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Objective: To evaluate the effects of nephrotomy on renal function in clinically normal cats., Animals: 20 specific-pathogen-free, 9- to 11-month-old female mixed-breed cats., Procedure: Serum chemistry analyses, CBC determinations, urinalyses, microbiologic urine cultures, renal ultrasonography, abdominal radiography, and single-kidney and total glomerular filtration rate (GFR) determinations by use of renal scintigraphy and measurements of plasma disappearance of technetium 99m-diethylenetriaminepentaacetic acid were performed before surgery and at 3, 12, 26, 52, and 78 weeks after surgery in 10 cats that underwent unilateral nephrotomy and in 10 control cats that underwent a sham surgical procedure., Results: Two cats (1 from each group) did not complete the study, and their data were eliminated from analyses. Unilateral nephrotomy resulted in a 10% to 20% reduction in mean single-kidney GFR, compared with that of nephrotomy contralateral control kidneys. However, mean total GFR in nephrotomy-group cats was not significantly different from that of sham-group cats. Over the 78 weeks of study, mean total GFR declined 34% and 40% in nephrotomy- and sham-group cats, respectively. Adverse events associated with nephrotomy included persistent microscopic hematuria, renal pelvis hyperechogenicity with distant shadowing on ultrasonographic evaluation, dilatation of renal pelves, and hydronephrosis., Conclusions and Clinical Relevance: Nephrotomy in normal functioning feline kidneys results in a modest relative reduction in renal function, compared with contralateral kidney controls, but has minimal effect on total GFR when compared with sham-operated control cats. However, any detrimental effects of nephrotomy may be magnified in cats with diseased kidneys, which may have little or no capacity for repair or compensation.