{"doi":"10.3389/fvets.2021.646087","title":"Chemokine Therapy in Cats With Experimental Renal Fibrosis and in a Kidney Disease Pilot Study","abstract":"Background: Chronic tubulointerstitial fibrosis is a common final pathway leading to end stage kidney disease in cats and has no effective treatment. The use of cell-based molecules to treat kidney fibrosis may be a promising approach. The objectives were to test the effects of intra-renal chemokine CXCL12 injection in a pre-clinical cat model of unilateral ischemia/reperfusion (I/R)-induced kidney fibrosis and then, within a clinical pilot study, test the safety/feasibility of CXCL12 injection in cats that might have early chronic kidney disease (CKD). Methods: Pre-clinical : Thirty cats received intra-renal injection of 100, 200, or 400 ng of recombinant human CXCL12, or sterile saline, into the I/R kidney 70 days post-injury, or were non-injured, non-injected controls ( n = 6/group). Kidney collagen content was quantified 4 months post-treatment using Masson's Trichrome and Picrosirius Red (PSR) stained tissues. In a separate study ( n = 2) exploring short-term effects of CXCL12, 200 ng CXCL12 was injected into I/R kidneys and then harvested either 30 min ( n = 1) or 1 month ( n = 1) post-injection. Kidney concentrations of CXCL12, matrix metalloproteinase 1 (MMP-1), and lysyl oxidase-like enzyme 2 (LOXL-2) were quantified via ELISA. Clinical Pilot : 14 client-owned cats with potential early kidney disease received a single-treatment, bilateral intra-renal injection of 200 ng CXCL12 ( n = 7), or received no injection ( n = 7). Blood/urine samples were collected monthly for 9 months to assess renal function and CKD staging. Results: Pre-clinical : I/R increased the affected kidney collagen content, which both mid and high doses of CXCL12 restored to normal ( ps < 0.05 vs. untreated). I/R increased collagen fiber width, which both mid and high doses of CXCL12 restored to normal ( p < 0.001 vs. untreated). Early changes in kidney MMP-1, associated with collagen breakdown, and subsequent decreases in LOXL-2, associated with collagen cross-linking, in response to CXCL12 treatment may contribute to these findings. Clinical Pilot : Bilateral intra-renal injection of CXCL12 using ultrasound guidance in cats with CKD was feasible and safe in a general practice clinical setting with no obvious side effects noted during the 9-month follow-up period. Conclusions: Intra-renal injection of CXCL12 may prove to be an effective treatment for kidney fibrosis in cats with CKD. Additional mechanistic and clinical evaluations are needed.","journal":"Frontiers in Veterinary Science","year":2021,"id":196922,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9631,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":770830,"name":"Shannon Lankford","orcid":null,"position":1,"is_corresponding":false},{"id":770831,"name":"Renata S. Magalhaes","orcid":null,"position":2,"is_corresponding":false},{"id":770832,"name":"Douglas Shankle","orcid":null,"position":3,"is_corresponding":false},{"id":307709,"name":"Jason Fanning","orcid":"0000-0002-5527-1698","position":4,"is_corresponding":false},{"id":770833,"name":"Cucu Kartini","orcid":null,"position":5,"is_corresponding":false},{"id":770161,"name":"Irma Herawati Suparto","orcid":"0000-0003-1682-6467","position":6,"is_corresponding":false},{"id":770834,"name":"Winda Kusumawardhani","orcid":null,"position":7,"is_corresponding":false},{"id":770835,"name":"M. ArRaniri Putra","orcid":null,"position":8,"is_corresponding":false},{"id":770162,"name":"Silmi Mariya","orcid":"0000-0002-6714-1276","position":9,"is_corresponding":false},{"id":770163,"name":"Gopal Badlani","orcid":"0000-0002-3158-8092","position":10,"is_corresponding":false},{"id":770164,"name":"J. Koudy Williams","orcid":"0000-0002-4610-6412","position":11,"is_corresponding":false},{"id":770829,"name":"Julie Bennington","orcid":null,"position":0,"is_corresponding":true}],"reference_count":87,"raw_metadata":null,"created_at":"2026-07-18T23:50:19.568641Z","pmid":"33748219","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}