Background: The purpose of our study was to quantify the extent of kidney involvement during a two-stage approach for PJI. Methods: We conducted a multidisciplinary, retrospective evaluation of all infected total hip arthroplasty (THA) and total knee arthroplasty (TKA) patients treated with a two-stage approach utilizing antibiotic impregnated cement spacers from August 2007-July 2011 at our institution. Data collected included demographics, medical co-morbidities, surgical data as well as risk factors for kidney injury, such as nephrotoxic agents, hypotensive episodes and baseline kidney function. Results: Acute Kidney Injury (AKI) occurred in 7/34 (21%) of patients at a median of 147 days (52-596 days) and represents the time with the antibiotic cement spacer. Six additional patients showed a doubling of serum creatinine concentrations over baseline beyond the first 48 hours after surgery, giving a total incidence of 47% of post-operative kidney injury. Serum creatinine concentrations recovered to baseline in 44% (7/16) of patients. Two patients underwent dialysis for persistent elevated creatinine. Kidney injury was more likely among older patients (HR 1.4 for every 10 year increase, confidence interval [CI] 1.2-2.6; p<0.01), those with Chronic Kidney Disease represented by a lower eGFR at baseline (HR 0.7 for every 10 ml/min higher baseline eGFR, CI 0.5-0.9, p<0.01) and cardiovascular disease (CVD) (HR 4.7, CI 1.6-13.6, p<0.01). Conclusions: Kidney injury with elevation of serum creatinine over baseline occurs frequently following the first stage of a two-stage revision arthroplasty using antibiotic cement spacers, especially in patients with baseline comorbidities. Changes in kidney function after surgery are multi-factorial therefore further prospective studies are necessary to understand the causes and consequences.