Research Update: Does FIV play a role in the development of chronic kidney disease in cats?

Chronic kidney disease (CKD) is common in cats, although in most cases the triggering toxic, infectious, or hypoxemic event remains undetermined. Commonly recognized causes include toxins such as nonsteroidal anti-inflammatory drugs (NSAIDs), ethylene glycol, and toxic plants; renal lymphosarcoma; pyelonephritis; polycystic kidney disease; ischemia (e.g. as a consequence of hypotension during anesthesia); and ureteral obstruction.

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In people, an association between human immunodeficiency virus (HIV) retroviral infection and renal failure secondary to glomerular disease is well-established. Previous studies comparing cats infected with feline immunodeficiency virus (FIV) with uninfected cats have demonstrated that FIV-infected animals are more likely to be azotemic and proteinuric.1 However, no study has specifically evaluated the prevalence of FIV infection in cats with idiopathic CKD, which the authors of this study hypothesized would be higher than in nonazotemic cats.

The authors prospectively enrolled cats presenting to two Australian veterinary hospitals over a 14-month period in this case-control study; this study period was prior to the introduction of the FIV vaccine to Australia, so false positive diagnosis of FIV due to vaccine-induced circulating antibodies was minimal. CKD was defined as concurrent serum creatinine concentration > 2 mg/dl (180 mol/L) and urine specific gravity < 1.035. The authors excluded any cats for which a presumptive or definitive cause of renal disease had been identified.

Age, sex, breed, creatinine concentration, urine specific gravity, and results of FIV antibody testing were collected from 73 cats with CKD and from 69 control cats with no laboratory evidence of CKD evaluated at the same hospitals over the same time period. The control group included both sick and healthy cats, and any cat with a concurrent medical condition that may be associated with kidney damage (e.g. urinary tract infection, hypokalemia, hyperthyroidism) was excluded. FIV antibody testing was performed using the anti-Gp40 antibody test, and a single positive result was considered diagnostic for FIV infection.

Twelve of 73 cats with CKD (16.4%) and six of 69 cats in the control group (8.7%) were infected with FIV based on antibody testing. Multivariable regression analysis revealed that FIV infection was significantly associated with CKD in cats less than 11 years of age, with an odds ratio of 10 that cats in this age group would be infected with FIV if CKD had been diagnosed. However, the presence of CKD in cats 11 years of age or older was not associated with a change in odds of infection with FIV.

COMMENTARY

Up to 40% of HIV-positive people develop variable degrees of lentivirus-associated nephropathy, which may be associated with glomerular damage, proteinuria, and progressive decreases in renal function. The abnormal histologic findings that have been associated with HIV infection are the collapsing form of focal segmental glomerulosclerosis with secondary microcystic tubular dilation.

Cats infected with FIV are known to be more likely to be proteinuric and azotemic than uninfected cats, and glomerulosclerosis, microcystic tubular dilation, a thickened Bowman's membrane, mononuclear interstitial infiltrates, and fibrosis have been reported, suggesting a possibly similar pathogenesis as that seen in people.1,2 Viral replication has been demonstrated in feline renal tubular cells in cats naturally infected with FIV by use of immunohistochemistry for the p24 viral antigen and polymerase chain reaction analysis for viral gag DNA and RNA sequences.3 Collectively, these findings support the authors' hypothesis of an association between FIV and the initiation and evolution of renal disease in cats.

Nevertheless, a direct pathogenic effect of FIV infection has been difficult to determine because of the many factors that alter the course of disease. For example, ethnicity (i.e. genetic background) significantly affects the risk of HIV-associated nephropathy in people, and coinfection with other viruses. In cats, coinfection with calicivirus is usually required for development of FIV-associated stomatitis and may be indirect evidence that uncharacterized environmental or genetic factors may be critical for the development of FIV-induced kidney disease, if such causal relationship exists. As demonstrated in this study, age may play an unclear role in whether FIV is associated with CKD. Concurrent diseases, the cat's overall health, and the viral strain or viral load may also be important factors that were not evaluated by these authors.

This study suggests that testing for FIV infection should be part of the diagnostic evaluation in young or middle-aged cats with CKD. It is still premature to conclude that the demonstrated association implies causality. For example, the presence of both diseases in younger animals may be due to these animals being more likely to lead indoor-outdoor lives and, therefore, exposed to risk factors that increase the likelihood of each disease separately. If the association between these two diseases in younger animals does hold true in the future, it may be that FIV is not found as commonly in the older CKD population because of a more rapid progression of disease in FIV-infected cats and, therefore, decreased survival. Regardless, this study establishes that additional studies are merited to investigate a causal association between lentiviral infection and kidney damage in cats and to determine whether survival time in young cats with CKD is affected by concurrent FIV infection.

White JD, Malik R, Norris JM, et al. Association between naturally occurring chronic kidney disease and feline immunodeficiency virus infection status in cats. J Am Vet Med Assoc 2010;236(4):424-429.

The information in "Research Updates" was provided by Erika Meler, DVM, MS, and Barrak Pressler, DVM, PhD, DACVIM, Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Purdue University, West Lafayette, IN 47907.

REFERENCES

1. Levy JK. CVT Update: feline immunodeficiency virus. In: Bonagura JD, ed. Kirk's current veterinary therapy XIII: small animal practice. Philadelphia, Pa: WB Saunders Co, 2000;284-291.

2. Baxter KG, Levy JK, Edinboro CH, et al. Renal disease in cats infected with feline immunodeficiency virus (abstr). J Vet Intern Med 2010;24:677.

3. Poli A, Abramo F, Matteucci D, et al. Renal involvement in feline immunodeficiency virus infection: p24 antigen detection, virus isolation and PCR analysis. Vet Immunol Immunopathol 1995;46(1-2):13-20.