{"doi":"10.1152/ajprenal.00100.2020","title":"Depletion of macrophages slows the early progression of renal injury in obese Dahl salt-sensitive leptin receptor mutant rats","abstract":"Recently, we reported that obese Dahl salt-sensitive (SS) leptin receptor mutant (SS LepR mutant) rats display progressive renal injury. The present study demonstrated that the early development of renal injury in the SS LepR mutant strain is associated with an increase in the renal infiltration of macrophages compared with lean SS rats. We also examined whether depletion of macrophages with clodronate would reduce the early progression of renal injury in the SS LepR mutant strain. Four-week-old SS and SS LepR mutant rats were treated with either vehicle (PBS) or clodronate (50 mg/kg ip, 2 times/wk) for 4 wk. While the administration of clodronate did not reduce renal macrophage infiltration in SS rats, clodronate decreased macrophages in the kidneys of SS LepR mutant rats by >50%. Interestingly, clodronate significantly reduced plasma glucose, insulin, and triglyceride levels and markedly improved glucose tolerance in SS LepR mutant rats. Treatment with clodronate had no effect on the progression of proteinuria or renal histopathology in SS rats. In the SS LepR mutant strain, proteinuria was markedly reduced during the first 2 wk of treatment (159 ± 32 vs. 303 ± 52 mg/day, respectively). However, after 4 wk of treatment, the effect of clodronate was no longer observed in the SS LepR mutant strain (346 ± 195 vs. 399 ± 50 mg/day, respectively). The kidneys from SS LepR mutant rats displayed glomerular injury with increased mesangial expansion and renal fibrosis versus SS rats. Treatment with clodronate significantly decreased glomerular injury and renal fibrosis in the SS LepR mutant strain. Overall, these data indicate that the depletion of macrophages improves metabolic disease and slows the early progression of renal injury in SS LepR mutant rats.","journal":"American Journal of Physiology-Renal Physiology","year":2020,"id":78645,"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":17,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9541,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":409170,"name":"Corbin A. Shields","orcid":"0000-0003-2607-051X","position":1,"is_corresponding":false},{"id":410434,"name":"Andrea K. Brown","orcid":null,"position":2,"is_corresponding":false},{"id":409171,"name":"Ubong S. Ekperikpe","orcid":"0000-0002-9962-5371","position":3,"is_corresponding":false},{"id":410435,"name":"Tyler Johnson","orcid":null,"position":4,"is_corresponding":false},{"id":302878,"name":"Denise C. Cornelius","orcid":"0000-0002-6730-6499","position":5,"is_corresponding":false},{"id":302881,"name":"Jan M. Williams","orcid":"0000-0002-7078-9567","position":6,"is_corresponding":false},{"id":409169,"name":"Bibek Poudel","orcid":"0000-0003-1353-7002","position":0,"is_corresponding":true}],"reference_count":35,"raw_metadata":null,"created_at":"2026-07-18T21:50:09.793321Z","pmid":"32390513","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":[]}