{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:35:01Z","timestamp":1760060101702,"version":"build-2065373602"},"reference-count":39,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,7,31]],"date-time":"2025-07-31T00:00:00Z","timestamp":1753920000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Veterinary Sciences"],"abstract":"<jats:p>Protein-losing nephropathy (PLN) involves a heterogeneous group of pathologies leading to selective glomerular damage and development of renal disease. ICGN, the main cause of PLN, requires immunosuppressive treatment. However, the scientific evidence in veterinary medicine on immunosuppressive therapeutic schemes in this condition is limited. The aim of this study is to describe the clinical and paraclinical evolution of five dogs with PLN, presumably associated with ICGN, treated with chlorambucil as immunosuppressive monotherapy. Suspected IGCN was established by the presence of a urine protein\u2013creatinine ratio (UPC) \u2265 3 without response to standard therapy, hypoalbuminemia &lt; 2, or progressive azotemia. Patients were treated with a dosage range of chlorambucil from 0.16 to 0.4 mg\/kg (mean 0.25 mg\/kg) every 24 h as the sole immunosuppressant. In the end, 4\/5 patients showed significant clinical improvement, 3\/3 had resolution of the nephrotic syndrome, 5\/5 had a sustained decrease in UPC values during follow-up and no relevant adverse effects were observed. In this report, chlorambucil proved to be a well-tolerated and potentially effective monotherapy for immune-mediated PLN in dogs.<\/jats:p>","DOI":"10.3390\/vetsci12080721","type":"journal-article","created":{"date-parts":[[2025,8,5]],"date-time":"2025-08-05T15:56:16Z","timestamp":1754409376000},"page":"721","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Chlorambucil Monotherapy in Dogs with Protein-Losing Nephropathy of Probable Immune Origin: A Preliminary Study"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4573-9944","authenticated-orcid":false,"given":"Felipe","family":"D\u00edaz-Soler","sequence":"first","affiliation":[{"name":"Escuela de Medicina Veterinaria, Facultad de Medicina y Ciencias de la Salud, Universidad Mayor, Santiago 8580745, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda Jos\u00e9","family":"Bernal","sequence":"additional","affiliation":[{"name":"Escuela de Medicina Veterinaria, Facultad de ciencias de la Vida, Universidad Andr\u00e9s Bello, Santiago 8370251, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4951-9669","authenticated-orcid":false,"given":"Franco","family":"Gonzalez","sequence":"additional","affiliation":[{"name":"Escuela de Medicina Veterinaria, Facultad de Medicina y Ciencias de la Salud, Universidad Mayor, Santiago 8580745, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ismael","family":"Pereira","sequence":"additional","affiliation":[{"name":"Escuela de Medicina Veterinaria, Facultad de Medicina y Ciencias de la Salud, Universidad Mayor, Santiago 8580745, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francisco","family":"Abusleme","sequence":"additional","affiliation":[{"name":"Escuela de Medicina Veterinaria, Facultad de Medicina y Ciencias de la Salud, Universidad Mayor, Santiago 8580745, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7735-1218","authenticated-orcid":false,"given":"Daniela","family":"Siel","sequence":"additional","affiliation":[{"name":"Escuela de Medicina Veterinaria, Facultad de Medicina y Ciencias de la Salud, Universidad Mayor, Santiago 8580745, Chile"},{"name":"Centro de Biomedicina, Universidad Mayor, Santiago 8580745, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Dadousis, C., Whetton, A.D., Mwacalimba, K., Merlo, A., Wright, A., and Geifman, N. (2024). Renal Disease in Cats and Dogs-Lessons Learned from Text-Mined Trends in Humans. Animals, 14.","DOI":"10.3390\/ani14233349"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1136\/vr.103059","article-title":"Incidence of and mortality from kidney disease in over 600,000 insured Swedish dogs","volume":"176","author":"Pelander","year":"2015","journal-title":"Vet. Rec."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1111\/jvim.12090","article-title":"Chronic kidney disease in dogs in UK veterinary practices: Prevalence, risk factors, and survival","volume":"27","author":"Elliott","year":"2013","journal-title":"J. Vet. Intern. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1977","DOI":"10.1111\/jvim.15322","article-title":"Factors associated with survival in dogs with chronic kidney disease","volume":"32","author":"Rudinsky","year":"2018","journal-title":"J. Vet. Intern. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"393","DOI":"10.2460\/javma.2005.226.393","article-title":"Evaluation of the association between initial proteinuria and morbidity rate or death in dogs with naturally occurring chronic renal failure","volume":"226","author":"Jacob","year":"2005","journal-title":"J. Am. Vet. Med. Assoc."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1144","DOI":"10.1038\/ki.1986.120","article-title":"Canine chronic renal disease: Prevalence and types of glomerulonephritis in the dog","volume":"29","author":"Macdougall","year":"1986","journal-title":"Kidney Int."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1459","DOI":"10.1111\/jvim.14796","article-title":"European Veterinary Renal Pathology Service: A Survey Over a 7-Year Period (2008\u20132015)","volume":"31","author":"Aresu","year":"2017","journal-title":"J. Vet. Intern. Med."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Crivellenti, L.Z., Silva, G.E., Borin-Crivellenti, S., Cianciolo, R., Adin, C.A., Dantas, M., Dos Anjos, D.S., Tinucci-Costa, M., and Santana, A.E. (2016). Prevalence of Glomerulopathies in Canine Mammary Carcinoma. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0164479"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"S67","DOI":"10.1111\/jvim.12247","article-title":"Prevalence of immune-complex glomerulonephritides in dogs biopsied for suspected glomerular disease: 501 cases (2007\u20132012)","volume":"27","author":"Schneider","year":"2013","journal-title":"J. Vet. Intern. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e17301","DOI":"10.1111\/jvim.17301","article-title":"Analysis of survival among biopsy-determined categories of kidney disease in dogs","volume":"39","author":"Schultz","year":"2025","journal-title":"J. Vet. Intern. Med."},{"key":"ref_11","first-page":"156","article-title":"Current data regarding the etiopathogenesis of glomerular and tubular disorders associated with kidney diseases in small animals: A review","volume":"35","author":"Pasca","year":"2025","journal-title":"Rev. Rom. Med. Vet."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1681\/ASN.2011030304","article-title":"Basic and translational concepts of immune-mediated glomerular diseases","volume":"23","author":"Couser","year":"2012","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.cvsm.2010.09.006","article-title":"Protein-losing nephropathy in small animals","volume":"41","author":"Littman","year":"2011","journal-title":"Vet. Clin. N. Am. Small Anim. Pract."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1177\/0300985815579996","article-title":"World Small Animal Veterinary Association Renal Pathology Initiative: Classification of Glomerular Diseases in Dogs","volume":"53","author":"Cianciolo","year":"2016","journal-title":"Vet. Pathol."},{"key":"ref_15","first-page":"S27","article-title":"Consensus recommendations for standard therapy of glomerular disease in dogs","volume":"27","author":"Brown","year":"2013","journal-title":"J. Vet. Intern. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2478","DOI":"10.1111\/jvim.15958","article-title":"Efficacy of telmisartan for the treatment of persistent renal proteinuria in dogs: A double-masked, randomized clinical trial","volume":"34","author":"Coleman","year":"2020","journal-title":"J. Vet. Intern. Med."},{"key":"ref_17","first-page":"S55","article-title":"Consensus guidelines for immunosuppressive treatment of dogs with glomerular disease absent a pathologic diagnosis","volume":"27","author":"Pressler","year":"2013","journal-title":"J. Vet. Intern. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1111\/jsap.13065","article-title":"Occurrence, management and outcome of immune-complex glomerulonephritis in dogs with suspected glomerulopathy in the UK","volume":"60","author":"Vessieres","year":"2019","journal-title":"J. Small Anim. Pract."},{"key":"ref_19","first-page":"S44","article-title":"Consensus recommendations for immunosuppressive treatment of dogs with glomerular disease based on established pathology","volume":"27","author":"Segev","year":"2013","journal-title":"J. Vet. Intern. Med."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Chiarenza, D.S., Verrina, E.E., La Porta, E., Caridi, G., Ghiggeri, G.M., Mortari, G., Lugani, F., Angeletti, A., and Bigatti, C. (2024). Biologics and Non-Biologics Immunosuppressive Treatments for IgA Nephropathy in Both Adults and Children. J. Clin. Med., 13.","DOI":"10.3390\/jcm13092465"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2036","DOI":"10.1016\/S0140-6736(16)00272-5","article-title":"Primary glomerulonephritides","volume":"387","author":"Floege","year":"2016","journal-title":"Lancet"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2567","DOI":"10.1093\/ckj\/sfad164","article-title":"Oral glucocorticoids with intravenous cyclophosphamide or oral glucocorticoids alone in the treatment of IgA nephropathy present with nephrotic syndrome and mesangioproliferative glomerulonephritis","volume":"16","author":"Du","year":"2023","journal-title":"Clin. Kidney J."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1016\/j.cvsm.2022.01.009","article-title":"Glucocorticoids, Cyclosporine, Azathioprine, Chlorambucil, and Mycophenolate in Dogs and Cats: Clinical Uses, Pharmacology, and Side Effects","volume":"52","author":"Viviano","year":"2022","journal-title":"Vet. Clin. N. Am. Small Anim. Pract."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Lai, Y.-Y., Horta, R.D.S., Valenti, P., and Giuliano, A. (2024). Retrospective Safety Evaluation of Combined Chlorambucil and Toceranib for the Treatment of Different Solid Tumours in Dogs. Animals, 14.","DOI":"10.3390\/ani14233420"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1111\/j.1365-3164.2004.00360.x","article-title":"Pemphigus: Current therapy","volume":"15","author":"Rosenkrantz","year":"2004","journal-title":"Vet. Dermatol."},{"key":"ref_26","unstructured":"Miller, W.H., Griffin, C.E., and Campbell, K.L. (2013). Autoimmune and Immune-Mediated Dermatoses. Muller and Kirk\u2019s Small Animal Dermatology, Elsevier Saunders. [8th ed.]."},{"key":"ref_27","first-page":"1465","article-title":"Immunosuppressive agents for treating IgA nephropathy","volume":"4","author":"Samuels","year":"2003","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1111\/j.1939-1676.2010.0669.x","article-title":"Comparison of signalment, clinicopathologic findings, histologic diagnosis, and prognosis in dogs with glomerular disease with or without nephrotic syndrome","volume":"25","author":"Klosterman","year":"2011","journal-title":"J. Vet. Intern. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1016\/j.pop.2020.08.002","article-title":"Nephrotic Syndrome","volume":"47","author":"Politano","year":"2020","journal-title":"Prim. Care"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Crivellenti, L.Z., Cintra, C.A., Maia, S.R., Silva, G.E.B., Borin-Crivellenti, S., Cianciolo, R., Adin, C.A., Tinucci-Costa, M., Pennacchi, C.S., and Santana, A.E. (2021). Glomerulotubular pathology in dogs with subclinical ehrlichiosis. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0260702"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1667","DOI":"10.1111\/jvim.14573","article-title":"Clinicopathologic and Histopathologic Renal Abnormalities in Dogs with Coccidioidomycosis","volume":"30","author":"Mehrkens","year":"2016","journal-title":"J. Vet. Intern. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1556\/avet.55.2007.4.10","article-title":"Histological and ultrastructural studies of renal lesions in Babesia canis infected dogs treated with imidocarb","volume":"55","year":"2007","journal-title":"Acta Vet. Hung."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1177\/0300985812459336","article-title":"Light and electron microscopic analysis of consecutive renal biopsy specimens from leishmania-seropositive dogs","volume":"50","author":"Aresu","year":"2013","journal-title":"Vet. Pathol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"101752","DOI":"10.1016\/j.ttbdis.2021.101752","article-title":"Mapping the distribution and risk factors of Anaplasmataceae in wild and domestic canines in Chile and their association with Rhipicephalus sanguineus species complex lineages","volume":"12","author":"Cevidanes","year":"2021","journal-title":"Ticks Tick Borne Dis."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1111\/vde.13253","article-title":"Pharmacology of drugs used in autoimmune dermatopathies in cats and dogs: A narrative review","volume":"35","author":"Tham","year":"2024","journal-title":"Vet. Dermatol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2215","DOI":"10.1111\/jvim.16209","article-title":"A retrospective study of adverse effects of mycophenolate mofetil administration to dogs with immune-mediated disease","volume":"35","author":"Fukushima","year":"2021","journal-title":"J. Vet. Intern. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1111\/vec.12791","article-title":"Consensus on the rational use of antithrombotics in veterinary critical care (CURATIVE): Domain 2\u2014Defining rational therapeutic usage","volume":"29","author":"Goggs","year":"2019","journal-title":"J. Vet. Emerg. Crit. Care"},{"key":"ref_38","first-page":"538","article-title":"Glomerular disease","volume":"Volume 1","author":"Bartges","year":"2011","journal-title":"Nephrology and Urology of Small Animals"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1111\/j.1939-1676.2010.0474.x","article-title":"Progressive juvenile glomerulonephropathy in 16 related French Mastiff (Bordeaux) dogs","volume":"24","author":"Day","year":"2010","journal-title":"J. Vet. Intern. Med."}],"container-title":["Veterinary Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2306-7381\/12\/8\/721\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:19:48Z","timestamp":1760033988000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2306-7381\/12\/8\/721"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,31]]},"references-count":39,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2025,8]]}},"alternative-id":["vetsci12080721"],"URL":"https:\/\/doi.org\/10.3390\/vetsci12080721","relation":{},"ISSN":["2306-7381"],"issn-type":[{"type":"electronic","value":"2306-7381"}],"subject":[],"published":{"date-parts":[[2025,7,31]]}}}