinese].

14Song JY1, Meng LQ, Li XM. “Therapeutic application and prospect of Astragalus membranaceus and Angelica sinensis in treating renal microvascular lesions”. Zhongguo Zhong Xi Yi Jie He Za Zhi. 2008 Sep;28(9):859-61.[Article in Chinese].

15Wojcikowski K1, Wohlmuth H, Johnson DW. “Effect of Astragalus membranaceus and Angelica sinensis combined with Enalapril in rats with obstructive uropathy”. Phytother Res. 2010 Jun;24(6):875-84.

16Muthenna P1, Raghu G1, Kumar PA, et al. “Effect of cinnamon and its procyanidin-B2 enriched fraction on diabetic nephropathy in rats”. Chem Biol Interact. 2014 Oct 5;222:68-76.

17Mollazadeh H1, Hosseinzadeh H2. “Cinnamon effects on metabolic syndrome: a review based on its mechanisms”. Iran J Basic Med Sci. 2016 Dec;19(12):1258-1270.

18Kaffash Elahi R. “The effect of the cinnamon on dog’s heart performance by focus on Kortkoff sounds”. J Animal Veterinary. 2012;11:3604–3608.

19Dashti-Khavidaki S1, Shahbazi F, Khalili H, et al. “Potential renoprotective effects of silymarin against nephrotoxic drugs: a review of literature”. J Pharm Pharm Sci. 2012;15(1):112-23.

20Sedighifard Z1, Roghani F1, Bidram P, et al.  “Silymarin for the Prevention of Contrast-Induced Nephropathy: A Placebo-Controlled Clinical Trial”. Int J Prev Med. 2016 Jan 22;7:23.

21Sonnenbichler J, Scalera F, Sonnenbichler I, et al. “Stimulatory effects of silibinin and silicristin from the milk thistle Silybum marianum on kidney cells”. J Pharmacol Exp Ther. 1999 Sep; 290(3):1375-83.

22Wang XL1, Zhou FJ2, Dou M3, et al “Cochlearoids F-K: Phenolic meroterpenoids from the fungus Ganoderma cochlear and their renoprotective activity”. Bioorg Med Chem Lett. 2016 Nov 15;26(22):5507-5512.

23Joob B1, Wiwanitkit V2 Linzhi. “(Ganoderma lucidum); evidence of its clinical usefulness in renal diseases”. J Nephropharmacol. 2015 Dec 27;5(1):9-10.

24Du F1, Li S2, Wang T, et al. “Cordyceps sinensis attenuates renal fibrosis and suppresses BAG3 induction in obstructed rat kidney”. Am J Transl Res. 2015 May 15;7(5):932-40.

25Yu JS1,2,3, Ho CH4,5, Wang HY6,7, et al. “Acupuncture on Renal Function in Patients with Chronic Kidney Disease: A Single-Blinded, Randomized, Preliminary Controlled Study”. J Altern Complement Med. 2017 Apr 19.

26Matsumoto-Miyazaki J1, Miyazaki N1, Murata I, et al “Traditional Thermal Therapy with Indirect Moxibustion Decreases Renal Arterial Resistive Index in Patients with Chronic Kidney Disease”. J Altern Complement Med. 2016 Apr;22(4):306-14.

27Marsden S. “Introduction to veterinary acupuncture course notes’> College Integrative Veterinary Therapies, 2017.

Dr. Barbara Fougere graduated in 1986, and was named the American Holistic Veterinary Medical Association Educator for 2011. Dr. Fougere is the principle and one of the founders of the College of Integrative Veterinary Therapies. She has continued studying over the last 26 years, and has three Bachelor degrees, two Masters degrees, three post Graduate Diplomas, several Certifications and numerous other courses under her belt.