Consumption of Two New Complementary Feeds (RENAL+MP) in Cats with Chronic Kidney Disease, a Single-Blinded Pet-Owner Evaluation

Abbreviations

CKD: Chronic Kidney Disease

D1: Day 1

FGF 23: Fibroblast Growth Factor 23

G1: Group 1

IRIS: International Renal Interest Society

RMA: Renal+MP Advanced

RME: Renal+MP Early

SDMA: Symmetric DiMethylArginine

SOD: SuperOxide Dismutase

Introduction

Chronic Kidney Disease (CKD) is a prevalent condition in older cats, characterised by progressive and irreversible damage to the kidneys, impairing their ability to filter waste products from the blood and maintain essential physiological functions [1]. The exact cause of CKD in many cases remains unknown, though specific factors such as genetic predisposition (e.g., polycystic kidney disease), infections, toxins, and other underlying conditions can contribute. CKD typically manifests gradually, with initial signs including weight loss, poor appetite, lethargy, increased thirst, and polyuria [1]. As a chronic condition, CKD is irreversible, and advanced cases can progress to renal failure associated with significant clinical complications. The progressive and insidious nature of CKD means that clinical signs often go unnoticed until the disease has reached an advanced stage. However, the introduction of symmetric dimethylarginine (SDMA) as a biomarker has improved early detection, enabling the diagnosis of earlier stages of CKD through routine screening of older cats [2]. The International Renal Interest Society (IRIS) has developed a staging system that classifies CKD into four stages based on the severity of azotaemia and the presence of proteinuria [3]. From a clinical perspective, CKD in cats is characterised by two primary phases: a silent, non-clinical phase corresponding to IRIS stages 1 and 2, and a clinical phase where signs of uraemia become evident due to the progressive loss of functional nephrons. Diagnosis typically involves blood tests (e.g., urea, creatinine, SDMA) to assess kidney function and urine tests to evaluate urine concentration and protein loss. Additional tests may be required to assess complications like anaemia, electrolyte imbalances, and hypertension [1].

A key metabolic complication of CKD is hyperphosphataemia, which arises from a decline in renal phosphorus excretion as the disease progresses. Persistently elevated serum phosphorus has been identified as a predictor of CKD progression in cats [4]. Elevated phosphorus levels stimulate increased parathyroid hormone (PTH) secretion, leading to the mobilisation of phosphorus and calcium from bone, ultimately resulting in secondary renal hyperparathyroidism.

While CKD cannot be reversed, supportive management aims to slow disease progression and address associated complications. Management strategies include dietary modifications to reduce kidney workload, medications to control blood pressure and manage secondary conditions like anaemia, and fluid therapy to manage dehydration [1]. Regular veterinary check-ups and diagnostic tests are crucial for adjusting treatment plans as needed. The disease's two distinct phases often necessitate tailored management approaches based on the specific biological and clinical signs observed in each case.

The management of CKD involves a multifaceted approach including use of phosphate binders, hypertension management, and quality of life enhancement [3]. Each of these aspects plays a crucial role in mitigating the progression of CKD and improving outcomes for affected cats.

The International Renal Interest Society provides specific recommendations for blood phosphorus levels according to the stage of kidney disease and suggests the use of phosphate binders starting from stage 2 to modulate these levels [3]. Human studies have shown that supplements including chitosan can reduce salivary and serum phosphorus levels in dialysis patients [5]. The interest of supplements combining chitosan with other phosphorus-binding ingredients has also been demonstrated in both cats and dogs [6,7]. In dogs at IRIS stages 3 or 4, one study reported a significant reduction in serum phosphorus levels following the administration of such supplements [8]. Similarly, another study found positive effects on uraemia and phosphataemia in cats with CKD at IRIS stages 3 and 4 [9]. Azotemia, characterised by elevated blood urea nitrogen, is a common issue in CKD. Compounds that help reduce azotemia include lespedeza (Lespedeza capitata), which has been shown to be beneficial for kidney health, with studies reporting protective actions on kidney cells and improvements in renal parameters in cats [10-12]. Chitosan is well-documented for capturing intestinal uraemic toxins and reducing intestinal absorption of ammonia, which is particularly beneficial in CKD [13]. Managing hypertension is crucial from the early stages of CKD (stage 1), as per IRIS recommendations. Orthosiphon (O. stamineus) exhibits vasorelaxant and antihypertensive actions, likely mediated by sinensetin [14,15]. Lespedeza (Lespedeza capitata) shows protective action on kidney cells and modulates the angiotensin-converting enzyme, which is beneficial for renal health [10,11]. In addition, CKD is associated with increased oxidative stress, leading to elevated cell apoptosis [16]. Markers of oxidative stress may be present even in the early stages of kidney disease [17]. Desmodium (Desmodium adscendens) is known for its antioxidant properties, attributed to anthocyanins, which protect cells from oxidative stress and benefit renal and cardiovascular functions [18,19]. Dandelion (Taraxacum oficinale) provides renal protection against nephrotoxic agents, likely due to its mild diuretic action and inhibits the formation of oxalate crystals in vitro [20,21]. Superoxide dismutases (SOD), found in melon juice and flesh, protect nephrocytes from oxidative stress, preserve nephrons, reduce fibrosis, and show potential use in diabetic nephropathy [22].

While plant extracts have demonstrated beneficial effects in the management of CKD in cats, their interest may be limited by the species’ notoriously selective appetite and feeding behaviour. This challenge is particularly pronounced in cats with CKD, where poor appetite further hinders the voluntary intake of feed supplements. As reduced food intake is a common concern in CKD cats, it can significantly impact their ability to consume complementary feeds, including phosphate binders, compared to healthy cats. Assessing the consumption rates of these products in CKD-affected cats is therefore crucial, as it has direct implications for compliance and therapeutic success. To address this, we conducted a study evaluating the consumption rates of two complementary feeds, Renal+MP Early and Advanced, in cats with CKD.

Materials and Methods

Study Objectives

The primary objectives of this study were to measure the acceptability of complementary feeds for cats, evaluate the palatability of these products, and identify any potential changes over time. This was specifically measured with spontaneous evaluation on Day 1 (D1) and a subsequent evaluation on Day 5 (D5) in cats suffering from chronic kidney disease.

Study Design

This study was conducted at the homes of the participating cats. Forty-one owners of cats diagnosed with chronic kidney disease (CKD) were randomly assigned to either Group 1 (G1 = RENAL+MP EARLY (RME) (MP Labo, France)) or Group 2 (G2 = RENAL+MP ADVANCED (RMA) (MP Labo, France)). The products were masked to ensure a blind format.

Animals

The study exclusively included cats diagnosed with chronic kidney disease by a veterinarian but having a creatinine level below 5.0 mg/dl. Cats were allowed to consume both dry and wet food, but the concurrent use of other renal-targeted complementary feeds was not permitted. If the animal was already undergoing stabilised medication for CKD, the treatment regimen remained unchanged.

Tested Products

RME contained calcium carbonate, desmodium, brewer’s yeast products, orthosiphon, dandelion, melon juice and flesh (source of SOD), and L-carnitine. RMA contained calcium carbonate, chitosan, desmodium, brewer’s yeast products, lespedeza, orthosiphon, ginkgo, melon juice and flesh (source of SOD), and L-carnitine.

The test products were given to the cats in their regular food bowl along with their usual diet, which could be dry food (kibble), wet food, or both. Each cat received one measuring spoon of powder per 5 kg of body weight, administered twice daily for 5 days, mixed with their meal. Owners could decide to mix the daily amount of powder into one or two of their cat's regular meals each day, depending on the cat's normal feeding routine.

Evaluations

A questionnaire was administered to the cat owners on Day 1 (D1) and Day 5 (D5). Owners rated the meal consumption as follows: 100%, 90 to 100%, 50 to 90%, 5 to 50%, less than 5%, or nothing. Total consumption was defined as 100% intake, while partial consumption was defined as more than 50% intake. Owners were also asked to rate product’s characteristics and to give an overall satisfaction score.

Statistical Analysis

Standard deviations and distribution were examined to evaluate normality. Any bimodal distributions or very large standard deviations were noted in the comments. The binomial law with p=1/2 was used to determine if one response category was significantly more cited than others for the same product. The chi- square (Khi2) test was applied to assess if two proportions were significantly different from each other, particularly comparing the proportions of cats between days within each group. Monte Carlo tests and Marascuilo tests (pairwise comparison tests) were used to compare k proportions and classify them when a significant difference was observed. Significance levels were denoted as follows: results were considered significantly different at 5% risk level, 1% risk level, and 0.1% risk level.

Results

Population: 41 cats with a diagnosis of CKD were included in the study. 21 cats were assigned to G1 and 20 to G2. The population’s characteristics are described in Figure 1.

<img src=" https://www.opastpublishers.com/scholarly-images/8597-6921520a43918-consumption-of-two-new-complementary-feeds-renalmp-in-cats-w.png" width="500" height="300">
Figure 1: Population Characteristics

Clinical results: At the end of the study, total consumption was reported for 43% and 30% of cats and partial consumption for 72% and 75% of cats in G1 and G2, respectively (Figures 2 & 3). No statistical differences were found on D5 vs D1, except in G2 for ’90 to 100%’ (increased in D5 versus D1) and ‘50 to 90%’ (decreased in D5 versus D1).

Figure 2: Consumption Rates in G1 on D1 and D5.

<img src=" https://www.opastpublishers.com/scholarly-images/8597-6921525d70297-consumption-of-two-new-complementary-feeds-renalmp-in-cats-w.png" width="500" height="300">
Figure 3: Consumption Rates in G2 on D1 and D5. * Denotes Statistically Significant Difference Versus D1 (p < 0.05).

Owners’ satisfaction: 76% and 75% of owners were satisfied with the product, and 86% and 90% of owners found products easy to give, in G1 and G2, respectively. Tolerance: 80% of owners did not report any adverse effects. A few slight digestive signs were reported at D5: 1 cat in each group had flatulence, 1 cat in G2 had bad breath, 1 cat in G2 had a change in the urine and 3 cats in each group had a change in stool consistency.

Discussion

The study demonstrated that a significant proportion of cats achieved total consumption of complementary feeds over the five- day evaluation period. Specifically, 72% and 75% of cats in the two groups achieved partial consumption, illustrating a generally positive acceptance of the products. These findings align with those of Bernachon et al., who evaluated the palatability of five supplements designed for cats with CKD (Figure 4). However, key differences exist between the studies: Bernachon et al. conducted tests on healthy cats, whereas our study targeted cats with CKD, a population likely to have reduced appetites due to their condition. Furthermore, our study's five-day daily administration provided a more robust assessment of sustained consumption compared to Bernachon et al.'s single-administration approach [23].

Figure 4: Consumption Rates Results Comparing Complementary Feeds Across Different Cat Populations

The higher acceptance rates observed in our study with CKD- affected cats suggest that Renal+MP products are appealing even to populations with potentially poorer appetites, highlighting their potential benefit in helping to manage CKD in a real-world clinical setting. Furthermore, the study noted minimal adverse effects, with 80% of owners reporting no negative reactions. Only a few cats exhibited mild digestive signs such as flatulence, bad breath, or changes in stool consistency, indicating good tolerability of the products in the study population. Notably, no cases of vomiting were observed. This is particularly important as vomiting can significantly affect the overall quality of life and complicate the management of CKD in cats [9].

CKD is more common in older cats, with prevalence increasing significantly with age. Early detection through routine screenings can enhance quality of life by enabling timely intervention. While CKD poses challenges due to its progressive nature and irreversible damage, proactive management can enhance a cat's well-being and extend life expectancy, emphasising the importance of regular veterinary care and tailored management strategies. Recent advancements, such as the development of a test based on Fibroblast Growth Factor (FGF23), allow for early CKD diagnosis, emphasising the importance of proactive veterinary care [24]. Additionally, offering two distinct formulations (Renal+MP Early and Renal+MP Advanced) allows tailored support for different CKD stages, aligning with the IRIS committee's recommendations. The IRIS committee highlights the need to manage quality of life from stage 2 CKD to address digestive issues and muscle mass loss. For instance, L-Carnitine has been shown to maintain muscle mass and weight in cats with CKD (IRIS stages 1 and 2). Similar benefits have been observed in older dogs, where an association containing L-Carnitine improved health and helped to reduce serum SDMA levels [25-27]. Brewer's yeast products help maintain a balanced intestinal microbiota, improve stool quality and digestibility, and support immune defences. These properties not only promote overall health but also favour product consumption [28].

Our study has several limitations. Cats were allowed to continue their regular diet alongside the complementary feeds, and it included a relatively small number of cats (41 in total), divided into two groups. A larger sample size would provide more robust statistical power and enhance the generalisability of the findings to a broader population of cats with CKD. Additionally, the five-day evaluation period may not fully capture long-term acceptance and potential effects on clinical outcomes. Future studies should consider longer-term evaluations, standardisation of the diet and incorporate objective measures of dietary intake and clinical outcomes. For instance, including biomarkers of kidney function and quality of life assessments would provide a more comprehensive understanding of the benefits of these supplements. While involving pet owners in the evaluation process provides valuable insights into the real-world applicability of the product, incorporating objective measurements of dietary intake and clinical outcomes would strengthen the study's findings. Finally, this study excluded cats with severe CKD (creatinine levels > 5.0 mg/dl), limiting the applicability of the findings to advanced disease stages. Future research should include cats with more severe CKD to evaluate the products' consumption across all CKD stages.

Conclusion

In conclusion, the management of CKD in cats involves a multifaceted approach, encompassing dietary phosphorus control, the use of phosphate binders, antioxidant therapies, hypertension management, azotemia reduction, and quality of life enhancement. This study is conducted specifically on cats with CKD, a population known for its poor appetite. The results demonstrated that the two new complementary feeds, Renal+MP Early and Renal+MP Advanced, were well accepted by cats with CKD over a five-day period, with acceptable levels of intake and ease of administration as reported by pet owners. Given the challenges associated with feeding cats suffering from CKD, these findings are promising and suggest that these complementary feeds could be consistent with what will be observed in broader field conditions. The incorporation of these feeds into CKD management protocols could provide a valuable addition to current strategies, helping to mitigate the progression of the disease and improve outcomes for affected cats. Regular monitoring and tailored management strategies remain crucial for enhancing the well-being and extending the life expectancy of cats with CKD, highlighting the importance of proactive veterinary care and the integration of new dietary interventions.

Conflict of interest: The study was funded by MP Labo, the manufacturer of the tested products. CN, CB & BJ are employees of MP Labo, the manufacturer of the tested products.

References

1. Sparkes, A. H., Caney, S., Chalhoub, S., Elliott, J., Finch, N., Gajanayake, I., ... & Quimby, J. (2016). ISFM consensus guidelines on the diagnosis and management of feline chronic kidney disease. Journal of feline medicine and surgery, 18(3), 219-239.
2. Relford, R., Robertson, J., & Clements, C. (2016). Symmetric dimethylarginine: improving the diagnosis and staging of chronic kidney disease in small animals. Veterinary Clinics: Small Animal Practice, 46(6), 941-960.
3. IRIS Treatment Recommendations, modified 2013
4. Laflamme, D., Backus, R., Brown, S., Butterwick, R., Czarnecki�Maulden, G., Elliott, J., ... & Polzin, D. (2020). A review of phosphorus homeostasis and the impact of different types and amounts of dietary phosphate on metabolism and renal health in cats. Journal of veterinary internal medicine, 34(6), 2187-2196.
5. Savica, V., Calo, L. A., Monardo, P., Davis, P. A., Granata, A., Santoro, D., ... & Bellinghieri, G. (2009). Salivary phosphate- binding chewing gum reduces hyperphosphatemia in dialysis patients. Journal of the American Society of Nephrology, 20(3), 639-644.
6. Brown, S. A., Rickertsen, M., & Sheldon, S. (2008). Effects of an intestinal phosphorus binder on serum phosphorus and parathyroid hormone concentration in cats with reduced renal function. Int J Appl Res Vet Med, 6(3), 155-160.
7. Martello, E., Perondi, F., Bruni, N., Bisanzio, D., Meineri, G., & Lippi, I. (2021). Chronic Kidney Disease and Dietary Supplementation: Effects on Inflammation and Oxidative Stress. Veterinary Sciences, 8(11), 277.
8. Martello, E., Perondi, F., Capucchio, M. T., Biasato, I., Biasibetti, E., Cocca, T., ... & Lippi, I. (2020). Efficacy of a new dietary supplement in dogs with advanced chronic kidney disease. PeerJ, 8, e9663.
9. Biasibetti, E., Martello, E., Bigliati, M., Biasato, I., Cocca, T., Bruni, N., & Capucchio, M. T. (2018). A long term feed supplementation based on phosphate binders in Feline Chronic Kidney Disease. Veterinary Research Communications, 42, 161-167.
10. Wagner, H., & Elbl, G. (1992). ACE-inhibitory procyanidins from Lespedeza capitata. Planta medica, 58(03), 297-297.
11. Cornara, L., Xiao, J., & Burlando, B. (2016). Therapeutic potential of temperate forage legumes: a review. Critical reviews in food science and nutrition, 56(sup1), S149-S161.
12. Di Cerbo, A., Iannitti, T., Guidetti, G., Centenaro, S., Canello, S., & Cocco, R. (2018). A nutraceutical diet based on Lespedeza spp., Vaccinium macrocarpon and Taraxacum officinale improves spontaneous feline chronic kidney disease. Physiological Reports, 6(12), e13737.
13. Zatelli, A., Pierantozzi, M., D′ Ippolito, P., Bigliati, M., & Zini, E. (2012). Effect of dietary supplements in reducing probability of death for uremic crises in dogs affected by chronic kidney disease (masked RCCT). The Scientific World Journal, 2012(1), 219082.
14. Azizan, N. A., Ahmad Mohamed, K., Ahmad, M. Z., & Asmawi, Z. (2012). The in vivo antihypertensive effects of standardized methanol extracts of Orthosiphon stamineus on spontaneous hypertensive rats: A preliminary study. African Journal of Pharmacy and Pharmacology, 6(6), 376-379.
15. Yam, M. F., Tan, C. S., & Shibao, R. (2018). Vasorelaxant effect of sinensetin via the NO/sGC/cGMP pathway and potassium and calcium channels. Hypertension research, 41(10), 787-797.
16. Silva, A. C. R. A., de Almeida, B. F. M., Soeiro, C. S., Ferreira,W. L., de Lima, V. M. F., & Ciarlini, P. C. (2013). Oxidative stress, superoxide production, and apoptosis of neutrophils in dogs with chronic kidney disease. Canadian Journal of Veterinary Research, 77(2), 136-141.
17. Granick, M., Leuin, A. S., & Trepanier, L. A. (2021). Plasma and urinary F2-isoprostane markers of oxidative stress are increased in cats with early (stage 1) chronic kidney disease. Journal of Feline Medicine and Surgery, 23(8), 692-699.
18. Muanda, F. N., Bouayed, J., Djilani, A., Yao, C., Soulimani, R., & Dicko, A. (2011). Chemical composition and, cellular evaluation of the antioxidant activity of Desmodium adscendens leaves. Evidence�Based Complementary and Alternative Medicine, 2011(1), 620862.
19. François C, Fares M, Baiocchi C, Maixent JM. (20215). Safety of Desmodium adscendens extract on hepatocytes and renal cells. Protective effect against oxidative stress. J Intercult Ethnopharmacol. 4(1):1-5.
20. KarakuÅ?, A., DeÄ?er, Y., & Yıldırım, S. (2017). Protective effect of Silybum marianum and Taraxacum officinale extracts against oxidative kidney injuries induced by carbon tetrachloride in rats. Renal failure, 39(1), 1-6.
21. Yousefi Ghale-Salimi, M., Eidi, M., Ghaemi, N., & Khavari- Nejad, R. A. (2018). Inhibitory effects of taraxasterol and aqueous extract of Taraxacum officinale on calcium oxalate crystallization: in vitro study. Renal failure, 40(1), 298-305.
22. Rosa, A. C., Corsi, D., Cavi, N., Bruni, N., & Dosio, F. (2021). Superoxide dismutase administration: A review of proposed human uses. Molecules, 26(7), 1844.
23. Bernachon, N., Fournel, S., Gatto, H., Monginoux, P., & McGahie, D. (2014). Comparative palatability of five supplements designed for cats suffering from chronic renal disease. Irish Veterinary Journal, 67, 1-7.
24. Miyakawa, H., Hsu, H. H., Ogawa, M., Akabane, R., Miyagawa, Y., & Takemura, N. (2022). Serum fibroblast growth factor-23 concentrations in young and mature adult cats with chronic kidney disease. Journal of Feline Medicine and Surgery, 24(8), 815-820.
25. Hall, J. A., Fritsch, D. A., Jewell, D. E., Burris, P. A., & Gross, K. L. (2019). Cats with IRIS stage 1 and 2 chronic kidney disease maintain body weight and lean muscle mass when fed food having increased caloric density, and enhanced concentrations of carnitine and essential amino acids. Veterinary Record, 184(6), 190-190.
26. Hall, J. A., & Jewell, D. E. (2012). Feeding healthy beagles medium-chain triglycerides, fish oil, and carnitine offsets age-related changes in serum fatty acids and carnitine metabolites.PLoS One, 7(11), e49510.
27. Hall, J. A., MacLeay, J., Yerramilli, M., Obare, E., Yerramilli, M., Schiefelbein, H., ... & Jewell, D. E. (2016). Positive impact of nutritional interventions on serum symmetric dimethylarginine and creatinine concentrations in client- owned geriatric dogs. PLoS One, 11(4), e0153653.
28. Lin CY, Alexander C, Steelman AJ, Warzecha CM, de Godoy MRC, Swanson KS. (2019). Effects of a Saccharomyces cerevisiae fermentation product on fecal characteristics, nutrient digestibility, fecal fermentative end-products, fecal microbial populations, immune function, and diet palatability in adult dogs. J Anim Sci. 3;97(4):1586-1599.