Submitted by: Patricia Shea, DVM
J Vet Intern Med. March-April 2013;27(2):227-33.
Fibroblast growth factor 23 (FGF-23) concentrations in cats with early nonazotemic chronic kidney disease (CKD) and in healthy geriatric cats.
Finch NC, Geddes, RF, et al.
Comments: FGF-23, a hormone, is known to have an important role in phosphate regulation; in conjunction with parathyroid hormone (PTH), it targets the kidney to cause phosphaturia. Studies in rats have demonstrated that in CKD high serum PTH and FGF-23 levels are present and the parathyroid glands are resistant to FGF-23; it is known that PTH acts on bone to increase FGF-23 expression. FGF-23 is known to be involved in the pathogenesis of renal secondary hyperparathyroidism in humans.
In this study, 62 healthy client-owned geriatric cats were recruited and followed for 12 months. During the 12 month follow-up period, 14 of the cats developed azotemia. Parameters including plasma creatinine, PTH, FGF-23, and other biochemical variables were assessed at the beginning of the study (baseline) and after 12 months. GFR was measured by an iohexol clearance method. At the end of the study, cats were divided into 3 groups according to plasma creatinine concentration. In the cats that developed azotemia, FGF-23 concentrations at baseline were significantly increased compared with cats that did not become azotemic. A positive correlation was found between FGF-23 and PTH, while there was a negative relationship between FGF-23 and GFR. This study demonstrated that increased FGF-23 concentrations predicted development of azotemia, and that the positive correlation between FGF-23 and PTH levels suggest an association between increased FGF-23 and renal secondary hyperparathyroidism.
J Am Vet Med Assoc. April 2013;242(8):1110-6.
Outcome following gastrointestinal tract decontamination and intravenous fluid diuresis in cats with known lily ingestion: 25 cases (2001-2010).
Bennett AJ, Reineke, EL.
Comments: Ingestion of an as yet unidentified water-soluble toxic principle present in plant material from lilies of the genera Lilium (“Easter”, “Madonna”, “Asiatic” or “Oriental Hybrid”, or “Turk’s Cap” lilies) and Hemerocallis (daylilies) by cats will result in acute kidney injury (AKI) and potentially, death. Hitherto no evidence-based guidelines for the treatment of cats with lily ingestion have been published. Medical records of 25 cats admitted to a university veterinary teaching hospital with a history of lily plant ingestion within less than 30 minutes up to 48 hours prior to presentation were evaluated in this retrospective case series study. Patients were divided into 2 groups. Group 1 consisted of 17 patients with a history of ingestion within 6 hours or less prior to presentation. Group 2 consisted of 8 patients with a history of ingestion within more than 6 hours up to 48 hours prior to presentation. Median age of patients was 2.5 years, and patients were either spayed females or castrated males, mostly mixed breed. Nineteen of the 25 cats received gastrointestinal tract decontamination (variously including induction of emesis, gastric lavage, administration of activated charcoal, or a combination of these procedures), including all Group 1 cats and 2 of the 8 Group 2 cats. Eight of the cats (3 in Group 1 and 5 in Group 2) had vomited at home prior to evaluation.
All 25 cats survived; of the 23 cats hospitalized because of lily ingestion (16 from Group 1 and 7 from Group 2), all received IV fluid diuresis with isotonic crystalloids, and all survived to discharge, with a low incidence of AKI. Hospitalization was declined for 2 of the cats, and both of these cats survived the lily ingestion without permanent azotemia for over 3 years. Although previously published information suggests that the mortality rate for cats treated more than 18 hours after lily ingestion is 100%, this study suggests a significantly more favorable outlook for these patients, possibly because 5 of the 8 Group 2 cats self-decontaminated by vomiting at home prior to presentation. For feline patients with a history of lily plant ingestion, these clinicians recommend early gastrointestinal tract decontamination with emesis induction or gastric lavage, followed by activated charcoal administration, as well as IV fluid diuresis (length of time not determined in this study) and monitoring of renal parameters.
J Am Vet Med Assoc. July 2013;243(1):91-95.
Survival time and prognostic factors in cats with newly diagnosed diabetes mellitus: 114 cases (2000-2009).
Callegari C, Mercuriali E, et al.
Comments: In this retrospective case study, medical records of 114 cats with newly diagnosed diabetes mellitus (DM), admitted to a university veterinary teaching hospital in Switzerland, were reviewed. None of the cats included in the study had received any treatment for their DM prior to admission to the hospital. The patients were of varying signalment and included 67.5% neutered males and 32.5% spayed females. Most of the cats (72.6%) were mixed breed domestic shorthairs or domestic longhairs; 27.4% were purebred cats representing a number of different breeds. The median age of the patients at diagnosis was 11 years; median body weight was 5 kg; and 11 of the cats had received corticosteroids or progestagens up to 4 months prior to admission. Median serum glucose concentration and medium serum fructosamine concentration were 427 mg/dL and 612 micromoles/L, respectively. Thirty-nine (34.2%) of the cats had ketoacidosis; and 51 patients had concurrent diseases, such as cholangitis, lung disease, suspected pancreatitis, cystitis, renal failure, and many others. Five of the 19 cats who died, died before insulin treatment was begun, and 95 of the cats survived to discharge.
Results of this study demonstrated that in the population evaluated, ketoacidosis was not significantly associated with survival time, and may not be a negative outcome predictor in diabetic cats; in fact 32% of the ketoacidotic cats in the study survived > 3 years. Median survival time of all the diabetic cats was 516 days, and 46% of the cats lived more than 24 months. Sex, breed, body weight, previous exposure to corticosteroids or progestagens, type of insulin selected (glargine or porcine zinc insulin suspension), and most all commonly measured biochemical and hematologic parameters were not associated with any impact on survival time. High serum creatinine concentration, however, was a negative prognostic factor, with the hazard of dying calculated as approximately 5% greater for each increase of 10 micrograms/dL in serum creatinine. Necropsy results of 31 cats enrolled in the study demonstrated hepatic lipidosis in 7, nephritis in 5, as well as other diseases such as cholangitis, pancreatitis, and a variety of other diseases in one or two individuals each. Amyloid deposits were found in the pancreatic islets of 20 of the 31 necropsied cats, and 25 of the 31 had a decreased number of islet cells.
Aust Vet J. April 2013;91(4):131-6.
Sedation of hyperthyroid cats with subcutaneous administration of alfaxalone and butorphanol.
Ramoo S, Bradbury LA, et al.
Comments: Alfaxalone is a relatively new neurosteroid injectable anesthetic agent. It is in use in cats in Australia, where it was developed, Europe, and Canada, and will probably be launched in the USA soon. Twenty client-owned hyperthyroid cats were enrolled in this prospective, single-center observational study. The patients were examined and then sedated with alfaxalone, 3 mg/kg, and butorphanol, 0.2 mg/kg, given subcutaneously. The animals were evaluated every 15 minutes for a total of 45 minutes for sedation level, heart rate, respiratory rate, and blood pressure. Cats were considered sufficiently sedated for oral administration of radioactive iodine (I-131; this is effective when given orally, and is actually given orally to human patients in a juice drink, but concerns about vomiting, gagging, patient struggling, and spillage of the drug during administration makes per os administration an unattractive route for cats) if the gag reflex was still intact and there was minimal patient resistance. Maximum median sedation score was reached 45 minutes after administration; significant decreases in respiratory rates occurred at 15, 30, and 45 minutes post-administration. The lowest mean heart and respiratory rates and blood pressures occurred at 30 minutes post-administration. Based on the results of this study, the subcutaneous alfaxalone-butorphanol combination may be a useful sedative for cats undergoing short procedures, but this study was limited to hyperthyroid cats, who are frequently hypertensive and tachycardic to begin with. Evaluation of the effects of this drug combination on cardiovascular parameters in euthyroid cats is required before it can be recommended for this population.
Emerg Infect Dis. July 2013;19(7):1066-73.
Mutation in spike protein cleavage site and pathogenesis of feline coronavirus.
Licitra BN, Millet JK, et al.
Comments: The presence of two biotypes of feline coronaviruses (FCoV), one, feline enteric coronavirus (FECV), relatively benign and the cause of subclinical, generally self-limiting enteric infections, and the other, feline infectious peritonitis virus (FIPV), a cause of systemic and fatal disease, has long posed a diagnostic and therapeutic conundrum. FIPV is thought to originate when mutation of the FECV allows the virus to infect feline blood monocytes and tissue macrophages, facilitating the development of FIP. Exactly how this mutation occurs is unknown.
As RNA viruses, coronaviruses mutate quickly, so replication is very error-prone. The outer surface of the viral particle is covered with spike proteins that activate the virus when they are cleaved by the right protease enzyme from the host cell. This study focused on a functional cleavage site at the boundary between the S1 and S2 subunits of the FECV spike protein. Using FIPV RNA obtained from tissues of cats in which FIP infection was confirmed postmortem by immunohistochemistry, these researchers found a junction mutation at the S1/S2 cleavage site that arises during development of FIP; one or more amino acids at this cleavage site are different from those present at the same site in FECV. It is possible that these mutations enhance cleavability at S1/S2 by proteases specific to monocytes and macrophages. Several of these proteases are listed in this paper; in particular, matrix metalloproteinase 9 is known to be upregulated in activated monocytes and macrophages during FIP infection. This study has documented the first known molecular basis for FIP development, which may pave the way for effective diagnostic, treatment, and preventative measures against this devastating disease.
Mamm Genome. October 2013;24(9-10):400-8.
Multiple mutant T alleles cause haploinsufficiency of brachyury and short tails in Manx cats.
Buckingham KJ, McMillan MJ, et al.
Comments: Almost all mammals possess a tail, with the exception of humans and great apes. The brachyury (from Greek brachus (short) and oura (tail)) gene, now called the T gene, is complex, and was first studied in mice. It affects not only tail length but sacral vertebrae in heterozygotes; in homozygous animals the mutation is lethal in early embryonic development. The T gene has a conserved role in defining the midline of bilaterian organisms such as chordates and molluscs. Five cat breeds have abnormal tail length: the Manx is the most well-known, and there are four others: the American Bobtail, the Kurilian Bobtail, the Japanese Bobtail, and the Pixie-Bob.
These researchers sequenced the T gene in several independent lineages of Manx cats from the USA and the Isle of Man, and found four mutations, three of which were deletions and one duplication/deletion in this gene. Ninety-five percent of the Manx with short-tail phenotypes were heterozygous for T mutations, and the mutant alleles were observed to be largely lineage-specific. One of the mutant T alleles found in Manx cats was shared with American Bobtails and Pixie-Bobs. The brachyury gene is less capable of causing transcription of a protein than the wild-type gene for normal tail length. This is an example of haploinsufficiency, a condition in which a diploid organism has only one single functional copy of a gene (the other copy being inactivated by mutation) that does not facilitate enough protein transcription to bring about a normal condition, in this case normal tail length in a cat.