Urosepsis After Percutaneous Nephrolithotomy (PCNL) - a New Prediction Rule and Scoring System

Objective: Development and validation of a scoring system to predict the risk of urosepsis after percutaneous nephrolithotomy. Methods: The risk factors associated with urosepsis following PCNL(Percutaneous Nephrolithotomy) were identied by meta-analysis. Based on the degree of association, different scores were assigned to these risk factors. Finally Risk assessment scoring system for urosepsis after percutaneous nephrolithotomy (PCNL) was established and validated using ROC (Receiver Operating Characteristic) curve. Results: Based on the degree of association, Women, age ( ≥ 60yrs), diabetes mellitus, blood routine (White blood cells ≥ 10×10 9 /L), Urinalysis (White blood cells ≥ +), Urine culture (Positive), stone size( ≥ 2cm), staghorn stone, hydronephrosis (moderate-severe) were assigned 3, 2, 3, 2, 2, 2, 2, 3, 2 points respectively with a total score of 21 points. The area under the ROC(Receiver Operating Characteristic) curve was 0.913, at the cut-off point of 8.5, the sensitivity and specicity were 90% and 89.4% respectively. Conclusions: assessment scoring system (PuRass) to predict the risk of following PCNL (Percutaneous nephrolithotomy)


Introduction
Kidney stone was common urological condition affecting about 12% of the world population. Percutaneous nephrolithotomy (PCNL) was the treatment of choice for larger kidney and ureteric stones. Urosepsis was rare but devastating complication associated with this procedure and was very di cult to predict [1] . Understanding risk factors associated with of post-operative urosepsis was necessary to identify high-risk patients and better counsel patients preoperatively. Clinicians and investigators had focused on pathogenesis, diagnosis and treatment of urosepsis following PCNL(Percutaneous Nephrolithotomy),but few attempts had been made in assessment and reorganization of the preoperative risk factors [2] . Thus, we developed a risk assessment scoring system (PuRass) to predict the risk of urosepsis following PCNL (Percutaneous nephrolithotomy) .

Materials And Methods
This study was conducted between January 2013 and December 2016 In Shihezi Medical college. In this study, we retrospectively included 293 patients with kidney stone who had undergone PCNL (Percutaneous nephrolithotomy).
Inclusion criteria: The diagnosis was made with either ultrasonography(USG) or computed tomography (CT), indication of surgery was based on 2014 Chinese diagnosis and treatment of urological disease guidelines.

Method
Page 3/11 The population was divided into two groups urosepsis and the non-urological cause of sepsis. Risk factors associated with the development of urosepsis were identi ed using meta-analysis. Also, scores were assigned to risk these factors according to the degree of association. Finally, a risk assessment scoring system was established and validated using ROC(Receiver Operating Characteristic) curve.
Degree of association: no association: 0, weak association: 1, moderate association: 2, strong association: 3, very strong association: 4 Preoperative data collection included Patient's demographics (sex, age), past medical history (Diabetes Mellitus,DM), Complete blood count, blood urea nitrogen, creatinine, liver function test, urinalysis, and urine culture were done. Imaging methods: Ultrasonography(USG) or computed tomography (CT) were used to determine stone size and location. Patients were evaluated using the newly established scoring system and receiver operating characteristic (ROC) curve and area under the ROC(Receiver Operating Characteristic )curve was used to determine the predictive ability of scoring system.

Statistical analysis
The database was established using Epidata 3.

Establishment of PuRass (Risk Assessment Scoring System)
The PuRass( Risk Assessment Scoring System)scale was established based on results of meta-analysis (Table.1.a) including the following nine risk factor: female, age (≥60 ), diabetes mellitus(DM), Full blood count (WBC ≥10×10 9 /L), urinalysis(positive), Urine culture(positive), stone size(≥2cm), stag horn calculi, Hydronephrosis(moderate,severe) and they were assigned 3,2,3,2,2,2,2,3,2 respectively, with a total score of 21. (Table 1. b) Effect analysis of the Risk assessment system: Two hundred and ninety-three patients scored between 0~16 points with an average score of (4.97SD3.19). The average score in urosepsis patient was higher than in non-urological cause sepsis and was statically signi cant (P<0.01) Table  2.b ROC curve: The predictive ability of the risk assessment system was determined by ROC(Receiver Operating Characteristic ) curve with AUC 0.913 95%CI [0.807-1.000] ). Youden's index (0.794) was used to determine the optimal cutoff values of 8.5 with a 90 % sensitivity and 89.4 speci city. See Figure 1 Degree of severity For easier and accurate evaluation, severity was graded as Low risk 0-7; medium risk 8-14, high risk 15-21. All the 293 patients were assessed for degree of severity, the difference among the groups was signi cant(P<0.01). See Table 2.c Discussion Percutaneous nephrolithotomy (PCNL) was the treatment of choice for large renal calculi however, it was not free of complications. Urosepsis was a potentially catastrophic complication which could progress to multiorgan dysfunction syndrome (MODS). The risk of post-PCNL(Percutaneous Nephrolithotomy) urosepsis is 0.3-4.7% and has a mortality of 25-60% [4][5] . Delay in diagnosis and treatment of sepsis increased mortality, prolonged length of hospital stay, and increased the costs [6][7] .
Incidence of urosepsis had increased with the increasing number of PCNL(Percutaneous nephrolithotomy) performed every year. Attempts had been made to identify factors contributing to the development of SIRS ( Systemic In ammatory Response Syndrome ). However, no single method or scoring system had been designed to predict the probability of urosepsis [8] . Risk assessment tools had been widely used in disease diagnosis and prognosis [9] . Early diagnosis and treatment of urosepsis was di cult due to lack of a predictive scoring system. The development of evaluation system based on different risk levels that could help in early recognition of urosepsis, decrease its rate of complication and improve prognosis was today's need. This study aims to evaluate the risk factors associated to urosepsis after percutaneous nephrolithotomy (PCNL) and establish a risk assessment tools that could help in early diagnosis of highrisk patients and prevent septic complications.
Tian et al [10] included 164 post PCNL(Percutaneous Nephrolithotomy) patients to study infectious complications after percutaneous nephrolithotomy (PCNL) and established a prediction tool for postoperative complications. They proposed that patients with larger stone size and preoperative urinary tract infection were high risk patient of developing SIRS (Systemic In ammatory Response Syndrome ) and fever after the procedure. In a retrospective study [11] over a period of 3 years Sumit Suresh Bansal and colleges concluded that stone size >25 mm, prolonged operative time >120 min, and signi cant bleeding requiring transfusion were signi cantly correlated with postoperative severe sepsis. In anorther prospective study [11] to determine the predictors of infectious complications following PCNL(Percutaneous Nephrolithotomy), 332 patients with renal or upper ureteric calculi were divided into 2 groups depending on incidence of infectious complications. In patients with renal failure, diabetes mellitus, preoperative PCN (Percukaneous Nephrostomy) placement, staghorn calculi, severe HDN(Hemolytic Disease of the Newborn), multiple punctures, and prolonged duration of surgery. Post-PCNL(Percutaneous Nephrolithotomy)infectious complications were more commonly observed.
All these studies had some limitation mainly the small number of sample size, single center study and limited number of variables considered for evaluations. Retrospective study from single institute, which might lead to selection bias and cause-effect relationship between different biochemical parameters and co-morbid conditions were left out. Thus we attempted to establish a scoring system based on the meta-analysis which including 12 factors and RCT (Randomized Controlled Trial) studies which was more accurate and comprehensive to establish a clinically useful evaluation system.
We carried a meta-analysis on risk factors of urosepsis following PCNL(Percutaneous Nephrolithotomy) and based on its results formulated the PuRass(Risk Assessment Scoring System) scale. In PuRass scale evaluation, post-PCNL(Percutaneous Nephrolithotomy) urosepsis group yielded higher score than in non urolological cause of urosepsis, indicating post-PCNL(Percutaneous Nephrolithotomy) urosepsis group prone to infection. The ROC(Receiver Operating Characteristic) cure with AUC (Area Under ROC Curve) 0.913 could effectively predict the probability of post-operative infection. At a cutoff value of 8.5 the speci city and sensitivity were 89.4% and 90.0% suggesting patients above the cutoff values having higher chance of acquiring post-operative infection. These were very important clinical information that could help urologist to prepare and take more precaution in these group of patients.
We performed risk assessment in 293 patients using the PuRass scale, majority of the post PCNL(Percutaneous Nephrolithotomy) patients were at moderate risk of urosepsis that was consistence to clinical practice and many published literatures.
But in majority of non-urological cause of urosepsis patients the score was low and there was a rapid decline in number of such patients with rise in the score. This helped surgeons to be more careful specially for high risk patients and avoiding associated complications.

Limitation of the study
The retrospective nature of the analysis from a region and a single institution might cause possible bias in the scoring system. Further veri cation from different regions or in multi center studies was needed before the widespread use of this evaluation score. Urosepsis following PCNL(Percutaneous Nephrolithotomy) depended on variety of the preoperative and perioperative factors. Earlier reports had identi ed number and size of tracts, bleeding, surgical time, irritants used, pelvic pressure, nephrostomy care as major factors associated with urosepsis [12][13][14][15][16] . But the surgeons experience and its association with incidence of urosepsis was not clear. Since preoperative factors played an important role in the incidence of urosepsis, the peri and postoperative factors were not included in the meta-analysis used to established this scoring system. Thus, this evaluation system might not be enough to precisely assess the risk of postoperative urinary sepsis.
We had developed a risk assessment system to assess the probability of urosepsis following PCNL(Percutaneous Nephrolithotomy). The clinical application and effectiveness were also validated. The risk assessment system was useful in quanti cation of the operative risk before surgery could help surgeons timely and accurate appraise the risk of postoperative urosepsis. It also enabled to screen high risk patients and strictly monitor these patients. Thus, this scoring system could identify the risk factors and guide to use appropriate measures to improve the prognosis of PCNL(Percutaneous Nephrolithotomy). ROC curve of risk assessment system for urinary sepsis after PCNL