Assessment of the Prognostic Effect of Blood Urea Nitrogen to Serum Albumin Ratio in Patients with Fournier’s Gangrene in a Referral Center Farzad Allameh1, Saeed Montazeri2, Vahid Shahabi2*, Seyyed Ali Hojjati2, Amir Alinejad Khorram2, Zahra Razzaghi4, Sahar Dadkhahfar3 Urology Journal/Vol 19 No. 4/ July-August 2022/ pp. 325-328. [DOI:10.22037/uj.v18i.6556] INTRODUCTION Fournier’s gangrene disease (FG), caused by a com-bination of aerobic and anaerobic organisms, is a life-threatening disease in which perineal and scrotal infections, followed by proliferation in the fascia, lead to soft tissue necrosis. The mortality risk is usually 20 to 40 %, but in some studies, it has been reported even at 88 %(1). FG mainly affects men through the third and sixth dec- ade of their life though it may occur in all age groups, even women and infants(2). The average age of involve- ment is 50.9 years, and the disease ratio in men to wom- en is 10 to 1(3). The mortality rate is higher in patients with delayed hospitalization, patients with diabetes mellitus, and those initially presented with sepsis(4). Risk factors for FG include diabetes, alcoholism, med- ications, immunodeficiency, malignancies, kidney failure, and liver failure(5). Female gender is also a risk factor for death in patients with FG, which is due to the increased prevalence of inflammation in the retroper- itoneal space and the abdominal cavity on account of anatomical causes(6). The optimal outcome of FG treatment is based on rapid diagnosis, debridement of all necrotic tissues, and ex- tensive antimicrobial experimental treatment, usually combined with antibiotics affecting aerobic and anaero- bic bacteria. Prevention of uroseptic shock is mandato- ry with the treatment of local infections(7). The prognostic role of the ratio of blood urea nitrogen (BUN) to albumin in diseases such as hospital-acquired pneumonia and community-acquired pneumonia and non-small lung cancer has been proven. In this way, with increasing the ratio of BUN to albumin, the risk of mortality and the need for ICU, and the length of hos- pital stay will increase as well(8-11). Given that no study has been performed on patients with FG, the current study could play a potentially beneficial role in reduc- ing the mortality of FG patients. MATERIALS AND METHODS Patients with FG were consecutively admitted and en- rolled to Shohada-e-Tajrish Hospital (Tehran, Iran) from March 2008 to April 2020 in the study. The Ethics Committee of the hospital permitted us to review the patients' medical data. The patients' health records were de-identified. The research terms included Fournier's gangrene (FG), soft tissue infection, and necrotizing fasciitis. Patients’ gender, age, comorbidities (diabetes mellitus, cerebrovascular accidents, malignancies, urinary incon- tinence, and so on), laboratory data, duration of hospi- tal stay, and final disease outcomes were included in 1Urology and Nephrology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 2Department of Urology, Shohada-e-Tajrish Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 3Skin Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 4Laser Application in Medical Sciences Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. *Correspondence: epartment of Urology, Shohada-e-Tajrish Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran. E mail: khafash88@gmail.com. IranReceived November 2020 & Accepted May 2021 UNCLASSIFIED Purpose: To assess the prognostic effect of blood urea nitrogen to serum albumin ratio in patients with Fournier’s gangrene (FG) in a referral center. Materials and Methods: Patients with FG were admitted and enrolled consecutively in this study from March 2008 to April 2020. Statistical analysis was done to evaluate the differences between the two groups and to identify the best cutoff value to predict mortality and the need for intensive care. Results: Of all 114 patients, 46 patients (40.35%) died in the course of hospitalization and 40 entered the study. No variable manifested a notable difference except for the BUN to albumin ratio, which was significantly different (P-value = 0.045). The ratio of BUN to albumin was not associated with any other variables and was independently a predictor of death in FG patients. Conclusion: The ratio of BUN to albumin was significantly different among deceased and survived patients with FG. Therefore, more studies with a larger sample size are still needed to access this parameter properly. Keywords: blood urea nitrogen; Fournier’s gangrene; intensive care unit; mortality; prognosis the medical data. Disease diagnosis was based on the symptoms of pain, erythema, ulcers, swelling, crepitus, necrosis, purulent discharge, and later confirmations with the tissue inspection in the operating room. Pa- tients were excluded from the study if they had been hospitalized 90 days prior to the study. They were also excluded if they were chronically immunosuppressed (such as chemotherapy, human immunodeficiency vi- rus infection, therapy with more than 20 mg prednisone or equivalent, and other immunosuppressive therapies) or if they had advanced liver disease or end-stage renal disease. The study was approved by the Ethics Committee of Shahid Beheshti University of Medical Sciences (IR. SBMU.SRC.REC.1399.005), and informed consent was obtained from all patients according to the hos- pital’s guidelines. Some patients had missing data, so they were excluded. As mentioned, among 114 patients, 40 patients were enrolled in the study. Results were expressed as mean ± SD frequency and confidence interval (CI). The normality of data was de- termined with the Shapiro-Wilk test. The nonparamet- ric Mann-Whitney U test was applied for continuous variables and the Chi-Square test for categorical varia- bles. Variables significantly associated with mortal¬ity or need for intensive care at the 0.20 level in univariate analysis were considered in a multivariate backward analysis. Analysis of a receiver-operating characteristic (ROC) curve was performed to identify the best cut- off value to predict mortality and the need for intensive care. A probability value less than 0.05 was considered to be statistically significant. RESULTS During the study period, a total of 114 FG patients were admitted; of these, 40 patients entered the study and 74 patients were excluded. The average age of the patients was 62.58 ± 14.36 years, and the mean value of hospi- talization days was 16.95 ± 12.14. Among 114 patients, 46 (40.35%) died in the course of hospitalization. Pa- tient charac¬teristics are shown in Table 1. The subjects were divided into two groups (deceased and surviving), and the variables were studied in both. None of the variables showed a significant difference, except for the ratio of BUN to albumin. The comparison of variables in the two groups is given in Table 2. According to the data, the ratio of BUN to albumin was not correlated with any of the other variables and was independently a predictor of death in FG patients. ROC curve was used to determine the optimal cut-off value of the BUN to albumin ratio. The value of 12.71 was determined with 79% sensitiv- ity and 62% specificity. The ROC curve for predicting mortality by the BUN to albumin ratio is depicted in Figure 1. [The Odds Ratio is 6.13 ( 1.17 – 32.10 ) and the Rel- ative Risk is 2.86 (1.08 – 7.58); AUC = 0.690 (0.522 – 0.858 ) ( P-Value = 0.040 )] No significant relationship was observed between the ratio of BUN to albumin and the number of hospitaliza- tion days (P = 0.48) by the Spearman Correlation test. Although patients who needed hospitalization in the ICU had a higher BUN to albumin ratio (18.90 ± 11.04 Letter 242 Minimum Maximum Mean Std. Deviation Age 25 87 62.58 14.360 Days of admission 3 62 16.95 12.140 Hemoglobin 7.1 15.6 10.6 2.07 Platelet (×1000) 28 461 216.6 107.3 White blood cells (×1000) 0.32 57 17.2 11.6 Albumin 1 .50 4.07 2.57 0.56 BUN 8 110 42.8 25.8 Estimated sedimentation rate 2 92 43.5 26.3 C-reactive protein 4 181 70.25 46.3 AST 6 75 31.37 17.45 ALT 4 146 24.74 27.12 Alkaline phosphatase 90 2364 338.96 455.41 BUN to albumin ratio 2.86 51.49 17.16 10.34 Table 1. Baseline characteristics of enrolled patients BUN:Blood Urea Nitrogen; AST:Aspartate Aminotransferase; ALT:Alanine aminotransferase BUN, Blood Urea Nitrogen; AST, Aspartate Aminotransferase; ALT, Alanine aminotransferase Deceased (n = 20) Surviving (n = 20) P value Age 66.45 ± 10.097 58.70 ± 17.02 0.88 Days of admission 18.45 ± 14.136 15.45 ± 9.897 0.44 Hemoglobin 10.12 ± 2.209 11.2 ± 1.836 0.1 Platelet (×1000) 206.1 ± 108.1 226.5 ± 108.3 0.55 White blood cells (×1000) 16.9 ± 13.5 17.5 ± 9.6 0.87 Estimated sedimentation rate 42.8 ± 29.2 44.3 ± 24.9 0.91 C-reactive protein 75.7 ± 54.3 64.7 ± 39.7 0.65 AST 35.3 ± 17.9 26.5 ± 16.3 0.2 ALT 30.2 ± 33.9 17.9 ± 13.5 0.25 Alkaline phosphatase 382 ± 577.4 288.7 ± 268.8 0.61 BUN to albumin ratio 20.4 ± 10.5 13.9 ± 9.3 0.045 Table 2. Comparison of characteristics between deceased and surviving patients Blood Urea Nitrogen to Albumin in Fournier’s Gangrene-Allameh et al.. Vol 19 No 4 July-August 2022 326 vs. 15.23 ± 9.42), this difference was not significant (P = 0.26). DISCUSSION FG is an uncommon disease; 110 cases of FG or ne- crotizing fasciitis admitted to our hospital for 10 years were reviewed, and finally, 40 patients were enrolled in the current study. Due to its progressive nature, the disease mortality rate remains high (43–53%) despite intensive care treatment and advances in medical ther- apy(8,9). The overall mortality rate in the present study was 40.35% (46 of 114 patients). The mean age of sur- vivors was 58.70 ± 17 years old, and deceased patients had a mean age of 66.45 ± 10 years old which was not statistically significant. Some studies showed similar findings(4,12,13), whilst others showed contradictory re- sults(2,7,8,14). Many factors have been reported that predispose pa- tients to the development of FG, with diabetes mellitus (DM), chronic renal failure (CRF), and malignancy as the main ones. For example, Tuncel et al.(13) found an association between DM and poor prognosis; however, Corcoran et al. reported no similar relationship in their study(15). In the present study, 24 (60%) patients had a positive past medical history of DM, which was not sig- nificant between survivors and deceased patients. No consensus is available on clinical variables for pre- dicting poor outcomes in FG(13). FGSI was developed to facilitate the prediction of the outcomes in FG patients. Laor et al. found an FGSI score of > 9 that consisted of 75% death probability, while a score of ≤ 9 was asso- ciated with 78% survival probability(16). This threshold for predicting mortality in patients has been confirmed in other studies(3,11). Recent studies have evaluated the ratio of BUN to al- bumin in predicting the prognosis of diseases. Feng et al.(8) studied its role on hospital-acquired pneumonia, while in three studies(9-11), community-acquired pneu- monia was the main disease to be evaluated. Moreover, Kos(17) and Gundpatil(18) assessed the BUN/albumin on non-small lung cancer and non-chronic kidney diseases, respectively. In this way, the risk of mortality, the need for ICU admission, and the length of hospital stay will increase with increasing the BUN to albumin ratio. In the current study, the ratio of BUN to albumin was sig- nificantly higher among deceased patients in compari- son to the survived ones. Despite the variations seen in the need for ICU admission and the length of hospital stay, the differences were not significant. There are several indexes used for Fournier gangrene prognosis like Fournier’s Gangrene Severity Index (FGSI), Uludag Fournier Gangrene Severity Index (UFGSI), Age-Adjusted Charlson Comorbidity Index (ACCI), Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) score, the Combined Urology and Plastics Index (CUPI) and neutrophil–lymphocyte ratio (NLR) and surgical APGAR (sAPGAR). According to the studies, the UFGSI does not seem to be more pow- erful than FGSI. In daily routine, we suggest applying ACCI because it is more easily calculated, generally ap- plicable, and well-validated. UFGSI has the most sensi- tivity rate (85%) and sAPGAR has the lowest sensitivity rate (55%). However, sAPGAR has the most specificity rate (91%) and UFGSI has the lowest specificity rate (67%).(19) In prediction for skin reconstruction in FG patients, FGSI, UFGSI, and NLR are more reliable.(20) Overall, UFGSI is the most common index for assess- ing FG patients. According to our results, the sensitivity of BUN/Alb is not as high as UFGSI, but it is accept- able and very useful due to the simplicity of performing tests. According to the findings, the ratio of BUN to albu- min was significantly different among the deceased and survived patients with FG. Further studies with a larger sample size are recommended to properly assess this parameter. Figure 1. Analysis of ROC curve for predicting mortality Blood Urea Nitrogen to Albumin in Fournier’s Gangrene-Allameh et al.. Unclassified 327 CONCLUSIONS The ratio of BUN to albumin was significantly different among deceased and survived patients with FG. There- fore, more studies with a larger sample size are needed to access this parameter properly. ACKNOWLEDGEMENT The authors would like to thank the staff of Shohada-e Tajrish Hospital for their care and sacrifices in treating patients. CONFLICT OF INTEREST The authors report no conflict of interest. REFERENCES 1. Benjelloun EB, Souiki T, Yakla N, et al.Fournier’s gangrene: our experience with 50 patients and analysis of factors affecting mortality. World J Emerg Surg. 2013 Dec 1;8(1):13. 2. Tenório CE, Lima SV, Albuquerque AV, Cavalcanti MP, Teles F. Risk factors for mortality in fournier's gangrene in a general hospital: use of simplified founier gangrene severe index score (SFGSI). Int Braz J Urol. 2018 Feb;44(1):95-101. 3. Chernyadyev SA, Ufimtseva MA, Vishnevskaya IF, et al. Fournier’s gangrene: literature review and clinical cases. Urol Int. 2018;101:91-7. 4. Yanar H, Taviloglu K, Ertekin C, et al. Fournier’s gangrene: risk factors and strategies for management. World J Surg. 2006 Sep 1;30(9):1750-4. 5. Danesh HA, Saboury M, Sabzi A, Saboury M, Jafary M, Saboury S. Don’t underestimate fournier’s gangrene: report of 8 cases in 10 month survey. Med J Islam Repub Iran. 2015;29:172. 6. Czymek R, Frank P, Limmer S, et al. Fournier’s gangrene: is the female gender a risk factor?. Langenbecks Arch Surg. 2010 Feb 1;395(2):173-80. 7. Kuzaka B, Wróblewska MM, Borkowski T, et al. Fournier’s gangrene: Clinical presentation of 13 cases. Med Sci Monit. 2018;24:548. 8. Feng DY, Zhou YQ, Zou XL, et al. Elevated Blood Urea Nitrogen-to-Serum Albumin Ratio as a Factor That Negatively Affects the Mortality of Patients with Hospital-Acquired Pneumonia. Can J Infect Dis Med Microbiol. 2019;2019. 9. Jyothi S, Basavaraj B, Gurupadappa K. The prognostic implication of serum albumin and BUN/Albumin ratio in assessing severity and mortality in community acquired pneumonia (CAP). Int J Clin Biochem Res. 2019;6:79-81. 10. Ugajin M, Yamaki K, Iwamura N, Yagi T, Asano T. Blood urea nitrogen to serum albumin ratio independently predicts mortality and severity of community-acquired pneumonia. Int J Gen Med. 2012;5:583. 11. Akpinar EE, Hosgun D, Doganay B, Gulhan M. The role of albumin level and blood urea nitrogen/albumin ratio in prediction of prognosis of community acquired pneuomonia. J Pulm Respir Med. 2013;3(159):2. 12. Yeniyol CO, Suelozgen T, Arslan M, Ayder AR. Fournier’s gangrene: experience with 25 patients and use of fournier’s gangrene severity index score. Elsevier Inc. 2004; 64:218-22. 13. Tuncel A, Aydin O, Tekdogan U, Nalcacioglu V, Capar Y, Atan A. Fournier’s Gangrene: Three Years of Experience with 20 Patients and Validity of the Fournier’s Gangrene Severity Index Score. Eur Urol. 2006; 50:838– 43. 14. Marco SL, Budía A, Capua CD, Broseta E, Cruz FJ. Evaluation of a severity score to predict the prognosis of Fournier’s gangrene. BJU Int. 2009; 106:373-6. 15. Corcoran AT, Smaldone MC, Gibbons EP, Walsh TJ, Davies BJ. Validation of the Fournier’s gangrene severity index in a large contemporary series. J Urol 2008; 180: 944– 814 16. Laor E, Palmer LS, Tolia BM, Reid RE, Winter HI. Outcome prediction in patients with Fournier’s gangrene. J Urol. 1995; 154:89-92. 17. Kos M, Hocazade, C, Kos F, et al. Association between blood urea nitrogen/albumin ratio and prognosis in non-small cell lung cancer. Acta Med Mediterr. 2015; 31:219-223. 18. Gundpatil DB, Somani BL, Saha TK, Banerjee M. Serum urea:albumin ratio as a prognostic marker in critical patients with non-chronic kidney disease. Indian J Clin Biochem: IJCB, 2014;29(1):97–100. 19. Roghmann F, von Bodman C, Löppenberg B, Hinkel A, Palisaar J, Noldus J. Is there a need for the Fournier's gangrene severity index? Comparison of scoring systems for outcome prediction in patients with Fournier's gangrene. BJU Int. 2012 Nov;110(9):1359-65. 20. Selvi I, Aykac A, Baran O, Burlukkara S, Ozok U, Sunay MM. A different perspective for morbidity related to Fournier’s gangrene: which scoring system is more reliable to predict requirement of skin graft and flaps in survivors of Fournier’s gangrene?. Int Urol Nephrol. 2019 Aug;51(8):1303-11. Blood Urea Nitrogen to Albumin in Fournier’s Gangrene-Allameh et al.. Vol 19 No 4 July-August 2022 328