Characterization of Kidney Injury Molecule‐1 in Cats

Bland, S Karlyn; Côté, Olivier; Clark, Mary E.; Delay, J; Bienzle, Dorothee

doi:10.1111/jvim.12428

Cited by 10 publications

(20 citation statements)

References 52 publications

(70 reference statements)

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“…As expected, the S3 portion of the proximal tubules were affected by this hypoxic insult. 16 These early changes were followed by chronic changes of interstitial fibrosis, tubular atrophy, and mononuclear cell inflammation both diffusely within the corticomedullary junction and as linear foci within the cortex, similar to those seen in cats with naturally occurring CKD (Fig. 12).…”

Section: Pathogenesis Of Feline Ckdsupporting

confidence: 60%

Chronic Kidney Disease in Aged Cats

et al. 2016

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Chronic kidney disease (CKD) is the most common metabolic disease of domesticated cats, with most affected cats being geriatric (>12 years of age). The prevalence of CKD in cats exceeds that observed in dogs, and the frequency of the diagnosis of CKD in cats has increased in recent decades. Typical histologic features include interstitial inflammation, tubular atrophy, and fibrosis with secondary glomerulosclerosis. In contrast to people and dogs, primary glomerulopathies with marked proteinuria are remarkably rare findings in cats. Although a variety of primary renal diseases have been implicated, the disease is idiopathic in most cats. Tubulointerstitial changes, including fibrosis, are present in the early stages of feline CKD and become more severe in advanced disease. A variety of factors-including aging, ischemia, comorbid conditions, phosphorus overload, and routine vaccinations-have been implicated as factors that could contribute to the initiation of this disease in affected cats. Factors that are related to progression of established CKD, which occurs in some but not all cats, include dietary phosphorus intake, magnitude of proteinuria, and anemia. Renal fibrosis, a common histologic feature of aged feline kidneys, interferes with the normal relationship between peritubular capillaries and renal tubules. Experimentally, renal ischemia results in morphologic changes similar to those observed in spontaneous CKD. Renal hypoxia, perhaps episodic, may play a role in the initiation and progression of this disease.

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Section: Pathogenesis Of Feline Ckdsupporting

confidence: 60%

Chronic Kidney Disease in Aged Cats

et al. 2016

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“…KIM-1 is among the most promising markers to detect injury of proximal tubules in humans and rats, and we previously identified KIM-1 in kidney tissue of cats with AKI due to ischemia/reperfusion (I/R) injury. 26,27 Attempts to use the human and rat Renastick (BioAssay Works) to detect feline urine KIM-1 resulted in inconsistent or no results, despite histologic evidence of kidney injury. 26,27 Therefore, feline-specific KIM-1 monoclonal antibodies were generated and configured into an LFA.…”

Section: Discussionmentioning

confidence: 99%

“…26,27 Attempts to use the human and rat Renastick (BioAssay Works) to detect feline urine KIM-1 resulted in inconsistent or no results, despite histologic evidence of kidney injury. 26,27 Therefore, feline-specific KIM-1 monoclonal antibodies were generated and configured into an LFA. The LFA was then used to measure KIM-1 in urine of healthy and diseased cats.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, the feline KIM-1 gene (fKIM-1) and protein were characterized; using a cross-reactive antibody, KIM-1 was detected in urine and tissue of cats with critical illness and suspected AKI. 26,27 In cats, as in other species, KIM-1 localized to the proximal tubule. More specifically, in an injury model of 45 mins of ischemia followed by reperfusion, KIM-1 was transiently expressed in S1 and S2, and persistently in S3 segments of proximal tubules.…”

Section: Introductionmentioning

confidence: 91%

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A specific immunoassay for detection of feline kidney injury molecule 1

Bland

Clark

Côté

et al. 2018

Journal of Feline Medicine and Surgery

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Objectives The aim of this study was to design and carry out a preliminary evaluation of a urine point-of-care test for kidney injury molecule 1 (KIM-1) in healthy and diseased cats. Methods Part of the feline KIM-1 gene was amplified, ligated into a plasmid with a signal peptide and monomeric human IgGFc, and transfected into a mammalian cell line. Supernatant was purified and tested for the fusion protein by gel electrophoresis and Western blot. Mice were immunized three times with purified proteins, and hybridomas were generated from splenocytes. Antibodies were tested by ELISA for detection of recombinant KIM-1 and naturally occurring KIM-1 in disease-state urine. Next, a lateral flow assay (LFA) with capture and detection antibodies was constructed, and tested with 34 urine samples from healthy and diseased cats. Antibodies were also tested for reactivity with formalin-fixed paraffin-embedded kidney tissue. Results Three antibodies were assessed. Antibodies detected between 0.4 and 60 ng/ml feline KIM-1 fusion protein in the LFA. Urine samples from healthy cats yielded faint bands in the LFA corresponding to optical density (OD) values of 4.8–8.8. Samples from cats with suspected or confirmed acute kidney injury (AKI) had OD values ranging from 1.6–20.5. Urine KIM-1 varied over multiple days in cats with sepsis or urethral obstruction despite normalizing serum creatinine concentration. In tissue sections, KIM-1 antibodies labeled tubular cells with morphological features of injury. Conclusions and relevance A practical patient-side assay for detection of KIM-1 in feline urine has been developed. Preliminary results show marked though transient increases in cats with sepsis and urethral obstruction-associated AKI, and expression in injured tubules. Although initial data indicating that the LFA is sensitive and specific for KIM-1 in cats with AKI are promising, values associated with different types of injury, urine collection, urine storage and specific gravity need to be investigated.

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“…KIM-1 gene and protein have been characterized in cats, and the protein has been detected in urine of critically ill cats but not those that were clinically healthy. 9 However, precise location of KIM-1 in kidney tissue and changes in expression with injury are unknown. Aquaporin-1 (AQP-1), previously identified in feline kidney tissue, functions to regulate water transport in proximal renal tubules and red blood cells.…”

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confidence: 99%

Expression of Kidney Injury Molecule-1 in Healthy and Diseased Feline Kidney Tissue

et al. 2017

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Sensitive markers to detect acute kidney injury (AKI) in cats are lacking. Kidney injury molecule-1 (KIM-1) is a promising marker of acute tubular injury in humans, and sequence and structure of feline KIM-1 have been determined. KIM-1 is shed into urine of cats with natural AKI. The objectives of this study were to characterize temporal and cellular expression of KIM-1 in kidneys from cats without and with experimental and natural AKI using histopathology and immunohistochemistry. Tissue sections from 8 cats without kidney disease, 3 to 4 cats with experimentally induced AKI on each day 1, 3, 6, and 12 after unilateral ischemia/reperfusion, and 9 cats with natural AKI were assessed. In sections from cats without kidney disease, patterns of periodic acid-Schiff and aquaporin-1 staining allowed identification of 3 distinct segments of the proximal tubule. KIM-1 staining was absent in segments 1 (S1) and S2, and faint in S3. Injury of S3 in cats with experimental and natural AKI was characterized by cell loss and necrosis, and remaining intact cells had cytoplasmic blebs and reduced brush borders. In experimental AKI, intensity of KIM-1 expression increased in proportion to the severity of injury and was consistently present in S3 but only transiently in other segments. Vimentin was absent in proximal tubules of healthy cats but expressed in injured S3. These findings indicate that S3 is the proximal tubular segment most susceptible to ischemic injury and that KIM-1 is a sensitive tissue indicator of AKI in cats.

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Characterization of Kidney Injury Molecule‐1 in Cats

Cited by 10 publications

References 52 publications

Chronic Kidney Disease in Aged Cats

Chronic Kidney Disease in Aged Cats

A specific immunoassay for detection of feline kidney injury molecule 1

Expression of Kidney Injury Molecule-1 in Healthy and Diseased Feline Kidney Tissue

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