Role of white blood cell and neutrophil counts in predicting spontaneous stone passage in patients with renal colic
Stavros Sfoungaristos, Urology resident, Patras University Hospital, Urology Department, Building A, 4th floor, Rion, Patras, 26500 Greece. e-mail: email@example.com
Study Type – Prognosis (case series)
Level of Evidence 4
What's known on the subject? and What does the study add?
Parameters that predict spontaneous stone passage is a subject that has been widely studied. Several factors have been proposed as potential predictors, however mainly stone size and location are the only ones that are consider in the clinical practice.
So far, it is well known that stone size is the most significant parameter. Actually, based on the latest guidelines, stones sized <4 mm have a great likehood to pass spontaneously a waiting period of 4–6 months should be proposed to the patient. On the other hand, stones >7 mm have minimum possibilities to pass spontaneously and immediate intervention might be the optimal management.
Another significant factor is stone location. Patients with stones placed in the distal ureter seem to have greater opportunities to be stone-free than those patients with calculi in the proximal or mid-ureter.
Even by considering size and location of a ureteral stone, a significant number of patients with favorable characteristics stones are not stone-free by surveillance and either ESWL or ureteroscopy is needed for definitive therapy. On the other hand, large stones in the proximal ureter are passing spontaneously and no intervention is needed. Based on the above, someone can consider that there are other parameters that enhance or not stones passage. The results of our study showed that increased WBC and neutrophils counts in blood serum can significantly contribute to the prediction of stone spontaneous passage. Using the present results in combination with the present knowledge (size and location) might help us to better define the best treatment protocol for each individual. Furthermore, both parameters can be easily, quickly and without significant cost assessed for every patient in the emergency department.
- • To determine the clinical, imaging and laboratory variables that can predict spontaneous passage of ureteral stones causing renal colic and the role of white blood cell (WBC) and neutrophil counts for the prediction of spontaneous calculi passage.
PATIENTS AND METHODS
- • A total of 156 patients who were referred to the emergency department complaining of renal colic due to a ureteral stone entered the analysis. Several clinical, laboratory and imaging parameters were evaluated for their potential ability to predict stone passage in a time interval of 1 month.
- • The study design had two objectives. Primarily we analyzed all patients irrespective of stone size and secondly we analyzed patients with calculi of 10 mm maximum length.
- • Spontaneous stone passage was observed in 96 (61.5%) patients in the overall population and in 84 (65.1%) of 129 patients with calculi <10 mm.
- • Increased concentrations of serum WBCs and neutrophils at the time of the acute phase of a renal colic were associated with increased likelihood of spontaneous passage.
- • In the multivariate analyses we found that WBC and neutrophil counts were the most important predictors of stone elimination.
- • Active surveillance of patients suffering from ureteral lithiasis is an acceptable option. Identifying the parameters which can predict those patients who will mostly benefit from this is of great importance.
- • Based on our results, WBC and neutrophil counts should be considered when patients with renal colic secondary to ureteral calculi are evaluated since they can significantly add to spontaneous elimination prediction.
- • Their consideration in addition to other important factors, like stone size and location, would maximize their predictive ability.
a plain abdominal film of kidney, ureter and bladder
spontaneous stone passage
white blood cells
Renal colic constitutes a common medical condition that the clinical doctor encounters in the emergency department [1–3]. The worldwide prevalence of renal stone disease is estimated to be between 2% and 20% and the reported lifetime risk of urolithiasis ranges from 5% to 12% [2,4]. Ureteral stones affect approximately 12% of the population worldwide and they are responsible for 20% of urolithiasis cases [5,6]. The incidence of ureteral stones has increased significantly in recent years especially in Western countries while the epidemiological data in the United States show an increasing trend [4,5]. Stone recurrence is also a common medical condition and the recurrence rates are estimated to be up to 50% within 5 to 10 years from the first episode of renal colic [2–4].
Renal colic due to ureteral stones may influence patients' quality of life causing pain and distress and furthermore it constitutes a significant economic burden [1,3,4,7]. It has been estimated that 122 of every 100 000 admissions to the hospital are due to urolithiasis while the annual expenditure on stone disease is reaching 2.1 billion US dollars [1,7]. The significant clinical and economical impact of ureteral colic emphasizes the importance of the meticulous management of the disease. Although the management of the initial renal colic episode is well established, further optimal management is still not defined. Actually there is still a gap in our knowledge regarding the factors that could guide clinicians to the appropriate treatment selection. The three main therapeutic options are watchful waiting with or without the addition of medical expulsive therapy, extracorporeal shockwave lithotripsy (ESWL) and ureteroscopy. The minimal invasive techniques have significant efficacy proven in several studies but even these procedures are not without complications. Furthermore, considering the fact that most ureteral stones can pass spontaneously, their application can be considered overtreatment adding unnecessary cost [5,7,8]. On the other hand conservative management, even though it is the most simple and cost effective treatment, also has complications like acute renal failure, febrile infections and urosepsis and recurrent renal colic [5–7].
Based on the above, the proper selection of those patients who would mostly benefit from active surveillance and those patients who would be better treated by immediate active stone removal is of great importance. In the present study we evaluated several clinical, laboratory and imaging parameters, in an effort to identify significant factors that could predict spontaneous ureteral stone passage.
PATIENTS AND METHODS
After we obtained Ethics committee approval from our institution, we conducted a prospective analysis of 265 consecutive patients admitted to the emergency department from June 2010 until June 2011 complaining of acute renal colic secondary to ureteral calculi. We analyzed the clinical, laboratory and imaging parameters that may predict spontaneous stone passage (SSP) in a time period of 1 month. The study design had two objectives. Firstly to evaluate the factors that could predict SSP irrespective of the stone size (overall analysis) and secondly to analyze and identify predictors for spontaneous passage of stones <10 mm (subgroup analysis).
Renal colic diagnosis was based on the clinical manifestations, mainly the pain location, type, duration, time of onset and reflection, filling symptoms during urination (frequency, urgency and dysuria) and/or nausea and vomiting. Pain severity was estimated with a numerical rating pain scale from 1 to 10. Confirmation of diagnosis was based on additional information from urine analysis (microscopic haematuria) and stone identification by imaging.
Patients' age, gender, weight and tobacco habits were recorded. Urine and blood samples were obtained at the acute phase and information regarding total serum white blood cell (WBC) count, neutrophil count (as a relative percentage value of total WBC count), creatinine, urea and potassium (K+) values were recorded. Normal values of the above laboratory data, as they are given by the microbiology department, are the following: total WBC count 4–11 × 109/L, neutrophils 50–70%, creatinine 0.9–1.6 mg/dL, urea 15–54 mg/dL and K+ 3.8–5.5 mmol/L.
A plain abdominal film of kidney, ureter and bladder (KUB) was made for the identification of ureteral calculi in all patients. When a radiopaque calculus was identified, the size (in mm), the side (right or left) and the location were recorded. Location was assessed by ureter topography which was defined as uretero-pelvic junction, proximal ureter (above sacroiliac joints), mid ureter (overlying sacroiliac joints), distal ureter (below sacroiliac joints) and vesico-ureter junction. A kidney, ureter and bladder ultrasound and a duplex Doppler ultrasound were performed in all study patients aiming to identify the presence of ureteral urine jet. In those cases in which stone identification was made during ultrasound imaging, the calculus characteristics (size, side and location) were recorded. These stones were characterized as radiolucent. Finally, in those cases in which both KUB and ultrasound were unable to identify a ureteral stone and when the diagnosis was doubtful, a non-contrast, spiral computer tomography (CT) scan was performed and when a stone was found, side, size and location were recorded. When the diagnosis of a suspected calculus on the KUB film was confirmed by CT, the stone was characterized as radiopaque while the cases with primary diagnosis by CT were characterized as radiolucent.
Exclusion criterion was a history of renal colic more than 2 h before the time admitted at the emergency department. Patients with fever (axillary temperature more than 37 °C) at the time of examination, a history of a recently diagnosed infection, antibiotic therapy intake in the last 2 weeks or an operation in the last 2 months were excluded from the study. Patients with positive urine culture or with pyouria on urine analysis were also excluded. Whenever the insertion of a double-j ureteral stent or a percutaneous nephrostomy was necessary, these patients were excluded. Patients with organic diseases that could affect the values of the data collected (congenital urinary anomalies, chronic renal failure, etc), patients with renal colic but with no calculi to be found in imaging techniques and those with more than one calculus found on the same ureter were not recorded. All patients had a solitary calculus.
A standard analgesic treatment protocol was followed in the acute phase of the renal colic consisting of diclofenac i.m. In cases of persistent pain and/or highly impaired renal function a double-j ureteral stent or a percutaneous nephrostomy was inserted and the patients were excluded from the study. No additional treatment was prescribed and a follow-up visit was planned after 1 month. Second visit standard examinations included a KUB film (after intestine preparation) for those patients diagnosed primarily by KUB. For those in whom ureteral calculi were found by ultrasound or CT, an intravenous pyelography was performed. Patients with contraindications for contrast material intake underwent a second CT scan. SSP was considered as the absence of the initially found calculus from the ureter.
All analyses were performed by using SPSS version 17 (SPSS Inc, Chicago, IL, USA). The descriptive statistics are presented as the mean ± standard deviation (sd) and interquartile range (IQR) for normally distributed variables and as the absolute and percent frequency for categorical variables.
The normality condition of the numerical variables was studied by means of the Kolmogorov–Smirnov test. None of them had normal distribution. For this reason, the Mann–Whitney test was used to compare means between numerical groups. The chi-squared test was used for categorical variables.
A univariate analysis was performed to identify the significance of age, gender, weight, pain severity, smoking, calculus side, location and size, serum total WBC count, neutrophil count, creatinine, urea and K+ and the presence of urine jet in the prediction of SSP. A multivariate analysis was then performed for the variables identified as statistically important in the univariate analysis, using logistic regression.
All tests were two-tailed with P value <0.05 considered as statistically significant.
A total of 156 patients fulfilled the inclusion criteria and were included in the study. Thirteen patients were excluded because of high temperature at the time of diagnosis, three patients were receiving antibiotics, three patients had a known history of chronic renal failure, five patients had colic because of non-lithiasis ureteral obstruction, 31 patients had at least two ureteral calculi, 28 patients were lost to follow-up and 26 patients were excluded because a pigtail or a nephrostomy tube was inserted.
The median age of the patients was 39 years (mean ±sd, IQR 41.4 ± 13.3, 20) and 84 patients (53.8%) were women. Calculi size was ranged between 2.3–15 mm (7.1 ± 3.5, 4.8) and 84 of them (53.8%) were radiopaque. Side location was equally distributed between the right (50%) and left (50%) ureter. Fifteen stones (9.6%) were identified in the uretero-pelvic junction, 16 (10.3%) were located at the proximal ureter, 23 (14.7%) at the mid ureter, 32 (20.5%) at the distal ureter and 70 (44.9%) at the vesico-ureter junction. SSP was identified in 96 cases (61.5%). The clinical, laboratory and imaging characteristics of the patients, according to the presence of SSP, are shown in Table 1. A significant correlation was observed between SSP and the stone size (P= 0.001), the WBC (P= 0.001) and neutrophil count (P < 0.001), the K+ concentration (P= 0.026) and the presence of ureteral jet during Doppler ultrasound (P= 0.002).
Table 1. Patients' characteristics
|Gender, n (%)|| || ||0.919†|
| Male||28 (38.9)||44 (61.1)|| |
| Female||32 (38.1)||52 (61.9)|| |
|Age (years)|| || ||0.431‡|
| Mean ±sd (IQR)||40.6 ± 14.8 (25)||42.0 ± 12.4 (18)|| |
|Weight (kg)|| || ||0.552‡|
| Mean ±sd (IQR)||68.1 ± 15.1 (22)||67.8 ± 15.6 (20)|| |
|Pain scale|| || ||0.232‡|
| Mean ±sd (IQR)||4.6 ± 2.0 (2)||5.0 ± 2.0 (3)|| |
|Side, n (%)|| || ||0.100†|
| Right||35 (44.9)||43 (55.1)|| |
| Left||25 (32.1)||53 (67.9)|| |
|Radiopaque, n (%)|| || ||0.576†|
| Yes||34 (40.5)||50 (59.5)|| |
| No||26 (36.1)||46 (63.9)|| |
|Location, n (%)|| || ||0.220†|
| UPJ||9 (60.0)||6 (40.0)|| |
| Proximal ureter||6 (37.5)||10 (62.5)|| |
| Mid ureter||5 (21.7)||18 (78.3)|| |
| Distal ureter||13 (40.6)||19 (59.4)|| |
| VUJ||27 (38.6)||43 (41.4)|| |
|Size (mm)|| || ||0.001*‡|
| Mean ±sd (IQR)||8.3 ± 3.8 (5.4)||6.3 ± 3.1 (3.4)|| |
|Smoking, n (%)|| || ||0.260†|
| Yes||20 (45.5)||24 (54.5)|| |
| No||40 (35.7)||72 (64.3)|| |
|Serum WBC count (109/L)|| || ||0.001*‡|
| Mean ±sd (IQR)||9939 ± 1959 (2575)||11 564 ± 2897 (4228)|| |
|Neutrophil count|| || ||<0.001*‡|
| Mean ±sd (IQR)||73.3 ± 9.4 (14)||81.4 ± 9.0 (16)|| |
|Creatinine (mg/dL)|| || ||0.435‡|
| Mean ±sd (IQR)||0.8 ± 0.4 (0)||0.8 ± 0.6 (1)|| |
|Urea (mg/dL)|| || ||0.755‡|
| Mean ±sd (IQR)||43.1 ± 10.9 (21)||43.2 ± 9.9 (18)|| |
|K+ (mmol/L)|| || ||0.026*‡|
| Mean ±sd (IQR)||4.0 ± 0.5 (0)||3.8 ± 0.6 (1)|| |
|Jet, n (%)|| || ||0.002*†|
| Yes||48 (34.3)||92 (65.7)|| |
| No||12 (75.0)||4 (25.0)|| |
A ureteral calculus <10 mm was identified in 129 patients (82.7%). The median size was 5.6 mm (5.8 ± 2.2, 3.3). Sixty-four stones (49.6%) were left-sided and 65 of them (50.4%) were radiopaque. Fourteen calculi (10.9%) were located at the uterero-pelvic junction, 16 (12.4%) were found at the proximal ureter, 21 (16.3%) at the mid ureter, 28 (21.7%) at the distal ureter and 50 of them (38.8%) at the vesico-ureter junction. SSP at the follow-up visit was observed in 84 patients (65.1%). The correlation between the mean values of the analyzed parameters and the presence of SSP is shown in Table 2. A statistically significant result was observed for stone side (P= 0.049), size (P= 0.013), the WBC (P= 0.002) and neutrophil count (P < 0.001), the K+ concentration (P= 0.014), the presence of ureteral jet (P= 0.006) and tobacco use (P= 0.020).
Table 2. Variables of patients with ureteral stones <10 mm
|Gender, n (%)|| || ||0.904†|
| Male||22 (34.4)||42 (65.6)|| |
| Female||23 (35.4)||42 (64.6)|| |
|Age (years)|| || ||0.581‡|
| Mean ±sd (IQR)||41.7 ± 15.5 (29)||42.7 ± 12.4 (18)|| |
|Weight (kg)|| || ||0.649‡|
| Mean ±sd (IQR)||69.6 ± 15.4 (22)||69.6 ± 15.6 (19)|| |
|Pain scale|| || ||0.193‡|
| Mean ±sd (IQR)||4.4 ± 1.9 (2)||4.9 ± 2.1 (3)|| |
|Side, n (%)|| || ||0.049*†|
| Right||28 (43.1)||37 (56.9)|| |
| Left||17 (26.6)||47 (73.4)|| |
|Radiopaque, n (%)|| || ||0.904†|
| Yes||23 (35.4)||42 (64.6)|| |
| No||22 (34.4)||42 (65.6)|| |
|Location, n (%)|| || ||0.133†|
| UPJ||8 (57.1)||6 (42.9)|| |
| Proximal ureter||6 (37.5)||10 (62.5)|| |
| Mid ureter||3 (14.3)||18 (85.7)|| |
| Distal ureter||10 (35.7)||18 (64.3)|| |
| VUJ||18 (36.0)||32 (64.0)|| |
|Size (mm)|| || ||0.013*‡|
| Mean ±sd (IQR)||6.5 ± 2.4 (4.8)||5.4 ± 1.2 (2.9)|| |
|Smoking, n (%)|| || ||0.020*†|
| Yes||19 (50.0)||19 (50.0)|| |
| No||26 (28.6)||65 (71.4)|| |
|Serum WBC count (109/L)|| || ||0.002*‡|
| Mean ±sd (IQR)||9948 ± 2011 (2285)||11 687 ± 2997 (4755)|| |
|Neutrophil count (%)|| || ||<0.001*‡|
| Mean ±sd (IQR)||72.8 ± 10.0 (14)||81.5 ± 8.7 (14)|| |
|Creatinine (mg/dL)|| || ||0.845‡|
| Mean ±sd (IQR)||0.8 ± 0.4 (0)||0.8 ± 0.6 (1)|| |
|Urea (mg/dL)|| || ||0.761‡|
| Mean ±sd (IQR)||44.6 ± 11.0 (21)||43.7 ± 10.0 (18)|| |
|K+ (mmol/L)|| || ||0.014*‡|
| Mean ±sd (IQR)||4.0 ± 0.6 (0)||3.7 ± 0.5 (1)|| |
|Jet, n (%)|| || ||0.006*†|
| Yes||37 (31.3)||81 (68.7)|| |
| No||8 (72.7)||3 (27.3)|| |
A univariate and multivariate analysis was conducted to identify the factors that might predict SSP. Concerning the total population, the univariate analysis revealed that stone size (P= 0.001), the presence of ureteral jet (P= 0.004), and the laboratory values of WBC count (P < 0.001), neutrophils (P < 0.001) and K+ (P= 0.028) were significant. The above parameters were entered in a multivariate analysis which showed that WBC (P= 0.028) and neutrophil (P < 0.001) counts were the most statistically important predictors (Table 3).
Table 3. Univariate and multivariate analysis of the factors predicting spontaneous stone passage in the overall population studied
The same statistical protocol was used to identify the significant predictors for SSP of stones <10 mm. Stone size (P= 0.001), tobacco use (P= 0.022), the presence of ureteral jet (P= 0.012), serum total WBC count (P= 0.001), neutrophil count (P≤ 0.001) and K+ concentration (P= 0.010) were found significant in univariate analysis. However, the results of the multivariate analysis revealed that the presence of urine jet (P= 0.047) was marginally statistically significant while WBC (P= 0.013) and neutrophil counts (P= 0.001) could predict SSP (Table 4).
Table 4. Univariate and multivariate analysis of the factors predicting spontaneous passage for stones <10 mm
After the primary management of a ureteral colic episode the clinician often encounters the dilemma of the further optimal management. There is a variety of options including conservative therapy or immediate stone removal by ESWL and/or ureteroscopy. The advances of minimal invasive techniques have resulted in their wide adoption for the treatment of ureteral stones and their efficacy has been proved by several studies [5,8,9]. Both ESWL and ureterorenoscopy (URS) have high success rates reaching 63%–86% and 57%–92% of stones respectively [8,9]. However these procedures are not complication-free and they add significantly to the cost of treatment [5,7,8,10]. On the other hand active surveillance is a simple and cost effective treatment given the fact that most ureteral stones pass spontaneously [7,10]. However conservative management is also not free of complications and may lead to recurrent colic episodes, urinary tract infection, sepsis and deterioration of renal function [5,6,10]. At the same time the goal of stone clearance is not always achieved during conservative management while intervention after a period of waiting results in a greater risk of complications because of stone impaction and the subsequent local ureteral inflammation .
The meticulous selection of patients who are candidates to be managed conservatively is based mainly on factors that characterize a stone as able or not able to pass spontaneously. The two most widely studied factors for SSP are stone size and location [6,8,11]. The importance of stone size in SSP has been confirmed in several studies proving that smaller stones have a higher probability to pass spontaneously. It has been reported that up to 68% of stones less than 5 mm can pass spontaneously . Other studies have shown that 76–100% of stones smaller than 5 mm can pass spontaneously while only 0–60% of stones with a size more than 5 mm will do so [11,12]. Hubner et al.  reported that 38% of stones measuring less than 4 mm may pass spontaneously while this rate decreased to 1.2% for stones larger than 6 mm. In our study stone size was a statistically significant predictor in the univariate overall (P= 0.001) and subgroup analysis (P= 0.007). However, this was not confirmed by the multivariate analysis.
Location is another factor that is considered to be important for SSP and it is usually examined in relation with stone size. Hubner et al.  reported that the likelihood of spontaneous passage was 45% for stones in the distal ureter, 22% for stones in the mid ureter and only 12% for those in the proximal ureter. Other studies have reported that SSP rates are 71%, 46% and 22% for stones located in the distal, mid and proximal ureter, respectively . Concerning the relation between size and location, several studies have reported that smaller stones located in the distal ureter have greater probability of SSP [12,15]. In our study although there was a trend showing that distal ureteral calculi have a higher likelihood to pass spontaneously, this was not confirmed either in the univariate or the multivariate analysis.
Apart from the size and location of a stone, there are several other factors that have been examined as potential predictors of ureteral SSP. In our study we found that increased WBC count statistically significantly predicted SSP, and this was observed in multivariate analyses in both the overall (P= 0.028) and subgroup population (P= 0.013).These results confirmed our previous findings . The new and interesting finding of the present study is that the neutrophil count is related even more to the prediction of SSP in both the overall (P < 0.01) and subgroup analysis (P= 0.01). WBC and neutrophil counts are general indices of inflammation. Consequently, a possible explanation of the above findings may be that the increase in their counts depicts the degree of inflammation caused to the ureteral mucosa during the passage of a stone, since it has been observed that the interaction between the mucosa of the ureter and the stone induces inflammation at the stone site . Probably stones that are incapable of moving and passing forward in the ureter are producing minimal inflammation during renal colic, or at least a less significant reaction than that produced by a stone which is travelling down the ureter producing an inflammatory reaction along the ureter. Although this is a potential explanation, it still remains a theory, since the pathophysiology at the ureteral level during renal colic has not been widely studied and defined. Several studies have also reported that some other factors which are associated with SSP are ureteral peristalsis, submucosal oedema and ureteral wall spasm at the stone site [2,18]. WBC and neutrophil counts may express the results of this ureteral trauma and inflammatory process due to stone progress during renal colic. Of course it is important to note that prolonged inflammation may decrease the ureteral compliance and the luminal diameter hindering stone passage . Thus, when we consider these laboratory expressions of a potential inflammation for the prediction of SSP, we should do this with the understanding that both WBC and neutrophil counts could have an upper cut off limit beyond which potential complications are masked. Of course it is mandatory to report that further treatment of a patient suffering from renal colic should be made in relation to other factors such as the size and location of the stone.
Summarizing the results of our study we may conclude that WBC and neutrophil counts can significantly contribute to the prediction of SSP and subsequently to the optimal management of ureteral stones causing renal colic. They constitute important and necessary examinations that are easily, quickly and without significant cost assessed for every patient in the emergency department. Of course as we have already mentioned their prediction ability should always be taken into account in relation to other factors, already proved as significant, and especially with calculus size and location in order to maximize their predictive ability.
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