1. Introduction
Urolithiasis is one of the most common urologic diseases with increasing prevalence each year around the world. The management of renal stones has evolved from traditional open nephrolithotomy to minimally invasive percutaneous nephrolithotripsy (PCNL) or retrograde intrarenal surgery. The percutaneous nephrolithotomy (PCNL) was first reported in 1976 to treat renal calculi and then become the mainstay treatment for renal stones, which stones size more than 2 cm.[ 1 ] However, infection after PCNL or urosepsis has been an important lethal problem.[ 2,3 ] Urosepsis is a severe postoperative complication of PCNL that can cause septic shock and become a cause of mortality.[ 4 ] Hence, the early detection of patients at potential risk for urosepsis is extremely important. In this study, we aimed to retrospectively analyze the clinical data of patients who had undergone PCNL treatment for renal stones and identify independent risk factors for systemic inflammatory response (SIRS ) after PCNL, which is used for early detection and prevention of urosepsis. Subsequently, we developed a prediction model for postoperative SIRS that help improve the early detection of urosepsis in patients undergoing PCNL.
2. Materials and Methods
2.1. Population of study
This study was approved by the ethical committee the Songklanagarind Hospital Ethics Committee granted approval for this study with a waiver of informed consent and compliance with the Declaration of Helsinki’s guiding principles (REC.62-159-10-1). We retrospectively analyzed the data of 262 patients who had undergone PCNL for renal stones at a university hospital, between June 2012 and December 2019. A computerized tomography (CT) scan of the kidneys was used to diagnose renal stones. Patients were excluded for the following reason: PCNL concurrently combined with other surgical methods such as ureteroscopic lithotripsy, patients who have tumors, congenital malformations such as polycystic kidney and horseshoe kidney, a solitary kidney, and those undergoing nephrectomy and missing data.
2.2. Clinical data
Preoperative preparations included complete blood count, serum creatinine, renal ultrasound, abdominal x-ray film, and CT scan of the kidneys, if necessary. Midstream urine was collected for routine urinalysis and culture. Positive preoperative urine white blood cells (WBC) were defined as >10 WBC per 109 /L. Positive urine white blood cells (WBC+) were defined as WBC ≥10 per high-power field (×400) in the resuspended sediment of a centrifuged aliquot of urine. For patients with positive urine WBC or nitrite, oral antibiotics were given immediately for 3 to 7 days and the operation was postponed. Antibacterial prophylaxis for patients with sterile urine consisted of a single-dose intravenous broad-spectrum antibiotic (cephalosporinum 3rd generation or fluoroquinolone) before PCNL; this continued at least 48 hours after surgery. Renal stones occurring in the renal pelvis and extending to at least one major calyces were classified as staghorn stones. All patients were monitored after PCNL with SIRS criteria assessment (WBC count <4000 × 109 /L or >12,000 × 109 /L; body temperature >38°C or <36°C; heart rate >90 beats/min; and respiratory rate >20 breaths/min), and hemoculture was performed, if patient developed SIRS or sepsis.[ 5 ] We diagnosed SIRS in patients who have two or more criteria (Tables 1 , 2 ).[ 4,6 ]
Table 1 -
Comparison of Clinical Parameters Between the Groups
Non-SIRS
SIRS
P
Total
145
117
Sex
0.121
Male
82 (60.3%)
54 (39.7%)
Female
63 (50%)
63 (50%)
Age, y
60 (52–67)
58 (48–64)
0.048
BMI, kg/m2
25 (22.1–28.2)
25.9 (22.6–28.1)
0.211
DM
1
No
110 (55.6%)
88 (44.4%)
Yes
35 (54.7%)
29 (45.3%)
ASA classification
0.398
1
4 (40%)
6 (60%)
2
117 (57.4%)
87 (42.6%)
3
24 (50%)
24 (50%)
No. stones
0.04
1
90 (51.1%)
86 (48.9%)
2
12 (50%)
12 (50%)
>3
43 (69.4%)
19 (30.6%)
Access tract
0.938
Multiple
23 (57.5%)
17 (42.5%)
Single
119 (55.3%)
96 (44.7%)
Staghorn stone
<0.001
No
101 (66%)
52 (34%)
Yes
44 (40.4%)
65 (59.6%)
Stone size, cm
2.5 (1.9–3.4)
3.2 (2.2–4.9)
<0.001
Hounsfield unit
904 (625–1212)
955 (648–1188.5)
0.927
Degree of hydronephrosis
0.489
Mild
36 (50.7%)
35 (49.3%)
Severe
23 (56.1%)
18 (43.9%)
Moderate
30 (65.2%)
16 (34.8%)
No
50 (57.5%)
37 (42.5%)
Skin to stone distance, cm
9.1 ± 2.1
9 ± 2
0.742
Guy’s stone score
0.001
GSS 1
30 (61.2%)
19 (38.8%)
GSS 2
61 (69.3%)
27 (30.7%)
GSS 3
17 (48.6%)
18 (51.4%)
GSS 4
37 (41.1%)
53 (58.9%)
Preoperative WBC (109 /L)
7.620 (6.510–9.060)
7.830 (6.427–9.087)
0.559
Preoperative hematocrit (%)
38.9 ± 5.3
37.4 ± 4.9
0.019
Preoperative creatinine, mg%
1.1 (0.8–1.4)
1.1 (0.9–1.4)
0.719
Preoperative urine WBC
0.001
Negative
57 (71.2%)
23 (28.7%)
Positive
83 (48.8%)
87 (51.2%)
Preoperative urine nitrite
0.085
Negative
125 (58.7%)
88 (41.3%)
Positive
16 (42.1%)
22 (57.9%)
Urine culture
<0.001
Negative
107 (65.2%)
57 (34.8%)
Positive
30 (40%)
45 (60%)
ASA, American Society of Anesthesiologists; BMI, body mass index; DM, diabetes mellitus; GSS, Guy’s stone score; SIRS , systemic inflammatory response syndrome ; WBC, white blood cells.
Table 2 -
Univariable and Multivariable Logistic Regression Analyses of Clinical Data and Postoperative
SIRS
Univariate analysis
Multivariate analysis
Variables
OR
95% CI
P
OR
95% cl
P
Age
>60
Ref
<60
0.71
0.43–0.15
0.163
No. stones
1
Ref
0.036
2
1.05
0.45–2.46
≥3
0.46
0.25–0.86
Staghorn stone
No
Ref
Yes
2.87
1.73–4.77
<0.001
Stone size, cm
<3
Ref
Ref
<0.001
>3
3.28
1.97–5.46
<0.001
3.61
2.08–6.26
Guy’s stone score
GSS 1–2
Ref
<0.001
GSS 3–4
2.6
1.58–4.29
Preoperative hematocrit, %
<35
Ref
>35
1.7
0.95–3.04
0.072
Preoperative urine WBC
Negative
Ref
Ref
0.028
Positive
2.82
1.6–4.94
<0.001
3.1
1.65–5.81
Urine culture
Negative
Ref
Ref
0.017
Positive
2.82
1.6–4.94
<0.001
2.89
1.63–5.13
CI, confidence interval; OR, odds ratio; GSS, Guy’s stone score; ref, reference value.
2.3. Statistical methods
All patients were classified into two groups according to postoperative SIRS . The χ2 test was used to compare categorical variables. Student t test was used to compare the means of continuous variables between groups. Variables that showed significant differences were included in a multivariable logistic regression analysis. A nomogram to predict postoperative SIRS based on the multivariate logistic regression results was set up. A total of 500 bootstrap samples were used to generate a calibration curve to reduce overfitting bias and followed with internal validation of the nomogram . The accuracy of the model was calculated and reported by using the consistency index (C-index), calibration curve, and the Hosmer-Lemeshow goodness-of-fit test was performed.[ 7 ] The discriminative performance was assessed using the receiver operating characteristic curve. Data were statistically analyzed using R software, version 4.1.1 (R Foundation for Statistical Computing, Vienna, Austria). A two-tailed test with P < 0.05 was considered statistically significant.
3. Results
3.1. Clinical data and surgical outcome
This study included 262 patients diagnosed with renal calculi in a university hospital who had received PCNL treatment from June 2012 to December 2019. They consisted of 136 males and 126 females, with ages ranging from 10 to 85 years, with a mean age of 58 years and a mean renal stone size of 2.81 ± 2.18 cm. The SIRS after PCNL occurred in 117 patients (44.0%), also all cases occurred within 24 hours postoperatively. Patients were classified into two groups based on the postoperative occurrence of SIRS symptoms: (1) the SIRS and (2) the non-SIRS . The clinical parameters between the groups are shown in Table 1 . The patients in the SIRS group compared with the non-SIRS group had a larger stone size (3.2 [2.2–4.9] cm vs. 2.5 [1.9–3.4] cm, P < 0.001), a greater number of staghorn stones (65 [59.6%] vs. 44 [40.4%], P < 0.001), and a higher group in Guy’s stone score (GSS; GSS 3: 18 [51.4%] vs. 17 [48.6%], GSS 4: 53 [58.9%] vs. 37 [41.1%], P = 0.001). We observed an increased incidence of SIRS in patients with positive preoperative urine WBC (P < 0.001) and positive urine culture (P < 0.001). There were no significant differences between the groups in terms of sex, body mass index, diabetes mellitus, American Society of Anesthesiologists classification, degree of hydronephrosis, and preoperative urine WBC.
3.2. Logistic regression analysis of clinical features and SIRS
We analyzed the important factors associated with SIRS postoperatively using univariable analysis (Table 2 ). The results showed that the factors significantly associated with postoperative SIRS included the number of stones (2 stones, odds ratio [OR], 1.05; 95% CI, 0.45–2.46; ≥3 stones [OR, 0.46; 95% CI, 0.25–0.86; P = 0.036]), staghorn stones (OR, 2.87; 95% CI, 1.73–4.77; P = 0.001), stone size ≥3 cm (OR, 3.25; 95% CI, 1.97–5.46; P < 0.001), Guy’s stone score of 3–4 (OR, 2.6; 95% CI, 1.58–4.29; P < 0.001), positive preoperative urine WBC (OR, 2.82; 95% CI, 1.6–4.94; P ≤ 0.001), and positive urine culture (OR, 2.82; 95% CI, 1.6–4.94; P < 0.001). In multivariable logistic regression analysis, the results showed that the following three significant variables could be used as independent risk factors for postoperative SIRS occur: stone size ≥3 cm (OR, 3.61; 95% CI, 2.08–6.26; P < 0.001), positive preoperative urine WBC (OR, 3.1; 95% CI, 1.65–5.81; P = 0.028), and positive urine culture (OR, 2.82; 95% CI, 1.63–5.13; P = 0.017).
We have used the scores corresponding to each independent risk factor on the nomogram to obtain the total score for clinical application in the probability of urinary tract infection and used it to predict the occurrence of SIRS after PCNL (Figs. 1–3 ).
Figure 1: Nomogram for predicting the probability of postoperative SIRS following PCNL. SIRS , systemic inflammatory response syndrome ; WBC, white blood cells.
Figure 2: Calibration curve of the prediction model for postoperative urosepsis following percutaneous nephrolithotomy .
Figure 3: Receiver operating characteristic curves for post-operative systemic inflammatory response syndrome and urosepsis. The AUC for the urosepsis model is 0.702. The model has a favorable ability of discrimination. AUC, area under the curve; WBC, white blood cells.
4. Discussion
Nowadays, with the advancement of medical devices and technology for the treatment of renal calculi, compared with other techniques of renal calculi treatment such as retrograde intrarenal surgery, PCNL still has the advantage of large-sized stone disintegration. However, postoperative infection remains a major complication and impacts the morbidity and mortality of patients who undergo PCNL. This emphasized the importance of our study in preventing urosepsis by detecting SIRS early after PCNL. We developed a nomogram to predict early urosepsis after PCNL using SIRS , and the associated risk factors can be obtained in the first preoperative period, allowing for an early assessment of the risk for postoperative urosepsis and ensuring early intervention and treatment. Previous research has found that the incidence of infectious complications after PCNL surgery ranges from 2.8% to 32.1%.[ 8 ] Septic shock can occur if a postoperative infection is not detected in time and no active anti-infective treatment is available or inappropriate management. Indeed, the mortality rates for severe sepsis and septic shock vary from 22% to 76% among different medication centers, regions, and countries.[ 9 ] The surviving sepsis campaign guideline 2021 recommends SIRS , NEWS, or MEWS as screening tools for sepsis or septic shock.[ 10 ] In our study, consider for used a screening tool as SIRS criteria for the early detection of postoperative urosepsis that may help urologists prevent complications of infection.
The incidence of SIRS after PCNL has been reported in many studies (23.4%,[ 11 ] 25.5%,[ 12 ] and 22%[ 13 ] ). Despite careful preoperative preparation, the incidence rate of SIRS in our study was up to 44%, higher than in other studies. As a result, 44% SIRS contained 41.6% of staghorn stones compared with another study in which the incidence of SIRS was only 23.4% (16.7% had staghorn stones).[ 11 ] However, the incidence is relatively high, and the reason for the increased incidence of postoperative SIRS caused by staghorn stones is currently unknown (OR, 2.87; 95% CI, 1.73–4.77, P < 0.001).[ 14 ]
Nevertheless, the timing of starting empirical antibiotics is very important, Kumar et al.[15] also demonstrated that starting empirical antibiotic therapy within an hour of the diagnosis of sepsis, playing a prognostic factor, was associated with 80% survival. The survival rate will decrease by 7.6% per hour of delayed antibiotic use.[ 12 ] As a result, detecting and treating SIRS before the patient develops urosepsis has significant clinical implications.
Moreover, some basic studies of renal stones exhibited that the bacteria may contribute to the stone formation by destroying the mucosa of the urinary tract, resulting in increased bacterial colonization and crystal adherence.[ 15 ] Furthermore, staghorn stones are caused by recurrent or persistent infection with urease-producing bacteria and may be associated with or exacerbated by urinary obstruction or stasis, which leads to stone recurrence.[ 16 ] Nonetheless, staghorn stones are quite difficult to treat in one time of PCNL. The morphology of staghorn stones is complex, with multiple calyces involved. Furthermore, lithotripsy was used for stone removal during surgery for a longer period of time, and multiple tracts may be required for complete stone removal. Rivera et al.[ 17 ] used multivariate analysis to examine several factors for infection prediction after PCNL and discovered that staghorn stones were independently associated with an increased risk of postoperative infectious complications (OR, 3.14; P = 0.02). That may help support a higher incidence of SIRS with a high amount of staghorn in a cohort study. Using multivariate analysis, positive preoperative midstream urine culture results were found to be an independent risk factor for predicting SIRS after PCNL in patients (OR, 2.89; 95% CI, 16.63–5.13; P = 0.017). However, some studies have confirmed that the sensitivity of preoperative midstream urine culture results for predicting postoperative SIRS is only 50% when compared with stone and pelvic urine cultures, which have higher sensitivity, implying that midstream urine culture cannot predict the occurrence of postoperative SIRS .[ 18 ] However, specimens for pelvic urine and stone cultures have to be obtained while PCNL performing, and there is an increased waiting time. As a result, effective postoperative infection intervention cannot be immediate, limiting the clinical utility of pelvic urine and stone cultures. Additional research demonstrated that the importance of preoperative midstream urine culture cannot be overstated. Indeed, Gutierrez et al.[ 19 ] studied 865 PCNL patients and discovered that positive preoperative midstream urine culture (OR, 2.12; P < 0.05) was an independent risk factor for fever after PCNL. Similarly, Uchida et al.[ 20 ] found that obstructive pyelonephritis, positive preoperative bladder urine culture results, and female sex were associated with postoperative SIRS in a multivariate analysis of 496 patients undergoing ureteroscopic laser lithotripsy. Our findings are consistent with previous studies, which found that positive preoperative midstream urine culture results are significantly associated with an increased risk of SIRS after PCNL. Furthermore, this result can be obtained before surgery, which is useful for predicting risk and preventing infection after PCNL. Furthermore, in the multivariable regression analysis, positive preoperative WBC, positive urine nitrite, and the Guy’s stone score were not independent risk factors for SIRS after PCNL. Preoperative WBC and urine nitrite levels, on the other hand, may help predict urinary tract infections and the need for subsequent treatment. Liang et al.[4] conducted a retrospective analysis of 287 stone surgery patients and discovered that preoperative WBC (WBC > 1 × 1010 /L) (P = 0.027) was associated with intraoperative and postoperative urosepsis in patients with calculous pyonephrosis. In addition, the same study found that patients who had urine nitrite had a 3.697-fold higher postoperative risk of urosepsis than those who did not have urine nitrite (P = 0.010). This phenomenon is explained by residual stones, which may contain bacteria and endotoxins and thus increase the risk of infectious complications after PCNL surgery.[ 21 ]
According to the outcomes of the multivariable analysis, we included the following three risk factors linked to SIRS evidence following PCNL: positive preoperative urine culture (P = 0.017), positive preoperative urine WBC (P = 0.028), and stones size more than 3 cm (P < 0.001). In accordance with the relative risk of each element, we created a nomogram . After internal validation using the receiver operating characteristic curve, the area under the curve of this nomogram was found to be 0.702, which has fair accuracy. The three risk factors listed previously can be acquired during the initial preoperative phase; as a result, when planning surgery for high-risk patients, the risk for SIRS must be fully taken into account. This tool’s usefulness aids in clinical decision making, and prompt intervention for patients at risk for serious infections, but it also offers a surgical prognosis and makes preoperative patient counseling easier, both of which are crucial for the postoperative care of patients undergoing PCNL.
This study has some limitations. First, this is a retrospective cohort study, and there are some confounding factors in postoperative SIRS , such as fever due to other causes such as atelectasis or inflammatory processes, that cannot be excluded, which might indicate selection bias. Second, there are some missing data in some factors, possibly resulting in nonsignificant results related to the prediction model, which made the results quite different from previous studies. Despite these limitations, to our knowledge, this study is the first to use a nomogram for SIRS prediction for early detected patients who will have SIRS secondary to PCNL surgery. Finally, although our predictive model shows good fit and discrimination, it still needs external validation.
5. Conclusions
In conclusion, positive preoperative urine WBC, positive urine culture, and stone size of more than 3 cm were independent risk factors for SIRS in patients who had undergone percutaneous nephrolithotomy . We created a unique nomogram that can be used to predict a patient’s risk of SIRS after PCNL and personalized treatment for renal calculi treated with PCNL.
Acknowledgments
We thank Ms Nannapat Pruphetkaew of the epidemiology unit for her help with the statistical analysis of this study.
Authors’ contributions
Nattawit Jakjaroenrit conceived and designed the study, collected data, interpreted data, and prepared for manuscript writing. Nattawit Jakjaroenrit, Monthira Tanthanuch, and Tanan Bejrananda collected data, interpreted data, and prepared for manuscript writing. Nattawit Jakjaroenrit, Monthira Tanthanuch, and Tanan Bejrananda designed the study, interpreted data, and improved writing. All authors read and approved the final manuscript submission.
Data availability statement
The data that support the findings of this study are available on request from the corresponding author, Tanan Bejrananda. The data are not publicly available because of ethical restrictions. Tanan Bejrananda is the guarantor of the article, taking responsibility for the integrity of the work as a whole, from inception to published article.
Financial support and sponsorship
Nil.
Conflict of interest statement
The authors declare that they have no conflict of interest with regard to the content of this report.
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