Continuous variables were expressed as median with interquartile range and were compared using the Mann-Whitney test. Categorical variables were expressed as number with percentage and were compared using the Chi-square test. Other covariates were selected using the backward elimination method by likelihood ratio test. CKD was used as a covariate rather than eGFR as the latter was not significantly associated with postoperative AKI when analyzed as a continuous variable.
Model fit was assessed with the Hosmer-Lemeshow goodness-of-fit test. As there were only patients with the outcome postoperative AKI , it was not possible to include several possible confounders in the logistic regression analyses.
To maximize the inclusion of possible confounders, the analyses were also performed using propensity score PS. The discrimination of the model was assessed using the c-statistic and receiver operating characteristic curve.
We performed three different sensitivity analyses: PS adjustment, PS matching, and inverse probability weighting. The PS quintiles were treated as a categorical variable.
PS matching was also performed. The odds of postoperative AKI in a propensity-matched cohort were examined using logistic regression analyses. P values were determined using the Mann-Whitney U test or Chi-square test. All analyses were performed using SPSS version The study protocol and waiver of consents were approved by the Ethics Committee of Kyoto Katsura Hospital and the study was conducted in accordance with the Declaration of Helsinki.
During the study period, 3, patients underwent non-cardiac surgeries under general anesthesia at Kyoto Katsura Hospital. Thus 2, patients were eligible for analyses. One hundred thirty-seven patients 5. In-hospital mortality was 1. Preoepratively, patients Patients with AKI were significantly older, more likely to be males, more likely to have undergone intra-thoracic, intra-abdominal or emergency surgeries, and more likely to have significantly lower eGFR, higher BMI and more comobidities, preoperatively.
Twenty-two patients were given diuretics during surgery to maintain urine output. The p value by Hosmer-Lemeshow test was 0. Other covariates significantly associated with the development of AKI included male sex, intra-thoracic surgery, intra-abdominal surgery, surgery with large fluid shifts, emergency surgery, the presence of CKD, BMI, the use of insulin, hypertension, CVA, pre-operative hematocrit and intra-operative use of vasopressors.
Demographics of the propensity-matched patients were well-balanced S1 and S2 Tables. Thus, inverse probability weighting was also performed as a sensitivity analysis. The results were similar to those of other analyses Table 3.
To examine whether propensity for diuretic use would affect the effect size of diuretic use, the associations of diuretic use and postoperative AKI were examined in each PS quintile for diuretic use. Among 99 diuretic users, 63 patients used loop diuretics, 23 used thiazides, 26 used potassium-sparing diuretics, and one used carperitide the sum exceeds 99 as 13 received both a loop and a potassium-sparing diuretics and 1 received both a thiazide and a potassium-sparing diuretics.
Diuretic use was significantly associated with postoperative AKI among patients with low propensity for diuretic use. Preoperative use of diuretics was not a significant predictor of AKI after cardiac surgery [ 15 , 18 , 19 ]. The reasons for this discrepancy are not completely clear. Whether ACE-I or ARB increases or decreases the risk of postoperative AKI might be determined by the balance between their beneficial effects on cardiac function and their effects of decreasing glomerular filtration pressure via dilation of efferent arterioles.
The surgical techniques used in these studies also differed on-pump, off-pump or both. Cardiopulmonary bypass was shown to increase plasma renin activity [ 36 ] and thus the effects of ACE-I or ARB could differ between on- and off-pump cardiac surgery. On the other hand, patients undergoing non-cardiac surgery are less likely to have left ventricular dysfunction than those undergoing cardiac surgery.
We speculated that the hemodynamic effect of these agents on kidneys would predominate and that they would be independently associated with AKI after non-cardiac surgery. Our cohort included only 7 0. As a result, the proportion of patients in this study who developed postoperative AKI was much lower 5. It is of note, however, that the use of diuretics was significantly associated with the development of postoperative AKI though patients in our study seemed to have renal reserve.
During the postoperative period, fluids shift from the intravascular space to the third space and administration of diuretics may exacerbate the intravascular volume contraction.
This may explain the significant increase in the risk of postoperative AKI observed in our study. Our results differed from those of several previous studies focusing on non-cardiac surgery.
The sample sizes and number of outcomes postoperative AKI were smaller than in our study and logistic regression models were either overfitted [ 26 ] or insufficiently adjusted [ 28 ]. In this study, we performed not only logistic regression analyses but also PS adjustment, PS matching, and inverse probability weighting to confirm the results and there were a very small number of patients with missing data.
Shah M et al. Their study included both patients undergoing cardiac and non-cardiac surgery and there was no subgroup analysis in the non-cardiac surgery cohort. In our study, the presence of CKD was not a significant effect modifier. We found that diuretic use was significantly associated with postoperative AKI but only in patients with a low propensity for diuretic use Fig 1.
It is suggested that elevated venous pressure is associated with worsening renal function, and animal studies demonstrated improvements in renal function after venous pressure was lowered [ 38 — 40 ]. Thus, in patients with high propensity for diuretic use, the benefit of avoiding volume overload might have offset the risk of volume contraction.
On the other hand, in patients with a low propensity for diuretic use, such as those with essential hypertension or those who received diuretics only to maintain urine output, diuretics might have resulted in intravascular volume contraction and caused postoperative AKI.
Among the different classes of diuretics, only loop diuretics were significantly associated with postoperative AKI. This is likely because it is the most potent diuretic and it causes greater intravascular volume contraction than other agents [ 41 ].
However, it is possible that the observed difference was due to the lack of statistical power with thiazides or other agents, leading to low accuracy of parameter estimates. The strength of our study is that our cohort included a large number of patients who underwent non-cardiac surgery at a community hospital and who were representatives of those being treated in a general medical practice setting.
We selected as many potential predictors of post-operative AKI as possible based on previous studies [ 5 — 30 ], and the covariates used for multivariable logistic regression analyses and PS estimation were more complete than those in previous studies [ 5 — 30 ]. Multivariable logistic regression analyses, PS adjustment, PS matching, and inverse probability weighting yielded similar results.
Our study also had several limitations. As this was an observational study, the possibility of unknown confounders cannot be excluded. Also, the relatively small number of patients with CKD precluded subgroup analysis in these patients. PS was estimated using the demographics at the time of preoperative evaluation, not those at the time of drug initiation. The effect size of diuretics was greater in patients with low propensity for diuretic use.
While the observational nature of our study did not establish causality and randomized controlled trials are warranted, it may be prudent to withhold diuretics preoperatively or to refrain from administering diuretics with the sole goal of maintain urine output in non-cardiac surgery, considering the minimal downsides of this approach in patients with preserved cardiac and renal function.
In unadjusted model, only quintiles of PS were included as covariates. National Center for Biotechnology Information , U.
PLoS One. Published online Jul 6. Dirce Maria Trevisan Zanetta, Editor. Author information Article notes Copyright and License information Disclaimer. Competing Interests: The authors have declared that no competing interests exist. Received Jan 29; Accepted Jun This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
This article has been cited by other articles in PMC. S1 Table: Demographics of the patients matched on propensity score for diuretic use. S3 Table: Odds ratio of postoperative acute kidney injury by inverse-probability weight test. Design, Setting, Participants, and Measurements This was a retrospective observational study.
Results There were AKI cases 5. Introduction Postoperative acute kidney injury AKI is a serious complication of surgical procedures that is associated not only with short-term increases in mortality [ 1 — 3 ] but also with long-term complications such as development of chronic kidney disease [ 4 ]. Statistical Methods Continuous variables were expressed as median with interquartile range and were compared using the Mann-Whitney test. Table 1 Clinical characteristics of patients.
Open in a separate window. Ethics Statement The study protocol and waiver of consents were approved by the Ethics Committee of Kyoto Katsura Hospital and the study was conducted in accordance with the Declaration of Helsinki. Results During the study period, 3, patients underwent non-cardiac surgeries under general anesthesia at Kyoto Katsura Hospital. Table 2 Multivariable logistic regression analysis. Table 3 Comparison of odds ratio of postoperative acute kidney injury estimated by different statistical analyses.
Fig 1. Odds ratio of postoperative acute kidney injury in diuretic user in each quintile of propensity score for diuretic use. TIF Click here for additional data file.
S1 Table Demographics of the patients matched on propensity score for diuretic use. DOCX Click here for additional data file. S3 Table Odds ratio of postoperative acute kidney injury by inverse-probability weight test. Funding Statement The authors have no support or funding to report. Data Availability All relevant data are within the paper and its Supporting Information files. References 1. Minimal changes of serum creatinine predict prognosis in patients after cardiothoracic surgery: a prospective cohort study.
J Am Soc Nephrol ; 15 : — Perioperative increases in serum creatinine are predictive of increased 90 day mortality after coronary artery bypass graft surgery. Circulation ; [ Suppl 1 ]: I — Independent association between acute renal failure and mortality following cardiac surgery.
Am J Med ; : — Temporary perioperative decline of renal function is an independent predictor for chronic kidney disease. Clin J Am Soc Nephrol ; 5 : — FDA Resources. Arms and Interventions. Outcome Measures. Primary Outcome Measures : Proportion of patients developing hypotension during the operative period. Eligibility Criteria. Information from the National Library of Medicine Choosing to participate in a study is an important personal decision.
Inclusion Criteria: All adults referred to preoperative assessment clinics by surgeons for elective non-cardiac surgery who routinely take furosemide.
Patients who take furosemide only on an 'as needed basis' rather than 'regularly'. Those patients who take less than 10 mg of furosemide daily Those patients who are undergoing local anesthetic only surgical procedures Patients who are unwilling or unable to give informed consent.
Contacts and Locations. Information from the National Library of Medicine To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials. More Information. Layout table for additonal information Responsible Party: Dr. National Library of Medicine U. National Institutes of Health U. Department of Health and Human Services. The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Drug: furosemide Drug: placebo. Phase 4. Study Type :. Interventional Clinical Trial.
Actual Enrollment :. Study Start Date :. Actual Primary Completion Date :. Actual Study Completion Date :. Experimental: 1 furosemide. Drug: furosemide for patients on chronic furosemide therapy, patients are randomized to furosemide at their previous dose or placebo given in identical form to ensure masking.
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