Takenaka M, Iio A, Sato R, Sakamoto T, Kurumatani H. A Double-blind, Placebo-controlled, Multicenter, Prospective, Randomized Study of Beraprost Sodium Treatment for Cats with Chronic Kidney Disease. J Vet Intern Med. 2018 Jan;32(1):236-248. PubMed PMID: 29131397.
Chronic kidney disease remains one of the most common diseases of domestic cats, and as such a myriad of therapies have developed to slow its progression and manage symptoms. ACE inhibitors, angiotensin receptor blockers, diets, phosphate binders, potassium supplements, fluid support, and many other therapeutics are used.
Beraprost Sodium (BPS) is a prostacyclin analogue used in humans to treat pulmonary artery hypertension and other diseases. It prevents platelet aggregation, leading to some potential utility as an anticoagulant. In some animal models of CKD, BPS has been shown to have a renoprotective effect potentially due to inhibition of renal tubular cell apoptosis, decrease in fibrosis, and improvement of oxygenation.
The purpose of this study was to evaluate the efficacy and safety of BPS in cats with naturally occurring CKD. The study was designed as a prospective, double blind, placebo controlled, multi center randomized trial at 22 primary care veterinary practices in Japan.
Cats were eligible for enrollment if they had a urine specific gravity < 1.035 and a serum creatinine of >141mmol/L, urine protein: creatinine ratio <1.5, and a normal serum total T4. These values included cats in IRIS stages II-IV. Values were measures at 14d and 7d pre enrollment and cats only entered if cats repeatedly met the criteria. Cats were excluded due to pregnancy, AKI, heart failure, diabetes, hyperadrenocorticism, UTI, FIV, FeLV, FIP, neoplasia, liver disease, or bleeding disorders. Renal diets were allowed to be fed but could not be changed. SQ fluids, antihypertensives, and phosphate binders were allowed. NSAIDs, steroids, and certain other drugs were not allowed.
Cats were randomly assigned to receive a BP tablet at 55ug/cat every 12 hours orally; or a similar tablet containing lactose instead of BPS. Cats were treated for 180 days with lab evaluations (basic urinalysis, chemistry and CBC) at 30 day intervals. Primary endpoints were creatinine, phosphorus:calcium ratio, and urine specific gravity. Secondary endpoints were BUN, body weight, UPC ratio, and owner and veterinarian assessments of efficacy and quality of life.
150 cats were screened, of whom 75 were enrolled in the study. 63 were included in the final analysis. Cats had an average age of 13.8 years and an approximately equal sex distribution, most cats being neutered. 77% of BPS group cats were IRIS II and 59% of placebo cats. Theramining cats were IRIS III. No Iris IV cats were enrolled.
Over the course of the study, serum creatinine increased by a statistically significant mean of 32mmol/L in the placebo group but remained stable in the BPS group. Serum phosphorus to calcium ratio also increased in the placebo group and not BPS, however there was no difference between groups at 180 days. No change was seen in USG in either group.
Serum BUN changes mimicked those seen in creatinine. No change was seen in UPCR. Body weight decreased in the placebo group but not in the BPS group, however there was no difference between groups at day 180. Fewer cats in the BPS group showed signs of lethargy than the placebo, and there was a significant increase in appetite on BPS. Dehydration score did not change. Owner assessment of quality of life was significantly better in the BPS group.
16 cats in the BPS group reported adverse events compared to 22 in the placebo group. No adverse changes in CBC or blood chemistries were seen.
The authors concluded that BPS is safe in cats and shows promise in the treatment of CKD. While creatinine values did not decrease in treated cats, they remained stable while placebo cats increased. Similar trends were seen for other markers of renal disease, as well as body weight. A plausible mechanism exists for potential renoprotective effects and experimental data in other species suggests a similar efficacy.
Several downsides to this study were present. Blood pressure was not measured, limiting full IRIS staging. A single dose was used in cats of various weights and stages of disease. There were also many confounding variables at play including varied stages of CKD and co administration of other drugs.
Further data is needed in order to recommend the routine administration of BPS to cats with CKD. This may include administration to larger sample sizes, for longer periods of time, in animals with concurrent or underlying disease, and at varied doses. However, this drug shows promise as a potential target for further research in the therapy of CKD in cats.
Sparkes AH, Caney S, Chalhoub S, et al. ISFM consensus guidelines on the diagnosis and management of feline chronic kidney disease. J Feline Med Surg 2016;18:219–239.