Description

Chronic kidney disease (CKD) is reported in 1-3% of cats with an estimated one-third of cats developing CKD in their lifetime. In the US, 15% of adults, 37 million people, have CKD. In both cases, the disease prevalence increases with age: an estimated 38% of people over 65 years old and approximately 30% to 80% of cats over 15 years old live with CKD. While glomerular disease, damage directly to the glomeruli, is usually the primary cause of CKD in humans and dogs, it is quite rare in cats. In feline patients tubulointerstitial fibrosis, deposition of connective tissue in the functional portions of the kidney, is the primary cause of CKD. However, in all species the final common pathways for CKD is thought to be renal fibrosis and hypoxia. There is no effective treatment that slows the progression of renal fibrosis for either cats or humans. Although there are similarities between the disease in these species, a significant difference exists in the etiology of CKD. In humans, the two primary causes are Type 2 diabetes and hypertension while in cats it is often of idiopathic origin.

Disease etiology

Hypertension and diabetes are leading causes of human CKD. Diabetes has not been identified as a risk factor for feline CKD, and hypertension appears to be a complication rather than etiology of feline CKD. Less common causes of CKD in both species include congenital kidney malformations (e.g. polycystic kidney disease), genetic diseases (e.g. amyloidosis), neoplasia, immune-mediated inflammation, infection, toxins, and ischemia. Unlike in humans, many feline CKD cases are idiopathic with non-specific tubulointerstitial inflammation and fibrosis. In areas of Central America, Europe, and Asia there are reports of idiopathic tubulointerstitial disease in humans, particularly sugar cane workers.  High temperatures may cause repeated episodes of acute kidney injury (AKI) in these individuals as chronic dehydration and repeat episodes of AKI may be a cause of feline CKD. Age related changes (telomere shortening, loss of repair functions) also likely play a role in feline CKD as incidence greatly increases with age. 

Clinical presentation

Shared clinical signs/associated conditions of CKD include polyuria, anorexia, lethargy, anemia, hypertension, nausea/vomiting, weight loss, renal secondary hyperparathyroidism, hyperkalemia, kidney stones, pyelonephritis, proteinuria, and hyperphosphatemia. Cats may have poor hair coat, polydipsia, halitosis, and constipation, while humans may experience insomnia, decreased mental acuity, muscle cramps/twitching, peripheral edema, GI ulcers, and persistent itching. Detection and staging of CKD involves blood tests to measure BUN and creatinine, urinalyses to assess specific gravity and proteinuria, and blood pressure monitoring. Imaging is used to identify kidney abnormalities. Glomerular filtration rate and kidney biopsy are often performed in humans but less frequent in cats. Studies are ongoing to determine if SDMA, used in veterinary medicine for early CKD detection, is reliable in humans. Urinary cytokines may be indirect measures of renal inflammation, directly correlate to kidney function, and serve as a non-invasive test for CKD progression. 

Treatment

CKD is a serious, life-threatening disease in both humans and cats. Treatments have traditionally focused on managing symptoms and slowing disease progression, including diet changes and medications to lower blood pressure, treat anemia, bind phosphate, and inhibit the renin-angiotensin-aldosterone system. Symptom management in cats often includes subcutaneous fluids, anti-nausea medications, and appetite stimulants. For severe cases, dialysis and kidney transplants are used primarily in humans and less commonly in cats. Dogs and humans tend to have proteinuria early in the disease process due to underlying glomerular disease, so angiotensin converting enzyme inhibitors and angiotensin receptor blockers are commonly used; feline patients usually present with proteinuria later in disease. Recent advances in treatments for CKD include new therapeutics to treat anemia and immunosuppressants to aid in kidney transplants. Research is ongoing to evaluate the potential for stem cell therapy to help restore kidney function, and CRISPR technology is being studied as a potential therapy when kidney disease has a genetic etiology.

Recent Publications

References

Brown CA, Elliott J, Schmiedt CW, Brown SA. Chronic kidney disease in aged cats: clinical features, morphology, and proposed pathogeneses. Vet Pathol. 2016; 53(2):309–326.

Habenicht LM, Webb TL, Clauss LA, Dow SW, Quimby JM. Urinary cytokine levels in apparently healthy cats and cats with chronic kidney disease. J Feline Med Surg. 2013;15(2):99-104.

Lawson J, Elliott J, Wheeler-Jones C, Syme H, Jepson R. Renal fibrosis in feline chronic kidney disease: known mediators and mechanisms of injury. Vet J, 2015; 203(1):18-26.

Lawson JS, Liu HH, Syme HM, Purcell R, Wheeler-Jones CPD, Elliott J. The cat as a naturally occurring model of renal interstitial fibrosis: characterization of primary feline proximal tubular epithelial cells and comparative pro-fibrotic effects of TGF-β1. PLoS One. 2018;13(8):e0202577.

McLeland SM, Cianciolo R, Duncan C, Quimby JM. A comparison of biochemical and histopathologic staging in cats with chronic kidney disease. Vet Pathol. 2015;52(2):524-534.

McLeland S, Quimby J, Lappin MR. Alpha-enolase staining patterns in the renal tissues of cats with and without chronic kidney disease. Vet Immune Immunopathol. 2019;212:23-26.

McLeland SM, Lunn KF, Duncan CG, Refsal KR, Quimby JM. Relationship among serum creatinine, serum gastrin, calcium-phosphorus product, and uremic gastropathy in cats with chronic kidney disease. J Vet Int Med. 2014;28(3):827-837.

Quimby JM, Dow SW. Novel treatment strategies for feline chronic kidney disease: A critical look at the potential of mesenchymal stem cell therapy. Vet J. 2015;204(3):241-246.

Quimby JM. Feline chronic kidney disease: understanding pathophysiology is the key to development of new treatments. Vet J 2015; 203(3):265-266. 

Quimby JM, Maranon DG, Battaglia CL, McLeland SM, Brock WT, Bailey SM. Feline chronic kidney disease is associated with shortened telomeres and increased cellular senescence. Am J Physiol Renal Physiol. 2013;305(3):F295-F303. 

Quimby JM, Webb TL, Gibbons DS, et al. Evaluation of intrarenal mesenchymal stem cell injection for treatment of chronic kidney disease in cats.  J Feline Med Surg. 2011;13(6):418.

Quimby JM, Webb TL, Habernicht L, et al.  Safety and efficacy of intravenous infusion of allogeneic cryopreserved mesenchymal stem cells for treatment of chronic kidney disease in cats: Results of three sequential pilot studies. Stem Cell Res and Ther. 2013;4(2):48.

Quimby JM, Webb TL, Randall E, et al. Assessment of intravenous adipose-derived allogeneic mesenchymal stem cells for the treatment of feline chronic kidney disease: a randomized, placebo-controlled clinical trial in 8 cats.  J Feline Med Surg. 2015;8(2):165.

Summers S, Quimby JM, Isaiah A, Suchodolski JS, Lunghofer PJ, Gustafson DL. The fecal microbiome and serum concentrations of indoxyl sulfate and p-cresol sulfate in cats with chronic kidney disease. J Vet Intern Med. 2019;33(2):662-669.

Thomson AL, Berent AC, Weisse C, et al. Intra-arterial renal infusion of autologous mesenchymal stem cells for treatment of chronic kidney disease in cats: phase 1 clinical trial. J Vet Intern Med. 2019;33(3):1353.

Vidane AS, Pinheiro AO, Casals JB, et al. Transplantation of amniotic membrane-derived multipotent cells ameliorates and delays the progression of chronic kidney disease in cats. Reprod Domest Anim. 2017;52(Suppl 2):316.