Tubulointerstitial fibrosis is a classic histologic feature of chronic kidney disease (CKD) in cats and a final common pathway toward end-stage renal disease. Domesticated cats have been used in models of ischemia-induced renal fibrosis. The objective of this study was to evaluate the performance of 2 variations of a transient unilateral renal ischemia and delayed contralateral nephrectomy model of tubulointerstitial fibrosis in cats. Purpose-bred, young adult, domesticated cats underwent 90 min of surgically induced ischemia to the right kidney followed by delayed contralateral nephrectomy performed 21 d (RI-CN21d group; n = 10) or 90 d postischemia (RI-CN90d group; n = 12). Control cats underwent sham surgery followed by left nephrectomy 21 d after (sham-CN group; n = 3). Renal functional parameters, including glomerular filtration rate and serum creatinine concentration, were evaluated before and after surgeries. The right kidneys were harvested 120 d postischemia/ sham. Renal histology with lesion scoring and histomorphometry for quantification of smooth muscle actin immunolabeling and collagen staining were performed on harvested kidneys. Severe acute kidney injury prompted euthanasia after left nephrectomy in 5/10 (50.0%), 2/12 (16.7%), and 0/3 (0%) of cats in the RI-CN21d, RI-CN90d, and sham-CN groups, respectively. A significant decrease in glomerular filtration rate by day 120, relative to baseline, occurred in cats in the RI-CN21d group (P < 0.001) and RI-CN90d group (P < 0.001) but not the sham-CN group (P = 0.76). All but one cat in the ischemia groups were azotemic at the study end. Kidneys subjected to ischemia had higher interstitial inflammation, tubular atrophy, and fibrosis scores compared with sham-operated kidneys. There were significant increases in smooth muscle actin immunolabeling and collagen staining in these kidneys, relative to the contralateral kidneys. In summary, 90 min of unilateral renal ischemia and delayed contralateral nephrectomy induced histologic and biochemical changes consistent with CKD in cats. A 90-d period between ischemia and nephrectomy resulted in improved survivability of the model.

OBJECTIVETo report acute and chronic outcomes of cats with chronic kidney disease (CKD) induced by a remnant kidney model.ANIMALS32 purpose-bred cats (n = 15 female, n = 17 male).PROCEDURESCats underwent a 2-stage reduction in renal mass through partial arterial ligation of 1 kidney (day 28) and delayed contralateral nephrectomy (day 0), targeting an 11/12th functional nephrectomy. Acute (days 28 to 29) survival and renal function parameters were compared over time, and the latter were evaluated as predictors for acute mortality. Chronic (days 30 to >1,100) survival, renal function, and morphology were described.RESULTSAcutely, renal function deteriorated in all cats (mean ± SD baseline and day 28 serum creatinine mean concentration, 1.13 ± 0.23 mg/dL and 3.03 ± 1.20 mg/dL, respectively; P < .001; and GFR, 3.22 mL/min/kg ± 0.12 and 1.21 mL/min/kg ± 0.08, respectively; P < .001). Seven (22%) cats were euthanized because of clinical signs of uremia after partial nephrectomy. Prenephrectomy renal function tests were not significant indicators for survival during this acute phase. Twenty-five cats entered the chronic phase. Ten cats were euthanized at a median of 163 days from nephrectomy because of progressive renal dysfunction. Median survival times were significantly different when stratified by acute kidney injury grade at day 29. Cats in the chronic phase had clinical courses similar to cats with naturally occurring CKD, and most (13/15) were in CKD stage 2.CLINICAL RELEVANCEThe remnant kidney model is effective at reducing kidney function to an extent that mimics important characteristics of spontaneous CKD in cats.

OBJECTIVE To use RNA sequencing (RNAseq) to characterize renal transcriptional activities of genes associated with proinflammatory and profibrotic pathways in ischemia-induced chronic kidney disease (CKD) in cats. SAMPLES Banked renal tissues from 6 cats with experimentally induced CKD (renal ischemia [RI] group) and 9 healthy cats (control group). PROCEDURES Transcriptome analysis with RNAseq, followed by gene ontology and cluster analyses, were performed on banked tissue samples of the right kidneys (control kidneys) from cats in the control group and of both kidneys from cats in the RI group, in which unilateral (right) RI had been induced 6 months before the cats were euthanized and the ischemic kidneys (IKs) and contralateral nonischemic kidneys (CNIKs) were harvested. Results for the IKs, CNIKs, and control kidneys were compared to identify potential differentially expressed genes and overrepresented proinflammatory and profibrotic pathways. RESULTS Genes from the gene ontology pathways of collagen binding (eg, transforming growth factor-β1), metalloendopeptidase activity (eg, metalloproteinase [MMP]-7, MMP-9, MMP-11, MMP-13, MMP-16, MMP-23B, and MMP-28), chemokine activity, and T-cell migration were overrepresented as upregulated in tissue samples of the IKs versus control kidneys. Genes associated with the extracellular matrix (eg, TIMP-1, fibulin-1, secreted phosphoprotein-1, matrix Gla protein, and connective tissue growth factor) were upregulated in tissue samples from both the IKs and CNIKs, compared with tissues from the control kidneys. CONCLUSIONS AND CLINICAL RELEVANCE Unilateral ischemic injury differentially altered gene expression in both kidneys, compared with control kidneys. Fibulin-1, secreted phosphoprotein-1, and matrix Gla protein may be candidate biomarkers of active kidney injury in cats.

Increased gene transcription of hypoxia-induced mediators of fibrosis in renal tissue has been identified in experimentally induced, ischemic chronic kidney disease (CKD). To characterize hypoxia-induced profibrotic pathways in naturally occurring CKD in cats. Twelve client-owned cats with CKD and 8 healthy control cats. In this prospective, cross-sectional study, bilateral renal tissue samples were assessed histologically for inflammation, tubular atrophy, and fibrosis, and by reverse transcription-quantitative PCR for characterization of transcript levels of hypoxia-inducible factor-1α ( HIF1A ), matrix metalloproteinases-2 ( MMP2 ), -7 ( MMP7 ), and -9 ( MMP9 ), tissue inhibitor of metalloproteinase-1 (TIMP1), transforming growth factor-β1 ( TGFB1 ), and vascular endothelial growth factor-A ( VEGFA ). Linear mixed models were used to compare gene transcription between diseased and healthy kidneys, and to examine the association between transcript levels and serum creatinine concentration for all cats, and between transcript levels and histologic scores of diseased kidneys. Kidneys from cats with CKD had significantly higher transcript levels of HIF1A , MMP2 , MMP7 , MMP9 , TIMP1 , and TGFB1 (all P < .001), and lower levels of VEGFA ( P = .006) than those from control cats. Transcript levels of MMP7 ( P = .05) and TIMP1 ( P = .005) were positively associated with serum creatinine in cats with CKD, but not in control cats. In diseased kidneys, transcript levels of MMP2 ( P = .002), MMP7 ( P = .02), and TIMP1 ( P = .02) were positively, whereas those of VEGFA ( P = .003) were negatively, associated with histologic score severity. Evaluation of the expression of the corresponding proteins in larger populations could identify therapeutic targets and/or biomarkers of tubulointerstitial fibrosis in cats.

Abstract Background Increased gene transcription of hypoxia‐induced mediators of fibrosis in renal tissue has been identified in experimentally induced, ischemic chronic kidney disease (CKD). Objective To characterize hypoxia‐induced profibrotic pathways in naturally occurring CKD in cats. Animals Twelve client‐owned cats with CKD and 8 healthy control cats. Methods In this prospective, cross‐sectional study, bilateral renal tissue samples were assessed histologically for inflammation, tubular atrophy, and fibrosis, and by reverse transcription‐quantitative PCR for characterization of transcript levels of hypoxia‐inducible factor‐1α (HIF1A), matrix metalloproteinases‐2 (MMP2), ‐7 (MMP7), and ‐9 (MMP9), tissue inhibitor of metalloproteinase‐1 (TIMP1), transforming growth factor‐β1 (TGFB1), and vascular endothelial growth factor‐A (VEGFA). Linear mixed models were used to compare gene transcription between diseased and healthy kidneys, and to examine the association between transcript levels and serum creatinine concentration for all cats, and between transcript levels and histologic scores of diseased kidneys. Results Kidneys from cats with CKD had significantly higher transcript levels of HIF1A, MMP2, MMP7, MMP9, TIMP1, and TGFB1 (all P < .001), and lower levels of VEGFA (P = .006) than those from control cats. Transcript levels of MMP7 (P = .05) and TIMP1 (P = .005) were positively associated with serum creatinine in cats with CKD, but not in control cats. In diseased kidneys, transcript levels of MMP2 (P = .002), MMP7 (P = .02), and TIMP1 (P = .02) were positively, whereas those of VEGFA (P = .003) were negatively, associated with histologic score severity. Conclusion and Clinical Significance Evaluation of the expression of the corresponding proteins in larger populations could identify therapeutic targets and/or biomarkers of tubulointerstitial fibrosis in cats.

OBJECTIVE To characterize transcription of profibrotic mediators in renal tissues of cats with ischemia-induced chronic kidney disease (CKD). SAMPLE Banked renal tissues from 6 cats with experimentally induced CKD (RI group) and 8 healthy control cats. PROCEDURES For cats of the RI group, both kidneys were harvested 6 months after ischemia was induced for 90 minutes in 1 kidney. For control cats, the right kidney was evaluated. All kidney specimens were histologically examined for fibrosis, inflammation, and tubular atrophy. Renal tissue homogenates underwent reverse transcription quantitative PCR assay evaluation to characterize gene transcription of hypoxia-inducible factor-1α (HIF-1α), matrix metalloproteinase (MMP)-2, MMP-7, MMP-9, tissue inhibitor of metalloproteinase-1 (TIMP-1), transforming growth factor-β1, and vascular endothelial growth factor A. Gene transcription and histologic lesions were compared among ischemic and contralateral kidneys of the RI group and control kidneys. RESULTS Ischemic kidneys had greater transcript levels of MMP-7, MMP-9, and transforming growth factor-β1 relative to control kidneys and of MMP-2 relative to contralateral kidneys. Transcription of TIMP-1 was upregulated and that of vascular endothelial growth factor A was downregulated in ischemic and contralateral kidneys relative to control kidneys. Transcription of HIF-1α did not differ among kidney groups. For ischemic kidneys, there were strong positive correlations between transcription of HIF-1α, MMP-2, MMP-7, and TIMP-1 and severity of fibrosis. CONCLUSIONS AND CLINICAL RELEVANCE Transcription of genes involved in profibrotic pathways remained altered in both kidneys 6 months after transient renal ischemia. This suggested that a single unilateral renal insult can have lasting effects on both kidneys.

Canine collagen type III glomerulopathy (Col3GP) is a rare juvenile nephropathy in which irregular type III collagen fibrils and fibronectin accumulate in glomerular capillary walls and the mesangium. Necropsy findings were reviewed from 5 puppies diagnosed with Col3GP at 6 to 18 weeks of age. Histologically, with hematoxylin and eosin stain, the glomerular capillary walls and mesangium were diffusely and globally expanded by homogeneous pale eosinophilic material. Ultrastructurally, the subendothelial zone and mesangium were expanded by fibronectin and cross-banded collagen type III fibrils, diagnostic of Col3GP. Two additional stains were employed to identify the material within glomeruli as fibrillar collagen using light microscopy. In all 5 cases, the material was red with picrosirius red and birefringent under polarized light, and was blue with periodic acid-Schiff/hematoxylin/trichrome (PASH/TRI), thereby identifying it as fibrillar collagen. Based on these unique staining characteristics with picrosirius red and PASH/TRI, Col3GP may be reliably diagnosed with light microscopy alone.

Previous work demonstrated renal fibrosis 70 days after a single unilateral in vivo renal ischemic event, but changes associated with a single episode of renal ischemia past this time are unknown. In this study, we evaluated renal function and structural changes 6 months after a 90-minute in vivo unilateral renal ischemic event. Six adult female cats underwent unilateral renal ischemia and renal function was followed for 6 months, at which time the kidneys were evaluated by histology and histomorphometry. Over time, there was a significant reduction in the glomerular filtration rate and an elevation of serum creatinine of 31% and 42%, respectively. All cats had tubulointerstitial lesions characterized by segmental interstitial inflammation, tubular atrophy, and interstitial fibrosis. Unlike short-term studies, ischemic kidneys had variable numbers of obsolescent glomeruli, consistent with the development of atubular glomeruli and subsequent ischemic glomerulosclerosis. Chronic changes associated with acute renal ischemia may include loss of function and glomerulosclerosis.

Reports of raw meat pet food containing zoonotic foodborne bacteria, including Salmonella, Escherichia coli, and Listeria monocytogenes, are increasing. Contaminated raw pet food and biological waste from pets consuming those diets may pose a public health risk. The U.S. Food and Drug Administration Veterinary Laboratory Investigation and Response Network conducted 2 case investigations, involving 3 households with animal illnesses, which included medical record review, dietary and environmental exposure interviews, animal sample testing, and whole genome sequencing (WGS) of bacteria isolated from the pets and the raw pet food. For each case investigation, WGS with core genome multi-locus sequence typing analysis showed that the animal clinical isolates were closely related to one or more raw pet food bacterial isolates. WGS and genomic analysis of paired animal clinical and animal food isolates can confirm suspected outbreaks of animal foodborne illness.

In contrast to pulmonary Langerhans cell histiocytosis (LCH), which is a proliferative disorder of Langerhans cells that affects the lungs and other organs of cats, LCH involving a single organ system has not been documented in cats, to our knowledge. Herein we describe a case of pancreatic LCH in a 9-y-old castrated male Domestic Shorthaired cat that was evaluated for possible renal transplantation. The cat was hypoglycemic, hyperinsulinemic, and azotemic. Ultrasound examination revealed a diffusely enlarged, normoechoic pancreas. The cat was euthanized because of severe renal azotemia and the possibility of pancreatic neoplasia. Grossly, the pancreas was enlarged, and both kidneys were pale white, firm, and had irregular capsular surfaces. Histologically, the pancreas was expanded with interlobular, intraparenchymal, and ductal clusters of round-to-polygonal cells admixed with fibrous connective tissue and scattered lymphocytes. Infiltrating cells had a moderate amount of eosinophilic cytoplasm, round-to-indented nuclei with finely stippled chromatin and 1 or 2 nucleoli, and were strongly immunoreactive for CD18, ionized calcium-binding adapter molecule 1, and e-cadherin. The morphologic and immunohistochemical features of the pancreatic changes were consistent with single-system LCH.