Chronic kidney disease (CKD) is a prevalent condition, particularly among aging dogs. This study investigates the effectiveness of a dietary supplement containing calcium carbonate, calcium-lactate gluconate, chitosan, and sodium bicarbonate in dogs diagnosed with IRIS stage 3 CKD. The research involved twenty dogs, with ten receiving the new supplement for 180 days (T group) and ten serving as a control group (C group). Regular hematologic, biochemical, and urinalysis assessments were conducted throughout the study.
Introduction to Canine Chronic Kidney Disease
CKD in dogs is characterized by structural or functional abnormalities in the kidneys persisting for at least three months. It is a common ailment, especially in older dogs, often progressing slowly over months to a couple of years. Current management strategies for CKD focus on slowing disease progression by addressing key risk factors and clinical signs. In veterinary practice, consistent monitoring of parameters like proteinuria, hypertension, and hyperphosphatemia is crucial for adjusting therapy as needed.
Specialized renal diets are formulated to mitigate CKD progression, improve the quality of life for affected dogs, and manage electrolyte and acid-base imbalances while ensuring adequate nutrition. These diets are considered a primary therapeutic approach, with management often guided by the International Renal Interest Society (IRIS) four-stage scale. Nutritional support is vital for controlling protein and phosphate intake to prevent malnutrition and dehydration, ultimately reducing mortality rates. When diet alone proves insufficient for managing phosphate levels, metabolic acidosis, or slowing CKD progression, the use of dietary supplements, such as phosphate binders and alkalizing agents, becomes a valuable veterinary strategy.
Veterinarians must select the most appropriate therapeutic approach to maintain serum phosphorus levels within the IRIS-recommended ranges for each CKD stage. A variety of commercially available phosphate binders work by chelating phosphorus in the intestines, forming inert compounds that are then eliminated. Metabolic acidosis also contributes to CKD progression and impairs protein nutrition. In CKD, increased retention of metabolic acids, heightened ammonia production, and reduced bicarbonate production occur. While the prevalence of metabolic acidosis in dogs with CKD is less documented than in cats, it is associated with poor appetite, hypokalemia, and muscle weakness. In human medicine, bicarbonate therapy has shown promise in slowing CKD progression and improving nutritional status. Alkalizing agents are commonly used to increase blood pH by binding hydrogen ions and are indicated for dogs with CKD stages 1-4 when blood pH and bicarbonate levels fall below normal.
Commercial dietary supplements containing compounds like chitosan, calcium carbonate, and potassium citrate have demonstrated benefits in managing hyperphosphatemia in dogs with CKD. A recent study on cats using a similar supplement (calcium carbonate, calcium-lactate gluconate, chitosan, and sodium bicarbonate) reported reduced serum phosphorus and increased serum bicarbonate, leading to improved clinical conditions. This current study aims to evaluate the phosphate-binding and acid-base correcting capabilities, as well as the ease of administration, of a new dietary supplement with these components in dogs with CKD.
Materials and Methods
This prospective, randomized, controlled study was conducted in 2015 at the Napolivet Veterinary clinic in Naples, Italy. Dogs diagnosed with advanced CKD (IRIS stages 3 and/or 4) were identified by screening the clinic’s database. CKD diagnosis was based on persistent azotemia, medical history of polyuria/polydipsia (over three months), clinical signs consistent with chronic disease (weight loss, reduced muscle mass), or ultrasound findings of structural abnormalities. Dogs were classified according to IRIS guidelines, considering serum creatinine, urine protein-to-creatinine ratio (UPC), and blood pressure.
Exclusion criteria included suspected or diagnosed concurrent diseases such as acute kidney injury, pre-renal or post-renal azotemia, genitourinary tract inflammation or infection, urinary tract obstruction, heart disease, chronic heart failure, neoplasia, hypothyroidism, or diabetes.
Owners provided informed consent after being fully informed about the study’s purpose and design. All procedures adhered to Italian and EU animal care and use guidelines. Dogs were randomly assigned to either a control group (C group, n=10) or a treated group (T group, n=10). Baseline assessments included history, physical examination (body weight and body condition score), complete blood count (CBC), serum biochemical profile, venous blood gas analysis, and blood pressure measurement. Urinalysis was also performed. These assessments were repeated every 30 days for 180 days.
All dogs were fed the same commercial renal diet (Royal Canin Renal Canine) throughout the study and for at least eight weeks prior. The T group received an additional supplement, “Renal P” (Candioli Pharma S.r.l.), containing calcium carbonate, calcium-lactate gluconate, chitosan, and sodium bicarbonate. The daily dosage was 0.2 g/kg body weight, divided into two administrations mixed with meals.
Dogs with pre-existing clinical signs (vomiting, poor appetite) or proteinuria and hypertension received appropriate treatments prior to enrollment. Owners monitored daily for vomiting, diarrhea, and anorexia. Proteinuric dogs were treated with benazepril, and hypertensive dogs were managed with a combination of benazepril and amlodipine as per IRIS guidelines.
Blood and Urine Analysis
Blood samples were analyzed for CBC and serum biochemistry, including blood urea nitrogen (BUN), creatinine (CREA), phosphorus (P), total protein (TP), albumin (ALB), glucose (GLU), liver enzymes (ALT, AST, ALP), bilirubin (BIL), and cholesterol (CHOL). Venous blood gas analysis assessed bicarbonate (HCO3) and ionized calcium (iCa). Urine samples collected via cystocentesis underwent analysis for specific gravity, sediment examination, and UPC measurement to assess proteinuria.
Statistical Analysis
Data were analyzed using GraphPad Prism software. The Shapiro–Wilk test assessed data normality. Repeated measures ANOVA and Friedman tests were used for intra-group comparisons, while Student t and Mann–Whitney U tests were used for inter-group comparisons. Significance was set at p < 0.05 or p < 0.008 for multiple comparisons.
Results
All twenty dogs completed the study. The median age was 10 years, with no significant differences in age, body weight, or body condition score between the groups at baseline or throughout the study. Hematological values and blood pressure also remained comparable between groups.
Biochemical analysis revealed a significant increase in BUN and creatinine in the C group over time, whereas these parameters remained stable in the T group. Serum phosphorus levels, which were initially similar between groups, significantly decreased in the T group from day 30 onwards, with most dogs returning to normal levels within 90 days. In contrast, the C group consistently exhibited elevated phosphorus levels.
Serum ionized calcium (iCa) levels showed a significant increase in the T group from day 120 compared to the C group, though all values remained within the normal physiological range. Serum bicarbonate (HCO3) levels, initially low in both groups, significantly increased in the T group from day 30 onwards, eventually becoming significantly higher than in the C group by day 180, though still below the normal reference range.
Urinalysis indicated that at baseline, most dogs in both groups were proteinuric. While UPC values did not significantly change within groups during the study, the T group showed a significantly lower UPC at days 150 and 180 compared to the C group. All dogs remained within IRIS stage 3 throughout the study. Owners unanimously reported the ease of administration and good palatability of the supplement, with no adverse effects observed.
Discussion
This study demonstrates the efficacy of a novel dietary supplement in managing IRIS stage 3 CKD in dogs. The supplement significantly reduced serum phosphorus levels and increased serum bicarbonate, outcomes consistent with previous research in both dogs and cats. The reduction in serum phosphorus was notable, with many dogs achieving normal levels within 90 days of supplementation. This suggests the supplement effectively binds dietary phosphorus.
While the supplement increased serum bicarbonate levels, they did not fully normalize, indicating that more severe cases of metabolic acidosis might require higher dosages or additional bicarbonate supplementation. The observed increase in ionized calcium in the T group, while statistically significant, did not lead to hypercalcemia, a potential concern with calcium-based phosphate binders. This suggests a balanced effect of the supplement’s components.
The decrease in UPC in the T group towards the end of the study, although not as rapid as observed in a similar cat study, indicates a potential improvement in kidney function or a reduction in proteinuria. Chitosan, a component of the supplement, is known to bind uremic toxins and aid in their elimination, potentially contributing to improved metabolic parameters. The high compliance rate reported by owners further supports the practicality of this supplement in clinical use.
Conclusions
The dietary supplement tested effectively reduced serum phosphorus and increased serum bicarbonate in dogs with IRIS stage 3 CKD, without inducing hypercalcemia. The ease of administration and palatability reported by owners highlight its practical application. Further research involving a larger cohort of dogs across different IRIS stages is warranted to fully elucidate its long-term benefits and effectiveness.
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