ENDOUROLOGY AND STONE DISEASE Is Absence of Hydronephrosis a Risk Factor for Bleeding in Conventional Percutaneous Nephrolithotomy? Hee Youn Kim, Hyun-Sop Choe, Dong Sup Lee, Je Mo Yoo, Seung-Ju Lee* Purpose: There is conflict of evidence regarding whether absence of hydronephrosis is a risk factor for bleeding in percutaneous nephrolithotomy (PNL). Moreover, among the stone complexity scoring systems used for PNL (Guy’s stone score, the S.T.O.N.E. nephrometry and the CROES nomogram), only the S.T.O.N.E. nephrometry score incorporates hydronephrosis as a risk factor. Therefore, this study aimed to compare perioperative outcomes according to the presence or absence of hydronephrosis in percutaneous nephrolithotomy (PCNL) patients and to investigate whether absence of hydronephrosis is a risk factor for blood transfusion rate. Materials and Methods: 281 patients who had undergone PCNL between December 2009 and April 2017 were divided according to the absence or presence of hydronephrosis (group I and group II, respectively). Perioperative outcomes were compared between the two groups. A multivariable regression analysis was performed to investi- gate whether hydronephrosis was a risk factor for blood transfusion rate. Results: Patients without hydronephrosis showed significantly longer operation time and admission period, lower stone-free rate and higher blood transfusion rate compared to patients with hydronephrosis (p < 0.05, p = 0.002, p = 0.011, and p < 0.05, respectively). Multivariate logistic regression analysis showed that hydronephrosis was a sig- nificant risk factor for blood transfusion (OR, 95% CI and p value was 0.353, 0.163-0.761 and 0.008, respectively). Conclusion: Based on the results of the current study, we found that absence of hydronephrosis was a significant risk factor for blood transfusion in conventional PCNL. Keywords: percutaneous nephrolithotomy; hydronephrosis; blood transfusion; urolithiasis INTRODUCTION Percutaneous nephrolithotomy (PCNL) remains an integral part of treatment for large complex renal stones. In studies where practice patterns of urolithiasis were surveyed, more than 80% of urologic practition- ers responded that they performed PCNL(6,7). Despite its wide use, complication rates are still relatively high. A large prospective study using the modified Clavien-Din- do classification system reported an overall complica- tion rate of 20.5% (8,9). Bleeding is the most significant complication of PCNL, with reported rates of bleeding requiring blood transfusion ranging between 0 and 20% (10). Numerous studies have attempted to elucidate the risk factors for bleeding (11-14). Among those factors, we focused on hydronephrosis. The presence or absence of hydronephrosis is associat- ed with various steps in the PCNL procedure, especially during the initial renal access. In the absence of hydro- nephrosis, iatrogenic hydronephrosis is usually made via ureteral catheter, which can assist in successful renal access and theoretically, bleeding should not be a problem. Nevertheless, there is conflicting evidence in the literature on whether the presence or absence of Department of Urology, St. Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Suwon, Republic of Korea. *Correspondence: Department of Urology, St. Vincent’s Hospital, College of Medicine, The Catholic University of Korea, 93, Jungbu-daero, Paldal-gu, Suwon-si, Gyeonggi-do 16247, Republic of Korea. Tel: 82 31 249 7473, Fax: 82 31 253 0949, E-Mail: seungju@catholic.ac.kr. Received September 2018 & Accepted January 2019 hydronephrosis affects bleeding during PCNL (11,13-15). Some claim that hydronephrosis did not have any ef- fect on blood loss, while others claim that absence of hydronephrosis was a significant risk factor for severe bleeding. Moreover, among the stone complexity scor- ing systems used for PNL (Guy’s stone score (16), the S.T.O.N.E. nephrometry (17) and the CROES nomogram (18)), only the S.T.O.N.E. nephrometry score incorpo- rates hydronephrosis as a risk factor. Therefore, the aim of this study was to compare periop- erative outcomes according to the presence or absence of hydronephrosis in PCNL patients and to investigate whether absence of hydronephrosis is a risk factor for blood transfusion. PATIENTS AND METHODS Study Population and Design The Institutional Review Board of St. Vincent’s Hos- pital, the Catholic University of Korea, approved the study protocol. This was a retrospectively case-con- trol study. Chart review of all patients who underwent PCNL with a follow up period of at least 3 months be- tween December 2009 and April 2017 was investigat- Urology Journal/Vol 17 No. 1/ January-February2020/ pp. 8-13. [DOI: 10.22037/uj.v0i0.4826] Vol 17 No 01 January-February 2020 09 ed. The following patients were excluded: patients who underwent bilateral PCNL, patients with kidney anom- alies (including horseshoe kidney), patients who under- went another operation simultaneously, patients who had multiple tracts, and patients with a preexisting per- cutaneous nephrostomy tract through which renal ac- cess was achieved. A total of 281 patients were eligible for the current study. The following information was recorded as patient characteristics: age, sex, body mass index (BMI), history of diabetes mellitus (DM), history of hypertension, and history of chronic kidney disease (CKD). The following information was recorded as stone characteristics: laterality, absence or presence of hydronephrosis, Guy’s stone score(16), stone volume(19) and staghorn stone. Staghorn stones were excluded for stone volume calculation. Finally, the following infor- mation was recorded as perioperative outcomes: opera- tion time (minutes), admission period (days), stone-free rate (%), blood transfusion rate (%) and infectious com- plication rate (%). Operation was considered successful when the follow up image showed no residual stones or clinically insignificant residual fragments (CIRFs). In the current study, CIRFs were considered to be ≤ 4mm, nonobstructing, noninfectious, and asymptomatic resid- ual fragments(20). Additionally, only microbiological- ly or radiographically confirmed febrile urinary tract infection was recorded as an infectious complication; simple postoperative fever was not included. The study population was divided into two groups: group I was defined as patients without hydronephrosis and group II as patients with hydronephrosis. Surgical Technique Urine culture with an antibiotic susceptibility test was done in every patient planned for PCNL. If the urine culture result was positive, then susceptible oral antibi- otics were administered for one week before admission. Otherwise, a prophylactic antibiotic was administered just before surgery. After general endotracheal anaes- thesia, a ureteral occlusion balloon catheter was insert- ed via cystoscope with the patient in lithotomy position. The patient was then turned to the prone position. Per- cutaneous renal access was achieved with fluroscopic assistance. The access tract was dilated with a balloon dilator and a 30F Amplatz sheath was inserted. A rigid 26F nephroscope was inserted and the stone was frag- mented with an ultrasonic lithotripter and removed with forceps. At the end of the operation, an antegrade ure- teral catheter was inserted and a 20F nephrostomy tube was placed. Data Analysis SPSS (IBM Corp. Released 2012. IBM SPSS Statistics for Windows, Version 21.0. Armonk, NY: IBM Corp.) was used for the statistical analysis. Descriptive sta- tistics were used to describe the results. The compar- ison of continuous variables was performed using the unpaired t-test or the Mann-Whitney test based on the result of the Shapiro-Wilk test for normality. The com- parison of categorical variables was performed using the chi-square test or Fisher’s exact test. A multivariate logistic regression analysis was conducted to investi- gate whether hydronephrosis was a risk factor for blood transfusion. P values < 0.05 were considered statistical- ly significant. RESULTS Baseline patient and stone characteristics are described in Table 1. Of the 281 patients, the number of patients without hydronephrosis (group I) was 95 (33.8%) and the number of patients with hydronephrosis (group II) was 186 (66.2%). There were no significant differences in age, sex, BMI, history of DM, history of hyperten- sion, history of chronic kidney disease or stone lateral- ity. A significant difference was noted in Guy’s stone score, as the percentage of grade 2 stones was higher in Table 1. Comparison of baseline patient and stone characteristics between group I (patients without hydronephrosis) and group II (patients with hydronephrosis) Group I Group II p value n (%) 95/281 (33.8%) 186/281 (66.2%) Age (years, mean ± SD) 54.9 ± 10.6 53.8 ± 12.3 0.4531 Sex (%) 0.1232 Male 51/95 (53.7%) 118/186 (63.4%) Female 44/95 (46.3%) 68/186 (36.6%) BMI (kg/m2, mean ± SD) 25.2 ± 3.1 25.4 ± 3.6 0.7443 DM (%) 27/95 (28.4%) 42/186 (22.6%) 0.3072 Hypertension (%) 36/95 (37.9%) 59/186 (31.7%) 0.3512 CKD (%) 4/95 (4.2%) 7/186 (3.8%) 1.0004 Laterality (%) 0.7032 Left 57/95 (60.0%) 107/186 (57.5%) Right 38/95 (40.0%) 79/186 (66.2%) Guy’s stone score (%) <0.053 Grade 1 19/95 (20.0%) 54/186 (29.0%) Grade 2 18/95 (18.9%) 88/186 (47.3%) Grade 3 40/95 (42.1%) 43/186 (23.1%) Grade 4 18/95 (18.9%) 1/186 (0.5%) Stone burden (mm3, mean ± SD) 153.7 ± 123.0 207.0 ± 146.2 0.0103 Staghorn stone (%) 50/95 (52.6%) 22/186 (11.8%) 0.0012 1 Unpaired t-test 2 Chi-square test 3 Mann-Whitney test 4 Fisher’s exact test SD = standard deviation, BMI = body mass index, DM = diabetes mellitus, CKD = chronic kidney disease Hydronephrosis as a risk factor for bleeding in PCNL-Kim et al. group II (p < 0.05) and the percentage of grade 3 and grade 4 stones was higher in group I (p = 0.001 and p < 0.05, respectively), implying that the group without hydronephrosis contained patients with more complex stones. The stone volume was significantly higher in group II (p = 0.01), but this was because staghorn stones were not included for stone burden calculation. The proportion of staghorn stones was significantly higher in group I (p = 0.001). The comparison of perioperative outcomes between group I and group II is described in Table 2. Significant differences were found in operation time, admission period, stone-free rate, and the blood transfusion rate between group I and group II (p < 0.05, p = 0.002, p = 0.011, and p < 0.05, respectively). In short, patients without hydronephrosis showed longer operation time and admission period, lower stone-free rates, and higher blood transfusion rate compared to patients with hydro- nephrosis. To determine whether hydronephrosis was a risk factor for transfusion, a univariate and multivariate logistic re- gression analysis was performed (Table 3). Absence of hydronephrosis was a significant risk factor for blood transfusion, with an odds ratio of 0.353, a confidence interval of 0.163-0.761, and a p value of 0.008. DISCUSSION The current study sought to investigate whether hy- dronephrosis was a significant risk factor for blood transfusion rate. The implication of hydronephrosis on surgical outcomes, especially bleeding, in PCNL is not well established. Previous studies showed conflicting results. Kukreja et al. reported in their prospective study in 2004 that hydronephrosis did not have any effect on blood loss (13). However, in their study, the PCNL pro- cedure was staged for a large stone burden, prolonged operation time and the occurrence of significant com- plications such as perforation or bleeding, which could have affected their results. In a study by Akman et al. in which factors affecting bleeding during PCNL were studied(11), hydronephrosis was not a significant factor, although the p value nearly showed significance (p = 0.06). In contrast, Lee et al. and Senocak et al. found out that the absence of hydronephrosis was a signifi- cant risk factor for bleeding during PCNL(14,15). More- over, among the stone complexity scoring systems used for PCNL (Guy’s stone score (16), the S.T.O.N.E. nephrometry(17) and the CROES nomogram(18)), only the S.T.O.N.E. nephrometry score incorporates hydro- nephrosis as a risk factor, again showing that hydrone- phrosis is not thought of as an important factor during PCNL. In the current study, the absence of hydronephrosis was found to be a significant risk factor for blood transfu- sion after PCNL. Several hypotheses can be proposed for the current result. First, the difference in Guy’s stone score between the two groups may be the main reason. Patients without hydronephrosis tended to have higher Guy’s stone scores, indicating more complex stones, which is thought to be due to diverticular and staghorn stones in the group without hydronephrosis. The high- er proportion of higher complexity stones may have caused the higher transfusion rate in the group without hydronephrosis. This result is validated by other studies as increased Guy’s stone scores were associated with increased complication rates (21). One interesting finding from the result of the current study is that even with the same Guy’s stone score, blood transfusion rate can vary depending on the presence or absence of hydrone- phrosis, suggesting that Guy’s stone score alone may be insufficient to predict the complication rate of PCNL. This may imply that hydronephrosis should be included Hydronephrosis as a risk factor for bleeding in PCNL-Kim et al. Table 2. Comparison of perioperative outcomes between group I (patients without hydronephrosis) and group II (patients with hydronephrosis) Group I Group II p-value Operation time (minutes, mean ± SD) 103.4 ± 47.4 82.7 ± 36.1 < 0.051 Admission period (days, mean ± SD) 3.9 ± 1.9 3.5 ± 1.6 0.0221 Stone-free rate (%) 60/95 (63.2%) 145/186 (78.0%) 0.0112 Transfusion rate (%) 27/95 (28.4%) 21/186 (11.3%) < 0.052 Infectious complication rate (%) 3/95 (3.2%) 4/186 (2.2%) 0.6923 1 Mann-Whitney test 2 Chi-square test 3 Fisher’s exact test SD = standard deviation Variables Univariate Multivariate OR (95% CI) p value OR (95% CI) p value Sex 2.483 (1.319-4.677) 0.005 2.315 (1.152-4.649) 0.018 BMI 0.832 (0.750-0.924) 0.001 0.823 (0.733-0.925) 0.001 Guy score Grade 1(reference) 0.302 0.036 Grade 2 1.699 (0.621-4.651) 0.005 3.212 (1.034-9.975) 0.044 Grade 3 4.027 (1.531-10.592) 0.012 5.050 (1.696-15.035) 0.004 Grade 4 5.154 (1.436 (18.500) 0.000 3.925 (0.923-16.685) 0.064 Hydronephrosis 0.321 (0.170-0.606) 0.000 0.353 (0.163-0.761) 0.008 OR = odds ratio, CI = confidence interval, BMI = body mass index Table 3. Univariate and multivariate logistic regression analysis to determine independent predictor of transfusion with regard to percu- taneous nephrolithotomy Endourology and Stones diseases 10 Vol 17 No 01 January-February 2020 11 in scoring systems to predict outcomes for PCNL. The only scoring system used for PCNL that includes hydro- nephrosis is, as previuously mentioned, the S.T.O.N.E. nephrometry score (17). However, although this system has been validated for its predictive ability of the stone- free rate, the utility of this scoring system for stratify- ing complication rates has not been asserted(22). Further study is needed in this aspect. The second possible reason for the result of the current study is that the absence of hydronephrosis may have led to increased bleeding due to vascular injury during initial renal access. The ideal location for initial renal access is through the calyceal fornix because this will avoid the interlobar (infundibular) arteries adjacent to the calyceal infundibula and the arcuate arteries along the renal pyramid (23). In the presence of hydronephro- sis, this process is relatively straightforward because of the dilated calyces. However, in the absence of hy- dronephrosis, the calyceal fornix may be missed and puncture through the infundibulum or directly into the renal pelvis may occur, leading to massive bleeding. In addition, with little hydronephrosis, repeated attempts may be necessary to puncture the desired calyx, which can be a significant risk factor for bleeding in PCNL(24). The third possible reason is that the absence of hydro- nephrosis affords less space for manipulation within the kidney, leading to traumatic injury of the renal vascula- ture and parenchyma(15). Several suggestions can be made to reduce bleeding complications during PCNL in patients without hydro- nephrosis. First, the utilization of ultrasound guidance for initial renal access may help reduce bleeding during PCNL. In a meta-analysis that compared fluoroscopy and ultrasound guidance during initial renal access, ul- trasound was found to be superior in terms of puncture time, the success rate of first puncture, blood loss, and transfusion requirements (25,26). However, utilizing ultra- sound alone for renal access can be difficult because of poor imaging of the renal anatomy in patients with a nondilated collecting system(27). Combining ultrasound and fluoroscopy can overcome this problem and help decrease bleeding by reducing puncture attempts and access time(28). Second, the utilization of smaller calib- er access sheaths may reduce bleeding. Compared to conventional PCNL that uses a 30F Amplatz sheath, mini-PCNL utilizes smaller-sized sheaths, ranging between 11-20F. Several studies have reported the ad- vantage of mini-PCNL over conventional procedure in terms of a reduced hemoglobin drop and the need for blood transfusion(29). Third, staging the procedure for patients with a large stone burden may reduce blood loss(13). Lastly, utilizing RIRS in well-selected patients with large renal stones may be helpful. Several studies have found that RIRS was a good alternative treatment to PCNL in patients with 2-4cm renal stones(30,31). The current study also showed significant results for other outcomes. The operation time and admission peri- od were significantly longer and the stone-free rate was significantly lower in the group without hydronephro- sis. Again, a higher proportion of more complex stones in the group without hydronephrosis may have caused this result as Guy’s stone score is known to be associ- ated with surgical outcomes in PCNL. Infectious com- plications did not show significant difference between the two groups. Several studies have implicated hydro- nephrosis as one of the risk factors for infectious com- plications after PCNL(32-34). One possible reason for our result is the strict definition of infectious complication in the current study. Unlike other studies that included a simple febrile episode as an infectious complication, only microbiologically or radiographically confirmed febrile urinary tract infections were included in the cur- rent study. Lastly, urine leakage was not investigated in this study because both the nephrostomy tube and the ureteral catheter were routinely inserted at the end of the operation. There were several limitations in the current study. Because of the retrospective nature of the study, there Supplementary table 1. Comparison of baseline patient and stone characteristics between patients who did not receive transfusion and patients who received transfusion. No transfusion Transfused p value n (%) 233/281 (82.9%) 48/281 (17.1%) Age (years, mean ± SD) 54.2 ± 12.0 54.0 ± 10.4 0.9301 Sex (%) 0.0042 Male 149/233 (63.9%) 20/48 (41.7%) Female 84/233 (36.1%) 28/48 (58.3%) BMI (kg/m2, mean ± SD) 25.7 ± 3.3 23.8 ± 3.5 0.0013 DM (%) 59/233 (25.3%) 10/48 (20.8%) 0.5112 Hypertension (%) 80/233 (34.3%) 15/48 (31.3%) 0.6812 CKD (%) 7/233 (3.0%) 4/48 (8.3%) 0.0994 Laterality (%) 0.7442 Left 137/233 (58.8%) 27/48 (56.3%) Right 96/233 (41.2%) 21/48 (43.8%) Guy’s stone score (%) < 0.053 Grade 1 19/95 (20.0%) 54/186 (29.0%) Grade 2 18/95 (18.9%) 88/186 (47.3%) Grade 3 40/95 (42.1%) 43/186 (23.1%) Grade 4 18/95 (18.9%) 1/186 (0.5%) Stone burden (mm3, mean ± SD) 192.1 ± 139.7 2 13.2 ± 169.2 0.7823 Staghorn stone (%) 48/233 (20.6%) 24/48 (50.0%) < 0.052 1 Unpaired t-test 2 Chi-square test 3 Mann-Whitney test 4 Fisher’s exact test SD = standard deviation, BMI = body mass index, DM = diabetes mellitus, CKD = chronic kidney disease Hydronephrosis as a risk factor for bleeding in PCNL-Kim et al. could have been selection bias. Another potential bias is misclassification bias, where patients may have been included into a wrong group especially when hydrone- phrosis is not distinct. Also, some data that could have been valuable for the purpose of the study were not available, such as the time taken for initial renal access and the number of puncture attempts. In addition, sur- gical experience was not taken into account in the anal- ysis, which may have caused higher a transfusion rate in our early cases. A relatively small number of study population is another limitation. CONCLUSIONS Based on the results of the current study, we found that absence of hydronephrosis was a significant risk factor for blood transfusion in conventional PCNL. CONFLICT OF INTEREST The authors report no conflicts of interest. REFERENCES 1. Turk C, Petrik A, Sarica K, et al. EAU Guidelines on Interventional Treatment for Urolithiasis. Eur Urol. 2016;69:475-82. 2. Ghani KR, Andonian S, Bultitude M, et al. 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