this study was a historical cohort conducted at a 1,000 bed community , teaching hospital . there was no funding received for the study , and all data collection and analysis was completed by the primary author . patients who had received intravenous contrast in 2011 were screened , via use of a random number generator , for inclusion into the study . patients who met inclusion criteria had at least two of the following characteristics : baseline serum creatinine 1.2 mg / dl or a creatinine clearance < 50 ml / min ( calculated via cockcroft  gault equation ) , age > 75 years , diabetes mellitus noted in their past medical history , systolic heart failure with documented ejection fraction < 40% , and/or hypertension evidenced by their past medical history or active use of antihypertensives . in addition , patients had to have a serum creatinine level drawn at baseline ( within 1 month prior to receiving contrast ) and within 1296 hours following contrast administration . excluded patients were those < 18 years of age , those who were pregnant or breast feeding , and those who were receiving dialysis prior to or during the study period . a list of all patients who received intravenous contrast during the defined study period was generated . from this list , an additional filter was added to separate patients who had also received n - acetylcysteine from patients who had not received n - acetylcysteine . patients from these two lists ( those who received n - acetylcysteine and those who did not ) were selected randomly . data on patients included in these two groups were then collected and analyzed ( fig . the primary outcome was the absolute difference in the proportion of patients who developed cin with and without the administration of n - acetylcysteine . cin was defined as a 0.5 mg / dl increase in serum creatinine or a 25% increase in serum creatinine within 1296 hours post - exposure to contrast . secondary outcomes included sub - analysis of the primary outcome according to patients with diabetes mellitus , patients aged > 75 years , patients with systolic heart failure , and patients with hypotension ( systolic blood pressure < 90 mmhg ) immediately prior to contrast administration ; absolute difference in blood urea nitrogen ( bun ) post - exposure to contrast ; and proportion of patients with an elevation in serum creatinine of at least 0.3 mg / dl . on the basis of reported rates of cin in previous studies , the anticipated incidence of cin without n - acetylcysteine was 15% . for the primary outcome , we determined that 302 patients would provide a power of 80% to detect a 10% absolute risk reduction ( arr ) with a two - sided alpha level of 0.05 . this study was a historical cohort conducted at a 1,000 bed community , teaching hospital . there was no funding received for the study , and all data collection and analysis was completed by the primary author . patients who had received intravenous contrast in 2011 were screened , via use of a random number generator , for inclusion into the study . patients who met inclusion criteria had at least two of the following characteristics : baseline serum creatinine 1.2 mg / dl or a creatinine clearance < 50 ml / min ( calculated via cockcroft  gault equation ) , age > 75 years , diabetes mellitus noted in their past medical history , systolic heart failure with documented ejection fraction < 40% , and/or hypertension evidenced by their past medical history or active use of antihypertensives . in addition , patients had to have a serum creatinine level drawn at baseline ( within 1 month prior to receiving contrast ) and within 1296 hours following contrast administration . excluded patients were those < 18 years of age , those who were pregnant or breast feeding , and those who were receiving dialysis prior to or during the study period . patients were identified through electronic prescription numbers in the electronic medical record . a list of all patients who received intravenous contrast during the defined study period was generated . from this list , an additional filter was added to separate patients who had also received n - acetylcysteine from patients who had not received n - acetylcysteine . patients from these two lists ( those who received n - acetylcysteine and those who did not ) were selected randomly . data on patients included in these two groups were then collected and analyzed ( fig . the primary outcome was the absolute difference in the proportion of patients who developed cin with and without the administration of n - acetylcysteine . cin was defined as a 0.5 mg / dl increase in serum creatinine or a 25% increase in serum creatinine within 1296 hours post - exposure to contrast . secondary outcomes included sub - analysis of the primary outcome according to patients with diabetes mellitus , patients aged > 75 years , patients with systolic heart failure , and patients with hypotension ( systolic blood pressure < 90 mmhg ) immediately prior to contrast administration ; absolute difference in blood urea nitrogen ( bun ) post - exposure to contrast ; and proportion of patients with an elevation in serum creatinine of at least 0.3 mg / dl . the primary hypothesis was that n - acetylcysteine would reduce the incidence of cin . on the basis of reported rates of cin in previous studies , the anticipated incidence of cin without n - acetylcysteine was 15% . for the primary outcome , we determined that 302 patients would provide a power of 80% to detect a 10% absolute risk reduction ( arr ) with a two - sided alpha level of 0.05 . the majority of patients had co - morbidities of diabetes and/or hypertension , with more patients with diabetes present in the group not receiving n - acetylcysteine compared to the group that did receive n - acetylcysteine . when comparing baseline renal function , mean pre - contrast serum creatinine in patients receiving n - acetylcysteine was 1.41 mg / dl compared to 0.95 mg / dl in those not receiving n - acetylcysteine ( p=0.0001 ) . baseline characteristics scr = serum creatinine , crcl = creatinine clearance ( as estimated by cockcroft  gault ) , bun = blood urea nitrogen , ibw = ideal body weight . cin occurred in 14 ( 9.3% ) patients who received n - acetylcysteine and in 27 ( 17.9% ) patients who did not ( arr 8.6% , p=0.0428 ) ( table 4 ) . the mean increase in serum creatinine post - contrast in patients receiving n - acetylcysteine and patients not receiving of the 41 patients who developed cin , 16 met both criteria in the definition of cin . twenty - four patients met the definition solely based on a relative increase in serum creatinine of 25% , and one patient met the definition solely based on an absolute increase in serum creatinine of 0.5 mg / dl . cin = contrast - induced nephropathy , bun = blood urea nitrogen , scr = serum creatinine . secondary outcomes are presented in table 4 . in a subgroup analysis of the primary outcome , significant differences in the incidence of cin were seen in patients aged at least 75 years and in patients with a history of hypertension . a significant difference was also noted in the percent change in bun . in the overall population ( n=302 ) , 77% of patients received fluids either prior to or immediately following contrast administration ; however , the mean percentage was different between the two study groups . in the group of patients receiving n - acetylcysteine , 85% of patients received fluids compared to only 69% of patients in the group that did not receive n - acetylcysteine . patients who received fluids had a lower incidence of cin than patients who did not receive fluids ( 10.8% vs. 22.9% , respectively ; p=0.0157 ) . the effect of fluid administration in the overall population , in those receiving n - acetylcysteine ( p=0.0411 ) , and in those not receiving n - acetylcysteine ( p=0.2561 ) , is presented in fig . the majority of patients had co - morbidities of diabetes and/or hypertension , with more patients with diabetes present in the group not receiving n - acetylcysteine compared to the group that did receive n - acetylcysteine . when comparing baseline renal function , mean pre - contrast serum creatinine in patients receiving n - acetylcysteine was 1.41 mg / dl compared to 0.95 mg / dl in those not receiving n - acetylcysteine ( p=0.0001 ) . baseline characteristics scr = serum creatinine , crcl = creatinine clearance ( as estimated by cockcroft  gault ) , bun = blood urea nitrogen , ibw = ideal body weight . cin occurred in 14 ( 9.3% ) patients who received n - acetylcysteine and in 27 ( 17.9% ) patients who did not ( arr 8.6% , p=0.0428 ) ( table 4 ) . the mean increase in serum creatinine post - contrast in patients receiving n - acetylcysteine and patients not receiving of the 41 patients who developed cin , 16 met both criteria in the definition of cin . twenty - four patients met the definition solely based on a relative increase in serum creatinine of 25% , and one patient met the definition solely based on an absolute increase in serum creatinine of 0.5 mg / dl . cin = contrast - induced nephropathy , bun = blood urea nitrogen , scr = serum creatinine . secondary outcomes are presented in table 4 . in a subgroup analysis of the primary outcome , significant differences in the incidence of cin were seen in patients aged at least 75 years and in patients with a history of hypertension . in the overall population ( n=302 ) , 77% of patients received fluids either prior to or immediately following contrast administration ; however , the mean percentage was different between the two study groups . in the group of patients receiving n - acetylcysteine , 85% of patients received fluids compared to only 69% of patients in the group that did not receive n - acetylcysteine . patients who received fluids had a lower incidence of cin than patients who did not receive fluids ( 10.8% vs. 22.9% , respectively ; p=0.0157 ) . the effect of fluid administration in the overall population , in those receiving n - acetylcysteine ( p=0.0411 ) , and in those not receiving n - acetylcysteine ( p=0.2561 ) , is presented in fig . in this historical cohort , we evaluated the use of n - acetylcysteine for the prevention of cin . based on the primary outcome , n - acetylcysteine is likely associated with a lower incidence of cin . patients included in this cohort had to have at least two risk factors for the development of cin . ( 2 ) , the majority of patients in this cohort would have been at a 7.514% risk of developing cin by our definition . the incidence of cin in patients not receiving n - acetylcysteine was approximately 18% , which is just above the average incidence in previously reported studies ( 15.7% ) ( 4 ) . similarly , in patients who did receive n - acetylcysteine , the incidence of cin in our study was similar to the average incidence reported in previous literature ( 4 ) ( 9.3% vs. 8.9% , respectively ) . this suggests that patients reviewed in this study were at similar baseline risk to those patients reviewed by others previously . in addition , this study analyzed the effect of fluids , both with regard to use and non - use of n - acetylcysteine , since adequate hydration has been shown to be effective in preventing cin . the definition of cin and the risk factors for cin used in this study are well agreed upon in the literature . in addition to the primary outcome being analyzed with a commonly accepted definition of cin , other important markers used to describe acute kidney injury and cin were included as secondary outcomes ( absolute change in serum creatinine and change in bun ) ( 14 , 15 ) . first , the retrospective nature of the study does not allow for cause and effect relationships to be analyzed , and we are only able to support an association between the incidence of cin and n - acetylcysteine use . second , the dose , route , and frequency of n - acetylcysteine were not analyzed in this study . all patients who received n - acetylcysteine received at least 600 mg / dose and received at least a total of four doses surrounding contrast administration , but no consistent pattern of administration was enforced . for example , some patients received one dose of n - acetylcysteine before contrast and three after , while others received two doses before and three after , and so on . this is a potential confounder as previous literature suggests that certain dosing strategies may be associated with better outcomes ( 16 , 17 ) . selection bias is a factor due to patients in the group receiving n - acetylcysteine having worse renal function at baseline . this is likely reflective of healthcare professionals being more likely to order n - acetylcysteine in patients with poor renal function at baseline due to the potential benefit seen in previous literature . in addition , there was an observed difference in the percentage of patients in each group that received intravenous fluids . since fluids are considered the first - line preventative strategy for cin , the difference in use could impact the results of this study . finally , while the study did meet power for the primary outcome , it is possible that the non - significant results noted in some subgroups is a result of type ii error . despite the limitations presented above , this study may provide information that can be used for the prevention of cin . in this time of nationwide drug shortages , based on the subgroup analysis of the primary outcome , a protocol can be developed that takes into account the patients at the highest risk for cin development . in addition to helping identify those at the highest risk , a protocol could help with the establishment of more consistent n - acetylcysteine dosing . developing this type of protocol would likely reduce drug cost and allow n - acetylcysteine to be used more resourcefully . this study conducted in a community , teaching hospital may provide information to healthcare professionals in numerous health - system settings . specifically , other community - based hospitals can use the data presented here to tailor or develop n - acetylcysteine protocols . while this study was retrospective , future prospective studies , analyzing a larger number of patients with various risk factors , would help in the development of a protocol for the optimal use of n - acetylcysteine . ideally , these future studies would take into account confounding factors such as the use of nephrotoxic drugs and the dosing strategy of n - acetylcysteine . in conclusion , n - acetylcysteine was likely associated with a lower rate of cin in patients at risk for cin development . subgroup analyses reveal patients who may have the greatest benefit , specifically those aged 75 years and those with a history of hypertension . the authors have not received any funding or benefits from industry or elsewhere to conduct this study .